RU2708250C1 - Method of producing chemical peeling gel - Google Patents

Abstract

FIELD: physiotherapy; cosmetology.

SUBSTANCE: invention relates to a method for producing a gel for chemical peeling, which involves dissolving an acidic exfoliating agent in an organic polar solvent, adding a polymer gelling agent and mixing, after which adding to the obtained base additives – preserving agents, moisturizers, analgesics and antimicrobial agents and mixing, wherein the organic polar solvent used is an organic non-volatile polar solvent which does not react with the acidic exfoliating agent, with polarizability expressed through the camphor-taffeta solvatochromic parameter π*, higher than 0.6, the polymer gelling agent is a polymer containing amine and/or amide groups, and after mixing said polymer reacts with an acidic exfoliating agent to form a salt which is soluble in said solvent.

EFFECT: reduced risk of skin damage without the need for neutralization, preservation of activity when applied on skin for a long time.

4 cl, 1 tbl, 13 ex

Description

The invention relates to the medical and chemical-pharmaceutical industry and can be used in medical institutions and at home for cosmetic procedures with the aim of deep exfoliation of the surface layers of the skin (peeling) for its rejuvenation, whitening, smoothing and combating inflammatory diseases, keratosis , melasma, alopecia, facial and age wrinkles and other skin problems.

To restore the youthfulness of the skin, rid it of scars, scars, wrinkles, age spots, and also to treat inflammatory diseases such as acne and rosacea, a peeling procedure is used to remove the upper layers of the skin. With chemical peeling, exfoliation of the skin is achieved by exposure to chemical reagents.

For chemical peeling, three groups of compounds (exfoliating agents) are used, which differ in the predominant principle of action on cells. The first group of compounds affects the metabolism of cells by reducing the content of sulfate and phosphate groups on the surface of corneocytes, which reduces their cohesion and provokes exfoliation of the epidermis. Such compounds include alpha-hydroxy acids (glycolic, lactic, citric, malic, tartaric, almond), alpha-keto acids (pyruvic), dicarboxylic acids (azelaic), beta-hydroxy acids (salicylic) and retinoic acid. As a rule, they are used as solutions in ethanol or water, and the concentration can vary over a wide range (10-70% for all compounds except retinoic acid, which is usually used in the form of 0.025-0.1% systems); in the case of a high concentration of glycolic (over 50%) or salicylic (over 40%) acids, their effect on cells ceases to be predominantly metabolic. The second group of compounds creates a low pH, destroying cells. For this purpose, solutions of dichloro or trichloroacetic acid, a concentrated solution of glycolic acid, are usually used; moreover, the higher the acid concentration, the lower the pH level and the more aggressive the effect of the reagent. The third group of exfoliating agents exerts a predominantly toxic effect, which consists in the inactivation of enzymes and protein denaturation, as well as a change in the permeability of cell membranes, which provokes cell death. The third group includes phenol, resorcinol and, to a lesser extent, salicylic acid, used in the form of aqueous or alcoholic solutions. In some cases, the compounds are combined in one solution to combine different mechanisms of action; for example, Jessner's solution is widely applicable (14% salicylic acid, 14% lactic acid, 14% resorcinol, 58% ethanol).

The peeling procedure consists in applying to the skin surface low-viscosity solutions of exfoliating agents with a cotton swab, one- or, to achieve a deeper peeling, repeatedly. The end of the procedure or the need for its termination is judged by a change in the skin - its redness or whitening, depending on the exfoliating agent used.

The disadvantage of the described procedure is the impossibility of uniformly applying a low-viscosity solution to the skin surface, especially in the case of facial peeling, due to dripping of the applied solution, and, as a result, uneven penetration of exfoliating agents into the skin, which can lead to injuries and scars if achieved hypodermis agent. To prevent the peeling composition from draining and to facilitate its application to the skin, it should be used in the form of a gel.

A known method of producing salicylic acid gel (see, application US 20170354734 A1, class IPC A61K 31/60, A61K 47/18, A61K 8/04, A61K 8/368, A61K 8/41, A61K 8/42, A61K 9 / 00, A61K 9/06, A61Q 19/00, A61Q 5/00, A61Q 5/02, publ. 12/14/2017) containing from 1 to 55% salicylic acid, the stabilizer is a nitrogen-containing compound selected from a number of alkyloxylated amides, alkyloxylated amines, alkyl substituted amino acids, alkyl amido amides, amides, N-oxides, amines and betaines, and the solvent is water, ethanol or isopropanol. A gel is prepared by mixing salicylic acid with a stabilizer by dissolving salicylic acid in a stabilizer and then diluting the concentrated gel with a solvent.

The disadvantage of this invention is the use as stabilizers of low molecular weight compounds containing amine or amide groups and are characterized for this reason by irritating or toxic effects. Another disadvantage of this solution is the use of volatile solvents (water, ethanol, isopropanol), which leads to their intense evaporation from the gel after applying it to the skin. This leads to the transition of the exfoliating agent (salicylic acid) from the dissolved state to the crystalline one, which is not effective for affecting skin cells and does not penetrate into them.

The closest to the proposed essential features and the achieved result is a method of obtaining a composition for treating the skin surface, which can be used as a gel for chemical peeling (see patent RU 2599027, class IPC A61K 8/36, A61K 9/06, A61P 17/00, publ. 10.10.2016), including the dissolution of trichloroacetic acid or its mixture with salicylic acid in a solvent and mixing with a thickening polymer, which is a gelling agent, in a ratio of components, wt.%:

trichloroacetic acid or its mixture with salicylic acid - 1-50% or more, thickener polymer - 0.5-3% or more, solvent - the rest.

The thickener polymer is selected from cross-linked polymers of acrylic acid, or mixtures thereof with another thickener selected from polysaccharide thickeners and polysiloxanes, natural rubber, glycerin, petrolatum, paraffin, lanolin, beeswax, rosin, xanthan gum, amylose, amylose, amylose, cellulose , carboxymethyl cellulose or its salts, ethyl cellulose, glycerol, hydroxypropyl cellulose and methyl cellulose, or mixtures thereof. It is a gelling agent. The solvent used is water or a volatile organic solvent — methanol, ethanol, propanol, methyl ethyl ketone, acetone, ethyl acetate, or a mixture thereof.

The disadvantage of the prototype is the use of a volatile solvent. For greater efficiency, the gel is left for several hours, and during this time the solvent evaporates, which, as mentioned above, reduces the ability of the gel to penetrate the skin. In addition, when mixing a polymer such as polysaccharide, crosslinked polyacrylic acid, polysiloxane, cellulose and its derivatives with trichloroacetic or salicylic acid using a volatile solvent, these acids will not be in a chemically bound state, which leads to an increase in gel aggressiveness: it causes skin irritation, burning and may require neutralization.

The objective of the invention is to obtain gels for peeling that do not require the procedure of neutralizing the exfoliating agent after use while reducing the risk of skin damage and retaining activity when applied to the skin for a long time.

The problem is solved in that in a method for producing a chemical peeling gel, comprising dissolving an acid exfoliating agent in an organic polar solvent, adding a polymer gelling agent and mixing, an organic non-volatile polar solvent that does not react with an acid exfoliating agent with polarizability is used as an organic polar solvent expressed through the solvatochromic parameter of Kamlet-Taft π *, above 0.6, as a polymer gelling agent is a polymer containing conductive amine and / or amide groups, and then mixing said polymer is reacted with an acid exfoliating agent to form a salt which is soluble in said solvent, with the following component ratio,% wt .:

acid exfoliating agent - 5-75, the specified polymer gel - 1-40, specified solvent - the rest.

When dissolving an acid exfoliating agent, resorcinol can additionally be introduced in the following ratio of components,% wt .:

acid exfoliating agent - 5-60, the specified polymer gel - 1-40, resorcinol - 1-50, specified solvent - the rest.

When dissolving an acid exfoliating agent, hydroquinone can also be additionally introduced in the following ratio, wt.%:

acid exfoliating agent - 5-60, the specified polymer gel - 1-40, hydroquinone - 1-10, specified solvent - the rest.

When dissolving an acid exfoliating agent, a hyaluronic acid salt can also be additionally introduced in the following ratio of components,% wt .:

acid exfoliating agent - 5-60, the specified polymer gel - 1-40, hyaluronic acid salt - 0.5-5, specified solvent - the rest.

It is important that the organic polar solvent does not react chemically with an acid exfoliating agent - for example, if trichloroacetic acid is used as an acid exfoliating agent and dimethyl sulfoxide is used as a solvent, a chemical reaction will take place between these compounds, which will lead to the formation of carbon dioxide, chloroform and dimethyl sulfide.

If necessary, flavorings, pigments, dyes, preservatives, moisturizers, analgesics and anesthetics, antimicrobial, cosmetic and healing agents are added to the peeling gel. After that, the resulting gel is applied to the skin.

According to the invention, polymers (or copolymers thereof, or mixtures of (co) polymers) such as polyvinylamine, polyvinylpyridine, polyvinylcaprolactam, polyhexamethylene guanidine, polydiallyl dimethylamine, chitosylprolidonovinyl polyvinylidene can be used as a polymer gelling agent containing amine and / or amide groups. polyethyleneimine, polyallylamine, polydimethylaminoethyl methacrylate, polyvinyl acetamide and others. The non-volatile polar solvent may be dimethyl sulfoxide (π * = 1.0), triethyl citrate (0.69), triacetin (0.63), triethanolamine (0.95), propylene glycol (0.76), polyethylene glycol (0.91), diethylene glycol monoethyl ether (0.66) and other solvents mixtures thereof.

Glycolic acid, citric acid, glucuronic acid, alpha-hydroxybutanoic acid, lactic acid, malic acid, mandelic acid, mucus acid, pyruvic acid, galacturonic acid, glutamic acid, kojic acid, azelaic acid, ascorbic acid can act as an acid exfoliating agent. retinoic acid, ferulic acid, beta-phenyl lactic acid, aminosulfonic acid, beta-phenylpyruvic acid, beta-hydroxybutanoic acid, sugar acid, tartaric acid, tartronic acid, dichloroacetic acid, trichloroacetic acid, salicylic acid, or mixtures thereof.

The technical result that can be obtained from the use of the present invention is to minimize the risk of skin damage without the introduction of a neutralizing agent and maintaining the gel stability properties (viscosity, concentration of exfoliating agent) during use.

The following examples illustrate the proposed technical solution.

Examples of carrying out the invention

Peeling gel can be prepared with a different concentration of exfoliating agent, for example, salicylic acid, which allows, as the concentration of exfoliating agent increases, to obtain gels with increasing aggressiveness on the tissue: this, on the one hand, leads to greater effectiveness of gels for exfoliating the skin surface, but on the other, to higher pain during the peeling procedure and a longer recovery period of the skin (Examples 1-4). To obtain a gel, both a copolymer (Examples 1-3) and a homopolymer (Example 4), as one non-volatile polar solvent (Examples 1 and 2), and their mixture (Examples 3 and 4) can be used; this does not affect noticeably the ability of the gel to exfoliate the skin. A change in composition affects the viscosity of the gel: the lower it is, the easier it is to apply the gel to the skin by spreading it on its surface, but the faster the gel can drain under the influence of gravity. The optimal range of gel viscosity is from 5 to 500 Pa 500s. To obtain higher viscosity systems, di- and tricarboxylic acids should be used, for example, malic (Example 5), citric (Example 6) or tartaric acid (Example 7). Such gels are inconvenient to smear on the skin, but can be applied to it in the form of preformed rollers or plates. As exfoliating agents, you can use compounds with different preferential mechanisms of action on the skin: toxic (Examples 2, 3, and 4), metabolic (Examples 1, 5-7) or acid (Examples 8-11), as well as combined (Example 12 ) Additional components can be introduced into the gel, such as resorcinol to enhance skin exfoliation (Example 12), hydroquinone to improve skin whitening (Example 8), and hyaluronic acid or its salt to moisturize the skin and accelerate its regeneration (Example 13).

The properties of the gel during use remain stable.

Example 1

To obtain a peeling gel, 35 g of a random copolymer of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate are mixed (molar ratio of units 2: 1: 1, respectively), 30 g of dimethyl sulfoxide (π * = 1.0) and 35 g of salicylic acid at 100 ° C for 15 min using a mechanical mixing device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for surface peeling. As a result of applying the gel for 30 minutes to peel the skin of the face, it causes its redness, accompanied by tingling. Upon contact with water, the gel forms an insoluble film, rolling it into lumps allows deep cleaning of the pores. After a few hours, the redness disappears, on the third or fourth day after application, moderate exfoliation of the skin surface occurs.

The properties of the gel during use remain stable.

Example 2

To obtain a peeling gel, 30 g of a random copolymer of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate (molar ratio of units 2: 1: 1, respectively) are mixed, 20 g of dimethyl sulfoxide (π * = 1.0) and 50 g of salicylic acid at 100 ° C for 15 minutes using a mechanical mixing device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling. As a result of applying the gel for 30 minutes to peel the skin of the face, it causes its redness, accompanied by heat for the first 15 minutes. Upon contact with water, the gel forms an insoluble film, rolling it into lumps allows deep cleaning of the pores. The next day, reddening of the skin mainly disappears, on the second day, it partially coarsens, on the third or fourth day after application, exfoliation of the skin surface occurs.

The properties of the gel during use remain stable.

Example 3

To obtain a peeling gel, 20 g of a random copolymer of dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate are mixed (molar ratio of units 2: 1: 1, respectively), 10 g of dimethyl sulfoxide (π * = 1.0), 15 g of triethanolamine (π * = 0.95) and 55 g salicylic acid at 100 ° C for 15 min using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling. As a result of applying the gel for 30 minutes to peel the skin of the face, it causes severe redness, accompanied by pain during the first 10 minutes. Upon contact with water, the gel forms an insoluble film, rolling it into lumps allows deep cleaning of the pores. The next day, redness of the skin with weak pain when touched is maintained. On the second day after application, there is a significant coarsening of the skin with the termination of its redness, on the third or fourth day after application, exfoliation of the skin surface occurs.

The properties of the gel during use remain stable.

Example 4

To obtain a peeling gel, 20 g of polyvinylpyrrolidone, 20 g of dimethyl sulfoxide (π * = 1.0) and 60 g of salicylic acid are mixed at 100 ° C for 15 min using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling. As a result of applying the gel for 30 minutes to peel the skin of the face, it causes severe redness, accompanied by significant pain, subsiding after the first 15 minutes. The next day, the skin has a dark red (brick) tint and weak pain when touched. On the second day, the color of the skin is preserved and its substantial coarsening occurs; on the third or fifth day after application, exfoliation of the skin surface occurs. Damage to the hypodermis of the skin does not occur.

The properties of the gel during use remain stable.

Example 5

The peeling gel is prepared analogously to the method described in example 1, but malic acid is used instead of salicylic acid.

The properties of the gel during use remain stable.

Example 6

The peeling gel is prepared in a similar manner to that described in Example 1, but citric acid is used instead of salicylic acid.

The properties of the gel during use remain stable.

Example 7

The peeling gel is prepared analogously to the method described in Example 1, but tartaric acid is used instead of salicylic acid, and polyvinylpyrrolidone is used instead of dimethylaminoethyl methacrylate copolymer.

The properties of the gel during use remain stable.

Example 8

To obtain a peeling gel, 25 g of polyvinylpyrrolidone, 25 g of dimethyl sulfoxide (π * = 1.0), 48 g of glycolic acid and 2 g of hydroquinone are mixed at 100 ° C for 15 minutes using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling.

The properties of the gel during use remain stable.

Example 9

To obtain a peeling gel, 20 g of polyvinylpyrrolidone, 15 g of dimethyl sulfoxide (π * = 1.0), 5 g of triethanolamine (π * = 0.95) and 60 g of glycolic acid are mixed at 100 ° C for 15 min using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling.

The properties of the gel during use remain stable.

Example 10

To obtain a peeling gel, 15 g of polyvinylpyrrolidone, 35 g of triacetin (π * = 0.63) and 50 g of trichloroacetic acid are mixed at 100 ° C for 15 min using a mechanical mixing device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for mid peeling.

The properties of the gel during use remain stable.

Example 11

To obtain a peeling gel, 10 g of polyvinylpyrrolidone, 20 g of triethyl citrate (π * = 0.69) and 70 g of trichloroacetic acid are mixed at 100 ° C for 15 min using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for deep peeling.

The properties of the gel during use remain stable.

Example 12

To obtain a peeling gel, 25 g of polyvinylpyrrolidone, 30 g of dimethyl sulfoxide (π * = 1.0), 15 g of glycolic acid, 15 g of salicylic acid and 15 g of resorcinol at 100 ° C are mixed for 15 minutes using a mechanical stirring device. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for peeling.

The properties of the gel during use remain stable.

Example 13

To obtain a peeling gel, 1 g of sodium hyaluronate, 15 g of polyvinylpyrrolidone, 46 g of propylene glycol (π * = 0.76), 28 g of dimethyl sulfoxide (π * = 1.0), 5 g of triethanolamine (π * = 0.95), 0.1 g of retinoic acid are mixed and 4.9 g of glycolic acid at 100 ° C. for 15 minutes using a mechanical stirrer. The required additives are added to the obtained base - preservatives, moisturizers, analgesics, antimicrobial agents - and mixed. After that, the finished gel can be applied to the skin for easy surface peeling of the dead cells of the stratum corneum of the epidermis to facilitate saturation of the skin with hyaluronic acid, which is part of the gel in the form of sodium salt.

The properties of the gel during use remain stable.

Claims (4)

1. A method of producing a gel for chemical peeling, including dissolving an acid exfoliating agent in an organic polar solvent, adding a polymer gelling agent and mixing, then adding additives - preservatives, moisturizers, analgesics and antimicrobials to the resulting base and mixing, characterized in that as organic polar solvent use an organic non-volatile polar solvent that does not react with an acid exfoliating agent, with a polarizability expressed as the solvatochromic parameter of Kamlet-Taft π *, above 0.6, as a polymer gellant is a polymer containing amine and / or amide groups, and after mixing, this polymer reacts with an acid exfoliating agent to form a salt soluble in the specified solvent. 2. The method according to p. 1, characterized in that when dissolving the acid exfoliating agent, resorcinol is additionally administered. 3. The method according to p. 1, characterized in that when dissolving the acid exfoliating agent, hydroquinone is additionally administered. 4. The method according to p. 1, characterized in that when dissolving the acid exfoliating agent, an additional salt of hyaluronic acid is added.