RU2707973C1 - Hydrogel material based on a chitosan-containing salt and a method for production thereof - Google Patents

Abstract

FIELD: medicine; biotechnology; pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, biotechnology, cosmetology and pharmaceutical industry, namely to production of therapeutic and preventive hydrogel material based on chitosan hydrochloride salt and/or chitosan, having antibacterial, anti-inflammatory and wound-healing action, which can be used for care and treatment of various types of wounds, ulcers, bedsores and burns, age and facial wrinkles, nutrition and moistening of the epidermis, for delivery of drugs and other biologically active compounds (locally, transdermally, through the mucosa), as well as in the field biotechnologies for producing matrices for growing cell cultures. Therapeutic hydrophile hydrogel material contains chitosan hydrochloride salt and/or chitosan, glycol or ascorbic or salicylic or azelaic and/or aminocapronic organic acids, a boron compound with polyvinyl alcohol, silicon polyolate, glycerin and water. Method comprises dissolving chitosan hydrochloride and/or chitosan in an aqueous solution of an organic acid, adding polyvinyl alcohol into the mixture, then adding silicon glycerolate in glycerol, adding sodium tetraborate in glycerine in molar ratio sodium tetraborate: glycerine 1:1.8–1:4.0, pouring into the mold of the obtained mixture and holding it until a film-like structure is obtained.

EFFECT: efficient, high-quality hydrogel material based on chitosan hydrochloride salt and/or chitosan, which can be used in form of a monolithic, elastic and highly complex (to surface with complex relief) glycerogyrogel plate, and having its own biological activity, antibacterial, anti-inflammatory and wound-healing action.

9 cl, 4 dwg, 1 tbl

Description

The group of inventions relates to the field of medicine, biotechnology, cosmetology and the pharmaceutical industry, namely, to obtain therapeutic and prophylactic hydrogel material based on a salt of chitosan and / or chitosan hydrochloride, which has an antibacterial, anti-inflammatory and wound healing effect, which can be used for the care and treatment of various types of wounds, ulcers, pressure sores and burns, age and expression lines, nutrition and hydration of the epidermis, for the delivery of drugs and other biologically active compounds inertia (locally, transdermally, through the mucous membrane), as well as in the field of biotechnology to obtain matrices for growing cell cultures.

M.V., Peresin M.S., et al. Cellulose. 2017. Vol. 24. No. 10. P. 4393-4403). Благодаря положительному заряду макроцепи при физиологическом значении рН хитозан проявляет высокие биоадгезивные свойства, обеспечивая целесообразность трансбуккального и интраназального путей введения для системной доставки активных фармацевтических ингредиентов (Киржанова Е.А., Хуторянский В.В., Балабушевич Н.Г. и др. Фармацевтич. технология и нанотехнологии. 2014. Т. 8. №3. С. 66-80). При этом, хитозан метаболизируется некоторыми ферментами человека, особенно лизоцимом, что позволяет рассматривать его как биорезорбируемый полимер (Muzzarelli R.A.A. Cell. Mol. Life Sci. 1997. Vol. 53. No. 2. P. 131-140).The presence of antimicrobial, anti-inflammatory and immunomodulating activity in the aminopolysaccharide of chitosan is associated with the presence of amino groups in its macromolecules whose protonation (-NH ³⁺ , pKa = 6.3) makes the polymer soluble in water (Schnell CN,

MV, Peresin MS, et al. Cellulose 2017. Vol. 24.No. 10. P. 4393-4403). Due to the positive charge of the macrochain at a physiological pH, chitosan exhibits high bioadhesive properties, providing the feasibility of the buccal and intranasal routes of administration for systemic delivery of active pharmaceutical ingredients (Kirzhanova E.A., Khutoryansky V.V., Balabushevich N.G. et al. Pharmaceutical. Technology and Nanotechnology. 2014. V. 8. No. 3. P. 66-80). At the same time, chitosan is metabolized by some human enzymes, especially lysozyme, which allows us to consider it as a bioresorbable polymer (Muzzarelli RAA Cell. Mol. Life Sci. 1997. Vol. 53. No. 2. P. 131-140).

The use of chitosan as a component of hydrogels stabilized by a network of covalent bonds or physico-chemical interactions (ionic, hydrogen, hydrophobic) is promising for the creation of medical, cosmetic, and pharmacological preparations. Covalent crosslinking of the structural units of chitosan macrochains with bifunctional reagents (glyoxal, glutaraldehyde, etc.) is accompanied by the formation of toxic aldol-croton condensation products, which limits the use of these systems for biomedical purposes (see RF patent No. 2099352, class IPC С08В 37 / 08, publ. 20.21.1997). To eliminate this drawback, dialdehyde derivatives of nucleotides and nucleosides are proposed as crosslinking reagents (see RF patent No. 2408618, class IPC C08L 5/08, A23P 1/08, C12N 11/04, A61K 9/50, A61L 15/28, A61L 27/50, publ. 01/10/2011). However, the biocompatibility of such hydrogels has not yet been proven. The best biocompatibility is exhibited by ion-crosslinked chitosan hydrogels, obtained by electrostatic interactions of protonated amino groups with low molecular weight anions, with oppositely charged polyelectrolytes and surfactants (Mocchiutti P., Schnell CN, Rossi GD Carbohydr. Polym. 2016. Vol. 98). However, ion-crosslinked chitosan hydrogels are kinetically unstable.

A relatively new direction in the creation of hybrid chitosan gels with a unique structure and a set of new useful properties is biomimetic sol-gel synthesis, which simulates the process of biomineralization in nature. At the same time, silicon polyolates are promising biologically active precursors (Shadrina E.V., Malinkina O.N., Khonina T.G., Shipovskaya A.B. et al. Izv. AN Ser. Chem. 2015. No. 7. S. 1633-1639).

Known tool based on silicon-chitosan-containing hydrogel, intended for the treatment of lichen planus of the oral mucosa and a method of treating lichen planus (see RF patent No. 2583945 according to IPC A61K 31/216, publ. 05/10/2016) containing a solution of silicon glycerolate in glycerol and an aqueous solution of chitosan with a degree of deacetylation of 82 mol. % and a molecular weight of 50-100 kDa, while furagin and anestezin are used as drug additives.

However, this tool can only be used in the form of a gel and does not imply the use in the form of plates for application to the outer surface of the skin or mucous membranes.

A known tool for the treatment of damage to the external tissues of the body (options) and a method for its preparation (see RF patent No. 2578969 according to class IPC A61L 15/28, published on 03/27/2016). The tool is made in the form of a multilayer film in which one of the layers contains a complex of chitosan with at least one carboxylic acid with a chain length of C ₂ -C ₇ , and the layer adjacent to the wound contains hyaluronic acid or its derivatives, and physiologically active substances are contained in micelles and are placed initially in a layer containing a chitosan complex for traumatic injuries, or in both layers. The tool is obtained by introducing micelles with physiologically active or auxiliary substances included in the solution of the selected polysaccharide, sequentially forming each individual layer from polysaccharide solutions containing micelles, and drying the layer to a moisture content of 10-35%, after which the films are removed from the substrate.

The disadvantage is the multi-stage and laboriousness of obtaining the multilayer film proposed in the method, the need for additional administration of physiologically active substances to impart the desired biological activity, as well as a large number of auxiliary ingredients (plasticizers, emulsifiers, taste regulators, colorants, preservatives, water-retaining agents). In this case, before the introduction of physiologically active substances are additionally transferred to the micellar phase. The inventive method provides for obtaining material only in air-dry film form.

Also known is biopolymer fiber, the composition of the molding solution to obtain it, the method of preparing the molding solution, a biomedical cloth, a method for its modification, a biological dressing and a method for treating wounds (see RF patent No. 2468129, class IPC D01F 4/00, publ. 11/27/2012). The composition contains chitosan, polyethylene oxide, organic acid and water, while chitosan is used with a molecular weight of 30-500 kDa, a degree of deacetylation of 80-95 mol. %, polyethylene oxide is used with a molecular weight of 2000-8000 kDa.

A method of preparing a molding solution involves dissolving chitosan and the corresponding polymer: polyethylene oxide or polyvinyl alcohol or polyvinylpyrrolidone or polyethylene oxide and cellulose diacetate, while before preparing the solution, these components are mixed in powder form, followed by their dissolution in an appropriate solvent on a magnetic stirrer until a homogeneous state for 2 -8 ocloc'k.

The biopolymer fiber contains chitosan as an organic acid salt and polyethylene oxide. A biomedical canvas is a non-woven fibrous-porous material formed from biopolymer fibers, characterized by an average fiber diameter from the range of 50-600 nm, a surface density from the range of 5-25 g / m ² , a tensile load under uniaxial tension of 0.61-33.6 N, relative elongation at break 6.0-16.4%, the degree of sorption of water vapor 55-110 wt. % and vapors of 0.5 N hydrochloric acid 450-1500 wt. %, the degree of sorption of physiological saline 600-800 wt. % and distilled water 450-650 wt. %

A method of modifying a web of biomedical use consists in swelling it in physiological saline and distilled water.

The biological dressing is a non-woven fibrous-porous fabric formed from biopolymer fibers of chitosan or a salt of chitosan and an organic acid.

However, this method provides for the production of air-dried biopolymer fibers by electrospinning, requiring expensive equipment. Obtaining a web of biomedical use and a biological dressing based on it in hydrogel form according to the method claimed in the invention is impossible.

Closest to the claimed group of inventions is a hydrogel based on a complex salt of chitosan and a method for its production (see RF patent No. 2617501 according to IPC C08J 3/075, publ. 04.25.2017). The method consists in dissolving a chitosan-containing substance in an aqueous solution of an organic acid and then introducing a gelling agent into the solution, using chitosan hydrochloride as a chitosan-containing substance, ascorbic or lactic acid as an organic acid, and silicon glycerolate in glycerol at a glycerol molar ratio as a gelling agent. silicon: glycerin 1: 2-1: 6, and the starting components are taken in quantities, wt. %:

chitosan hydrochloride 1.5-20.0 vitamin C 1.5-10.0 or lactic acid 0.5-2.0 silicon glycerolate in glycerin 10.0-60.0 water rest

The hydrogel contains ascorbate hydrochloride or chitosan hydrochloride lactate, in which 3.2-35 wt. % glycerol and 0.3-2.9 wt. % silicon.

However, this material can only be used as a gel. The formation according to the claimed in the invention method for producing hydrogel plates for application to the outer surface of the skin or mucous membranes is not possible.

The technical problem of the claimed group of inventions is the creation of an effective, high-quality hydrogel material based on a salt of chitosan and / or chitosan hydrochloride, made with the possibility of using a glycerohydrogel plate in a monolithic, elastic and highly competitive (to a surface with complex relief), and having its own biological activity, antibacterial , anti-inflammatory and wound healing effect.

The technical result is to obtain a monolithic, form-stable and flexible glycerohydrogel plate based on a salt of chitosan and / or chitosan hydrochloride by combining ion gelation with biomimetic sol-gel synthesis, i.e. without the use of catalysts, cross-linking agents of covalent type and the formation of by-products that adversely affect the components of the initial gelling mixture and the finished hydrogel material in the form of a glycerohydrogel plate, while maintaining the high biological activity of the finished material, its biocompatibility with human tissues, simplifying the process and reducing gelation time.

The technical problem of the group of inventions is achieved in that the therapeutic and prophylactic hydrogel material having antibacterial, anti-inflammatory and wound healing effects contains a salt of chitosan and / or chitosan hydrochloride, glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acids, a polyvinyl boron compound , silicon polyolate, glycerin and water in the following ratio, wt. %:

salt of chitosan and / or chitosan hydrochloride 2.77-4.81 glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acid 0.35-2.19 compound of boron with polyvinyl alcohol 1.71-1.74 silicon polyolate 4.9-11.3 glycerol 3.4-6.85 water rest

A method of obtaining a therapeutic and prophylactic hydrogel material consists in dissolving chitosan and / or chitosan hydrochloride in an aqueous solution of an organic acid, introducing an aqueous solution of polyvinyl alcohol into this mixture, then silicon glycerolate in glycerol, and then sodium tetraborate in glycerol is added at a molar ratio of sodium tetraborate: glycerol 1: 1.8-1: 4.0, after which the resulting mixture is poured into a mold and kept until a film-like structure is obtained, and the initial components are taken in the ratio, wt. %:

chitosan hydrochloride and / or chitosan 2.57-4.28 glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acid 0.9-3.54 silicon glycerolate in glycerin 8.3-16.7 polyvinyl alcohol 1.66 sodium tetraborate in glycerin 0.05-0.08 water rest

In the method, it is preferable to use silicon glycerolate in glycerol at a molar ratio of 1: 2-1: 3.

The mixture is kept in the form at a temperature of 50-80 ° C for 0.5-2 hours, or at a temperature of 20 ± 2 ° C for 1-3 days.

In the method, it is preferable to use chitosan hydrochloride and / or chitosan with a molecular weight of 30-700 kDa and a deacetylation degree of ≥75-80 mol. %, while using chitosan hydrochloride in an amount of 2.57-3.3 wt. %, or chitosan in the amount of 2.64-2.83 wt. %, or a mixture of chitosan hydrochloride with chitosan with a molar ratio of chitosan hydrochloride: chitosan 1: 0.35-1: 0.82 in an amount of 2.66-4.28 wt. %

Currently, in the patent and scientific literature unknown hydrogel material in the form of a biocompatible silicon-chitosan-containing glycerohydrogel plate containing the proposed combination of components within the certain claimed limits of their content, characterized by satisfactory strength, good elasticity and high congruence to the surface with complex relief, as well as its own biological activity, antibacterial, anti-inflammatory and wound healing effects.

It was experimentally established that as a result of the interaction of chitosan-containing substance, organic acid, silicon glycerolate, polyvinyl alcohol and sodium tetraborate (Na ₂ B ₄ O ₇ ) in a water-glycerol medium, a hydrogel material is formed in the form of a monolithic glycerohydrogel plate with satisfactory strength, good elasticity and high elasticity congruence to a surface with a complex relief. The product is stable in time, phase separation is absent.

The hydrogel material contains a compound of boron with polyvinyl alcohol (B-polyvinyl alcohol), which is formed due to the formation of intermolecular hydrogen as well as double and / or triple associates during the interaction of the hydroxyl groups of the polymer with borate ions in an aqueous glycerol medium, in an amount of 1.71-1.74 wt. . %

At the same time, the matrix of the glycerohydrogel plate is represented by interpenetrating polymer networks of organic (including with the participation of protonated amino groups of chitosan) and inorganic nature (covalent polysiloxane network of “Si-O-S≡ bonds) in an aqueous-glyceric medium.

The use of bioactive silicon glycerolates allows catalytic sol-gel synthesis of silicon polyolates under mild conditions without the formation of by-products during hydrolysis and condensation that adversely affect the components of the gel-forming mixture, the properties of the glycerohydrogel plate and human tissue.

The biologically inert polyvinyl alcohol acts as a template for the condensation of ≡Si-OH groups to disiloxane groups ≡Si-O-Si≡.

Glycerin in the composition of the glycerohydrogel plate acts as a plasticizer and a water-retaining component, prevents syneresis.

The group of inventions is illustrated by photographs and a table on which are presented:

in FIG. 1 - photo of a hydrogel material in the form of a plate based on a salt of chitosan hydrochloride and glycolic acid (Example No. 1);

in FIG. 2-3 - photo of a hydrogel material in the form of a plate based on a salt of chitosan and glycolic acid (Example No. 3);

in FIG. 4 is a photo of a hydrogel material in the form of a plate based on a salt of chitosan hydrochloride, a salt of chitosan and azelaic and aminocaproic acids (Example No. 9).

The table shows the content and mass composition of the starting components for obtaining a hydrogel material and the content of the components in the finished hydrogel material based on a salt of chitosan hydrochloride and / or a salt of chitosan with glycolic or ascorbic or salicylic or azelaic and / or aminocaproic acid (examples No. 1-9) .

A method of obtaining a hydrogel material is as follows.

Prepare an aqueous solution of chitosan and / or chitosan hydrochloride concentration of 3.0-7.0 wt. % in an aqueous solution of an organic acid concentration of 1.5-6.0 wt. % At the same time, chitosan hydrochloride and chitosan with a molecular weight of 30-700 kDa and a degree of deacetylation of ≥75-80 mol are used. %, glycolic or ascorbic or salicylic or azelaic and / or aminocaproic acids are used as organic acids.

An aqueous solution of a high molecular weight template, polyvinyl alcohol, with a concentration of 8.0-10.0 wt. %, then the gelling agent is silicon glycerolate in glycerol (Si (C ₃ H ₇ O ₃ ) ₄ ⋅ (2-3) C ₃ H ₈ O ₃ ) concentration of 55-70 wt. % for the flow of sol-gel synthesis and an ionic crosslinker - sodium tetraborate in glycerol (Na ₂ B ₄ O ₇ ) concentration of 10-20 wt. % The mixture of the starting components is carried out in a mixer equipped with a mechanical homogenizer, according to the recipe.

The resulting hydrogel material is poured into a special plastic or silicone mold (sterile, single-use form from an inert material with side sizes 50 × 50 × 5.0 mm, 50 × 70 × 5.0 mm, 70 × 70 × 5.0 mm, 70 × 100 × 5.0 mm or others .), placed in a heating cabinet with a temperature of 50-80 ° C and left under static conditions at 20 ± 2 ° C for gel formation for 0.5-3 hours to obtain a hydrogel material in the form of a silicon-chitosan-containing glycerohydrogel plate 50-70 × 50-100 mm in size or others and with a thickness of 2-7 mm, which is placed in a sealed package and stored at 25 ± 5 ° C clearly instructions. If necessary, the preparation of the plate can be carried out at room temperature (20 ± 20 ° C) for 1-3 days, and in the case of using aminocaproic acid - for 5-20 minutes. The choice of the temperature range of 50-80 ° C upon receipt of the hydrogel material is due to the most optimal gelation time. At temperatures below 50 ° C, gelation slows down and the time of formation of the hydrogel material becomes comparable with the time of its formation at a temperature of 20 ± 2 ° C. At temperatures above 80 ° C, along with the acceleration of the gelation process, thermal decomposition of the components and a decrease in the biological activity of the hydrogel material are possible.

The group of inventions is illustrated by examples No. 1-9.

Example No. 1. To prepare 100 g of hydrogel material in the form of a silicon-chitosan-containing glycerohydrogel plate, 1.43 ml of 70% glycolic acid, 62.5 g of distilled water, 3.3 g of chitosan hydrochloride powder are placed in a mixer and stirred continuously for 1-1.5 hours at 20 ± 2 ° С (normal temperature in indoors, there is no need to heat or cool) until a homogeneous solution is obtained. In parallel, a solution of polyvinyl alcohol is prepared. To do this, 14.4 g of distilled water is placed in a special container, 1.66 g of polyvinyl alcohol powder is added with stirring, placed in a microwave oven (at a power of ~ 850 W) for 1-2 minutes until the polymer is completely dissolved, poured into a mixer with a chitosan solution and homogenized within 5-10 minutes. The resulting system is filtered through a fabric filter, 16.7 g of silicon glycerolate is introduced in a two-molar excess of glycerol, after which 0.4 ml of 20% sodium tetraborate in glycerol is added and homogenized by mechanical stirring for 5 minutes.

The composition and content of the starting reagents to obtain a hydrogel material, wt. %:

glycolic acid - 1.00;

chitosan hydrochloride - 3.30;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerol - 0.08;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The resulting composition is poured into a special plastic or silicone mold (sterile, disposable form of an inert material with side sizes of 50 × 50 × 5.0 mm, 50 × 70 × 5.0 mm, 70 × 70 × 5.0 mm, 70 × 100 × 5.0 mm, etc. ), placed in a heating cabinet with a temperature of 50 ± 0.1 ° C, left under static conditions for gelation for no more than 2 hours until a silicon-chitosan-containing glycerohydrogel plate is obtained in the form of a gel-like film-like structure 50-70 × 50-100 mm in size or others and 2-7 thick mm, which is placed in a sealed package and stored at 25 ± 5 ° C according to and Instructions.

The composition and content of the components in the plate, wt. %:

salt of chitosan hydrochloride with glycolic acid - 3.47;

glycolic acid - 0.83;

compound of boron with polyvinyl alcohol - 1.74;

silicon polyolate - 11.3;

glycerin - 5.3;

water is the rest.

Example No. 2. All stages of obtaining a hydrogel material are similar to example 1, however, chitosan powder is additionally used. The difference also lies in the content of the components, gelation at a temperature of 80 ± 0.1 ° C. The gelation time to obtain a silicon-chitosan-containing glycerohydrogel plate is 0.5 hours. The composition and content of the starting reagents to obtain a hydrogel material, wt. %:

glycolic acid - 1.00;

chitosan hydrochloride - 1.66;

chitosan - 1.33;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerin - 0.06;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

a salt of chitosan and chitosan hydrochloride with glycolic acid - 3.39;

glycolic acid - 0.60;

compound of boron with polyvinyl alcohol - 1.72;

silicon polyolate - 11.3;

glycerin - 5.3;

water is the rest.

Example No. 3. All stages of obtaining a hydrogel material are similar to Example 1, however, chitosan powder is used instead of chitosan hydrochloride. The difference also lies in the content of the components. The composition and content of the starting reagents to obtain a hydrogel material, wt. %:

glycolic acid - 1.00;

chitosan - 2.64;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerin - 0.05;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan with glycolic acid - 3.31;

glycolic acid - 0.35;

a compound of boron with polyvinyl alcohol - 1.71;

silicon polyolate - 11.3;

glycerin - 5.3;

water is the rest.

Example No. 4. All stages of obtaining a hydrogel material are similar to Example 1, however, aminocaproic acid powder, silicon glycerolate in a three-molar excess of glycerol are used. The gelation process is carried out at room temperature (20 ± 2 ° C). The difference also lies in the content of the components. The composition and content of the starting components, wt. %:

aminocaproic acid - 1.30;

chitosan hydrochloride - 2.57;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerol - 0.07;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan hydrochloride with aminocaproic acid - 2.77;

aminocaproic acid - 1.1;

compound of boron with polyvinyl alcohol - 1.73;

silicon polyolate - 9.85;

glycerin - 6.85;

water is the rest.

Example No. 5. All stages of obtaining a hydrogel material are similar to Example 4, however, salicylic acid powder and optionally chitosan powder are used, the dissolution of the chitosan-containing substance is carried out at 60-80 ± 2 ° C for 0.5-1.0 hours. The difference also lies in the content of the components. The composition and content of the starting components, wt. %:

salicylic acid - 0.90;

chitosan hydrochloride - 1.66;

chitosan - 1.00;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerin - 0.05;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan and chitosan hydrochloride with salicylic acid - 4.64;

salicylic acid - 0.58;

a compound of boron with polyvinyl alcohol - 1.71;

silicon polyolate - 9.85;

glycerin - 6.85;

water is the rest.

Example No. 6. All stages of obtaining a hydrogel material are similar to Example 4, however, ascorbic acid powder is used; chitosan powder is used instead of chitosan hydrochloride. The difference also lies in the content of the components. The composition and content of the starting components, wt. %:

ascorbic acid - 2.83;

chitosan - 2.83;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerin - 0.05;

silicon glycerolate in glycerin - 8.30;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan with ascorbic acid - 3.51;

ascorbic acid - 2.15;

a compound of boron with polyvinyl alcohol - 1.71;

silicon polyolate - 4.90;

glycerin - 3.40;

water is the rest.

Example No. 7. All stages of obtaining hydrogel material are similar to example 6, however, chitosan hydrochloride powder is additionally used. The difference also lies in the content of the components. The composition and content of the starting components, wt. %:

ascorbic acid - 3.54;

chitosan hydrochloride - 2.62;

chitosan - 1.66;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerol - 0.08;

silicon glycerolate in glycerin - 8.30;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan and chitosan hydrochloride with ascorbic acid - 4.81;

ascorbic acid - 2.19;

compound of boron with polyvinyl alcohol - 1.74;

silicon polyolate - 4.90;

glycerin - 3.40;

water is the rest.

Example No. 8. All stages of obtaining a hydrogel material are similar to Example 5, however, azelaic and aminocaproic acid powder is used. The difference also lies in the content of the components.

The composition and content of the starting components, wt. %:

azelaic acid - 0.90;

aminocaproic acid - 1.00;

chitosan hydrochloride - 2.00;

chitosan - 1.00;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerin - 0.05;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan and chitosan hydrochloride with azelaic and aminocaproic acids - 3.72;

azelaic and aminocaproic acids - 1.18;

a compound of boron with polyvinyl alcohol - 1.71;

silicon polyolate - 9.85;

glycerin - 6.85;

water is the rest.

Example No. 9 All stages of obtaining a hydrogel material are similar to Example 8, the difference lies in the content of the components. The composition and content of the starting components, wt. %:

azelaic acid - 0.90;

aminocaproic acid - 1.00;

chitosan hydrochloride - 2.00;

chitosan - 1.00;

polyvinyl alcohol - 1.66;

sodium tetraborate in glycerol - 0.08;

silicon glycerolate in glycerol - 16.7;

water is the rest.

The composition and content of the components in the plate, wt. %:

salt of chitosan and chitosan hydrochloride with azelaic and aminocaproic acids - 3.72;

azelaic and aminocaproic acids - 1.18;

compound of boron with polyvinyl alcohol - 1.74;

silicon polyolate - 9.85;

glycerin - 6.85;

water is the rest.

It was experimentally established that when using the ratio of components in the hydrogel material taken in greater or lesser amounts of the intervals stated in examples No. 1-9, the technical result of the group of inventions is not achieved. With a lower content of components, a hydrogel material in the form of a monolithic and form-stable glycerohydrogel plate is not formed, with a larger content, the elasticity of the hydrogel material is reduced, and there is a syneresis.

It was determined that when the content of sodium tetraborate in the system is in the range of 0.05-0.08 wt. % optimal conditions are observed for the formation of a network of the intermolecular compound of polyvinyl alcohol with borate ions (B-polyvinyl alcohol). The introduction of sodium tetraborate in an amount of less than 0.05 wt. % does not affect the process of formation and properties of the glycerohydrogel plate, and more than 0.08 wt. % complicates the mixing of the components of the gelling composition.

Assessed the biocompatibility and cytotoxicity of the initial composition used to obtain hydrogel material according to examples No. 1, 4, 7.

Each test composition was prepared using sterile bidistilled water (pH 6.8–7.0), followed by dilution with DMEM sterile nutrient medium to a concentration of 0.1 wt. % The resulting solutions at a dilution of 1: 10-1: 14 were placed in a sterile Petri dish, filled with DMEM growth medium supplemented with 10% cattle fetal serum, and a suspension of dermal fibroblast cells at a concentration of at least 10 ⁶ cells / ml was added. Cultivation was carried out in a CO ₂ incubator in an atmosphere of 5% CO ₂ at 37 ° C. Cell viability was assessed using a MikMed-2 fluorescence microscope (Russia); staining was performed with acridine orange and ethidium bromide. Cell adhesion and proliferation were monitored using a Biolam biological microscope (JSC LOMO, St. Petersburg, RF).

In all experiments, the formation of a complete monolayer of cells was observed within 3 to 5 days. This indicates the absence of cytotoxicity and high biocompatibility of the initial composition of the silicon-chitosan-containing gel-forming composition with dermal cells, which allows us to give positive recommendations for the use of hydrogel material in the form of silicon-chitosan-containing glycerohydrogel plates in medicine, pharmacology, cosmetology, and other fields.

Claims (11)

1. Treatment and prophylactic hydrogel material with antibacterial, anti-inflammatory and wound healing effects, characterized in that it contains a salt of chitosan and / or chitosan hydrochloride, glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acids, a polyvinyl boron compound, polyvinyl boron compound silicon polyolate, glycerin and water in the following ratio, wt. %: salt of chitosan and / or chitosan hydrochloride 2.77-4.81 glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acid 0.35-2.19 compound of boron with polyvinyl alcohol 1.71-1.74 silicon polyolate 4.9-11.3 glycerol 3.4-6.85 water rest 2. A method of obtaining a therapeutic and prophylactic hydrogel material according to claim 1, which consists in dissolving chitosan and / or chitosan hydrochloride in an aqueous solution of an organic acid, introducing silicon glycerolate in glycerol into this mixture, characterized in that before introducing silicon glycerolate in glycerol into the mixture an aqueous solution of polyvinyl alcohol is added to chitosan hydrochloride and / or chitosan with an organic acid, and after the introduction of silicon glycerolate in glycerol, sodium tetraborate in glycerol is added at a molar ratio of tetra sodium borate, glycerin 1: 1.8-1: 4.0, and the resulting mixture was poured into a mold and allowed to stand to obtain a film-structure, wherein the starting components are taken in the ratio, by weight. %: chitosan hydrochloride and / or chitosan 2.57-4.28 glycolic or ascorbic or salicylic or azelaic and / or aminocaproic organic acid 0.9-3.54 silicon glycerolate in glycerin 8.3-16.7 polyvinyl alcohol 1.66 sodium tetraborate in glycerin 0.05-0.08 water rest 3. The method according to p. 2, characterized in that they use a solution of silicon glycerolate in glycerol with a molar ratio of 1: 2-1: 3. 4. The method according to p. 2, characterized in that the mixture is kept in shape at a temperature of 50-80 ° C for 0.5-2 hours. 5. The method according to p. 2, characterized in that the mixture is kept in shape at a temperature of 20 ± 2 ° C for 1-3 days. 6. The method according to p. 2, characterized in that the use of chitosan hydrochloride and / or chitosan with a molecular weight of 30-700 kDa and a degree of deacetylation of ≥75-80 mol. % 7. The method according to p. 2, characterized in that the use of chitosan hydrochloride in an amount of 2.57-3.3 wt. % 8. The method according to p. 2, characterized in that chitosan is used in an amount of 2.64-2.83 wt. % 9. The method according to p. 2, characterized in that a mixture of chitosan hydrochloride with chitosan is used with a molar ratio of chitosan hydrochloride: chitosan 1: 0.35-1: 0.82 in an amount of 2.66-4.28 wt. %

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