RU2161974C1 - Treatment-and-prophylactic agent for skin care - Google Patents

Abstract

FIELD: pharmaceutical industry. SUBSTANCE: treatment-and-prophylactic agent contains biologically active substance and cosmetic base applicable for external use in the form of cream or emulsion, or gel. Biologically active substance is a complex of polypeptides with molecular mass 1000-10000 Da prepared from organs and tissues of animals in the amount of 0.1-2.0% from cosmetic base; or a complex of nucleoprotein complex with molecular mass 10000-90000 Da prepared from animals organs and tissues by extraction in the amount of 0.1-2.0% from cosmetic base; or oligopeptide prepared by method of peptide synthesis in solution in the amount of 0.001-0.01% from cosmetic base. EFFECT: broadened assortment of agents for skin care. 10 cl, 16 ex

Description

 The invention relates to the pharmaceutical industry and is intended for use as a therapeutic and prophylactic agent for skin care.

 As part of cosmetic preparations, various biologically active components are used that contribute to increasing skin turgor, smoothing small wrinkles, giving the skin freshness and velvety [1, 2, 3].

 Cosmetics containing substances isolated from various organs and tissues of mammals are widely used.

 Known cream [4], containing simple and complex lipids of animal origin, cocoa butter, glycerin, emulsifier, amino acids, mineral salts, vitamins, preservative and water.

 Known cosmetic preparations [5] containing polypeptides from collagen and elastin with a molecular weight of from 2000 to 20,000 Da.

 A cosmetic product is known [6], containing retinal extract as a biologically active substance and a cosmetic base suitable for external use in the form of a lotion, gel, cream or ointment. This tool is taken as the closest analogue for each of the three claimed therapeutic and prophylactic agents containing a biologically active substance and a fatty, or emulsion, or gel cosmetic base.

 A skin care product [7] is known that contains thymogen (synthetic peptide -Glu-Trp) from 4 to 8% of the total weight of the mixture and a cosmetic base - olive oil, calendula tincture, cocoa butter, lanolin, sea buckthorn oil and spermaceti.

 Known synthetic oligopeptide [8], which is used as a drug that stimulates reparative processes, including for local use, and which is a Lys-Glu dipeptide. The specified tool is taken as an analogue for products containing a synthetic oligopeptide as a biologically active substance.

 The problem to which the invention is directed is to expand the range of skin care products, as well as the range of biologically active components used in their preparation.

The essence of the invention lies in the fact that in a therapeutic and prophylactic skin care product containing a biologically active substance and a cosmetic base suitable for external use - fatty or emulsion, or gel, it is proposed to use a biologically active substance, which is:
a complex of polypeptides with a molecular weight of 1000-10000 Yes, obtained from animal organs and tissues by extraction of prepared raw materials with 3% acetic acid solution with the addition of zinc chloride and treatment of the supernatant with acetone [9];
according to the invention, the number of polypeptides with a molecular weight of 1000-10000 Yes (hereinafter cytomedins) is 0.1-2.0% of the cosmetic base;
or a nucleoprotein complex with a molecular weight of 10000-90000 Yes, obtained from animal organs and tissues by extraction of prepared animal raw materials using 1-2.5% sodium carbonate solution as an extractant at a pH of 10.4-10.8 for 2-4 hours with the addition of 0.1-0.5% magnesium chloride, followed by separation of the precipitate by filtration, acidification of the extract to pH 3.8-5.5, removal of ballast substances, washing the precipitate with an organic solvent and drying the precipitate at a temperature not exceeding 55 ^o C [10];
according to the invention, the number of nucleoprotein components with a molecular weight of 10,000-90000 Yes (hereinafter cytamines) is 0.1-2.0% of the cosmetic base;
or an oligopeptide obtained by the classical method of peptide synthesis in solution [11];
according to the invention, the amount of oligopeptide (hereinafter - cytogens) is 0.001-0.01% of the cosmetic base.

 The introduction of the inventive therapeutic and prophylactic cosmetic agent of a biologically active substance below the indicated values reduces the effectiveness of the agent, and excessive concentration is not advisable.

According to the invention, the fat-based therapeutic and prophylactic agent contains a biologically active substance - cytomedins or cytamines, or cytogens, paraffin, ceresin, beeswax, chamomile oil extracts, nettles, calendula, olive oil, perfume oil in the following ratio, wt.%:
Active substance 0.1-2.0% (cytomedins or cytamines) or 0.001-0.01% (cytogens)
Paraffin - 6-10
Ceresin - 5-10
Beeswax - 4-8
Plant oil extracts - 2-6
Olive Oil - 10-20
Perfume oil - Up to 100
According to the invention, the therapeutic and prophylactic agent on an emulsion basis with a high oil content contains a biologically active substance - cytomedins or cytamines, or cytogens, sorbitanoletate, lanolin alcohol, high molecular weight fatty alcohols, lanolin, beeswax, olive oil, perfume oil, glycerin in the following ratio components, wt.%:
Active substance 0.1-2.0% (cytomedins or cytamines) or 0.001-0.01% (cytogens)
Sorbitan Aletate - 2 - 5
Lanolin alcohol - 1 - 3
High Molecular Fatty Alcohols - 4 - 6
Lanolin - 5 - 7
Beeswax - 3 - 6
Olive Oil - 15 - 20
Perfume oil - 10 - 15
Glycerin - 2 - 4
Water - Up to 100
According to the invention, a therapeutic and prophylactic agent on an emulsion base with a high water content contains a biologically active substance - cytomedins or cytamines, or cytogens, stearin, fatty acid monoglycerides, high molecular weight fatty alcohols, lanolin, glycerol monostearate, olive oil, perfume oil, glycerol, triethanol , alcohol-water-glycerin extracts of calendula, chamomile, nettle, in the following ratio of components, wt.%:
Active substance 0.1-2.0% (cytomedins or cytamines) or 0.001-0.01% (cytogens)
Stearin - 2 - 4
Fatty Acid Monoglycerides - 3 - 5
High molecular weight fatty alcohols - 2-4
Lanolin - 3 - 4
Glycerol Monostearate - 1 - 3
Olive oil - 7 - 12
Perfume oil - 5 - 10
Glycerin - 2 - 3
Triethanolamine - 0.2 - 0.7
Alcohol-water-glycerin extracts of calendula, chamomile, nettle - 1 - 5
Water - Up to 100
According to the invention, the gel-based therapeutic and prophylactic agent contains a biologically active substance - cytomedins or cytamines, or cytogens, carbopol, hydroxyethyl cellulose, propylene glycol, triethanolamine, alcohol-water-glycerin extracts of calendula, chamomile, nettle, in the following ratio, wt.%:
Active substance 0.1-2.0% (cytomedins or cytamines) or 0.001-0.01% (cytogens)
Carbopol - 0.2 - 0.6
Hydroxyethyl cellulose - 0.1 - 1.0
Propylene glycol - 1 - 5
Triethanolamine - 0.1 - 0.6
Alcohol-water-glycerin extracts - 1 - 4
The process of preparing appropriate cosmetics based on the above components is traditional and does not have any fundamental features.

 The following are examples of obtaining therapeutic agents on a fat basis (examples 1-6), on an emulsion basis: emulsions with a high oil content (examples 7-10), emulsions with a high water content (examples 11-13), based on a gel ( examples 14-16).

Example 1
Fat-based therapeutic and prophylactic agent containing cytomedines as a biologically active substance
Recipe:
Biologically active substance - 0.1
Paraffin - 6 - 10
Ceresin - 5 - 10
Beeswax - 4 - 8
Oil extracts of chamomile, nettle, calendula - 2 - 6
Olive Oil - 10 - 20
Perfume oil - Up to 100
The tool is prepared as follows.

Biologically active substance is a complex of thymus peptides with a molecular weight of 6000 Da. To obtain this substance, the crushed animal thymus is treated with acetic acid at a pH of 2.5 - 4.0 for 24 to 36 hours at a temperature of 0 to 4 ^o C with the addition of 0.3 - 0.7 g / l of zinc chloride. The deposition of polypeptides is carried out in an amount of 8 to 12 volumes per 1 volume of extract at a temperature of from -2 to -8 ^o C for 10 to 16 hours. The precipitate was separated by filtration, dried, and then redissolved in distilled water, filtered and lyophilized.

The components indicated in the formulation are fed through dispensers to the reactor. In the reactor (at t = 70 ^° C), the components are melted by sequential application, starting with refractory waxes. The resulting mixture was cooled to room temperature. Then, with active stirring, the biologically active substance — cytomedins — a complex of thymus peptides with a molecular weight of 6000 Da is introduced into the cooled mixture. Then filter and pack.

Example 2
Fat-based therapeutic and prophylactic agent containing cytomedines as a biologically active substance
Recipe:
Biologically active substance - 0.5
Paraffin - 6 - 10
Ceresin - 5 - 10
Beeswax - 4 - 8
Oil extracts of chamomile, nettle, calendula - 2 - 6
Olive Oil - 10 - 20
Perfume oil - Up to 100
The tool is prepared as follows.

 The composition according to example 1, characterized in that as a biologically active substance using a complex of polypeptides with a molecular weight of 8000 Yes, isolated from the pineal gland of animals, in the amount of 0.5% of the cosmetic base. A complex of polypeptides is prepared in the same manner as described in example 1.

The components indicated in the formulation are fed through dispensers to the reactor. In the reactor (at t = 70 ^° C), the components are melted by sequential application, starting with refractory waxes. The resulting mixture was cooled to room temperature. Then, with active stirring, the biologically active substance — cytomedines — a complex of pineal gland peptides with a molecular weight of 8000 Da is added to the cooled mixture. Then filter and pack.

Example 3
Fat-based therapeutic and prophylactic agent containing cytomedines as a biologically active substance
Recipe:
Biologically active substance - 1.5
Paraffin - 6 - 10
Ceresin - 5 - 10
Beeswax - 4 - 8
Oil extracts of chamomile, nettle, calendula - 2 - 6
Olive Oil - 10 - 20
Perfume oil - Up to 100
The tool is prepared as follows.

 The composition according to example 1, characterized in that as a biologically active substance using a complex of polypeptides with a molecular weight of 9000 Yes, isolated from the prostate of animals, in the amount of 1.5% of the cosmetic base. A complex of polypeptides is prepared in the same manner as described in example 1.

The components indicated in the formulation are fed through dispensers to the reactor. In the reactor (at t = 70 ^° C), the components are melted by sequential application, starting with refractory waxes. The resulting mixture was cooled to room temperature. Then, with active stirring, the biologically active substance - cytomedines - a complex of prostate peptides with a molecular weight of 9000 Da - is introduced into the cooled mixture. Then filter and pack.

Example 4
Fat-based therapeutic and prophylactic agent containing cytamines as a biologically active substance
The composition according to example 1, characterized in that as a biologically active substance using a nucleoprotein complex isolated from cartilage of animals in the amount of 2.0% of the cosmetic base, obtained by extraction of the prepared raw materials using an extractant of 1-2.5% solution sodium carbonate at a pH of 10.4-10.8 for 2-4 hours with the addition of 0.1-0.5% magnesium chloride, followed by separation of the precipitate by filtration, acidification of the extract to a pH of 3.8-5.5, removal of ballast substances washing the precipitate with an organic solvent eating and drying the precipitate at a temperature not exceeding 55 ^o C.

 Next, the tool is prepared in the same manner as described in example 1.

Example 5
Fat-based therapeutic and prophylactic agent containing cytogens as a biologically active substance
The composition according to example 1, characterized in that cytogens are used as the biologically active substance, namely the Lys-Glu dipeptide in an amount of 0.001% of the cosmetic base.

 The synthesis of the dipeptide was carried out by the classical method in solution.

1.N ^α , N ^ε -dibenzyloxycarbonyllysyl-γ-benzyl-glutamic acid (1).

0.154 g (0.65 mmol) of γ-benzyl-glutamic acid is suspended in 3 ml of dimethylformamide, 0.091 ml (0.65 mmol) of triethylamine are added with stirring, then 0.300 g (0.59 mmol) of N - oxysuccinimide ester N ^α , N ^ε- dibenzyloxycarbonyllysyl. The reaction mixture was stirred for 12 hours at room temperature. After which the solvent was evaporated in vacuo at 40 ^° C., 10 ml of 1N was added to the residue. H ₂ SO ₄ and the product is extracted twice with ethyl acetate (30 x 2). The organic layer is washed with 1 N. H ₂ SO ₄ , water until neutral, dried over Na ₂ SO ₄ . The solvent is distilled off in vacuo at 40 ^o C, the residue is dissolved in 1 to 2 ml of ethyl acetate and the product is precipitated with hexane. Recrystallization in ethyl acetate / hexane. The product is filtered off and dried in vacuo over P ₂ O ₅ . Yield 0.330 g (88%). Rg = 0.81 (benzene: acetone 1: 1, silofol).

 2. L-lysyl - L-glutamic acid.

Protected dipeptide (1) 0.330 g is dissolved in 10 mg of methanol, 3 ml of water are added and hydrogenated over palladium on charcoal. TCX control. After hydrogenation, the catalyst is filtered off, the residue is dissolved in a minimum amount of water and precipitated with methanol. The product is filtered off, washed with ethanol, dried in vacuo over P ₂ O ₅ . Yield 0.110 g (85%).

 Next, the tool is prepared in the same manner as described in example 1.

Example 6
Fat-based therapeutic and prophylactic agent containing cytogens as a biologically active substance
The composition according to example 1, characterized in that cytogens are used as the biologically active substance, namely the tetrapeptide Glu - Asp - Ala - Gly in an amount of 0.001% of the cosmetic base.

The synthesis of tetrapeptide
1) BOC-Glu (OBzl) -Asp (OBzl) -OH (I), N-tert. butyloxycarbonyl- (γ-benzyl) glutamyl- (β-benzyl) aspartate.

N-tert-butyloxycarbonyl- (γ-benzyl) glutamic acid N-oxysuccinimide ester BOC-Glu (OBzl) -OSu 4.34 g (0.0100 mol) is dissolved in 20 ml of dimethylformamide, triethylamine 1.72 ml (0, 0125 mol) and β-benzyl aspartate 2.80 g (0.0125 mol). Stirred at room temperature for 24 hours. The product is planted 0.5 N. a solution of sulfuric acid (150 ml), extracted into ethyl acetate (3 x 30 ml), washed with 0.5 N. sulfuric acid solution (2 x 20 ml), water, 5% sodium bicarbonate solution (1 x 20 ml), water, 0.5 N. sulfuric acid solution (2 x 20 ml), water and dried over anhydrous sodium sulfate. Ethyl acetate was filtered, evaporated in vacuo at 40 ^o C, the residue was dried in vacuo over P ₂ O ₅ . An oil of 5.68 g (≈ 100%) is obtained. R _f = 0.42 (benzene-acetone 2: 1, PTCX-P-B-UV Sorbfil plates, CTX-1VE silica gel 8-12 μm, UV manifestation and chlorine / benzidine).

2) TFA ^. H-Glu (OBzl) -Asp (OBzl) -OH (II), trifluoroacetate (γ-benzyl) glutamyl - (β-benzyl) aspartate.

N-tert. butyloxycarbonyl - (γ-benzyl) glutamyl- (β-benzyl) aspartate (I) 5.68 g (≈0.01 mol) is dissolved in 20 ml of a mixture of dichloromethane-trifluoroacetic acid (3: 1). After 2 hours, the solvent was evaporated in vacuo at 40 ^° C., the evaporation was repeated with a new portion of dichloromethane (2 x 10 ml), and the residue was dried in vacuo over NaOH. An oil of 5.80 g (≈100%) is obtained. R _f = 0.63 (n-butanol-pyridine-acetic acid-water, 15: 10: 3: 12).

 3) Z-Ala-Glu (OBzl) -Asp (OBzl) -OH (III), N-carbobenzoxyalanyl - (γ-benzyl) glutamyl - (β-benzyl) aspartate.

Trifluoroacetate (γ-benzyl) glutamyl - (β-benzyl) vehicle (II) 5.65 g (0.01 mol) is dissolved in 10 ml of dimethylformamide, triethylamine 2.80 ml (0.02 mol) and N-oxysuccinimide ether are added N-carbobenzoxyalanine 4.14 g (0.013 mol). The mixture was stirred for 24 hours at room temperature. The product is planted 0.5 N. a solution of sulfuric acid (150 ml), extracted into ethyl acetate (3 x 30 ml), washed with 0.5 N. sulfuric acid solution (2 x 20 ml), water, 5% sodium bicarbonate solution (1 x 20 ml), water, 0.5 N. sulfuric acid solution (2 x 20 ml), water and dried over anhydrous sodium sulfate. Ethyl acetate was filtered, evaporated in vacuo at 40 ^o C, the residue was crystallized in ethyl acetate / hexane. The product is filtered off and dried in vacuo over P ₂ O ₅ . Yield 4.10 g (66%). T _mp = 154 ^° C. R _f = 0.48 (benzene-acetone, 1: 1), R _f = 0.72 (n-butanol-pyridine-acetic acid-water, 15: 10: 3: 12).

 4) Z-Ala-Glu (OBzl) -Asp (OBzl) -Gly-OBzl (III), N-carbobenzoxyalanyl- (γ-benzyl) glutamyl- (β-benzyl) aspartylglycine benzyl ester.

Tosoh ^. H-Gly-OBzl, glycine benzyl ester tosylate 1.01 g (3 mmol) is suspended in 15 ml of tetrahydrofuran and triethylamine 0.4 ml (3 mmol) is added with stirring, then after 5 min N-carbobenzoxyalanyl - (γ-benzyl) glutamyl - (β-benzyl) aspartate (III) 1.28 g (2 mmol), N-hydroxybenzotriazole 0.27 g (2 mmol) and cool the mixture to 0 ^° C. Then, solution N cooled to 0 ^° C is added. , N'-dicyclohexylcarbodiimide 0.42 g (2 mmol) in 5 ml of tetrahydrofuran, the mixture is stirred at this temperature for 2 hours and stirred at room temperature overnight. The dicyclohexylurea precipitate was filtered off, the solvent was evaporated in vacuo, the residue was dissolved in 30 ml of ethyl acetate, and the solution was washed with 1 N hydrochloric acid solution, water, 5% sodium bicarbonate solution, water, 1 N. hydrochloric acid solution, water and dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo and the product was crystallized in ethyl acetate / hexane. Yield 1.30 g (82%). T _mp = 146-148 ^o C. R _f = 0.75 (benzene-acetone, 2: 1).

 5) H-Ala-Glu-Asp-Gly-OH (IV), alanyl-glutamyl-aspartyl-glycine.

N-carbobenzoxyalanyl - (γ-benzyl) glutamyl - (β-benzyl) aspartylglycine (III) benzyl ester 1.25 g was hydrogenated in methanol-water-acetic acid (3: 1: 1) over a Pd / C catalyst. Monitoring the completeness of the release in TLC systems benzene-acetone (2: 1) and acetonitrile-acetic acid-water (5: 1: 3). At the end of the reaction, the catalyst was filtered off, the filtrate was evaporated in vacuo and the residue was crystallized in a water / methanol system. The product is dried in vacuo over KOH. Yield 520 mg (95%). R _f = 0.73 (acetonitrile-acetic acid-water, 5: 1: 3). For purification, 390 mg of the preparation was dissolved in 4 ml of 0.01% trifluoroacetic acid and subjected to high performance liquid chromatography on a 50 x 250 mm reverse phase column Diasorb-130-C16T, 7 mkm. Chromatograph Beckman System Gold, 126 Solvent Module, 168 Diode Array Detector Module. Chromatography conditions A: 0.1% TFA; B: 50% MeCN / 0.1% TFA, gradient B 0 ---> 5% in 80 min. Sample volume 5 ml, detection at 215 nm, scanning 190-600 nm, flow rate 10 ml / min. A fraction of 54.0-66.0 minutes was taken. The solvent was evaporated in vacuo at a temperature not exceeding 40 ^o C, evaporation was repeated (5 times) with 10 ml of 10% acetic acid solution. The residue was finally dissolved in 20 ml of deionized water and lyophilized. Received 290 mg of a purified preparation in the form of an odorless white amorphous powder.

The obtained peptide in the form of acetate is converted into the free form by treatment with IRA anion exchange resin or similar in (OH ^- ) form. Then, salts are obtained by the amino group, adding the equivalent of the corresponding acid (hydrochloric or oxalic). The resulting aqueous solution is lyophilized and analyzed as a finished product.

To obtain the corresponding salts of the carboxyl groups, the calculated amount of an aqueous hydroxide solution of the corresponding metal (NaOH, KOH, ZnOH ₂ , LiOH, CaOH ₂ , MgOH ₂ , NH ₄ OH) is added to the free tetrapeptide. To obtain a triethylammonium salt, the treatment is carried out in a similar manner using triethylamine as the base.

 6) Analysis of the finished product.

 The content of the main substance was determined by HPLC on a Supelco LC-18-DB column 4.6 x 250 mm, gard. LC-18-DB. A: 0.1% TFA; B: 50% MeCN / 0.1% TFA; grad. At 0 ---> 20% in 30 minutes. Flow rate 1 ml / min. Detection at 220 nm, scanning 190-600 nm, sample 20 μ1.

 The content of the main substance is 98.45%.

Amino acid analysis was performed on an AAA T-339 Prague analyzer. Hydrolysis in 6 N. HCl at 125 ^° C for 24 hours. Glu 1.02; Asp 1.00; Ala 1.01; Gly 1.00.

TLC: individual, R _f = 0.73 (acetonitrile-acetic acid-water, 5: 1: 3 plates of PTSX-P-B-UV Sorbfil, silica gel STX-1VE 8-12 μm, manifestation of chlorine / benzidine).

Moisture content: 5% (gravimetrically by weight loss during drying 20 mg at 100 ^o C).

 pH of a 0.001% solution: 4.37 (potentiometric).

Specific optical rotation: [α] $\genfrac{}{}{0ex}{}{\text{2}}{\text{D}}$ ² : -32 ^° (c = 1, H ₂ O), "Polamat A", Carl Zeiss Jena.

 Next, the tool is prepared in the same manner as described in example 1.

Example 7
A therapeutic and prophylactic agent based on an emulsion with a high oil content containing cytomedines as a biologically active substance
Recipe:
Biologically active substance - 2.0
Sorbitan Aletate - 2 - 5
Lanolin alcohol - 1 - 3
High Molecular Fatty Alcohols - 4 - 6
Lanolin - 5 - 7
Beeswax - 3 - 6
Olive Oil - 15 - 20
Perfume oil - 10 - 15
Glycerin - 2 - 4
Water - Up to 100
The tool is prepared as follows.

Biologically active substance (cytomedines) - a complex of thymus peptides in an amount of 2.0% of the cosmetic base, is obtained by the method described in example 1. The components are fed into the reactor through dispensers. Separately, the fat components are melted and the aqueous phase is separately prepared. The emulsification process is carried out with vigorous stirring, the aqueous phase is gradually added to the preheated (up to t = 70 ^° C) fat phase. The resulting emulsion is cooled to room temperature. Then, with stirring, the biologically active substance - cytomedines - is introduced. Then produce filtering and packaging.

Example 8
A therapeutic and prophylactic agent based on an emulsion with a high oil content containing cytamines as a biologically active substance
The composition according to example 7, characterized in that as a biologically active substance using cytamines is a nucleoprotein complex isolated from the pineal gland of young animals, in an amount of 0.1% of the cosmetic base.

 The specified nucleoprotein complex is obtained by the method described in example 4.

 Next, the tool is prepared in the same manner as described in example 7.

Example 9
A therapeutic and prophylactic agent based on an emulsion with a high oil content containing cytogens as a biologically active substance
The composition according to example 7, characterized in that as the biologically active substance used dipeptide Lys-Glu, in an amount of 0.01% of the cosmetic base.

 The Lys-Glu dipeptide is prepared by the method described in Example 5.

 Next, the tool is prepared in the same manner as described in example 7.

Example 10
A therapeutic and prophylactic agent based on an emulsion with a high oil content containing cytogens as a biologically active substance
The composition according to example 7, characterized in that as a biologically active substance use tetrapeptide Glu - Asp - Ala - Gly, in an amount of 0.01% of the cosmetic base.

 The Glu-Asp-Ala-Gly tetrapeptide is prepared by the method described in Example 6.

 Next, the tool is prepared in the same manner as described in example 7.

Example 11
A therapeutic and prophylactic agent based on an emulsion with a high water content containing cytomedines as a biologically active substance
Recipe:
Biologically active substance - 1.5
Stearin - 2 - 4
Fatty Acid Monoglycerides - 3 - 5
High Molecular Fatty Alcohols - 2 - 4
Lanolin - 3 - 4
Glycerol Monostearate - 1 - 3
Olive oil - 7 - 12
Perfume oil - 5 - 10
Glycerin - 2 - 3
Triethanolamine - 0.2 - 0.7
Alcohol-water-glycerin extracts of calendula, chamomile, nettle - 1 - 5
Water - Up to 100
The tool is prepared as follows.

 Biologically active substance is a complex of thymus peptides obtained by the method described in example 1.

The components are fed to the reactor through dispensers. Separately, the fat components are melted and the aqueous phase is separately prepared, introducing water-soluble components at t = 70 ^° C. The emulsification process is carried out with vigorous stirring, fatty components are gradually added to the aqueous phase. The resulting emulsion is cooled to room temperature.

 Then, with stirring, the biologically active substance - cytomedines - is introduced. Then produce filtering and packaging.

Example 12
A therapeutic and prophylactic agent based on an emulsion with a high water content, containing cytamines as a biologically active substance
The composition according to example 11, characterized in that as a biologically active substance using cytamines is a nucleoprotein complex isolated from the vessels of young animals, in an amount of 1.0% of the cosmetic base.

 The specified nucleoprotein complex is obtained by the method described in example 4. Next, the tool is prepared in the same manner as described in example 11.

Example 13
A therapeutic and prophylactic agent based on an emulsion with a high water content containing cytogens as a biologically active substance
The composition according to example 11, characterized in that as the biologically active substance used dipeptide Lys-Glu, in an amount of 0.001% of the cosmetic base. The Lys-Glu dipeptide is prepared by the method described in Example 5.

 Next, the tool is prepared in the same manner as described in example 11.

Example 14
A gel-based therapeutic and prophylactic agent containing cytomedines as a biologically active substance.

Recipe:
Biologically active substance - 0.5
Carbopol - 0.2 - 0.6
Hydroxyethyl cellulose - 0.1 - 1.0
Propylene glycol - 1 - 5
Triethanolamine - 0.1 - 0.6
Alcohol-water-glycerin extracts of calendula, chamomile, nettle - 1 - 4
Water - Up to 100
The tool is prepared as follows.

 A biologically active substance — a complex of thymus peptides, in an amount of 0.5% of the cosmetic base — is obtained by the method described in Example 1. The components are fed to the reactor through dispensers. The components are sequentially introduced into the reactor and mixed.

The gel-forming components are dispersed in water at 150 ^o C. After swelling and uniform distribution, i.e. the formation of a dispersion, the homogeneous mass is neutralized and cooled, with stirring, to room temperature. Then, with stirring, the biologically active substance, cytomedines, is introduced. Then filter and pack.

Example 15
Gel-based therapeutic and prophylactic agent containing cytamines as a biologically active substance
The composition according to example 14, characterized in that as a biologically active substance using cytamines is a nucleoprotein complex isolated from the vessels of young animals, in an amount of 0.5% of the cosmetic base.

 The specified nucleoprotein complex is obtained by the method described in example 4. Next, the tool is prepared in the same manner as described in example 14.

Example 16
Gel-based therapeutic and prophylactic agent containing cytogens as a biologically active substance
The composition according to example 14, characterized in that as a biologically active substance using the tetrapeptide Glu - Asp - Ala - Gly, in an amount of 0.01% of the cosmetic base. The Glu-Asp-Ala-Gly tetrapeptide is prepared by the method described in Example 6.

 Next, the tool is prepared in the same manner as described in example 14.

 As a result of experimental studies, it was found that the claimed tool does not cause toxic reactions, and also does not have allergenic, locally irritating and carcinogenic effects.

 The inventive tool increases the body's resistance to damaging effects. So, on the model of experimental linear and purulent cut-wounded wounds in rats with the external use of the agent obtained according to the recipe described in examples N 1 and N 5, acceleration of complete healing of the skin defect was observed. The activation of regeneration processes, the improvement of trophism and metabolic processes in the skin when using the product is also due to its stimulating effect on immunity indicators. External use of these agents helps to increase the number of lymphocytes, increase the functional activity of peripheral blood mononuclear cells and cellular indicators of local immunity compared to the control.

 The use of funds obtained according to the recipe described in example No. 4 enhances the elasticity of the skin and strengthens the contours of the face, prevents the destruction of the structure of the fibers of the skin of the face and neck, restores the skin surface and strengthens the elasticity of the skin.

 The use of the agent obtained according to the recipe described in examples N 5, 6 slows down the aging process, promotes accelerated regeneration of skin cells, has a pronounced anti-inflammatory effect, has a long soothing effect, helps to prevent skin irritation and maintains its protective properties.

 The use of funds obtained according to the recipe described in example No. 9 slows down the aging process, stimulates metabolic processes in the skin cells, restores the skin surface, eliminates the negative effects on the skin of external adverse factors, slows down the aging process.

 The use of funds obtained according to the recipe described in examples N 12, 15, provides enhanced nutrition of skin cells, stimulates and activates the activity of skin cells, accelerates their renewal, restores the natural skin barrier.

SOURCES OF INFORMATION
1. A.S. N 822824, 1979.

 2. A.c. N 822825, 1979.

 3. A.c. N 1335288, 1985.

 4. RF patent N 2013088, 1994.

 5. US Patent N 4,585.797, 1986.

 6. US patent N 4.670.257, 1987.

 7. RF patent N 2008894, 1994.

 8. RF patent N 2139085, 1999.

 9. Morozov V.G., Havinson B.X. Peptide bioregulators (25 years of experience in experimental and clinical studies). - St. Petersburg: Nauka, 1996 .-- 74 p.

 10. RF patent N 2075944, 1997.

 11. Yakubke H.-D., Escait X. Amino acids, peptides, proteins: Per. with him. - M.: Mir, 1985 .-- 456 p.

Claims (4)

 1. A therapeutic and prophylactic skin care product containing a biologically active substance and a cosmetic base suitable for external use, fatty, or emulsion, or gel, characterized in that it contains a complex of polypeptides obtained from animal organs and tissues as a biologically active substance with a pier. m. 1000 - 10000 Yes in an amount sufficient for the manifestation of its biological activity and constituting 0.1 - 2.0% of the cosmetic base.  2. A therapeutic and prophylactic skin care product containing a biologically active substance and a cosmetic base suitable for external use, fatty, or emulsion, or gel, characterized in that it contains a nucleoprotein complex derived from organs and tissues of animals as a biologically active substance with a pier. m. 10000 - 90,000 Yes in an amount sufficient for the manifestation of its biological activity and constituting 0.1 - 2.0% of the cosmetic base.  3. Therapeutic and prophylactic skin care product containing a biologically active substance and a cosmetic base suitable for external use, fatty, or emulsion, or gel, characterized in that as a biologically active substance contains a synthetic oligopeptide in an amount sufficient to manifest it biological activity and constituting 0.001 - 0.01% of the cosmetic base. 4. The tool according to claims 1 to 3 on a fat basis, characterized in that it contains paraffin, ceresin, beeswax, oil extracts of chamomile, nettle, calendula, olive oil, perfume oil in the following ratio, wt.%:
Paraffin - 6 - 10
Ceresin - 5 - 10
Beeswax - 4 - 8
Oil extracts of chamomile, nettle, calendula - 2 - 6
Olive Oil - 10 - 20
Perfume oil - Up to 100
5. The tool according to claims 1 to 3 on an emulsion basis with a high oil content, characterized in that it contains sorbitanletate, lanolin alcohol, high molecular weight fatty alcohols, lanolin, beeswax, olive oil, perfume oil, glycerin in the following ratio of components wt.% :
Sorbitan Aletate - 2-5
Lanolin alcohol - 1 - 3
High Molecular Fatty Alcohols - 4 - 6
Lanolin - 5 - 7
Beeswax - 3 - 6
Olive Oil - 15 -20
Perfume oil - 10 - 15
Glycerin - 2 - 4
Water - Up to 100
6. The tool according to paragraphs. 1 - 3 on an emulsion basis with a high water content, characterized in that it contains stearin, monoglycerides of fatty acids, high molecular weight fatty alcohols, lanolin, glycerol monostearate, olive oil, perfume oil, glycerin, triethanolamine, alcohol-water glycerin extracts of calendula, rum, the ratio of components, wt.%:
Stearin - 2 - 4
Fatty Acid Monoglycerides - 3 - 5
High Molecular Fatty Alcohols - 2 - 4
Lanolin - 3 - 4
Glycerol Monostearate - 1 - 3
Olive oil - 7 - 12
Perfume oil - 5 - 10
Glycerin - 2 - 3
Triethanolamine - 0.2 - 0.7
Alcohol-water-glycerin extracts of calendula, chamomile, nettle - 1 - 5
Water - Up to 100
7. The tool according to claims 1 to 3, on the basis of a gel, characterized in that it contains carbopol, hydroxyethyl cellulose, propylene glycol, triethanolamine, alcohol-water glycerin extracts of calendula, chamomile, and grapes in the following ratio, wt.%:
Carbopol - 0.2 - 0.6
Hydroxyethyl cellulose - 0.1 - 1.0
Propylene glycol - 1 - 5
Triethanolamine - 0.1 - 0.6
Alcohol-water-glycerin extracts of calendula, chamomile, kraviva - 1 - 4
Water - Up to 100