Method for improving transdermal permeability of therapeutic or cosmetic topical preparations, method for dermal administration of liquid xenon

FIELD: medicine.

SUBSTANCE: invention refers to cosmetic and pharmaceutical industry and represents a method for improving the transdermal permeability of therapeutic or cosmetic topical preparations involving the dermal administration of 1.0 to 300.0 vol. % of liquid xenon as a part of an acceptable neutral carrier or a therapeutic or cosmetic preparation.

EFFECT: invention provides the higher therapeutic or cosmetic effectiveness ensured by improving the transdermal transport of bioactive compounds.

8 cl, 13 ex, 4 dwg

 

The group of inventions relates to the field of cosmetic/dermatology, namely, to methods of enhancing transdermal permeability cosmetic or therapeutic agents for external use through the introduction into the skin of the inert gas xenon.

The principle of increasing the efficacy of drugs intended for external use (creams, ointments, plasters), is well known. At the present time for this purpose more and more widely used transport system transdermal delivery of active substances included in the composition of these funds (Mbah C.J., Uzor P.F., Omeje E.O.. Perspectives on transdermal drug delivery / J Chem. Pharm. Res. to 2011 - V.3 (3), - P.680-700; Milind M.T., Pancholi SS Review of penetration enhancement techniques in the transdermal delivery system / American J of PharmTech Research. - 2012, - V.2(1). - P.256-273). In 2009 in the United States from 129 different transport systems for drugs undergoing clinical trials, 51% were systems transdermal and dermal delivery. Currently in the United States approved 20 original transport systems for a number of drugs for the treatment of skin diseases, diabetes, heart disease and blood vessels, nicotine dependence, conduct of hormone replacement therapy in women, as well as analgesics and anesthetics.

There are several major technological trends in the development of transdermal systems of active transportation is ubstance:

1. The use of carriers (liposomes, transfersome, economy, Nozomi, uspacom, nanosomes, dendrimers, eutectic systems, and so on).

2. Physical methods of increasing the permeability of the skin iontophoresis, ultrasound, electroporation, termporary, magnetophoresis, microneedle, without needle injection, etc.

3. Chemical compounds - enhancers - sulfoxidov, alcohols, polyols, alkanes, ethers, terpenes, etc.

Advantages enhancers in comparison with other methods is that they just entered into the composition of funds, this eliminates the need for additional carriers (liposomes, and so on), and does not require additional apparatus for iontophoresis, ultrazvukovoj impact, etc. the Main mechanism of action of enhancers ("enhance" is to increase, enhance) the modification of the physico-chemical parameters of the stratum corneum, loosening his integrity and orderliness of the structure of the intercellular lipid layer of the epidermis, which improves the fluidity of this layer and the solubility of the active substances in the stratum corneum.

The disadvantage of chemical enhancers is the risk of adverse inflammatory effects associated with irritation, redness, scaling, etc. Penetration of these chemicals or their metabolites into the skin and enters the blood can the t to have undesirable systemic effect on the entire body. In addition, these enhancers increase the risk of overdose or modify the biological activity of substances contained in cosmetic or therapeutic tools (Patel H.J., Trivedi D.G., A.K. Bhandari, D.A. Shah Penetration enhancers for transdermal drug delivery system: A review / IJPI''s Journal of Pharmaceutics and Cosmetology. - 2011. - V.1(2). - Page 67-80).

Finding ways to increase the effectiveness of cosmetic and therapeutic agents for external use by introducing into the composition of their transport systems enhancers remains relevant.

Known methods of treatment of various diseases using phytochitodes and chitosan-containing ointments, for example, in surgical practice for impact on the wound process in order to accelerate healing of wounds and prevent suppuration [EN 2151601 C1, 2000], in the treatment of chronic gastritis, gastric ulcer and duodenal ulcer [EN 2150271 C1, 2000], acute purulent periostitis [EN 2153318 C1, 2000].

A known method of improving the treatment of atopic dermatitis [EN 2170092 C1, 2001]. The method is topically applied on the lesions steroid ointment, optionally containing heparin, the dose of steroids decrease in 13-40 times. The method increases the effect of treatment and reduce complications of steroid therapy.

The level technique known device for transdermal delivery of lekarstvennayaforma, containing O-Desmethylvenlafaxine (ODV) or its salt [RU 2008106935 A, 2009], essentially representing a transdermal patch for the introduction of topical compositions containing a therapeutically effective dose of ODV or its pharmaceutically acceptable salt and at least one physiologically acceptable carrier or excipient.

Renowned pharmaceutical composition for increasing the permeability of the skin for enhanced local drug delivery [EN 94019942 A1, 1995], including safe and effective amount of pharmaceutically active substances, 0,05%-5% non-ionic polyacrylamide with a molecular mass of 1000000-30000000.

The prior art also known pharmaceutical composition for local application [EN 2005132004 A, 2006], in which agent to improve permeability through the skin, the substance selected from the group of urea, pyrrolidone, N-methylpyrrolidine, decelerated, sodium lauryl sulphate and dimethyl sulfoxide.

Known biologically active substance cosmetics, stimulating metabolism in epithelial tissues [EN 2033789 C1, 1995], in which the biologically active component is applied block copolymer of ethylene oxide and of propylene oxide (copolymer of polyoxy-ethylene-polyoxypropylene) General structural formula

having a molecular weight of 3-25 g and the ratio oxypropylene and oxyethylene parts (20-2):(80-2).

Known tetracyclic compound used to increase the permeability of the skin for pharmaceutically active compounds and a method for increasing the permeability of the skin for pharmaceutically active compounds [RU 2007105687 A, 2008], including skin treatment tetracyclic compound and the introduction of pharmaceutically active compounds.

Among the gaseous enhancers known oxygen [EN 2191566 C1, 2002; EN 2119790 C1, 1998; EN 2304959 C2, 2007]. This technology is used by the Russian company Faberlic using in their products Aquachem connection the nano-sizes (200 nm) on the basis of perfluorocarbons (performanceline), actively absorbing molecular oxygen. The authors argue that the main effect of such "oxygen cosmetics" is to stimulate the metabolism of skin cells as a result of increasing education level of energy substrates in the mitochondria and, as a consequence, stimulation of regeneration and processes "rejuvenation" by increasing the protein content of collagen and elastin in the dermis and restore skin elasticity, as well as effects in the treatment of burns. Indeed, oxidase path (when molecular oxygen is incorporated into the molecule of oxidized substrate) is cytochromoxidase airway mitochondria. However, in the two ways - mono - and dioxygenase the th in the molecule substrates embedded either one or all of the oxygen molecule, resulting in formation of reactive oxygen species (ROS) - the initiators of free radical oxidation (CPO) and lipid peroxidation (LPO), protein, DNA molecules with a violation of their functions and irreversible destruction [Kuzmenko DI, silver V.Y., S. Udintsev. Free radical lipid oxidation, reactive oxygen species and antioxidants: their role in physiology and pathology of cells / Tomsk, 2007. - 214 S.]. Similar processes occur in the skin, in particular, against the background of excessive UV exposure (photoaging of the skin). Oxygen, according to them, among the above effects, also increases the penetration into the deeper layers and the absorption by the skin cells of biologically active substances, for example, popular in cosmetology recently RALA (R-alpha lipoic acid), and enhances the activity of other cosmetic preparations, in particular sunscreen. Thus, Aquachem is also considered as an enhancer.

The disadvantage of this invention is the formation of excess reactive oxygen species - oxidative stress and the effect of Aquaflame as enhancer should be considered not only as a consequence of increasing utilization of active compounds by the cells of the skin resulting in activation of metabolism, but more in the aggressive reactive to what Sloboda, initiating processes of free radical oxidation and peroxidation of lipids, proteins, DNA molecules with a violation of their functions and irreversible destruction. Similar processes in the skin cells, lead to loosening and integrity of the intercellular lipid structures, thus increasing its permeability for the active substance. The risk of oxidative stress on the background of excess oxygen requires additional introduction into the composition of antioxidants, which was done by the company Faberlic - after creating Aquaftem appeared Aquaftem Protect, to which was added the compound propylene, antioxidant properties, which is higher than that of vitamin E. This product is also used by the company as an enhancer for components of essential oils with which it is combined.

His action interest lipophilic inert gases such as krypton, argon, xenon. Especially among them we would like to highlight the xenon, which is known as inhalation anesthetic, because this inert gas has anesthetic and analgesic effect.

Well-known United States patent [US 2005255169, 2005], where the authors propose to use anesthesia (inhalation) xenon or a gas mixture containing xenon as a means to enhance the effect (enhancer) pharmacolo the practical preparations designed for antiviral, antibacterial, antifungal therapy, as well as neuroprotective agents, anticancer drugs, parasympathomimetics, antispasmodics, sympathomimetics, tranquilization, vitamins, hormones.

The disadvantage of this invention is that anesthesia with xenon requires special equipment, can be performed only in hospitals specialist anaesthetists and, accordingly, are not available for mass use and, moreover, as a means to improve the efficiency of cosmetics.

Known adaptogenic drug for therapy and method of its manufacture [EN 2228739 C1, 2004]. The product is equipped with sealed packaging and contains a filler - fat emulsion or solid sorbent, in which is dissolved or adsorbed gaseous active component representing at least one gas from the group including: xenon, krypton, nitrous oxide. Preferably the filler is a fat emulsion having a pH not below 6.0, fat emulsion contains fat, namely: milk large or small cattle or other emulsion-based animal oil, or as filler contains vegetable oil or activated charcoal or tarmacced. The invention provides for obtaining non-toxic preparation is that with the increased ability to regulate the body's resistance under extreme impacts due to humoral regulation, regulation of metabolism and emotional regulation of the patient.

The method of producing drug for adaptogenic therapy selected the closest way to the same destination to the claimed method in a group of inventions.

An object of the invention is to create a new way to increase the efficiency of medicinal or cosmetic products by introducing (delivery) in the skin of the inert gas xenon due to the manifestation of the xenon effect enhancer.

Another technical problem faced by the developers, was to develop a new method of introduction into the skin of gaseous xenon.

The objective of the implementation of the claimed group of inventions is achieved by the inventive method of enhancing transdermal permeability of therapeutic or cosmetic preparations for external use includes the introduction in the skin from 1.0 to 300,0% vol. gaseous xenon in the composition acceptable neutral media or therapeutic, or cosmetic preparation.

In addition, as an acceptable neutral gaseous media xenon choose at least one substance.

An effective amount of gaseous xenon dissolved in an acceptable neutral medium, or therapeutic or cosmetic preparation.

If this is acceptable neutral media xenon, therapeutic or cosmetic is systematic drug use in gaseous or liquid, or semi-solid, or solid form.

For skin care, nails, hair, mucous membranes, an effective amount of gaseous xenon is the amount of xenon sufficient to achieve the improved condition of skin, nails, hair, and mucous membranes.

For the treatment of diseases of the skin, nails, hair, mucous membranes, subcutaneous fat, connective tissue, musculoskeletal system, muscle tissue an effective amount of gaseous xenon is the amount of xenon, sufficient to improve the effectiveness of therapy.

The task is achieved by the fact that the inventive method of introduction into the skin of gaseous xenon is that to increase the transdermal permeability of therapeutic or cosmetic preparations for external use introduction in the skin from 1.0 to 300,0% vol. gaseous xenon in the composition acceptable neutral media or therapeutic, or cosmetic preparation, conduct tapicerki according to any one of claims 1 to 6.

Introduction to skin gaseous xenon to enhance transdermal permeability of therapeutic or cosmetic preparations performed with the passing of time and sequence or simultaneously.

Xenon is an inert noble gas is not toxic, does not react with biological molecules, no manifestation is yet mutagenic, teratogenic, cyto - and immunotoxic properties. Used in medicine since 1951 for inhalation anesthesia. When introduced into the body the gas completely excreted within 4 hours (R.D. Sanders, N.P. Franks, Maze M. Xenon: no stranger to anaesthesia / Brit J Anaesthesia, 2003. - V.91 (5). - P.709-717). Shows therapeutic effect of gas in the neurotoxicity of various origins, Parkinson's disease, schizophrenia, cerebral ischemia [Burov N.E., Potapov V.N., Makeev GN. Xenon in anesthesiology - m., Puls., 2000. - 356 S.; Abraini J.H., David, H.N., M. Lemaire Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon - Ann. N.Y. Acad. Sci. 2005, 1053: P.289-300]. More gas is widely used in subarctica (small) doses for therapeutic anaesthesia for neurotoxicity of various origins (Abraini J.H., David, H.N., M. Lemaire Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon - Ann. N.Y. Acad. Sci. 2005, 1053: P.289-300). Xenon effective and when injected into the cerebral vessels of liposomes with this gas, it contributes to a significant acceleration of recovery repair brain tissue and reduce the neurotoxicity after stroke (Britton G.L., Kim N., Kee R.N. et al. In Vivo Therapeutic Gas Delivery for Neuroprotection with Echogenic Liposomes / Circulation. 2010, 122(16): 1578-1587).

As the primary mechanism of action of xenon is considered its impact on system mediators, provide the conduction of nerve impulses in the first place, the blockade of N-methyl-D-aspartate (NMDA)receptors. This signaling system original OPI is Ana for the Central nervous system, but in the future was also detected in the bone and hematopoietic tissues, pancreas, in deep tissues (muscles, tendons, joints), the nerve endings in the heart muscle, myocardiocytes (T.M. Skerry, Genever P.G. Glutamate signalling in non-neuronal tissues / Trends Pharmacol Sci, 2001. V.22. - P.174-181; Alfredson H., Lorentzon R.J. Chronic tendon pain: no signs of chemical inflammation but high concentrations of the neurotransmitter glutamate. Implications for treatment/Curr Drug Targets, 2002. - V. 3. - P.43-54). Identified NMDA receptors in the basal spinous and granular layers of the human skin - (Kinkelin I, Brocker E B, Koltzenburg M. et al. Localization ionotropic glutamate receptors in peripheral axons of human skin/Neurosci Lett, 2000. - V. 283. - P.149-152; Nahm W.K., Philpot B.D., M.M. Adams et al. Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes/J Cell Physiol, 2004. - V. 200 (2). - P.309-317; M. Fischer, D. Glanz, William T. et al. N-methyl-D-aspartate-receptors influence the intracellular calcium concentration of keratinocytes/Experimental Dermatology, 2004. - V.13 (8). - P.512-519). Currently, NMDA receptors are considered as targets for the treatment of skin diseases (Nahm W.K., Philpot B.D., M.M. Adams et al. Significance of N-methyl-D-aspartate (NMDA) receptor-mediated signaling in human keratinocytes/J Cell Physiol, 2004. - V. 200 (2). - P.309-317). With the impact on them is the effectiveness of topical application of calcium channel antagonists, accelerating the repair of the epithelial barrier (Fuziwara, S., Inoue K., Denda M NMDA-type glutamate receptor is associated with cutaneous barrier homeostasis/J. Invest. Dermatol, 2003, - V..120. - P. 1023-1029). Shown to decrease the severity of hyperalgesia, inflammatory hyperemia and muscle is Oli people in the local superficial intradermal introduction of the NMDA antagonist ketamine and opioid pentamine (Koppert W., Zeck, S., Blunt J.A., Schmelz M. The Effects of Intradermal Fentanyl and Ketamine on Capsaicin-Induced Secondary Hyperalgesia and Flare Reaction / Anesth play mode display, 1999. - V. 89 (6). - p.1521-1527; Cairns, B.E., Svensson P., Wang K. et al. Activation of Peripheral NMDA Receptors Contributes to Human Pain and Rat Afferent Discharges Evoked by Injection of Glutamate into the Masseter Muscle J Neurophysiol, 2003. - # 90. - P.2098-2105).

Hyperactivation of NMDA receptors is an important factor in the mechanisms of tissue damage by oxidative stress (Said S.I., Pakbaz N., Berisha H.I., Raza S. NMDA receptor activation: critical role in oxidant tissue injury /Free Radical Biology and Medicine, 2000. - V. 28 (8). - P. 1300-1302). In this respect, the above mechanism of action of xenon is directly linked to another of its mechanism - the ability to regulate the antioxidant status of the organism. This phenomenon was discovered by Russian scientists in experiments on animals where the introduction of gas decreased activity of processes of lipid peroxidation (Burov N.E., Potapov V., G. Makeev. Xenon in anesthesiology/M, Pulse, 2000. - 356; the Use of xenon in medicine. Edited Neasloss, Menspokane, Vinotopia/Tomsk, 2008. - 300). Because xenon is an inert gas, it is not able to directly inactivate toxic products of lipid peroxidation, and its effect is determined by the structural properties (nonspecific) antioxidant. Such compounds alter the configuration of the structural elements of the membrane lipid bilayer, increasing it is resistant to the toxic effects of peroxy radicals (Kuzmenko DI, Serebrov V.Y., S. Udintsev. Free radical lipid oxidation, reactive oxygen species and antioxidants: their role in physiology and pathology of cells/Tomsk, 2007. - 214). Xenon also has a high affinity to the main lipid component of membranes - phosphatidylcholine, solubility in which gas 6 times higher than in other lipids. Joining him, xenon headlights changes the indices of the surface area and thickness of the membranes, as well as the configuration of the fatty acid chains, screening areas lipids, predisposed to the formation of active radicals (Stimson L.M., Vattulainen L, Rog T. Et al. Exploring the effect of xenon on biomembranes. Cellular & Molecular biology letters, v. 10, 2005, p.563-569; Yuan, H.; Jameson C.J.; Murad S. Exploring gas permeability of lipid membranes using coarse-grained molecular dynamics. Molecular Simulation, Volume 35, Issue 10 & 11 September 2009, pages 953-961). Changing the physicochemical properties of membranes, including their viscosity, xenon affects their permeability, thereby showing the properties of the enhancer, the effect of which is two-stage. In the first phase xenon reduces the viscosity of lipids, changes the conformation of membranes, on the one hand, increasing their capacity for molecules active substances, on the other hand is showing a protective effect as an antioxidant. The second stage - the impact of gas on NMDA receptors in the skin, resulting in changing its homeostasis (Fuziwara, S., Inoue K., Denda M NMDA-type glutamate receptor is associated with cutaneous barrier omeostasis/J. Invest. Dermatol, 2003, - V.. 120. - P. 1023-1029). Finally, xenon exhibits specific described above analgesic effect, which creates conditions for amplification (potentiating) effect of active substances with a similar effect.

Found that the introduction of xenon or a gas mixture containing xenon, in an acceptable carrier, increases the efficiency of the medicinal or cosmetic products applied on the skin or mucous membrane, as a result of increased transepidermal transport of bioactive compounds included in the composition of these funds.

The term "acceptable neutral carrier" means a gaseous, liquid, solid, semi-solid media. The media may also contain various active and targeted supplements, and carriers may include standard components.

The term "standard components"included in acceptable carrier used in this specification implies the necessary ingredients that make up any composition, i.e. a mixture of natural and synthetic products, namely, vegetable and animal oils, stabilizers, builders, thickeners, geleobrazovanie, emulsifiers and simulatory, silicones and their derivatives, preservatives, flavouring agents, rheological additives, active substances and their mixtures, and any other known and used in p is izvodstve cosmetic products.

The amount of xenon in the final composition in the proposed versions of the composition is about 1-300.%. In this case, the number of entered xenon determined mainly on the basis of the content of fat (oil) phase in an acceptable neutral medium, any pharmaceutical and/or cosmetic preparation.

The upper limit of the concentration of xenon (300%) substantiated possible maximum solubility of gas in pure oil. The lower limit of the concentration of xenon in acceptable neutral medium, any pharmaceutical and/or cosmetic preparation (1%) based on the fact that with this value content of xenon becomes visible manifestation of the properties of this gas.

Offer acceptable neutral carrier, any pharmaceutical and/or cosmetic preparation may be in liquid form, for example, in the form of a solution, spray, foam, drops, suspensions, emulsion, gel, liquid, ointment, or other forms suitable for application to the skin or mucous membranes. Can also be in solid or semisolid form, for example, in the form of powder, granules, pessary, suppository, cream, gel, solid ointments or other forms suitable for application to the skin or mucous membranes.

The term "effective amount of gaseous xenon in cosmetics for skin care, nails, in the wasps, mucous membranes involves a quantity sufficient to achieve the improved condition of skin, nails, hair, and mucous membranes. And means for the treatment of diseases of the skin, nails, hair, mucous membranes, subcutaneous fat, connective tissue, musculoskeletal system, muscle tissue an effective amount of gaseous xenon is the amount of xenon, sufficient to improve the effectiveness of therapy.

The invention is illustrated by examples and illustrations displayed in figures 1-4.

Figure 1 - shows the border of normal skin and panolayou wounds.

Figure 2 - shows the creeping epithelium after 7 days of the experiment.

Figure 3 - shows the recovery of the skin on day 15 of the experiment.

Figure 4 - shows the normal structure of the sebaceous glands on the 15th day of the experiment.

Example 1

To demonstrate the claimed effects of xenon on increasing the permeability of the skin for components external funds, conducted tests using standard equipment (diffusion chamber Franz), skin outbred rabbits. As a sample of external funds used base emulsion of the following composition:

deionized water - 85,0%,

emulsifier DC 5329 (PEG-12 Dimethicone) - 3,0%,

cyclomethicone - 4,0%,

capric/Caprylic triglyceride - 6,0%,

Aligator/thickener SEPIGEL EG - 2,0%

In this base emulsion during preparation were added ascorbic acid in an amount of 2.0% as an active ingredient. The skin test was prepared in the standard way. The area of diffusion of the skin was 2,55 cm, the volume is lower, the reception, the camera was 15 ml In the lower chamber was phosphate buffer (pH 7.4). Chamber temperature was 37C. At the beginning of the test on top of the skin inflicted 1 ml of emulsion with ascorbic acid. The test was performed within 24 hours. The effectiveness of skin permeability was determined by measuring the amount of ascorbic acid spectrophotometric method. For this purpose, samples were taken with a volume of 1 ml from the bottom of the camera. By a standard calculation and summation of the results within 24 hours of received amount of ascorbic acid, passed through the skin in the lower chamber. The results were expressed in % of the amount of ascorbic acid contained in the emulsion, applied in the upper part above the skin.

The above-described testing method used to study the effects of xenon in various ways in the skin.

The first way: the introduction of xenon in the emulsion containing ascorbic acid. When this method is used in the preparation of the emulsion, in advance, in an oil phase was injected xenon in various quantities in the following way: in the syringe a volume of 10 ml was gaining a certain amount of oil phase, then through the tube from the container there was enough xenon, then intensively stirred, dissolving xenon and compensating for the decrease in volume with movement of the piston. The oil phase in the emulsion is 10%. Accordingly, in volume%, the content of the xenon in the experimental samples of the emulsion was 2 vol.%, 5 vol.%, 10 vol.%, 20% vol. and 30 vol.% 100 g of the emulsion. On the control skin samples was applied emulsion without xenon.

Got the following results shown in table 1.

Table 1
The effect of xenon on the transport of ascorbic acid through coucasica
The amount of ascorbic acid, passed through the skin, in % of the content in the emulsion
The control emulsion without xenon35,1%
Experience No. 1,2.% xenon38,2%
Experience No. 2, 5 vol.% xenon37,7%
Experience No. 3, 10 vol.% xenon42,5%
Experience No. 4, 20 vol.% xenon56,6%
Experience No. 5 to 30 vol.% xenon 58,2%

The results showed that the maximum effect on the permeability of the skin has the introduction of xenon at a concentration of 20% vol. and 30 vol.%. A small effect is observed when the content of xenon in the emulsion in amounts of 2% vol. and 5%vol.

The second method: pre-treatment skin carrier xenon. As carriers of xenon used deionized water or polyisobutene. In water xenon was administered in the following doses: 1 vol.%, 5 vol.%, 10 vol.%. In polyisobutene - 5 vol.%, 10 vol.%, 50 vol.%, 100 vol.%, 200 vol.%, 300 vol.%. The introduction of xenon in water and polyisobutene was performed using a syringe, as described above.

Control skin samples pre-treated separately with water and polyisobutene without xenon by 3-fold wetting the surface of the skin samples. Samples were processed in the same way, but with the content of xenon, as described above. Immediately after the treatment was applied emulsion with ascorbic acid.

The test results are shown in tables 2, 3.

Table 2
The effect of xenon on the transport of ascorbic acid through the skin of the rabbit
Media xenon - waterThe amount of ascorbic acid, proseds is through the skin, in % of the content in the emulsion
Control No. 1 (water without xenon)33,2%
Experience No. 1-1, 1% vol. xenon32,8%
Experience No. 1-2, 5% vol. xenon38,2%
Experience No. 1-3, 10 vol.% xenon45,1%

The results showed that pre-treatment of the surface of the skin with water and xenon increase its permeability for ascorbic acid. The greatest effect is observed when the content of xenon 10%vol.

Table 3
The effect of xenon on the transport of ascorbic acid through the skin of the rabbit
Media xenon - polyisobuteneThe amount of ascorbic acid, passed through the skin, in % of the content in the emulsion
Control # 2 (polyisobutene without xenon)27,8%
Experience No. 2-1, 5% vol. xenon31,2%
Experience No. 2-2, 10% vol. xenon37,3%
Experience No. 2-3, 50% vol. xenon is 43,4%
Experience No. 2-4, 100% vol. xenonto 49.9%
Experience No. 2-5,200% vol. xenon54,7%
Experience No. 2-6, 300% vol. xenon57,4%

After the test, got the results indicate that pre-treatment of the surface of the skin by the media (polyisobutene) with xenon increases the permeability of skin to ascorbic acid. The effect increases with the increasing content of xenon in the media.

Similar effects were obtained when applied to the skin of the media xenon before the emulsion with ascorbic acid, or during the simultaneous application of the two compositions.

Example 2

To investigate the impact of intensive xenon water hidratantes skin tested on human volunteers (15 women) aged 24 to 39 years, not having any apparent changes of the facial skin. All subjects were divided into 3 groups of 5 people each.

For research deionized water was prepared with different contents of xenon: 1%; 5%; 10%. As control was used deionized water.

The test: within 8 days, the subjects in the groups covered the left side of the face with a gauze cloth, richly soaked in water to what may within 10 minutes, in appropriate concentrations, daily afternoon and evening. The right side of the face (control) all patients were also treated with water without xenon.

Hidratantes of the skin was determined using a portable device for determining the moisture content of the skin Moisture Monitor (SK, China) in % after 2 days in the morning. The results in groups evaluated in %, summed and expressed in averages.

The test results are shown in table 4.

On the basis of the obtained data shows that the greater the moisturizing effect was observed when using water containing xenon 10% vol. after 4 days of observations. Less pronounced effect was observed when using water containing xenon 5 vol.%. When the content of xenon in water in the amount of 1% vol. no effect was observed. The results show that the surface treatment of the skin with water and xenon increase the permeability of skin to water, thus restoring its natural moisture balance.

Example 3

In the following experiments, we studied the effect of xenon on the wound healing process of damaged skin in the experiment. This work was performed at 30 outbred white rats-males weighing 150-180, All the animals under light ether anesthesia, in the Central area of the upper third of the back was made Dolnoslaskie excision of the site is expected. Previously on this surface was removed hair. The wound had a rounded shape with a diameter of 6 mm

Healing of the wound area in all rats was done by primary tension with the formation of the characteristic scab dark brown color. Material for the study was taken at 7 and 15 days after surgery. Histological specimens were stained with conventional survey methods (hematoxylin-eosin, neutral red, azure II-eosin). All experimental animals were divided into 3 groups. The first group (10 rats) control, i.e. these animals after excision of the skin is not subjected to any stress. The second group (10 rats) - experienced. These animals after excision of skin on the wound inflicted cream without xenon daily, morning and evening. The third group (10 rats) - experienced. This group of animals after excision of skin was exposed to cream with xenon daily in the morning and also evening, the results are shown in figure 1-4.

The cream was prepared in accordance with one of the simple recipes, which includes: olive oil, water extracts of Hypericum, xenon headlights, thickener/emulsifier DC RM 2051, preservative (mixture of parabens). The use of DC RM 2051 can be entered into the composition of this cream is a large amount of oil (40%). Before mixing and homogenization of the components in olive oil was injected Xeno is the rate of 200 ml xenon 100 ml of oil. The final concentration of xenon in the cream was 80%vol.

In the morphological studies in animals of the first group macroscopically observed a slight decrease in the size of the wound during the first 7 days. Morphologically marked the beginning of napoletane epithelium at the wound surface. By day 15 animals of this group macroscopically observed wound healing with the exclusion of the scab. On histological preparations seen in the epithelium, however, the elements of the dermis and skin appendages are weak.

In the second group of rats painting regeneration (macro - and microscopically) were slightly different and corresponded described above. Scab almost disappeared at 9-10 day.

In the third group on day 7 was observed more pronounced wound healing. The size of the wound was reduced by about 2/3, scab almost disappeared. Observed accelerated restoration of hair in the wound. By day 15 the structure of the epidermis was close to normal, there was an active regeneration of the dermis and skin appendages due to the proliferation of cellular dermal cells, tumor vessels.

In the experimental work we have shown the effectiveness of the introduction of xenon in the cream, applied to the wound surface, to activate the skin's regenerative processes. In addition to the, it was observed accelerated recovery hairline.

Example 4

For research and confirm the claimed effect used two songs. The first track carrier with xenon. As the carrier used aminobutiramida adipat (DIA), which was dissolved xenon in the range of from 1 to about 300.% (1%; 3%; 5%; 10%; 50%; 100%; 200%; 300%;). The second composition is a cream-gel, including the following common ingredients: deionized water, carbopol 974, hyaluronic acid, poloxamer 188, aminobutiramida adipat, vitamin a, turmerone (extract of turmeric), ethanolamine, preservative, taken in known ratios. Used cosmetic composition of the cream, the skin is moisturizing, antioxidant, smoothing effect.

Clinical study, which was attended by volunteers - 45 women aged 35-56 years with signs of age-related skin changes. The experiment involved women not taking hormones, not suffering from dermatitis and allergic diseases.

Both compositions have previously been investigated in accordance with the requirements of SanPiN 1.2.681-97 "Hygienic requirements for production and safety of perfumery and cosmetic products", approved by Resolution of the Chief State sanitary inspector of the RF dated 20/11/97, N 26".

The results of p is obedennyh microbiological, chemical-analytical, Toxicological studies have shown that the studied compositions are safe for human health, no irritants, do not cause allergies.

Women were divided into 9 groups of 5 people each. The participants of each group twice a day (morning and evening) for 30 days was applied to the skin in both compositions according to the scheme: after easy cleaning of the skin is first deposited first song, then, after uniform distribution and absorption (after 5 minutes), this same region was applied the second composition. Evaluation of effectiveness was estimated by the method of questioning. A preliminary skin test control and test samples creams all participants gave a negative result: 100% of the subjects were no signs of irritation and/or Allergy. Overall satisfaction with the results of all women was positive.

A subjective assessment of the efficacy of the compositions was carried out according to the following criteria:

- organoleptic characteristics of the product: texture, comfort when applied, no stickiness and Shine.

the skin condition indicators: the level of keratinization, hydration, elasticity, the microrelief of the skin, lifting effect.

- psycho-emotional state of patients: health, activity level n is brutishly (no worries, irritability)activity.

The indicators were evaluated every 3 days testing on a 5-point scale by summing the scores for each group. A positive result was considered total rank not below 20 points.

The test results are shown in table 5.

The positive results obtained in this study showed that the efficiency of the cream for the face is achieved when applying the first composition containing xenon is already at 3-5%. The most rapid effect in this test is achieved by using the concentration of xenon in the first song starting with 50 vol.%.

Similar effects were obtained when applied to the skin of the media xenon before application of the cream-gel or during the simultaneous application of the two compositions.

Example 5

Clinical study, which was attended by volunteers - 26 women aged 42-56 years with complaints of pain in the lumbar spine. On the basis of clinical examination, was diagnosed with Lumbar degenerative disc disease, syndrome, lumbalgia under mild exacerbation.

In the experiment did not participate women undergoing in the last 6 months of surgery, receiving any drug or biological and active additives to food, hormonal drugs, suffering from dermatitis and allergic diseases.

For treatment was used the drug DICLAC-gel (active substance diclofenac, excipients - isopropyl alcohol, macrogol-7-literallayout, hypromellose, aromatic oil, water) for local effects on the lumbar region.

The content of xenon in the preparation was 1.0 vol.%, 5,0%vol., 10,0%vol 30,0%vol.

Women were divided into 5 groups of 3-5 people each. The participants of each group twice a day (morning and evening) rubbed in 1-2 minutes in the skin of the lumbar region drug without xenon (control), or the tool containing xenon in accordance with the above concentrations (experimental group).

Evaluation of effectiveness was assessed on the basis of the analysis of the timing of the disappearance of pain.

The following results are obtained:

Group 1 (control): the disappearance of pain after 9-10 days. (5 patients). Group 2 (the content of xenon in the cream of 1.0 vol.%): the disappearance of pain after 7-11 days (3 patients).

Group 3 (the content of xenon in the cream of 5.0 vol.%): the disappearance of pain after 4-5 days (5 patients).

Group 4 (the content of xenon in the cream of 10.0 vol.%): the disappearance of pain after 4-5 days (5 patients).

Group 5 (contents of xenon in the cream 30,0%vol.): the disappearance of pain after 2-3 days (4 patients).

The results showed that the visible effect is seen when the content of the xenon 5,0% vol. in preparation DICLAC-gel. The greatest effect is when the content of xenon 30,0%vol.

Example 6

Clinical study, which was attended by volunteers 24 women aged 42-56 years with complaints of pain in the lumbar spine. On the basis of clinical examination, was diagnosed with lumbar degenerative disc disease, syndrome, lumbalgia under mild exacerbation.

For treatment was used the drug DICLAC-gel (active substance diclofenac, excipients - isopropyl alcohol, macrogol-7-literallayout, hypromellose, aromatic oil, water) for local effects on the lumbar region.

As a second tool used composition in the form of an emulsion of the following composition: water, olive oil (20%), thickener/emulsifier RM 2051 (sodium polyacrylate and Dimethicone and Cyclopentasiloxane and Trideceth-6 and PEG/BCP-18/18 Dimethicone). This composition was injected xenon concentrations in: 1%; 5%; 10%; 50%; 100%; 200%; 300% in terms of oil content. The final contents of the xenon experimental composition was: 0,2%; 1%; 2%; 10%; 20%; 40%; 60%. Control sample of this composition did not contain xenon.

Women were divided into 8 groups of 3 people each. The participants of each group twice the day (morning and evening) rubbed in 1-2 minutes in the skin of the lumbar region of the medicinal product followed by the application of the second tools/composition. The interval between application of drugs and cooked songs/cream was 5 minutes.

Evaluation of the effectiveness of the compositions was evaluated on the basis of the analysis of the timing of the disappearance of pain.

The following results are obtained:

Group 1 (control): the disappearance of pain after 9-11 days.

Group 2 (the content of xenon in the tool of 0.2 vol.%): the disappearance of pain through 8-11

days.

Group 3 (the content of xenon in the tool 1 vol.%): the disappearance of pain after 6-8 days Group 4 (the content of xenon in the tool 2 vol.%): the disappearance of pain through 5-8

days.

Group 5 (contents of xenon in the tool 10 vol.%): the disappearance of pain after 3-4

day.

Group 6 (the content of xenon in the tool 20 vol.%): the disappearance of pain after 4-6

days.

Group 7 (the content of xenon in the tool 40 vol.%): the disappearance of pain after 2-3

day.

Group 8 (contents of xenon in the tool 60 vol.%): the disappearance of pain after 2-Sdna.

In the test result we can say that a small effect was observed when the content of the second tool xenon 1 vol.%. The maximum effect was observed when the content of xenon 10-60 vol.%.

Similar effects were obtained when applied to the skin of the media xenon before application of the drug DICLAC-gel or during the simultaneous application of the two compositions.

Example 7

Held clinches the e study in the participation of volunteers - 18 men aged 30-48 years with infected household wounds of the soft tissues of various etiologies (cuts, burns).

In the complex treatment was used the drug LEVOCIN-ointment for external use (active substance - chloramphenicol sulfadimetoksin, methyluracil, trimekain).

The drug was administered xenon. The gas content in the product was 1.0 vol.%, 5,0%vol., to 10.0 vol.%, 50,0%vol., 100,0%vol.

Participants were divided into 6 groups of 3 people each. Participants in each group once in the morning put on the wound with sterile gauze, impregnated drug without xenon (control)or drug content of xenon in accordance with the above concentrations (experimental group).

Evaluation of the effectiveness of the drug was assessed on the basis of the analysis of time epithelialization of the wound surface.

The following results are obtained:

Group 1 (control): epithelialization after 6-7 days.

Group 2 (the content of xenon in the cream of 1.0 vol.%): epithelialization after 6-7 days.

Group 3 (the content of xenon in the cream of 5.0 vol.%): epithelialization after 6-7 days.

Group 4 (the content of xenon in the cream of 10.0 vol.%): epithelialization in 4-6 days.

Group 5 (contents of xenon in the cream 50,0%vol.): epithelialization after 4 days.

Group 6 (the content of xenon in crime,0 vol.%): epithelialization after 3 days. Results: the maximum effect was observed with the concentration of xenon in the preparation 100,0%. A noticeable effect occurred when the contents of the xenon 10,0%vol.

Example 8

Clinical study, which was attended by volunteers - 17 men aged 28-54 years with open household wounds of the soft tissues of the hands of various etiologies (cuts, burns) small square (4-7 cm2).

In the complex treatment was used the drug LEVOCIN-ointment for external use (active substance - chloramphenicol sulfadimetoksin, methyluracil, trimekain).

As a second tool used composition in the form of an emulsion of the following composition: water, olive oil (20%), thickener/emulsifier RM 2051 (sodium polyacrylate and Dimethicone and Cyclopentasiloxane and Trideceth-6 and PEG/BCP-18/18 Dimethicone). This composition was injected xenon concentrations in: 1%; 5%; 10%; 50%; 100%; 200%; 300% in terms of oil content. The final contents of the xenon experimental composition was: 0,2%; 1%; 2%; 10%; 20%; 40%; 60%. Control sample of this composition did not contain xenon.

Participants were divided into 7 experimental groups of 2 people each, in the control group was 3 people. Participants in each group once in the morning put on the wound with sterile gauze, impregnated drug over to the th impose the same cloth, impregnated with a second tool without xenon (control), or means with the contents of xenon in accordance with the above concentrations (experimental group).

Evaluation of the effectiveness of the compositions was evaluated on the basis of the analysis of time epithelialization of the wound surface.

The following results are obtained:

Group 1 (control): epithelialization after 6-8 days.

Group 2 (the content of xenon in the tool of 0.2 vol.%): epithelialization after 6-7 days.

Group 3 (the content of xenon in the tool AB.%): epithelialization after 5days.

Group 4 (the content of xenon in the tool 2 vol.%): epithelialization after 5-6 days.

Group 5 (contents of xenon in the tool 10 vol.%): epithelialization after 4-5 days.

Group 6 (the content of xenon in the tool 20 vol.%): epithelialization after 3-5 days.

Group 7 (the content of xenon in the tool 40 vol.%): epithelialization after 3 days.

Group 8 (contents of xenon in the tool 60 vol.%): epithelialization after 3 days.

In the result we can conclude that the effect occurs already at a concentration of xenon in the second tool 1 vol.%, and the maximum effect when the content of xenon 20-60 vol.%.

Similar effects were obtained when applied to the skin of the media xenon before applying ointment - LEVOCIN or during the simultaneous application of the two compositions.

Example 9

The study used olive oil, which was dissolved whether athelny dye - Sudan black in a concentration of 1%. In the prototype was dissolved xenon at a concentration of 100 vol.%. Both samples, control (without xenon) and an experienced, was applied onto the front surface of the skin in the forearm area, the area of application was 1 cm2, at a distance of 5 cm from each other. The monitoring was conducted continuously for 20 minutes, visually determining the square of the effective flowing property and absorption on the skin. Just spent five observations, using different areas of the anterior surface of the forearm in both hands. The survey results were expressed in percentage. The result of the observations it was noted that the prototype had the ability to spread on the skin, on average, 38% more than the control. In addition, after removing the samples from the skin by gentle prokachivanija filter paper, it was noted that a more intense staining in places prototypes. Thus, samples of the oil with xenon showed higher permeability in the skin epidermis.

Example 10

Two tools were used: lotion for tanning GARNIER (tool No. 1) and the body lotion also with the effect of tanning DOVE (tool No. 2). In the medium No. 1 was injected xenon at a concentration of 30 vol.%. In tool # 2 was introduced xenon at a concentration of 25 vol.%. In the test used both tools with xenon (prototypes) and without xenon (control samples). Control and test samples were applied to the skin of the anterior surface of the forearm. The area of deposition was 3 see the Appearance of pigmentation was observed within 24 hours. The test was repeated 5 times with each tool.

The results are presented in table 6.

Table 6
The effect of xenon on the effectiveness of tools for tanning
2 hoursAfter 6 hoursAfter 12 hoursAfter 18 hours
Gamier, the controlNo pigmentationThe appearance of pigmentationClearly visible pigmentationMaximum pigmentation
Gamier, experienceThe appearance of pigmentationClearly visible pigmentationMaximum pigmentationMaximum pigmentation
Dove, the controlNo pigmentationSlight pigmentationIncreased pigmentation Maximum pigmentation
Dove, experienceNo pigmentationSlight pigmentationThe distinct appearance of pigmentationMaximum pigmentation

The result of the observations shows that the introduction of xenon in the composition of commercial products Gamier and Dove at a concentration of 25-30% vol. accelerated appearance of skin pigmentation.

Example 11

We conducted a study of the influence of xenon on the effectiveness of the treatment of acne. Were used for treatment and sulfur ointment (10%) without xenon and xenon at a concentration of 100 ml of xenon per 100 ml of ointment. Control and experimental samples ointment was applied to the affected area of the skin 3 times a day, morning, afternoon, evening. By results of work was received very good results in all 9 patients using sulfur ointment with xenon. therapeutic effect was observed already after 1 day after application. Moreover, patients were observed acceleration of the absorption of the ointment. After 4-5 days there was a steady signs of recovery. When applying sulfur ointment without xenon signs of recovery appeared only after 7-8 days.

Conclusion: xenon significantly increases the efficiency of sulfur ointment in the treatment of acne.

Example 12

We have conducted the dermatological study of xenon in patients with athlete's foot, complicated allergic contact dermatitis, and in patients with saboraim dermatitis. For the tests were selected patients with pronounced symptoms of skin diseases. For the tests were prepared olive oil with xenon (200 ml xenon 100 ml of oil).

Two patients (female, 52 years old and 48 years old) was diagnosed with athlete's foot, complicated by allergic contact dermatitis. For treatment was used cream Terbisil", 1%. Treatment: local impact on the right foot cream "Terbisil" in interleaving - morning-evening; on left leg - cream "Terbisil in mixture with xenon butter (1/2) in the same mode. The results were evaluated after 7 and 14 days. Assessment results: in the left limb through days erythematous color foci and peeling utensils much more than on the right. Clearly there is a regression of the elements of the rash. 14 days left leg had a normal skin color, items rash regressed, cracks in the skin of the heel is not defined; skin right limb peeling remained, cracks on the heel was observed. At both extremities microscopically fungus was not detected. Thus there was already a marked shortening of lechenie when exposed to the skin of traditional medicines (cream "Terbisil", 1%) in combination with xenon oil.

The use of the 13

Our study was conducted, which included 2 patients (women, 18 and 22 years)with a diagnosis - subarray dermatitis in the area of the scalp, forehead and nose. In the treatment of patients within 14 days used lotion "Elocon" scheme: the right part of the head - lotion "Elocon" 2 times a day; the left part of the head - lotion "Elocon in mixture with xenon butter (1/2) is also 2 times a day. As a result of treatment, it was noted that after 7 days on the left side of the scalp erythema and desquamation were observed, on the right side - the number of plaques and the redness has decreased, but still with the retained. After 14 days, the left side was completely healthy, on the right side were visible small pockets of peeling, erythematoses. Based on these results we conclude about a rapid clinical recovery from the effects of traditional medicines (lotion "Elocon") in combination with xenon oil. *

1. The way to increase the transdermal permeability of therapeutic or cosmetic preparations for external use, including the introduction in the skin from 1.0 to 300,0% vol. gaseous xenon in the composition acceptable neutral media or therapeutic or cosmetic preparation.

2. The method according to claim 1, in which as an acceptable neutral gaseous media xenon choose the, at least one substance.

3. The method according to claim 1, wherein the effective amount of gaseous xenon dissolved in an acceptable neutral medium, or therapeutic or cosmetic preparation.

4. The method according to claim 1, in which acceptable neutral media xenon, therapeutic or cosmetic product used in gaseous or liquid or semi-solid, or solid form.

5. The method according to claim 1, in which for the care of skin, nails, hair, mucous membranes, an effective amount of gaseous xenon is the amount of xenon sufficient to achieve the improved condition of skin, nails, hair, and mucous membranes.

6. The method according to claim 1, in which for the treatment of diseases of the skin, nails, hair, mucous membranes, subcutaneous fat, connective tissue, musculoskeletal system, muscle tissue an effective amount of gaseous xenon is the amount of xenon, sufficient to improve the effectiveness of therapy.

7. The method of introduction into the skin of gaseous xenon, namely, that to increase the transdermal permeability of therapeutic or cosmetic preparations for external use introduction in the skin from 1.0 to 300,0% vol. gaseous xenon in the composition acceptable neutral media or therapeutic or cosmetic preparation carry out tapicerki according to any one of claims 1 to 6.

8. The method according to claim 7, in which the introduction into the skin an effective amount of gaseous xenon to enhance transdermal permeability of therapeutic or cosmetic preparations performed with the passing of time and sequence or simultaneously.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention represents a method for assessing the water resistance of an antiperspirant, involving: a) sampling participants; b) fulfilling the requirement not to use any products or using the products containing no antiperspirant in the axillary region for a specific period of time; c) cleansing the axillary regions of each participant, d) applying a required amount of the antiperspirant product on one axillary region and a placebo product on the other axillary region of each participant; e) performing the stage d) until the required number of applications is completed provided more than one application is preferred; f) the last application is followed by a water test comprising a rotary motion of the participants in the swimming pool and/or swimming for a period of time of the activity in the swimming pool at a depth adequate to wet the axillary regions; g) performing a perspiration test; and h) stating if the antiperspirant shows at least the standard antiperspirant activity.

EFFECT: method improvement.

9 cl

FIELD: medicine.

SUBSTANCE: method for measuring in situ an oral agent applied from a dental care product on a substrate containing: (a) contacting the substrate and the oral agent for applying some oral agent on the substrate with the substrate being coated with saliva, and (b) analysing the substrate with the use of a probe being a part of a toothbrush and applied for infrared spectroscopy (IRS) or ultraviolet spectroscopy (UVS); a wave length used at the stage b) is specific for the above oral agent; a reference signal of the dental care product without the oral agent is deducted from an analysis result to calculate the amount of the oral agent.

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16 cl, 15 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention represents a method for biomechanical stimulation of collagen synthesis in skin cells and reduction of skin small lines and wrinkles involving: (a) forming a polymer composition containing a first polymer and a second polymer that are dissolved or dispersed in a solvent system containing water, wherein the above first polymer represents a water-soluble or water-dispersible anionic polymer able to be reduced after solvent evaporation, and wherein the above second polymer represents a water-soluble or water-dispersible cationic polymer able to form a polymer complex able to bind to a skin surface, (b) applying the polymer composition on a first skin region and a second skin region, wherein the first and second regions are separated from each other at a specified distance by at least one small line or wrinkle in between; and (c) drying the polymer composition in the first and second skin regions in the first and second skin regions so that water evaporates in the solvent system and the polymer composition is initiated to be reduced in the first and second skin regions, wherein the above reduction creates a tension over the skin surface between the first and second regions; the tension provides the biomechanical stimulation of collagen in skin cells and reduction of skin small lines and wrinkles.

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16 cl, 7 dwg

FIELD: medicine.

SUBSTANCE: as active ingredients, the presented toothpaste contains troxerutin in the amount of 0.1-0.3 wt %, ectoin in the amount of 0.01-0.1 wt % and nicotinamide in the amount of 0.05-0.1 wt %, as well as a biologically active additive containing aloe vera and herbal infusion; an anti-caries additive and target additives in the amounts to make the above functions be fulfilled; a cosmetically acceptable base containing an abrasive, a humectant, a thickening agent, a cleansing and foaming agent, a sweetening agent, and water as a medium.

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14 cl, 5 tbl, 2 ex

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SUBSTANCE: combined dental whitening and oral therapeutic composition for delaying and inhibiting dental caries, delaying or inhibiting demineralisation and promoting dental remineralisation. The composition contains an effective amount of a whitening agent and arginine in a salt form in the amount of 0.1 wt % to 50 wt % with the whitening agent and arginine dispersed in a matrix material.

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17 cl, 11 ex

FIELD: medicine.

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20 cl, 7 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: invention relates to cosmetology and represents regenerating composition for skin care which contains regulator pH-triethanolamine, BAA, base Salcare SC80, cyclomethicone DC345, preservative, odorant, water, which is characterised by the fact, that as biologically active additive it contains protein substance from quail egg and antioxidant, and base includes UV-filter, olive oil, glycerin, emulsifier Solubilisant LRL preservative Sharomix MCI an purified water, and components in composition are in specified ratio in wt %.

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3 ex, 2 tbl

FIELD: medicine, pharmaceutics.

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6 cl, 13 dwg, 2 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetic industry and represents a cosmetic preparation containing water-dispersible polyurethane with linear main chains generally consisting of alternating hydrophilic and hydrophobic sections; herewith: a) both terminal sections (T) are hydrophibic and at least one of both sections (T) are a branched alkyl residue, b) a hydrophilic section (S) is attached to each section immediately (T), c) at least one hydrophobic section (D) is attached to at least one end of each section (S) immediately, and d) the main chain contains at least one hydrophilic section (P), if there are more than one sections (P) are provided, two sections (P) are divided by at least one hydrophobic section (D).

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9 cl, 13 ex, 4 tbl

Anti-wrinkle agents // 2503443

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and represents wrinkle-reducing agents containing compounds presented by general formula (1), stereoisomers or pharmacologically acceptable salts thereof, wherein R1 represents a hydrogen atom or a linear or branched alkyl group with 1-8 carbon atoms; R2 represents -SH, -SO3H, -S-X2, -SO-X3, -S02-X4, X2-X4 represents carbon atoms or aliphatic hydrocarbon groups with 1-8 carbon atoms independently, R3 represents a hydrogen atom or an acyl group with a linear or branched alkyl chain with 1-8 carbon atoms, R4 represents a phenyl, tolyl, ethyl phenyl, propyl phenyl, butyl phenyl, pentyl phenyl, hexyl phenyl, methoxyphenyl, ethoxyphenyl, propyl oxyphenyl, butyl oxyphenyl, pentyl oxyphenyl, hexyl oxyphenyl or biphenyl group, m is equal to 0, n is equal to the integer 1 or 2.

EFFECT: invention provides preparing the compounds and cosmetic products possessing the anti-wrinkle effectiveness.

10 cl, 11 ex, 2 tbl, 7 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to neurology, and may be used for treating spasticity accompanied by improved consciousness in the patients in the vegetative state. That is ensured by administering Xeomin (botulinumtoxinA free from complexing proteins) into the spastic muscles of all the extremities and related body segments regardless of the contractions in total dose of 400-1300 units. The dose shall not exceed 24 unit/kg of body weight in 1-3 stages. The stages follow at least every 3 days. Every 1-day stage involves administering 5-50 units in each accessible muscle or muscle group with the maximum tone in max. total dose 500 units dissolved in 12.5 unit/ml. The injections are distributed uniformly along the area without electromyography. The following courses are similar if observing spasticity and/or if clinically reasonable. The length of one course is up to 3 weeks.

EFFECT: method enables improving the therapeutic effect in the vegetative states.

3 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to physiology and space medicine. The method for prevention of skeletal muscle atrophy after functional unloading involves administering 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) which increases an amount of muscle heat shock proteins and further reduces a level -calpain.

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9 dwg

FIELD: medicine.

SUBSTANCE: invention refers to organic chemistry and pharmaceutics and concerns a new benzoxazole-5-(ethylsulphonyl)-2-(naphthalinyl-2-yl)benzo[d] oxazole derivative and a pharmaceutical composition for treating or preventing Duchenne muscular dystrophy or Becker muscular dystrophy.

EFFECT: high clinical effectiveness.

3 cl, 4 dwg, 1 tbl, 50 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and concerns the use of a non-immunosuppressive derivative of cyclosporine A for reducing mitochondrial dysfunction and a degree of apoptosis in patient's cells with diagnosed congenital Ullrich myopathy or Bethlem myopathy.

EFFECT: invention provides considerable reduction of a degree of apoptosis and mitochondrial dysfunction.

5 cl, 5 ex, 6 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of invention refers to medicine, and concerns treating nonsense mutation(s) associated diseases: Duchene muscular dystrophy and cystic fibrosis. What is presented is the use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid or its pharmaceutically acceptable salts, solvate or hydrate in preparing a drug for treating Duchene muscular dystrophy associated with nonsense mutation in position 1417, 3625 or 492 of dystrophin; and cystic fibrosis associated with nonsense mutation in position 414, 493, 1316, 553, 542, 1162, 122, 1455, 822, 60, 764, 1291, 849, 434, 88, 1158 or 6542 CTFR. What is also presented is the use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid or its pharmaceutically acceptable salts, solvate or hydrate in preparing a drug for producing a functional readthrough protein in a subject having Duchene muscular dystrophy and cystic fibrosis.

EFFECT: use of 3-[5-(2-fluorophenyl)-[1,2,4]oxadiazole-3-yl]benzoic acid provides suppression of premature termination of translation in a subject by mediating nonsense codon reading and producing the functional protein in the amount sufficient for treating the disease.

3 cl, 3 dwg, 17 tbl, 16 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmacology, medicine and concerns using Trecresan as a PGC-1 coactivator gene expression stimulator.

EFFECT: invention leads to increasing mitochondrion count in muscular tissue, growing performance of striped muscles.

2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly neurotraumatology. A method involves using pharmacological preparations and physiotherapeutic procedures. As pharmacological preparations, neuromedin, vitamins B1 B12, trental are administered. The physiotherapeutic procedures involve trasspinal exposure of the spinal cord and cerebrospinal roots at a level of the occurrence of the roots involved in injured nerve formation to pulse magnetic field. The exposure includes rhythmed pulses at frequency 3 Hz at intensity 1.5-2 T. Duration of a session is 5-7 minutes. The therapeutic course is 10-15 procedures.

EFFECT: method provides reduced length of treatment and higher degree of body functional recovery ensured by the integrated treatment involving exposure on the injured region.

1 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine and is applicable for treating diseases and disorders by introducing a composition containing a neurotoxic component of the toxin complex Clostridium botulinum. The composition is free from any other protein of the toxin complex Clostridium botulinum The composition is introduced in short intervals and/or in large doses.

EFFECT: group of inventions allows increasing doses and rate of treatment not causing formation of neutralised antibodies to the neurotoxic component.

18 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to substituted imidazopyridine derivatives of general formula (I) or enantiomers, diastereomers and tautomers and pharmaceutically acceptable salts thereof, in which A denotes -NH-, -CH2-, -CH2-CH2- or a bond; X denotes phenyl, phenyl condensed with a saturated heterocyclic 5- or 6-member ring, where the heterocyclic ring can contain one or two heteroatoms selected from O and N, and where the heterocyclic ring can further be substituted with an oxo group, a 6-member saturated heterocyclyl containing O as a heteroatom, a 5-6-member heteroaryl containing 1 or 2 heteroatoms selected from N, O and S, and where each phenyl and heteroaryl is possibly substituted with 1 to 2 R14 and/or 1 substitute R4b and/or 1 substitute R5; R1 and R2 are independently selected from the following groups: C1-6-alkyl and C1-6-alkylene-C3-7-cycloalkyl, and where each alkyl is possibly substituted with a OH group, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5-6-member ring which is possibly substituted with one substitute selected from C1-6-alkyl and O-C1-6-alkyl; R4b denotes C(O)NH2, C(O)OH, C(O)NH-C1-6-alkyl, C(O)N-(C1.6-alkyl)2, SO2-C1-6-alkyl, oxo group, and where the ring is at least partially saturated, NH2, NH-C1-6-alkyl, N-(C1-6-alkyl)2; R5 denotes a 6-member heteroaryl containing N as a heteroatom; R3 denotes -(CR8R9)n-T; R8 and R9 are independently selected from the following groups: H and C1-6-alkyl; n equals 1, 2, 3, 4, 5 or 6; T denotes or NR12R13; R10 denotes H, NH2, OH, C1-6-alkyl, possibly substituted with one OH, a halogen atom, NH(C1-6-alkyl) or N(C1-6-alkyl)2; q equals 1 or 2; Y denotes CH2, NR11 or O; R11 denotes H, or C1-6-alkyl; R12 and R13 are independently selected from the following groups: H, C1-6-alkyl, C1-6-alkynyl, (CH2)0-2-C3-7-cycloalkyl, and C1-6-alkylene-O- C1-6-alkyl, where C1-6-alkyl is possibly substituted with one halogen; R14 denotes a halogen atom, CN, C1-6-alkyl, possibly substituted with 1-3 substitutes selected from halogen atom, OH, O- C1-6-alkyl, O-C(O)C1-6-alkyl, O- C1-6-alkyl, possibly substituted with one substitute selected from OH, O- C1-6-alkyl, and O-C(O) C1-6-alkyl, or OH. The invention also relates to a pharmaceutical composition based on the compound of formula (I).

EFFECT: novel imidazopyridine derivatives are obtained, which can be used as melanocortin-4 receptor modulators.

17 cl, 8 tbl, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention refers to chemical-pharmaceutical and food industry, and concerns a food composition containing food fibres which is effective for treating or reducing rate of muscular atrophy and/or chronic muscular atrophy and/or sarcopenia, and the food fibre contain at least 30 wt % of indigestible oligosaccharides having a chain length of 3-10 monosaccharide units. Besides, the composition may contain others oligo- or polysaccharides, especially polysaccharides having a majority of anhydropyranose units.

EFFECT: composition possesses high clinical effectiveness in chronic muscular atrophy.

15 cl, 5 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: intramedullary osteosynthesis is followed by a bone grafting of a lytic lesion with using a composition prepared as follows: Veroklast dry concentrate 4 mg is dissolved in water for injections 1 ml; the prepared solution is mixed with Kollapan granules 2 g and incubated at room temperature until absorbed completely.

EFFECT: composition prepared in such a way provides stabilising the involved segment, reducing the pain syndrome and inhibiting the bone lysis ensured by prolonged preparation release inhibiting the bone resorption from a collagen matrix.

1 ex

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