Compositions, containing anti-inflammatory mixture

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

 

The SCOPE of the INVENTION

In the present invention proposed a composition comprising a mixture of anti-inflammatory drugs. The composition may be used, e.g., for topical application to the skin.

Background of the INVENTION

Anti-inflammatory drugs are well known. The authors present invention believe that there is a need to identify new combinations of anti-inflammatory drugs with improved characteristics.

The authors present invention found that anti-inflammatory drugs known as inhibitors of nuclear factor NF-kB (inhibitor of NF-kB), with its ability to decrease the immune response by signaling pathways NF-kB, is sometimes promote secretion of the inflammatory cytokine IL-1. The authors present invention also found that anti-inflammatory drugs that have a high ability to suppress the production of cytokines by human lymphocytes stimulated with activating receptors of T cells (TCR) agent phytohemagglutinin, especially those that have an IC50 of about 70 μg/ml or less, is able to reduce the immune response, but sometimes tend to activate the secretion of the inflammatory cytokine IL-8.

Thus, it was discovered that the combination of the inhibitor of NF-kB and anti-inflammatory PR�preparations with low concentrations IC50, especially with the IC50 value of approximately 70 μg/ml or less, allow to obtain a composition with an unexpected reduction in the secretion of both inflammatory cytokines IL-1 and IL-8 in skin and other tissues, as well as generally provide the desired inhibition of NF-kB in the skin and other tissues.

BRIEF description of the INVENTION

In one aspect of the present invention proposed a composition comprising the inhibitor of NF-kB and anti-inflammatory medication. Specified anti-inflammatory medication is not an inhibitor of NF-kB and has a concentration IC50 of about 70 μg/ml or less when tested according to the described in the present application is a TEST FOR anti-INFLAMMATORY ACTIVITY.

According to another aspect, the present invention provides a method of treating signs of aging skin, including local application to the skin, which requires such treatment, a composition containing an inhibitor of NF-kB and anti-inflammatory medication. Specified anti-inflammatory medication is not an inhibitor of NF-kB and has a concentration IC50 of about 70 μg/ml or less when tested according to the described in the present application is a TEST FOR anti-INFLAMMATORY ACTIVITY.

Other distinctive features and advantages of the present invention will be clear from the text of the detailed description of the invention and its formula.

p> DETAILED description of the INVENTION

It is assumed that the person skilled in the art can, based on this description, to use the present invention to the maximum extent. Below are typical embodiments of the invention should be considered only as examples, which in no way limit the disclosed the essence of the present patent application.

Unless otherwise stated, all used in this document the technical and scientific terms have the conventional meaning, clear to any expert in the field, to which is related the present invention. In addition, all publications, applications for patent, patents, and other references in this document sources included in the document by reference. Unless otherwise indicated, all the percentages are given in weight percent (%wt.). Unless otherwise stated, all ranges include the endpoints - for example, the range of "4 to 9" includes points 4 and 9.

Described in this document, the products may not necessarily be in finished and packaged form. In one embodiment, the implementation of the packaging is a container, such as plastic, metal or glass tube or jar containing the composition. Also, the product can have additional packaging (e.g., plastic or cardboard package with a s�u) for placement of such container. In one embodiment, the implementation of the product comprises a composition constituting the subject of the present invention, and instructions for the user by applying the composition to the skin or hair for the treatment of signs of skin aging. The instructions can be printed on the container, nested annotations or any additional packaging.

In this document, the term "topical application" means the direct application or distribution on the surface of the skin, scalp or hair, in particular, by hand or with special tools, wipes, roller or spray.

In this document, the term "cosmetically acceptable" means that ingredients which the term refers, acceptable for use in contact with tissues (e.g., skin or hair), without exerting toxic effects, showing incompatibility, instability, without irritation, allergic reactions, etc.

In some variants of the present invention the compositions forming the subject of the present invention, can be used to treat the signs of skin aging. In this document, the term "signs of aging" refers to the presence of furrows, wrinkles, blemishes, uneven skin and loss of elasticity. In a particularly preferred embodiment, the tag�of arena is the presence of furrows, wrinkles and loss of elasticity.

In this document, the term "treatment of signs of skin aging" refers to decreasing, reducing, preventing, correcting or eliminating the above-described signs of skin aging.

In this document, the term "wrinkle" means thin furrows, fine lines or deep wrinkles. Examples of wrinkles include, among other things, fine lines around the eyes (such as crow's feet), wrinkles on the forehead and cheeks, frown wrinkles and expression lines around the mouth.

In this document, the term "loss of elasticity" refers to the loss of elasticity or structural integrity of skin or tissue, including, without limitation, sagging, dullness and sagging tissue. Loss of elasticity or structural integrity of the tissue may be the result of many factors, including, without limitation, diseases, aging, hormonal changes, mechanical trauma, negative environmental effects, or the result of drawing on fabric products such as cosmetics and pharmaceuticals.

In this document, the term "rough skin" means a skin condition associated with diffuse or patchy pigmentation, which can be classified as hyperpigmentation, for example, postinflammatory hyperpigmentation.

In this document, the term "�anistonthe" means the condition of the skin, associated with redness or erythema.

In this document, the term "cosmetic" refers to a composition or substance that improves the appearance, which preserves, restores, gives that mimics or enhances physical attractiveness or has the effect of increasing the attractiveness or youth, especially in relation to the appearance of tissue or skin.

In this document, the term "cosmetically effective amount" means an amount of a physiologically active compound or composition sufficient to treat one or more signs of skin aging, but low enough not to cause serious side effects. Cosmetically effective amount of a compound or composition varies depending on your specific condition, treatment which is carried out, the age and physical condition of the end user, the severity of the condition, treatment/prevention of which is effected, the duration of treatment, the nature of other treatments, the specific compound or product/composition, concrete used cosmetically acceptable carrier, and other similar factors.

In the composition includes an inhibitor of NF-kB and anti-inflammatory medication that is not an inhibitor of NF-kB, but has a low IC50 value. Both to�component have anti-inflammatory effect to the skin and other tissues, such anti-inflammatory effects complement each other. The authors of the present invention unexpectedly found that the anti-inflammatory drug with an IC50 of about 70 μg/ml or less in combination with an inhibitor of NF-kB suppresses the increase in the secretion of cytokines IL-1 and IL-8, which otherwise might be caused by the use of specific drugs.

In one embodiment of the present invention the specified combination of the inhibitor of NF-kB and anti-inflammatory drug with IC50 of about 70 μg/ml or less reduces the secretion of cytokine IL-1α of at least about 35 percent when measured as described in example V TEST for IL-1α.

In another embodiment of the present invention the specified combination of the inhibitor of NF-kB and anti-inflammatory drug with IC50 of about 70 μg/ml or less reduces the secretion of cytokine IL-8 by at least about 80% when measured as described in example VIII TEST for IL-8.

Accordingly, the present invention also proposed ways to reduce the secretion of cytokine IL-1α in the skin or other tissue by at least about 35 percent when measured according to the TEST for IL-1α by topical application to a skin or other tissues of a combination of an inhibitor of NF-kB � anti-inflammatory drug, which is not an inhibitor of NF-kB and has an IC50 of about 70 μg/ml or less. The specified combination of the inhibitor of NF-kB and anti-inflammatory drugs can be used as a composition for topical application, as described in more detail below.

Proposed ways of reducing the secretion of cytokine IL-8 in the skin or other tissue by at least about 80% when measured according to the TEST for IL-8 by topical application to a skin or other tissues of a combination of an inhibitor of NF-kB and anti-inflammatory drug that is an inhibitor of NF-kB and has an IC50 of about 70 μg/ml or less. The specified combination of the inhibitor of NF-kB and anti-inflammatory drugs can be used as a composition for topical application, as described in more detail below.

The inhibitor of NF-kB

In this document, the term "inhibitor of NF-kB" means a compound that inhibits cell nuclear transcription factor Kappa B (NF-kB). In one embodiment of the inhibitor of NF-kB, tested in accordance with TEST FOR INHIBITION of NF-kB described below provides the percentage of inhibition of NF-kB, at least about 30%, preferably at least about 50%, preferably at least about 70%, most preferably at least approx�siteline 90%, the concentration in the testing process is preferably from 1 microgram per milliliter to about 100 micrograms per milliliter. This means that the compound demonstrates a specified percentage of inhibition of NF-kB in at least one concentration in the range of from 1 microgram per milliliter to 100 micrograms per milliliter. The connection does not have to provide a specified percentage of inhibition of NF-kB in all concentrations of 1 microgram per milliliter to 100 micrograms per milliliter, but must ensure that a specified percentage of inhibition of NF-kB in at least one concentration in this range.

In a preferred embodiment, the percentage of inhibition of NF-kB inhibitor of NF-kB is at least about 35%, preferably at least about 55%, more preferably at least about 70%, most preferably at least about 90% when tested at a concentration of 10 micrograms per milliliter.

TEST FOR INHIBITION of NF-kB is conducted as follows. Use cages FB293, representing a stable line transfected human epithelial cells containing reporter gene to determine the expression of NF-kB. They can be purchased, for example, in the comp�AI Panomics (G. Fremont, California). Cells FB293 is applied to the tablet at a concentration of 5×104cells/ml in the appropriate medium, for example, in modified according to the method of Dulbecco environment Needle (DMEM) with addition of 10% fetal bovine serum (Invitrogen, San Diego, California). Cells FB293 stimulate a solution of 100 ng/ml of tumor necrosis factor α (TNF-α, supplied by Sigma-Aldrich, St. Louis, Missouri) in the presence of test samples. Separately testing a control sample that does not contain the test sample. After incubation for 24 hours at 37°C in atmosphere of 5% CO2cells lisarow 40 ál of buffer for lysis reporter (Promega company, Madison, Wisconsin). An aliquot of the lysate volume of 20 µl were analyzed using a kit for luciferase assays (Promega) and do the counting in 10 seconds in a Lmax luminometer (Molecular Devices, Sunnyvale, CA). The data obtained are expressed in relative light units per second. The percentage of inhibition of NF-kB for the test sample is calculated as follows:

Inhibition of NF-kB=[1-(Lsample/Lcontrol)]*100

where Lsample- luminescence of the sample, and Lcontrol- luminescence of control.

One or more inhibitors of NF-kB may be present in compositions that are the subject of the present invention, in Liu�ohms allowable amount, for example, from about 0.01% by weight. to about 10% by weight., preferably from about 0.1% to about 20%, more preferably from about 0.1% to about 5%, even more preferably from about 0.2% to about 2%.

In one embodiment of the inhibitor of NF-kB is selected from the group consisting of the following compounds: substituted resorcinol, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile (such as Bay 11-7082, which is supplied by Sigma-Aldrich, St. Louis, Missouri), tetrahydrocurcuminoids (such as tetrahydrocurcuminoids CG, which is supplied by the company Sabinsa Corporation, G. Piscataway, state of new Jersey), extracts of Paulownia wood felt, and combinations thereof.

In a preferred embodiment the inhibitor of NF-kB is a substituted resorcinol. Resorcinol is a compound based dihydroxyindole (for example, 1,3-dihydroxybenzene) having the following structure:

In this document, the term "substituted resorcinol" means resorcinol containing at least one substituent in position 2, 4, 5 or 6. Thus, the substituted resorcinol may contain from one to four substituents. In positions 1 and 3 substituted resorcinol groups are-OH, as shown above.

Ve�mA preferably so none of the substituent groups of the substituted resorcinol did not contain phenyl (-C6H5aromatic) residues. In some embodiments, none of the substituents does not contain aromatic residues (with or without heteroatoms).

In other embodiments, it is preferable that none of the substituents in the substituted resorcinol did not contain a ketone functional groups (carbonyl group linked to two other carbon atoms).

In some preferred embodiments, none of the substituents in the substituted resorcinol contains not phenyl or ketone functional groups.

In some preferred embodiments, the substituted resorcinol comprises at least one Deputy containing from 5 to 11 carbon atoms, preferably from 5 to 10 carbon atoms, more preferably from 5 to 9 carbon atoms, most preferably from 5 to 8 carbon atoms. In some other embodiments, at least one alternate contains an alkyl group containing the above number of carbon atoms. Preferably, the alkyl group was unsaturated.

In some embodiments, the Deputy is polozhenii 4 resorcinol, in some embodiments, the Deputy is only in position 4 of resorcinol. In another embodiment, the substituent in position 4 is an alkyl group. In some preferred embodiments, the substituted resorcinol is the only substituent in position 4 with an alkyl group. In some other embodiments, the substituted resorcinol comprises a single substituent in position 4 representing an alkyl group directly connected to the benzene ring.

For particularly suitable substituted resorcinols include 4-geksilrezorzinol and 4-octylbenzene, especially 4-geksilrezorzinol. Patterns 4-hexylresorcinol and 4-octylbenzene shown below:

4-geksilrezorzinol

4-octylbenzene

4-geksilrezorzinol comes called SYNOVEA HR company Sytheon, Lincoln Park, new Jersey. 4-Octylbenzene supplied by City Chemical LLC, West haven, Connecticut.

In some embodiments, the substituted resorcinol comprises at least two of the substituent in positions 2, 4, 5 or 6. Such substituents can sometimes be connected in a ring, as, for example, cyclic Ali�interactive-hydrocarbon, which sometimes can contain heteroatoms, such as sulfur or oxygen. This coupled Deputy may contain from 5 to 10 carbon atoms, for example, from 8 to 10 carbon atoms, and may optionally contain 1 to 3 heteroatoms. Examples of appropriate substituted resorcinols containing cyclic aliphatic residual groups which unite States 2 and 3 are zearalenol and β-zearalenol:

Zearalenon

β-Zearalanol

Zearalenol and β-zearalenol supplied by Sigma Chemicals, St. Louis, Missouri.

In some other embodiments, the substituted resorcinol comprises halogenated and (or) nitrosoanabasine Vice. Examples contain the group-Cl, or-N=O directly connected to the benzene ring. Such substituents can be, for example, in positions 2 and 4, 2 and 6 or 4 and 6. Example dehalogenation of resorcinol is 2,6-declaratoria. Example dinitrotoluenes of resorcinol is 2,4-dinitroresorcinol:

2,4-dinitroresorcinol

2,6-declaratoria and 2,4-dinitroresorcinol supplied by City Chemical LLC, West haven, Connecticut.

Substituted resorcinol get known in this area�and ways, for example, using the techniques described in U.S. patent No. 4337370, the contents of which are incorporated herein by reference.

Substituted resorcinol may be of any acceptable molecular weight. In some embodiments, the molecular weight of the substituted resorcinol is in the range from about 175 to about 300.

Paulownia is a genus of plants originating from Asia and gradually spread in Europe and the USA. In Japan called Paulownia Kiri, and the title refers to one particular, Paulownia felt (Paulownia tomentosa), also called the "Princess tree". Other common names it should be noted the "Empress tree", "neprestannoe tree", "Royal Paulownia", "PAO Tong (China) and "Tong namu" (in Korea). Scientific name of this plant - Paulownia tomentosa (Paulownia felt), the literature also uses a number of synonyms, such as Paulownia imperialis, Paulownia recurva and Bignonia tomentosa. Paulownia felt belongs to the family pavlovniya, sometimes called nornicotine. In the database of the Ministry of agriculture of the USA (plants.USDA.gov) the Paulownia has a unique code PATO2 synonymous with Paulownia tomentosa and Paulownia imperialis.

For the purposes of the present invention can be any suitable extracts of Paulownia wood Waylon�th. Overall Paulownia wood includes a felt the wood of the trunk, branches, or combinations thereof. Valid extracts of Paulownia wood and felt can be derived from wood chips, wood dust and (or) small fragments of wood, etc.

Substituted resorcinol is present in the composition in a safe and effective amount, for example, from about 0.01% to about 10%, preferably from about 0.1% to about 5%, more preferably from about 0.2% to about 2%, even more preferably from about 0.5% to about 1.5% by weight. composition.

Anti-inflammatory drug

The structure of the compositions that are the subject of the present invention also includes anti-inflammatory medication, which is an inhibitor of NF-kB. More specifically specified anti-inflammatory medication provides the percentage of inhibition of NF-kB, as measured in accordance with the TEST FOR INHIBITION of NF-kB, less than about 30%, preferably less than about 20%, more preferably less than about 10% when tested in concentrations up to about 100 micrograms per milliliter. In other words, the drug demonstrates the percentage of inhibition of NF-kB to less than approximately 30%, preferably less than h�m approximately 20%, more preferably less than approximately 10% at all concentrations up to 100 micrograms per milliliter.

In a preferred embodiment of the specified anti-inflammatory medication provides the percentage of inhibition of NF-kB to less than approximately 30%, preferably less than about 20%, more preferably less than about 10% when tested in concentrations up to about 10 micrograms per milliliter.

Specified anti-inflammatory drug has an IC50 (concentration at which the degree of inhibition of inflammation drug reaches 50%) of approximately 70 μg/ml or less for interleukin-2 in the TEST FOR anti-INFLAMMATORY ACTIVITY described in this application. In a preferred embodiment of the IC50 for the indicated anti-inflammatory drug is approximately 50 μg/ml or less, preferably about 40 μg/ml or less, more preferably about 30 μg/ml or less.

In the TEST FOR anti-INFLAMMATORY ACTIVITY evaluates the ability of compounds to reduce the secretion of cytokines by human lymphocytes stimulated with activating receptors of T cells (TCR) agent phytohemagglutinin (PHA). The test is conducted as follows. Using leukocytopenia, in healthy adult male Zabira�t leukocytes of man and bring the density up to 1×10 6cells/ml in serum-free medium for the cultivation of lymphocytes (ExVivo-15, Biowhittaker company. Walkersville, Maryland). Pbls stimulated by 10 μg/ml PHA in the presence or in the absence of test samples, following published methods (Y. hamamoto's, et al. Exp Dermatol 2:231-235, 1993). After incubation for 48 hours of exposure at 37°C in atmosphere of 5% CO2take supernatant and examined it for cytokine content using a commercially available kit for multiplex determination of cytokines.

Relevant to the purposes of the present invention anti-inflammatory drugs with IC50 of about 70 μg/ml or less include:

the extract of bast Amur velvet (Phellodendron amurense);

feverfew (Tanacetum parthenium);

ginger (Zingiber officinale);

Ginkgo (Ginkgo Biloba);

smoke tree (Cotinus coggygria);

Lycium (Lycium barbarum);

extract Thistle marine (Silybum marianum);

honeysuckle (Lonicera japonica);

Peruvian balsam (Myroxylon pereirae);

sage (Salvia officinalis);

cranberry extract (Vaccinium oxycoccos);

amaranth oil (Amaranthus cruentus);

pomegranate (Punica granatum);

grass mate (leaf extract Ilex paraguariensis);

the extract of white Lily flowers (Lilium Candidum);

the extract of olive leaf (Olea europaea);

the phloretin (Apple extract);

lifeno (extract of hops ordinary, Humulus lupulus);

Licochalcone (licorice root: the extract from�odki, Glycyrrhiza inflata);

simself (bisabolol and ginger extract).

In some preferred embodiments the specified anti-inflammatory drug is selected from the following preparations: extract of bast Amur velvet (Phellodendron amurense), feverfew (Tanacetum parthenium), Ginkgo (Ginkgo Biloba), smoke tree (Cotinus coggygria), Lycium (Lycium barbarum) extract, Thistle marine (Silybum marianum), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), grass mate (leaf extract Ilex paraguariensis) extract, white Lily flowers (Lilium Candidum) extract, olive leaf (Olea europaea) and phloretin (Apple extract).

In some additional preferred embodiments, the specified anti-inflammatory drug is selected from the following drugs: feverfew (Tanacetum parthenium), Lycium (Lycium barbarum) extract, Thistle marine (Silybum marianum), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), grass mate (leaf extract Ilex paraguariensis) extract, white Lily flowers (Lilium Candidum) extract, olive leaf (Olea europaea) and phloretin (Apple extract).

Under the extracts of pyrethrum refers to extracts of the plant Tanacetum parthenium, which can be obtained, for example, in accordance with information provided in published patent application U.S. No. 2007/0196523 "BIOACTIVE COMPONENTS THAT do NOT CONTAIN PARTHENOLIDE OBTAINED FROM FEVERFEW� (TANACETUM PARTHENIUM), AND METHODS FOR THEIR PREPARATION". One particularly suitable pyrethrum extract in the form containing approximately 20% active pyrethrum, the company delivers Integrated Botanical Technologies, town of Ossining, state of new York.

The compositions forming the subject of the present invention may include a cosmetically effective amount of one or more anti-inflammatory drugs. The composition of said compositions as the active drug is preferably included from about 0.1% to about 10%, more preferably from about 0.5% to about 5% of the second anti-inflammatory drug.

In the compositions which are the subject of the present invention, the weight ratio of inhibitor of NF-kB and anti-inflammatory drug can vary. For example, the inhibitor of NF-kB and anti-inflammatory medication may be present in the ratio of the weight concentrations (which is determined by dividing the mass concentration of the inhibitor of NF-kB on the mass concentration of anti-inflammatory drug) from about 0.001 to about 100, preferably from about 0.01 to about 10, more preferably from approximately 0.1 to approximately 10.

Compositions for local application

The compositions forming the subject of the present invention, are used� for topical application to the skin or hair of a person. Along with the first and second anti-inflammatory drugs, the composition may further include a cosmetically acceptable carrier for topical application that may make up from about 50% to about 99.99% weight of the composition (e.g., from about 80% to about 99% weight of the composition). In a preferred embodiment of the invention cosmetically acceptable carrier for topical use contains water.

Compositions can be prepared in the form of a wide range of products, which include, among other things, lotions, creams, gels, pencils, sprays, ointments, cleansing liquid and solid bars for washing, shampoos and hair conditioners, tools, fixing hair, pastes, foams, powders, mousses, shaving cream, wipes, adhesive bandages, hydrogels, film-forming products, facial masks and skin protectors and decorative cosmetics, such as Foundation cream, Foundation and mascara. These product types may contain several types of cosmetically acceptable carriers for topical application, including, without limitation, solutions, suspensions, emulsions, for example, micro-emulsions and nano-emulsion, gels, solids and liposomes. Below are non-limiting examples of such media. Specialist in this field can prepare and other carriers.

The compositions used in the present invention, can be made in the form of solutions. The solutions generally contain water or an organic solvent (for example, from about 50% to about 99.99% or from about 90% to about 99% of a cosmetically acceptable aqueous or organic solvent). Examples of appropriate organic solvents include propylene glycol, polyethylene glycol (200-600), polypropylene glycol (425-2025), glycerol, 1,2,4-butanetriol, esters of sorbitol, 1,2,6-hexanetriol, ethanol and mixtures thereof.

Compositions used in the present invention, can be prepared in the form of a solution containing the softener. Such compositions preferably contain from about 2% to about 50% of the softener(s). In this document the term "softeners" are materials used to prevent or treat dry skin, for example, by preventing transepidermal water loss. Examples of the softeners include vegetable oils, mineral oils, esters of fatty acids, etc.

From the specified solution can be prepared lotion. Lotions typically comprise from about 1% to about 20% (e.g., from about 5% to about 10%) of the softener (s) and from about 50% to about 90% (e.g., from about�individual 60% to about 80%) is water.

Another type of product that can be produced from solution, is cream. A cream typically comprises from about 5% to about 50% (e.g., from about 10% to about 20%) of the softener (s) and from about 45% to about 85% (e.g., from about 50% to about 75%) is water.

Despite the fact that the composition constituting the subject of the present invention, preferably comprises water, in an alternative embodiment, the composition may be anhydrous or it may be a salve containing water and organic and (or) silicone solvents, oils, fats and waxes. The ointment may contain a simple base of animal or vegetable oils or semi-solid hydrocarbons. An ointment may contain from about 2% to about 10% softener(s) and from about 0.1% to about 2% thickener(s).

The composition may be prepared in the form of an emulsion. If a carrier for topical application is an emulsion, from about 1 to about 10% (e.g. from about 2 to about 5%) of the media is(s) emulsifier(s). The emulsifiers can be nonionic, anionic or cationic. Examples of appropriate emulsifiers are substances, usually identified as emulsifiers in the field of lisnagarvey and cosmetics.

Lotions and creams can be manufactured in the form of emulsions. Typically, such lotions contain from approximately 0.5 to approximately 5% of emulsifier(s). Such creams usually contain from about 1% to about 20% (e.g., from about 5% to about 10%) of the softener(s); from about 20% to about 80% (e.g. from 30% to approximately 70%) of water; and from about 1% to about 10% (e.g., from about 2% to about 5%) of emulsifier(s).

Preparations for skin care based on unilateral emulsions, such as lotions and creams of the type oil-in-water and water-in-oil is well known in the cosmetic industry and can be used in the present invention. Multiphase emulsion compositions, for example, of the type water-in-oil-in-water or oil-in-water-in-oil, can also be used in the present invention. Typically, such one-way or multiphase emulsions contain as a mandatory component of water softeners and emulsifiers.

The compositions forming the subject of the present invention can also be manufactured in the form of a gel (e.g. aqueous, alcoholic, aqueous-alcoholic or oil gel using a suitable gelling agent(s)). Appropriate gelling agents for water and (or) alcohol gels from�Osada, among other things, natural gums, acrylic acid, acrylate polymers and copolymers, cellulose derivatives (e.g., hydroxyethylcellulose and hydroxypropyl cellulose). Appropriate gelling agents for oils (such as mineral oil) include, among other things, the hydrogenated copolymer of butylene, ethylene and styrene and a hydrogenated copolymer of ethylene, propylene and styrene. In such gels, the content of gelling agents, usually ranges from approximately 0.1 to 5 wt%.

The compositions forming the subject of the present invention can also be produced in solid form (e.g., in the form of sticks on wax, bars of soap, powder or wipes containing powder).

Compositions that can be used in the present invention may contain, in addition to the aforementioned components, a wide variety of additional oil-soluble materials and (or) water-soluble materials conventionally used in compositions for skin care and hair care in known concentrations.

Additional cosmetically active substances

In one embodiment, the composition further contains another cosmetically active agent. Herein "cosmetically active agent" is called agents� (for example, synthetic or isolated from a natural source or a natural extract) providing a cosmetic or therapeutic effect on the skin or hair, including, among other things, remedies against acne, oily, antimicrobial agents, additional anti-inflammatory agents, antifungal agents, antiparasitic agents, analgesics external use, sunscreens, photoprotective agents, antioxidants, keratolytic remedies, surfactants, moisturizers, nutrients, vitamins, means that increase energy level, antiperspirants, means for tightening pores, deodorants, boosters, corn means and means for conditioning the hair and / or skin.

In one embodiment, the means chosen, inter alia, from the group consisting of Spartacist, benzoyl peroxide, D-panthenol, octylmethoxycinnamate acid, titanium dioxide, octisalate, homosalate, avobenzone, carotenoids, amines (e.g., neutral), retinoids such as retinol and remineralised, ceramides, polyunsaturated fatty acids, of fatty acids from essential oils, enzymes, enzyme inhibitors, minerals, hormones such as estrogens, steroids such as hydroco�Tyson, 2-dimethylaminoethanol, copper salts such as copper chloride, peptides containing copper such as Cu:Gly-His-Lys, coenzyme Q10, peptides, amino acids such as Proline, vitamins, lactobionic acid, acetyl-coenzyme A, Niacin, Riboflavin, thiamin, ribose, electron transporters such as NADH and FADH2, and other Botanical extracts such as aloe Vera, feverfew, oatmeal and derivatives and mixtures. Cosmetically active agent can generally be present in compositions that are the subject of the present invention, in an amount of from about 0.001 to about 20% by weight. compositions, for example, from about 0.005 to about 10%, in particular from about 0.01 to about 5%.

Examples of vitamins include vitamin a, b vitamins, e.g., vitamin B3, vitamin B5, and vitamin B12, vitamin C, vitamin K and various forms of vitamin E such as alpha-, beta-, gamma - or Delta-tocopherol, or mixtures thereof and derivatives.

Examples of spirocyclic include glycolic acid, lactic acid, malic acid, salicylic acid, citric acid and tartaric acid.

Examples of antioxidants include water soluble antioxidants such as sulfhydryl compounds and their derivatives (e.g., sodium metabisulfite and N-acetyl-cysteine), lipoic acid and dihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid and derivatives of ascorbic acid (e.g. ascorbyl palmitate and askorbinovoyj polypeptide). To fat-soluble antioxidants suitable for use in the compositions forming the subject of the present invention include, inter alia, butylated hydroxytoluene, retinoids (such as retinol and remineralised), Tocopherols (e.g., tocopherol acetate), tocotrienols, and ubiquinone. Natural extracts containing antioxidants suitable for use in the compositions forming the subject of the present invention include, inter alia, extracts containing flavonoids and isoflavones and their derivatives (e.g., genistein and diadzein), extracts containing resveratrol and etc. are examples of such natural extracts include grape seed extracts, green tea, pine bark, and propolis.

Other materials

The composition may be present and various other materials known in the art. These include humectants, pH regulators, chelating agents (such as EDTA), perfume and preservatives (e.g., parabens).

For use in the compositions that are the subject of the present invention, are also suitable dyes, soluble in water and in alcohol. Examples of dyes, �zgodnych for use in the present invention, are caramel, Carmine, fluorescein derivatives, methoxsalen, trioxsalen, azo dyes, anthraquinone dyes, blue azulene, guaiazulene, chamazulene, Erythro, tea rose, Floxin, cyanosis, defining, eosin G, Kozin 10B, acid red 51, red dye 4, red dye 40, blue dye 1, yellow dye 5, or mixtures thereof.

When using the dye, its concentration in the composition may vary from about 0.0001-0.1, preferably from about 0,0025 to approximately 0,025 (in percent of the total weight of the composition).

Composition, as well as compositions and products containing these compositions can be prepared using methods well known to those skilled in this field.

Methods of application

The compositions forming the subject of the present invention, can be applied topically by application to the skin of mammals requiring treatment with one or more signs of skin aging described above. In one embodiment the composition is applied to the skin that needs treatment of furrows, wrinkles and (or) in the treatment of loss of elasticity. The compositions can be applied to require that the skin in the appropriate regimen, e.g., monthly, weekly, every other day, daily, twice daily, etc.

In some�which embodiments of the composition, forming the subject of the present invention can also be used to treat other conditions associated with skin. For example, the compositions forming the subject of the present invention can be used to treat post-inflammatory hyperpigmentation, to reduce the size of pores, treat acne, reduce sebum secretion of the sebaceous glands and reduce scarring. In some other embodiments, the compositions forming the subject of the present invention, can be applied simultaneously or within a few hours after the use of mechanical or physical exfoliation, for example, mikroshlifov skin, or chemical scrub or keratolytic agents, for example, salicylic acid. In some other embodiments, the compositions forming the subject of the present invention, is applied to the mucosa or other tissue, e.g., tissue of the vagina, mouth or eyes. In some other embodiments, the compositions forming the subject of the present invention, applied to minor wounds or post-surgical skin for faster healing of insect bites, burns with poison sumac or other skin conditions, or in General to reduce itching. In some other embodiments, osushestvlyaetsya compositions forming the subject of the present invention, is applied to reduce the irritation of the skin. Irritation can be caused by external reasons and due to the presence in cosmetic products and products for skin care components such as a retinoid and its derivatives, benzoyl peroxide, alpha-hydroxy acids and their derivatives, salicylic acid, surfactants, natural plant extracts, active ingredients of sunscreens, urea, preservatives, etc. Irritation can also be caused by other external causes such as sun, wind or shaving. Irritation can also be caused by internal pathological conditions, such as acne different type, atopic dermatitis and other pathological conditions.

It is assumed that the specialist, based on this description, can utilize the present invention to the maximum extent. Below are typical embodiments of the invention should be considered only as examples, which in no way limit the disclosed the essence of the present patent application. The following non-limiting examples serve to further illustrate the invention.

Example I

As described above, the TEST FOR INHIBITION of NF-kB was performed on the test samples of substances Bay 11-7082 (Sigma-Aldrich, St. Louis, �tat mo tetrahydrocurcuminoids CG (Sabinsa Corporation, G. Piscataway, state of new Jersey) and various concentrations of 4-hexylresorcinol. The results are shown in table 1, in which for test samples and a control sample indicates the importance of activation of reporter gene for NF-kB (luminescence, L). Also shown is the percentage of inhibition of NF-kB.

TABLE 1
Activation of reporter gene for NF-kB (luminescence, L)The percentage of inhibition of NF-kB
Without treatment1,2±0,3_
Stimulation with TNF-α
(100 ng/ml), Lcontrol
To 108.2±8,5_
TNF-α + 4-geksilrezorzinol
(50 µg/ml)
9,3±0,991,4%
TNF-α + 4-geksilrezorzinol
(10 µg/ml)
29,3±9,272,9%
TNF-α + 4-geksilrezorzinol
(5 µg/ml)
55,1±1,750,9%
TNF-α + 4-hexyl�sarcina
(1 µg/ml)
106,1±1,91,9%
TNF-α + tetrahydrocurcuminoids CG (10 µg/ml)37,8±2,665,1%
Bay 11-7082 (25 µm)11,3±5,689,5%

Bay 11-7082 and tetrahydrocurcuminoids CG showed a strong inhibition of NF-kB. Unexpected way 4-geksilrezorzinol also caused a significant reduction in activation of NF-kB. Even more unexpectedly, 4-geksilrezorzinol caused a significant inhibition of NF-kB even at low concentrations.

Example II

As described above, the TEST FOR INHIBITION of NF-kB was performed for a series of substituted resorcinols, the concentration of each of which was 10 µg/ml. the Results are shown in table 2.

TABLE 2
StructureThe percentage of inhibition of NF-kB
4-octylbenzene99,5%
4-geksilrezorzinol 92,4%
β-zearalenol
CAS No. 71030-11-0
87,1%
β-zearalanol
CAS No. 42422-68-4
76,56%

2,4-dinitroresorcinol51,78%
4-chlororesorcinol51,63%
2,6-dichlororesorcinol51,54%
Zearalenon50,95%
Geneticresources31,8%
4-dodecylbenzene20,87%
4-ciprolisinaOf 10.25%

C-undecylenic[4]
-resorcinarene4,87%3-methoxyphenol0%2',4'-dihydroxypropane-0,7%2,4-DIHYDROXYACETONE acid-1,7%1,3-dimethoxybenzene-1,7%

From the table 2 data shows that the greatest inhibition of NF-kB provide substituted resorcinol in which the substituents do not contain phenyl functional groups, substituted resorcinol in which the substituents do not contain a ketone functional groups, and substituted resorcinol in which the Deputy contains from 5 to 11 carbon atoms.

Example III

As described above, the TEST FOR INHIBITION of NF-kB and the TEST FOR anti-INFLAMMATORY ACTIVITY was carried out for a plurality of compounds. The results are shown below in tables 3a and 3b.

Table 3a lists the PR�tivovospalitiona drugs in accordance with the present invention with an IC50 of about 70 μg/ml or less. In table 3b are shown for comparison of anti-inflammatory drugs with IC50 greater than 70 μg/ml.

TABLE 3a
ExtractThe activity of NF-kB
(10 µg/ml)
Anti-inflammatory activity
(IC50, µg/ml)
The extract of bast Amur velvet (Phellodendron amurense)0%42,5
Feverfew (Tanacetum parthenium)0%38,1
Ginger (Zingiber officinale)6%61,2
Ginkgo (Ginkgo Biloba)5%45,2
Smoke tree (Cotinus coggygria)0%44,2
Lycium (Lycium barbarum)9,50%19,0
Extract Thistle marine (Silybum marianum)9,60%13,8
Honeysuckle (Lnicera japonica )0%64,2
Peruvian balsam (Myroxylon pereirae)Of 3.60%52,9
Sage (Salvia officinalis)0,68%56,9
Cranberry extract (Vaccinium oxycoccos)Of 5.36%60,9

Amaranth oil (Amaranthus cruentus)0%39,8
Pomegranate (Punica granatum)0,885,9
Grass mate (leaf extract ofIlex paraguariensis)0,76%A 20.7
The extract of white Lily flowers (Lilium Candidum)0%32,1
The extract of olive leaf (Olea europaea)8,78%28,3
The phloretin (Apple extract)0%19,9
Lifeno (hop extract Oba�novenas, Humulus lupulus)0,60%63,7
Licochalcone (licorice root: a component of licorice extract,Glycyrrhiza inflata)0%54,1
Simself (bisabolol and ginger extract)0%58,9

TABLE 3b
ExtractThe activity of NF-kB
(10 µg/ml)
Anti-inflammatory activity
(IC50, µg/ml)
Non-denatured soybean (Glycine max)0%84,1
Madecassoside (a component of the extract of Centella asiatica,Centella asiatica)0%77,3
Bugrane P (harrow prickly,Ononis spinosa)0%71,1

Example IV

Component object of the present invention the composition described in example 1, prepared from the components listed below in table 4.

TABLE 4
The name according to INCITrade nameWeight fraction, %
Deionized waterPurified water77%
PentylindolHYDROLITE 55%
GeksilrezorzinolSYNOVEA HR1%
OleosomeOleosome NATRULON OSF10%
C12-15 alkylbenzoicFINSOLV TN4%
Acryloyldimethyltaurate ammonium/VP copolymerARISTOFLEX AVC2%
The juice of the leaves/flowers/stems of Chrysanthemum Parthenium (feverfew)The extract ofTanacetum parthenium1%
FINSOLV TN supplied by the company Finetex, Inc., G. Elmwood Park, new Jersey.
HYDROLITE 5 supplied by the company Symrise, H. Teterboro, state of new Jersey.
SYNOVEA HR supplies company Sytheon, Lincoln Park, state of new jer�I.
ARISTOFLEX AVC supplied by the company Clariant, Frankfurt, Germany.
Oleosome NATRULON OSF supplied by the company Lonza, Allendale, new Jersey.

The composition is prepared in the following manner. Prepared the linkage component Synovea HR, which was dissolved in HYDROLITE 5, and then added deionized water. Thus, there was obtained a phase A. Oleosome and Finsolv TN were mixed and received phase B. Phase B very slowly, with constant stirring, added to phase A. the Stirring was continued for 15 minutes to obtain a homogeneous emulsion. To the emulsion at a constant fast stirring added ARISTOFLEX, whereby was obtained a dense homogeneous structure.

Example V

To study the secretion of proinflammatory mediator, cytokine IL-1α, in the epithelial cells of the person tested for IL-1α with many agents.

The test for IL-1α was performed as follows. Cell line KB was acquired from ATCC (ATCC no CCL-17, city of Manassas, Virginia). Cells were seeded on treated 96-well plates for culturing with a density of 5000 cells per well in modified according to the method of Dulbecco environment Needle (DMEM) with addition of 10% fetal bovine serum (Invitrogen, San Diego, California). After 48 hours the cells were processed within 24 hours of the following drugs at the indicated concentrations, after which otbi�Ali supernatants and analyzed them to the level of secretion of the cytokine IL-1α using commercially available kits (Millipore Corp., city of Woburn, Massachusetts). The results are presented below in table 5.

TABLE 5
ExampleProcessing
(dosage in mcg/ml)
The average level of secretion of IL-1α (PG/ml)
Comparative example comp. 1Without treatment0,72
Comparative example comp. 24-geksilrezorzinol
(20 µg/ml)
21,34
Comparative example comp. 3Tetrahydrocurcuminoids
(20 µg/ml)
2,51

The obtained results indicate that inhibitors of NF-kB, such as 4-geksilrezorzinol and tetrahydrocurcuminoids, with its ability to inhibit factor NF-kB, can increase the secretion of cytokine IL-1α.

Example VI

Conducted additional tests on IL-1α as described in example 5. For easier comparison of the results is the degree of increase in the secretion of IL-1α for 4-hexylresorcinol, phloretin, and combinations thereof was normalized to the corresponding value for 4-hexylresorcinol (20 μg/ml, compare�individual example 2). Given the degree of increase in the secretion of IL-1α of tetrahydrocurcuminoids, pyrethrum and their combinations was normalized to the corresponding value for tetrahydrocurcuminoids (20 μg/ml, comparative example 3). The results are presented below in table 6.

TABLE 6
ExampleTreatment (dose in micrograms/ml)An increase in the secretion of IL-1α compared with the untreated control sample (normalized)Decreased secretion of IL-1α, %
Comparative example comp. 24-geksilrezorzinol (20 µg/ml)100-
Comparative example comp. 4The phloretin (10 µg/ml)3,82-
Comparative example comp. 5The phloretin (50 µg/ml)2,39-
Comparative example comp. 6The phloretin (100 µg/ml)3,34-
Example 2 according to the present invention4-geksilrezorzinol
(20 μg/ml) + phloretin (10 µg/ml)
55,5144,49%
Example 3 according to the present invention4-geksilrezorzinol (20 μg/ml) + phloretin (50 µg/ml)10,1389,87%
Example 4 according to the present invention4-geksilrezorzinol (20 μg/ml) + phloretin (100 µg/ml)17,0182,98%

Comparative example comp. 3Tetrahydrocurcuminoids (20 µg/ml)100-
Comparative example comp. 7Feverfew (50 µg/ml)49,35-
Comparative example comp. 8Feverfew (100 µg/ml)43,42-
Example 5 according to the present invention42,0957,91
Example 6 according to the present inventionTetrahydrocurcuminoids (20 μg/ml) + feverfew (100 µg/ml)62,3937,61

The results show that, although the inhibitors of NF-kB can induce the secretion of cytokine IL-1α, it can be converted using the inhibitor of NF-kB in combination with anti-inflammatory drug with IC50 of about 70 μg/ml or less (e.g., feverfew or phloretin).

Example VII

Were conducted additional tests on IL-1α as described in example 5. For easier comparison of the results is the degree of increase in the secretion of IL-1α was normalized to the corresponding value for 4-hexylresorcinol (20 μg/ml, comparative example 2).

TABLE 7
ExampleProcessing
(dosage in mcg/ml)
An increase in the secretion of IL-1α compared with the untreated control sample (normalized)Decreased secretion of IL-1α, %
Comparative example comp. 24-geksilrezorzinol (20 µg/ml)100-
Comparative example comp. 9Soy (10 µg/ml)2,62-
Comparative example comp. 10Soy (50 µg/ml)2,59-
Comparative example comp. 11Soybeans (100 µg/ml)4,61-
Comparative example comp. 124-geksilrezorzinol (20 μg/ml) + soya (10 µg/ml)81,8418,16%
Comparative example comp. 134-geksilrezorzinol (20 μg/ml) + soya (50 µg/ml)65,3534,65%
Comparative example comp. 144-geksilrezorzinol (20 μg/ml) + soya (100 µg/ml)82,5517,45%
Comparative example comp. 15Madecassoside (10 m�g/ml) 43,02
Comparative example comp. 16Madecassoside (50 µg/ml)41,59
Comparative example comp. 17Madecassoside (100 µg/ml)Of 44.24

Comparative example comp. 184-geksilrezorzinol (20 μg/ml) + madecassoside (10 µg/ml)149,68-49,68%
Comparative example 194-geksilrezorzinol (20 μg/ml) + madecassoside (50 µg/ml)119,12-19,11%
Comparative example 204-geksilrezorzinol (20 μg/ml) + madecassoside (100 µg/ml)71,3828,62%
Comparative example 21Bugrane P (10 µg/ml)41,90
Comparative example 22Bugrane P (50 µg/ml) 46,73
Comparative example 23Bugrane P (100 µg/ml)54,45
Comparative example 244-geksilrezorzinol (20 μg/ml) + Bugrane P (10 µg/ml)83,0416,96%
Comparative example 254-geksilrezorzinol (20 μg/ml) + Bugrane P (50 µg/ml)89,3410,66%

The results show that combinations of inhibitors of NF-kB inflammatory drugs with higher IC50 of about 70 μg/ml may not provide such a decrease in the secretion of cytokine IL-1α, as a combination of inhibitors of NF-kB inflammatory drugs with IC50 of about 70 μg/ml or less. The above data indicate that combinations of inhibitors of NF-kB inflammatory drugs with higher IC50 of about 70 μg/ml decreases the secretion of cytokine IL-1α less than 35%.

It should be noted that in comparative examples 9-14 soy is not dissolved in the medium for the test and instead were dispersed.

Example VIII

Using the method described in example 5, but analysts�of iroa the secretion of cytokine IL-8, several compositions were tested for IL-8. For each sample calculate the percentage degree of reduction in the secretion of IL-8. The results are shown in table 8. For samples containing a combination of an inhibitor of NF-kB and anti-inflammatory drug, refers to the percentage degree of reduction in the secretion of IL-8 in relation to interest and the reduction in the secretion of IL-8 for the appropriate dosage of anti-inflammatory drug.

TABLE 8
ExampleProcessing
(dosage in mcg/ml)
The average level of secretion of IL-8 (PG/ml)The percentage degree of reduction in the secretion of IL-8 (referenced to the appropriate dosage of anti-inflammatory drug without the inhibitor of NF-kB)
Comparative example 26Without treatment46,05-
Comparative example 274-geksilrezorzinol (20 µg/ml)14,58-
Comparative example 28Feverfew (10 µg/ml)52,94/td> -
Comparative example 29Feverfew (50 µg/ml)85,48-
Comparative example 30Feverfew (100 µg/ml)110,10-
Example 7 according to the present invention4-geksilrezorzinol (20 μg/ml) + feverfew (10 µg/ml)7,1185,56%
Example 8 according to the present invention4-geksilrezorzinol (20 μg/ml) + feverfew (50 µg/ml)14,5882,94%

Example 9 according to the present invention4-geksilrezorzinol (20 μg/ml) + feverfew (100 µg/ml)Of 8.7992,02%
Comparative example 31Phytoterra (10 µg/ml)157,32--
Comparative example 32 Phytoterra (50 µg/ml)211,33
Comparative example 33Phytoterra (100 µg/ml)183,02
Example 10 according to the present invention4-geksilrezorzinol (20 μg/ml) + Phytoterra (10 µg/ml)Of 7.3695,32%
Example 11 according to the present invention4-geksilrezorzinol (20 μg/ml) + Phytoterra (50 µg/ml)Is 8.8495,82%
Example 12 according to the present invention4-geksilrezorzinol (20 μg/ml) + Phytoterra (100 µg/ml)The 5.2597,13%

The results show that combinations of inhibitors of NF-kB and anti-inflammatory drugs with IC50 of about 70 μg/ml or less sharply decrease the level of expression of IL-8 compared with the effect of any of the drugs individually.

Example IX

Spent another TEST for IL-8 as described in example 8, but varied the ratio of the inhibitor of NF-kB and anti-inflammatory drug with IC50 of about 70 μg/ml or less. Rece�e the results are presented below in table 9.

TABLE 9
ExampleTreatment (dose in micrograms/ml)The average level of secretion of IL-8 (PG/ml)The percentage degree of reduction in the secretion of IL-8 (referenced to the appropriate dosage of anti-inflammatory drug)
Comparative example 34Without treatment84,46-
Comparative example 354-geksilrezorzinol
(10 µg/ml)
73,23-
Comparative example 364-geksilrezorzinol
(20 µg/ml)
27,05-
Comparative example 37Phytoterra (2 µg/ml)275,31-
Comparative example 38Phytoterra (20 µg/ml)403,49-
Comparative example 39Phytoterra (00 µg/ml) 479,59-
Example 13 according to the present invention4-geksilrezorzinol (20 μg/ml) + Phytoterra (2 µg/ml)18,0093,46%
Example 14 according to the present invention4-geksilrezorzinol (20 μg/ml) + Phytoterra (20 µg/ml)29,1692,78%
Example 15 according to the present invention4-geksilrezorzinol (10 μg/ml) + Phytoterra (100 µg/ml)36,8492,32%

The results indicate that the pronounced increase in efficacy of the combination of inhibitors of NF-kB and anti-inflammatory drugs with IC50 of about 70 μg/ml or less is observed in a wide range of weight ratios of the concentrations of the two active ingredients (checked weight ratio of 10:1, 1:1 and 1:10 for examples 13, 14 and 15 according to the present invention, respectively).

In General, anti-inflammatory mixture, forming the subject of the present invention, decreases the secretion of both inflammatory cytokines IL-1 and IL-8, and, as a rule, provide inhibition of NF-kB.

Despite�I the fact that the disclosure of the present invention is accompanied by a similar description, it is implied that the purpose of the descriptions is to illustrate but not limit the scope of the present invention, which is defined by the scope of the annexed claims. Other aspects, advantages and modifications are determined by these claims.

1. Composition for treating signs of skin aging, increase the secretion of cytokine IL-1α containing:
the inhibitor of NF-kB selected from the group consisting of substituted resorcinols, (E)-3-(4-methylphenylsulfonyl)-2-propenenitrile, tetrahydrocurcuminoids, extracts of Paulownia wood felt, and combinations thereof; and
anti-inflammatory compound is not an inhibitor of NF-kB and has a concentration IC50 of about 70 μg/ml or less,
where the inhibitor of NF-kB and anti-inflammatory compound are present in a weight ratio of from about 1:10 to about 10:1.

2. Composition for treating signs of skin aging, increase the secretion of cytokine IL-1α containing:
the inhibitor of NF-kB selected from the group consisting of substituted resorcinols, and
anti-inflammatory compound selected from the group consisting of extract of bast Amur velvet (Phellodendron amurense), pyrethrum parthenium (Tanacetum parthenium), Ginkgo (Ginkgo Biloba), smoke tree (Cotinus coggygria), Lycium (Lycium barbarum), extract of CER�Aloha sea (Silybum marianum), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), herb maté (leaf extract Ilex paraguariensis), extract of white Lily flowers (Lilium Candidum), extract of olive leaf (Olea europaea), phloretin (Apple extract), and combinations thereof,
where substituted resorcinol do not contain phenyl functional groups;
anti-inflammatory compound has a concentration IC50 of about 70 μg/ml or less, and
the inhibitor of NF-kB and anti-inflammatory compound are present in a weight ratio of from about 1:10 to about 10:1.

3. Composition for treating signs of skin aging, increase the secretion of cytokine IL-1α containing:
the inhibitor of NF-kB selected from the group consisting of substituted resorcinols, and
anti-inflammatory compound selected from the group consisting of extract of bast Amur velvet (Phellodendron amurense), pyrethrum parthenium (Tanacetum parthenium), Ginkgo (Ginkgo Biloba), smoke tree (Cotinus coggygria), Lycium (Lycium barbarum), extract of Thistle marine (Silybum marianum), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), herb maté (leaf extract Ilex paraguariensis), extract of white Lily flowers (Lilium Candidum), extract of olive leaf (Olea europaea), phloretin (Apple extract), and combinations thereof,
where substituted resorcinol is 4-geksilrezorzinol,
anti-inflammatory compound has a concentration�tion IC50 of about 70 μg/ml or less; and
the inhibitor of NF-kB and anti-inflammatory compound are present in a weight ratio of from about 1:10 to about 10:1

4. Composition for treating signs of skin aging, increase the secretion of cytokine IL-1α containing:
the inhibitor of NF-kB selected from the group consisting of substituted resorcinols, and
anti-inflammatory compound selected from the group consisting of extract of bast Amur velvet (Phellodendron amurense), pyrethrum parthenium (Tanacetum parthenium), Ginkgo (Ginkgo Biloba), smoke tree (Cotinus coggygria), Lycium (Lycium barbarum), extract of Thistle marine (Silybum marianum), amaranth oil (Amaranthus cruentus), pomegranate (Punica granatum), herb maté (leaf extract Ilex paraguariensis), extract of white Lily flowers (Lilium Candidum), extract of olive leaf (Olea europaea), phloretin (Apple extract), and combinations thereof,
where the inhibitor of NF-kB and anti-inflammatory compound are present in a weight ratio of from about 1:10 to about 10:1; and
anti-inflammatory compound has a concentration IC50 of about 70 μg/ml or less.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention aims at pharmaceutical compositions containing a number of microparticles with taste masking, containing high-/low-dose therapeutic agents, at dosage forms containing the above pharmaceutical compositions (such as orally dispersible tablets), and at methods for producing these pharmaceutical compositions and dosage forms.

EFFECT: dosage forms containing the pharmaceutical compositions according to the invention represent the improved homogenous mixtures of the high-dose and low-dose therapeutic agents, which enable controlling the release rate of the therapeutic agent from particles by various ways, as well as flexible correction of dosages when administering the combinations of the therapeutic agents, eg in pain management.

31 cl, 4 dwg, 12 tbl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of the general formula

,

wherein R1/R2 independently represent hydrogen, (CR2)o-C3-7 cycloalkyl optionally substituted by a lower alkyl or hydroxy, or represent a lower alkyl or tetrahydropyranyl, and o represents 0 or 1; and R can be identical or different, and represent hydrogen or a lower alkyl; or R1 and R2 can form together with a N atom to which they are attached, a heterocycloalkyl group specified in a group consisting of pyrrolidinyl, piperidinyl, 3-aza-bicyclo[3.1.0]hex-3-yl or 2-aza-bicyclo[3.1.0]hex-2-yl which are optionally substituted by hydroxy; R3 represents an S-lower alkyl, lower alkyl, lower alkoxy or C3-7 cycloalkyl; R3′ represents hydrogen, a lower alkyl substituted by a halogen, lower alkyl or lower alkoxy; R4 represents a lower alkyl substituted by a halogen; X represents -O- or -CH2-; X' represents -O- or -CH2-; provided one of X or X' always represent -O- and the other represents -CH2-; or a pharmaceutically acceptable acid-additive mixture, a racemic mixture, or a respective enantiomer and/or an optical isomer.

EFFECT: compounds of the general formula (I) are good inhibitors of glycine transporter 1 (GlyT-1) and hence can be used for treating schizophrenia and other neurological conditions, including pain.

13 cl, 1 tbl, 63 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel N-containing heteroaryl derivatives of formula I or II or their pharmaceutically acceptable salts, which possess properties of JAK kinase, in particular JAK3, and can be applied for treating such diseases as asthma and chronic obstructive pulmonary disease (COPD). In formulae A represents carbon and B represents nitrogen or A represents nitrogen and B represents carbon; W represents CH or N; R1 and R2, independently represent hydrogen, C1-4alkyl, halogenC1-4alkyl, -CN; R3 represents C1-4alkyl, R9-C1-4alkyl, Cy1, where Cy1 is optionally substituted with one or several substituents R10; R4 represents hydrogen, C1-4alkyl, R12R7N-C0alkyl, where one of R7 and R12 represents hydrogen, and the other represents C1-4alkyl or group R13, which is selected from C1-5alkyl, Cy2-C0alkyl; R5 represents hydrogen; R6 represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, R12R7N-C1-4alkyl, R16CO-C0alkyl, Cy1; R7 represents hydrogen or C1-4alkyl; R9 represents halogen, -CN, -CONR7R12, -COR13, CO2R12, -OR12, -SO2R13, -SO2NR7R12, -NR7R12, -NR7COR12; R10 represents C1-4alkyl or R9-C0-4alkyl; R11 represents C1-4alkyl, halogen, -CN, -NR7R14; R12 represents hydrogen or R13; R13 represents C1-5alkyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, Cy2-C0alkyl or R14R7N-C1-4alkyl; where Cy2 is optionally substituted with one or several constituents R11; R14 represents hydrogen or C1-4alkyl; R16 represents C1-4alkyl, halogenC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl or cyanoC1-4alkyl; Cy1 represents monocyclic carbocyclic unsaturated or saturated ring, selected from C3-C6cycloalkyl, phenyl, or saturated monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or partially unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available C atom, and where one or several ring C or S atoms are optionally oxidised with formation of CO or SO2; and Cy2 represents monocyclic carbocyclic unsaturated ring, selected from C3-C6cycloalkyl, or aromatic monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available atom C or N.

EFFECT: obtaining novel heteroaryl derivatives.

27 cl, 41 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I, possessing ability of binding with delta-opioid receptors. In formula R1 is selected from the group, consisting of i) phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxyl, di(C1-4alkyl), aminocarbonyl, chlorine and fluorine, in such a way that only one di(C1-4alkyl)aminocarbonyl is present; ii) naphthyl; iii) pyridinyl, optionally substituted with one substituent, selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxy, fluorine, chlorine and cyano; iv) pyrimidin-5-yl; v) furanyl; vi) thienyl; vii) 5-oxo-4,5-dihydro-[1,2,4]oxodiazol-3-yl; and viii) di(C1-2alkyl)aminocarbonyl; Y represents ethyl, vinyl or bond; or Y represents O, when R1 represents optionally substituted phenyl, where substituent represents C1-4alcoxy; R2 represents phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, fluorine, chlorine and cyano, trifluoromethoxy and hydroxy; or R2 represents phenyl, substituted with one aminocarbonyl, di(C1-4alkyl)aminocarbonyl, C1-4alcoxycarbonyl or carboxysubstituent; R3 is selected from the group, consisting of i) 3-aminocyclohexyl; ii) 4-aminocyclohexyl; iii) piperidin-3-yl; iv) piperidin-4-yl; v) pyrrolodin-2-yl-methyl, in which pyrrolodin-2-yl is optionally substituted by 3-rd or 4-th position with one or two fluorine-substituents; vi) azetidin-3-yl; vii) 2-(N-methylamino)ethyl; viii) 3-hydroxy-2-aminopropyl; ix) piperidin-3-yl-methyl; x) 1-azabicyclo[2.2.2]octan-3-yl; and xi) 8-azabicyclo[3.2.1]octan-3-yl; or R3 together with Ra and nitrogen atom, which they both are bound to, form piperazinyl, optionally substituted with 4-C1-4alkyl; Ra represents hydrogen, 2-(N-methylamino)ethyl or C1-2alkyl, optionally substituted with azetidin-3-yl.

EFFECT: compounds can be used in treatment of pain in the range from medium to strong, caused by diseases or conditions, such as osteoarthritis, migraine, burn, fibromyalgia, cystitis, rhenite, neuropathic pain, idiopathic neuralgia, toothache, etc.

21 cl, 4 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to substituted phenylureas and phenylamides of formula in which X stands for CR3 or N, where R3 stands for H; C1-10alkyl, saturated or unsaturated, branched or non-branched, non-substituted; or CF3; A stands for N or CR5b; R1 stands for substructure , which has the formula, given below. The other radicals and symbols have the values, given in the invention formula. The invention also relates to methods of obtaining formula (If) compounds, to pharmaceutical compositions, containing the said compounds, as well as to the application of the said compositions for the preparation of the pharmaceutical compositions.

EFFECT: formula (If) compounds possess activity with respect to the vanilloid receptor of I subtype (receptor VR1/TRPV1).

7 cl, 1 tbl, 147 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a novel compound of formula

(I)

or its pharmaceutically acceptable salt, possessing properties of the IKKβ and TNFα inhibitor. The compound can be used with an additional therapeutic agent, selected from vincristine, camptothecin hydrochloride (CPT-11), lefunomid, dexamethasone and TNFα. Preferable are compounds of formula (I), corresponding to 2-{5-chloro-2-[(1R,2R)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide and 2-{5-chloro-2-[(1R,2S)-2-hydroxycyclopentylamino]pyrimidin-4-yl}-N-cyclopropyl-1H-indole-4-carboxamide.

EFFECT: compound can be applied in the treatment of inflammatory diseases such as rheumatoid arthritis, chronic obstructive lung disease, bronchial asthma, multiple sclerosis and intestinal inflammatory diseases, or cancer diseases, such as multiple myeloma, colon cancer, pancreas cancer and ovary cancer, by IKKβ inhibition.

30 cl, 4 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: method includes treating crushed Echinacea purpurea (L.) Moench roots and rhizome with steam, extraction with ethyl alcohol, then steeping, stirring, steeping, draining a portion of the extract which is equal to the amount of the loaded Echinacea purpurea (L.) Moench roots and rhizome, after draining a portion of the extract, adding ethyl alcohol to the treated material, draining the whole extract; extracting crushed Echinacea purpurea (L.) Moench herbs with ethyl alcohol, steeping, then stirring, steeping, draining a portion of the extract which is equal to the amount of the loaded Echinacea purpurea (L.) Moench herbs, after draining a portion of the extract, adding ethyl alcohol to the treated herbs, draining the whole extract; all obtained extracts are mixed, cooled and filtered under certain conditions. An Echinacea purpurea (L.) Moench tincture. Use of the method to obtain an Echinacea purpurea (L.) Moench tincture.

EFFECT: method preserves the biological activity of components of the tincture and medicinal properties.

3 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I), their pharmaceutically acceptable salts, tautomers or stereoisomers. In formula R1 represents benzimidazolyl optionally substituted by C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, dimethylaminoC1-4alkyl or oxo group; benzioxazolyl optionally substituted by C1-4alkyl or amino group; benzotriazolyl optionally substituted by C1-4alkyl; dihydrobenzisothiazol-1,1-dionyl; pyrimidyl; dihydroisoquinolinonyl optionally substituted by oxo group; imidazopyridyl; indazolyl optionally substituted by C1-4alkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, tetrahydropyranylamino, piperidinylamino, halogen, trifluoromethyl or amino group; indolinyl optionally substituted by C1-4alkyl, hydroxyC1-4alkyl, carboxylate or oxo group; isoindolinyl optionally substituted by C1-4alkyl, aminoC1-4alkyl, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl or oxo group; phenyl optionally substituted by C1-4alkyl, C1-4alkoxy, halogen, cyano, trifluoromethyl, carbamoyl, methylcarbamoyl, piperidinylcarbamoyl, methylpiperidinylcarbamoyl, aminoC1-4alkyl, carboxyl, amino, dialkylamino, imidazolyl, pyrrolidin-2-one, triazolyl, morpholinyl, C1-4alkylcarbonylamino, C1-4alkoxyC1-4alkoxy or hydroxyC1-4alkyl; pyrazolopyridyl optionally substituted by C1-4alkyl; pyridyl optionally substituted by C1-4alkyl, C1-4alkoxy, halogen, cyano, hydroxy, amino, morpholinyl, carbamoyl, monoC1-4alkylamino, diC1-4alkylamino, aminoC1-4alkoxy, aminoC1-4alkylamino, hydroxypiperidinyl, hydroxyC1-4alkyl, hydroxyC1-4alkoxy, pyrrolidinylC1-4alkylamino, pyrrolidinylC1-4alkoxy; pyrrolopyridinyl optionally substituted by oxo group; quinolinyl optionally substituted by amino or hydroxy group; or triazolopyridyl substituted by C1-4alkyl. The other radical values are presented in the patent claim. The invention also refers to individual compounds, to a pharmaceutical composition, possessing kinase inhibitory activity and containing an effective amount of the compound of the invention, to a method for kinase inhibition in a cell, to a method of treating or preventing inflammatory conditions, immunological conditions, allergic conditions, rheumatic conditions, cancer, and neuroinflammatory diseases.

EFFECT: there are prepared new compounds possessing Syk, FLT3, JAK1, JAK2 inhibitory activity.

21 cl, 1 tbl, 133 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a new hydrate of 2-amino-2-(2-(4-octylphenyl)ethyl)propane-1,3-diol hydrochloride salt in the crystalline form with the characteristics below. The hydrate can be used for producing a drug or for treating or preventing a transplanted organ or tissue rejection, or autoimmune diseases in a therapeutically effective amount. The above hydrate is characterised by an X-ray powder diffractogram having peaks at approximately 2.9, 17.2, 30.6, 28.2, 24.4, 8.6 and 25.9 degrees 2-Theta with a limit of error of ±0.2 degrees for each value of 2θ, having a purity of 90% or more, and containing 5.2 to 5.9% of water.

EFFECT: invention also characterises a pharmaceutical composition with using the above hydrate.

4 cl, 4 dwg, 8 tbl, 14 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to a low-toxic (E)-2-(4-{[3-(2,4-dimethoxyphenyl)acrylamido]methyl}-1H-1,2,3-triazole-1-yl)-2-isopropyl-9-(4-methyl piperazine-1-yl)-3,7-dioxo-3,7-dihydro-2H-furo[3,2-g]chromen of formula (I) , having the analgesic activity in the test "acetic acid-induced writhing". The said property enables to use this compound in medicine.

EFFECT: compound of formula I is prepared from furocoumarin peucedanine contained in the plant Peucedanum morisonii.

1 tbl, 5 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: chemistry.

SUBSTANCE: group of inventions relates to a process of producing organic substrate particles bonded to switchable ferromagnetic nanoparticles with a mean particle diameter ranging from 10 to 1000 nm, to the use of such nanoparticles for hyperthermic treatment of an organism and to a drug for the hyperthermc treatment. As the ferromagnetic nanoparticles used are nanoparticles, which are non-ferromagnetic at first, but become ferromagnetic when the temperature is lowered, these initially non-ferromagnetic dispersed nanoparticles are bonded to the organic substrate particles, and then the nanoparticles bonded to the substrate particles become ferromagnetic as a result of the temperature decrease, initially the switchable ferromagnetic nanoparticles at the temperature of 22°C or higher are not ferromagnetic and become ferromagnetic as a result of cooling down to the temperatures below 22°C. The switchable ferromagnetic nanoparticle comprises Mn and additionally Fe and/or As and preferably have the Fe2P-structure or Na-Zn-13-structure, alternatively, or may comprise La, Fe and Si.

EFFECT: invention prevents the agglomeration of particles and an increase in the mean particle size.

10 cl, 1 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: using dense extract of cowslip primrose (Primula veris L.) herb as a hepatoprotective agent.

EFFECT: agent is effective as a hepatoprotector.

1 tbl

FIELD: chemistry.

SUBSTANCE: invention represents method of obtaining thermosensitive iodine-containing radiopharmaceutical (RP) with radiochemical purity 95-98%, consisting in covalent binding of radioactive iodine isotopes to tyrosine groups, included into chain of poly-N-isopropylacrylamide, with further separation of labelled polymer component from low molecular compounds on chromatographic gel column by elution with water, characterised by the fact that as mobile phase used are water solutions of chemical compounds, mainly inorganic salts, possessing coefficient of polymer-hydrate-iodine complex γ=dTftdCs destabilisation from the interval γ=30-60 degree·l/mol, where Tft is temperature of phase transition in solution, containing destabilising additive, Cs is concentration of additive, limited from above by condition γCs<Tft0Tк (Tft0=Tft, at Cs=0, Tc is temperature in column).

EFFECT: creation of RP with high radiochemical frequency and reduction of radioactive pollution of the environment.

6 dwg, 2 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: 20-25 minutes after surgical intervention, a mouth bath of an implantation area with the Tonsinal phytopreparation diluted in an amount of 2.5 g in 100 ml of boiled water of room temperature is executed. 20-25 minutes later the Plastin CM-1 phytopreparation is applied on the alveolar process mucosa within the implantation area from the vestibular side for 1.5-2 hours. That is preceded by the desalivation of the oral cavity and mouth rinsing carefully with the Tonsinal solution trying to avoid any dynamic movements. The above procedures are performed 3-4 times a day for at least 10 days.

EFFECT: more effective dental implantation by improving microcirculation, fast normalising of oral microbiocoenosis, wound surface healing by immediate union, reliable implant attachment to gums and providing the implant stability.

3 ex

FIELD: medicine.

SUBSTANCE: ointment contains wax 13-15 wt %, glycerol 15-20 % and vegetable oil; the prepared ointment mass is exposed to ozone for 15-20 min in a yield amount of 10 mg/l.

EFFECT: invention provides the advanced healing efficacy with no side effects by reducing the time of wound cleansing from purulo-necrotic tissues.

3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, particularly to a composition for treating asthenic syndrome in patients with dyscirculatory encephalopathy. An ester-oil composition for treating asthenic syndrome in the patients with dyscirculatory encephalopathy contains eucalyptus, mint, pine, cedar, lavender, carnation, flax essences taken in certain relations.

EFFECT: composition is effective for treating asthenic syndrome in the patients with dyscirculatory encephalopathy; it causes the selective harmonising action on the central nervous system, regulates the emotional status, improves cognitive functions, reduces clinical manifestations of asthenic syndrome considerably and improves the quality of life in the patients with dyscirculatory encephalopathy.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to dentistry, therapeutic-prophylactic preparation for tooth and oral cavity care, and can be applied for prevention and complex treatment of inflammatory diseases of gums, parodentium, stomatitis or elimination of gingival hemorrhage. Therapeutic-prophylactic toothpaste includes glycerin, laurylglycoside, sorbitol, xylite, aerosol, calcium hydrogen phosphate, xanthane resin, sodium benzoate, CO2-extracts of thyme, sage, rosemary, white clay, green clay, red clay and water with specified content of components. For CO2-extracts of thyme, sage and rosemary fulfilled is ratio Wt/Ws/Wr=(0.40-0.50)/(0.25-0.35)/0.20-0.25), where Wt, Ws, Wr are weight parts of respectively CO2-extracts of thyme, sage and rosemary, with particles of green, white and red loam having sizes in interval 0.1-100 mcm and being obtained from clay, dried at 80-400°C.

EFFECT: technical result consists in increased efficiency of prevention and treatment of inflammatory diseases of oral cavity, parodentium, in particular gingivitis, periodontitis, as well as increase of cleaning ability of toothpaste with simultaneous reduction of abrasive influence on tooth enamel; and technical result consists in extension of arsenal or toothpastes of complex action, which render healing and preventive action on organs and tissues of oral cavity.

9 cl

FIELD: agriculture.

SUBSTANCE: invention relates to the poultry husbandry and can be used to stimulate the growth of poultry, increase in egg production. The proposed biologically active stimulant for poultry husbandry is an aqueous-alcoholic extract of the vegetative part of plants - Acanthopanax sessiliflorum and Patrinia scabiosifolia, taken in equal amounts.

EFFECT: invention enables to increase the weight gain of chickens, egg production of poultry, the preservation of birds, rate of fertilisation and hatchability of eggs.

3 tbl

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to dentistry, and can be used for the treatment of conditions, related with the increased expression of MMP-13, selected from the group, consisting of loss of one or more teeth fixation, teeth loss, teeth mobility, formation of recesses, bone tissue loss and a combination of two and more of the said conditions. For this purpose the application of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate in the production of a medication for the treatment of the said conditions is claimed. A composition for teeth care, containing an orally acceptable carrier and a therapeutically effective quantity of a MMP-13 inhibitor in the form of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate is also claimed.

EFFECT: group of inventions provides the effective treatment of the said conditions die to effective MMP-13 suppression.

3 cl, 5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to dentistry, and can be used for the treatment of conditions, related with the increased expression of MMP-13, selected from the group, consisting of loss of one or more teeth fixation, teeth loss, teeth mobility, formation of recesses, bone tissue loss and a combination of two and more of the said conditions. For this purpose the application of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate in the production of a medication for the treatment of the said conditions is claimed. A composition for teeth care, containing an orally acceptable carrier and a therapeutically effective quantity of a MMP-13 inhibitor in the form of 4-acetamidophenyl 2-isopropyl-5-methylcyclohexylcarbonate is also claimed.

EFFECT: group of inventions provides the effective treatment of the said conditions die to effective MMP-13 suppression.

3 cl, 5 tbl, 5 ex

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