WO2015057110A2 - Cosmetic for rapid skin regeneration - Google Patents

Cosmetic for rapid skin regeneration Download PDF

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Publication number
WO2015057110A2
WO2015057110A2 PCT/RU2014/000776 RU2014000776W WO2015057110A2 WO 2015057110 A2 WO2015057110 A2 WO 2015057110A2 RU 2014000776 W RU2014000776 W RU 2014000776W WO 2015057110 A2 WO2015057110 A2 WO 2015057110A2
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WIPO (PCT)
Prior art keywords
skin
cosmetic
vitamin
composition
product
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PCT/RU2014/000776
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French (fr)
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WO2015057110A3 (en
Inventor
Ilya Vladimirovich DUKHOVLINOV
Alexander Aleksandrovich REZYAPKIN
Petr Ivanovich GOLYSHEV
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Limited Liability Company "Pharma Gen" (Llc "Pharma Gen")
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Publication of WO2015057110A2 publication Critical patent/WO2015057110A2/en
Publication of WO2015057110A3 publication Critical patent/WO2015057110A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/44—Oxidoreductases (1)
    • A61K38/446—Superoxide dismutase (1.15)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/362—Polycarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/673—Vitamin B group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/678—Tocopherol, i.e. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/005—Preparations for sensitive skin

Definitions

  • An embodiment of the present invention relates to medicine and cosmetology, notably to deep acting cosmetics, and can be used for the purpose of recovery of the physiological skin functions and elimination of defects of endogenous (e.g.: systemic condition) and exogenous (e.g.: ultraviolet (UV) irradiation, high or low temperatures, wrong cosmetic care) origins.
  • endogenous e.g.: systemic condition
  • exogenous e.g.: ultraviolet (UV) irradiation, high or low temperatures, wrong cosmetic care
  • Physiological impairment and skin defects are a widely spread problem. Inter alia, those are represented by sebum oversecretion, irritations, hyperemia, ecdysis, skin incarceration, and a sense of discomfort, oedema as the result of traumatic cosmetic procedures (e.g.: after peeling, face cleansing, depilation, epilation, mesotherapy, and biorevitalization — oedema around papules at the injection sites), burns (e.g.: thermal, chemical), abscesses, and eruptions, consequences of acne, capillary nets, uneven skin tone. The discomfort is caused by the skin recovery duration.
  • the aim of the present invention is to achieve rapid skin recovery of skin with dysfunction and cosmetic defects, without induction of irritative and allergic reactions.
  • a cosmetic is put forward, containing superoxide dismutase (SOD), arginine, water-soluble vitamin E analogue Trolox, dexpanthenol (D-panthenol), and succinic acid, in water solution.
  • SOD superoxide dismutase
  • arginine arginine
  • Trolox water-soluble vitamin E analogue
  • D-panthenol dexpanthenol
  • succinic acid in water solution.
  • the present composition is unique, due to thorough selection of the components.
  • SOD which eliminates superoxide radicals and prevents formation of oxygen radicals, more dangerous for the body [2]. Products based on SOD are the most perspective ones among anti-inflammatory pharmaceuticals.
  • Arginine is an aliphatic basic a-acid; it is a substrate for NO-synthases in the nitrogen oxide (NO) synthesis, which is a local tissue hormone regulating blood microcirculation in skin tissues. Intensification of blood circulation is vital for maintenance and regulation of the main biochemical processes. Not many cosmetics exist nowadays that stimulate microcirculation in the skin tissues. Due to vasodilatation and intensification of blood flow, components of the product penetrate into skin more easily, which enhances its effect in a short exposition period. Arginine also accelerates the repair of damaged tissues. Arginine is considered to be an "indirect anti-oxidant", because it activates ferments responsible for rejuvenation and repair of tissue before the cells are damaged by free radicals and is used in cosmetics, for example, for sun-protection [3].
  • NO nitrogen oxide
  • L-arginine is also a good stabilizer, which allows to preserve the product at room temperature, without loss of its entity and activity of the product components, and, consequently, of its properties.
  • the water-soluble vitamin E analogue Trolox performs the role of an antioxidant.
  • Trolox (TEAC) is an equivalent for measuring of the antioxidant effectivity of complex compositions, as well as ferric reducing ability of plasma (FRAP).
  • Trolox is known as a preserving agent for stem cells or progenitor cells in a hypothermic solution [4]. It has been revealed that it allows to preserve neuronal stem cells for two days in normal saline at room temperature.
  • Trolox vitamin E or its derivates
  • Trolox in association with gallate is known to be used as a cytoprotective composition against oxygen radical damage (in form of injection or as a food compound), and also in the form of a composition for the delay of edible and inedible (fuel) oils decay [6].
  • This compound is also known to be used for initiation of reduction of amino acid radicals that are being produced as a result of radiolytic degradation of a protein in solution [7].
  • a composition is known, in which a protein is protected from ionizing irradiation via addition of such antioxidants as o-vanillin and trolox [8].
  • Dexpanthenol (R-2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-butanamide) is a water-soluble vitamin. Applied locally, it is rapidly absorbed by skin and transforms into pantothenic acid, which is also known as vitamin B5; and as a coenzyme A component it plays central role in skin metabolism. Besides, dexpanthenol, being locally applied, increases the ability of skin to retain moisture, as well as improves elasticity of the treated skin. Treatment with dexpanthenol accelerates regeneration of the damaged tissue. Besides, dexpanthenol and pantothenic acid are anti-inflammatory and antipruritic agents. Dexpanthenol is distinct in its superior tolerability [9].
  • Succinic acid is a water-soluble dibasic saturate carboxylic acid.
  • succinic acid shows multiple effects: it acts as a powerful antioxidant preventing lipid peroxidation and inhibiting the process of free radicals formation; it cleans oil gland ducts, preventing blocking of pores and consequently prevents formation of comedos, inhibits inflammatory processes normalizing histamine and serotonin concentrations, eliminates acneiform rash and acne, exfoliates cellular debris of stratum comeum, making the skin look younger, healthier, and more cared-for, promotes skin cells oxygenation, normalizes cell respiration (it takes part in the tricarboxylic acid cycle); it also helps to flatten scars and striae cutis distensae, allows to pass superfluous water from the body, removing oedemas, lifts skin, increases its elasticity and plasticity, provides perception of other active agents by skin cells,
  • compositions are known containing from one to three components mentioned above, for different esthetic aims, which are administered in different ways. Basically, such compositions are used for the organism general state improvement, including improvement of the skin state.
  • a cosmetic wrinkles remover is known containing botulinus toxin A, ozone, and normal saline, which can also contain vitamin E (0.1-1), a-hydroxy acids (0.1-1), or SOD (0.1-1), as well as human serum albumin [10].
  • This agent is for injections. It is not specified how the human serum albumin is obtained.
  • Application of only recombinant protein provides safety of the composition containing this protein.
  • a health preserving essence which contains boxthorn fruit, SOD, taurin, arginine, phytic acid, shrimp extract, and vitamin C [1 1]. The essence is used as vine.
  • An anti-aging composition for administration in warm-blooded animals which contains one or more mono-, di-, or trivalent metal salts, one or more amino acids, aminoalcohol, and a vitamin B-complex [12].
  • the amino acid fraction is represented by glutamine, arginine, lysine, ornithine, proline, or histidine, the vitamin B-complex— by para-aminobenzoic acid, Bl (thiamine), B2 (riboflavin), B3, B5, B6 (pyridoxine), or B12 (cobalamine).
  • the composition can also contain L-taurin, inosite, choline, vitamin P, oligopeptide, resveratrol, folic acid, biotin, vitamin D, vitamin A, Ginkgo biloba extract, lycopin, proanthocyanidine, black seeds extract, bromeline, lipase, catalase, colloidal silicon dioxide, iodine, and an immunostimulant.
  • This composition is to be administered orally.
  • a multi-purpose facial cream is known, containing Sargassum fusiforme extract, which in its turn contains polysaccharides, vitamin E, vitamin C, SOD and other components for skin care [13].
  • polysaccharides are a rich substrate for different microorganisms, which can cause their active reproduction and metabolism both during storage and on skin, which can lead, for example, to skin inflammation.
  • vitamin C can lighten skin [14]— the property desired not by all customers.
  • the disadvantage of this invention is the amount of control reduction on composition due to its complexity.
  • a cosmetic which contains royal jelly, ginseng extract
  • the active agent is represented by one or more from vitamin C, ethylic ether, vitamin E acetate, allantoin, ethoxyurea, Glycyrrhiza flavonoids, Aloe barbadensis extract, papain, Melaleuca oil, Spiraea phenolic acid, Hamamelis virginiana extract, pine pollen, matrin, vitamin A, buckeye extract, or portulaca [15].
  • Saponins, polysaccharides, amino acids, vitamins, minerals, SOD are formulated into royal jelly and ginseng extract.
  • One of the disadvantages of this invention is the amount of control reduction on agent due to its complexity, as well as the risk of side-effects, connected with the presence of allergens and the components in the product that can be a substrate for microorganisms (polysaccharides) under the absence of an antimicrobial agent.
  • An antiseptic in its turn, can eliminate the beneficial microorganisms.
  • a composition which contains SOD, as well as vitamins E and C [16].
  • SOD is isolated from animal blood, in particular, from the steer blood, which is the disadvantage of this invention, as this method of isolation is connected with a high probability of obtaining contaminated product (e.g.: virus contamination).
  • contaminated product e.g.: virus contamination.
  • Production of SOD via biotechnology or chemical synthesis allows obtaining a sterile product.
  • a composite liposoluble antioxidant for protection of the lipid part of the cell membrane from free radicals is known containing liposoluble vitamin E, coenzyme Q10 and SOD [17].
  • liposolubility determines following requirement: these agents are to be used with a fatty base, which also creates conditions for reproduction of different microorganisms under the absence of an antimicrobial agent.
  • a cosmetic composition for improvement of the skin barrier function for skin aging prevention, initiation of regeneration, and long-lasting skin moisturizing, which contains natural ingredients with long-lasting moisturizing effect:: 0.1-5% weight— soy extract, 0.05- 0.2% weight— scented essential oil, 1-30% weight— hyaluronic acid, 1.5-3.5% weight— vitamins (0.3-0.7% weight— vitamin C, 0.3-0.7% weight— vitamin B3, 0.3-0.7% weight— vitamin B5, 0.3-0.7% weight— vitamin B6, 0.3-0.7% weight— vitamin E), 0.1-5%— sodium citrate, 0.1-5% weight— citric acid, 0.1-5% weight— lactic acid, 0.5-2% weight— arginine, the rest— purified water [18].
  • the composition also contains jojoba oil (2-8% weight), lecithin (3-8% weight), and xantham gum (0.01-10% weight).
  • the disadvantage of this invention is the amount of control reduction on the agent due to its complexity. Presence of the citric acid and vitamin C in the composition provides skin lightening, which is the property desired not by all customers.
  • a composition for hair care is known containing macadamia nut oil, Shorea stenoptera seed oil, D-panthenol, dl-alpha tocopherol acetate, vitamin E in liposomes, and a nonionic emulgating agent [19].
  • This composition is to obtain products for dry and damaged hair treatment, particularly in form of creams, shampoos, balms after shampooing, gels, and milk.
  • a nanoemulsion for external treatment is known containing polyethylenglycol modified SOD (mPEG-SOD), which is produced of isopropyl myristate, caprylocaproyl macrogolglyceride, polyglyceryl-3-dioleate, mPEG-SOD water solution, vitamin E [20].
  • mPEG-SOD polyethylenglycol modified SOD
  • An oil series product is known - a SOD containing composition, SOD and vitamin A containing composition, SOD, vitamins A and D containing composition, SOD, vitamins A, D and E containing composition [21].
  • An eyelid care product is known containing cosmetic base, eftiderm, malavit, Eleutherococcus extract, juniper oil, jojoba oil, citric and succinic acids, tocopherol acetate (vitamin E) and retinol acetate (vitamin A) [22].
  • a composition for external use on skin containing a combination of panthenol, fish oil, a-tocopherol acetate, arginine, isoleucine, leucine, methionine, phenylalanine, threonine, and valine with an appropriate carrier [23].
  • the composition is applied to treat burns, cuts, scratches, insect stings, inflammations caused by sun exposure or wind, skin dryness, psoriasis, seborrheic dermatitis and eczema.
  • the oil-based products (seed and animal fats) without antiseptic agents in the composition are a substrate for different microorganisms, which can lead to their reproduction and can have a negative effect after application on skin.
  • the application of antiseptics can have a negative effect on the quantitative and qualitative composition of the beneficial human microbiota.
  • a liquid for damaged cells recovery which contains SOD, aloe juice, hyaluronic acid solution, a-lipoic acid and vitamin E (0.5-4). Every 100 g of the recovery liquid contain 40000-4000000 SOD activity units.
  • the disadvantage of this invention is in the complexity of the solution production, in particular, the necessity to obtain each component and only then to produce the composition (production of plant extracts).
  • a composition which aids with sexual disorders and has an effect of an aphrodisiac
  • its active agents are lycopin, vitamin Bl, vitamin B2, vitamin B3, vitamin B5 (less than 0.2%, or 0.2% - 0.6%), vitamin B6, vitamin B12, vitamin C, coffein, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, L-arginine (less than 3.5%, or 3.5% - 12.0%), quercetin, and vitamin E (up to 1.4%, or 1.4% - 18.0%) [24].
  • One of the disadvantages of this invention is the absence of the route of administration of this composition indication.
  • the purpose of this composition is to treat sexual dysfunction, which is different to the one in the present invention.
  • the closest analogue to the present invention is a skin lightening composition, containing components A and B [25].
  • the A-component is astaxanthin
  • the B-component is one of the diverse compounds, among which there are also succinic acid, vitamin E, vitamin B and its derivates, SOD.
  • One of the disadvantages of the prototype of the mentioned invention is the fact that complementary to the compounds listed above, a big number of other components is claimed in the composition, which increases the probability of cross-reaction of the compounds in the composition and can possess a negative effect on the composition properties. It is rather difficult to detect such compounds: the disadvantage is in the difficulty of the composition agents control. Moreover, the quantitative ingredients' proportions are not given, which makes the reproduction of this composition and the estimation of its efficacy more difficult.
  • the disadvantage of this composition is also the fact that it is not specified which vitamin from the vitamin B-group is used — and this is essential for determination of the composition's properties.
  • the B- components of the composition are subordinate additives, while the main properties of the composition in the invention are determined by the A-component.
  • the claimed invention is free from these disadvantages.
  • the technical result of application of the cosmetic in the present invention is also its noninvasiveness, due to external use of the composition, which allows decreasing the risks of side-effects (in comparison to injectional, predominantly, and oral administration routes, there is no effect on the gastrointestinal tract (GIT)).
  • the technical result of application of the cosmetic in the present invention is also the non- induction of allergic and irritant reactions.
  • the present technical result is accomplished by the facts that the composition is water-based and contains only water-soluble components, does not contain substrates for microorganisms, and, consequently, there is no necessity to use antiseptics.
  • the water-soluble components inter alia, the water-soluble form of vitamin E, and aqueous base are applied, which allows eliminating the probability of reproduction and metabolism of microorganisms on the patient's skin, irritation, and inflammation of the skin respectively.
  • the pharmaceutical form of the product contemplates the application of a single dose of the product (an ampule or a vial), which eliminates the possibility of penetration and reproduction of microorganisms in the product during storage.
  • the technical result of application of the cosmetic described in the present invention is also the increase of the product's safety.
  • the present technical result is accomplished by the fact that only innocuous compounds are used for the product creation.
  • the recombinant SOD is used, and the components - substrates for microorganisms are not used, no antiseptics are added.
  • the technical result of application of the cosmetic described in the present invention is its universalism—the product is not irritant, it is applicable for all skin types, all ages, both genders, for different skin areas, due to the fact that the product normalizes the function of skin cells and improves the visual appearance of the skin— it eliminates functional and cosmetic defects, possessing at the same time no lightening effect, lifts skin, being not an "anti-aging" product.
  • the technical result of application of the cosmetic described in the present invention is also the rapid (see examples) recovery of the normal function and improvement of the visual appearance of the skin, as the result of elimination of after-effects of aggressive environmental factors and/or physical disorders, respectively, as the result of combination of the optimally matched components in the product and specificity of its application — external local administration for the time period enough for the deep action.
  • the active agents are address-deliverable, which increases the efficacy of the product and allows to apply it in smaller doses, in comparison to oral administration, due to the reduction of quantitative and qualitative losses during passing through the GIT.
  • the technical result of application of the cosmetic described in the present invention is also the decrease of risk of the reduction of the effect controlling as the result of non-complexity of the product.
  • the technical result is also the simplification of production of this composition.
  • the claimed result is achieved due to application of ready-to-use components, which are mixed under no special conditions for obtaining the product described in the present invention.
  • a cosmetic for a rapid skin regeneration is put forward, containing superoxide dismutase, vitamin of the B-group, succinic acid, characterized in that it additionally contains a water- soluble analogue of vitamin E, trolox, and L-arginine; the activity of superoxide dismutase is 200 000 - 300 000 U/mg, vitamin of the B-group is represented by dexpanthenol; the proportion of the components is as follows, weight%: superoxide dismutase 0.1% (0.01% - 32%), dexpanthenol 0.2% (0.1% - 20%), succinic acid 0.6% (0.5% - until pH 6.0), trolox 0.23% (0.13% - 45%), L-arginine 1% (0.9% - 64%), water for injections.
  • the composition is applied on skin for 20 minutes (15-20 minutes) to eliminate cosmetic defects and functional abnormality using the cosmetic retaining material giving off the product to the skin during the period of exposition.
  • the product allows rapid skin recovery without induction
  • Example 2 A dermatologist's patient after biorevitalization procedure.
  • Example 3 A patient of the dermatologist after laser peeling procedure.
  • Example 4 A patient— greasy skin care.
  • Example 5 A cosmetologist's patient— finishing masks of a complex care (use at home).
  • Example 6 A cosmetologist's patient after the enzyme peeling.
  • Skin characteristics before application skin hyperemia as the result of papain enzyme peeling.
  • Example 7 A cosmetologist's patient after a wax epilation.
  • Example 8 A cosmetologist's patient— sunburn.
  • Example 9 A dermatocosmetologist's patient after thermal burn.
  • UV-irradiation and skin effects, problems, solutions, collection of articles: publishing house “Cosmetics and Medicine", 2004, 391 p.
  • Alexis AF Blackcloud P. Natural ingredients for darker skin types: growing options for hyperpigmentation. J Drugs Dermatol. 2013 Sep l ; 12(9):sl23-7.

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Abstract

An embodiment of the present invention relates to medicine and cosmetology, notably to deep acting cosmetics, and can be used for the purpose of recovery of the physiological skin functions and elimination of defects of endogenous and exogenous origins. A cosmetic for rapid skin regeneration is put forward containing superoxide dismutase, dexpanthenol, succinic acid, trolox and L-arginine. The cosmetic is applied on skin for 20 minutes (15-20 minutes) using the cosmetic retaining material giving off the product to the skin during the period of exposition. The cosmetic allows to expand the arsenal of tools for skin state improvement, to decrease the risk of reduction of the effect control and probability of allergic and inflammatory reactions. The product is safe, simple to produce and possesses a universal skin normalizing effect, the administration is noninvasive.

Description

Cosmetic for rapid skin regeneration
DESCRIPTION
Field of the invention
An embodiment of the present invention relates to medicine and cosmetology, notably to deep acting cosmetics, and can be used for the purpose of recovery of the physiological skin functions and elimination of defects of endogenous (e.g.: systemic condition) and exogenous (e.g.: ultraviolet (UV) irradiation, high or low temperatures, wrong cosmetic care) origins.
Background of the invention
Physiological impairment and skin defects are a widely spread problem. Inter alia, those are represented by sebum oversecretion, irritations, hyperemia, ecdysis, skin incarceration, and a sense of discomfort, oedema as the result of traumatic cosmetic procedures (e.g.: after peeling, face cleansing, depilation, epilation, mesotherapy, and biorevitalization — oedema around papules at the injection sites), burns (e.g.: thermal, chemical), abscesses, and eruptions, consequences of acne, capillary nets, uneven skin tone. The discomfort is caused by the skin recovery duration.
The aim of the present invention is to achieve rapid skin recovery of skin with dysfunction and cosmetic defects, without induction of irritative and allergic reactions.
In order to achieve this aim, a cosmetic is put forward, containing superoxide dismutase (SOD), arginine, water-soluble vitamin E analogue Trolox, dexpanthenol (D-panthenol), and succinic acid, in water solution.
The present composition is unique, due to thorough selection of the components.
In the course of the skin inflammation, free radicals are being produced [1 ], which damage the surrounding healthy tissues and hinder reparative processes. The key ferment protecting tissues against free radicals is SOD, which eliminates superoxide radicals and prevents formation of oxygen radicals, more dangerous for the body [2]. Products based on SOD are the most perspective ones among anti-inflammatory pharmaceuticals.
Arginine is an aliphatic basic a-acid; it is a substrate for NO-synthases in the nitrogen oxide (NO) synthesis, which is a local tissue hormone regulating blood microcirculation in skin tissues. Intensification of blood circulation is vital for maintenance and regulation of the main biochemical processes. Not many cosmetics exist nowadays that stimulate microcirculation in the skin tissues. Due to vasodilatation and intensification of blood flow, components of the product penetrate into skin more easily, which enhances its effect in a short exposition period. Arginine also accelerates the repair of damaged tissues. Arginine is considered to be an "indirect anti-oxidant", because it activates ferments responsible for rejuvenation and repair of tissue before the cells are damaged by free radicals and is used in cosmetics, for example, for sun-protection [3].
L-arginine is also a good stabilizer, which allows to preserve the product at room temperature, without loss of its entity and activity of the product components, and, consequently, of its properties.
The water-soluble vitamin E analogue Trolox performs the role of an antioxidant. Trolox (TEAC) is an equivalent for measuring of the antioxidant effectivity of complex compositions, as well as ferric reducing ability of plasma (FRAP).
Trolox is known as a preserving agent for stem cells or progenitor cells in a hypothermic solution [4]. It has been revealed that it allows to preserve neuronal stem cells for two days in normal saline at room temperature.
Trolox (vitamin E or its derivates) is known to be used in a composition for the purpose of decrease of potassium ion leakage from erythrocytes under photoinactivation in the presence of a photosensibilizer [5].
Trolox in association with gallate is known to be used as a cytoprotective composition against oxygen radical damage (in form of injection or as a food compound), and also in the form of a composition for the delay of edible and inedible (fuel) oils decay [6].
This compound is also known to be used for initiation of reduction of amino acid radicals that are being produced as a result of radiolytic degradation of a protein in solution [7]. A composition is known, in which a protein is protected from ionizing irradiation via addition of such antioxidants as o-vanillin and trolox [8].
Dexpanthenol (R-2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethyl-butanamide) is a water-soluble vitamin. Applied locally, it is rapidly absorbed by skin and transforms into pantothenic acid, which is also known as vitamin B5; and as a coenzyme A component it plays central role in skin metabolism. Besides, dexpanthenol, being locally applied, increases the ability of skin to retain moisture, as well as improves elasticity of the treated skin. Treatment with dexpanthenol accelerates regeneration of the damaged tissue. Besides, dexpanthenol and pantothenic acid are anti-inflammatory and antipruritic agents. Dexpanthenol is distinct in its superior tolerability [9].
Succinic acid (butanedioic acid, ethane- 1 ,2-dicarboxylic acid) is a water-soluble dibasic saturate carboxylic acid. Under external application succinic acid shows multiple effects: it acts as a powerful antioxidant preventing lipid peroxidation and inhibiting the process of free radicals formation; it cleans oil gland ducts, preventing blocking of pores and consequently prevents formation of comedos, inhibits inflammatory processes normalizing histamine and serotonin concentrations, eliminates acneiform rash and acne, exfoliates cellular debris of stratum comeum, making the skin look younger, healthier, and more cared-for, promotes skin cells oxygenation, normalizes cell respiration (it takes part in the tricarboxylic acid cycle); it also helps to flatten scars and striae cutis distensae, allows to pass superfluous water from the body, removing oedemas, lifts skin, increases its elasticity and plasticity, provides perception of other active agents by skin cells, increasing their effect.
The compositions are known containing from one to three components mentioned above, for different esthetic aims, which are administered in different ways. Basically, such compositions are used for the organism general state improvement, including improvement of the skin state.
A cosmetic wrinkles remover is known containing botulinus toxin A, ozone, and normal saline, which can also contain vitamin E (0.1-1), a-hydroxy acids (0.1-1), or SOD (0.1-1), as well as human serum albumin [10]. This agent is for injections. It is not specified how the human serum albumin is obtained. Application of only recombinant protein provides safety of the composition containing this protein.
A health preserving essence is known, which contains boxthorn fruit, SOD, taurin, arginine, phytic acid, shrimp extract, and vitamin C [1 1]. The essence is used as vine.
An anti-aging composition for administration in warm-blooded animals is known, which contains one or more mono-, di-, or trivalent metal salts, one or more amino acids, aminoalcohol, and a vitamin B-complex [12]. The amino acid fraction is represented by glutamine, arginine, lysine, ornithine, proline, or histidine, the vitamin B-complex— by para-aminobenzoic acid, Bl (thiamine), B2 (riboflavin), B3, B5, B6 (pyridoxine), or B12 (cobalamine). The composition can also contain L-taurin, inosite, choline, vitamin P, oligopeptide, resveratrol, folic acid, biotin, vitamin D, vitamin A, Ginkgo biloba extract, lycopin, proanthocyanidine, black seeds extract, bromeline, lipase, catalase, colloidal silicon dioxide, iodine, and an immunostimulant. This composition is to be administered orally.
A multi-purpose facial cream is known, containing Sargassum fusiforme extract, which in its turn contains polysaccharides, vitamin E, vitamin C, SOD and other components for skin care [13]. Among the disadvantages of this invention there is a fact that several components of the abovesaid plant extract can possess negative effect on skin, for example, polysaccharides are a rich substrate for different microorganisms, which can cause their active reproduction and metabolism both during storage and on skin, which can lead, for example, to skin inflammation. It has been revealed that vitamin C can lighten skin [14]— the property desired not by all customers. The disadvantage of this invention is the amount of control reduction on composition due to its complexity.
A cosmetic is known, which contains royal jelly, ginseng extract; the active agent is represented by one or more from vitamin C, ethylic ether, vitamin E acetate, allantoin, ethoxyurea, Glycyrrhiza flavonoids, Aloe barbadensis extract, papain, Melaleuca oil, Spiraea phenolic acid, Hamamelis virginiana extract, pine pollen, matrin, vitamin A, buckeye extract, or portulaca [15]. Saponins, polysaccharides, amino acids, vitamins, minerals, SOD are formulated into royal jelly and ginseng extract. One of the disadvantages of this invention is the amount of control reduction on agent due to its complexity, as well as the risk of side-effects, connected with the presence of allergens and the components in the product that can be a substrate for microorganisms (polysaccharides) under the absence of an antimicrobial agent. An antiseptic, in its turn, can eliminate the beneficial microorganisms.
A composition is known which contains SOD, as well as vitamins E and C [16]. SOD is isolated from animal blood, in particular, from the steer blood, which is the disadvantage of this invention, as this method of isolation is connected with a high probability of obtaining contaminated product (e.g.: virus contamination). Production of SOD via biotechnology or chemical synthesis allows obtaining a sterile product.
A composite liposoluble antioxidant for protection of the lipid part of the cell membrane from free radicals is known containing liposoluble vitamin E, coenzyme Q10 and SOD [17]. However, the liposolubility determines following requirement: these agents are to be used with a fatty base, which also creates conditions for reproduction of different microorganisms under the absence of an antimicrobial agent.
A cosmetic composition is known for improvement of the skin barrier function for skin aging prevention, initiation of regeneration, and long-lasting skin moisturizing, which contains natural ingredients with long-lasting moisturizing effect:: 0.1-5% weight— soy extract, 0.05- 0.2% weight— scented essential oil, 1-30% weight— hyaluronic acid, 1.5-3.5% weight— vitamins (0.3-0.7% weight— vitamin C, 0.3-0.7% weight— vitamin B3, 0.3-0.7% weight— vitamin B5, 0.3-0.7% weight— vitamin B6, 0.3-0.7% weight— vitamin E), 0.1-5%— sodium citrate, 0.1-5% weight— citric acid, 0.1-5% weight— lactic acid, 0.5-2% weight— arginine, the rest— purified water [18]. The composition also contains jojoba oil (2-8% weight), lecithin (3-8% weight), and xantham gum (0.01-10% weight). The disadvantage of this invention is the amount of control reduction on the agent due to its complexity. Presence of the citric acid and vitamin C in the composition provides skin lightening, which is the property desired not by all customers.
A composition for hair care is known containing macadamia nut oil, Shorea stenoptera seed oil, D-panthenol, dl-alpha tocopherol acetate, vitamin E in liposomes, and a nonionic emulgating agent [19]. This composition is to obtain products for dry and damaged hair treatment, particularly in form of creams, shampoos, balms after shampooing, gels, and milk.
A nanoemulsion for external treatment is known containing polyethylenglycol modified SOD (mPEG-SOD), which is produced of isopropyl myristate, caprylocaproyl macrogolglyceride, polyglyceryl-3-dioleate, mPEG-SOD water solution, vitamin E [20].
An oil series product is known - a SOD containing composition, SOD and vitamin A containing composition, SOD, vitamins A and D containing composition, SOD, vitamins A, D and E containing composition [21].
An eyelid care product is known containing cosmetic base, eftiderm, malavit, Eleutherococcus extract, juniper oil, jojoba oil, citric and succinic acids, tocopherol acetate (vitamin E) and retinol acetate (vitamin A) [22].
A composition for external use on skin is known containing a combination of panthenol, fish oil, a-tocopherol acetate, arginine, isoleucine, leucine, methionine, phenylalanine, threonine, and valine with an appropriate carrier [23]. The composition is applied to treat burns, cuts, scratches, insect stings, inflammations caused by sun exposure or wind, skin dryness, psoriasis, seborrheic dermatitis and eczema.
As mentioned above, the oil-based products (seed and animal fats) without antiseptic agents in the composition are a substrate for different microorganisms, which can lead to their reproduction and can have a negative effect after application on skin. At the same time, the application of antiseptics can have a negative effect on the quantitative and qualitative composition of the beneficial human microbiota.
A liquid for damaged cells recovery is known which contains SOD, aloe juice, hyaluronic acid solution, a-lipoic acid and vitamin E (0.5-4). Every 100 g of the recovery liquid contain 40000-4000000 SOD activity units. The disadvantage of this invention is in the complexity of the solution production, in particular, the necessity to obtain each component and only then to produce the composition (production of plant extracts). A composition is known which aids with sexual disorders and has an effect of an aphrodisiac, its active agents are lycopin, vitamin Bl, vitamin B2, vitamin B3, vitamin B5 (less than 0.2%, or 0.2% - 0.6%), vitamin B6, vitamin B12, vitamin C, coffein, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, L-arginine (less than 3.5%, or 3.5% - 12.0%), quercetin, and vitamin E (up to 1.4%, or 1.4% - 18.0%) [24]. One of the disadvantages of this invention is the absence of the route of administration of this composition indication. The purpose of this composition is to treat sexual dysfunction, which is different to the one in the present invention.
The closest analogue to the present invention is a skin lightening composition, containing components A and B [25]. The A-component is astaxanthin, and the B-component is one of the diverse compounds, among which there are also succinic acid, vitamin E, vitamin B and its derivates, SOD. One of the disadvantages of the prototype of the mentioned invention is the fact that complementary to the compounds listed above, a big number of other components is claimed in the composition, which increases the probability of cross-reaction of the compounds in the composition and can possess a negative effect on the composition properties. It is rather difficult to detect such compounds: the disadvantage is in the difficulty of the composition agents control. Moreover, the quantitative ingredients' proportions are not given, which makes the reproduction of this composition and the estimation of its efficacy more difficult. The disadvantage of this composition is also the fact that it is not specified which vitamin from the vitamin B-group is used — and this is essential for determination of the composition's properties. The B- components of the composition are subordinate additives, while the main properties of the composition in the invention are determined by the A-component.
The claimed invention is free from these disadvantages.
The technical result of application of the cosmetic described in the present invention is widening of the range of agents for the improvement of skin state.
The technical result of application of the cosmetic in the present invention is also its noninvasiveness, due to external use of the composition, which allows decreasing the risks of side-effects (in comparison to injectional, predominantly, and oral administration routes, there is no effect on the gastrointestinal tract (GIT)). The technical result of application of the cosmetic in the present invention is also the non- induction of allergic and irritant reactions. The present technical result is accomplished by the facts that the composition is water-based and contains only water-soluble components, does not contain substrates for microorganisms, and, consequently, there is no necessity to use antiseptics. The water-soluble components, inter alia, the water-soluble form of vitamin E, and aqueous base are applied, which allows eliminating the probability of reproduction and metabolism of microorganisms on the patient's skin, irritation, and inflammation of the skin respectively.
The pharmaceutical form of the product contemplates the application of a single dose of the product (an ampule or a vial), which eliminates the possibility of penetration and reproduction of microorganisms in the product during storage.
The technical result of application of the cosmetic described in the present invention is also the increase of the product's safety. The present technical result is accomplished by the fact that only innocuous compounds are used for the product creation. The recombinant SOD is used, and the components - substrates for microorganisms are not used, no antiseptics are added.
The technical result of application of the cosmetic described in the present invention is its universalism— the product is not irritant, it is applicable for all skin types, all ages, both genders, for different skin areas, due to the fact that the product normalizes the function of skin cells and improves the visual appearance of the skin— it eliminates functional and cosmetic defects, possessing at the same time no lightening effect, lifts skin, being not an "anti-aging" product.
The technical result of application of the cosmetic described in the present invention is also the rapid (see examples) recovery of the normal function and improvement of the visual appearance of the skin, as the result of elimination of after-effects of aggressive environmental factors and/or physical disorders, respectively, as the result of combination of the optimally matched components in the product and specificity of its application — external local administration for the time period enough for the deep action. As a result of external application of the product, the active agents are address-deliverable, which increases the efficacy of the product and allows to apply it in smaller doses, in comparison to oral administration, due to the reduction of quantitative and qualitative losses during passing through the GIT.
The products containing only water-soluble components, different from those with liposoluble components, do not form a film on skin interrupting exchange processes with the environment and, in particular, affecting cellular respiration. This fact allows achieving rapid skin recovery. The technical result of application of the cosmetic described in the present invention is also the decrease of risk of the reduction of the effect controlling as the result of non-complexity of the product.
The technical result is also the simplification of production of this composition. The claimed result is achieved due to application of ready-to-use components, which are mixed under no special conditions for obtaining the product described in the present invention.
Description of the invention
A cosmetic for a rapid skin regeneration is put forward, containing superoxide dismutase, vitamin of the B-group, succinic acid, characterized in that it additionally contains a water- soluble analogue of vitamin E, trolox, and L-arginine; the activity of superoxide dismutase is 200 000 - 300 000 U/mg, vitamin of the B-group is represented by dexpanthenol; the proportion of the components is as follows, weight%: superoxide dismutase 0.1% (0.01% - 32%), dexpanthenol 0.2% (0.1% - 20%), succinic acid 0.6% (0.5% - until pH 6.0), trolox 0.23% (0.13% - 45%), L-arginine 1% (0.9% - 64%), water for injections. The composition is applied on skin for 20 minutes (15-20 minutes) to eliminate cosmetic defects and functional abnormality using the cosmetic retaining material giving off the product to the skin during the period of exposition. The product allows rapid skin recovery without induction of irritative or allergic reactions.
Trials were carried out that reflect the concrete examples of implementation of the present invention. The trials were carried out to prove the technical result.
Example 1. Production of the composition.
Following compounds were mixed under sterile conditions at room temperature until the designated percentage to total weight was reached:
SOD (LLC «RPE «Enzyme technologies)), Russia)— 0.1%
Trolox (HYDROXY-2,5,7,8-TETRAMETHYLCHROMANE-2-CARBOXYLIC ACID)
(Aldrich, Russia)— 0.23%
L-arginine (Panreac, Spain)— 1%
Succinic acid (CJSC «Lenreaktiv», Russia)— 0.6%
Dexpanthenol (Fluka, Switzerland)— 0.2%
Water for injections— the rest.
The same components of other producers may be used for production of the cosmetic. Example 2. A dermatologist's patient after biorevitalization procedure.
Gender, age: female, 32 years old.
Applications number, duration of exposition: 1, 20 minutes.
Skin characteristics before application: capillary net, papules (the patient with evident vascular pathology).
Skin characteristics after application: notable flattening of the skin color tone, lightening, vasoconstriction.
Example 3. A patient of the dermatologist after laser peeling procedure.
Gender, age: male, 27 years old.
Applications number, duration of exposition: 1 , 20 minutes.
Skin characteristics before application: definitive rubor, incipient inflammation, subjective discomfort in the area of treatment.
Skin characteristics after application: decrease of inflammation, notable decrease of rubor and tightness feeling.
Dermatologist's comment:
1. The ease of product's application and especially removal (no additional washing needed);
2. Easy to apply after injectional and aggressive procedures;
3. Indispensable after peeling, laser, and warming procedures;
4. Easy to apply on the man's skin.
Example 4. A patient— greasy skin care.
Gender, age: female, 24 years old.
Applications number, duration of exposition: 5, 15 minutes. Frequency: alternate days.
Skin characteristics before application: greasy skin with acne consequences, chemical burn mark on the cheek.
Skin characteristics after application: decrease of rubor, regeneration after the burn (the mark has significantly lightened after five applications, the wounds have closed), and general improvement of the skin state (greasiness decreased and a good state remained the whole day).
Patient's comment: pleasant sensations during the application of the product— the feeling of freshness, relaxing effect.
Example 5. A cosmetologist's patient— finishing masks of a complex care (use at home).
Gender, age: female, 29 years old. Applications number, duration of exposition: daily application, 3 days, for 20 minutes. Skin characteristics before application: dermatitis complicated by mixed seborrhea, eruptions with insular suppuration.
Skin characteristics after application: significant decrease of sebum secretion and eruptions with insular suppuration.
Example 6. A cosmetologist's patient after the enzyme peeling.
Gender, age: female, 43 years old.
Applications number, duration of exposition: 1, 20 minutes.
Skin characteristics before application: skin hyperemia as the result of papain enzyme peeling.
Skin characteristics after application: reduction of hyperemia.
Example 7. A cosmetologist's patient after a wax epilation.
Gender, age: female, 36 years old.
Applications number, duration of exposition: 1 , 10 minutes.
Skin characteristics before application: irritation in the epilation area (bikini).
Skin characteristics after application: reduction of hyperemia, oedema reduction during treatment with the product.
Example 8. A cosmetologist's patient— sunburn.
Gender, age: male, 34 years old.
Applications number, duration of exposition: daily application, 2 days, for 15 minutes.
Skin characteristics before application: hyperemia, skin flaking.
Skin characteristics after application: reduction of hyperemia, no skin flaking, in comparison with other areas exposed to intensive sun radiation. Cosmetologist's comment: the results are good; it would be interesting to apply the product in other cosmetic procedures, during the care period, and for the use at home.
Example 9. A dermatocosmetologist's patient after thermal burn.
Gender, age: female, 23 years old.
Applications number, duration of exposition: 2, the first application - 5 hours after burn for 20 minutes, the second— on the next day for 20 minutes.
Skin characteristics before application: redness, blistering at the burn area.
Skin characteristics after application: acceleration of the rehabilitation process— the injured skin completely recovered over a period of 7 days. Example 10. A dermatocosmetologist's patient after mesotherapy.
Gender, age: female, 40 years old.
Applications number, duration of exposition: 3 procedures in total, daily, directly after each mesotherapy one time a day. The exposition period— 20 minutes.
Skin characteristics before application: papules at the injection sites (face).
Skin characteristics after application: papules at the injection sites (face), no oedema around the papules.
REFERENCES: 1. Gourley S.T., Rice R.M., Hegueli A.F., et al.// J. Biomed Mat. Res. 1978, -V.12, N 2, -
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2. Datsenko B.M., Belov S.G., Tamm G.I. Septic Wound. Kiev: Rufder, 1985. - 136p.
3. UV-irradiation and skin: effects, problems, solutions, collection of articles: publishing house "Cosmetics and Medicine", 2004, 391 p.
4. WO2010064054 (Al), priority date 20081205.
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Claims

Cosmetic for rapid skin regeneration
Cosmetic for rapid skin regeneration containing superoxide dismutase, vitamin of the B- group, succinic acid, characterized in that it additionally contains a water-soluble analogue of vitamin E, trolox, and L-arginine, the activity of superoxide dismutase is 200 000 - 300 000 U/mg, vitamin of the B-group is represented by dexpanthenol, the proportion of the components is as follows, weight%: superoxide dismutase 0.1% (0.01% - 32%), dexpanthenol 0.2% (0.1% - 20%), succinic acid 0.6% (0.5% - up to pH 6.0), trolox 0.23% (0.13% - 45%), L-arginine 1 % (0.9%) - 64%), water for injections, the cosmetic is applied on skin for elimination of defects using the cosmetic retaining material giving off the product to the skin during the period of exposition, the exposition period is 20 minutes (15-20 minutes).
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