Compositions, containing cyclic peptides and methods of applying thereof

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to liposomal compositions for application in cosmetic industry, including i) from 0.001 to 1 wt % of cyclo-(Arg-Gly-Asp-DPhe-Acha) and/or its salt or solvate, ii) from 0.01 to 20 wt % of one or more lipids; iii) from 60 to 99.99 wt % of one or more physiologically acceptable solvents, as well as to method of their obtaining and application for care and preservation of general condition of skin or hare, for prevention or reduction of wrinkles.

EFFECT: claimed compositions demonstrate favourable properties: improved effectiveness, higher stability, reduced immunogenic reactions in comparison with known properties.

18 cl, 3 dwg, 29 tbl, 18 ex

 

The invention in General relates to cyclic peptides and their use in compositions, in particular compositions for topical, cosmetic application and/or personal hygiene, and compositions containing these cyclic peptides.

A variety of natural and synthetic peptides are widely used in cosmetic compositions. Typically, the peptides included in cosmetic products due to their functional characteristics, such as inhibition of enzymes, antiviral and antibacterial activity.

Common examples of the use of peptides for cosmetic applications are known in the literature, for example, WO 2007/100874 and the literature mentioned there.

All publications, including patents and patent applications cited in this application are introduced here as a reference in its entirety.

Despite the desirability of the introduction of peptides in cosmetics, there are some disadvantages associated with their use. For example, the active peptide agents may suffer from weak efficiency of application due to, for example, their conformational flexibility and/or ease of digestion of peptides by proteases at sites of potential impacts. In addition, the efficiency may be blocked due to^the difficulty with which the peptides are transported�I through the membrane, such as the skin, and due to their poor solubility in many cosmetic carriers. In addition, the risk of immunogenic response to the peptide is also a problem in cosmetic compositions.

Thus, the object of the invention is to provide a useful peptides for cosmetic applications, with high efficiency, to provide suitable peptides for cosmetic applications, which, among others, have a high resistance to proteolytic degradation, and/or to provide beneficial peptides for cosmetic applications, which reduce the risk of immunogenic reactions. In addition, the present invention is to provide a new and mostly improved compositions which preferably have the best profile of action, the best side-effect profile and/or improved ability to process.

Thus, a preferred object of the invention is to provide new compositions, preferably cosmetic compositions and/or personal care composition incorporating the useful peptides. New compositions exhibit favorable properties, preferably selected from the group consisting of improved efficiency, higher stability and/or �nizinny immunogenic reactions.

Cyclic peptides as described in this application, and compositions containing them are preferably favorable or advantageous in respect of the application in cosmetics and personal care products, medical products, preferably in cosmetics and personal care products, particularly when they are applied topically. Topically in this respect preferably means that the cyclic peptides and compositions containing them, in the General case are applied to the body surface of a human or animal. The surface of the body is in this connection preferably includes skin, hair, preferably includes the roots of the hair and/or mucous membranes, preferably the eyes and ears, more preferably the skin and/or hair. Accordingly, the use of compositions for topical use on the skin and/or hair of a human body or an animal, preferably a human body, is in General preferred. Mostly local application to a specific area of the skin involves only or mainly on the area that is treated. Thus, preferably topically means applying opposite system.

The present invention thus relates to compositions comprising one or more cyclic peptides, preferably one or oleellisesti peptides as described above, to obtain and use it for the care, preservation or improvement of the General condition of skin or hair and for the prevention of induced time-and/or light the aging process of human skin or human hair, and also for the prophylaxis and/or treatment of skin diseases. The invention also relates to a composition having an effective content of the specified one or more cyclic peptides. Preferably, the invention also relates to the application of one or more cyclic peptides for the prevention and/or treatment of skin diseases, inflammations, allergies, irritation and/or improvement of wound healing and skin. Preferably, when the cyclic peptides for use in accordance with the invention have properties of modulation of integrin, more preferably, either integranova antagonistic activity (i.e., preferably the activity of inhibiting integrin), or integranova agonistic activity (i.e., preferably the activity of stimulation of integrin) and, in particular, integranova antagonistic activity (i.e., preferably the activity of inhibiting integrin), as well as integranova agonistic activity (i.e., preferably the activity of stimulation of integrin). The appropriate type of modulating integrin activity can�t is preferably subjected to control by using the appropriate applied cyclic peptide and/or the amount/concentration. Can be demonstrated that cyclic peptides, preferably cyclic peptide in accordance with the invention, showing integranova antagonistic activity in the same concentration interval, preferably in the range of high concentrations, and demonstrate integranova antagonistic activity in a different range of concentrations, preferably in the range of low concentrations, for example, in accordance with the method described by Legler et J Cell Sci. 2001 Apr;114 (Pt 8): 1545-53) or similar methods. More preferably, when the cyclic peptides according to the invention are ligands of integrins selected from the group consisting of αvβ3, αvβ5, αvβ1, αvβ6, αvβ8 and α2β3 integrins, and in particular selected from the group consisting of αvβ3 and αvβ5 integrins. These activities can be demonstrated, for example, in accordance with the method described by J. W. Smith and others, J. Biol. Chem. 265, 12 to 67-1 to 271 (1990), or an equivalent method.

Integrins are heterodimeric transmembrane receptors for extracellular matrix, consisting of alpha and beta subunits. Nature of integrin ligands include laminin, fibronectin and vitronectin, but they also include fibrinogen and fibrin, thrombospondin, MMP-2 and fibroblast growth factor 2. Integrins bind ligands by recognizing to�short amino acid residues on the exterior unprotected loops, in particular, the sequence arginine-glycine-aspartic acid (ROD). Upon ligation of integrins mediate the complex signaling events, alone or in combination with the receptor of the growth factor, regulating cell adhesion, proliferation, survival and migration by activating canonical pathways, such as those associated with the integrin kinase (ILK), protein kinase B (PKB/Akt), mitogen activated protein kinase (MARK), Rac or nuclear factor Kappa B (NF-κb). In the quiescent vessels integrins interact with the basement membrane, supporting, thus, the rest of the vessels. [Stupp and Ruegg, Journal of Clinical Oncology, vol 25, no 13 (May 1), 2007: pp. 1637-1638].

av integrins bind ligands in the extracellular matrix (ECM). These ligands include collagen, fibronectin, vitronectin, laminin, thrombospondin and osteopontin. The collagens are a family of filamentous proteins, and as a major component of skin and bones they are the most abundant proteins in mammals. The collagens serve as counter receptors for some (31 and (33 integrins. Fibrinogen, which is a soluble dimeric protein of blood plasma, having a vital importance in the process of blood clotting, wound healing and inflammation, is a ligand for integrins, including Mac-1, αXβ2, αllbβ3, � αvβ3 (Berman and others, 2003; Springer and Wang, 2004).

The dependence of angiogenesis on the interaction between vascular integrins and extracellular matrix proteins is described by R. S. Brooks, R. A. Clark and D. A. Cheresh, Science 264. 569-71 (1994).

The possibility of inhibiting this interaction and is associated with initiation of apoptosis (programmed cell death) of angiogenic vascular cells by a cyclic peptide is described by R. C. Brooks, A. M. Montgomery, M. Rosenfeld, R. A. Reisfeld, T.-Hu, G. Klier and D. A. Cheresh, Cell 79, 1157-64 (1994).

Connecting ROD integrins are necessary latent TGF-P1 activators in development and in the immune system (Yang, Zhiwei; Mu, Zhenyu; Dabovic, Branka; Jurukovski, Vladimir; Yu, Dawen; Sung, Joanne;

Xiong, Xiaozhong; Munger, John S. Journal of Cell Biology(2007), 176 (6), 787-793 Transforming growth factor (TGF)-p process induces the contraction of fibroblasts, which is involved in wound healing and the formation of keloid. It is assumed that the inhibitor activity of TGF-P type I receptor kinase may have therapeutic potential for excessive contraction of the skin, as observed in the formation of keloid (Hasegawa, Toshio;

Nakao, Atsuhito; Sumiyoshi, Koji; Tsuchihashi, Hitoshi; Ogawa, Hideoki, he is considered to be Journal of Science(2005), 39 (1), 33-38.). Thus, inhibitors of integrins binding RGD lead to less active TGF-β1.

Okigami reported on the use of tamoxifen and quercetin for the local treatment of mo�cracks of the skin. At concentrations of 0.1-5% they also prevent development of wrinkles by inhibiting fibronectin, TGF-and IGF-I (Okigami, Henry; Okigami, Paulo Takao. Braz. Pedido PI (2006), 9 pages)

The accumulated confirmations indicate that integrins of endothelial cells that bind matrix proteins associated with inflammation and wound healing are involved in the processes of angiogenesis. Integrins containing the av subunit, has been especially important. To study the involvement of these receptors in human angiogenesis model is developed associated with wound angiogenesis man in the transplantation of human skin on the mice with severe combined immunodeficiency (SCID). When using this model, we have studied the expression of some av integrins and investigated the hypothesis that the αvβ3 integrin will inhibit angiogenesis in humans during wound healing. These studies showed that αvβ3, αvβ5 and avp6 integrins in a short period of time are stimulated during wound angiogenesis by using different patterns of expression and that inhibition of αvβ3 integrin blocks the formation of new vessels in the wound healing process in humans (Christofidou-Solomidou, Melpo; Bridges, Mark; Murphy, George F.; Albelda, Steven M; Delisser, Horace M. Pulmonary and Critical Care Division, Department of Medicine and Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA, USA. American Journal of Pathology(1997), 151 (4), 975-983.)

Damage �WA, for example, acute UV induced skin damage;

may be reduced in a subject by introducing to a subject having acute UV induced skin damage or having the risk of such, the agent that inhibits VEGF signal transmission (WO 2005/097187).

VEGF is an important growth factor for microvascular and macrovascular endothelial cells that include arteries, veins, lymphatic vessels throughout the body (Leung DW, etc., Science 1989; 246:

1306-9). VEGF is produced by a wide variety of cell types. In skin keratinocytes are the main source of VEGF (Ballaun With, etc., J Invest Dermatol 1995; 104:7-10).

Human skin is subject to certain aging processes, some of which are due to internal processes (chronological aging), and some of which are due to exogenous factors (environmental, e.g. photoaging). In addition, you may experience temporary or even long-term changes in the picture of the skin, such as acne, greasy or dry skin, keratoses, pink or red acne, the light-sensitive, inflammatory, erythematous, allergic or autoimmune reactive reactions, such as dermatosis or photodermatosis.

Exogenous factors include, in particular, sunlight or artificial radiation sources, compared with�= range, and compounds that can form when exposed to radiation, such as undefined reactive photo products, which can also be a free radicals or ions. Such factors include cigarette smoke and reactive compounds present in it, such as ozone, free radicals, for example, the free hydroxyl radical, atomic oxygen and other reactive oxygen compounds or nitrogen, which cause harm to the natural physiology or morphology of the skin.

The influence of these factors may result, in addition to direct DNA damage of skin cells and collagen, elastin or molecules of glycosaminoglycan extracellular matrix, which are responsible for the strength of the skin. In addition, can affect the signal transduction chain, which is interrupted by activation of enzymes that decompose the matrix.Important representatives of these enzymes represent metalloproteinases (MMP, for example, collagenase, gelatinase and stromelysin), which activity is additionally regulated by TIMP (tissue inhibitors of matrix metalloproteinases).

The consequences of the above processes of aging are thinning of the skin, weaker plexus of the epidermis and dermis, as well as a decrease in the number of cells and supplying them with blood vessels. This is when�odit to the formation of fine lines and wrinkles and wrinkles the skin becomes hard, and there can be defects pigments.

The same factors also affect the hair, which also may be corrupted. Hair becomes brittle, less elastic and dull. Damaged hair surface structure.

Cosmetic and dermatological products that possess the claimed properties to counteract the described processes or comparable processes, or reduce or reverse the development of harmful consequences, are often characterized by the following properties:

the removal of free radicals, antioxidant effects, properties of inhibiting inflammation or skin hydration. They prevent or reduce, among others, the activity of enzymes that destroy the matrix, or regulate a new synthesis of collagen, elastin or proteoglycans. The above-mentioned aging processes lead to thinning of the skin, reduction of adhesion between the epidermis and dermis, reduction in the number of cells, and a decline in collateral blood vessels. These processes are accompanied by the formation of fine lines and wrinkles and wrinkles, the skin shrinks and/or demonstrates the defects of pigmentation.

These factors also affect the condition of the hair, which also results in hair damage, in particular damage to the surface of the hair, which leads to scrap�spine and loss of elasticity and Shine.

Products for the care and/or cosmetic products with properties that will counteract the described or similar processes and/or which will cause return development of the results of damage, often provide one or more of the following properties: removal of free radicals, antioxidant effect, anti-inflammatory and/or moisturizing effect. Preferably, they block or reduce the activity of enzymes that destroy the matrix or control of de novo synthesis of collagen, elastin and/or proteoglycans.

The use of antioxidants or agents that remove free radicals in cosmetic compositions is known per se. Thus, the use of the antioxidant vitamin E in sunscreen compositions is familiar. However, the effect achieved even in this case is shorter than the expected effect.

Vitamin a and derivatives of vitamin A, such as retinoic acid, retinol and esters of retinol, affect the differentiation of epithelial cells and, thus, are used for the prevention and treatment of numerous phenomena, which damage the skin condition, for example, described its use against acne, psoriasis, senile keratosis, violations coloration of the skin and wrinkles (see, e.g., WO 93/19743 and WO 02/02074).

However, the effect of irritation to�LM retinol and its derivatives is also described in the literature (for example, WO 94/07462). These side effects limit the use of retinol to narrowly limited areas, and is important to avoid overdose. Thus, there is a need for active ingredients that have similar retinol spectrum of activity, but have no described side effects or at least have them in reduced form.

Thanks to the ever-increasing needs of the active ingredients for the preventative treatment of human skin and hair against ageing processes and harmful environmental influences, the task of this invention was to provide new active ingredients that demonstrate the aforementioned effects initially, are sufficiently stable against oxidation and exposure to light and can be easily receptioni. Composition obtained with these substances will also be to the maximum extent possible to have low irritating potential to the skin, to the maximum extent possible to possess a positive influence on the water binding in the skin, to maintain or increase the elasticity of skin and thus promote smoothing of the skin. In addition, they should preferably be pleasant skin sensation when applied to the skin. Preferably, when the active ingredients are mostly show and one�and more properties, selected from the group consisting of anti-aging, anti-inflammatory, preventing the formation of wrinkles properties and wound healing properties. Preferably, they can be used in products for the treatment and/or prevention of capillary fragility, products for the treatment and/or prevention of infiltration, products for the treatment and/or prophylaxis of psoriasis, products for the treatment and/or prevention of cellulite, and/or products for the treatment and/or prevention of gray hair.

Cyclic peptides for use in accordance with the present invention represent additional active ingredients. Preferably, the cyclic peptides for use in accordance with the invention have advantageous properties, such as improved processing properties, improved properties of stability and/or preferred activity modulation of integrin.

Linear peptides from extracts obtained from natural sources, or obtained by synthesis, are known as additives/ingredients/ incipiency in cosmetics, for example, from the log Brewster Cosmetics&Toiletries 121(11) 20-24 (2006), W007/113356, W007/100874, W007/093839, W007/068998, W005/025505, US Huang 2005226839, US 2005050656 and DE 102006046076.

However, the skeleton and the end portion, geteroliticheskoi (peptides having at least one bond between the amino acids, which is different from e�peptide) and gorodeisky (peptides, which all bonds between amino acids are peptide bonds) peptides, cyclization of linear peptides can improve their stability against degradation by the action of peptidases and metabolism (Bogdanowich-Knipp et J Pept Res. 1999 May; 53 (5): 530-41, Li. Current Topics in Medicinal Chemistry 2002, 2, 325-341, Hess J. Med. Chem. 2007, 50, 6201-6211, Matsoukas, etc. J Med Chem. 2005 Mar 10; 48 (5): 1470-80). In some cases, physical and chemical stability even allows the sublimation of cyclic Pentapeptide (Bodanszky Int J Pept Protein Res. 1983 Nov; 22 (5): 590-6).

In addition, cyclization of RGD peptides may be designed to improve binding affinity with a certain target, such as integrin, and to achieve selectivity for a group of targets, preferably of the group of integrins (Samanen et J Med Chem. 1991 Oct; 34 (10): 3114-25, Dechantsreiter, etc. J Med Chem. 1999 Aug 12; 42 (16); 3033-40, Heckmann, etc. Methods Enzymol. 2007; 426: 463-503).

Integrins are a superfamily consisting of more than 20 heterodimeric covering the cell membrane of cell adhesion receptors that bind to ECM ligands, ligands of cell surface and soluble ligands (Takada et Genome Biol. 2007; 8 (5): 215, Ffrench-Constant, etc. Trends Cell Biol. 14 (12) 678-686 (2004), Akiyama Hum Cell. 1996 Sep; 9(3): 181-6).

Dependent on RGD ligand of integrin αvβ3 is known as such, which is involved in several pathologies like tumor development, angiogenesis, R�stenosis, osteoporosis and inflammatory diseases similar to arthritis (Le Tourneau Oncology (Williston Park). 2007 Aug; 21 (9 SuppI 3): 21-4, Ellis Surg Am. 2003 Jan; 69 (1): 3-10, Moussa and others. Curr Opin Investig Drugs. 2002 Aug; 3 (8): 1191-5, Hartmann, etc. Exp. Opin. Invest. Drugs 9 (6) 1281-1291 (2000), Tweti, etc. Calcif Tissue Int. 2002 Oct; 71 (4): 293-9, Wilder Ann Rheum Dis. 2002 Nov; 61 SuppI 2: ii96-9).

Inhibitors of integrin αvβ3, is known from clinical studies contain antibody BHTaKCHH/MEDI-522 and cyclic Pentapeptide of cilengitide (Cai et Hum Cell. 1996 Sep; 9 (H): 181-6, Tucker Curr. Opin. Invest. Drugs 4 (6) 722-731 (2003), Nemeth, etc. Cancer Investigation(2007), 25 (7), 632-646).

Structure and function of integrin αvβ3 is known in more detail (Arnaout Annual Review of Cell and Developmental Biology 21: 381-410, 2005, J Cell Biol. 2005 Mar 28; 168 (7): 1109-18, Xiong et Science. 2002 Apr 5; 296 (5565): 151-5)

There are several soluble and associated with the matrix of the natural ligand that binds to av-integrins. Fibrinogen, vitronectin, fibronectin, osteopontin and denatured collagen are examples of such (Ruoslahti et Cell 44, 517-518 (1986), Hynes, Cell 69, 11-25 (1992), Lin and others J Biol Chem. 1997 Sep 19; 272 (38): 23912-20). He received a lot of synthetic ligands (Cacciary. Curr. Med. Chem. 12, 51-70 (2005), Duggan Exp. Opin. Ther. Patents 10 (9) 1367-1383 (2000))

One existing in nature RGD ligands for av-integrins is a LAP, ligating the portion of the latent transforming growth factor LAP-TGFR. Was described his role in the activation and release of active TGFβ (Sheppard Cancer and Metastais Reviews 24: 395-402, 2005). Briefly, it is assumed that TGFβ must be activated in order to possess pleiotropic activity. Activation occurs by decomposition of the LAP peptide, which runs locally integrins, including αvβ3 and/or αvβ6. In addition, αvβ3 interacts with other receptors, such as receptors of growth factors (e.g., VEGF receptor, PDGF receptor and/or receptor IGF1). Since TGFβ is associated with fibrosis, it is assumed that fibrotic disorders and/or symptoms of fibrotic disorders of the skin can be weakened by using active modulators of integrins αvβ3 and/or αvβ6, preferably, inhibitors of integrins.

In addition to its inhibitory activity at high concentration of RGD ligands at low concentrations has been demonstrated as such which are able to activate integrins (Legler et J Cell Sci. 2001 Apr; 114 (Pt 8): 1545-53). Thus, activation-dependent av-integrin cellular processes with RGD ligands, preferably selected from cyclic peptides in accordance with the invention, more preferably the cyclic peptides according to the present invention, which include Arg-Gly-Asp sequence (also referred to as "cyclic RGD peptides" or "cRGD peptides") at low concentration is possible. For example, the cRGD peptide�, receptionand for local use, may be subject to fine-tuning the concentration and dose to modulate angiogenesis, or the activation of TGFβ from its predecessor, facilitating, thus, the process of scarring, wounds, inflammation, aging, and/or the formation of wrinkles.

TGFβ is a pleiotropic cytokine and a growth factor, repeatedly involved in physiological and pathological processes, which transmits signals through its receptor, TGFβ receptor tyrosine kinase and the substrate, Smad. (Pennington Curr Opin Oncol. 2007 Nov; 19 (6): 579-85). It plays an important role in suppressing the immune system in the periphery to prevent the immune response. TGFp family is a regulatory molecule with multiple effects on cell proliferation, differentiation, migration and survival to influence numerous biological processes such as development, carcinogenesis, fibrosis, wound healing, immune response.

The reduction of dermal scarring was demonstrated using neutralizing antibodies to TGFp (Shah et J Cell Sci. 1994 Sep; 107 (Pt5): 1137-57), J Cell Sci. 1995 Mar; 108 (Pt 3): 985-1002).

The role of TGFβ in wound healing is known (Martin Science. 1997 Apr4; 276(5309): 75-81).

In addition, TGFβ is known for its function in the cycle of a person's hair by suppression of proliferation of epithelial cells and stimulate� synthesis of caspases, and, thus, is included in catagen cascade in a model of male pattern baldness. Modulation of TGFβ may, therefore, delay premature entry growth of hair in the catagen phase (Hibino et J Dermatol Sci. 2004 Jun; 35 (1): 9-18).

Angiogenesis, the formation of the vascular system from existing blood vessels, is described for decades (Folkman, Nat Rev Drug Discov. 2007 Apr; 6 (4); 273-86, Annu Rev Med. 2006; 57: 1-18, Curr Mol Med. 2003 Nov; 3(7): 643-51, Semin Oncol. 2001 Dec;28 (6): 536-42, Alghisi Endothelium. 2006 Mar-Apr; 13 (2): 113-35, Stupack et Curr Top Dev Biol. 2004; 64: 207-38,).

It is a highly dynamic and complex process, dependent on a receptor of the growth factor and adhesion receptors. Integrins are the major adhesion receptors on endothelial cells, designed to interact with their extracellular environment. Inhibition of αvβ3 and αvβ5-integrins have been shown as such that violates angiogenesis (Eliceiri et Curr Opin Cell Biol. 2001 Oct; 13 (5): 563-8, Nisato and Angiogenesis.. 2003; 6 (2): 105-19, Eliceiri et Cancer J. 2000 May; 6 SuppI 3: S245-9).

In the skin αv-integrins also play an important role in angiogenesis (Perruzzi, etc. J Invest Dermatol. 2003 Jun; 120 (6): 1100-9).

Moreover, it was shown that some pathogens, like viruses, can use the interaction with integrins for cell reproduction. Thus, it is probable that inhibitors of integrins can prevent infection by pathogens �through damage to the skin, when used in compositions for topical application. Stewart, Phoebe L; Nemerow, Glen R. Cell integrins: commonly used receptors for diverse viral pathogens.

Trends in Microbiology(2007), 15 (11), 500-507. For example, a glycoprotein In the membrane of the herpes virus 8 mediates cell adhesion via its RGD sequence (Wang et J Virol. 2003 Mar; 77 (5): 3131-47). Other examples are: the human cytomegalovirus (Wang et Nat Med. 2005 May; 11 (5):515-21), and Hantavirus (Gavrilovskaya et Nat Med. 2005 May; 11 (5); 515-21).

Provides a special link to Simon L. Goodman, Horst Kessler and others, J. Med. Chem. 2002, 45, 1045-1051, Martin Pfaff, Horst Kessler and others, THE JOURNAL OF BIOLOGICAL CHEMISTRY, volume 269, No. 32, edition August 12, p. 20233-20238, 1994, Sally J. DeNardo, etc., CANCER BIOTHERAPY &RADIOPHARMACEUTICALS, vol 15, No. 1, 2000, and Wipff, P.-J., Hinz, B., Integrins and the activation of latent transforming growth factor β1-An intimate relationship, Eur. J. Cell Biol. (2008), the disclosure of which in its entirety is introduced in this application solely as a reference.

The present invention preferably relates to:

Compositions, preferably non-therapeutic compositions for use, including one or more cyclic peptides and one or more carriers.

Compositions, preferably compositions for topical application comprising one or more cyclic peptides and one or more carriers acceptable for local use.

Understanding of the term "peptide" or "peptides" is known in the art. In accordance with and�gaining the peptides are preferably defined as amides, derived from two or more (identical or different) molecules aminocarbonyl acids (i.e., amino acids) by forming covalent bonds between carbon carbonylbis group with one nitrogen atom of another with formal loss of water. The term is usually applied to structures formed from α-amino acids, but it also preferably includes those which are obtained from any aminocarbonyl acids or amino acids.

Cyclic peptides and methods for obtaining cyclic peptides are known in the art. In accordance with the invention, cyclic peptides preferably are peptides in which the bridge or a bond is formed between two amino acids, which are part of the peptide or constitute the peptide. The bridge can be formed between amino acids having a reactive group other than amino and carboxyl groups, which is essential for the corresponding amino acid), preferably, such as sulfhydryl groups. In General, the peptides comprising two or more, preferably two amino acids containing such a reactive group can be cyklinowanie. For example, a peptide comprising two amino acids that have a sulfide group can be cyklinowanie under conditions where disulfide bridge is formed between�the sulfide groups of two amino acids, containing a sulfide group. Examples of amino acids having a sulfide group and, thus, capable of forming a bridge, i.e., disulfide bridge include, but are not limited to, penicillamine and cysteine. Peptides in which links forming the ring are not exclusively peptide bonds (or eupatridae connections in accordance with IUPAC), preferably are called heterogenecity cyclic peptides. In this case, the relation between reactive groups other than the amino and carboxyl groups, which are essential for the corresponding amino acids), forming a ring, preferably called "bridge". Alternatively, peptides in which links forming the ring are exclusively by peptide bonds (or eupatridae connections in accordance with IUPAC), preferably are called gorodeiskiy cyclic peptides. In accordance with the invention can be used as geteroliticheskoi cyclic peptides and gorodeisky cyclic peptides. In General, the peptides consisting of three or more, preferably four or more amino acids can be cyklinowanie. In principle, the number of amino acids in the cyclic peptide is not limited. However, targeted and specific drugs of cyclic peptides, which consist of 30 or more AMI�of ocelot, constitute a set. Additionally, in many cases, preferred properties, which are inherent in the "lesser" cyclic peptides such as cyclic peptides which consist of or preferably 4-30, 4-20 amino acids, tend to disappear with increasing ring size and, thus, the increase in the number of amino acids constituting these cyclic peptides.

The competence of the specialist in the art is to obtain cyclic peptides, equally as cyclic peptides, which are exclusively composed of naturally existing amino acids and cyclic peptides comprising unnatural amino acids. For example, can be used traditional protection and activation of chemical groups. Typically, the amino group of the first amino acid is protected with the help able to the removal of the protective group for amino group, and carboxyl group of the second amino acid is protected with the help able to the removal of the protective group for carboxyl group. Acceptable group to protect the amine include, without limitation, benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (t-Boc) and 9-fluorenylmethoxycarbonyl (FMOC). A carboxyl group can be protected by formation of unstable to acid and is unstable to the formation of the ester, such as methyl, ethyl, benzyl�vy or trimethylsilyloxy esters. After protecting the first and second amino acids amino acids react in a suitable solvent, such as water or DMF in the presence of in situ activating agent such as N. N'-dicyclohexylcarbodiimide (DCCI), diisopropylcarbodiimide (DIPCDI) or 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide (EDCI) to implement the formation of the peptide bond. Reactive residues of the side chains of any amino acid protected by protective groups, such as teff-butyl or benzyl for IT and SH; methyl, ethyl, tert-butyl or benzyl for carboxyl groups, 2,2,5,7,8-pentamethylchroman-6-sulfonyl for-NHC(NH2)=NH AGD group and trityl for the imidazole group of His. After of fusion reaction is carried out selective release of the amino group of the first amino acid using acid hydrolysis, under conditions that do not remove the protection with a carboxyl group of the second amino acid. The procedure was repeated with additional aminoadenine amino acids. Solid-phase synthesis, such as, a well-known method of Merrifield is particularly useful for the synthesis of peptides in accordance with the invention. In General, the synthesis of cyclic peptides is carried out first with the synthesis of a linear peptide with the desired sequence, for example, as described above, followed by phase cyclization. Acceptable methods and conditions cyclizes�and linear peptide, a cyclic peptide are known in the art.

The introduction of unnatural amino acids into peptides is described in Hohsaka T, Sisido M "the Introduction of unnatural amino acids into proteins" Curr. Opin. Chem. Biol. 6: 809-815 (2002); Noren CJ, etc., "General method for site-specific introduction of unnatural amino acids into proteins," Science 244: 182-188 (1989); Hodgson, David R. W., Sanderson, John M., "Synthesis of peptides and proteins containing unnatural amino acids", Chem. Soc. Rev., 2004, 33, 422-430, the disclosure of which is introduced into this application by reference.

The present invention preferably relates to:

Composition as described above/below, where the specified cyclic peptide is geodetically cyclic peptide. Understanding of the terms "gorodeisky" and "geodetically cyclic peptide" is known in the art. In accordance with the invention geodetically cyclic peptide preferably is a cyclic peptide in which the ring (or the skeleton of the cyclic peptide) consists only of amino acid residues in a peptide bond (or in eupariini communication in accordance with IUPAC nomenclature).

Composition as described above/below, where the specified cyclic peptide consists of 4-30 amino acids, preferably 4 to 20 amino acids, more preferably from 4 to 15 amino acids, even more preferably 4-12, and, in particular, 4-10 amino acids selected from the group consisting of a naturally existing amino acids and �ecosistema in the nature of amino acids. Examples of preferred cyclic peptides, preferably geodetically cyclic peptides composed of 4 amino acids, 5 amino acids, 6 amino acids, 7 amino acids, 8 amino acids, 9 amino acids, 10 amino acids or 12 amino acids selected from the group consisting of a naturally existing amino acids and non-existent in nature amino acids. Examples of naturally existing amino acids and non-existent in nature amino acids are shown below.

Composition as described above/below, where the specified cyclic peptide includes one or more of a non-existent amino acids.

Composition according to one of items 1 to 4, where the specified cyclic peptide comprises the sequence Arg-Gly-Asp (or RGD sequence in single letter code for amino acids). In accordance with the invention, the sequence Arg-Gly-Asp preferably exclusively consists of the corresponding L-amino acids, i.e., consists of L-Arg, L-Gly and L-Asp.

As used in this application, the term "amino acid" is preferably intended to include naturally existing amino acids and non-existent in nature, amino acids, and preferably also includes any small molecule, having at least one carboxyl group and at least one primary or secondary amino group capable �the education of the peptide bond. The term "peptide" is preferably intended to include any molecule containing at least one peptide bond. The term "peptide" is preferably also covers the structure, as defined above, having one or more linkers, spacers, terminal groups or side chains, which are amino acids.

The terms "existing in nature amino acid" and "non-existent amino acids" are well understood in the art.

However, a non-exhaustive list of non-existent amino acids as well as naturally existing amino acids may preferably be found in "The Peptides", vol. 5 (1983), Academic Press, Chapter VI, edited by D. C. Roberts and F. Vellacio.

In accordance with the invention exist in nature amino acids are preferably selected from the group consisting of Gly, Ala, (3-Ala, Asn, Asp, Arg, Cys, Gin, Glu, His, lie, Leu, Lys, Met, NIe, Orn, Phe, Pro, Ser, Thr, Trp, Tight and Val, or more preferably, exclusively selected from their L forms.

In accordance with the invention non-existent in nature, amino acids are preferably selected from the group consisting of:

(i) D forms of naturally existing amino acids, i.e., D forms of Gly, Ala, β-Ala, Asn, Asp, Arg, Cys, Gin, Glu, His, lie, Leu, Lys, Met, NIe, Orn, Phe, Pro, Ser, Thr, Trp, Tight and Val,

ii) N-alkyl derivatives of Gly, Ala, β-Ala, Asn, Asp, Arg, Cys, Gin, Glu, His, lie, Leu, Lys, Met, NIe, Orn, Phe, Pro, Ser, hr, Trp, Tight and Val, preferably including their D and L forms, and

(iii) Lys(Ac), Lys(AcNH2), Lys(AcSH), Tic, Asp(OR), Cha, Nal, 4-Hal-Phe, Homo-

Phe, Phg, Pya, Abu, Acha, Acpa, Aha, Ahds, Aib, Aos, N-Ac-Arg, Dab, Dap, Deg, hPro, Nhdg, Homo-Phe, 4-Hal-Phe, Phg, Sar, Tia, Tic and Tie, preferably including their D and L forms;

where

R represents alkyl containing 1-18 carbon atoms,

Hal is F, Cl, Br, I

AC is alkanoyl containing 1-10 carbon atoms, aroyl containing 7-11 carbon atoms, or arkanoid containing 8-12 carbon atoms.

The term "dermatologically acceptable," as used in this application, preferably means that the described composition or components are acceptable for use in contact with human skin without risk of toxicity, incompatibility, instability, allergic response and the like. All terms such as "skin aging", "aging skin", "topical application" or the like is preferably used in the sense in which they are commonly and widely used in the fields of development, research and marketing of cosmetic products and products and personal care products.

The term "cosmetic composition" or more preferably only briefly "composition" in accordance with the present invention preferably relates to compositions that can be used for cosmetic Zell�, purposes of hygiene and/or as the basis for delivery of one or more pharmaceutical ingredients. Is also possible, when these compositions are used for two or more purposes simultaneously. Thus, the terms "cosmetic", "cosmetic composition" and/or "composition", as used in this application, preferably include, without limitation, lipstick, mascara, blush, concealer, eye shadow, pencil to summarize the eye, the pencil contour lip, lip gloss, face powder and body powder, sunscreen and a reflector for ultraviolet rays, nail Polish, foam hair sprays, gels for hair styling, nail care, in any one of the forms of creams, lotions, gels, ointments, emulsions, colloids, solutions, suspensions, pressed powder products, solids, pencils, spray compositions, applied with a brush compositions and the like. "Personal care products" preferably include, without limitation, gels, bath and shower, shampoos, conditioners, creams, conditioners, hair dyes and products for coloring, leave-in conditioners, sunscreens and reflectors for UV rays, lip balms, skin conditioners, coldcream, moisturizers, hair sprays, Soaps, body scrubs, �ate, exfoliating, agents, tightens pores, means for hair removal and solutions for permanent waving, song-dandruff compositions against sweating and deodorants, shaving products, to shave and after shave, moisturizers, deodorant means, coldcream, cosmetic cleansers, gels for the skin, rinses, either in solid, powder, liquid form, in the form of cream, gel, ointment, lotion, emulsions, colloids, solutions, suspensions or in another form. "Pharmaceuticals" in accordance with the present invention preferably include, without limitation, carriers for dermatological purposes, including local and transdermal application of pharmaceutically active ingredients. These can be in the form of gels, patches, creams, nasal sprays, ointments, lotions, emulsions, colloids, solutions, suspensions, powders and the like. Compositions in accordance with the invention preferably include cosmetics, personal care products and pharmaceuticals.

The term "skin aging" or "aging skin" preferably include, but without limitation, all externally visible and tactilely perceptible manifestations, as well as other macro - and microfiche caused by the aging of the skin. Such signs may be induced or�to syatica internal factors or external factors, for example, chronological aging and/or environmental pollution. These signs may result from processes which preferably include, but are not limited to, the development of structural damage, such as wrinkles and coarse deep wrinkles, fine lines, small cracks, uneven skin, enlarged pores (e.g., associated with adnexal structures, such as ducts of sweat glands, sebaceous glands or hair follicles), or the roughness or redness of the skin, loss of skin elasticity (loss and/or disruption of the formation of functional skin elastin), sagging (including bags under the eyes and double chin), loss of skin firmness, loss of tension of the skin, loss of skin recovery after deformation, discoloration (including (black) under eye hollows), cover spots, earthy color, the appearance of hyperpigmented areas of the skin such as age spots and lentigines, keratoses, abnormal differentiation, hyperkeratinization, degenerative changes in the elastic tissue, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, vascular system of the skin (e.g., telangiectasia or receptacles in the form of a web) and underlying tissues, in particular those that are close fitting to the skin. Especially preferred in with�according to the present invention, the signs of skin aging are wrinkles, and compositions in accordance with the present invention are in certain embodiments useful for combating wrinkles, treat, or prevent.

As used in this application, routine regulation of skin condition preferably includes delay, minimizing and/or preventing visible and/or tactile feel of the heterogeneity of the skin (for example, irregularities in skin texture, which can be determined visually or by touch), including the signs of skin aging.

As used in this application, therapeutic regulation of skin condition preferably includes improvements, such as reduction, minimization, and/or the unevenness of the skin, including signs of skin aging. Some of the products obtained using the composition according to the present invention, and, undoubtedly, the compositions themselves can be used for prophylactic or therapeutic regulation of skin condition.

Some of the products and compositions in accordance with the present invention are useful for improving the appearance and/or feel of the skin showing the signs of skin aging. For example, preferred compositions in accordance with the present invention are useful for regulating the external signs of the skin condition by ensuring�to enable immediate improvement in your appearance after applying the composition to the skin. In General, the compositions according to the present invention, which additionally contain material in the form of particles, will be most useful for providing an immediate visual improvement.

Some of the compositions in accordance with the present invention can also provide additional benefits, including stability, absence of significant (not acceptable to the consumer) of skin irritation, anti-inflammatory activity and good aesthetics.

In some preferred aspects of the present invention is useful to improve physiological condition and/or physical appearance of human skin, particularly to reduce the signs of skin aging caused by sun exposure, physical and hormonal stress, friction, dietary effects and other similar reasons. The composition can often be used to prevent the signs of aging and/or to treat them in order to provide the customers who use them to have a more youthful appearance.

Preferred cyclic peptides according to the invention are cyclic peptides according to formula 1

Cyclo-(AGD-Gl-s-Ω) I,

where

Ω is an amino acid suppositionally, including �the bottom or more amino acids, selected from the group consisting of L - and D-forms:hPro, Ahds, Aos, Nhdg, Acha, Aib, Acpa, Tie, Gly, Ala, β-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gin, Glu, His, lie, Leu, Lys, Lys(Ac), LysCAcNhh), Lys(AcSH), Met, Nal, Nie, Orn, Phe, 4-Hal-Phe, Homo-Phe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tight or Val,

and their N-alkyl derivatives,

where

R represents alkyl containing 1-18 carbon atoms,

Hal is F, Cl, Sh, I,

AC is alkanoyl containing 1-10 carbon atoms, aroyl containing 7-11 carbon atoms, or arkanoid containing 8-12 carbon atoms,

and their salts and solvates.

In a cyclic peptide in accordance with formula l

Ω is preferably from 1-20 amino acids as defined above/below, more preferably comprises 1-10 amino acids as defined above/below, even more preferably comprises 1-6 amino acids as defined above/below, and, in particular, consists of 1, 2, 3 or 4 amino acids as defined above/below.

In a cyclic peptide in accordance with the formula

Ω in particular, preferably consists of two amino acids as defined above/below.

Preferred cyclic peptides according to the invention are cyclic peptides of the formula la

Cyclo-(AGD-Gl-s-X-Y) la,

in which

X is an amino acid selected from the group consisting of Cha, Nal, Phe, 2-R1-Phe, S-R1-Phe, 4-R1-Phe, Homo-Phe, Phg, Thi, Trp, Tight and �roizvodnykh Tight, where Oh group can be etherified with alkyl radicals containing 1-18 carbon atoms, preferably including their D and L forms, more preferably consists of their D or L forms, and, in particular, consists of their D forms,

R1represents NH2, NO2, I, Br, Cl, F, alkyl having 1-18 carbon atoms, AG, AG-O or3H, AG represents phenyl which can be optionally singly or doubly substituted with NH2, NO2, I, Br, Cl, F, alkyl having 1-6 carbon atoms, or3H,

Y is an amino acid selected from the group consisting of Gly, Gly derivatives, in which α N-atom is substituted by R2derived Gly, in which the α-C atom is substituted by R3and/or R4and derivatives of Gly, in which both α N-atom is substituted by R2and α C-atom is substituted by R3and/or R4provided that Gly is substituted at least once above manner,

preferably including both their D and L forms, more preferably consists of their D or L forms, and, in particular, consists of their L forms,

R2, R3,

or R4each is independently an alkyl having 1-18 atoms

carbon, or also

R2and R3

or

R3and R4in each case together represent otherwise branched chain alkylene with a 3-Alimov carbon, so that α N atom and α together with the atom chain alkylene, or only With α atom chain alkylene, form a ring,

and derivatives of these amino acids, preferably selected from the group consisting of N-alkyl derivatives of these amino acids, preferably N-C1-C4-alkyl derivatives of these amino acids, β-esters of aspartic acid and N-guanidinosuccinic arginine derivatives, and their physiologically acceptable salts and solvates.

Abbreviations of amino acid residues given above and below, represent the residues of the following amino acids:

Abu 4-aminobutyric acid

h α-aminocyclohexanecarboxylic acid

ASRA α-aminocyclopentane acid

Aha 6-aminocaproic acid

Ahds 16-aminohexanoate acid

Aib 3-aminoadamantane acid

Ala alanine

Aos 8-aminooctanoic acid

Asn asparagine

Asp aspartic acid

Asp(OR), aspartic acid (β Esther)

AGD arginine

N-Ac-N AGD-guanidinosuccinic

Cha 3-cyclohexylamin

Dab 2,4-diaminobutane acid

Dap 2,3-diaminopropionic acid

Deg detillion

Gin glutamine

Glu glutamic acid

Gly glycine

hPro gamopolis=pipecolinate acid

His histidine

Not isoleucine

Leu leucine

Lys lysine

Nal 3-(2-naphthyl)alanine

Nhdg N-hexadecylamine

NIe �glazin

Phe phenylalanine

ooPhe homophenylalanine

4-Hal-Phe 4-halogenallanes

The Phg phenylglycine

Pro Proline

Sar sarcosine (N-methylglycine)

Tia 3-(2-thienyl)alanine

Tic tetrahydroisoquinoline-3-carboxylic acid

Thr threonine

Tie tert-leucine(Cαtert-butylglycol)

TGR tryptophan

Tight tyrosine

Val valine.

In addition, values are given below abbreviations are as follows:

BOC tert-butoxycarbonyl

Bzl benzyl

The DCCI dicyclohexylcarbodiimide

DMF dimethylformamide

EDCI M-ethyl-M'-(3-dimethylaminopropyl)carbodiimide x Hcl

Et ethyl

Fmoc 9-fluorenylmethoxycarbonyl

HOBt 1-hydroxy-benzotriazole

Me methyl

Mtr 4-Metacity-2,3,6-trimethylphenylsulfonyl

NMe N-methylated α-amino group

OBut tert-butyl ester

OMe methyl ester

OEt ethyl ester

ROA phenoxyacetyl

TBTU 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate

TFA trifluoroacetic acid.

When the above-mentioned amino acids can occur in several enantiomeric forms, all these forms and also their mixtures (e.g. the DL forms) are included above and below, for example, as components of compounds of the formula I. Amino acids, for example, as constituents of the compounds in accordance with formula I, can also be provided with acceptable protective groups, which are�known by themselves.

Above and below, the radicals X and Y have the meanings given in case of formulas Ia and Ib, unless explicitly stated otherwise. The letters used for the radicals X and Y preferably have nothing corresponding one-letter code for amino acids.

In relation to cyclic peptides in accordance with the invention, the amino acids and/or derivatives of amino acids, in particular N-alkyl derivatives of these amino acids, alkyl is preferably selected from methyl, ethyl, isopropyl, n-butyl, sec-butyl and tert-butyl. However, the alkyl, in addition, also preferably is selected from n-pentile, isopentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, n-nanila, n-decyl and n-hexadecyl.

In cyclic peptides according to formulae 1A - X preferably represents RPE, also preferably D-Phe, but also h(4-l), in particular, Phe(4-F) or h(4-CL) and Homo-h or Phg, (D shapes are also equally preferred.

In cyclic peptides according to formulae la-le, Y preferably represents the residue of a hydrophobic amino acid, preferably the residue of a hydrophobic amino acid selected from the group consisting of Gly, Ala, Val, Leu, NIe, lie, and Acha.

The invention relates in particular to such compounds of formula I in which at least one was mentioned radical� has one of the above-mentioned preferred values.

A preferred group of cyclic peptides in accordance with the invention is a cyclic peptide of formula podhorany 1b,

cyclo-(AGD-Gl-s-X-Y) 1b

in which

X is selected from the group consisting of D-Phe, Phe, D-Gomori, roMoPhe, D-Phg, Phg, Phe(4-F), D-Phe(4-F), D-Phe(4-CI) and Phe(4-CI); and

Y is selected from the group consisting of NIe, hPro, Ahds, Aos, Nhdg, Acha, Aib, Acpa, Tie, Ala, Leu or lie, where dhl forms are equally preferred,

and their salts and solvates.

Even more preferred group of cyclic peptides in accordance with the invention is a cyclic peptide of formula podhorany 1,

cyclo-(AGD-Gl-s-X-Y) 1C,

where

X is selected from the group consisting of D-Phe or Phe, and

Y is selected from the group consisting of Ahds, hPro, Aos, Nhdg, Acha, Aib, Acpa or Tie, D and L forms are equally preferred,

and their salts and solvates.

An additional preferred group of cyclic peptides in accordance with the invention is a cyclic peptide of formula podhorany Id,

cyclo-(nArg-nGly-nAsp-nX-nY) Id,

where

X and Y in each case independently from each other represent: Gly, Ala, β-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gin, Glu, His, lie, Leu, Lys,

Lys(Ac), Lys(AcNH2), Lys(AcSH), Met, Nal, NIe, Orn, Phe, 4-Hal - Phe, Homo-

Phe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tight or Val, where amino acid

residues can t�activate to be derivationally,

R represents alkyl having 1-18 carbon atoms,

Hal is F, CI, VG, I,

AC is alkanoyl having 1-10 carbon atoms, aroyl having 7-11 carbon atoms, or arkanoid having 8-12 carbon atoms,

n means no or Deputy means the Deputy of the α-amino group of the corresponding amino acid residue selected from the group consisting of alkyl radical R, benzyl and kalkilya radicals having 7-18 carbon atoms,

provided that at least one amino acid residue has a Deputy n and with the further proviso that in that case, if the involved residues of optically active amino acids and amino acid derivatives,are included as D and L forms, and their salts and solvates.

A more preferred group of cyclic peptides according to formula Id represents the cyclic peptides of the formula Ie,

cyclo-(nArg-nGly-nAsp-nX-nY) Ie,

where

X and Y in each case independently from each other represent Gly, Ala, β-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gin, Glu, His, lie, Leu, Lys, Lys(Ac), Lys(AcNH2), Lys(AcSH), Met, Nal, NIe, Orn, Phe, 4-Hal-Phe, Homo-Phe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tight or Val,

R represents alkyl having 1-18 carbon atoms,

Hal is F, Cl, Br, I,

Ac is alkanoyl having 1-10 carbon atoms, aroyl having 7-11 carbon atoms, iliaresion, having 8-12 carbon atoms,

n means a hydrogen atom or represents C1-C4-alkyl radical on the alpha amino group of the corresponding amino acid residues

provided that at least one amino acid residue n represents C1-C4-alkyl radical, and that in the case that involved residues of optically active amino acids and amino acid derivatives, are included as D and L forms, and their salts and solvates.

Preferably, when the cyclic peptide of formula I, Ia, Ib, Ic, Id and/or Ie is not cyclo-(AGD-Gl-s-PME-h-ly).

In cyclic peptides in accordance with the invention, which comprise the sequence Arg-Gly-Asp, all amino acid residues Arg, Gly and Asp are preferably present in the natural L configuration.

An additional preferred group of compounds can be expressed by formulas I, Ia, Ib, Ic, Id and/or Ie, more preferably of the formulae Ia, Ib, Ic, Id and/or Ie, in which only one of the amino acid residues X or Y is present in the D form, while others are in the L configuration.

In addition, particular preference is given to physiologically compatible salts of the compounds, which fall under one or more of formulas I, Ia, Ib, Ic, Id and/or Ie.

An additional preferred group of compounds can be expressed by dogformulas IC, which �correspond to dogformulas 1A and 1b and the formula I, but in which only one of the amino acid residues X or Y is present in the D form, while others are in the L configuration.

In addition, particular preference is given to physiologically compatible salts of the compounds, which fall under one or more of formulas I, la, Ib, IC, Id and/or 1E.

Cyclic peptides in accordance with the invention and, in particular, cyclic peptides in accordance with (I, Ia, Ib, Ic, Id and/or 1E, and also the starting materials for their preparation, preferably obtained using known methods, preferably as described in the literature (e.g. in standard works such as Houben-Weyl, Methoden der organischen Chemie [Methods of organic chemistry], Georg-Thieme-Verlag, Stuttgart), specifically under reaction conditions which are known and acceptable for these reactions. In this context, the application can also be carried out with known variants which are not mentioned in detail in this application.

If it is desirable that the initial substance can also be obtained in situ, so that they are not isolated from the reaction mixture, and immediately enter into further reaction with the formation of cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie. Cyclic peptides in accordance with the invention and, in private�ti, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ia may be obtained by freeing them from their functional derivatives by solvolysis, in particular hydrolysis, or by experimental data showed.

Preferred starting materials for the solvolysis or are experimental data showed that contain acceptable protected amino and/or hydroxyl groups instead of one or more free amino and/or hydroxyl groups, preferably those which carry a protective group for the amino group instead of a hydrogen atom that is attached to a nitrogen atom, and examples include those which conform to the formula I, but which instead of NH2groups contain an NHR' group (where R' represents a group for protecting the amino group, for example BOC or CBZ).

Other preferred starting materials are those which carry a protective group instead of a hydrogen atom, a hydroxyl group, for example, those corresponding to the formula I but contain, instead hydroxyproline group, R”O-phenyl group (where R" represents a protective group for hydroxyl).

It is also possible for two or more identical or different-protected amino groups and/or hydroxyl groups present in the molecule of the starting material. If present protective groups differ from each other, in� many cases they can be selectively removed.

The expression "protective group for the amino group" is generally known and relates to groups which are suitable for protecting (for blocking) an amino group from chemical reactions but which can easily be removed after the desired chemical reaction in other positions of the molecule. Such typical groups are, in particular, unsubstituted or substituted acyl, aryl, arelaxation or aracelio group. As the protective group for amino groups are removed after the desired reaction (or sequence of reactions), their nature and size in this respect are not crucial; however, preference is given to those who have 1-20, in particular 1-8, carbon atoms. The term "acyl group" is interpreted in its broadest sense in connection with the present process. It includes acyl groups originating from aliphatic, alifaticheskih, aromatic or heterocyclic carboxylic acids or sulfonic acids and, in particular, alkoxycarbonyl, aryloxyalkyl and, above all, alcoxycarbenium groups.Examples of such acyl groups are alkanoyl such as acetyl, propionyl, butyryl; arkanoid, such as phenylacetyl; aroyl, like this, cambisol or toluoyl; aryloxyalkanoic, such as ROA; alkoxy�ronil, such as methoxycarbonyl, ethoxycarbonyl, 2,2,2-trichlorocyanuric, barefoot, 2-iodoxybenzoic; Uralelectromed, such as CBZ ("carbobenzoxy"), 4-methoxybenzeneboronic, FMOC; and arylsulfonyl, such as Mtr. A preferred protective group for amino groups is a BOC and Mtr, and also CBZ, Fmoc, benzyl and acetyl.

The expression "protective group for hydroxyl" is also in General known and relates to groups which are suitable for protecting a hydroxyl group from chemical reactions but which can easily be removed after the desired chemical reaction in other positions of the molecule. Such typical groups are the abovementioned unsubstituted or substituted aryl, kalkilya or acyl groups, and alkyl groups. The nature and size of the protective groups for hydroxyls are not critical since they are removed after the desired reaction or sequence of reactions;

preference is given to groups that have 1-20, in particular 1-10, carbon atoms. Examples of protective groups for hydroxyl include benzyl, p-nitrobenzoyl, p-toluensulfonyl, tert-butyl and acetyl, with a special preference is given to benzyl and tert-butyl. The COOH group in aspartic acid and glutamic acid are preferably protect�built in the form of their tert-butyl esters (for example, Asp(OBut)).

Functional derivatives of cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, which are used as starting materials can be obtained by conventional methods of amino acid and peptide synthesis, as described, for example, in patent applications and referred to the standard works including, for example, solid-phase method in accordance with Merrifield (B. F. Gysin and R. B. Merrifield, J. Am.Chem. Soc. 94,3102 ff.(1972)).

The release of the compounds of cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie from their functional derivatives is preferably carried out depending on the protecting groups, using, for example, strong acids, acceptable manner using TFA or perchloro acid, but also using other strong inorganic acids such as hydrochloric acid or sulfuric acid, strong organic carboxylic acids, such as trichloroacetic acid, or sulfonic acids, such, as benzene - or p-toluensulfonate acid. The presence of an additional inert solvent is possible, but not always necessary. Acceptable inert solvents are preferably present in the body�ical, for example, carboxylic, acids such as acetic acid, eter, such as tetrahydrofuran or dioxane, amides, such, icdmp, halogenated hydrocarbons such as dichloro methane, and alcohols, such as methanol, ethanol or isopropanol, and water. Also acceptable are mixtures of the aforementioned solvents. TFA is preferably used in excess without the addition of additional solvent, Perlina acid in the form of a mixture of acetic acid and 70% perchloro acid in the ratio 9:1. Reaction temperatures for the cleavage advantageously ranges from approximately 0 to approximately 50°; it is preferred to carry out the reaction at a temperature between 15 and 30° (room temperature).

The groups BOC, OBut and Mtr can be removed, for example, preferably using TFA in dichloromethane or using approximately 3-5 N HCI in dioxane at a temperature of 15-30°, while the FMOC group can be removed using approximately 5-50% solution of dimethylamine, diethylamine or piperidine in DMF at 15-30°.

Protective groups which can be removed by experimental data showed (for example CBZ or benzyl) can be removed, for example, by treatment with hydrogen in the presence of a catalyst (e.g., catalyst based on a noble metal such as palladium, preferably on a substrate, such as driven�th coal). Acceptable solvents in this context are as mentioned above, in particular, for example, alcohols, such as methanol or ethanol or amides such as DMF. Hydrogenolysis is carried out usually at temperatures from about 0 to 100° and at pressures from about 1 to 200 bar, preferably at 20-30° and 1-10 bar. Hydrogenolysis of CBZ group, for example, is easily accomplished when using 5-10% Pd-C in methanol or using ammonium formate (instead of Hz) on Pd-C in methanol/DMF at 20-30°.

Cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie can also be obtained by cyclization of linear peptides having the same amino acid sequence as that of the desired cyclic peptide, preferably under the conditions of peptide synthesis. In this case the reaction is advantageously carried out in accordance with conventional methods of peptide synthesis as described, for example, Houben-Weyl, 1., volume 15/II, pages 1 to 806(1974).

The reaction is preferably effected in the presence of dehydrating substances, such as carbodiimide, such as DCCI or EDCI, and an additional papapostolou anhydride (see Angew. Chem. 92, 129 (1980)), diphenylphosphoryl azide or 2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline, in an inert solvent, e.g.�measures the halogenated hydrocarbon, such as dichloro methane, eter, such as tetrahydrofuran or dioxane, amide, such, icdmp or dimethylacetamide, a nitrile such as acetonitrile, or in mixtures of these solvents at temperatures from about -10° to 40°, preferably from 0 to 30°. In order to improve the intramolecular cyclization when intramolecular peptide binding, it is expedient to work in dilute solutions (principle of breeding).

Instead of a linear peptide having the same amino acid sequence as the desired cyclic peptide, acceptable reactive derivatives of these linear peptides can also be used in the reaction, for example those in which reactive groups indirectly blocked by protective groups. These linear peptides may be used, e.g., in the form of their activated esters, which are suitable, receive in situ, for example by addition of HOBt or N-hydroxysuccinimide.

The starting materials for the production of cyclic peptides are either new, commercially available, or they can be easily prepared by methods known in the art. In either case, they can preferably be obtained by known methods, for example, the above-mentioned methods of peptide SYN�ESA and removal of protective groups.

The derivatization of cyclopeptide, which essentially corresponds to the compound of formula I, la, Ib, Ic, Id and/or Ie, preferably also achieved by using methods known as such, as is known for the alkylation of amines, esterification of carboxylic acids or nucleophilic substitution at aliphatic carbon atoms, and is described in textbooks on organic chemistry e.g. J. March, Adv. Org.Chem., John Wiley & Sons, N.Y. (1985).

The basis of the cyclic peptide in accordance with the invention and, in particular, the cyclic peptide in accordance with formula I, Ia, Ib, Ic, Id and/or Ie can be converted to the corresponding salt accession acid using acid. Acceptable acids for this reaction are, in particular, that provide a physiologically acceptable salt. Thus, can be used inorganic acids, examples are sulfuric acid, nitric acid, halogenation acid, such as hydrochloric acid or Hydrobromic acid, phosphoric acid such as orthophosphoric acid, sulfamic acid, and also organic acids, in particular aliphatic, alicyclic, alifaticheskie, aromatic or heterocyclic mono - or polienovmi carboxylic, sulfonic or sulfuric acids, e.g.�p, formic acid, acetic acid, propionic acid, Pikalevo acid, ditlucan acid, malonic acid, succinic acid, timelineview acid, fumaric acid, maleic acid, lactic acid, tartaric acid, malic acid, benzoic acid, salicylic acid, 2 - or 3-phenylpropionate acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinoyl acid, methane - or econsultancy acid, etanislao acid, 2-hydroxyethanesulfonic acid, a mixture of Benzenesulfonic acid, p-toluensulfonate acid, naphthalene-mono - and-disulfonate acid, lauridsen acid. Can be used salts with physiologically acceptable acids, for example picrates for isolation and/or purification of the compounds of formula I.

Alternatively, acid cyclic peptide in accordance with the invention and, in particular, acid cyclic peptide in accordance with formula I, Ia, Ib, Ic, Id and/or Ie may traditionally become physiologically acceptable metal salts or ammonium salts by reaction with a base. Especially acceptable salts in this context are salts of sodium, potassium, magnesium, calcium and ammonium, and salts of substituted ammonium, for example, dimethyl-, diethyl - or diisopropylamino, salt monoethanol, diethanol - or triethanolamine, �Oli of cyclohexylamine, salt dicyclohexylamine, salt dibenzylethylenediamine, as well as, for example, salts with N-methyl-O-glucamine or with arginine or lysine.

Preferred cyclic peptides for all aspects in accordance with the present invention are preferably selected from the group consisting of the cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferably selected from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and especially preferred selected from the group consisting of the cyclic peptides according to formula Ic.

Preferred cyclic peptide for all aspects in accordance with the present invention is a cyclo-(AGD-Gly-s-Dh-h, and/or its salt or solvate.

Cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie have very valuable properties. In particular, they act as inhibitors of integrins, in the context of what they are preferably modulate, and in particular, preferably inhibit the interaction of receptors of β3- or β5-integrin legandary. Compounds are preferred�Stateline particularly active in the case of integrins ours, avRs and/or ACRs, but also in relation to the receptors avβ1, β6and/or β8- receptors. Such impacts can be demonstrated, for example, in accordance with the method described by J. W. Smith and others in J. Biol. Chem. 265. 12267-12271 (1990). In addition, they have anti-inflammatory effects.

The dependence of angiogenesis on the interaction between vascular integrins and extracellular matrix proteins is described by R. S. Brooks, R. A. dark and D. A. Cheresh in Science 264, 569-71 (1994).

The possibility of inhibiting this interaction is described by R. C. Brooks, A. M. Montgomery, M. Rosenfeld, R. A. Reisfeld, T.-Hu, G. Klier and D. A. Cheresh in Cell 79, 1157-64 (1994).

Pro-angiogenic activity, preferably mediated by integrins, cyclic peptides in accordance with the invention preferably results in the reduction of wrinkles of the skin, darkening the hair and/or accelerate wound healing. Preferably, when the cyclic peptides can also be used to treat dermatological conditions such as hyperkeratosis, aging skin when exposed to ultraviolet rays, burns, wounds in the donor area of the flap in the case of skin grafts, ulcers (cutaneous, pressure, as a result of venostasis and diabetic), psoriasis, skin rashes and photoreactive processes sunburn.

Induction of hair growth by modulation of the vascular endothelia�professional growth factor (VEGF) and/or receptor vascular endothelial growth factor (VEGFR) has been described in WO 2003/072049 Waugh and Dake. Because integrins interact with VEGF and/or VEGFR, cyclic peptides in accordance with the invention can preferably be used as modulators in this regard, inducing, therefore, hair growth.

Due to its described above/below the valuable properties of cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or 1E, can preferably also be used as antimicrobial agents. The effectiveness of the antimicrobial activity can be demonstrated using the method described by R. Valentin-Weigund, etc., in Infection and Immunity, 2851-2855(1988).

Thus, these compounds have the property of inhibiting the binding of natural or synthetic ligands to integrins, in particular, αvβ integrins3, αvβ5and αIIbβ3and αvβ1, αvβ6and αvβ8.

Moreover, the compounds in accordance with formula I, Ia, Ib, Ic, Id and/or Ie, the preferred α-N-alkylation or α-C-alkylation of one or more amino acids, preferably Y-amino acids, leads to metabolic stabilization and high solubility in fats. Through the restoration of possible hydrogen bonds, as N-alkyl, for example, may not be the donor of N for C=0, the ability to penetrate membranes increase�recover it, so that it becomes possible to obtain an increased ability of oral absorption; moreover, can have an increased protein binding in plasma. α-N-alkylation or α-C-alkylation of one or more amino acids, predpochtitelno-amino acid units, increases the inhibitory efficacy of compounds and increases the selectivity of inhibition against specific integrins. The selectivity can be influenced, in particular, with N-alkyl groups.

It is assumed that the profile of the favorable properties of cyclic peptides in accordance with the invention and, in particular, cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie for all applications in accordance with the invention is attributed, at least a significant portion discussed above activities modulation of integrin specified connection.

In accordance with this present invention more preferably relates to:

Compositions, preferably non-therapeutic compositions, such as described above/below, where the specified cyclic peptide is selected from the group consisting of the cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferred�Thelen, selected from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and in particular, preferably selected from the group consisting of the cyclic peptides according to formula Ic.

Compositions, preferably non-therapeutic compositions, such as described above/below, where the specified one or more cyclic peptides include cyclo-(AGD-Gl-s-Dh-h) and/or its salt or solvate.

Composition, preferably a composition for topical application, including

one or more cyclic peptides as described above/below, preferably one or more cyclic peptides selected from the group consisting of the cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferably selected from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and, in particular, preferred selected from the group consisting of the cyclic peptides according to formula I,

(ii) one or more acceptable for the skin of the carrier and, optionally,

(iii) one or more additional active compounds, which have the function of skin care, hair care and/or activity of inhibition of inflammation, preferred�a valid, which have the function of skin care and/or activity of inhibition of inflammation.

Composition, preferably a composition for topical application, including

(i) one or more cyclic peptides as described above/below,

preferably one or more cyclic peptides selected from the group consisting of the cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferably selected from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and especially preferred selected from the group consisting of the cyclic peptides according to formula Ic,

(ii) one or more acceptable for the skin of the carrier and, optionally,

(iii) one or more additional active compounds, which have the function of skin care, hair care and/or activity of inhibition of inflammation, preferably having the function of skin care and/or activity of inhibition of inflammation.

Composition, preferably a composition for topical application, including

(i) cyclo-(AGD-Gl-s-Dh-h) and/or its salt or solvate,

(ii) one or more acceptable for the skin of the carrier and, optionally,

(iii) one or more additional�individual active compounds, which have the function of skin care, hair care and/or activity of inhibition of inflammation, preferably having the function of skin care and/or activity of inhibition of inflammation.

Compositions such as described above/below, where the specified one or more cyclic peptides are contained in the compositions in amounts of from 0.00001% by weight to 10 percent by weight, preferably in amounts of from 0.001% by weight to 10 percent by weight, more preferably in an amount of from 0.1 percent by weight to 10 percent by weight, even more preferably from 0.001% by weight to 5 percent by weight and in particular from 0.1% by weight to 5 percent by weight.

Compositions comprising one or more cyclic peptides such as described above/below, and at least one additional ingredient for skin care products and at least one carrier that is acceptable for local use.

The use of one or more cyclic peptides such as described above/below, for the production of the composition, preferably non-therapeutic compositions, and in particular, preferably, the cosmetic composition or composition for local application.

The use of one or more cyclic peptides such as described above/below, for the production of compositions that JW�makes acceptable for the prevention and/or treatment of skin diseases, associated with pathological keratinisation relating to differentiation and cell proliferation, in particular for treating common acne, inflammation sebaceous gland, polymorphic acne, acne rosacea, nodular acne, nodular acne, age-related acne, acne which arises as a side effect, such as induced by solar radiation acne, acne-related medication, or professional acne, for treating other pathologies of keratinization, in particular ichthyosis, ichthyosiform States, follicular dyskeratosis (disease Darya), Palmar-plantar keratosis, leukoplakia, States, like leukoplakia, eczema (lichen) skin and mucous membranes (buccal), for the treatment of other skin diseases associated with abnormal keratinisation and have an inflammatory and/or allergic component, and in particular all forms of psoriasis relating to the skin, mucous membranes and finger-and toe nails, and psoriatic rheumatism and skin atopy, such as eczema or respiratory atopy, as well as hyperplasia of the gums.

The use of one or more cyclic peptides such as described above/below, for the care, preservation or improvement of the General condition of skin or hair.

The use of one or more cyclic peptides such as description�but above/below, to prevent or reduce skin irregularities such as deep lines, wrinkles, rough skin or skin with deep pores.

The use of one or more cyclic peptides as described in one or more of paragraphs 1 to 7, for the prevention of chronological and/or light induced ageing processes of the human skin or human hair, in particular, for the prevention of dry skin, wrinkle formation and/or pigment defects, and/or to reduce or prevent the harmful effects of UV rays on the skin.

Preferably, the cyclic peptides in accordance with the invention and compositions containing them, are mainly those which have the advantage in relation to cell regeneration. As expected, this is due to their ability to modulate, preferably to stimulate the production of certain useful biomolecules, including, but without limitation, collagen I, fibronectin, collagen IV and/or hyaluronic acid in skin cells.

Thus, cyclic peptides in accordance with the invention and compositions containing them, can preferably be used to improve the visible signs of skin aging, including fine lines, deep wrinkles, enlarged pores, roughness, dryness and other defects of the skin texture, such as banners (for�to caused by pregnancy, injury or other effects), bags under the eyes, also called "puffy eyes" and dark (under eye) circles, which was mainly caused by the thinning of the skin, insufficient blood circulation and/or weakness of the fabric, particularly when repeated local application.

Thus, additional objects in accordance with the invention preferably include:

Method and/or composition to reduce the visible signs of aging, it is preferable to reduce the visible signs of aging of the skin and/or hair of an animal, preferably a human, comprising: applying to an animal showing signs of ageing, preferably, to a portion of the skin and/or hair showing the signs of aging, the composition comprising one or more cyclic peptides, more preferably, compositions, such as described above/below, and including one or more cyclic peptides such as described above/below, at least once a day for a time period at least sufficient to reduce the visible signs of ageing, preferably, the visible signs of aging of the skin and/or hair.Period of time at least sufficient to reduce the visible signs of ageing, is usually from one day to 12 months, preferably from three days to 6 months, bol�e preferably from two weeks to two months,

Method and/or composition to reduce stretch marks of the skin, comprising: applying to the skin, preferably, at least part of the skin, showing the stretching of a composition comprising one or more cyclic peptides, more preferably, compositions, such as described above/below, and including one or more cyclic peptides such as described above/below, at least once a day during the period of time at least sufficient to reduce the visible signs of stretch marks. Period of time at least sufficient to reduce the visible signs of stretch marks, is usually from one day to 12 months, preferably, from three days to 6 months, more preferably, from two weeks to two months.

Method and/or composition to reduce stretch marks of the skin, including:

application to the skin, preferably, at least part of the skin, showing the stretching of a composition comprising one or more cyclic peptides, more preferably, compositions, such as described above/below, and including one or more cyclic peptides such as described above/below, at least once a day during the period of time at least sufficient to reduce the visible signs of stretch marks. Period of time at least sufficient to provide�to enable reduce the visible signs of stretch marks, is usually from one day to 12 months, preferably, from three days to 6 months, more preferably, from two weeks to two months.

Method and/or composition to reduce dark circles under the eyes, including;

application to the skin, preferably, at least part of the skin showing dark circles, compositions comprising one or more cyclic peptides, more preferably, compositions, such as described above/below, and including one or more cyclic peptides such as described above/below, at least once a day during the period of time at least sufficient to reduce dark circles under the eyes. Period of time at least sufficient to reduce dark circles, is usually from one day to 12 months, preferably, from three days to 6 months, more preferably, from two weeks to two months.

One aspect in accordance with the present invention relates to the use of cyclic peptides to protect the skin from the action of agents for hair treatment, in particular, to protect the scalp from pigments, coloring agents, dyes and/or colorarray agents that are commonly used for hair coloring.When processing the hair cosmetic compositions a contact composition for the treatment of heads� with downstream normal skin is not completely inevitable. Contact compositions for the treatment of head from below the skin, in particular, is unfavorable in the case of compositions for dyeing the hair, since the colouring parts of the skin around the hair strands and/or hair roots, in General, is considered unsightly and therefore undesirable.

Thus, it is desirable to protect the skin from harmful effects of the compositions for hair treatment.Is known in the field of engineering through a variety of compositions, such as emulsions, or other agents, such as petrolatum, to achieve such protection of the skin. However, the compositions and agents of the prior art exhibit only limited effectiveness and/or need to be removed after application of the composition for treatment of a head. For example, petrolatum is difficult to remove from the skin and/or hair due to its insolubility in water. For sufficient removal may be necessary to use strong detergents and/or organic solvents, which, therefore, affects the intended result of applying the composition for hair treatment and/or has a negative impact on the skin and/or hair.

In accordance with the present invention, cyclic peptides, as defined above/below, can preferably be applied to protect the skin from agents for hair treatment and I�and, to protect the scalp from the harmful effects of pigments, coloring agents, dyes and/or colorarray agents or compositions for hair coloring in General.

Thus, an additional object of the present invention lies in:

The application of one or more cyclic peptides as described above/below, to protect the skin from agents for hair treatment, in particular, to protect the scalp from pigments, coloring agents, dyes and/or colorarray agents or compositions for hair coloring in General.

The application of one or more cyclic peptides as described above/below, in the compositions to protect the skin from agents for hair treatment, in particular, to protect the scalp from pigments, coloring agents, dyes and/or colorarray agents or compositions for hair coloring in General.

The application of one or more cyclic peptides as described above/below, to obtain a preparation for protecting the skin from compositions for hair treatment, preferably, compositions that can dye, to tint, to shape, to strengthen, to maintain in a certain state, soften, restore and design the hair style, and in particular compositions that can dye or tint hair.

The application of one or more cyclic peptides t�to, as described above/below, in the compositions for the simultaneous protection of the skin from compositions for hair treatment and for skin care.

Compositions in accordance with the invention, in General, include one or more cyclic peptides, preferably one or more cyclic peptides as described in this application, and one or more solvents or carriers, preferably, one or more cosmetically acceptable solvents or carriers. One or more solvents or carriers can be independently selected from the group of hydrophobic and hydrophilic solvents or carriers. Acceptable manner hydrophobic solvents or carriers include, for example, waxy non-ionic substances, preferably waxy non-ionic substances that are commonly used in cosmetic products, including, without limitation, esters and ethera fatty alcohols and fatty acids with carbon chain length from C4 to C22, preferably from C8 to C18, and most preferably from C12 to C18. Examples of fatty hydrophobic inert substances or carriers are preferably selected from the group consisting of isopropyl myristate, isopropyl palmitate, octyl palmitate, isopropyl lanolate, acetylated lanolin alcohol, benzoate of C12-C15 alcohols, Cetearyl of octanoate, cetyl palmitate, m�ristil of myristate, myristyl lactate, cetyl acetate, propylene glycol of dicaprylate/caprate, decyl oleate, acetylated lanolin, stearyl of heptanoate, diisostearate malate, octyl of hydroxystearate, octyl of hydroxystearate, isopropyl of isostearate and similar. Examples of hydrophilic solvents or carriers, in particular, for the solutions are preferably selected from the group consisting of glycols and alkoxysilane glycols, preferably glycols and alkoxysilane glycols, which are commonly used in cosmetic products, including, but without limitation, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropyleneglycol and the like.

Compositions in accordance with the invention, in particular cosmetic compositions in accordance with the invention can be receptionby in the form of creams, lotions, serums, sprays, pencils and other shapes known to those skilled in the art. Creams and lotions currently represent the preferred form of the product.

Preferably, the concentration of peptides in a cosmetically acceptable carriers may range from 1 frequent. on billion to 10,000 frequent.per million, preferably from 10 frequent. on bn up to 1000 frequent.per million, more preferably from 100 frequent. at 100 billion to frequent.per million, and most preferably from 1 frequent. on 00 billion to frequent.on million.

Preferably, the cosmetic composition can typically include a media solution described above, at levels from about 0.01% to about 90% by weight, preferably from approximately 0.1% to approximately 50%.more preferably from about 0.1% to about 20%, and more preferably from about 1% to about 10% by weight.

Preferably, when the concentration of cyclic peptides in the composition for application, preferably for application to the skin and/or hair, may vary from 1 frequent.on billion to 10,000 frequent.per million, preferably from 10 frequent. on bn up to 1000 frequent. per million, more preferably from 100 frequent. at 100 billion to frequent. per million, even more preferably from 0.5 to frequent. at 150 billion to frequent. per million and most preferably from 1 frequent. at 100 billion to frequent. per million, for example, approximately 0.5 to frequent.on million, approximately 1 frequent. on million, approximately 1.5 frequent. on million, approximately 5 frequent. on million, approximately 10 frequent. on million, approximately 25 frequent. on million, approximately 50 frequent. on million, approximately 75 frequent. on million, approximately 100 frequent. on or about 125 million frequent. on million.

If this is acceptable then frequent.at billion and frequent.per million preferably are considered on the basis of the respective weights such as the weight of the respective components (for example, the CEC�quarter peptide, media) and/or weight of the respective component and the total weight of the composition. In accordance with this, frequent 1.per million preferably is regarded as 1 mg/kg or 10-4weight.

Compositions in accordance with the invention can optionally include additional active and inactive ingredients that are different from cyclic peptides in accordance with the invention, including, but without limitation, carriers, fillers, emulsifying agents, antioxidants, surfactants, film formers, chelating agents, gelling agents, thickeners, emollient means, wetting agents, moisturizing substances, vitamins, minerals, viscosity modifiers and/or rheological properties, sunscreen, substances that cause the loosening of the epidermis, depigmenting agents, retinoids, hormonal compounds, alpha-hydroxy acids, alpha keto acids, antimycobacterial agents, antifungal agents, antimicrobial agents, antiviral agents, analgesics, lipidic compounds, anti-allergic agents, H1 and/or H2 antihistamines, anti-inflammatory agents, agents against irritation, antitumor agents, agents for stimulating the immune system, agents for suppressing the immune system, zit agents, analgesics, antiseptics, agents DL� insect repellent connections for cooling of the skin, agents for protecting the skin, agents that promote penetration through the skin, scrubs, lubricants, flavorings, colorants, colorants, depigmenting agents, agents that reduce pigmentation, preservatives, stabilizers, pharmaceutical agents, photostabilizers agents and mixtures thereof. Furthermore, in addition to the above, products of personal hygiene in accordance with the invention may contain any other compound for the treatment of skin diseases.

The invention also provides a method for reducing and/or preventing signs of natural aging and photoaging of human skin, comprising the topical application of cosmetic compositions in accordance with the invention. Cosmetic compositions in accordance with the invention preferably are applied to the affected/damaged skin areas once or twice daily for as long as is necessary to achieve desired anti-aging results.

The present invention furthermore relates to compositions, preferably non-therapeutic compositions comprising one or more cyclic peptides according to the invention, in particular one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, and at least one additional�nitely ingredient for skin care and at least one carrier which is acceptable for topical application and for the application of the above-mentioned compounds for the care, preservation or improvement of the General condition of skin or hair.

Applications, which are preferred in accordance with the invention

(i) cyclic peptides in accordance with the invention, in particular,

cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie and/or

(ii) compositions, preferably non-therapeutic compositions,

compositions for topical application and/or cosmetic compositions comprising one or more cyclic peptides according to the invention, in particular one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, are, in particular, for such applications, with the aim of preventing aging of the skin or hair of a person induced by time and/or sunlight, in particular, for the prevention of dry skin, wrinkle formation and/or pigment defects, and/or mitigate or prevent the harmful effects of ultraviolet rays on the skin and to prevent or reduce skin irregularities, such as wrinkles, fine lines, rough skin or skin with enlarged pores.

Applications, which are preferred in accordance with the invention

(i) the CEC�quarter of peptides in accordance with the invention, in particular

cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie and/or

(ii) compositions, preferably non-therapeutic compositions, compositions for topical application and/or cosmetic compositions comprising one or more cyclic peptides according to the invention, in particular one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie,

are also such for use for the prevention and/or prevent premature aging of the skin, in particular, for prophylaxis and/or prevention induced by sunlight and/or wrinkling of skin, for reducing pigmentations and actinic keratosis, and for the prevention and/or treatment of all diseases associated with normal ageing processes of the skin, induced by time and/or sunlight, as well as for the prevention and/or treatment of skin diseases associated with abnormal keratinisation relating to differentiation and cell proliferation, in particular for treating common acne, inflammation of the sebaceous glands, polymorphic acne, acne rosacea, nodular acne, nodular acne, age-related acne, acne which arises as a side effect, such as induced by solar radiation acne, acne related to Priya�ohms drug or occupational acne, for treating other pathologies of keratinization, in particular ichthyosis, ichthyosiform States, follicular dyskeratosis (disease Darya), Palmar-plantar keratosis, leukoplakia, conditions such as leukoplakia, eczema (lichen) skin and mucous membranes (buccal) for the treatment of other skin diseases associated with abnormal keratinisation and have an inflammatory and/or allergic component, and in particular all forms of psoriasis relating to the skin, mucous membranes and finger-and toe nails, and psoriatic rheumatism and skin atopy, such as eczema or respiratory atopy, as well as hyperplasia of the gums, and for the prevention and/or treatment of benign or malignant tumors of the dermis or epidermis, which may be of viral origin, such as a simple wart, flat wart, verruciform epidermodysplasia, oral papillomatosis, papillomatosis Florida, and entities that are caused by UV radiation, in particular, basocellular epithelioma spinocellular apitheliomas.

The present invention also relates to the application of one or more cyclic peptides according to the invention, in particular one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, to obtain compositions that are acceptable�bubbled to the above-mentioned applications.

Cyclic peptides for use in accordance with the invention preferably are applied and/or receptions in the presence of surface-active or amphiphilic compounds, preferably surface-active or amphiphilic compound which is capable of forming self-organized structures, such as vesicles or capsules. Such vesicles or capsules, in General, prepared from amphiphilic compounds (compounds having both a hydrophobic part and a hydrophilic (polar) part), with such vesicles or capsules are most often derived from lipids, in particular phospholipids. When vesicles or capsules prepared from lipids or lepidoptery materials, they are most often referred to as a liposome. In addition, these lipids or Lepidoptera materials can form nanosomes and/or nano-emulsion.

Preferably, liposomes, nanosomes and/or nano-emulsion, preferably, liposomes and/or nanosomes and, in particular, liposomes can be formed in the same manner as the encapsulation material, including, for example, one or more cyclic peptides in accordance with the invention, within the liposomes, nanosomes and/or nano-emulsion. For example, these liposomes were used to encapsulate biologically active materials; for example, those�piticescu medicines. In accordance dealt invention liposomes, nanosomes and/or nano-emulsion can advantageously be used for interaction with the cyclic cepcidi, as described in this application. For example, cyclic cepcidi, as described in this application can be encapsulated or enclosed in liposomes, nanosomes and/or nano-emulsion, preferably, liposomes and/or nanosomes and, in particular, liposomes; or otherwise be associated with them.

Liposomes, nanosomes and/or nano-emulsion can be obtained from a wide variety of lipids, including phospholipids, glycol lipids, and as typical examples may be mentioned lecithin, spingomyelin, dipalmitoyl, distearoylphosphatidylcholine, and others. Amphiphilic lipids, which are used to obtain liposomes typically contain a hydrophilic group, such as phosphoryl, carbon, sulfonylurea group or amino group, and a hydrophobic group, such as saturated and unsaturated aliphatic hydrocarbons, and aliphatic hydrocarbon groups substituted by one or more aromatic or cycloaliphatic groups. However, the connection to obtain liposomes of sediment and/or nano-emulsion are generally known in the art, and no further details in this regard for a full understanding of this �of subramania Connection which form the wall when obtaining liposomes, optionally optionally include a steroid component, such as cholesterol, cholestan, and the like.

Phosphatidylcholine and purified fraction of lecithin, may advantageously be used to obtain vysokomineralizovannyh systems. Such systems preferably include nano-emulsion and/or liposomes, and preferably are able to absorb or encapsulate a large variety of active substances through their membrane lipids. With the help of their outstanding penetration characteristics of these membranes are capable of carrying these active substances quickly and effectively into the skin and/or hair. For example, this preferably leads to the fusion of lipids, preferably lipids identical to those of the skin, these nano-emulsion and/or liposomes with membrane lipids of the skin. Because the liposomal structure and nanosomal systems differs from each other, it preferably makes it possible to load different active substances in each of them. Nevertheless, the transport properties of both systems are very similar. In some cases, a thin dispersion and size can improve their function.

Liposomes:

The liposomes preferably are small, sphere-like vesicles formed ampivillin�mi lipids, comprising a hydrophilic core. They are typical carriers/carriers, which preferably include the active compound in a two-layer membrane and/or the hydrophilic core. The placement of the active agent depends on their hydrophilic properties. Because they are related to the skin, the liposomes preferably improve the penetration of active substances in a cosmetically relevant areas, such as the different layers of the epidermis and/or hair. Thus, preferably maintain the desired fixation of the active substances, for example, in the lower layers of the epidermis. The liposomes preferably exhibit favorable dispersibility inside the skin and create a depot of active substances under the stratum corneum.

Nano-emulsion:

Nano-emulsion is preferably characterized by a lipophilic core, which is separated lipid monolayer, preferably a lecithin monolayer, from the external water phase. Such nano-emulsion are preferably acceptable as carriers for lipophilic components. Similar to liposomes, they preferably support the penetration of active substances into the skin. When the penetration into the skin in this way, the bioavailability and the effectiveness of the active substances, for example, can be optimized. Can be obtained a stable emulsion with low viscosity and, thus, �which, which is able to spray, which preferably does not leave a sticky and/or oily residues on the skin. Nano-emulsion, in particular nano-emulsion-based lecithin, preferably demonstrate a great disparity in the skin and/or create a depot of the active under the stratum corneum.

The pH of liposomes, sediment and/or nano-emulsion to a large extent depends on the choice of appropriate lipids and/or other ingredients. If it is desired, the pH may be adjusted by addition of bases, acids and/or buffers. In the General case, for application in accordance with the invention, preferred is a pH value that is acceptable for the skin and/or hair.Thus, the pH value in the range from 4.5 to 8.5, preferably from 5 to 8 and in particular from 5.5 to 7.5, for example, the pH around 5.5, about 6, about 7, or about 7.5 and, in particular, about 6, is in General preferred.

Thus, the desired object in accordance with the present invention relates to a composition, preferably a liposome, nanosome and/or nanoemulsion composition, including

(i) one or more cyclic peptides as described above/below, preferably one or more cyclic peptides selected from the group consisting of cyclic�ski peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferably selected from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and in particular, preferably selected from the group consisting of the cyclic peptides according to formula Ic,

(ii) one or more lipids,

iii) one or more physiologically acceptable solvents, and, optionally.

one or more additional active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect.

Thus, the desired object in accordance with the present invention relates to a composition, preferably a liposome, nanosome and/or nanoemulsion composition, including

(i) from 0.00001 to 20% by weight, preferably from 0.0001 to 10% by weight and in particular from 0.001 to 1% by weight, of one or more cyclic peptides as described above/below, preferably one or more cyclic peptides selected from the group consisting of the cyclic peptides according to formula I, Ia, Ib, Ic, Id and/or Ie, more preferably selected from the group consisting of the cyclic peptides according to formula Ia, Ib, Ic and/or Id, even more preferably, selected� from the group consisting of the cyclic peptides according to formula Ib, Ic and/or Ie, and in particular, preferably selected from the group consisting of the cyclic peptides according to formula Ic,

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight, of one or more lipids,

(iii) from 50 to 99.999% by weight, preferably from 60 to 99.99% by weight and in particular from 70 to 99% by weight, of one or more physiologically acceptable solvents, and, optionally,

(iv) from 0.00001 to 30% by weight, preferably from 0.0001 to 20% by weight and in particular from 0.001 to 10% by weight, of one or more additional ingredients selected from the group consisting of

v) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect,and

(vi) β further cosmetically acceptable excipients.

(vii)

In this regard, one or more cyclic peptides preferably are cyclic peptides cyclo-(AGD-Gl-s-Dh-h) and/or their salt or solvate.

In this regard, one or more lipids, preferably include one or more of the following compounds:

(a) phospholipids,

(b) glycosphingolipid,

(c) lecithin,

(d) sphingomyelin,

(e) dipalmitoyl lecithin,

(f) distearoylphosphatidylcholine,

(g) phosphatidylcholine,

i) unsaturated phosphatidylcholine,

j) polystyrene,

(k) octyldodecanol, optionally in combination with silicon dioxide

(l) octyldodecanol, optionally, in combination with phospholipids,

cholesterol and/or glycosphingolipids, and their salts, preferably their alkali metal salts and/or ammonium.

In this regard, one or more lipids are, in particular, preferably selected from the group consisting of:

(c) lecithin,

(d) sphingomyelin,

(e) dipalmitoyl lecithin,

f) distearoylphosphatidylcholine,

(g) phosphatidylcholine,

(h) a saturated phosphatidylcholine,

i) unsaturated phosphatidylcholine,

j) and mixtures thereof,

and their salts, preferably their alkali metal salts and/or ammonium.

In this regard, one or more physiologically acceptable solvents are, in particular, preferably selected from the group consisting of:

(a) water,

(b) alcohols, diols or polyols having a low carbon number, and ethera, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol of monoethyl or monobutyl of ATERA, propylene glycol monomethyl, monoethyl or monobutyl of ater, of diethylene glycol monomethyl or monoethyl of ATERA and similar products

c) alcohols containing from 2 to 6 and in particular 2 carbon atoms,�reamer, ethanol, isopropanol, 1,2-PROPANEDIOL or glycerol, preferably, ethanol or isopropanol, and/or

(d) alcohol (ethanol), glycerin, propylene glycol (1,2-propylene glycol), butyleneglycol (1,4-butanediol), pestilences, pestilences in combination with ethanol, sorbitol, preferably, ethanol, glycerol, 1,2-propylene glycol, 1,4-butanediol, pestilences, sorbitol and mixtures thereof, more preferably ethanol and pestilences and mixtures thereof, and, in particular, ethanol.

In this regard, one or more physiologically acceptable solvent preferably comprises water, preferably in amounts in the range from 10 to 99.9% by weight, more preferably from 20 to 99% by weight, even more preferably from 30 to 95% by weight, even more preferably from 50 to 90% by weight and in particular from 60 to 80% by weight, for example, approximately 65% by weight, about 70% by weight, about 75% by weight, about 80% by weight, or about 85% by weight, based on the total weight of the specified composition.

In this regard, one or more physiologically acceptable solvents preferably include an alcohol, preferably an alcohol containing from 2 to 5 carbon atoms, more preferably selected from ethanol, isopropanol, glycerol, 1,2-propylene glycol, 1,4-butanediol, pestilences, sorbitol and mixtures thereof, more preferred�about, ethanol and pestilences and mixtures thereof, and, in particular, ethanol, preferably in an amount in the range from 0.1 to 50% by weight, more preferably from 1 to 40% by weight, even more preferably from 5 to 30% by weight, even more preferably from 10 to 25% by weight and in particular from 15 to 20% by weight, for example, approximately 8% by weight to approximately 12% by weight, about 15% by weight, about 17% by weight or about 20% by weight, based on the total weight of the specified composition. Said alcohols, preferably in the amounts indicated, preferably have a preserving influence on the composition. Such inclusion, preferably in the above amounts, can help to avoid or reduce the addition of preservatives, as described in this application, to the said composition.

In this regard, additional active compounds having the action of skin care, hair care and/or inhibition of inflammation (a) preferably include ectoin, preferably in amounts in the range from 0.1 to 30% by weight, more preferably from 1 to 20% by weight, even more preferably from 3 to 15% by weight and in particular about 5% by weight, about 8% by weight, about 10% by weight or approximately 12% by weight, based on the total weight of the specified composition.

In this regard, additional cosmetically n�ielemia fillers (?) include connections, which are the preservatives. Examples of such compounds that are acceptable for use in compositions in accordance with the invention, are one or more compounds, preferably selected from the group which consists of:

a), Phenoxyethanol, methylparaben, ethylparaben, propylparaben and/or butylparaben and combinations thereof;

(b) alcohol, Phenoxyethanol, methylparaben, butylparaben,

ethylparaben, isopropylparaben, propyl paraben, and combinations thereof;

(c) chlorphenesin;

a) benzoic acid

(e) digitoxose acid, benzoic acid and/or Phenoxyethanol, and combinations thereof.

If additional cosmetically acceptable excipients ((5) include compounds that are considered preservatives, preferably preservatives, which are described above, they preferably contain in their number that are in the range of from 0.01 to 5% by weight, more preferably from 0.05 to 3% by weight, even more preferably from 0.1 to 2% by weight and in particular from 0.2 to 1.5% by weight.

Thus, the compositions described in this application, in particular, the composition containing a lipid, described in this application, does not necessarily include, preferably based on the total weight of the composition, one or more compounds selected from the group which consists of:

f) Phenoxyethanol, methyl�of arabena, ethylparaben, propylparaben and/or

butylparaben and combinations thereof;

(g) alcohol, Phenoxyethanol, methylparaben, butylparaben,

ethylparaben, isopropylparaben, propyl paraben, and combinations thereof;

(h) chlorphenesin;

(i) benzoic acid,

digitoxose acid, benzoic acid and/or Phenoxyethanol, and combinations thereof, preferably in a total quantity in the range of from 0.01 to 5% by weight, more preferably from 0.05 to 3% by weight, even more preferably from 0.1 to 2% by weight and in particular from 0.2 to 1.5% by weight.

Thus, the desired object in accordance with the present invention relates to a composition, preferably a liposome, nanosome and/or nanoemulsion composition comprising (i) from 0.00001 to 20% by weight, preferably from 0.0001 to 10% by weight and in particular from 0.001 to 1% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or its salt or solvate,

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight, of one or more lipids selected from the group consisting of lecithin, sphingomyelin, dipalmitoyl of lecithin, distearoylphosphatidylcholine, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine, and in particular, from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof with�her,

(iii) from 50 to 99.999% by weight, preferably from 60 to 99.99% by weight and in particular from 70 to 99% by weight, of one or more physiologically acceptable solvents, preferably selected from water and, optionally,

(iv) from 0.00001 to 30% by weight, preferably from 0.0001 to 20% by weight and in particular from 0.001 to 10% by weight, of one or more additional ingredients selected from the group consisting of

v) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect, and

(vi) β) further cosmetically acceptable excipients.

Preferably, in the composition described above and/or below, more preferably a liposome, nanosome and/or nanoemulsion composition as described above and/or below, and, in particular, liposome, nanosome composition as described above and/or below at least a portion of one or more cyclic peptides is enclosed in a liposome, nanosome and/or nanoemulsion particles, more preferably, liposomes and/or nanosomes, and, in particular, liposome, which are formed by using one or more of the lipids contained in said composition. Typically, a portion of one or more cyclic peptides, prisoners in these liposome, nanosome and/or nanoemulsion particles, �predpochtitelno is in the range from 1% to 99.99%, more preferably from 10% to 99.9%, even more preferably from 20% to 99% and in particular from 50% to 95% based on the total number of said one or more cyclic peptides contained in said composition.

In liposomal compositions, as described in this application, the particle size of liposomes is preferably in the range from 1 to 1000 nanometers (nm), more preferably from 5 to 500 nm, even more preferably from 10 to 400 nm and in particular in the range from 50 to 200 nm.

In liposomal compositions, as described in this application, the average particle size, preferably the average particle size D50 and/or D90, liposomes preferably lies in the range from 1 to 1000 nanometers (nm), more preferably from 5 to 500 nm, even more preferably from 10 to 400 nm and in particular in the range from 50 to 200 nm.

In liposomal compositions, as described in this application, the average particle size is in particular preferably 90 nm+/- 80 nm and even more preferably 70 nm +/- 50 nm, preferably as determined by using photon correlation spectroscopy(RGD), preferably at an angle of 90°, and preferably with the use of helium-neon laser.

Preferably, the particle size and/or mean particle size is preferably determined at room temperature (20°C).

i) from 0.001 to 10% by weight, preferably from 0.001 to 5% by weight and in particular from 0.005 to 1% by weight, e.g., about 0.005% or less by weight, about 0.01% per cent, by weight, of about 0.05% by weight or about 0.5% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or its salt or solvate,

ii) from 0.1 to 20% by weight, preferably from 1 to 15% by weight and in particular from 2 to 10% by weight, e.g. about 3% by weight, approximately 5% by weight, about 7% by weight or about 10% by weight of one or more lipids selected from the group consisting of lecithin, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts, and in particular from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts,

(iii) from 50 to 95% by weight, preferably from 60 to 90% by weight and in particular from 70 to 85% by weight of water,

iv) from 0 to 40% by weight, preferably from 5 to 30% by weight and in particular from 10 to 20% by weight, of one or more physiologically acceptable solvents, other than water, preferably selected from alcohols having from 2 to 4 carbon atoms, and more preferably selected from ethanol and isopropanol,

v) from 0 to 25% by weight, preferably from 1 to 15% by weight and in particular from 2 to 10% by weight of ectoine and/or its salts and, optionally,

vi) from 0 to 25% by weight, preferably from 0.1 to 15% by weight and in particular from 0.5 to 10% by weight of one or more additional ingredients selected from the group consisting of

(vii) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect than ectoine, and

(viii) β) further cosmetically acceptable excipients.

Thus, a particularly preferred object of the present invention relates to a composition, preferably a liposome, nanosome and/or nanoemulsion and, in particular, to a liposome or liposomal composition, comprising or essentially consisting of

i) from 0.001 to 0.1% by weight, preferably from 0.005 to 0.05% by weight and, in particular, about 0.01% by weight of cyclo-( AGD-Gl-s-Dh-h) and/or its salt or solvate,

ii) 1 to 10% by weight, preferably from 3 to 8% by weight and in particular about 5% by weight of one or more lipids selected from the group consisting of lecithin, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts, and in particular from the group consisting�her from phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts,

iii) from 5 to 25% by weight, preferably from 10 to 20% by weight and, in particular, about 15, about 17, or about 20% by weight of one or more physiologically acceptable solvents, other than water, selected from ethanol and isopropanol,

iv) from 0 to 10% by weight, preferably from 0.5 to 10% by weight and in particular 0 or approximately 5% by weight of ectoine and/or its salts, preferably ectoin, and, optionally,

v) from 0 to 10% by weight, preferably from 0.1 to 5% by weight and in particular from 0.5 to 5% by weight of one or more additional ingredients selected from the group consisting of

(vi) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect than ectoine, and

(vii) β) further cosmetically acceptable excipients, more preferably cosmetically acceptable excipients as described in this application, preservatives, preferably preservatives, as described in this application, and acids, bases or buffers, preferably, acids, bases or buffers, as described in this application.

Thus, a particularly preferred object of the present invention relates to compositions, preferably if�osanai, nanosomes and/or nanoemulsions and, in particular, liposome or liposomal composition, comprising or essentially consisting of

(i) about 0.01% by weight of cyclo-( AGD-Gl-s-Dh-h) and/or its salt or solvate, preferably cyclo-( AGD-Gl-s-Dh-h),

(ii) about 5% by weight, of one or more lipids selected from the group consisting of lecithin, phosphatidylcholine, saturated phosphatidylcholine and, in particular, from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof,

(iii) from 15 to 20% by weight and, in particular, about 17% by weight of ethanol and/or isopropanol,

iv) 5 to 10% by weight to approximately 5% by weight of ectoine and/or its salts, preferably ectoin,

v) optionally from 0 to 10% by weight, preferably from 0.1 to 5% by weight and in particular from 0.5 to 5% by weight of one or more additional ingredients selected from the group consisting of

(vi) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect than ectoine, and

(vii) β) further cosmetically acceptable excipients, more preferably cosmetically acceptable excipients as described in this application, preservatives, preferably preservatives, as described� the application and acids, bases or buffers, preferably, acids, bases or buffers, as described in this application,

viii) and water to 100% by weight of the total weight of the composition.

Thus, a particularly preferred object of the present invention relates to a composition, preferably a liposome, nanosome and/or nanoemulsion and, in particular, liposome or liposomal composition, essentially consisting of

(i) about 0.01% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or its salt or solvate, preferably cyclo-(AGD-Gl-s-Dh-h),

(ii) about 5% by weight of one or more lipids selected from the group consisting of lecithin, phosphatidylcholine, saturated phosphatidylcholine and, in particular, from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof,

(iii) from 15 to 20% by weight and, in particular, about 17% by weight of ethanol and/or isopropanol, preferably ethanol,

iv) optionally from 0 to 10% by weight, preferably from 0.1 to 5% by weight and in particular from 0.5 to 5% by weight, of one or more additional ingredients, other than ectoine selected from the group consisting of

v) α) further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect than ectoine, and

vii) and water to 100% by weight of the total weight of the composition.

Liposomes, nanosomes and/or nano-emulsion can be obtained by using procedures that are typically available in the prior art. For example, compositions in accordance with the invention can be obtained in accordance with any of the methods for obtaining liposomal suspensions, which are known to a qualified specialist in the art, for example, such as from the book "Liposomes - a practical approach" published by R. S. New (Oxford University Press, 1990). Such compositions in accordance with the invention that contain alcohol, can, for example, be obtained by dissolving the phospholipids in alcohol, then adding other soluble in alcohol active ingredients and mixing them until dissolved. The obtained lipid solution was added slowly to water in which were dissolved any other active substance, and then the mixture was stirred.Liposomes, which are formed spontaneously, and then reduced in size using an energy source, for example, �UTEM mixing at high speed, filtration high pressure, ultrasound, extrusion or homogenization, to obtain the desired particle size. If you are using the oxygen-sensitive phospholipids, the receiving process may be carried out partly or completely under protective gas or under reduced pressure.

Liposomes can be alternatively obtained using the methods of back-phase evaporation, where the compound or compounds used to produce liposomes, first dissolved in the organic phase, followed by the addition of the aqueous phase and the formation of a homogeneous emulsion. After formation of the emulsion, the organic solvent is evaporated with the formation of gel-like material, and the gel can be turned into a liposome by mixing and dispersion in an aqueous medium, such as water, a mixture of water/alcohol and/or buffer solutions. Additional procedures to obtain liposomes are described, for example, in U.S. patent No. 4,241,046; U.S. patent No. 4,342,826 and international publication PCTWO 80-01515, the disclosure of which is introduced into this application by reference in its entirety.

If the material is encapsulated in a liposome, such material may be encapsulated in the liposome by including material in the aqueous solution, which forms a liposome. Alternatively, the material �can be encapsulated into preformed empty liposomes (without encapsulated material) using the procedure described in the patent application U.S. serial number 659,200, filed September 13, 1984, the disclosure of which is introduced into this application by reference in its entirety.

Liposomes can also be obtained by using the procedure disclosed in U.S. patent No. 4,522,803, the disclosure of which is introduced into this application by reference in its entirety.

The material that is included or encapsulated inside liposomes (material is located within the water compartment or in a membrane bilayer liposomes), may represent any of a wide variety of materials, including cyclic peptides, as described in this application, and/or ectoin, as well as dyes of various cosmetic and/or therapeutic agents; and the like. Liposomes containing material enclosed in them, are in General known in the art. Additional description of such liposomes is not necessary for a complete understanding of the present invention.

Thus, a particularly preferred object in accordance with the invention, mainly comprising the preferred compositions and their application is given below:

Composition comprising

(i) from 0.0001 to 20% by weight, preferably from 0.001 to 10% by weight and in particular from 0.01 to 1% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h),

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight of one or more lipids.

Composition comprising

(i) from 0.0001 to 20% by weight, preferably from 0.001 to 10% by weight and in particular from 0.01 to 1% by weight of cyclo-(AGD-G1-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h),

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight of one or more lipids, and

(iii) from 30 to 99,9989% by weight, preferably from 40 to 99.9% by weight, more preferably from 50 to 98% by weight, even more preferably from 60 to 95% by weight and in particular from 70 to 90% by weight of water.

Composition comprising

(i) from 0.0001 to 20% by weight, preferably from 0.001 to 10% by weight and in particular from 0.01 to 1% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h),

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight of one or more lipids, and

iii) from 10 to 99,9989% by weight, preferably from 40 to 99.9% by weight, more preferably from 50 to 98% by weight, even more preferably from 60 to 95% by weight and in particular from 70 to 90% by weight of water,

iv) from 0.001 to 20% by weight, preferably from 0.01 to 15% by weight, more preferably from 0.1 to 10% by weight, even more preferably from 1 to 10% by weight and in particular from 2 to 5% by weight, p� least one additional ingredient, preferably selected from ectoin, Biotin, taurine, caffeine, taurine, purine and/or their derivatives.

In the compositions provided above and/or below, the lipid is preferably selected from the group consisting of lecithin, sphingomyelin, dipalmitoyl of lecithin, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine, more preferably selected from lecithin, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine, and in particular, from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine.

Composition comprising

(i) from 0001 to 20% by weight, preferably from 0.001 to 10% by weight and in particular from 0.01 to 1% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h),

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight of one or more lipids selected from the group consisting of lecithin, sphingomyelin, dipalmitoyl of lecithin, distearoylphosphatidylcholine, phosphatidylcholine, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine, more preferably selected from lecithin, phosphatidylcholine, saturated phosphatidyl�oline and unsaturated phosphatidylcholine, more preferably selected from lecithin, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine, and in particular, from the group consisting of phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts, and

(iii) from 30 to 99,9989% by weight, preferably from 40 to 99.9% by weight, more preferably from 50 to 98% by weight, even more preferably from 60 to 95% by weight and in particular from 70 to 90% by weight of water.

In the above and/or below the one or more compositions of lipids preferably form liposomes, nanosomes and/or nano-emulsion, preferably liposomes. More preferably, at least 20%, more preferably at least 50% and particularly at least 70%, but typically 100% or less 95% or less, or 85% or less of one or more lipids, based on the total amount of one or more lipids, which are present in said composition are present in the form of liposomes.

In the above and/or below the tracks, at least a portion of cyclo-(AGD-Gl-s-Dh-h) and/or its salts is in these liposomes, nanosomes and/or nano-emulsion, preferably liposomes. Preferably, at least 5%, more preferably at least 10%, even more preferably at least 25%, even more preferably, at least 50% and in particular at least 75% of cyclo-(AGD-u-Asp-DPhe-Acha), and/or its salts is in these liposomes, nanosomes and/or nano-emulsion, preferably liposomes, based on the total amount of cyclo-(AGD-u-Ar-Ers ASPA) and/or its salts, contained in these compositions, the amount is preferably determined at room temperature (20°C).

Preferably, when the amount of cyclo-(AGD-Gl-s-Dh-h) and/or its salts, enclosed in the liposomes, nanosomes and/or nano-emulsion, is preferably not less than 25%, more preferably not less than 50%, even more preferably, not less than 75% and particularly not less than 95%, based on the total amount of cyclo-(AGD-Gl-s-Dh-h) and/or its salts, contained in these compositions, the amount is preferably determined at room temperature (20°C).

Thus, the amount of cyclo-(AGD-Gl-s-Dh-h) and/or its salts, enclosed in the liposomes, nanosomes and/or nano-emulsion,

preferably is in the range from 25 to 100%, more preferably in the range of from 50 to 99.9%, even more preferably in the range of from 60 to 99% and in particular in the range from 70 to 95%, based on the total amount of cyclo-(AGD-Gl-s-Dh-h) and/or its salts, contained in these compositions, the amount is preferably determined at room temp�the temperature (20°C).

Thus, a further preferred feature according to the present invention is a liposomal composition, comprising

(i) from 0.0001 to 20% by weight, preferably from 0.001 to 10% by weight and in particular from 0.01 to 1% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h),

ii) from 0.001 to 50% by weight, preferably from 0.01 to 20% by weight and in particular from 0.01 to 10% by weight of one or more lipids selected from the group consisting of lecithin, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof; and salts,and

(iii) from 30 to 99,9989% by weight, preferably from 40 to 99.9% by weight, more preferably from 50 to 98% by weight, even more preferably from 60 to 95% by weight and in particular from 70 to 90% by weight of water.

(iv) preferably where

v) α) at least 20% of one or more lipids on the basis

the total number of one or more lipids, which are present in said composition are present in the form of liposomes, and

(vi) β) at least 20% of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h), based on the total amount of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof, preferably cyclo-(AGD-Gl-s-Dh-h) present in said composition is enclosed in the liposome.

Composition comprising

(i) from 0.0001 to 20% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof,

ii) from 0.001 to 50% by weight of one or more lipids,

iii) from 10 to 99,9979% by weight of water, and

iv) from 0.001 to 20% by weight of at least one additional ingredient selected from the group consisting of ectoin, Biotin, taurine, caffeine, taurine, purine and/or their derivatives.

v)

In compositions in accordance with the invention as described above and/or below one or more lipids are preferably selected from the group consisting of lecithin, sphingomyelin, dipalmitoyl lecithin. distearoylphosphatidylcholine, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and mixtures thereof and salts.

The object of the present invention is a composition comprising

(i) one or more cyclic peptides as described in this application,

(ii) one or more lipids,

iii) one or more physiologically acceptable solvents, and

optionally iv) one or more further active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect.

<> v)

The above composition can preferably be used as the composition for local use, cosmetic compositions, pharmaceutical compositions and/or medical products, preferably as compositions for topical use, a cosmetic or pharmaceutical compositions, in particular as composition for topical application or cosmetic composition.

Alternatively, they may preferably be applied in the form of supplements, active ingredient and/or active ingredients in compositions for topical application, cosmetic compositions, pharmaceutical compositions and/or medical products, preferably in the composition for local use, a cosmetic or pharmaceutical composition, and, in particular, in the composition for local application or cosmetic composition, preferably a traditional composition for topical application, cosmetic compositions, pharmaceutical compositions and/or medical products, preferably of the composition for local use, a cosmetic or pharmaceutical composition, and, in particular, compositions for local application or cosmetic composition.

In accordance with another preferred object of the present invention is a use of the composition as described above and, in �astnosti, liposome composition as described above, to produce one or more compositions selected from the group consisting of compositions for topical application, as described in this application, external compositions, cosmetic compositions, pharmaceutical compositions and medical products, preferably selected from the group consisting of the outer, cosmetic or pharmaceutical compositions and, in particular, preferably chosen from the exterior or cosmetic compositions. For example, the compositions as described above and, in particular, the liposome composition as described above, may advantageously be added as an additional Supplement or ingredient to existing or other typical or traditional compositions, preferably selected from external compositions, cosmetic compositions, pharmaceutical compositions and medical products, preferably the outer, cosmetic or pharmaceutical compositions and, in particular, the outer or cosmetic compositions. In the specified application of the composition in accordance with the invention as described above and below, preferably used in that production in the amount of from 0.0001 to 50% by weight, preferably from 0.001 to 40% by weight, more preferably from 0.01 to 30% by weight, even more preferably from 0.5 to 20% by weight and, in cha�particularly, from 2 to 10% by weight, based on the total weight of the external composition, cosmetic composition, pharmaceutical composition and/or medical product.

Thus, another preferred feature according to the present invention is a composition for topical application, as described in this application, the outer composition, cosmetic composition, pharmaceutical composition, medical product, comprising from 0.0001 to 50% by weight, preferably from 0.001 to 40% by weight, more preferably from 0.01 to 30% by weight, even more preferably from 0.5 to 20% by weight and in particular from 2 to 10% by weight of the composition in accordance with the invention, as described above and/or below, based on the total weight of the specified outer compositions, cosmetic compositions, pharmaceutical compositions and/or medical product.

The method of producing a composition for topical application, as described in this application,

including

(a) providing the composition in accordance with one or more of the paragraphs 18-21,

(b) providing one or more carriers acceptable for external use, and, optionally,

(c) providing one or more additional active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect,

d) and connection, smeshivaniem/or homogenization (a) and (b), and optionally C), in any order.

Methods and devices for connecting, mixing and/or homogenizing a) and (b) and optionally C) are known in the field of technology and described in this application. Made additional reference to the methods and devices described in the Examples.

The object of the present invention is also a composition for topical application, which is available or which is preferably obtained in the manner described above.

The object of the present invention is also a composition for topical application, as described in this application, characterized in that it contains from 0.0001 to 50% by weight, based on the total weight of the specified composition for topical application of the cyclic peptide, containing the lipid composition, as described above, and more preferably a composition

including

(i) from 0.0001 to 20% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or salts thereof,

ii) from 0.001 to 50% by weight of one or more lipids;

and, in particular, the composition including

(i) from 0.0001 to 20% by weight of cyclo-(AGD-Gl-s-Dh-h) and/or its

salt,

ii) from 0.001 to 50% by weight of one or more lipids, and

iii) from 10 to 99,9979% by weight water and, optionally,

iv) from 0.001 to 20% by weight of at least one additional ingredient, preferably selected from the group comprising�th of ectoine, Biotin, taurine, caffeine, taurine, purine and/or their derivatives.

Especially preferred in this regard is the use of described above and/or below the compositions in accordance with the invention for the prevention induced by time and/or sunlight, the ageing process of human skin or human hair, in particular, for the prevention of dry skin, wrinkle formation and/or pigment defects, and/or to mitigate or prevent the harmful effects of UV rays on the skin.

Especially preferred in this regard is the use of compositions in accordance with the invention as described above and/or below, (a) as compositions for hair care, skin care, hair growth, anti-aging compositions and/or anti-wrinkle; and/or

(b) as an ingredient or the active agent compositions for hair care, skin care, hair growth, anti-aging compositions and/or anti-wrinkle, preferably traditional compositions for hair care, skin care, hair growth, anti-aging compositions and/or anti-wrinkle.

Another object in accordance with the invention is a medical product, comprising one or more cyclic peptides as described above and/or below, and, in particular comprising from 0.0001 to 50% by weight, preferably from 0.001 to 40% by weight, bol�e is preferably from 0.01 to 30% by weight, even more preferably from 0.5 to 20% by weight and in particular from 2 to 10% by weight, the composition in accordance with the invention as described above and/or below, based on the total weight of the specified medical product, and one or more carriers and/or excipients.

The compositions of this application are preferably non-therapeutic, or more preferably compositions that can be used topically, for example cosmetic or dermatological compositions or food products or food additives. In this case, the compositions include kosmetologicheskii or dermatologically acceptable or suitable for food media and, depending on the desired profile of properties, optionally, additional acceptable ingredients.

Application in accordance with the invention, cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, in the compositions provides, inter alia, protection against damage caused directly or indirectly by UV radiation or processes caused by reactive compounds, such as, for example, skin ageing, loss of skin moisture, loss of skin elasticity, formation of wrinkles or facial wrinkles or pigment defects or age spots.

The present invention also relates to the use of the above-mentioned compositions to prevent unwanted changes in the painting of the skin, such as, for example, acne or oily skin, keratosis, light-sensitive, inflammatory, erythematous, allergic or autoimmunization reaction.

However, the compounds and compositions in accordance with the invention preferably also serve for soothing effects on sensitive and irritated skin, for the preventative regulation of collagen, hyaluronic acid and elastin synthesis, stimulation of DNA synthesis, in particular, in the case of scarce and hypoactive skin conditions, regulation of transcription and translation of enzymes which degrade the matrix, in particular, MMP, increase cell regeneration and skin regeneration, improve skin protective and restorative mechanisms for DNA, lipids and/or proteins,

In addition, compounds which are preferred in accordance with the invention, have the advantage of introducing into the composition:

- mono - and/or oligoglycosides radicals improve the water solubility of the compounds used in accordance with the invention;

is unbranched or branched C1- - C20-alkoxy group, in particular, long-chain alkoxygroup, such as group ethylhexyloxy, comfort�Ute solubility in oil connections;

that is, the hydrophilicity or lipophilicity of the compounds in accordance with the invention can be enhanced with reasonable choice of components.

Glycosidic radicals, which may be used, in particular, represent a mono - or oligosaccharide chains radicals. Preference is given to radicals hexosyl, in particular, radicals rhamnosyl and radicals glucosyl. However, there may also advantageously be used other radicals hexosyl, for example, Alusil, ultrasil, galactosyl, gulail, icosyl, mannosyl and talloil. It may be preferable to use the radical Pancasila. Radicals of glycosyl can contact the principal structure with α - or β-glycosidic bonds. Preferred is a disaccharide, such as, 6-0-(6-deoxy-α-L-mannopyranosyl)-R-0-glucopyranoside.

However, the preferred embodiment in accordance with the invention, the compositions in accordance with the invention can also include cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, which are sparingly soluble or insoluble in the matrix composition. In this case, the compound is preferably dispersed in finely divided form cosmetic compositions.

Cyclic peptides in accordance with ISO�the acquisition, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, are typically used in accordance with the invention in quantities from 0.01 to 20% by weight, preferably in quantities of from 0.1% by weight to 10% by weight and especially preferably in amounts of from 1 to 8% by weight. Specialist in the art will not be absolutely no difficulty to choose the number depending on the intended action of the composition.

Protective action against oxidative stress or against the free radicals can, thus, be further improved if the compositions comprise one or more additional antioxidants, with a qualified specialist in the art will not be absolutely no difficulty to choose antioxidants, which have acceptable or quick stitched in time action. In a preferred embodiment according to the present invention, at least one additional ingredient for skin care represents one or more of the main and/or vitamins.

For reasons mentioned above is particularly preferred in this application, when the composition does not include any derivative of retinol.

There are many proven substances known from the specialist literature, which m�may be used as the main, for example, amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazolov (e.g. wroclawiu acid) and derivatives thereof, peptides, such as D. L-carnosine, D-carnosine, L-carnosine and derivatives thereof (for example, anserine), carotenoids, carotenes (for example, α-carotene, β-carotene, lycopene) and their derivatives, Karaganov acid and its derivatives, lipoic acid and its derivatives (for example, dihydrolipoic acid), aurothioglucose, p. and other thiols (for example, thioredoxin, glutathione, cysteine, cystine, cystamine and the glycoside, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, Palmitoyl, oleyl, gamma linoleic, cholesterol and their esters of glycerol) and their salts dilauryl thiodipropionate, DISTEARYL thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethera, peptides, lipids, nucleotides, nucleosides and salts), and connections sulfoximine (e.g. buthionine sulfoximine, homocysteine, sulfoximine, buthionine sulfones, Penta-, hexa - and heptatonic sulfoximine) in very low tolerated doses (for example, from Pola to µm/kg), furthermore (metal) chelating agents (e.g. a-hydroxyzine acid, palmitic acid, phytic acid, lactoferrin), a-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, extras�CT ox bile, bilirubin, biliverdin, EDTA, EGT and their derivatives, unsaturated fatty acids and their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbicacid),Tocopherols and derivatives (for example, acetate vitamin E), and conferimento benzoic resin, retinabuy acid and their derivatives, a-glucosylrutin, Frolovo acid, furfurylalcohol, carnosine, butyl hydroxytoluene, trouble soothing, nordihydroguaiaretic acid, trihydroxyacetophenone, quercetin, uric acid and derivatives thereof, mannose and derivatives, zinc and its derivatives (e.g. ZnO, ZnSO4), selenium and its derivatives (e.g. Selenomethionine), stilbene and their derivatives (e.g. stilbene oxide, oxide TRANS-stilbene).

Acceptable main are further described in WO 2006/111233 and WO 2006/111234.

Acceptable main are also compounds of the General formula A and/or b

where

R1is selected from the group consisting of-C(O)CH3, -CO2R3, -C(O)NH2and-C(O)N(R4)2,

X is O or NH,

R2represents a linear or branched alkyl containing from 1 to 30 C-atoms,

R3represents a linear or branched alkyl having from 1 to 20 C-atoms,

R4is�tsya in each case independently selected from the group consisting of H and linear or branched alkyl having 1 to 8 C-atoms,

R5is selected from the group consisting of linear or

branched alkyl having 1 to 8 C-atoms, and linear or branched alkoxy having 1 to 8 C-atoms, and

R6is selected from the group consisting of linear or branched alkyl containing from 1 to 8 C-atoms, preferably selected from derivatives of 2-(4-hydroxy-3,5-dimethoxybenzamide)malonic acid and/or 2-(4-hydroxy-3,5-dimethoxybenzyl)malonic acid, and in particular, preferably selected from bis(2-ethylhexyl)ester of 2-(4-hydroxy-3,5-dimethoxybenzamide)malonic acid (for example, Oxynex® ST liquid) and/or bis(2-ethylhexyl)ester of 2-(4-hydroxy-3,5-dimethoxybenzyl)malonic acid (for example RonaCare® AP).

A mixture of main are also acceptable for use in cosmetic compositions in accordance with the invention. Known and commercial mixtures are, for example, mixtures comprising as active ingredients, lecithin, 1--(+)-ascorbyl palmitate and citric acid (for example, Oxynex® AP), natural Tocopherols, 1--(+)-ascorbyl palmitate, 1--(+)-ascorbic acid and citric acid (for example, Oxynex® K LIQUID), tocopherole extracts from natural sources, 1_-(+)-ascorbyl Palmi�at, 1_-(+)-ascorbic acid and citric acid (for example, Oxynex® L LIQUID), DL-a-tocopherol, L-(+)-ascorbyl palmitate, citric acid and lecithin (for example, Oxynex® LM) or butyl guide toxicoloy (BHT), L-(+)-acKop6nn palmitate and citric acid (for example, Oxynex® 2004). The main of this type can be used with cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, in the compositions in proportions in the range from 1000:1 to 1:1000, preferably in amounts of from 100:1 to 1:100.

Compositions in accordance with the invention may include vitamins as further ingredients. Cosmetic compositions in accordance with the invention preferably include vitamins and derivatives of vitamins selected from vitamin b, diningarea, hydrochloride (vitamin B1), Riboflavin (vitamin b2), nicotinamide, vitamin C (ascorbic acid), vitamin D, ergocalciferol (vitamin D2), vitamin E, DL-α-tocopherol, tocopherol E acetate, tocopherol of hydrosylate, vitamin K1esculin (the active ingredient of vitamin e), thiamine (vitamin B1), nicotinic acid (Niacin), pyridoxine, pyridoxal, pyridoxamine (vitamin B6), Pantothenic acid, Biotin, folic acid and cobalamin (vitamin B12), persons�DNAs preferably vitamin C and its derivatives, DL-α-tocopherol, tocopherol E acetate, nicotinic acid, Pantothenic acid and Biotin. Vitamins are commonly used in this application with cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, in proportions in the range from 1000:1 to 1:1000, preferably in amounts of from 100:1 to 1:100.

Phenols with antioxidant effects, some of which are existing in nature, are of particular interest for applications in pharmaceutical, cosmetic or food sector. For example, flavonoids or bioflavonoids, which in principle are known as vegetable dyes and often possess antioxidant potential. Publication K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, I. M. C. M. Rietjens; Current Topics in Biophysics 2000, 24 (2), 101-108, is associated with effects of the model of substitution of mono - and dihydroxyflavone. In this regard, it was observed that dihydroxyflavone, IT contains a group which is adjacent to geography or HE groups in 3',4'- or 6,7 - or 7,8-position have antioxidative properties, while mono - and dihydroxyflavone in some cases do not reveal antioxidant properties.

Quercetin (cyanidanol, cyanidanol 1522, meletin, Coporation, ericin, 3,3',4',5,7-integer�Keflavik) is often mentioned as a particularly effective antioxidant (for example, C. A. Rice-Evans, N. J. Miller, G. Paganga, Trends in Plant Science 1997, 2(4), 152-159). K. Lemanska, H. Szymusiak, B. Tyrakowska, R. Zielinski, A. E. M. F. Soffers, I. M. C. M. Rietjens; Free Radical Biology &Medicine 2001, 31 (7), 869-881, has been studied pH-dependent antioxidant activity of hydroxyflavones. Quercetin shows the highest activity among the studied structures within the entire pH range.

Acceptable main also are compounds of the formula II

where R1-R10may be identical or different and are selected

from

N

- OR11

is unbranched or branched C1- - C20-alkyl groups,

is unbranched or branched C3- - C20-alkenyl groups,

is unbranched or branched C1- - C20-hydroxyalkyl

groups, where the hydroxyl group may be associated with primary or

secondary carbon atom of the chain and the alkyl chain may

be interrupted by oxygen, and/or

- C3- - C10-cycloalkyl groups and/or C3- -C12-cycloalkenyl groups, where each of the rings may also be associated with -(CH2)n-groups, where n=1-3,

- where all OR11independently from each other represent

"HE

is unbranched or branched C1- - C20-alkoxylic one group,

is unbranched or branched Ci - So-hydroxyalkoxy groups, where the hydroxyl(s) group(s) may be associated(bubbled) with a primary or secondary carbon atom of the chain and the alkyl chain may be interrupted by oxygen, and/or

- C3- - C10-cycloalkyl groups and/or groups With3- - C12-cycloalkenyl, where each ring can also be connected by a bridge with the help of -(CH2)n- groups, where n=1-3, and/or

- mono - and/or oligoglycosides radicals, provided that at least 4 radicals from R1-R7represent IT, and that the molecule contains at least two pairs of adjacent-Oh groups,

or R2, R5and R6represent IT, and the radicals R1, R3, R4and R7-10are H, as described in the earlier patent application DE Germany 10244282.7.

In addition to the benefits mentioned above, the advantages of the compositions in accordance with the invention, comprising at least one antioxidant, represent, in particular, antioxidant effect and good skin tolerability. In addition, the compounds described in this application, are preferably colorless or have only a weak coloration and, thus, lead to only a weak color change of the composition or not at all Pref�come to this Particular advantage preferably represents a distinct profile of action of cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, which can preferably be demonstrated in DPPH free radical assay. The advantage is the high ability to remove free radicals (ESDI), delayed in time action (tecso>120 min) and thus medium - high effectiveness against free radicals (AE). In addition, cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, preferably can combine the antioxidant properties of the UV absorption in a plot of UV-A and/or UV-b in the molecule. Preference is therefore also given to compositions, preferably non-therapeutic compositions comprising at least one compound of the formula II, characterized by the fact that at least two adjacent radicals of the radicals R1-R4are HE and at least two adjacent radicals of the radicals R5-R7represent IT. Particularly preferred compositions comprise at least one compound of the formula II, which is characterized in that at least three adjacent radicals of the radicals R1-R4represent IT, preferably the radicals R1-R3representing IT.

For cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, were preferably able to develop their positive action as scavengers of free radicals in the skin particularly well, it is preferably necessary to enable the cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, to penetrate into the deeper layers of the skin. For this purpose, are some of the features. First, cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, can have adequate lipophilicity in order to be able to penetrate the outer skin layer into epidermal layers. As an additional benefit, the composition can also be provided corresponding transport agents, for example liposomes, which are able to transport cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, la, Ib, Ic, Id and/or Ie, through the outer layers of skin. In conclusion, the systemic transport of cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, preferably is also possible. Then the composition recepticals, for example, in such a way that it is acceptable for oral administration.

Is also preferred to introduce the compound of formula II in encapsulated form, e.g. in the form of cellulose or chitin capsules, gelatin or wax matrix or encapsulated with cyclodextrins.

It is anticipated that the preferred cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, also act as enzyme inhibitors. They mainly inhibit protein kinases, elastase, aldose reductase and hyaluronidase, and, thus, are able to maintain the serviceability of the basic substance lining vascular fiber bundles. In addition, they are mostly nonspecific inhibit catechol O-methyltransferase, causing a change in the number of available and catecholamine, thus increasing the strength of blood vessels. Moreover, they are supposed to inhibit AMP phosphodiesterase, and thus give the potential substances for inhibition of platelet aggregation.

Due to its properties of the composition in accordance with the invention are, in General, acceptable for immune protection and for the protection of DNA and RNA. In �astnosti, composition are acceptable for the protection of DNA and RNA against oxidative attack, against free radicals and against damage caused by radiation, in particular UV radiation. An additional advantage of the composition in accordance with the invention is cell protection, in particular protection of Langerhans cells against damage caused by the above-mentioned influences. All of these applications and the use of cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, to obtain compositions that can be used appropriately, are also an object of the present invention. Particularly preferred compositions in accordance with the invention are also acceptable for the treatment of skin diseases associated with abnormal keratinisation relating to differentiation and cell proliferation, in particular for treating common acne, inflammation sebaceous gland, polymorphic acne, acne rosacea, nodular acne, nodular acne, age-related acne, acne which arises as a side effect, such as induced by solar radiation acne, acne-related medication or professional acne, for treating other pathologies of keratinization, in particular, their�Jose, ichthyosiform States, follicular dyskeratosis (disease Darya), Palmar-plantar keratosis, leukoplakia, conditions such as leukoplakia, eczema (lichen) skin and mucous membranes (buccal) for the treatment of other skin diseases associated with abnormal keratinisation and have an inflammatory and/or allergic component, and in particular all forms of psoriasis relating to the skin, mucous membranes and finger-and toe nails, and psoriatic rheumatism and skin atopy, such as eczema, or respiratory atopy, or hyperplasia of the gums, also is it possible for connections to be used for the treatment of some inflammatory conditions which are not associated with abnormalities of keratinization, for the treatment of all benign or malignant tumors of the dermis or epidermis, which may be of viral origin, such as a simple wart, flat wart, verruciform epidermodysplasia, oral papillomatosis, papillomatosis Florida, and entities that are caused by UV radiation, in particular, basocellular apitheliomas and spinocellular apitheliomas, for the treatment of other skin diseases such as bullous dermatitis, and diseases affecting the collagen, for the treatment of certain eye diseases, in particular corneal diseases, to overcome or barbaso skin aging, induced by light, or associated with normal ageing, for reducing pigmentation and actinic keratosis and treatment of all diseases associated with normal aging or aging, induced by light, for the prevention or treatment of wounds/scars of atrophy of the epidermis and/or dermis caused by local or systemic application of corticosteroids, and all types of skin atrophy, for the prevention or treatment of pathologies of wound healing, to prevent or eliminate stretch marks caused by pregnancy, or to facilitate the healing of wounds, to fight with abnormalities in sebum production, such as hyperseborrhea in acne or simple seborrhoea, to fight and bait to prevent States or of precancerous lesions, in particular promyelocytic leukaemia, for the treatment of inflammatory diseases such as arthritis, for the treatment of all virus-induced diseases of the skin or other parts of the body, for the prevention or treatment of alopecia, for the treatment of diseases of the skin or other parts of the body with an immunological component, for the treatment of cardiovascular diseases, such as arteriosclerosis or hypertension, and insulin dependent diabetes and for the treatment of skin problems caused by UV irradiation.

Compositions which are particularly preferred in accordance with�tvii with the invention, also include UV filters in addition to one or more of the cyclic peptides in accordance with the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie.

The use of derivatives dibenzoylmethane that are particularly preferred as UV-A filters, in combination with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, also provides an additional advantage:

sensitive to UV derivative dibenzoylmethane preferably further stabilized in the presence of cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie. The present invention therefore preferably further relates to the use of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, to stabilize the derivatives dibenzoylmethane in the compositions.

In principle, all UV filters are suitable for combination with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides� in accordance with formula I, Ia, Ib, Ic, Id and/or Ie. Particular preference is given to UV filters, physiological acceptability of which has already been demonstrated. Both UV-A and UV-b filters are studied numerous substances which are known from the specialist literature, for example:

derivative benzyladenine, such as 3-(4'-methylbenzylidene)-dl-camphor (for example Eusolex® 6300), 3-benzylideneamino (for example Mexoryl® SD), polymers of N-{(2 and 4)-[(2-oxoborn-3-Illidan)methyl]benzyl}acrylamide (for example Mexoryl® SW), N,N,N-trimethyl-4-(2-oxoborn-3 - ylidenemethyl)aniline methylsulfate (for example Mexoryl® SK) or (2 oxoborn-3-Illidan)toluene-4-sulfonic acid (for example Mexoryl® SL),

benzoyl - or dibenzoylmethanes, such as 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione (for example Eusolex® 9020) or 4-isopropylbenzylamine (for example Eusolex® 8020),

benzophenone, such that Ca2-hydroxy-4-methoxybenzophenone (for example Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (e.g. Uvinul® MS-40),

esters methoxyphenylacetic acid, such as octyl methoxycinnamate (e.g. Eusolex® 2292) or isopentyl 4-methoxycinnamate, for example, in the form of a mixture of the isomers (e.g. Neo Heliopan® E 1000),

derivatives of salicylate such as 2-ethylhexyl salicylate (for example Eusolex® OS), 4-isopropylbenzyl salicylate (for example Megasol®) or 3,3,5-trimethylcyclohexylisocyanate (for example, Eusolex® HMS),

4-aminobenzoic acid and derivatives, such as 4-aminobenzoic acid, 2-ethylhexyl 4-(dimethylamino)benzoate (for example Eusolex® 6007) or ethoxylated ethyl 4-aminobenzoate (e.g. Uvinul® P25),

phenylbenzimidazole acids such as 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine (e.g. Eusolex® 232), 2,2-(1,4-phenylene)bisbenzimidazole-4,6-disulfonate acid and its salts, for example, Neoheliopan® AP) or 2,2-(1,4-phenylene)bisbenzimidazole-6-sulfonic acid; and further substances, such as

- 2-ethylhexyl 2-cyano-3,3-diphenylacetate (for example Eusolex® OCR)

- 3,3'-(1,4-phenylenedimethylene)bis(7,7-dimethyl-2-oxobicyclo [2,2,1]hept-1-immeasureably acid and its salts (e.g. Mexoryl® SX),

- 2,4,6-trainline-(p-Carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine (for example Uvinul®T150)H

- hexyl 2-(4-diethylamino-2-hydroxybenzoyl)benzoate (for example Uvinul® UVA Plus, BASF).

The compounds mentioned in the above list will be considered as examples only. Is also possible to use other UV filters.

These organic UV filters in the General case is introduced into the cosmetic composition in an amount of from 0.5 to 10 percent by weight, preferably 1-8%.

Additional acceptable organic UV filters are, for example,

- 2-(2H-benzotriazole-2-yl)-4-methyl-6-(2-methyl-3-(1,3,3,3-�tetramethyl-1-(trimethylsilyloxy)disiloxanyl)propyl)phenol (for example, Silatrizole®),

- 2-ethylhexyl 4,4'-[(6-[4-((1,1-dimethylethyl)aminocarbonyl) phenylamino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate) (for example Uvasorb® HEB),

- α-(trimethylsilyl)-ω-[trimethylsilyl)oxy]poly[oxy(dimethyl [and about 6% methyl[2-[p-[2,2-bis(ethoxycarbonyl]vinyl]phenoxy]-1-methyltetra] and about 1.5% methyl[3-[p-[2,2-bis(ethoxycarbonyl)vinyl]phenoxy]propenyl] and from 0.1 to 0.4% (metalhydride]silylene]] (n ≈ 60) (CAS No. 207 574-74-1)

- 2,2'-methylenbis(6-(2H-benzotriazole-2-yl)-4-(1,1,3,3-tetramethyl-butyl)phenol) (CAS No. 103 597-45-1)

- 2,2'-(1,4-phenylene)bis(1H-benzimidazol-4,6-disulfonate acid, salt of moonacre) (CAS No. 180 898-37-7),

- 2,4-bis{[4-(2-ethylhexyloxy)-2-hydroxy]phenyl}-6-(4-methoxyphenyl)-1,3,5-triazine (CAS No. 103 597-45-, 187 393-00-6) and

- 2-ethylhexyl 4,4'-[(6-[4-((1,1-dimethylethyl)aminocarbonyl) phenylamino]-1,3,5-triazine-2,4-diyl)diimino]bis(benzoate) (for example Uvasorb® HEB).

Additional acceptable UV filters are also methoxyflavones corresponding to the earlier patent application DE Germany 10232595,2.

Organic UV filters in the General case is introduced into the cosmetic composition in an amount of from 0.5 to 20 percent by weight, preferably 1-15%.

Possible inorganic UV filters are those from the group consisting of titanium dioxides, such as, for example, titanium dioxide coated (e.g. Eusolex® T-2000, Eusolex® T-AQUA), zinc oxide (e.g.�, Sachtotec®), iron oxide, and cerium oxide. These inorganic UV filters in the General case is introduced into the cosmetic composition in an amount of from 0.5 to 20 percent by weight, preferably 2-10%.

Preferred compounds having properties of UV filter, represent 3-(4'-methylbenzylidene)-dl-camphor, 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione, 4-isopropylbenzylamine, 2-hydroxy-4-methoxybenzophenone, octyl methoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl 4-(dimethylamino)benzoate, 2-ethylhexyl 2-cyano-C 3-diphenylacetate, 2-phenylbenzimidazol-5-sulfonic acid and its potassium, sodium and triethanolamine.

Through a combination of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, with additional UV filters can be optimized protective action against harmful effects of UV radiation.

Optimized compositions can include, for example, a combination of the organic UV filters 4'-methoxy-6-hydroxyflavone with 1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione and 3-(4'-methylbenzylidene)-dl-camphor. This combination provides protection in a wide interval, which may be supplemented by the addition of inorganic UV filters, such as microparticles dioxide� titanium.

All of these UV filters may also be used in encapsulated form. In particular, it is preferred to use an organic UV filters in encapsulated form. More details are provided with the following benefits:

The hydrophilicity of the capsule wall can be set regardless of the solubility of the UV filter. Thus, for example, is also possible to introduce hydrophobic UV filters in water composition. In addition, it suppressed the effects of oil on the use of a composition comprising hydrophobic UV filters, which is often considered undesirable.

- Some UV filters, in particular, derivatives dibenzoylmethane, only demonstrate reduced stability in cosmetic compositions. Encapsulation of these filters or compounds which impair the photostability of these filters, such as, for example, cinnamic acid derivatives, allows to increase the photostability of solid compositions.

- The permeability of the skin for organic UV filters and the associated potential for irritation on direct application to human skin has been discussed in the literature. Encapsulation of the corresponding substances, which are offered in this application, suppresses this effect.

- In General, the encapsulation of UV filters or other ingredients, let�et compositions to avoid the problems due to the interaction of the individual components of the composition with each other, such as crystallization, precipitation and agglomeration, since the interaction is suppressed.

Is, therefore, preferred in accordance with the invention for one or more of the above-mentioned UV filters are to be in encapsulated form. In accordance with the invention is preferred for capsules to be so small that they cannot be observed with the naked eye. To achieve the above-mentioned effects, it is also necessary for the capsules to be sufficiently stable and the encapsulated active ingredient (UV filter) is released into the environment only to a small extent, or not at all released.

Acceptable capsules can have walls made of inorganic or organic polymers. For example, US 6,242,099 B1 describes obtaining acceptable capsules with walls of chitin derivatives or polyhydroxylated polyamines. Capsules which can particularly preferably be used in accordance with the invention have walls which can be obtained using the process of the Sol-gel, as described in applications WO 00/09652, WO 00/72806 and WO 00/71084. Preference in this application is again given to the capsule, the wall of which is built �W gel silica (silicon dioxide; uncertain hydroxide silicon dioxide). Acquisition of corresponding capsules is known to those skilled in the art, for example, referred to patent applications, the contents of which are definitely also belongs to the object of this proposal.

The capsules are preferably present in the compositions in accordance with the invention in amounts which ensure that the encapsulated UV filters are present in the composition in the above amounts.

Active ingredients to protect skin or for skin care products can in principle be any active ingredients known to those skilled in the art.

In one embodiment in accordance with the present invention a particularly preferred active ingredients are pyrimidinecarbonitrile acid and/or aryloxy.

Pyrimidinecarbonitrile acids exist in halophilic microorganisms and play a role in osmoregulation of these organisms (E. A. Galinski, etc., Eur. J. Biochem., 149 (1985) pages 135-139). From pyrimidinecarboxylic acids, in particular, should be mentioned in this application ectoin ((S)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarbonitrile acid) and hydroxyacetone ((S,S)-1,4,5,6 - tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarbonitrile acid) and their derivatives. These compounds stabilize enzymes and other biomolecules in aqueous Rast�Orach and organic solvents. In addition, they stabilize, in particular, enzymes against denaturing conditions, such as salts, extreme pH values, surfactants, urea, guanidinium and other compounds.

Ectoin and derivatives actoin, such as hydroxyacetone, can advantageously be used in medicines. In particular, hydroxyacetone can be used for getting medicines for the treatment of diseases of the skin. Other uses hydroxyacetone and other derivatives ectoine preferably located in areas where, for example, is used as an additive trehalose. Thus, derivatives of actoin, such as hydroxyacetone, can be used as a protective means in the dried yeast and bacterial cells. Pharmaceutical products, such as deglycosylation, pharmaceutically active peptides and proteins, such as t-PA, can also be protected with the help of ectoine or its derivatives.

Of cosmetic applications, particular mention should be made use of ectoine and derivatives of ectoine to care for aging, dry or irritated skin. Thus, European patent application EP-A-0 671 161 describes, in particular, that ectoin and hydroxyacetone used in cosmetic compositions, such as powders, Soaps containing surface�but-active substances products for cleaning, lipstick, blush, etc, creams for skin care and composition solar filters.

Preference in this application is given pyrimidinecarboxylic acid of the following formula III

in which

R1is a radical H or (d-8-alkyl,

R2is a radical H or d-4-alkyl,

and

R3, R4, R5and R6each independently of the other represents a radical selected from the group consisting of H, HE, NHz and d-4-alkyl. Preference is given to using pyrimidinecarboxylic acids, in which R2represents a methyl group, or ethyl, and R1or R5and R6represent N.

Particular preference is given to using pyrimidinecarboxylic acids of ectoine ((8)-1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarbonitrile acid) and hydroxyacetone ((S,S)-1,4,5,6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarbonitrile acid). Compositions in accordance with the invention preferably include pyrimidinecarbonitrile acids of this type in an amount up to 15% by weight. Pyrimidinecarbonitrile acid is preferably used in this application in an amount of from 100:1 to 1:100 in relation to compounds of the formula one or more of the cyclic peptides in accordance with the invention, in particular, one or more cyclic peptides according to the Fort�Alami I, la, Ib, Ic, Id and/or Ie, with ratios in the range from 1:10 to 10:1, are especially preferred.

From aryloxides preference is given to the use of oxime 2-hydroxy-5-metalloprotein, which is also known as HMLO, LPO or F5. Its suitability for use in cosmetic compositions are disclosed, for example, in DE-A-41 16 123. Compositions that include the oxime of 2-hydroxy-6-metalloprotein, in accordance with that are acceptable for the treatment of skin diseases, which are accompanied by inflammation. It is known that compositions of this type can be used, for example, for therapy of psoriasis, various forms of eczema, irritable and toxic dermatitis, UV dermatitis and allergic and/or inflammatory diseases of the skin and cover adventitious formations. Compositions in accordance with the invention that, in addition to one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or S, optionally include aryloxy, preferably, the oxime of 2-hydroxy-6-metalloproteinase demonstrate a surprising antiinflammatory suitability. Compositions in accordance with the present application preferably comprise from 0.01 to 10% by weight aryloxy is especially preferred�titanium for songs to include from 0.05 to 5% by weight aryloxy.

All connections or components that can be used in the compositions are either known or commercially available or can be synthesized by known processes. Getting new cyclic peptides is described below.

One or more cyclic peptides according to the invention, in particular one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, can be introduced into cosmetic or dermatological compositions in the usual way. Acceptable compositions are those for external use, for example, in the form of cream, lotion or gel, or in the form of a solution that can be sprayed on the skin. Acceptable for internal use are forms of administration, such as capsules, coated tablets, powders, solutions, tablets or solutions.

The forms of application of compositions in accordance with the invention that may be mentioned are, for example, solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, Soaps, cleansers containing surfactants, oils, aerosols and spray solutions. Examples of other forms of use are pencils, lipsticks, shampoos and compositions for the soul. Any desirable carriers, excipients and, if JW�makes desirable additional active ingredients may be added to the composition.

Preferred auxiliaries originate from the group consisting of preservatives, main, stabilizers, solubilizing agents, vitamins, dyes and agents that improve the smell.

Ointments, pastes, creams and gels may include conventional carriers, such as animal and vegetable oils, waxes, paraffins, starch, tragakant, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.

Powders and atomized forms may include conventional carriers, for example lactose, talc, silicon dioxide, aluminum hydroxide, silicate silicon and polyamide powder, or mixtures of these substances. Sprays can additionally include conventional propellants, for example chlorofluorocarbons, propane/butane or dimethyl eter.

Solutions and emulsions may include conventional carriers such as solvents, solubilizers agents and emulsifiers, for example water, ethanol, isopropanol, ethylcarbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol, oils, in particular cottonseed oil, peanut oil, oil of wheat germ, olive oil, castor oil and sesame oil, fatty acids esters of glycerol, polyethylene glycols and ect�ry fatty acids sorbitol, or mixtures of these substances.

Suspension may include conventional carriers such as liquid diluents, e.g. water, ethanol or propylene glycol, suspendresume agents, for example ethoxylated isostearyl alcohols, the esters polyoxyethylene sorbitol, and the esters polyoxyethylene sorbitan, microcrystalline cellulose, metaservices aluminum, bentonite, agar-agar, tragakant, or mixtures of these substances.

The soap may include conventional carriers such as alkali metal salts of fatty acids, salts of monoesters fatty acids, protein hydrolysates, fatty acids, isetionate, lanolin, fatty alcohol, vegetable oils, plant extracts, glycerol, sugars, or mixtures of these substances.

Cleaning products containing surfactants may include conventional carriers such as sulfate salts of fatty alcohols, sulfates of ATERA fatty alcohols, monastery sultanhani acids, protein hydrolysates, fatty acids, isetionate, derivatives imidazoline, methyltaurine, sarcosinate, amide sulfates of ATERA fatty acids, alkylamidoamines, fatty alcohols, glycerides of fatty acids, diethanolamine fatty acids, vegetable and synthetic oils, lanolin derivatives, ethoxylated esters of glycerol fatty acids, or mixtures of these substances.

Oil for the face and body can include normal wear�ate, such as synthetic oils, such as esters of fatty acids, fatty alcohols, silicone oils, natural oils, such as vegetable oils and oily plant extracts, paraffin oils or lanolin oils, or mixtures of these substances.

Additional typical form for cosmetic applications are also a lip stick, chapstick for lip care, concealer, eyeliner, eyeshadow, blush, face powder, emulsion, cream Foundation and concealer on wax, as well as sunscreens, drugs used before sun exposure and after exposure.

The preferred form of the composition in accordance with the invention include, in particular, emulsions.

Emulsions in accordance with the invention are preferred and include, for example, the said fats, oils, waxes and other fatty substances, and water and an emulsifier, as usually used for compositions of this type.

The lipid phase may preferably be selected from the following groups of substances:

- mineral oils, mineral waxes;

- oils such, centripetality capric or Caprylic acid, also natural oils, such as, for example, castor oil;

fats, waxes and other natural and synthetic fatty substances, preferably esters W�dark acids with alcohols, having a low carbon number, e.g. with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with alkanolamine acids having a low carbon number or with fatty acids;

- silicone oils, such as dimethylpolysiloxane,

diethylpropions, diphenylpropylamine and their mixed forms.

For the purposes of the present invention, the oil phase of the emulsions, oleogel or hydrodispersion or optispray are preferably selected from the group consisting of esters of saturated and/or unsaturated, branched and/or unbranched alkenylboronic acids having a chain length of 3 to 30 carbon atoms and saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of 3 to 30 carbon atoms, or from the group consisting of esters of aromatic carboxylic acids and saturated and/or unsaturated, branched and/or unbranched alcohols, having a chain length of 3 to 30 carbon atoms. Oil-based esters of this type can preferably also be selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl of laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl of isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl Lau�ATA 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl of erukala, erucyl oleate, erucyl of erukala and synthetic, semisynthetic and natural mixtures of esters of this type, for example, jojoba oil.

The oil phase may preferably be selected from the following group consisting of branched and unbranched hydrocarbons and waxes, silicone oils, dialkylamino of ethera, or the group consisting of saturated and unsaturated, branched and unbranched alcohols, and triglycerides of fatty acids, in particular, triglyceride esters of saturated and/or unsaturated, branched and/or unbranched alkenylboronic acids having a chain length of 8 to 24, in particular 12-18, carbon atoms. Triglycerides of fatty acids may be preferably selected, for example, from the group consisting of synthetic, semisynthetic and natural oils, e.g. olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, oil from the kernel of a coconut and the like.

Any mixture of oil and wax components of this type can also preferably be used for the purposes of the present invention. May also be preferable to use waxes, for example, tetralite, as the only to�mponent oil phase.

The oil phase is preferably selected from the group consisting of 2-ethylhexylacrylate, octyldodecanol, attributemetadata, isoeicosane, 2-Cocoate, C12-15-alkyl benzoate, Caprylic triglyceride/capric acid and dicaprylate of ATERA.

Especially preferred are mixtures With12-15alkylbenzoates and 2-ethylhexylphthalate, mixed C12-15alkylbenzoates and attributemetadata, as well as mixtures With12-15alkylbenzoates, 2-ethylhexylacrylate and attributemetadata.

From hydrocarbons for the purposes of the present invention preferably can be used paraffin oil, squalane and squalene.

In addition, the oil phase may also preferably contain cyclic or linear silicone oils or consist entirely of oils of this type, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.

Silicone oil, which is used in accordance with the invention, preferably is a cyclomethicone (octamethylcyclotetrasiloxane). However, it is also preferable for the purpose in accordance with the present invention to use other silicone oils, for example, hexamethylcyclotrisiloxane�EN, polydimethylsiloxane or poly(methylphenylsiloxane).

Also particularly preferred are mixtures of cyclomethicone of isothiazolinones and cyclomethicone and 2-ethylhexylphthalate.

The aqueous phase of the composition in accordance with the invention optionally and preferably includes alcohols, diols or polyols having a low carbon number, and ethera, preferably ethanol, isopropanol, propylene glycol, glycerin, ethylene glycol, ethylene glycol monoethyl or monobutyl eter, propylene glycol monomethyl, monoethyl or monobutyl eter, diethylene glycol monomethyl or monoethyl eter and analogous products, also alcohols having a low carbon number, eg ethanol, isopropanol, 1,2-PROPANEDIOL or glycerol, and in particular one or more thickeners, which can be preferably selected from the group consisting of silicon dioxide, aluminum silicates, polysaccharides and their derivatives, e.g. hyaluronic acid, xanthan gum, hydroxypropylmethylcellulose, particularly preferably from the group consisting of polyacrylates, preferably a polyacrylate selected from the group consisting of the so-called Carbopol, for example, HPMC grades 980,981, 1382, 2984 5984 or, in each case individually or in combination.

In particular, mixtures of monsters�NLRB above solvents. In the case of alcoholic solvents, water can be an additional component.

Emulsions in accordance with the invention are preferred and include, for example, the said fats, oils, waxes and other fatty substances, and water and an emulsifier, as usually used for compositions of this type.

In a preferred embodiment the composition in accordance with the invention include hydrophilic surfactants.

Hydrophilic surfactants are preferably selected from the group consisting of Alkylglucoside, acollection, betinov and coconut ampharete.

Alkylglucoside themselves are preferably selected from the group consisting of Alkylglucoside, which are characterized by the structural formula

where R represents a branched or unbranched alkyl radical containing from 4 to 24 carbon atoms, and whereDPthe mean degree of glucosidase up to 2.

The value ofDPrepresents the degree of glucoseamine of Alkylglucoside that �sed in accordance with the invention, and is defined as

where p1,R2,R3...Piare the ratios of mono-, di-, tri-... i-fold glucosideuronic products in percent by weight. The foods that are preferred in accordance with the invention, are those which have a degree of glucosidase 1-2, particularly preferably from 1.1 to 1.5, very preferably from 1.2 to 1.4, in particular of 1.3.

The value DP takes into account the fact that Alkylglucoside, usually by the method of their production are in the form of a mixture of mono - and oligoglycosides. Relatively high content of monoglucosides, typically of the order of 40-70% by weight, is preferred in accordance with the invention.

Alkylglucoside, which are particularly preferred for the purposes in accordance with the invention are selected from the group consisting of octyl glucopyranoside, nonyl glucopyranoside, decyl glucopyranoside, undecyl glucopyranoside, dodecyl glucopyranoside, tetradecyl glucopyranoside and hexadecyl glucopyranoside.

It is also preferable to use natural or synthetic raw materials and auxiliary agents or mixtures that are characterized by an effective content of active ingredients used in accordance with the Fig�the group for example Plantaren® 1200 (Henkel KGaA), Oramix® NS 10 (Seppic).

Allactivity themselves are preferably selected from the group consisting of substances which are characterized by a structural formula

where R1represents a branched or unbranched alkyl radical containing from 1 to 30 carbon atoms, and M* is selected from the group consisting of alkali metal ions and the group consisting of ammonium ions which are substituted by one or more alkilani and/or one or more hydroxyalkyl radicals, or corresponds to half equivalent of an alkaline earth metal ion.

For example, isostearate sodium, for example, the product Pathionic® ISL from the American Ingredients Company, is preferred.

Betaine are preferably selected from the group consisting of substances which are characterized by a structural formula

where R2represents a branched or unbranched alkyl radical containing from 1 to 30 carbon atoms.

R2in particular, preferably represents a branched or unbranched alkyl radical containing from 6 to 12 carbon atoms.

For example, cypridophobia, for example the product Tego® Betain 810 OTP. GoldschmidtAG, is preferred.

To�kasowy emphatetic, which is preferred for purposes in accordance with the invention is, for example, coconut emphatetic sodium, which is available under the name Miranol^ Ultra C32 from Miranol Chemical Corp.

Compositions in accordance with the invention preferably are characterized by being hydrophilic(s) surfactant(s) substance(s) is (are) present in concentrations of 0.01-20% by weight, preferably 0.05 to 10% by weight, particularly preferably 0.1 to 5% by weight, in each case based on the total weight of the composition.

When using cosmetic and dermatological compositions are applied in a sufficient amount to the skin and/or hair, in accordance with the usual cosmetics.

Cosmetic and dermatological compositions in accordance with the invention can exist in various forms. Thus, they can be, for example, in the form of a solution, free of water of the composition, of an emulsion or microemulsion of the type water-in-oil (W/o) or oil-in-water (M/In), multiple emulsions, e.g. water-in-oil-in-water (V/M/C), gel, pencil, ointment or spray. Is also preferred to introduce ectoine in encapsulated form, for example in collagen matrices and other conventional materials for encapsulating, for example, in the form of incaps�irovannyh in cellulose, in gelatin, wax matrices or encapsulated in liposomes. In particular, wax matrices, as described in DE-A 43 08 282, have been demonstrated as the preferred. Preferred emulsions. M/In the emulsion are particularly preferred. Emulsions In/M emulsion and the emulsion get in the traditional way.

Emulsifiers that may be used are, for example, known In/M and M/emulsifiers. It is preferred to use more traditional simulatory in a preferred M/In emulsions in accordance with the invention.

Simulatory, which are preferred in accordance with the invention, are, for example, M/emulsifiers, principally selected from the group consisting of substances having HLB values of 11-16, particularly preferably having HLB values of 14.5 to 15.5, provided that M/emulsifiers have saturated radicals R and R'. If M/emulsifiers have unsaturated radicals R and/or R' or in the case of derivative isoalkyl the preferred HLB value of such emulsifiers may also be lower or higher.

Is preferable to choose ethoxylate fatty alcohol from the group consisting of ethoxylated stearyl alcohols, cetylated spirits of cetylstearyl alcohols (tatarinowii alcohols). Sabaridana is given by the following: stearyl eter of polyethylene glycol (13) (steareth-13), stearyl eter of polyethylene glycol (14) (steareth-14), steadily eter of polyethylene glycol (15) (steareth-15), stearyl eter of polyethylene glycol (16) (steareth-16), stearyl eter of polyethylene glycol (17) (steareth-17), stearyl eter of polyethylene glycol (18) (steareth-18), stearyl eter of polyethylene glycol (19) (steareth-19), stearyl eter of polyethylene glycol (20) (steareth-20), isostearoyl eter of polyethylene glycol (12) (isostearic-12), isostearoyl eter of polyethylene glycol (13) (isostearic-13), isostearoyl eter of polyethylene glycol (14) (isostearic-14), isostearoyl eter of polyethylene glycol (15) (isostearic-15), isostearoyl eter of polyethylene glycol (16) (isostearic-16), isostearoyl eter of polyethylene glycol (17) (isostearic-17), isostearoyl eter of polyethylene glycol (18) (isostearic-18), isostearoyl eter of polyethylene glycol (19) (isostearic-19), isostearoyl eter of polyethylene glycol (20) (isostearic-20), cetyl eter of polyethylene glycol (13) (ceteth-13), cetyl eter of polyethylene glycol (14) (ceteth-14), cetyl eter of polyethylene glycol (15) (ceteth-15), cetyl eter of polyethylene glycol (16) (ceteth-16), cetyl eter of polyethylene glycol (17) (ceteth-17), cetyl eter of polyethylene glycol (18) (ceteth-18), cetyl eter of polyethylene glycol (19) (ceteth-19), cetyl eter of polyethylene glycol (20) (ceteth-20), societally eter of polyethylene glycol (13) (isoceteth-13), societally et�R of polyethylene glycol (14) (isoceteth-14), societally eter of polyethylene glycol (15) (isoceteth-15), societally eter of polyethylene glycol (16) (isoceteth-16), societally eter of polyethylene glycol (17) (isoceteth-17), societally eter of polyethylene glycol (18) (isoceteth-18), societally eter of polyethylene glycol (19) (isoceteth-19), societally eter of polyethylene glycol (20) (isoceteth-20), alerby eter of polyethylene glycol(12) (will be 12), alerby eter of polyethylene glycol (13) (will-13), alerby eter of polyethylene glycol (14) (will-14), alerby eter of polyethylene glycol (15) (will-15), lauryl eter of polyethylene glycol (12) (Laureth-12), isolability eter of polyethylene glycol (12) (isolaureth-12), cetylstearyl eter of polyethylene glycol (13) (ceteareth-13), cetylstearyl eter of polyethylene glycol (14) (ceteareth-14), cetylstearyl eter of polyethylene glycol (15) (ceteareth-15), cetylstearyl eter of polyethylene glycol (16) (ceteareth-16), cetylstearyl eter of polyethylene glycol (17) (ceteareth-17), cetylstearyl eter of polyethylene glycol (18) (ceteareth-18), cetylstearyl eter of polyethylene glycol (19) (ceteareth-19), cetylstearyl eter of polyethylene glycol (20) (cetearate-20).

Further, it is preferable to choose ethoxylate fatty acid from the following group:

the polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) St�Arat, polyethylene glycol (25) stearate, polyethylene glycol (12) isostearate, polyethylene glycol (13) isostearate, polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate, polyethylene glycol (20) isostearate, polyethylene glycol (21) isostearate, polyethylene glycol (22) isostearate, polyethylene glycol (23) isostearate, polyethylene glycol (24) isostearate, polyethylene glycol (25) isostearate, polyethylene glycol (12) oleate, polyethylene glycol (13) oleate, polyethylene glycol (14) oleate, polyethylene glycol (15) oleate, polyethylene glycol (16) oleate, polyethylene glycol (17) oleate, polyethylene glycol (18) oleate, polyethylene glycol (19) oleate, polyethylene glycol (20) oleate.

Ethoxylated alkyl eter carboxylic acid or its salt, which can preferably be used are Laureth-11 carboxylate, sodium. The alkyl sulfate of ATERA, which can preferably be used is a Laureth-14 sodium sulphate. Ethoxylated derivative of cholesterol, which can preferably be used is cholesterolosis eter of polyethylene glycol (30). Soy Sterol peg (25) also established itself as a successful. Ethoxylated triglycerides, cat�which can preferably be used represent the primrose glycerides of polyethylene glycol (60).

It is also preferable to choose the polyethylene glycol esters of glycerol fatty acid from the group consisting of polyethylene glycol (20) of glycerol laurate, polyethylene glycol (21) of glycerol laurate, polyethylene glycol (22) of glycerol laurate, polyethylene glycol (23) of glycerol laurate, polyethylene glycol (6) of glycerol caprate/caprinate, polyethylene glycol (20) glycerol oleate, polyethylene glycol (20) of glycerol isostearate, polyethylene glycol (18) glycerol oleate/Cocoate.

Is also preferable to choose esters sorbitan from the group consisting of polyethylene glycol (20) sorbitan of monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan of monoisostearate, polyethylene glycol (20) sorbitan of monopalmitate, polyethylene glycol (20) sorbitan of monooleate.

Optional/M emulsifiers, but which, nevertheless, may be preferred for the purpose in accordance with the invention may be as follows:

fatty alcohols containing from 8 to 30 carbon atoms, monoglyceride esters of saturated and/or unsaturated, branched and/or unbranched alkenylboronic acids having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerin esters of saturated and/or unsaturated, razwell�abilities and/or unbranched alkenylboronic acids, having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms, monoglyceride ethera saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms, diglycerin ethera saturated and/or unsaturated, branched and/or unbranched alcohols having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms, propilenglikolem esters of saturated and/or unsaturated, branched and/or unbranched alkenylboronic acids, having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms, and esters sorbitan of saturated and/or unsaturated, branched and/or unbranched alkenylboronic acids having a chain length of 8 to 24 carbon atoms, in particular 12-18 carbon atoms.

Especially preferred V/M emulsifiers are glycerol monostearate, glycerol monoisostearate, the glycerol monomanical, the glycerol monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene glycol monoisostearate, the propylene glycol monocaprate, the propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monocaprylin, sorbitan monitorear, the sucrose distearate, cetyl alcohol, stearyl alcohol, Arachidyl�vy alcohol, beganovic alcohol.salegeneral alcohol, selfirony alcohol, himaloy alcohol, polyethylene glycol (2) stearyl eter (steareth-2), the glycerol monolaurate, glycerol monocaprate and the glycerol monocaprylin.

Preferred compositions in accordance with the invention are particularly acceptable for the protection of human skin against ageing processes and against oxidative stress, i.e. against damage by free radicals, as is caused, for example, with the help of sunlight, temperature and other influences. In this regard, they are in various forms of administration, which are typically used for this application. For example, they can be, in particular, in the form of a lotion or emulsion, such as in the form of a cream or milk (M/b, b/M, M/In/M,/M/), in the form of oil-alcohol, an oily-aqueous or aqueous-alcoholic gels or solutions, in the form of a hard pencils or can be receptionby in aerosol form.

The composition may include cosmetic excipients that are commonly used in this type of compositions, such as, for example, thickeners, softeners, humectants, surfactants, emulsifiers, preservatives, antifoaming agents, fragrances, waxes, lanolin, propellants, dyes and/or pigments which colour the composition or skin, and other ingredients, to�which are commonly used in cosmetics.

Used dispersing or solubilizers agents can be an oil, wax or other fatty substance, a lower monosplit or lower polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, isopropanol, propylene glycol, glycerine and sorbitol.

A preferred embodiment in accordance with the invention is an emulsion in the form of a protective cream or milk which is separate from one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, includes, for example, fatty alcohols, fatty acids, fatty acids esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and emulsifiers in presence of water.

Further preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, esters of fatty acids, in particular triglycerides of fatty acids, or an oily-alcoholic lotions based on a lower alcohol, such as ethanol, or a glycerol, such as propylene glycol and/or polyol, such as glycerol, and oils, waxes and esters of fatty acids, such, centripetality fatty acids.

The composition in accordance with the invention may�e is in the form of alcohol gel, which includes one or more lower alcohols or polyols. such, Okatana, propylene glycol or glycerol, and a thickener, such as diatomite.An oily-alcoholic gels include natural or synthetic oil or wax.

Hard pencils are composed of natural or synthetic waxes and oils, fatty alcohols, fatty acids, esters of fatty acids, lanolin and other fatty substances.

If the composition recepticals in aerosol form, it is usually used traditional propellants, such as alkanes, floralina and chlorphenamine.

Cosmetic composition may also be used to protect hair against photochemical damage in order to prevent changes of tone color, fading or damage of a mechanical nature. In this case, an acceptable composition is in the form of a liquid for rinsing of shampoo, lotion, gel or emulsion, the composition is applied before or after shampooing, before or after colouring or bleaching or before or after permanent waving. Is also possible to select a composition in the form of a lotion or gel for styling or hair treatment, in the form of a lotion or gel for brushing or blow drying, in the form of a hair lacquer, composition for permanent waving, dye or lightener to the hair.POM�mo of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, the composition having the properties of protection from exposure to light, may include various excipients used in this type of compositions, such as surfactants, thickeners, polymers, softeners, preservatives, foam stabilizers, electrolytes, organic solvents, derivatives of organosilicon compounds, oils, waxes, agents against fat, dyes and/or pigments which colour the composition or hair, or other ingredients, are usually used for hair care.

The present invention furthermore relates to a process for the production of the composition, which is characterized in that one or more of the cyclic peptides in accordance with the invention, in particular one or more cyclic peptides according to formulae I, la, Ib, Ic, Id and/or 1E, mixed with a cosmetically or dermatologically acceptable medium or carrier acceptable for food products, and to the use of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, la, Ib, Ic, Id and/or 1E, to obtain a composition.

Compositions in accordance with the invention can be floor�obtained in this case by using the methods which are well known to those skilled in the art.

The mixing can result in dissolution, emulsification or dispersion of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, nasilele.

It should also be noted that the cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, can have a stabilizing effect on the composition. When used in the relevant products, the latter, therefore, are also stable over a long period of time and do not change their appearance. In particular, the effectiveness of ingredients, such as vitamins, even in the case of applications for long periods of time or during prolonged storage. This is, among others, especially preferred in the case of a composition for protecting skin from UV rays, since these cosmetics are subjected to particularly heavy stresses under UV irradiation.

The positive effects of cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, provides their particular suitability for approx�tion in cosmetic compositions pharmaceutical compositions and/or medical products, and preferably in cosmetic or pharmaceutical compositions.

In accordance with one aspect in accordance with the invention the compositions contain one or more acceptable for local use media, one or more portable skin and/or portable hair media, and/or one or more compounds having the action of skin care, hair care and/or inhibiting inflammation effects, preferably selected from the group consisting of:

- UREA, PHOSPHATE, DENETRIA, BIOTIN, CITRIC ACID, NIACINAMIDE, HYDROXYPROPYL GUAR, COCOAMPHOACETATE SODIUM, PROPYLENE GLYCOL, 5-BROMO-5-NITRO-1,3-DIOXANE, CAFFEINE, IS A COP ID AND GLYCOL, PROPYLENE GLYCOL, BUTYLENEGLYCOL, SODIUM BENZOATE, POTASSIUM SORBATE, PANTHENOL, ALCOHOL, TOCOPHERYL ACETATE, MENTHOL, PEG-40 HYDROGENATED CASTOR OIL, SALICYLIC ACID, ISOPROPYL ALCOHOL, ISOQUERCETIN, PROPYLENE GLYCOL, ACRYLATES/C 10-30 ALKYL ACRYLATE, CROSSLINKED POLYMER, SUCROSE STEARATE, DECOLLETE, DIMETIKONA, SODIUM HYDROXIDE, CETEARYL ALCOHOL, CETEARETH-20, RETINILATSETAT DENETRIA, OLE SILT ERA KATA, PROPYLPARABEN, METHYLPARABEN, CETEARYL ALCOHOL, CHLORIDE BEHENTRIMONIUM (Incroquat Behenyl TMS), CYCLOPENTASILOXANE, CYCLOHEXASILOXANE, propylene GLYCOL, DI�of SOLEMNISATION, Of METHYLPARABEN/PROPYLPARABEN (Germaben II), ECTOINE, BENZOPHENONE-3, POLYVINYLPYRROLIDONE (PVP), PVP/VA/VINYL PROPIONATE COPOLYMER, PHENOXYETHANOL, ACRYLATES/C 10-30 ALKYL ACRYLATE, CROSSLINKED POLYMER (Carbopol Ultrez21), propylene GLYCOL, DIAZOLIDINYLUREA, METHYLPARABEN, PROPYLPARABEN, sodium CHLORIDE, CERIMONIA, WATER (AQUA), ETHYLHEXYL, METHOXYCINNAMATE, SILICON DIOXIDE, CHLORPHENESIN, BHT (Eusolex UV-Pearls 2292), THIOGLYCOLATE AMMONIUM, AMMONIUM BICARBONATE, KO KO SLUDGE HYDROLYZED COLLAGEN, POTASSIUM, NONOXYNOL-14, TOCOFERIL ACETATE;

- Biotin, taurine, purine and/or their derivatives, melatonin, agomelatine and/or their salts, L-carnitine and/or salts thereof, pantolactone, taurine and/or their salts;

- vitamins, in particular, Niacinamide, Biotin, Pantothenic acid and tocopherol and/or derivatives,

- ubiquinone, ectoine, allantoin,

- plant extracts of Echinacea and the Ben plant;

- xanthines, in particular caffeine, theophylline and theobromine;

- flavonoids, Favorov, bisabolol and creatine, coumarin, and/or

- ZN-1,2-dithiol-3-thione (I), animaldistribution, sulforaphane, phenethyl of isothiocyanate, 6-(methylsulfinyl)hexyl of isothiocyanate and the allyl isothiocyanate, preferably attraction graying;

more preferably, selected from

- taurine, caffeine, theophylline and theobromine.

Properties of cyclic peptides in �accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, also regarded as positive for use in foods or in food additives or as food. Further explanation given for food, also appropriately applied to food additives or functional foods.

Foods which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, la, Ib, Ic, Id and/or 1E, include all materials that are acceptable for consumption by animals or consumption by humans, for example vitamins and provitamins, fats, minerals or amino acids. (Food can be solid, but also liquid, i.e., can be in the form of drinks).

The present invention accordingly also relates to the application of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, as food additives for human food or animal, and to compositions which are foods or food supplements and comprise corresponding media.

Food products�s, which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, are, for example, also foods which originate from a single natural source, such as, for example, sugar, unsweetened juice, eggs or puree of a single plant species, such as, for example, unsweetened Apple juice (for example also a mixture of different types of Apple juice), grapefruit juice, orange juice, Apple juice, apricot puree, tomato juice, tomato sauce, tomato puree, etc. Additional examples of foodstuffs which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, are corn or cereals from a single plant species and materials produced from plant species of this type, such as, for example, syrups, cereals, rice flour, wheat flour or oat bran. Mixtures of foods of this type are also acceptable for enrichment of one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, for example, I�p, the multivitamin preparations, mineral mixtures or sweetened juice. As further examples of foods which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, you can mention a food composition, for example prepared cereals, biscuits, mixed drinks, foods prepared, particularly for children, such as yoghurt, diet foods, low calorie foods or animal feed.

Foods which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, la, Ib, Ic, Id and/or Ie, and thus include all edible combinations of carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolites of plants and animals.

Foods which can be enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, preferably are introduced orally, for example in the form of flour, granules, tablets, capsules, powders, syrups, solutions or�of spenti.

Food products in accordance with the invention, enriched with one or more cyclic peptides according to the invention, in particular, one or more cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, can be obtained using techniques that are well known to those skilled in the art.

Due to its cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, preferably are also acceptable as medicinal ingredients. Cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, can be used, for example, for the preventive treatment of inflammations and allergies of the skin and in some cases for preventing certain types of cancer. Cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, are particularly suitable for production of a medicine for the treatment of inflammation, allergies and irritation, in particular of the skin. Also is it possible to get medicines that act as a drug, vein tonic, as an inhibitor of couperose as chemical, physical or Akti�quarter inhibitor of erythema, as an agent for the treatment of sensitive skin, as a means of reducing swelling as an absorber of moisture, as agent for weight loss, as an agent directed against wrinkles, as a stimulator of the synthesis of extracellular matrix components, as a reinforcing agent to improve skin elasticity, as an agent against aging. In addition, cyclic peptides in accordance with the invention, in particular, cyclic peptides according to formulae I, Ia, Ib, Ic, Id and/or Ie, which are preferred in this regard, show anti-allergic, anti-inflammatory and interstriae action. They, therefore, are acceptable to obtain drugs for the treatment of inflammation and allergic reactions.

Especially preferred in accordance with the invention are objects, as described in this application, where the characteristics of two or more preferred, more preferred and/or particularly advantageous embodiments, aspects and/or features combine in one embodiment, the aspect and/or the object.

Agents, compositions and/or formulations described in this application can include or comprise, essentially consist of or consist of the required and/or optional components. All connections or components that can be used in the agents, compositions and/�whether the formulations are either known and commercially available, or can be synthesized using known methods.

The invention is explained in more detail below using examples. The invention can be carried out all over the stated interval and is not limited to the examples given in this application.

Besides the Examples given below are presented in order to assist the specialist in the art better understand the present invention by examples. The examples are not intended to limit the scope of protection represented by the claims. The characteristics, properties and advantages as described for compounds, compositions and/or applications specified in the Examples, can be designed for other compounds, compositions and/or applications, which are specifically described and/or defined in the Examples, but fall under the scope of the invention as defined in the claims.

Experimental part

All temperatures stated above and below, are in°C. In the examples below, "conventional" means: water is added if necessary, the mixture is neutralized and subjected to extraction with the help of ATERA or dichloromethane, separate the phases, the organic phase is dried over sodium sulfate, filtered and concentrated by evaporation, and the residue was purified by chromatography �and silica gel and/or by crystallization. RT=retention time (minutes). The analysis is carried out using HPLC on Lichrosorb® RP select In column (7 μm)-250×4 mm, Eluent A: 0.3% TFA in water; Eluent B: 0.3% TFA in a mixture of 2-propanol/water (8:2) gradient 1-99% within 50 minutes at a speed of flow 1 ml/min, and the determination is carried out at 215 nm. M+=molecular peak in the mass spectrum, obtained by using the "bombardment of accelerated atoms (FAB).

Example 1

A solution of 1.1 g of H-Arg(Mtr)-Gly-Asp(OBut)-D-Phe-hPro-ONa [obtainable, for example, Fmoc-HMe-Arg(Mtr)-Gly-Asp(OBut)-D-Phe-hPro-O-Wang, -O-Wang represents the radical of 4-oxymethyluracili polistirolovoy resin used in the modified methods of Merrifield, by removal of Fmoc group using a mixture of piperidine/DMF and removing the resin using TFA/CH2With12(1:1)] in 15 ml of DMF was diluted with 85 ml of dichloromethane and added 50 mg Manso3. After cooling the mixture on ice/acetone, was added 40 μl diphenylphosphinite. After settling at room temperature for 16 hours the solution was concentrated. The concentrate was subjected to gel filtration (Sephadex G10 column in a mixture of isopropanol/water 8:2) and then purified using the HPLC in the usual way. Treatment with a mixture of TFA/H2Oh (98:2) provided receiving cyclo-(AGD-Gl-s-D-Phe-hPro); RT=18,5; FAB-MS (M+H): 587.

The following compounds are obtained analogously by cyclization of the corresponding linear peptides and removal of protections�'s groups;

cyclo-(Arg-Gly-Asp-DPhe-Nle);RT=25.3;FAB-MS(M+H):589;

cyclo-(Arg-Gly-Asp-Phe-Ahds);RT=35,1;FAB-MS(M+H):730;

cyclo-(Arg-Gly-Asp-DPhe-Ahds);RT=35.4;FAB-MS(M+H):730;

cyclo-(Arg-Gly-Asp-Phe-DAhds);RT=35.7;FAB-MS(M+H):730;

cyclo-(Arg-Gly-Asp-DPhe-Aos);

cyclo-(Arg-Gly-Asp-DPhe-DAos);

cyclo-(AGD-SW-ASR-CE-OO);

cyclo-(Arg-Gly-Asp-DPhe-Nhdg);RT=36.7;FAB-MS(M+H):758;

cyclo-(Arg-Gly-Asp-Phe-Nhdg);RT=36,5;FAB-MS(M+H):758;

cyclo-(Arg-Gly-Asp-DPhe-DNhdg);FAB-MS(M+H):758;

cyclo-(Arg-Gly-Asp-Phe-DNhdg);FAB-MS(M+H):758;

cyclo-(Arg-Gly-Asp-DPhg-Nhdg);

cyclo-(Arg-Gly-Asp-Phg-Nhdg);

cyclo-(Arg-Gly-Asp-DPhg-DNhdg);

cyclo-(Arg-Gly-Asp-Phg-DNhdg);

cyclo-(Arg-Gly-Asp-DPhe-Acha);RT=25,2;FAB-MS(M+H):601;

cyclo-(Arg-Gly-Asp-Phe-Acha);FAB-MS(M+H):601;

cyclo-(Arg-Gly-Asp-DPhe-DAcha);FAB-MS(M+H):601;

cyclo-(Arg-Gly-Asp-Phe-DAcha);FAB-MS(M+H):601;

cyclo-(Arg-Gly-Asp-DPhe-Aib);FAB-MS(M+H):575;

cyclo-(Arg-Gly-Asp-Phe-Aib); RT=36,5;FAB-MS(M+H):575;

cyclo-(Arg-Gly-Asp-DPhe-DAib);FAB-MS(M+H):575;

cyclo-(Arg-Gly-Asp-Phe-DAib);FAB-MS(M+H):575;

cyclo-(Arg-Gly-Asp-DPhe-Acpa);RT=17,1;FAB-MS(M+H):587;

cyclo-(Arg-Gly-Asp-Phe-Acpa);FAB-MS(M+H):587;

cyclo-(Arg-Gly-Asp-DPhe-DAcpa);FAB-MS(M+H):587;

cyclo-(Arg-Gly-Asp-Phe-DAcpa);FAB-MS(M+H):587;

cyclo-(Arg-Gly-Asp-DPhe-Tle);RT=19,1;FAB-MS(M+H):589;

cyclo-(Arg-Gly-Asp-Phe-Tle);FAB-MS(M+H):589;

cyclo-(Arg-Gly-Asp-DPhe-DTIe);FAB-MS(M+H):589;

cyclo-(Arg-Gly-Asp-Phe-DTIe);FAB-MS(M+H):589;

cyclo-(Arg-Gly-Asp-Dphe(4-CI)-Tle);RT=23,2;FAB-MS(M+H):623;

cyclo-(Arg-Gly-Asp-Phe(4-CI)-Tle);FAB-MS(M+H):623;

cyclo-(Arg-Gly-Asp-DPhe(4-CI)-DTIe);FAB-MS(M+H):623;

cyclo-(Arg-Gly-Asp-Phe(4-CI)-DTIe);FAB-MS(M+H):623;

cyclo-(Arg-Gly-Asp-Dphe(4-F)-Tle);RT=20,2;FAB-MS(M+H):607;

cyclo-(Arg-Gly-Asp-Phe(4-F)-Tle);FAB-MS(M+H):607;

cyclo-(Arg-Gly-Asp-DPhe(4-F)-DTIe);FAB-MS(M+H):607;

cyclo-(Arg-Gly-Asp-Phe(4-F)-DTIe);FAB-MS(M+H):607.

Example 2

<> A solution of 0.28 g of cyclo-(AGD(tr)-l-s-Dh-Dhr) [obtained by cyclization in accordance with Example 1] in 8.4 ml of TFA, 1,7 ml of dichloromethane and 0.9 ml of thiophenol was allowed to stand at room temperature for 4 hours, then concentrated, the residue was diluted with water and then dried by freezing. Gel filtration on Sephadex G 10 (acetic acid/water 1:1) and subsequent purification using preparative HPLC under the above conditions to ensure that the cyclo-(AGD-Gl-s-Dh-Dhr); FAB-MS (M+H):587.

The following compounds are obtained analogously:

from cyclo-(AGD(tr)-Gl-s-h-Dhr):

cyclo-(Arg-Gly-Asp-Phe-DhPro); FAB-MS (M+H): 587;

from cyclo-(Arg(Mtr)-Gly-Asp(OBut)-DPhg-Tle):

cyclo-(D-Arg-HMeGly-Asp-DPhg-Tle);

from cyclo-(Arg(Mtr)-Gly-Asp(OEt)-DPhg-hPro):

cyclo-(Arg-Gly-Asp-DPhg-hPro);

from cyclo-(Arg(Mtr)-Gly-Asp-Phg-DAhds):

cyclo-(Arg-Gly-Asp-Phg-DAhds);

from cyclo-(Arg(Mtr)-Gly-Asp-DPhg-Acpa):

cyclo-(Arg-Gly-Asp-DPhg-Acpa);

from cyclo-(Arg(Mtr)-Gly-Asp-DPhg-Aos):

cyclo-(Arg-Gly-Asp-DPhg-Aos).

Example 3

80 mg of cyclo-(Arg-Gly-Asp-DPhe-hPro) [obtained in accordance with Example 1] was dissolved in 0.01 ml of HCI from five to six times and freeze dried after each dissolving. Subsequent purification by HPLC provided receiving cyclo-(AGD-l-s-Dh-hr)×Hcl.

The following compounds are obtained analogously:

from cyclo-(Arg-Gly-Asp-DPhe-Nle):

cyclo-(HMeArg-Gly-Asp-DPhe-Nle) x NC1;

from cyclo-(Arg-Gly-Asp-DPhe-Ahds):

cyclo-(Arg-Gly-Asp-DPhe-Ahds) x NC1;

from the CEC�o-(Arg-Gly-Asp-DPhe-Ahds):

cyclo-(Arg-Gly-Asp-DPhe-Ahds) x HC1.

Example 4

To obtain affinity phases, 0.9 g M-maleimido-(CH2)5-CO-MN-(CH2)3polymer [obtainable by condensation of N-maleimido-(CH2)5-COOH with H2N-(CH2)3polymer] was suspended in 10 ml of 0.1 M buffer on the basis of sodium phosphate at pH 7, and one equivalent of HHKno-(Arg-Gly-Asp-DPhe(4-N-CO(CH2)2SH)-hPro) [obtained by cyclization of H-Dphe(4-NH-BOC)-hPro-Arg(Mtr)-Gly-Asp-HE removal of the protective groups and acylation with, for example, CL-CO(CH2)2SH] was added at 4°. The reaction mixture was stirred for 4 hours with simultaneous heating to room temperature, the solid residue was filtered and washed twice with 10 ml each time buffer solution (pH 7) and then three times using 10 ml of water each time. Received cyclo-(AGD-l-s-Dh(4-N-(CH2)2S-3-(N-maleimido-(CH2)5-DUBIO-(CH2)3-polymer)-hr)).

Example 5

Analogously to Example 4, condensation of polymer-O-(CH2)3-NH2[commercially available] and cyclo-(AGD-ly-s-Dh(4-N-(CH2)4-COOH)=hr) [obtainable by condensation of adipic acid with cyclo-(AGD(tr)-Gly-Asp-DPhe-(4-NH-BOC)-hPro) under the conditions described in Example 4] provided the following polymeric phase: cyclo-( AGD-l-s-Dh(4-N-CO-(CH2)4-CO-MN-(CH2 )3-O-polymer)-hr. In the Examples below, "conventional" means: water is added if necessary, the mixture is neutralized and subjected to extraction with the help of ATERA or dichloromethane, separate the phases, the organic phase is dried over sodium sulfate, filtered and concentrated by evaporation, and the residue was purified by chromatography on silica gel and/or by crystallization. RT=retention time (minutes). The analysis is carried out using HPLC on Lichrosorb® RP select In column (7 μm)-250×4 mm, Eluent A: 0.3% TFA in water; Eluent B: 0.3% TFA in a mixture of 2-propanol/water (8:2) gradient 1-99% within 50 minutes at a speed of flow 1 ml/min, and the determination is carried out at 215 nm. M+=molecular peak in the mass spectrum, obtained by using the "bombardment of accelerated atoms (FAB).

Example 6

A solution of 0.6 g H-HMe-Arg(Mtr)-Gly-Asp(OBut)-D-Phe-Val-ONa [obtainable, for example, Fmoc-HMe-Arg(Mtr)-Gly-Asp(OBut)-D-Phe-Val-O-Wang, -O-Wang represents the radical of 4-oxymethyluracili polistirolovoy resin used in the modified methods of Merrifield, by removal of Fmoc group using a mixture of piperidine/DMF and removing the resin using TFA/CH2CL2(1:1)] in 15 ml of DMF was diluted with 85 ml of dichloromethane and was added 50 mg of Mancos. After cooling the mixture on ice/acetone, was added 40 μl diphenylphosphinite. After settling at room� temperature for 16 hours the solution was concentrated. The concentrate was subjected to gel filtration (Sephadex G10 column in a mixture of isopropanol/water 8:2) and then purified using the HPLC in the usual way. Treatment with a mixture of TFA/H20 (98:2) provided receiving cyclo-(Him-AGD-Gly-Asp-D-Phe-Val); RT=18,1; FAB-MS (M+H): 589.

The following compounds are obtained analogously by cyclization of the corresponding linear peptides and removal of the protective groups:

cyclo-(AGD-Gl-s-Dh-V1); RT=17,9; FAB-MS (M+H): 589;

cyclo-(Arg-Gly-HMeAsp-DPhe-Val); RT=18.3; FAB-MS (M+H): 589;

cyclo-(Arg-Gly-HMeAsp-DPhe-Val) x TFA; RT=15.4; FAB-MS(M+H): 589;

cyclo-(Arg-Gly-Asp-HMeDPhe-Val); RT=18,9; FAB-MS (M+H): 589;

cyclo-(Arg-Gly-Asp-DPhe-HMeVal); RT=19,5; FAB-MS (M+H): 589;

cyclo-(Arg-Gly-Asp-DPhe-HMeLys); RT=11.1 V; FAB-MS(M+H): 618;

cyclo-(AGD-l-s-Dh-Ls(benzyloxycarbonyl)×TFA=23.4; FAB-MS (M+H): 752;

cyclo-(NEtArg-Gly-Asp-DPhe-Val); FAB-MS (M+H): 603;

cyclo-(Arg-NEtGly-Asp-DPhe-Val); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-NEtAsp-DPhe-Val); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-Asp-NEtDPhe-Val); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-Asp-DPhe-NEtVal); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-Asp-DPhe(4-l)-HMeVal); RT=23,5; FAB-MS(M+H): 715;

cyclo-(NPrArg-Gly-Asp-DPhe-Val); FAB-MS (M+H): 617;

cyclo-(Arg-NPrGly-Asp-DPhe-Val); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-NPrAsp-DPhe-Val); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-Asp-NPrDPhe-Val); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-Asp-DPhe-NPrVal); FAB-MS (M+H): 617;

cyclo-(NBzlArg-Gly-Asp-DPhe-Val); FAB-MS (M+H): 665;

cyclo-(Arg-NBzlGly-Asp-DPhe-Val); FAB-MS (M+H): 665;

cyclo-(Arg-Gly-NBzlAsp-DPhe-Val); FAB-MS (M+H): 665;

cyclo-(Arg-Gly-Asp-NBzlDPhe-Val); FAB-MS (M+H): 665;

cyclo-(Arg-Gly-Asp-DPhe-NBzlVal); FAB-MS (M+H): 665;

cyclo-(Arg-Gly-Asp-Phe-DHMeVal)×TFA; RT=18,2; FAB-MS(M+H): 589;

cyclo-(HMeArg-Gly-AspDPhe-Leu); FAB-MS (M+H): 603;

cyclo-(Arg-HMeGly-Asp-DPhe-Leu); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-HMeAsp-DPhe-Leu); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-Asp-HMeDPhe-Leu); FAB-MS (M+H): 603;

cyclo-(Arg-Gly-Asp-DPhe-HMeLeu); FAB-MS (M+H): 603;

cyclo-(NEtArg-Gly-Asp-DPhe-Leu); FAB-MS (M+H): 617;

cyclo-(Arg-NEtGly-Asp-DPhe-Leu); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-NEtAsp-DPhe-Leu); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-Asp-NEtDPhe-Leu); FAB-MS (M+H): 617;

cyclo-(Arg-Gly-Asp-DPhe-NEtLeu); FAB-MS (M+H): 617;

cyclo-(NPrArg-Gly-Asp-DPhe-Leu); FAB-MS (M+H): 631;

cyclo-(Arg-NPrGly-Asp-DPhe-Leu); FAB-MS (M+H): 631;

cyclo-(Arg-Gly-NPrAsp-DPhe-Leu); FAB-MS (M+H): 631;

cyclo-(Arg-Gly-Asp-NPrDPhe-Leu); FAB-MS (M+H): 631;

cyclo-(Arg-Gly-Asp-DPhe-NPcLeu); FAB-MS (M+H): 631;

cyclo-(NBzlArg-Gly-Asp-DPhe-Leu); FAB-MS (M+H): 679;

cyclo-(Arg-NBzlGly-Asp-DPhe-Leu); FAB-MS (M+H): 679;

cyclo-(Arg-Gly-NBzlAsp-DPhe-Leu); FAB-MS (M+H): 679;

cyclo-(Arg-Gly-Asp-NBzlDPhe-Leu); FAB-MS (M+H): 679;

cyclo-(Arg-Gly-Asp-DPhe-NBzlLeu); FAB-MS (M+H): 679;

cyclo-(HMeArg-Gly-Asp-DPhe-Ala);

cyclo-(Arg-HMeGly-Asp-DPhe-Ala);

cyclo-(Arg-Gly-HMeAsp-DPhe-Ala);

cyclo-(Arg-Gly-Asp-HMeDPhe-Ala);

cyclo-(Arg-Gly-Asp-DPhe-HMeAla); RT=16,2; FAB-MS (M+H): 561;

cyclo-(NEtArg-Gly-Asp-DPhe-Ala);

cyclo-(Arg-NEtGly-Asp-DPhe-Ala);

cyclo-(Arg-Gly-NEtAsp-DPhe-Ala);

cyclo-(Arg-Gly-Asp-NEtDPhe-Ala);

cyclo-(Arg-Gly-Asp-DPhe-NEtAla);

cyclo-(NPrArg-Gly-Asp-DPhe-Ala);

cyclo-(Arg-NPrGly-Asp-DPhe-Ala);

cyclo-(Arg-Gly-NPrAsp-DPhe-Ala);

cyclo-(Arg-Gly-Asp-NPrDPhe-Ala);

cyclo-(Arg-Gly-Asp-DPhe-NPrAla);

cyclo-(NBzlArg-Gly-Asp-DPhe-Ala);

cyclo-(Arg-NBzlGly-Asp-DPhe-Ala);

cyclo-(Arg-Gly-NBzlAsp-DPhe-Ala);

cyclo-(Arg-Gly-Asp-NBzlDPhe-Ala);

cyclo-(Arg-Gly-Asp-DPhe-NBzlAla);

cyclo-(HMeArg-Gly-Asp-DPhe-Gly);

cyclo-(Arg-HMeGly-Asp-DPhe-Gly);

cyclo-(Arg-Gly-HMeAsp-DPhe-Gly);

cyclo-(Arg-Gly-Asp-HMeDPhe-Gly);

cyclo-(Arg-Gly-Asp-DPhe-HMeGly); RT=14.3; FAB-MS(M+H): 547;

cyclo-(DArg-Gly-Asp-DPhe-HMeVal)×TFA; RT=18.7; FAB-MS(M+H): 589;

cyclo-(NEtArg-Gly-Asp-DPhe-Gly);

cyclo-(Arg-NEtGly-Asp-DPhe-Gly);

cyclo-(Arg-Gly-NEtAsp-DPhe-Gly);

cyclo-(Arg-Gly-Asp-NEtDPhe-Gly);

cyclo-(Arg-Gly-Asp-DPhe-NEtGly);

cyclo-(NPrArg-Gly-Asp-DPhe-Gly);

cyclo-(Arg-NPrGly-Asp-DPhe-Gly);

cyclo-(Arg-Gly-NPrAsp-DPhe-Gly);

cyclo-(Arg-Gly-Asp-NPrDPhe-Gly);

cyclo-(Arg-Gly-Asp-DPhe-NPrGly);

cyclo-(NBzlArg-Gly-Asp-DPhe-Gly);

cyclo-(Arg-NBzlGly-Asp-DPhe-Gly);

cyclo-(Arg-Gly-NBzlAsp-DPhe-Gly);

cyclo-(Arg-Gly-Asp-NBzlDPhe-Gly);

cyclo-(Arg-Gly-Asp-DPhe-NBzlGly);

cyclo-(HMeArg-Gly-Asp-Phg-Val) (SEQ ID NO: 1);

cyclo-(Arg-HMeGly-Asp-Phg-Val) (SEQ ID NO: 2);

cyclo-(Arg-Gly-HMeAsp-Phg-Val) (SEQ ID NO: 3);

cyclo-(Arg-Gly-Asp-HMePhg-Val) (SEQ ID NO: 4);

cyclo-(Arg-Gly-Asp-Phg-HMeVal) (SEQ ID NO: 5);

cyclo-(NEtArg-Gly-Asp-Phg-Val) (SEQ ID NO: 6);

cyclo-(Arg-NEtGly-Asp-Phg-Val) (SEQ ID NO: 7);

cyclo-(Arg-Gly-NEtAsp-Phg-Val) (SEQ ID NO: 8);

cyclo-(Arg-Gly-Asp-NEtPhg-Val) (SEQ ID NO: 9);

cyclo-(Arg-Gly-Asp-Phg-NEtVal) (SEQ ID NO: 10);

cyclo-(NPrArg-Gly-Asp-Phg-Val) (SEQ ID NO: 11);

cyclo-(Arg-NPrGly-Asp-Phg-Val) (SEQ ID NO: 12);

cyclo-(Arg-Gly-NPrAsp-Phg-Val) (SEQ ID NO: 13);

cyclo-(Arg-Gly-Asp-NPrPhg-Val) (SEQ ID NO: 14);

cyclo-(Arg-Gly-Asp-Phg-NPrVal) (SEQ ID NO: 15);

cycles-(BzlArg-Gly-Asp-Phg-Val) (SEQ ID NO: 16);

cyclo-(Arg-NBzlGly-Asp-Phg-Val) (SEQ ID NO: 17);

cyclo-(Arg-Gly-NBzlAsp-Phg-Val) (SEQ ID NO: 18);

cyclo-(Arg-Gly-Asp-NBzlPhg-Val) (SEQ ID NO: 19);

cyclo-(Arg-Gly-Asp-Phg-NBzlVal) (SEQ ID NO: 20);

cyclo-(HMeArg-Gly-Asp-Trp-Val) (SEQ ID NO: 21);

cyclo-(Arg-HMeGly-Asp-Trp-Val) (SEQ ID NO: 22);

cyclo-(AGD-l-s-TGR-V1) (SEQ ID NO: 23);

cyclo-(AGD-l-s-Nothr-Vl) (SEQ ID NO: 24);

cyclo-(AGD-Gl-s-TGR-Vl) (SEQ ID NO: 25);

cyclo-(NEtArg-Gly-Asp-Trp-Val) (SEQ ID NO: 26);

cyclo-(Arg-NEtGly-Asp-Trp-Val) (SEQ ID NO: 27);

cyclo-(Arg-Gly-NEtAsp-Trp-Val) (SEQ ID NO: 28);

cyclo-(Arg-Gly-Asp-NEtTrp-Val) (SEQ ID NO: 29);

cyclo-(Arg-Gly-Asp-Trp-NEtVal) (SEQ ID NO: 30);

cyclo-(NPrArg-Gly-Asp-Trp-Val) (SEQ ID NO: 31);

cyclo-(Arg-NPrGly-Asp-Trp-Val) (SEQ ID NO: 32);

cyclo-(Arg-Gly-NPrAsp-Trp-Val) (SEQ ID NO: 33);

cyclo-(Arg-Gly-Asp-NPrTrp-Val) (SEQ ID NO: 34);

cyclo-(Arg-Gly-Asp-Trp-NPrVal) (SEQ ID NO; 35);

cyclo-(NBzlArg-Gly-Asp-Trp-Val) (SEQ ID NO: 36);

cyclo-(Arg-NBzGlyy-Asp-Trp-Val) (SEQ ID NO: 37);

cyclo-(Arg-Gly-NBzlAsp-Trp-Val) (SEQ ID NO: 38);

cyclo-(Arg-Gly-Asp-NBzlTrp-Val) (SEQ ID NO: 39);

cyclo-(Arg-Gly-Asp-Trp-NBzlVal) (SEQ ID NO: 40).

Example 7

A solution of 0.28 g of cyclo-(Arg(Mtr)-Gly-Asp-HMePhe-Dval) [obtained by cyclization in accordance with Example 1] in 8.4 ml of TFA, 1,7 ml of dichloromethane and 0.9 ml of thiophenol was allowed to stand at room temperature for 4 hours, then concentrated, the residue was diluted with water and then dried by freezing. Gel filtration on Sephadex G10 (acetic acid/water 1:1) and subsequent purification using preparative HPLC under the above conditions to ensure that the cyclo-(Arg-Gly-Asp-HMePhe-DVal); FAB-MS (M+H): 589.

The following compounds are obtained analogously:

from cyclo-(Arg(Mtr)-Gly-HMeAsp-DPhe-lle): cyclo-(AGD-ly-s-Dh-ll); FAB-MS (M+H): 603;

from cyclo-(D-Arg(Mtr)-HMeGly-Asp(OBut)-DPhe-Nle): cyclo-(D-Agde-Gl-s-DPhe-NIe);

from cyclo-(HMeArg(Mtr)-Gly-D-Asp(OEt)-DPhe-lle): cyclo-(Nmead-Gl-D-s-DPhe-lle);

cyclo-(HMeArg(Mtr)-Gly-Asp-Phe-Dlle): cyclo-(Nmead-Gl-s-h-Dll);

from cyclo-(Arg(Mtr)-Gly-HMeAsp-Phe-DLeu): cycle�-(AGD-Dl-s-h-DL);

from cyclo-(Arg(Mtr)-HMeGly-Asp-Phe-DSer): cyclo-(Arg-HMeGly-Asp-Phe-DSer);

from cyclo-(Arg(Mtr)-HMeGly-Asp-DNal-Leu): cyclo-(Arg-HMeGly-Asp-DNal-Leu);

from cyclo-(HMeArg(Mtr)-Gly-Asp-Nal-Dlle): cyclo-(Nmead-Gl-s-Nl-Dll);

from cyclo-(Arg(Mtr)-Gly-Asp-h4MePhg-DVal): cyclo-(AGD-gl-s-hg-DVl);

from cyclo-(Arg(Mtr)-Gly-HMeAsp-Trp-DVal): cyclo-(AGD-G1-s-TGR-DVl).

Example 8

80 mg of cyclo-(Arg-Gly-Asp-DPhe-HMeVal) was dissolved in 0.01 ml of HCI from five to six times and freeze dried after each dissolving. Subsequent purification by HPLC provided receiving cyclo-(AGD-Gl-s-Dh-Vl)×HCI; FAB-MS (M+H): 589.

The following compounds are obtained analogously:

from cyclo-(HMeArg-Gly-Asp-DPhe-Val): cyclo-(HMeArg-Gly-Asp-DPhe-Val×HCI;

from cyclo-(Arg-HMeGly-Asp-DPhe-Val): cyclo-(Arg-HMeGly-Asp-DPhe-Val)×HCI; FAB-MS (M+H): 589;

from cyclo-(Arg-Gly-HMeAsp-DPhe-Val): cyclo-(Arg-Gly-HMeAsp-DPhe-Val)×HCI;

from cyclo-(Arg-Gly-Asp-HMeDPhe-Val); cyclo-(Arg-Gly-Asp-HMeDPhe-Val) x HCI;

from cyclo-(Arg-Gly-Asp-DPhe-HMeVal): cyclo-(Arg-Gly-Asp-DPhe-HMeVal)×HCI;

RT=18,2; FAB-MS(M+H): 589.

The following compounds are obtained analogously by treatment with acetic acid (Acoh):

from cyclo-(Arg-Gly-HMeAsp-DPhe-Val): cyclo-(Arg-Gly-HMeAsp-DPhe-Val)×Acoh;

RT=15,4; FAB-MS(M+H): 589.

The following compounds are obtained analogously by treatment with methanesulfonic acid (S3N):

from cyclo-(Arg-Gly-Asp-DPhe-HMeVal): cyclo-(Arg-Gly-Asp-DPhe-HMeVal)×S3N; RT=17,8; FAB-MS(M+H): 589;

Example 9

To obtain affinity phases, 0.9 g M-maleimido-(CH2)5-CO-MN-(CH2)3polymer resin�and [obtainable by condensation of M-maleimido-(CH 2)5-COOH with H2N-(CH2)3polymer] was suspended in 10 ml of 0.1 M buffer on the basis of sodium phosphate at pH 7, and one equivalent of cyclo-(Arg-Gly-Asp-DPhe-HMeVal(CO(CH2)2SH) was added at 4°. The reaction mixture was stirred for 4 hours with simultaneous heating to room temperature, and the solid residue was filtered and washed twice with 10 ml each time buffer solution (pH 7) and then three times using 10 ml of water each time. Received cyclo-(Arg-Gly-Asp-DPhe-HMeLys(CO(CH2)2S-3-(N-maleimido-(CH2)5-DUBIO-(CH2)3polymer)).

Example 10

Analogously to Example 9, the condensation of polymer-O-(CH2)3-MN2[commercially available] and cyclo-(Arg-Gly-Asp-HMe-DPhe-Lys(CO(CH2)4COOH) [obtainable by condensation of adipic acid with cyclo-(AGD-Gl-s-Him-Dh-Lys) under the above conditions] provided the following polymeric phase: cyclo-(AGD-Gl-s-Him-Dh-Lys-(CO-(CH2)4-CO-MN-(CH2)3-O-resin) the Following compounds are obtained analogously by condensation of:

cyclo-(HMe-Arg-Gly-Asp-DPhe-Lys-(CO-(CH2)5-NH2)) with HOOC-CH2-On-polymer:

cyclo-(HMe-Arg-Gly-Asp-DPhe-Lys-(CO-(CH2)5-MN-CO-CH2-O-resin)).

Example 11

Biological activity

(i) Analysis of the binding of isolated integrin-ligand

Receiving�IU of recombinant human integrin is known from the literature. Inhibitory activity of the substances listed above

were subjected to the study in the analysis of ligand binding using immobilized integrin as a target, and biotinylating human serum vitronectin as a ligand for αvβ3. Briefly, tablets ELISA 96 wells were coated by adsorption of a neutral aqueous buffer containing 1 μg/ml of integrin. After blocking residual sites on the tablet using BSA biotinylated ligands (1 μg/ml) was added in the presence or in the absence of serial dilutions of the inhibitor and after incubation and washing of the bound Biotin was determined using fused with horseradish peroxidase antibioticsare antibody and TMB substrate. IC50, concentration of inhibitor required to inhibit the binding of ligand in the absence of inhibitor at 50%, was determined by curve fitting, and the values presented were usually the average of three or more independent determinations.

Cyclo-(AGD-l-s-Dh-(Him)l)=cyclo(RGDf(Him):

IC50the integrin αvβ3is 24 nm Cyclo-(AGD-Gl-s-Dh-(Him)Vl)=cyclo(RGDf(Him) (V):

IC50the integrin αvβ3is 3 nm

(ii) Analysis of inhibition of receptor

Purified human integrin αvβ3from the placenta x were absorbed on the cell MICR�title tablet and subjected induction biotinylating complementary ligand - vitronectin (VN) for αvβ3in the presence of increasing concentrations of tested compound.

Method: 1 μg ml-1Biotin-ligand were incubated with 1 μg ml-1receptors of the coating in the presence of serial dilutions of the peptides. After 3 hours at 30°C was measured with the bound ligand using the complex of the antibody to the Biotin fused with alkaline phosphatase.

Literature: Charo, I. F., Nannizzi, L, Smith, J. W., and Cheresh, D. A., J. Cell. Biol. 111, 2795-2800(1990).

The values of IC50for binding biotinylated ligands with human placental αvβ3

SequenceIC50[NM]
VN: αvβ3
Cyclo-(AGD-Gl-s-Dh-ib)20
Cyclo-(AGD-Gl-s-Dh-ASRA)9
Cyclo-(AGD-Gl-s-Dh-hr)170
Cyclo-(AGD-Gl-s-h-Nhdg)8
Cyclo-(AGD-Gl-s-Dh-h)2
Cyclo-(AGD-Gl-s-Dh-Tle)6
Cyclo-(AGD-Gl-s-Dh(4l)-l) 1,5
Cyclo-(AGD-Gl-s-Dh(4-F)-l)3
Cyclo(AGD-Gl-h-Gly)400

(iii) Pentapeptides as inhibitors of αvβ3(immobilized)

The preparation and characterization of integrin αvβ3:

Integrin αvβ3was purified from extracts of human placenta with affinity chromatography on GRGDSPK the peptide. Extraction and chromatography is carried out in accordance with previously published formulations, except that Triton X-South Ossetia was replaced by 25 mm octyl-P-D-glucopyranoside. Bound integrin was diluted using 10 mm EDTA in test tubes 1.5 ml, containing 25 PL of 1 M MgCl, and concentrated on the device for concentrating small samples Centricon 100. The samples were stored at 4°C in a neutral buffer containing 25 mm octylglucoside and 0.05% sodium azide. Protein concentration was determined using the ICA analysis (Pierce). The purified integrin characterized using electrophoresis in SDS-gel, and then was carried out by staining the protein and immunoblotting, which showed the purity and identity of the two subunits.

Analyses of solid-phase inhibition was performed for inhibition of binding vitronectin receptor αvβ3their COO�respective protein ligands with cyclic peptides. Inhibitory activity (IC50) cyclic peptides containing RGD to bind vitronectin (VN). Integrins used in the form of immobilized ligands.

SequenceIC50[µm]
VN: αvβ3
Cyclo-(Drg-Gl-s-h-Vl) (=cyclo(rGDFV))72
Cyclo-(AGD-DGl-s-h-Vl) (=cyclo(RDFV))>240
Cyclo-(AGD-Gl-Ds-h-Vl) (=cyclo(RGdFV))152
Cyclo-(AGD-Gl-s-Dh-Vl) (=cyclo(RGDfV))0,049
Cyclo-(AGD-Gl-s-Dh-Vl) (=cyclo(RADfV))4
Cyclo-(Arg-Gly-Asp-Phe-DVal) (=cyclo(RGDFv))11

(iv) Characterization of an inhibitor of integrin

Biological activity the following RGD peptide cyclo-(AGD-Gl-s-Dh-(HMe)Val), HHKno-(Arg-Gly-Asp-DPhe-Val), Gly-Arg-Gly-Asp-Ser-Pro-Lys-OH and L(HKno-(Arg-Gly-Asp-DPhe-Acha) were compared in the analysis of the binding of isolated integrin as described in any literature. Briefly, in the study of the recombinant human receptor αvβ3int�green were absorbed on tablets of 96 cells and biotinylating natural ligand (vitronectin blood plasma) was added in the presence of serially diluted RGD peptides. After 3 hours at 37°C was determined by the bound ligand using monoclonal antibodies against Biotin-labeled alkaline phosphatase (Sigma, St. Louis, MO). Gly-Arg-Gly-Asp-Ser-Pro-Lys-OH: IC50=120 nm

Cyclo-(Arg-Gly-Asp-DPhe-Val): IC50=1.5 nm

Cyclo-(Arg-Gly-Asp-DPhe-(HMe)Val): IC50=5,1 nm

Cyclo-( Arg-Gly-Asp-DPhe-h): IC50=2,1 nm

Example 12: Study using micrometric cDNA

Studies using micrometric cDNA

Below is a study to determine the gene expression profiles of human skin, treated with Cyclo-(Arg-Gly-Asp-DPhe-Acha) (=SRC 1).

For the analysis of disturbed gene expression induced by substance SRRS 1 treated and control samples from a model of human skin was analyzed as described below:

- Used the model of full thickness skin (primary epidermal keratinocytes and human fibroblasts), such as Phenion® FTSM, commercially available from Phenion GmbH & Co. KG, DQsseldorf, Germany. Cells were pooled or was not subjected to genetic modification.

- Analysis of gene expression was performed using cDNA microarray PIQORTM leather, which contained 1312 genes that are involved in target p�ti, associated with stress, inflammation, pigmentation and depigmentation, damping mechanisms against aging and development of hair follicles in humans. For example, the cell cycle, apoptosis, DNA repair, oxidative metabolism, angiogenesis, interactions between cell adhesion cell-matrix adhesion and signal transmission. Genes are represented using four replicative spots.

- Processing using SRS 1 carried out at a concentration of 0.5 µm (incubation for 4 days, n=3 per parameter). Processed buffer dermal equivalents were used as controls.

- Selection of genes was based on statistical methods (p<0.05, and at least a 1.5-fold dysregulation).

- 345 genes with impaired regulation were taken at a concentration of 0.5 µm.

Analysis of gene expression profile - the original genes

The value of the ratio (log2) of zero indicates the absence of regulation, while positive ratios (log2) indicate increased regulation, and the negative of the ratio (log2) - down-regulation of the corresponding genes.

Genes with impaired regulation for samples of the skin, treated with a concentration of 0.5 μm, was used for further analysis.

The experiment included all genes with decreased and increased regulation with a threshold value.

Analysis� data

Software GeneGO's Metacore (road).

Analysis of experiments, automatic counting using GeneGO

The experimental analysis consisted of matching identification numbers for sets of genes volumes of files uploaded with identification numbers of genes in functional ontologies in MetaCore. Ontology included canonical maps routes, GeneGo cellular processes, GO cellular processes and disease categories. The degree of "relevance" in relation to different categories for uploaded data sets was determined using p-values, so that a lower p-value provided a higher priority.

Influence SRRS 1 on the gene expression profile in primaryepidermal human keratinocytes and human fibroblasts

Cellular process

Analysis when using micrometric cDNA revealed the leading cellular and molecular processes of interest, such as: the development of anatomical structures (p-value: 1,1217 e-20), response to external stimulus (p-value: 7,9497 e-20), positive regulation of cell proliferation (p-value: 1.8286 e-10), response to wounding (p-value: 4,1539 e-14), cell proliferation (p-value: 1,1825 e-08), regulation of cell proliferation (p-value: 1,4041 e-13), response to extracellular stimulus (p-value: 2,4436 e-09), the development of the skin (p-value: 1,5864 e-06),�the organization and biogenesis of the extracellular matrix (p-value; 1,1147 e-06), extracellular structures (p-value: 1.8748 e-b), regulation of proliferation of epithelial cells (p-value: 5,9339 e-06) and adhesion cell-matrix adhesion (p-value: 1.3430 e-05).

Example 1. Positive regulation of cell proliferation

The positive regulation of cell proliferation represents any process that activates or increases the rate and extent of cell proliferation.

Categories GO/biological process are overpredicting in the presence of increasing regulation and down regulation of genes after treatment with substances SRS 1. The following genes with a step-up and step-down regulation play an important role in positive regulation of cell proliferation (table 1).

C19orf10
The process(es) genes Positive regulation of cell proliferation
#The gene symbolProteinThe protein nameThe signalRancheria
263TMR11_HUMANInhibitor of metalloproteinases 10,73120,0000029
138IL6IL6_HUMANInterleukin-60,48540,00013
208PTGS2PGH2_HUMANSynthase prostaglandin G/H 20,4222Of 0.021
256TGFB1TGFB1_HUMANTransforming growth factor beta-10,36740,014
85FGF7FGF7_HUMANGrowth factor keratinocyte035610,0012
60DDR2DDR2_HUMANReceptor 2, containing the domain of discoidin0,28690,0086
15BCL2L1BCLX_HUMANRegulator of apoptosis Bcl-XTo 0.2630,017
20CS010_HUMANUPF0556 protein C19orf10To 0.2630,0022
32CD81CD81_HUMANCD81 antigen0,2510,002
39CDK2CDK2_HUMANProtein kinase 2 cell division0,22650,0046
200PGFPLGF_HUMANPlacental growth factor0,21410,0058
40CDK4CDK4_HUMANThe cell division protein kinase 40,13750,034
245STAT5BSTA5B_HUMANSignal transducer and activator of transcription 5 In-0,18440,011
71EGF EGF_HUMANProvidentially growth factor-0,23450,044
269TNFSF13BTN13B_HUMANA member of a family of ligands of the tumor necrosis factor 13-0,26880,0097
140IL7IL7_HUMANInterleukin-7-0,35850,0051
67E2F3E2F3_HUMANTranscription factor E2F3-0,39590,0031
148JUNJUN_HUMANTranscription factor AP-1-0,57780,00000026

Table 1: Process: positive regulation of cell proliferation. Signal: the ratio in log2 values. Genes with down-and increasing regulation.

The results of the research most relevant systems and cards ways

The analysis on the basis of micrometric cDNA processed using SRS 1 skin revealed a set g�new with impaired regulation, related to cell organization and transmission of information, also mediated by integrins. The most relevant objects in the system based on system analysis and maps of the routes (the best card) was a adhesive interactions cell-matrix (p-value: 4,204 e-18), integrin-mediated cell adhesion and migration (p-value: 1,697 e-07), the reconstructed map of cell adhesion to extracellular matrix (p-value: 4,076 e-16). Adhesion of cells to extracellular matrix (ECM) is a dynamic process, mediated by a series associated with the matrix and with the surface of the cells of molecules that interact with each other regulated spatially and temporally. These interactions play a major role in tissue formation, cell migration and induction mediated by transmembrane adhesion signals.

Extracellular matrix (ECM) is the extracellular part of tissue that usually provides structural support to the cells in addition to the implementation of the various important functions. The formation of the ECM is essential for processes such wounds healing and fibrosis. The extracellular matrix is a distinguishing characteristic of connective tissues. The ESM and the processes of adhesion and migration of cells actually play, at least Tr� important role in relation to cosmetic products:

(i) Mechanical: tensile and compressive strength elasticity.

(ii) Protection: buffer effect in relation to changes in the extracellular environment and water retention.

iii) Organization: control of cell behaviour by binding of growth factors and the interaction with cell surface receptors.

The main components of the ECM are different glycoproteins, similar to collagen, fibrin, elastin, fibronectin, laminin and nidhanam, and other molecular compounds, such proteoglycans and hyaluronic acid.

Results for cosmetic use

Results for SRS 1 on the level of genes provide insight into the potential impact SRS 1 as integranova ligand in a variety of processes of regeneration of the skin/hair, skin care/hair and/or disorders. The interaction between integrins and thus, promoting extracellular matrix proteins and, consequently, increased organizational capacity matrix, as expected, has an effect against wrinkles, anti-inflammatory effect and promotes hair growth in the hair cycle, but also affects the development of hair follicles.

Thus, the result of data analysis cDNA is shown in Tables 2 and 3 and is divided into two cat�the category of cosmetics applications, as shown below:

Action directed against wrinkles, anti-aging and anti-inflammatory action,

Hair growth/restoration of hair growth - the development of follicles.

Examples. Description of gene Association with impaired rasulala. obtained after treatment of the skin using SRS 1

S100 calcium binding protein A7, S100 calcium binding protein A8 S100 calcium binding protein A9 (S100A7, S100A8 and S100A9) represent genes with reduced regulation after treatment of skin cells SRRS 1.

S100A7A is assumed to be involved in epidermal differentiation and inflammation and, thus, is presumably important for the pathogenesis of psoriasis and other diseases. S100A7 protein, also known as psoriasin, has important functions as a mediator and regulator of the differentiation and skin disease (psoriasis), cancer of the mammary glands, and as a chemotactic factor for inflammatory cells (Kulski et, Journal of Molecular Evolution(2003), 56 (4), 397-406).

In addition, Lener investigated the genes involved in the natural aging process of human skin. They found that a total of 105 genes change their expression by 1.7 times during the aging process of human skin.

S100A7 and S100A9 have been described as genes that are subjected to increasing regulation in the old skin (T. Lener, etc., Experimental Geontology 41 (2006), 387-397).

S100 proteins represent the largest group of proteins binding of Ca2+structural domain EF-hands. The unique property of this family of proteins is that individual members are localized in specific cellular compartments. For example, various S100 proteins exressions in very limited areas of the hair follicle (Kizawa K, etc., Methods Mol Biol. (2005).

Extracellular proteases are important regulators of cell functions. The family of matrix metalloproteinases (MMP) has been classically described in the context of remodeling of the extracellular matrix (ECM), which occurs throughout life in various processes of tissue morphogenesis to healing. Recently received the findings confirmed that MMP are involved in the regulation of other functions, including survival, angiogenesis, inflammation and signal transmission.

MMP are secreted from keratinocytes and fibroblasts and break down collagen and other proteins, which includes the dermal extracellular matrix.Defective recovery of damages damages the functional and structural integrity of the extracellular matrix. Repeated exposure to the sun causes the accumulation of dermal damage, which ultimately leads to the characteristic shrinkage of the damaged light skin (Gary J. Fisher, etc., ARCH DERMATOL, vol 138 2002). In the skin the primary role of MMP enzymes is recirculated matrix of the skin, in particular, the structural proteins collagen and elastin. The reduction of MMP activity leads to the degradation of the connective tissue of the skin and prevents loss procollagenase expression.

Reducing the expression or activity of matrix metalloproteinases influences the biological process of catabolism of collagen in the direction of treatment of skin aging and psoriasis.

Subjected to down-regulation of MMP genes after treatment of skin cells with SRS 1 are MMR, 13, 16, 23, 25. Is probable that the down regulation of MMP leads to increased amounts of collagen fibers. Also greatly subjected to down-regulation of the laminin-alpha-3, laminin-alpha 4, laminin beta 1 laminin, gamma 1, collagen alpha I (XV), collagen alpha I (IV), collagen alpha II (IV).

Laminin is assumed that mediates the attachment, migration and organization of cells into tissues during embryonic development by interacting with other components of the extracellular matrix.

Tissue inhibitor of metalloproteinases (TMR-1) is highly subjected to increasing regulation after treatment of skin cells with SRS 1. TMR was described as a factor in the survival of cells. TMR-1 is a performance of one of�of actors, of the family of natural inhibitors of MMP, which covers 4 members. Its expression decreases with aging of fibroblasts, ex vivo, and in vivo, contributing, thus, increased catabolic activity in the dermis. TIMP-1 exhibits numerous biological functions. It inhibits the majority of MMP. Thus, SRS 1 activates enhance the regulation of collagen production by fibroblasts of the dermis and down regulation of collagen degradation.

Phenomena integrin-mediated cell adhesion and signal transmission are essential for development and homeostasis of most epithelial tissues.

Ultraviolet (UV) solar irradiation decreases the production of procollagen type I (COL I), the main structural protein in human skin. Photoaging is the most common form of skin damage and is associated with carcinoma of the skin. UV irradiation inhibits the expression of procollagenase gene induced TGF-beta 1 in cultured skin fibroblasts (Quan, etc., AJP(2004), 165, №3, 741-751). TGF-beta is a multifunctional protein that controls proliferation, differentiation and other functions in many cell types. The path of TGF-beta/Smad is a primary regulator of the synthesis of procollagen type I in human skin.

In this experiment, gene expression genes of TGF-beta 1, TGF-b�3 and LTBP1 (latent binding of TGF-beta protein) subjected to increasing regulation after treatment of skin cells with SRS 1.

LTBP1 is one existing in nature RGD ligands for av-integrins. His role in the activation and release of TGF-beta was described (Sheppard, Mogotsi and Metastasis Reviews 24 (2005), 395-402).

In addition, CTGF (the growth factor of connective tissue) is produced by skin fibroblasts after activation with TGF-beta.

In addition, superoxide dismutase (SOD2), which catalyzes dismutation of superoxide into oxygen and hydrogen peroxide, is subject to increasing regulation in a big way. SOD is an important antioxidant defense in nearly all cells exposed to oxygen (skin/hair).

Integrins are heterodimers the adhesion receptors, which consist of alpha and beta subunits. Most integrins recognize some ECM proteins, including laminin, fibronectin and collagen (types I, II, and IV), elastin, fibulin, osteonectin, hyaluronic acid and nitogen (Lee JW, etc., Molecules and Cells(2004), 17(2): 188-202). SRS 1 is a high-level av beta 3/5 ligand and active low av beta 6 ligand (in vitro study).

As it was established with the help of the findings in relation to the data using micrometric cDNA and published links, it helps cells�: proliferation, cell adhesion and organization of the extracellular structure.

In biology of skin and hair follicles beta 1 integrins and their ligands are of particular interest (Kloepper, J. E. Experimental Cell Research (2008).

Integrin beta 1 (ITGB1) demonstrates a significant increase regulation in this study.

Integrin alpha 5, and alpha 3 (fibronectin receptor alpha, ITGA5 and ITGA3) also subject to increasing regulation in the skin treated by SRS 1. It is known that the integrin alpha 5/beta 1 mediates induced fibronectin proliferation of epithelial cells via activation of EGFR. Fibronectin represent proteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM.

Superamento TGF-beta signaling molecules is involved in the regulation of many developmental processes, including the interaction between mesenchymal and epithelial tissues. Smad7 is a potent inhibitor of many members of the family of TGF-beta, in particular, TGF-beta and activin. Klopcic, etc. In reported that the signal transmission of the superfamily of TGF-beta is essential for the development of hair, teeth, T-cells, and control of differentiation and proliferation in the tissues of adults (EurJ.Cell Biol. (2007), 86 (11-12): 781-99).

It is known that the inhibition of BMP signal transmission who�actuat on growth and differentiation in anagenic the hair follicles. BMP stimulates the differentiation of epidermal keratinocytes and keratinocytes of hair follicles, inhibits initiation of growth, promotes proliferation of melanocytes and regulates melanogenesis, but also increases the expression of the peptide linked to the genome caldonia in sensory neurons that innerview the skin. Down regulation of BMP-2 delays the entry into the catagen phase in the cycle of hair follicles. Inhibition of BMP signal transmission also leads to stimulation of proliferation of new stem cells in the gastrointestinal tract (noggin is a natural inhibitor of BMP signal transmission - L. M. Nodep, etc., The EMBO Journal (2000)).

BMP-2 inhibits the proliferative activity and supports differentiation, whereas FGF-7 (fibroblast growth factor-7) induces anagennao phase in the growth of hair follicles (Paus R., Physiol Rev (2001), 81-.449-494).

In the skin treated by SRS 1, BMP-1, -2, -3, -7, and -10 are subjected to down-regulation, whereas FGF-7 is subjected to a significant increase regulation.

Processing FGF-7 at a concentration of 10 ng/ml or more significantly stimulates the elongation of the hair fibers in cultures of hair follicles of the scalp (Lino M, etc., Journal of Investigative Dermatology (2007)). Thus, stimulation of gene expression of fibroblast growth factor 7, as expected, stimulates hair growth.

Fibulin and -2 represent proteins of extracellular matrix, which belong to the RGD class of proteins with unique structural characteristics. Locally limited model mRNA expression and protein fibulin-1 and fibulin-2 in the field of mesenchymal-epithelial interaction is defined in two cultures, developing teeth, and hair follicles (Hang HY, etc., Dev Dyn(1996), 205(3): 348-64).

SRS 1 is assumed as the one that binds on the website of the integrin RGD, like fibulin and thus, obviously, contributes to improve the regulation of fibulin and other RGD-containing proteins of the extracellular matrix like fibronectin, procollagen, laminin, etc..

DNA topoisomerase (TOP) is a family of enzymes that are involved in DNA replication and metabolism. Enzymes bind or unbind the knots of the DNA so that the DNA can be effectively replicated. They regulate double-stranded helical structure of DNA by cleavage of one (topoisomerase type I) or both (topoisomerase type II) chains of the DNA helix (Wang J., Adv. Pharmacol. (1994), 29A: 1-19). TOP-2 belongs to the genes that are down-regulated way in the enhanced formation of follicles anagenic hair (Manabu Ohyama, etc., J. Clin. Invest. (2006), 116: 249-260). Hair loss is known as a side effect of topoisomerase inhibitors.

From the analysis of gene expression and literature (Ludbrook SB, etc., Biochemical Joural (2003)), it is known that integrins regulate superselector signal transmission. In our study, as the TCP-beta 1 and TGF-beta 3 was subjected to increasing regulation. TGF-beta 1 and-beta 3, as expected, are being administered by means of various transcription factors (SP1, SMADs, AP-1, Wnt, SR1, OASIS, etc.) to regulate similar targets bone morphogenetic protein (BMP: down regulation), Neogen (NID: enhancing regulation), fibulin (up regulation), antigen Ki-67 (up regulation), and TORA (up regulation). In addition, TGF-beta/BMP transmission path of the signal is known for the development and regulation of cyclical development of hair follicles (Kobielak, K. et al., J. Cell Biol. (2003), 163: 609-623)

APP. Tables 2 and 3
ID. No. geneThe gene nameUniProtReference number sequenceConnection vs. control,the value of the ratio Log(2)P-value
5IL2P60568P01585Q13169NM-0,5777669990,051
16IL7P13232NM-0,3584539710,0051
32TXLNQ66K62 Q86T54 Q86T85 Q86T86 Q86Y86 Q86YW3 P40222 Q8N2Y3NM-0,8365012680,049
37IL17AQ16552NM-0,6665762660,00097
41TNFP01375 043647 Q9P1Q2 Q9U1V3NM-0,3040061870,06
83TNFSF13BQ9Y275HM_306573-0,2688167580,0097
99TNFSF10P50591NM-0,2688167580,012
105TNFRSF25Q93038 Q93036 Q93037 Q92983P78515Q99831 Q99722 P78507 Q99830 0 NM NM NM NM NM-0,2688167580,00065
251TNFRSF1BP20333 Q6YI29 Q16042 Q9UIH1NM-0,3584539710,036
2344TIMP1P01033Q14252Q9UCU1NM0,7311832420,0000029
4085SOCS1015524015097Q9NSA7NM0,3334237340,000095
7972S100A8P05109Q9UC92Q9UCJONM-0,494109070,000037
7975S100A9P06702 Q9NYMO Q9UCJ1NM-0,4150374990,0000036
9156S100A7P31151 Q9H1E2NM-0,5145731730,00004
37885TNFCQ06643 P78370 Q99761NM NM-0,3400754420,02
18IL8Q9C077P10145Q6FGF6 Q6LAE6 Q96RG6NM0,321928095Is 0.019
55TUBBP07437HM_780140,6599245580,0005
499ITGB1P05556 P78466 P78467 Q 13089 Q14647Q13090Q13212 Q13091 Q14622NM NM NM NM NM NM0,3785116230,0014
552ITGA3P26006NM NM0,344828497With 0.0013

ID no.geneThe gene nameUniProtReference number sequenceWith�unity against control,the value of the ratio Log(2) P-value
5561TGA5P08648 Q96HA5NM0,3785116230,000067
1221KI67P46013Q5VWH2NM0,3103401210,011
2275COL15A1P39059 Q5T6J4 Q9Y4W4NM0,3673710660,011
2289COL4A1P02462 Q9NYC5NM0,505890930,0000005
2305COL4A2P08572NM0,3219280950,00022
2344TMRP01033Q14252Q9UCU1NM0,7311832420,0000029
2364LAMA3 Q96TGOQ16787 Q13679 Q13680NM HM_981290,2986583160,045
2366LAMA4Q9UE18Q9UJN9Q16363 Q15335Q14735Q14731 Q4LE44 Q5SZG8NM0,6040713240,00000058
2370LAMB1P07942NM0,3219280950,0036
2377LAMG1P11047NM0,3219280950,00007
2493MRP45452NM-0,4739311880,0089
2505MRP09237 Q9BTK9NM-0,3959286760,001
2533SPARCP09486NM0,3673710660,025
4749ELA2P08246 P09649 Q6BOD9 Q6LDP5NM-0,2344652540,073
5239MMP23A-MMP23BQ9UBR9 075900 075894 075895 Q5QPQ8 Q76P96 Q7LDM6 Q7LDM7 Q9UJK8 0NM NR_002946-0,643856190,00000059
6926LCN2P80188P30150Q92683NM-0,5563933490,0000004
7972S100A8P05109 Q9UC92 Q9UCJONMB-0,494109070,000037
7975S100A9P06702 Q9NYMO Q9UCJ1NM-0,4150374990,0000036
9156S100A7P31151 Q9H1E2NM-0,5145731730,00004
11207KRT9/td> P35527 000109 Q14665HM_000226-0,2688167580,012
20743MMP25Q9NPA2 Q9H3QONM NM-0,2688167580,093
30439TGFB1P01137Q9UCG4NM0,3673710660,014

ID no.geneThe gene nameUniProtReference number sequenceConnection vs. control,the value of the ratio Log(2)P-value
30442TGFB3P10600NM0,3219280950,027
35735MMR 2P51512Q14824Q52H48HM_322564-0,3400754420,036
38095 SPRR1AP35321 Q9UDG4NM-0,3040061870,00069
38182SOD2P04179P78434Q16792 Q96EE6 Q9P2Z3 Q5TCM1NM NM NM0,2986583160,005

Table 2: Effects against aging and inflammation associated with changes in regulation of genes of the skin, which is treated SRS 1.

ID no.geneThe gene nameUniProtReference number sequenceConnection vs. control,the value of the ratio Log(2)P-value
2356WMRQ9NTQ7Q9H512P18075NM-0,8889686880,0019
9302WMR095393NM-0,4150374990,015
38095 SPRR1AP35321 Q9UDG4NM-0,3040061870,00069
3151ASCQ9HBDO Q9NXJ8 Q9BSZ5 Q9ULZ3Q96D12NM-0,3040061870,012
35633CASP8Q14790 014676 Q14791 Q 14792 Q 14793 Q 14794 Q14795Q14796Q15780QNM NM NMB NM-0,3040061870,016
2104GDF10Q9UCX6P55107NM-0,2863041850,044
7969S100A12P80511 P83219NM-0,251538767Is 0.019
1282BMP2P12643NM-0,2515387670,0072
35624BMP1_2P13497 Q13292 Q13872 Q14874 Q9421 Q99422 Q99423 Q9UL38 P46721 Q NM NM NM-0,2344652540,098

ID no.geneThe gene nameUniProtReference number sequenceConnection vs. control,the value of the ratio Log(2)P-value
1221KI67P46013Q5VWH2NM0,3103401210,011
4091STAT1P42224NM NM0,3103401210,0014
30442TGFB3P10600NM0,3219280950,027
11184KRT19P08727 Q5XG83 Q6NW33 Q7L5M9 Q96A53 Q96FV1 Q9BYF9 Q9P1Y4NM0,3334237340,032
552 ITGA3P26006NM NM0,344828497With 0.0013
5203FGF7P21781NM0,356143810,0012
30439TGFB1P01137Q9UCG4NM0,3673710660,014
281MCL1Q07820 Q9UNJ1 Q9NRQ3 Q9NRQ4 Q9HD91 Q9UHR7 Q9UHR8 Q9UHR9NM NM0,3673710660,0069
2533SPARCP09486NM0,3673710660,025
499ITGB1P05556 P78466 P78467 Q13089 Q14647Q13090Q13212 Q13091 Q14622NM NM NM NM NM NM0,3785116230,0014
556ITGA5P08648 Q96HA5 NM0,3785116230,000067
2457FBLN2P98095NM NM0,3785116230,00029
1613SDCBP000173000560043391NM0,3895668120,000026
11190KRT2AP35908NM0,400537930,072
2437QSOX1000391 Q13876 Q59G29 Q5T2XO Q8WVP4 Q8TDL6NM NM0,4329594070,0015
7586CLUP10909 P11380 P11381 Q7Z5B9NM NM0,4436066510,0048
11154FLOT2Q14254NM0,4541758930,0052
118CCNB2095067NM0,4646682670,000027
2515NIDOGEN: (NID)P14543 Q14942 Q59FL2 Q5TAF2 Q5TAF3 Q86XD7NM0,4750848830,000093
2483ADAM9Q8NFM6Q10718Q13443NM NM0,4854268270,0051

Of 0.0016
ID no.geneThe gene nameUniProtReference number sequenceConnection vs. control,the value of the ratio Log(2)P-value
17158IGFBP4RNM0,4854268270,00089
5177FGF1R RNM NM NM0,50589093
21796FBLN14Q8TBH8 Q9HBQ5 Q9UH41 R R R R Q9UGR4 Q5TIC4 QNM NM NM NM0,5160151470,000016
10509SEPRASEQ12884 000199 Q86Z29 Q99998 Q9UID4NM0,5459683690,00000071
2465LTBP1P22064Q14766Q8TD95NM NM0,5558161550,000065
9410TORAQ9UP44Q9UQP9P11388 Q9HB24 Q9HB25 Q9HB26 Q71UN1 Q71UQ5NMB0,6229303510,000024
Table 3: Impact on hair, associated with changes in regulation of genes of the skin, which is treated SRRS 1

Example 13: Composition

Formulations for the compositions, preferably non-therapeutic compositions, cosmetic compositions and/or compositions for topical application comprising compounds selected from cyclic peptides in accordance with Fig�taniam, are presented as an example below. Also the names given to in accordance with INCI (international nomenclature of cosmetic ingredients) are commercially available compounds.

UV-Pearl, OMC stands for the composition having the following INCI name:

water (for EU: Aqua), ethylhexyl methoxycinnamate, silica, PVP, chlorphenesin, BHT; this composition is commercially available under the name Eusolex®UV Pearl™ OMC from Merck KGaA, Darmstadt. Other UV Pearl products specified in the tables, each model is similar compositions with OMC in accordance with the specified UV filter.

Table 1A: b/M emulsions (data in % by weight)
1-11-21-31-41-51-61-71-81-91-10
Titanium dioxide25 3
Cyclo-(AGD-Gl-s-DPhe-Acha)0,0 10,00 50,00 10,00 050,00 50,00 50,00 5
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00 050,010,00 5
Zinc oxide52
UV-Pearl, OMC301515151515 15151515
Polyglyceryl-3-demerit3333333333
White wax0.30.30.30.30.30.30.30.30.30.3
Gidrogenizirovannoe castor oil0,20,20,20,20,20,20,20,20,20,2
Liquid paraffin77777 77777
Caprylic/capric triglyceride7777777777
Exellent4444444444

1-11-21-31-41-51-61-71-81-91-10
The copolymer PVP/akasen222 2222222
Propylene glycol4444444444
Magnesium sulfate0,60,60,60,60,60,60,60,60,60,6
Tocopherol0,50,50,50,50,50,50,50,50,50,5
Tocopheryl acetate0,50,50,5 0,50,50,50,50,50,50,5
Cyclomethicone0,50,50,50,50,50,50,50,50,50,5
Propylparaben0,0 50,050,050,050,050,050,050,050,050,05
Methylparaben0,1 50,150,150,150,150,150,150,150,150,15
WaterTO 100TO 100 TO 100TO 100To 100TO 100TO 100TO 100TO 100TO 100

Table 1b
1-111-121-131-141-151-161-171-18
Titanium dioxide32325
Benzylidenemalonate polysiloxane10,5
Methylene bis-benzotriazolyl tetramethylbutylphenol11 0,5
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,00 50,0010,00 050,00 5
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00 050,010,00 5
Polyglyceryl-3-demerit3333
White wax0.30.30.30.32222
Hydrogen�created castor oil 0,20,20,20,2
Liquid paraffin7777
Caprylic/capric triglyceride7777
Exellent4444
The copolymer PVP/akasen2222
Propylene glycol4444
Magnesium sulfate0,60,60,60,6

1
1-111-121-131-141-151-161-171-18
Tocopherol0,50,50,50,5
Tocopheryl acetate0,50,50,50,5111
Cyclomethicone0,50,50,50,5
Propylparaben0,050,050,050,050,050,050,050,05
Methylparaben0,150,150,150,150,150,150,150,15
Citrate decoherentization (and) sorbitan sesquioleate (and) white wax (and) aluminum stearate6666
PEG-7 GI�ravensbane castor oil 1111
Zinc stearate2222
Realroot6666
Decollet6666
Dimethicone5555
Tromethamine1111
Glycerin5555
Allantoin0,20,20,20,2
Waterto 100to 100to 100to 100to 100to 100to 100to 100

Table 1C
1-191-201-21 1-221-231-241-251-261-271-281-29
Titanium dioxide2533
Benzylidenemalonate polysiloxane111
Cyclo-(AGD-Gl-s-DPhe-Acha)0,0 10,0 050,0 010,0 00 50,0 050,0 050,0 01 0,0 00 5
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,0 00 50,0 10,0 05
Zinc oxide52
UV-Pearl, OCR105
UV-Pearl, ethylhexyloxymethyl RAV10

1-191-201-211-221-231-241-251-261-271-281-29
UV-Pearl, homosalate10
UV-Pearl, ethylhexyl salicylate10
UV-Pearl, OMC. BP-3 10
UV-Pearl, OCR. BP-310
UV-Pearl, ethylhexyloxymethyl RAV, BP-310
UV-Pearl, homosalate, BP-310
UV-Pearl, ethylhexyl salicylate, BP-310
BMDBM2
UV-Pearl, OMC, 4-methylbenzylidene camphor25
Polyglyceryl-3-demerit3333 3333333
White wax0.30.30.30.30.30.30.30.30.30.30.3
Gidrogenizirovannoe castor oil0,20,20,20,20,20,20,20,20,20,20,2
Liquid paraffin77777777777
Caprylic/capric triglyceride77777777777
Exellent44444444444
The copolymer PVP/akasen22222222222
Propylene glycol4444444 4444
Magnesium sulfate0,60,60,60,60,60,60,60,60,60,60,6
Tocopherol0,50,50,50,50,50,50,50,50,50,50,5
Tocopheryl acetate0,50,50,50,50,50,50,50,50,50,50,5
Cyclomethicone0,50,50,50,50,50,50,50,50,50,5
Propylparaben0,050,050,050,050,050,050,050,050,050,050,05
Methylparaben0,150,150,150,150,150,150,150,150,150,150,15
Waterto 100

Table 2A: M/In emulsions, data in % by weight
2-12-2 2-32-42-52-62-72-82-92-10
Titanium dioxide253
Methylene bis-benzotriazolyl tetramethylbutylphenol121
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,0050,0010,00050,0050,0050,001
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val) 0,00050,010,005
Ectoin13512
4-Methylbenzylidene camphor23432
BMDBM1333333
Stearyl alcohol (and) steareth-7 (and) steareth-10 3333333333
Glicerinstearat(and) ceteth-203333333333
Glicerinstearat3333333333
Microvasc1111111111
Clearaction 11,511,511,511,511,511,511,511,511,511,5
Caprylic/capric triglyceride6666666666
Aerolef6666666666
Propylene glycol4444444444
Glycerite�Rath SE
Stearic acid
Avocado
Propylparaben0,050,050,050,050,050,050,050,050,050,05
Matilda�Auburn 0,150,150,150,150,150,150,150,150,150,15
Tromethamine1.8
Glycerin
Waterto 100to 100to 100to 100to 100to 100to 100to 100to 100to 100

Table 2b2-112-122-132-142-152-162-172-18Titanium dioxide3225Benzylidenemalonate polysiloxane10,5Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,0050,0010,00050,005Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)td align="left"> 0,00050,010,005Ectoin0,5131Zinc oxide2UV-Pearl, OMC15151530303015154-Methylbenzylidene3BMDBM 1Phenylbenzimidazol sulfonic acid4Stearyl alcohol (and) steareth-7 (and) steareth-103333Glicerinstearat(and) ceteth-203333Glicerinstearat3333 Microvasc1111Clearaction11,511,511,511,5Caprylic/capric triglyceride666614141414Aerolef6666Propylene glycol4444 Glicerinstearat SE6666Stearic acid2222Avocado8888Propylparaben0,050,050,050,050,050,050,050,05Methylparaben0,150,150,15 0,150,150,150,150,15Tromethamine1.8Glycerin3333

2-112-122-132-142-152-162-172-18
Waterto 100to 100to 100to 100to 100to 100to 100to 100

Table 2C
2-192-202-212-222-232-242-252-262-272-28
Titanium dioxide332
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,0050,0010,00050,0050,0050,001
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00050,01 0,005
Zinc oxide522
UV-Pearl, OMC15151515151515151515
Caprylic/capric triglyceride14141414141414141414
Aerolef
Propylene glycol
Glicerinstearat SE6666666666
Stearic acid2222222222
Avocado888888 888
Propylparaben0,050,050,050,050,050,050,050,050,050,05
Methylparaben0,150,150,150,150,150,150,150,150,150,15
Glicerinstearat.Cetearate-20. Cetearate-10. Cetearyl alcohol.Tetralet
Cetearate-30
Disabililty eter
Hexyldecanol, hexyldecyl
Cocoglycerides
Tromethamine
Glycerin3333333333
Waterto 100to 100to 100to 100to 100to 100to 100to 100to 100to 100

Table 3; Gels, data in % by weight
3-13-23-33-43-53-63-73-83-93-10
a=water�th gel
Titanium dioxide253
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,0050,0010,00050,0050,0050,001
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00050,010,005
Benzylidenemalonate polysiloxane11211
Methylene bis-benzotriazolyl tetramethylbutylphenol1121
Zinc oxide252
UV-Pearl, ethylhexyl methoxycinnamate3015151515151515 1515
4-Methylbenzylidene camphor2
Butylperoxybenzoate EN1
Phenylbenzimidazol sulfonic acid4
Sweet plum5555555 555
Tocopheryl acetate0,50,50,50,50,50,50,50,50,50,5
Caprylic/capric triglyceride3333333333
Octyldodecanol2222222222
Decollet2222222 222
PEG-8 (and) tocopherol (and) ascorbyl palmitate (and) ascorbic acid (and) citric acid0,050,050,050,050,050,050,050,050,050,05
Sorbitol4444444444
Polyacrylamide (and) C13-14 isoparaffin (and) Laureth-73333333333
Propylparaben0,050,050,05 0,050,050,050,050,050,050,05

3-13-23-33-43-53-63-73-83-93-10
Methylparaben0,1 50,1 50,1 50,1 50,1 50,1 50,1 50,1 50,1 50,1 5
Tromethamine1.8
Waterto 100 to 100to 100to 100to 100To 100to 100to 100to 100to 100

Table 2d:M/B emulsions, data in % by weight

2-192-202-212-222-232-242-252-262-272-28
Titanium dioxide332
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010.0050,0010,00050,005 0,0050,001
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00050,010,005
Ectoin13512
Methylene bis-benzotriazolyl tetramethylbutylphenol121110,5
Zinc oxide52 2
UV-Pearl, OMC15151515151515151515
Caprylic/capric triglyceride14141414141414141414
Aerolef
Propylene glycol
Glicerinstearat SE6666666666
Stearic acid2222222222
Avocado8888888888
Propylparaben0,050,050,050,050,050,050,05 0,050,050,05
Methylparaben0,150,150,150,150,150,150,150,150,150,15
Glycerol stearate, ceteareth-20, cetearate-10, Cetearyl alcohol, tetralet
Cetearate-30

2-192-202-21 2-222-232-242-252-262-272-28
Disabililty eter
Hexyldecanol, hexyldecyl
Cocoglycerides
Tromethamine
Glycerin3333333333
WaterTO 100TO 100TO 100TO 100TO 100TO 100TO 100100TO 100TO 100

Table 3: Gels, data in % by weight
3-13-23-33-43-53-63-73-83-9 3-10
a=water-based gel
Titanium dioxide253
Cyclo-(AGD-Gl-s-DPhe-Acha)0,010,0050,0010,00050,0050,0050,001
Cyclo-(AGD-Gl-s-DPhe-(HMe)Val)0,00050,010,005
Benzylidenemalonate polysiloxane11211
Methylene bis-benzotriazolyl tetramethylbutylphenol1121
Zinc oxide252
UV-Pearl, ethylhexyl methoxycinnamate301515151515 15151515
4-Methylbenzylidene camphor2
Butylperoxybenzoate EN1
Phenylbenzimidazol sulfonic acid4
Plum sweet55555 55555
Tocopheryl acetate0,50,50,50,50,50,50,50,50,50,5
Caprylic/capric triglyceride3333333333
Octyldodecanol2222222222

3
3-13-23-3 3-43-53-63-73-83-93-10
Decollet2222222222
PEG-8 (and) tocopherol (and) ascorbyl palmitate (and) ascorbic acid (and) citric acid0,050,050,050,050,050,050,050,050,050,05
Sorbitol4444444444
Polyacrylamide (and) C13-14 isoparaffin (and) Laureth-7333333333
Propylparaben0,050,050,050,050,050,050,050,050,050,05
Methylparaben0,150,150,150,150,150,150,150,150,150,15
Tromethamine1,8
Water TO 100TO 100TO 100TO 100TO 100TO 100TO 100TO 100TO 100TO 100

Example 14: anti-Cellulite compositions Composition 1 Composition 2

Components%Components%
Phase aPhase a
Cetyl alcohol2Cetyl alcohol2
Glicerinstearat5Glicerinstearat5
Caprylic/capric triglyceride8Caprylic/capric triglyceride8
Isopropylpalmitate9Isopropy�palmitate 9
Phase InPhase In
Glycerin3Glycerin3
Preservative (Germaben II)0,8Preservative (Germaben II)0,8
Cyclo-(AGD-Gl-s-DPhe-Acha)0,005Cyclo-(AGD-Gl-s-DPhe-Acha)0,0005
Water, demineralizedTO 100Water, demineralizedto 100

Method:

Method: Phase A and b were heated to 65-70°C. was Added to Phase b to Phase A without stirring. Homogenized, and left the mixture to cool to room temperature.

Example 15: the Composition for hair care

Cyclopeptide or SRRS 1 is a cyclo-(AGD-W-CBA-Ers ASPA);

CPPL 1 CPPL and 2 represent the liposomes with the following composition:

CPPL1:

- SRS 1 (0,01%)

- Ethanol (17,00%)

- Lecithin (5,00%)

- Water (to 100)

CPPL 2:

- SRS 1 (0,01%)

- Ethanol (17,00%)

- Ectoin (5,00%)

- Lecithin (500%)

- Water (to 100)

1. Conditioning shampoo

Formula 1
Ingredients/name in accordance with INCI (trade name)weight./wt.%
SRS 10,001-0,01
UREA, PHOSPHATE, DENETRIA, BIOTIN, CITRIC ACID (RonaCare® Biotin Plus)1,0
NIACINAMIDE0,1
HYDROXYPROPYL GUAR0,2
COCOAMPHOACETATE SODIUM (Miranol Ultra C-32)10
AQUA (WATER), SODIUM LAURETH (Texapon NSO)32
PANTHENOL0,5
SODIUM CHLORIDE1,0
FLAVORINGdost. Qty
CITRIC ACIDdost. Qty
AQUA (WATER)to 100

2. Dandruff shampoo
Formula 1
Ingredients/Name in accordance with INCI (trade name)weight./wt.%
SRS 10,001-0,01
MICA, Cl 77891 (Timiron® Diamond Cluster MP-1490,05
XANTHAN GUM0,7
WATER, SODIUM LAURETH (Techrep NSO)
PIROCTONE OLAMINE0,50
COCAMIDOPROPYL BETAINE5,00
Propylene GLYCOL, 5-BROMO-5-NITRO-1,3-DIOXANE (Bronidox L)0,20
FLAVORING0,20
AQUA (WATER)to 100

3. Toning composition for hair growth
Formula 1Formula 2Forms�La 3
Ingredients/Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
SRRS0,001-0,01--
CPPL1-2,00-10,00-
CPPL2-2,00-10,00
CAFFEINE0,500,500,50
ethoxydiglycol,propylene GLYCOL, BUTYLENEGLYCOL, SODIUM BENZOATE, POTASSIUM SORBATE (Exptapon Birke Spezial)3,003,003,00
PANTHENOL0,400,400,40
ALCOHOL10,0010,0010,00
TOCOPE�YL ACETATE 0,300,300,30
MENTHOL0,100,100,10
PEG-40 GIDROGENIZIROVANNOE CASTOR OIL1,501,501,50
AQUA (WATER)to 100to 100to 100

3. Toning composition for hair growth with vitamins

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
SRS 10,001-0,01--
CPPL1-2,00-10,00 -
CPPL2--A 2.00-10.00
NIACINAMIDE2,002,002,00
BIOTIN0,020,020,02
SALICYLIC ACID0,100,100,10
ISOPROPYLENE ALCOHOL10,0010,0010,00
FLAVORING0,050,050,05
AQUA (WATER)to 100to 100to 100

4. Emulsion, stimulating hair growth, for treating scalp

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.% weight./wt.%weight./wt.%
SRS 10,001-0,01--
CPPL1-2,00-10,00-
CPPL2--2,00-10,00
ISOQUERCETIN0,20,20,2
Propylene GLYCOL5,005,005,00
ACRYLATES/C10-30 ALKYLACRYLATE, cross-linked POLYMER0,200,200,20
STEARATE SUCROSE1,001,001,00
DECOLLET3,003,003,00
DIMETHICONE4,00 4,004,00
SODIUM HYDROXIDE0,030,030,03
AQUA (WATER)to 100to 100to 100

5. Emulsion for the treatment of scalp

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
SRRS0,001-0,01--
CPPL1-2,00-10,00-
CPPL2--2,00-10,00
TATARINOWII ALCOHOL2,50 2,502,50

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
Cetearate-201,001,001,00
RETINYL DISULFATE DENETRIA1,001,001,00
REALROOT1,001,001,00
PROPYLPARABEN0,050,050,05
METHYLPARABEN0,150,150,15
AQUA (WATER)to 100to 100to 100

6. Hair conditioner

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
SRRS0,001-0,01--
CPPL1-2,00-10,00-
CPPL2--2.00-10,00
TATARINOWII ALCOHOL, CHLORIDE BEHENTRIMONIUM (Incroquat Behenyl TMC)4,504,504,50
CYCLOPENTASILOXANE, CYCLOHEXASILOXANE4,004,004,00
Propylene GLYCOL, DIAZOLIDINYLUREA, METHYLPARABEN, PROPYLPARABEN (Germaben 11)0,70 0,700,70
AQUA (WATER)to 100to 100to 100

7. Hairspray aerosol

Formula 1
Ingredients/Name in accordance with INCI (trade name)weight./wt.%
SRRS0,001-0,01
ectoin1,00
BENZOPHENONE -30,50
PVP/ VA/ FINALPROJECT COPOLYMER5,00
PROPANE/ BUTANE (40:60)30,00
AQUA (WATER)10,00
ETHANOLto 100

8. Gel for hair styling with UV protection

Formula 1Formula 2Formula 3
Ingredients/ Name in accordance with INCI (trade name)weight./wt.%weight./wt.%weight./wt.%
SRRS0,001-0,01--
CPPL1-2,00-10,00-
CPPL2--2,00-10,00
ACRYLATES/C10-30 ALKYLACRYLATE, cross-linked POLYMER (Carbopol Ultrez 21)0,500,500,50
ISOPROPYLENE ALCOHOL15,0015,0015,00
PVP1,501,501,50
Propylene GLYCOL, DIAZOLIDINYLUREA, METHYLPARABEN, PROPYLPARABEN0,200,200,20
WATER, CHLORIDE CERIMONIA0,300,300,30
AQUA (WATER), ETHYLHEXYL, METHOXYCINNAMATE, SILICA,PVP, CHLORPHENESIN, BHT (Eusolex UV-Pearls 2292)10,0010,0010,00
AQUA (WATER)to 100to 100to 100

9. The solution for the cold irons

Formula 1
Ingredients/Name in accordance with INCI (trade name)weight./wt.%
SRS 10,001-0,01
THIOGLYCOLATE AMMONIUM, WATER16,00
AMMONIUM BICARBONATE0,50
PVP2,00
COCOYL POTASSIUM HYDROLYZED COLLAGEN1,00
NONXYNOL-14 5,60
TOCOPHERYL ACETATE1,00
AQUA (WATER)to 100

Example 16: Improve skin smoothness and decrease wrinkle depth in vivo

The purpose of the study:

To determine the effect of cyclopeptide cyclo-(AGD-Gl-s-DPhe-Acha) (=SRC 1) the topography of the skin in vivo using Primes. Local use of the study products was carried out on certain areas of the inner part of the forearm, and in the "crow's feet (eye area).

Model research:

Subjects: the Number of the individual.: 20 (+1 redundant. subject)

Gender: female Age range: 37 - 63 years (AVG. age: 44,8)

Issled. plot: the Inner side of the forearm

"Crow's feet" Issled. parameters: 1. Definition of skin irregularities with PRIMOS®

5.6 (GFMe&technik GmbH, Teltow, Germany) 2. The definition of depth of wrinkles with

PRIMOS® 5.6 (GFMeBtechnik GmbH, Teltow, Germany)

Model research: the Day Of Determination of parameters of the investigated sites

The first application of the test product

Day 14

Determination of the parameters 8-12 hours following the last daily application of the test product

Day 28

Determination of the parameters 8-12 hours following the last daily application of the test product

Measurement of roughness �WA:

PRIMOS (the study of skin in vivo using the method of rapid phase shift) is a noncontact measurement device, which enables a spatial dimension in vivo real-time microtopography human skin on the basis of triangulation of the active image. The measuring head consists of devices containing digital micromirrors in view,projection device and a CCD camera as a recording apparatus mounted on an adjustable tripod. For triangulation of the active image, the intensity of the encoded design point M on the surface that is subjected to investigation. HER image on the surface is recorded using a CCD camera from a specific angle. Point M is a function of parameters like intensity, the triangulation angle between the projection system and camera and some other internal to external coordinates of the camera and projection plan. Information about the height of the structured surface is encoded in the deformed model of intensity that is registered. Resolution and clarity depend on optical and topographical characteristics of the measurement system. For accurate in vivo measurements of human skin, depending on subjected to measurement of the human body (internal p�the surface of the forearm, the forehead, eye area), will be used for the various parameters of the effective wavelength and the gain. To account for differences between human skin and in order to avoid unwanted distortion when driving, and the measurement was used the technique of rapid phase shift (phase width: 16, and 64 pixels). For each measurement was performed at least 3 measurements, and the sharpest image without distortion as a result of movements or artifacts were selected for further processing.

At the end of the study the distortions caused by the presence of hairs on the body, was removed digitally and macrostructure (calculated using polynomial approximation), i.e., the curvature of the whole study area, were subtracted in order to provide the analysis of the microstructure, i.e., roughness of the surface.

The surface roughness was then assessed using the parameter Rz(average depth of roughness). To suppress potential have direction of effects was assessed using the arithmetic mean Rzof the 32 radial cuts. The average depth of roughness was defined as:

where n represents the number of equal segments in which the scanned length 1 was divided into Rzi the last value represents the maximum of the peak with respect to the depth of the cavity in each of the segments. In accordance with German Standard Din 4768/1, Rzcalculated using 5 segments of equal length.

Measurement of depth of wrinkles.

Plot "crow's feet" was recorded as a 3D topography using the PRIMOS system, as described above. For a precise definition of deeper structures used different settings quick-shift (phase width: 16, 64 and 128 pixels). For each measurement was performed at least 3 measurements, and the sharpest image without distortion as a result of movements or artifacts were selected for further processing. In subsequent visits the original recorded data was projected on the skin of a volunteer to help in the process of re-discovery of the investigated area. At the end of the study the distortions caused by the presence of hairs on the body, was removed in digital format, and macrostructure (calculated using polynomial approximation), i.e., the curvature of the whole study area, were subtracted in order to provide the analysis of the microstructure, i.e., roughness of the surface. The depth of wrinkles was evaluated using a parameter Rmaxwhich is defined as the maximum vertical distance from the highest�about peak to the lowest trough of the five segments of equal length. To suppress potential, have direction of effects was assessed using the arithmetic mean Rmax50 parallel cuts.

The implementation of the study

The age of the subjects was 37-63 years (mean age 44,8).

Subjects were instructed not to use any drugs for local application on the study sites, ranging from seven days before the study and before the end of the study. To clean the skin were allowed only water or a mild synthetic detergent (whole study covered phase settings).

Before the first use of the study products the measurements were taken at clearly defined sites of the inner side of the forearm (the humidity level, biomechanical parameters, roughness of the skin) and region "crow's feet" (wrinkles). One portion of the inner side of the forearm was left without treatment, and he served as controls. Additional measurements were taken after 14 and 28 days after 8-12 hours after the last daily use (the adaptation time: 30 min, room temperature: 21±1°C, relative humidity: 50±5%). The subjects used the study products (approximately 2 mg/cm2) twice a day (morning and evening) and thus, as much as possible with�corresponds to Tacoma, practiced by the future consumer.

Table 01: composition of the liposome raw material (liposome RM)

IngredientAmount [%]
Ectoin5,00
Ethanol, denator.17,2
Lecithin5,00
Waterto 100

Table 02:composition of the liposome raw material incl. SRS 1 (liposome RM containing 100 frequent.on menlook frequent.on million SRRS 1)

IngredientAmount [%]
Ectoin5,00
Ethanol, denator.17,2
Lecithin5,00
SRRS100 frequent.at million or 1000 frequent.on million
Waterto 100

Table 03:the composition of the tested compositions
Name of test product
Raw materialINCI% weight./weight.PlateauRM-0RM-100RM-1000
gggG
AndMontanov 202Arachidonoyl alcohol (and) beganovic alcohol (and) arkedelphia3,0030303030
Tegosoft DECDiethylhexyl carbonate4,0040404040
Exellent8,0080808080
InWaterAqua76,00800760760760
1,2-PropandiolPropylene glycol3,0030303030
/td>
Sepigel 305Polyacrylamide (and) C-13-14 isoparaffin (and) Laureth-71,0010101010
DThe liposome RM-0 (without SRRS 1)Aqua (water), alcohol dinator., lecithin, ectoin4,00-40--
The liposome RM-100 (containing 100 frequent.on million SRRS 1)Aqua (Water), alcohol dinator., lecithin, ectoin4,00--40-
The liposome RM-1000 (containing 1000 frequent.on million SRRS 1)Aqua (Water), alcohol dinator., lecithin, ectoin 4,0---40
Germaben IIPropylene glycol (and) diazolidinylurea (and) methylparaben (and) propylparaben1,0010101010
100,00001000,00001000,0000;1000,00001000,0000

Production of liposome composition:

Phase A and b separately heated to 80°C;

Phase And mixed phase (1-2 min (200 Upm)) Phase C was added at 60°C (500-600 Upm) Homogenization at 50°C/2 min, 3000 Upm (U-Turax T-50) was Then added to phase D (stirred) at<40°C is not necessary, the measured pH value and was adjusted to pH 6, if necessary(10% citric acid)

Skin irregularities (Rz)

Estimated changes�t parameter Rz in the areas treated with investigational product, compared with changes at the sites treated with placebo (A), and compared with changes in untreated control plot. Absolute changes in accordance with the plot and the point of time shown below in Figure 1. The lower values of Rzconsistent with the increase smoothness of the skin.

Figure 01

Researched product with 4% RM-0 significantly improves the smoothness of the skin as compared to untreated control. This improvement is further stimulated by the introduction of cyclopeptide cyclo-(AGD-u-Ar-Ers ASPA) (=SRC 1) liposome (Fig.01, investigational product 4% RM-100).

The depth of wrinkles

Been evaluated by the parameter Rmaxcompared to the baseline condition in the respective study area and between plots treated with investigational product and placebo. Absolute changes in area and time points are shown in Figure 02. The decrease in Rmaxcorresponds to the reduction of depth of wrinkles.

Figure 02:

The depth of wrinkles was reduced after application of a placebo, as well as the main composition containing 4% of RM-1000 (containing 0,004% of cyclopeptide cyclo-(Arg-Gly-Asp-DPhe-Acha) (=SRC 1). After 4 weeks of treatment depth also decreased when using the RM-1000, containing 0,004% of cyclopeptide (=SRS 1), compared with placebo and in �nachitelny extent compared with the beginning (Fig.02).

The decrease in the volume of wrinkles was visualized in the Figure 03.

Figure 03: the Topography of the surface of the skin. (A.) the Colorization wrinkle depth in mm (In.) Surface before treatment, t=0 (P) Surface after 4 weeks of treatment with 4% RM-1000 (containing 0,004% SRC 1).

Example 18: Composition/metered dose forms

A: Vials

A solution of 100 g of cyclopeptide of the formula I and 5 g hydrophosphate denetria in 3 l pedestrianonly water was adjusted to pH of 6.5 with 2 N hydrochloric acid, subjected to sterile filtration, distributed into vials for injection and liofilizirovanny under sterile conditions and sterile vials sealed. Each vial for injection contains 5 mg of active substance.

In: Suppositories

A mixture of 20 g of cyclopeptide of the formula I is melted with 100 g of soya lecithin and 1400 g of cocoa butter, and the mixture was poured into molds and left to cool. Each suppository contains 20 mg of active substance.

From: Solution

Solution prepared from 1 g of cyclopeptide of formula I, at 9.38 g of NaH2PO4×2 N2O, 28,48 g Na2HPO××12 (H2O and 0.1 g of benzalkonium chloride in 940 ml

bidistilled water. The pH was adjusted to 6.8, the volume of the solution was adjusted to 1 l and sterilized by irradiation. This solution can be used, for example, in the form of eye drops.

D: Ointment

500 mg of the Cyclops�Chida formula I is mixed with 99.5 g of vaseline oil under aseptic conditions.

E: Pills

A mixture of 100 g of cyclopeptide formula I, 1 kg of lactose, 600 g of microcrystalline cellulose, 600 g of corn starch, 100 g of polyvinylpyrrolidone, 80 g of talc and 10 g of magnesium stearate was condensed with obtaining tablets in the usual way so that each tablet contained 10 mg of active substance.

F: coated Tablets

Tablets were condensed as described in Example E, and then covered by traditional coating of sucrose, corn starch, talc, Tarakanova gum and dye.

G: Capsule

Hard gelatin capsules were filled in the usual way by cyclopeptides formula I so that each capsule contained 5 mg of active substance.

N.: Aerosol

14 g of cyclopeptide of formula I was dissolved in 10 l of isotonic NaCl solution and the solution used to fill the commercially available containers for aerosol containing the mechanism for inflating. The solution can be sprayed in the mouth or nose. One release spray (approximately 0.1 ml) corresponds to a dose of about 0,14 mg.

1. Liposome composition for use in the cosmetic industry, including
i) from 0.001 to 1 wt.% cyclo-(Arg-Gly-Asp-DPhe-Acha), and/or its salt or solvate,
ii) from 0.01 to 20 wt.% one or more lipids;
(iii) 60 to 99.99 wt.% one or more physiologically acceptable solvents.

2. Liposomal composition according to claim , characterized in that it additionally contains
(iv) from 0.0001 to 20% wt.% one or more additional ingredients selected from the group consisting of
α) further active compounds having effect on skin care, hair care and/or inhibiting the inflammatory effect,
β) further cosmetically acceptable excipients.

3. Liposomal composition according to claim 1, wherein the lipids comprise one or more:
(a) phospholipids,
(b) glycosphingolipids,
(c) lecithin,
(d) sphingomyelin,
(e) dipalmitoyl of lecithins,
f) distearoylphosphatidylcholine,
g) phosphatidylcholine,
(h) saturated phosphatidylcholine,
i) unsaturated phosphatidylcholines,
j) polystyrene,
(k) octyldodecanol,
(l) octyldodecanol
and/or their salts.

4. Liposomal composition according to claim 3, in which octyldodecanol is in combination with silica or in combination with phospholipids, cholesterol and/or glycosphingolipids.

5. Liposomal composition according to claim 1, in which one or more physiologically acceptable solvents selected from the group consisting of:
(a) water,
(b) alcohols, diols or polyols having a low carbon number, and ethers and/or ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol of monoethyl or monobutyl ether, propylene glycol monomethyl, Manoa�silt or monobutyl ether, diethylene glycol monomethyl or monoethyl ether,
c) alcohols containing from 2 to 6 carbon atoms and/or ethanol, isopropanol, 1,2-PROPANEDIOL or glycerol, and/or
(d) alcohol (ethanol), glycerin, propylene glycol (1,2-propylene glycol), butyleneglycol (1,4-butanediol), pestilences, pestilences in combination with ethanol, sorbitol, and mixtures thereof.

6. Liposomal composition according to claim 1, including
i) from 0.001 to 1% by weight of cyclo-(Arg-Gly-Asp-DPhe-Acha), and/or its salt or solvate,
ii) from 0.01 to 20% by weight of one or more lipids,
(iii) from 70 to 99% by weight of one or more physiologically acceptable solvents.

7. Liposomal composition according to claim 6, further comprising,
(vi) from 0.001 to 10% by weight, of one or more additional ingredients selected from the group consisting of
α) further active compounds having effect on skin care, hair care and/or inhibiting the inflammatory effect, and
β) further cosmetically acceptable excipients.

8. Liposomal composition according to claim 2, which further active compounds having effect on skin care, hair care and/or inhibiting the inflammatory effect contain Exton in an amount of from 0.1 to 30 wt.%.

9. Liposomal composition according to claim 1, including
i) from 0.01 to 1% by weight of cyclo-(Arg-Gly-Asp-DPhe-Acha), and/or its salt or solvate,
ii)from 0.01 to 10% by weight of one or more lipids,
(iii) from 50 to 98% by weight of water and
iv) from 0.1 to 10 wt.% at least one additional ingredient selected from ectoin, Biotin, taurine, caffeine, taurine, purine and/or their derivatives

10. Liposomal composition according to any one of the preceding claims, where at least 10% of cyclo-(Arg-Gly-Asp-DPhe-Acha), and/or salts thereof is placed in liposomes.

11. Liposomal composition according to claim 3, wherein the one or more lipids selected from the group consisting of lecithin, sphingomyelin, dipalmitoyl of lecithin, distearoylphosphatidylcholine, phosphatidylcholine, saturated phosphatidylcholine and unsaturated phosphatidylcholine and their salts.

12. The use of liposomal composition according to any one of claims. 1-11 to obtain cosmetic compositions.

13. The application of the cosmetic composition according to claim 12 for the care and preservation of the General condition of skin or hair.

14. The application of the cosmetic composition according to claim 12 for the prevention or reduction of wrinkles.

15. The use according to claim 12, wherein said care, preservation or improvement of the General condition of skin or hair includes
a) prevention of induced time-and/or light induced ageing processes of the human skin or human hair,
b) prevention of dry skin, wrinkle formation and/or pigment defects, and/or
C) reducing and/or preventing harmful effects on the skin the UV rays.

16. Kosmeticheski� composition, the resulting application according to claim 12, containing from 10 a.m. to billion to 1000 billion including cyclo-(Arg-Gly-Asp-DPhe-Acha), and/or salts thereof and one or more carriers and/or excipients.

17. A method of obtaining a cosmetic composition according to claim 12 and/or claim 16, including
(a) obtaining a composition in accordance with one or more of claims. 1-11,
b) obtaining one or more carriers acceptable for external use,
d) combining, mixing and/or homogenization (a) and (b) in any order.

18. A method according to claim 17, which further
(c) receive one or more additional active compounds having the action of skin care, hair care and/or inhibiting the inflammatory effect,
and combined, mixed and/or homogenized (C) with (a) and (b) in any order.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to cosmetology and hygiene and provides a foaming detergent composition which contains: a) surfactants consisting of decyl glucoside and coco glucoside, where the decyl glucoside is present in an amount by weight which is 1.8 to 2.2 times the weight of coco glucoside, and b) water, where the amount of decyl glucoside is 10 to 30 wt % of the composition, wherein the composition is free of anionic surfactants.

EFFECT: invention enables to produce a detergent composition having foaming properties in the absence of an anionic surfactant that are equally effective as with a composition with an anionic surfactant.

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FIELD: chemistry.

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6 cl, 5 tbl, 1 ex

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7 cl, 4 dwg, 5 ex

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10 cl, 10 ex, 6 tbl

Hair care product // 2553347

FIELD: cosmetology.

SUBSTANCE: hair care product is made in the form of gel, shampoo, lotion. All embodiments comprise aqueous vegetable extracts, phosphonate complex containing potassium-sodium salts of oxyethylidenebisphosphonic acid or their mixture with trisodium salt hexahydrate of phosphonformic acid and a cosmetically acceptable base.

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5 cl

FIELD: cosmetology.

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5 ex

FIELD: chemistry.

SUBSTANCE: group of inventions relates to a two-phase mouth wash liquid and a method for use thereof. The disclosed two-phase mouth wash liquid contains a hydrophilic phase, a hydrophobic phase, a hydrotrope and a preservative, wherein the preservative contains (i) sodium benzoate and (ii) potassium sorbate and/or methylisothiazolinone (MIT), and the hydrotrope component contains glycerine and/or propylene glycol. The mouth wash liquid contains (a) 0.05-0.11 wt % sodium benzoate and (b) 0.05-0.2 wt % potassium sorbate and/or 0.0005-0.01 wt % MIT. The hydrophilic phase of the mouth wash liquid can additionally contain cetylpyridinium chloride in amount of 0.01-0.1 wt %, wherein the disclosed method of improving oral health includes using an effective amount of said liquid in the mouth of a subject to reduce the level of cariogenic bacteria.

EFFECT: use of said combination of preservatives coupled with said hydrotrope provides good resistance to microbial contamination without any adverse effect on taste properties or appearance of the mouth was liquid.

12 cl, 1 ex

FIELD: chemistry.

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EFFECT: obtaining novel fragrant 5-benzyl-1,3-diazaadamantan-6-ones, which can be used in perfume compositions, as medicinal substances, repellents and as starting substances for producing novel 1,3-diazaadamantan derivatives.

6 ex

FIELD: chemistry.

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23 cl, 6 ex

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3 dwg, 1 tbl

FIELD: medicine.

SUBSTANCE: implementing the presented method involves mixing gel Hyaludent 1 ml on a slide with Betaleukin 0.0005 ml dissolved in water for injections 1 ml; the produced content is applied with a single application syringe on a desalivated treated area of the involved periodontal tissues and left until completely absorbed for 1-3 minutes; the involved area is exposed to laser light generated by the laser semiconductor dental therapeutic apparatus Optodan with a periodontal tip in the mode II, with the exposure length for 3-5 minutes; the therapeutic course is 8 days daily.

EFFECT: using the method enables achieving the fast regeneration length, ensuring the intact periodontal state in the most patients.

4 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention aims at treating drug-induced dry eye syndrome (DI-DES). Treating DI-DES implies taking the past medical history, measuring tear production and eye xerosis values reduced and increased respectively in relation to the norm. Unpreserved ocular hypotensive medications are prescribed in the patient. Unpreserved artificial tears are also applied. The lachrymal fluid is analysed by a multicytokine technique. If the analysis shows increased concentrations of proinflammatory cytokines - interleukin-6, interleukin-8, interleukin-12, Th-1 - interleukin-2, interferon-gamma, and Th-2 - interleukin-4, by min 30% in relation to the patient's age norm, a chronic immune ocular inflammation is detected. That requires transpalpebral Blepharogel-1 phonophoresis and 1% hydrocortisone ointment phonophoresis on the sub-mastoidal region from both sides; the therapeutic course is 8-10 daily procedures.

EFFECT: optimal conditions for diagnosing and reasoned differentiated therapy of DI-DES that enables prescribing the pathogenetically reasoned therapy in due time and increasing the efficacy of the therapeutic exposure.

1 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: invention represents an agent for treating a pulp inflammation differing by the fact that it contains Bezornil ointment and Dycal ivory paste in ratio 1:1 blended until smooth.

EFFECT: invention provides relieving oedema and pain on the day of doctor's appointment, accelerating the pulp tissue regeneration process, creating the reparative dentin within 30 days, and ensures the higher clinical effectiveness in the pulp inflammations.

2 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: group of inventions relates to an oral care composition and method of making thereof. An oral care composition comprising a film in an amount of 0.1 wt % to 5.0 wt %, entrained in a carrier, wherein the film comprises a non-ionic surfactant polysorbate 80 in an amount from 10.5 wt % of the film to 20 wt % of the film and a solid calcium peroxide in the amount of 20% to 65% of the film weight. The film may further comprise a therapeutic active in the amount of 0.01 to 30 wt % of the film. The method of making an oral care composition being a dental care product, comprises as follows: (a) providing the carrier; (b) adding lamellar fragments of the film comprising polysorbate, in an amount of from 10.5 wt % of the film to 20 wt % of the film and a solid ingredient comprising calcium peroxide in an amount of from 20 wt % of the film to 65 wt % of the film; and (c) homogenizing the mixture, whereas the film is present in the amount of 0.1 wt % to 5.0 wt % of the of the total weigh of the composition.

EFFECT: higher active material loading in the film formula provides benefits, including reduced amount of film needed in a product, which is at the same time delivering improved efficacy with lower (0,1-5,0 wt %) loading of the film in the dental care composition.

6 cl, 5 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to phytomixture with sedative effect. Phytomixture contains mixture of Leonurus cardiaca herb, hop cones, Origanum vulgare herb, and hawthorn fruit, taken in specified quantity.

EFFECT: claimed phytomixture possesses increased sedative effect, improved organoleptic properties, as well as reduced side effects.

3 cl, 3 ex

FIELD: medicine.

SUBSTANCE: a phytopreparation containing bee wax 1.9 g and a herbal extract 0.1 g with the above herbal extract containing common oak bark, common St. John's wort herb and creeping thyme (Thymus) herb in equal proportions is used.The preparation is used as a chewing substrate (a chewing gum) for two weeks 3 times a day 15 minutes after meals.

EFFECT: using the invention improves clinical manifestations of the disease; oral inflammations are supposed to relieve or reduce; the length of erosion and ulcer epithelisation is reduced; the oral fluid structural properties are normalised by increasing phosphorus and magnesium, reducing protein, calcium and TBA.

1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to pharmaceutical industry, namely to composition for treating skin ageing. Composition for treating signs of skin ageing, increase of cytikin IL-1α secretion, contains: NF-kB inhibitor, selected from the group, consisting of substituted resorcinols, (E)-3-(4-methylphenylsulphonyl)-2-propenenitrile, tetrahydrokurkuminoids, extracts of Paulownia tomentosa wood, as well as their combinations, and anti-inflammatory compound, which is not NF-kB inhibitor. Composition for treating signs of skin ageing, increase of cytokine IL-1α, containing NF-kB inhibitor, selected from the group, consisting of substituted resorcinols, and anti-inflammatory compound (versions).

EFFECT: compositions are effective for treating signs of skin ageing.

4 cl, 9 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining 7-hydroxyroyleanon, possessing antimicrobial action. said method includes extraction of crushed roots of salvia officinalis with 96% ethyl alcohol with further extract evaporation, processing with water, alcohol distillation and processing with hydrophobic solvent or extraction of said raw material with chloroform with further extract processing with water and evaporation; after which target product is extracted from organic phase by transfer into water-soluble phenolates, with processing with sodium hydroxide water solution; alkali solution is washed with chloroform; acidified with hydrochloric or sulphuric acid; obtained sediment is filtered; dried and crushed.

EFFECT: invention is characterised by improved process manufacturability and provides obtaining individual substance with higher antimicrobial activity than previously extracted royleanon derivatives from salvia officinalis.

2 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns using rhCC10 protein for preparing a therapeutic agent for the therapeutic or preventive effect on influenza virus.

EFFECT: invention provides reducing a pulmonary titre of influenza virus.

11 cl, 4 dwg, 1 tbl, 5 ex

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