RU2535141C1 - Gel composition of wide spectrum of biological action - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and represents a gel biologically active composition for topical application containing chitosan hydrochloride in an amount of 10-20 wt %, an organic acid in an amount of 1-10 wt %, distilled water - the rest. The above organic acid is specified in acetic, ascorbic, glycolic, lactic, citric or succinic acids.

EFFECT: providing a lower toxicity and a wider spectrum of biological action of the composition ensured by the synergetic effect of a reaction of chitosan hydrochloride and the organic acid.

11 ex, 11 tbl, 2 dwg

Description

The invention relates to biologically active preparations and can be used in medicine, namely in dentistry, gynecology and laryngology, as well as in the pharmaceutical, food industry, veterinary medicine, cosmetology and biotechnology.

) и др. обеспечивают широкий ассортимент образцов хитозана и материалов на его основе для решения целого ряда проблем в разных сферах жизни [Хитозан/Под ред. Р.А.А. Муццарелли. Пер. с англ. Л.С. Пачковской. Н. Новгород: Изд-во «Вектор-ТиС». 2001. 372 с.; Гальбрайх Л.С. Хитин и хитозан: строение, свойства, применение //Соросовск.Образоват. журн. 2001. Т.7. №1. С.51-56; Хитин и хитозан: Получение, свойства и применение /Под ред. К.Г. Скрябина, Г.А. Вихоревой, В.П. Варламова. М.: Наука. 2002. 368 с.; Немцев С. В. Комплексная технология хитина и хитозана из панциря ракообразных. М.: Изд-во ВНИРО. 2006. 134 с.].Среди множества разновидностей препаратов на основе хитозана гели и гелеобразные формы имеют ряд преимуществ. Они обладают вязкой консистенцией, обеспечивают большую биодоступность, оказывают увлажняющее действие на кожу и по сравнению с мазями лучше всасываются. Их фармакотерапевтическое действие пролонгированное и более выраженное. Кроме того, в отличии от мазей при попадании на кожу или одежду они легко смываются водой, не оставляя никаких следов.Chitosan, a derivative of chitin biopolymer, is known to have a valuable combination of physicochemical and biological properties. Non-toxicity, features of the chemical structure (the presence of —OH, —NH ₂ and —NHCOCH ₃ groups in the elementary macromolecules), the possibility of varying the content of amino groups and the degree of protonation, a wide range of molecular weight (

) and others provide a wide range of chitosan samples and materials based on it to solve a number of problems in various fields of life [Chitosan / Ed. R.A.A. Muzzarelli. Per. from English L.S. Pachkovo. N. Novgorod: Vector-TiS Publishing House. 2001.372 s .; Galbraich L.S. Chitin and chitosan: structure, properties, application // Sorosovsk. Obrazovat. journal 2001. V.7. No. 1. S.51-56; Chitin and Chitosan: Preparation, Properties, and Use / Ed. K.G. Scriabin, G.A. Vikhoreva, V.P. Varlamova. M .: Science. 2002.368 s .; Nemtsev S.V. Integrated technology of chitin and chitosan from the shell of crustaceans. M .: Publishing house VNIRO. 2006. 134 pp.] Among the many varieties of chitosan-based preparations, gels and gel forms have several advantages. They have a viscous consistency, provide greater bioavailability, have a moisturizing effect on the skin and are better absorbed than ointments. Their pharmacotherapeutic effect is prolonged and more pronounced. In addition, unlike ointments, if they come in contact with skin or clothing, they are easily washed off with water, leaving no residue.

A known method of obtaining a biologically active complex based on chitosan lactate (ecogel) and the composition of the biologically active complex for the protection of agricultural plants [see RF patent No. 2316963, IPC A01N59 / 00, A01N25 / 04, A61K31 / 722, A01N37 / 02]. An active complex based on chitosan lactate is obtained by dissolving chitosan in an aqueous solution of lactic acid at a reagent ratio of 1: 1, a temperature of 65-75 ° C and a fixed pH (6.5-7.0) with constant stirring with the vortex motion of the mass flow, when the mass is saturated with silver ions with subsequent magnetic treatment. In this case, a gel is obtained that has undergone magnetic treatment and contains in g / l: chitosan with SD = 75-88 mol.% −1.0-50.0 (0.1-5.0 wt.%), Lactic acid - 1.0-50.0 (0.1-5.0 wt. %), silver ions - 7.5-10.0 mg / l and water - the rest.

The disadvantage of this active complex based on chitosan lactate is multicomponent, multi-stage production, strict temperature and pH control, the use of an expensive silver ion preparation, as well as additional equipment for magnetic processing. It is difficult to imagine on the basis of the data presented that the authors are dealing with a “gel”, because they do not use a crosslinking agent. In addition, it is known that the effect of activation after treatment in a magnetic field persists for a short time (up to one day) [Sokolsky Yu.M. Magnetized water: truth and fiction. L .: Chemistry. 1990. 144 p.].

Known "gel" for skin care and treatment of its diseases and composition for its preparation [see RF patent No. 2085187, IPC A61K7 / 48]. This composition in addition to chitosan, a vitamin preparation and distilled water additionally contains an antiseptic and anesthetic.

The disadvantage of this gel is the difficulty of obtaining and content of toxic substances (antiseptic and anesthetic) that can cause allergic reactions, reduce immune status, etc.

Closest to the claimed invention in its technical essence is a gel composition based on chitosan, which has wound healing, anti-burn, anti-inflammatory, hepatoprotective, anti-diabetic and antitumor effects [see RF patent No. 2366408, IPC A61K9 / 00, A61K31 / 519, A61K31 / 722, A61P1 / 16, A61P3 / 10, A61P17 / 02, A61P29 / 00, A61P35 / 00]. The claimed composition in addition to chitosan 15-25 g / l (1.5-2.5 wt.%) And distilled water contains tryptantrine 1.5-2.5 g / l (0.15-0.25 wt.%).

The disadvantage of the gel composition is multicomponent, multi-stage production, the use of organic solvents such as acetic acid and dimethyl sulfoxide (these components are not shown in the gel composition in the claims). To enhance the biological activity of the composition, it was necessary to introduce an additional component, the tryptantrine alkaloid, whose effect on human cells has not been sufficiently studied to date. Tryptantrine is poorly soluble in water; a solution of this alkaloid in dimethyl sulfoxide is used to introduce it into the gel composition. Dimethyl sulfoxide is contraindicated in a number of diseases of the liver, kidneys, angina pectoris, cataract, glaucoma, pregnancy, etc.

The objective of the invention is the creation of a gel-like composition based on low molecular weight (= 38 kDa) chitosan hydrochloride with a wide spectrum of biological effects: antibacterial, anti-inflammatory, wound healing and cosmetic.

The technical result provided by the invention is to reduce the toxicity and expand the spectrum of the biological action of the composition due to the synergistic effect of the interaction of chitosan hydrochloride and pharmacopoeial organic acid selected from the following: acetic, ascorbic, glycolic, lactic, citric and succinic.

The problem is solved in that the gel-like composition containing the active substance and distilled water, according to the solution, contains chitosan hydrochloride as the active substance, the composition additionally contains an organic acid selected from the range: acetic, ascorbic, glycolic, lactic, citric, succinic; in the following ratio of starting components, wt.%:

chitosan hydrochloride 10-20 organic acid 1-10 distilled water rest

The invention is illustrated by drawings.

In FIG. 1 shows the structural formula of the polymer composition.

In FIG. 2 shows the dynamics of the wound healing process in laboratory animals.

It was experimentally established that the concentration of the polymer (C _p ) of chitosan hydrochloride, less than 10 wt.% Is not sufficient to obtain a gel-like consistency, and more than 20 wt.% Under the accepted dissolution conditions does not lead to the full participation of the polymer in the formation of the gel-like composition, which is pharmacotherapeutic and economic point of view is impractical.

The concentration of organic acid (C _k ) in the composition was determined empirically by a pH value of up to 3, taking into account the type of biological action (for example, GOST RF on “Cosmetic Gels”).

Comparing the experimental data of elemental analysis of the initial sample and the potentiometric titration of aqueous, aqueous-acidic (0.1 NHCl) solutions of the initial sample and the composition of chitosan hydrochloride in an aqueous solution of an organic acid (for example, ascorbic acid), we can conclude that a double salt of chitosan is formed in the gel-like composition, which, in addition to hydrochloride groups includes at least one group of ascorbate achitosan in the macromolecule (or counterion of another acid).

The proposed structural formula of the polymer composition is shown in FIG. 1, where x is the number of monomer units of chitosan ascorbate, y is chitosan hydrochloride, z-N-acetyl-D-glucosamine.

Studies have shown an increase in biological activity and an extension of the biological spectrum of the inventive gel composition.

The inventive gel composition is obtained as follows.

Use an industrial sample of chitosan hydrochloride (c = 38kDa, SD = 80 ± 2 mol.%), Produced by Bioprogress CJSC. A portion of chitosan hydrochloride is dissolved in an aqueous solution of acetic, or ascorbic, or glycolic, or lactic, or citric, or succinic acid at a fixed concentration with continuous stirring for 3 hours at a temperature of 20-22 ° C. The resulting gel-like (highly viscous) system is kept under static conditions for one day. Then the composition is filtered through a fabric filter and Packed in sterile containers. All operations are carried out in compliance with sanitary and epidemiological requirements. The gel-like composition is stored in a refrigerator at a temperature of + 4 ° - + 6 ° C.

To assess cytotoxicity and mutagenic effect, we used a micronuclear test (МЯ-test) and an express method for evaluating the general toxic and skin-irritating effect on a culture of mobile cells (Methodical recommendations. MP No. 29FC / 394 of the Ministry of Health of Russia. M., 2002).

The antibacterial effect was studied on the example of test strains Escherichiacoli 113-13, or Staphylococcusaureus 209 P, or Bacilluscereus 8035 using sterile liquid nutrient medium - meat-peptone broth (MPB) and solid nutrient medium - meat-peptone agar (MPA).

The anti-inflammatory effect was evaluated in in vitro (cell culture) and in vivo (in clinical practice) models.

The wound healing effect of the samples was carried out invivo in animal models (white male mice and outbred female rats). When working with experimental animals, they are guided by the order of the USSR Ministry of Health No. 755 of 08/12/1977 and the requirements of the European Convention for the Protection of Laboratory Animals. All manipulations with animals were performed under ether anesthesia.

Cosmetic effects were evaluated on in vivo volunteer models using questionnaires.

All testing and testing methods are given in specific examples.

The applicability of the proposed solutions are illustrated by the following examples.

Example 1. Assessment of cytotoxicity and mutagenic effect.

Assessment of cytotoxicity and mutagenic effect on the example of a gel-like composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid. The gel-like composition is subjected to preclinical toxicological studies using a micronucleus test (MY test) and an express method for evaluating the general toxic and skin-irritating effects on a culture of mobile cells (Methodological recommendations. MP No. 29FC / 394 of the Ministry of Health of Russia. M., 2002). The results are shown in tables 1 and 2.

Table 1

The results of determining the acute toxicity of a sample of a gel-like composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid on an in vitro mobile cell culture

Test object Dilution Toxicity Index It,% Test Sample Evaluation ND at MVI Hazard Class ER ₅₀ Bostaurustaurus one 75.4 Non toxic MP 2.1.7.2279-07 <5
Grade 4 Less dangerous 0.1 81.4 Non toxic 0.01 96.5 Non toxic 0.001 100.2 Non toxic

table 2

The results of determining the acute toxicity of a sample of a gel-like composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid by the MY method

The duration of incubation of cell cultures with the drug The concentration of water extract 1 g in 10 ml of water Analysis results Test Sample Evaluation ND at MVI 24 hours one hundred 0.51 ± 0.05%
The control
0.48 ± 0.01% No mutagenic effect No.224.01.17.066 / 2009

As can be seen from the data given in tables 1 and 2, by the degree of impact on human health, the studied sample of a gel-like composition based on chitosan hydrochloride and an aqueous solution of ascorbic acid belongs to hazard class 4 (low hazard, GOST 12.1.007-76) and does not mutagenic effect on human cells.

Example 2. Antibacterial effect.

A sample of a gel-like composition based on chitosan hydrochloride and an aqueous solution of an organic acid (acetic, ascorbic, glycolic, lactic, citric, succinic) in a volume ratio of 1: 1 is added to a separate tube with a sterile meat-peptone broth (MPB) and mixed thoroughly. After that, 0.1 ml of a cell suspension (10 ⁵ CFU / ml) of test strains Escherichiacoli 113–13 or Staphylococcusaureus 209 P or Bacilluscereus 8035 is introduced into each of the obtained broth solutions of the samples of the composition of chitosan salts. The tubes are placed in a thermostatic shaker and cultivated for three days at 37 ° C. As a control, suspension of test strains in BCH taken at the same concentrations without adding samples of a gel-like composition are used. Antibacterial activity is evaluated after 24, 48 and 72 hours visually by the turbidity of the solution and by plating the contents of the test tubes (0.1 ml each) on meat-peptone agar (MPA). The results are shown in table 3.

Table 3

Physico-chemical characteristics and antibacterial activity of samples of a gel-like composition based on a complex of chitosan salts

Characterization of the gel composition Characteristic of the BCH system + gel composition + microorganisms * Source polymer Solvent pH Turbidity
after 24 hours Culture growth after seeding on MPA after t h Functional group With _P , wt.% Title _P C% 24 48 72 BCH + microorganisms 7.2 Muddy + + + Chitosan Water - 7.5 Opalescent - + + -NH ₂ four Chitosan Hydrochloride Water - 5.9 Opalescent - + + -NH ₃ ⁺ Cl ^- four fifteen Acetic acid 2 3.5 Transparent - - - fifteen Vitamin C 9 3.1 Transparent - - - fifteen Lactic acid one 3.1 Transparent - - - fifteen Glycolic acid 5 3.0 Transparent - - - fifteen Lemon acid 2 3.1 Transparent - - - fifteen succinic acid 2 3.4 Transparent - - -

* Microorganisms: E. coli 113-13, S.aureus 209 P, B.cereus 8035;

"-" the lack of growth of strains of microorganisms;

"+" The presence of growth of strains of microorganisms.

From the data given in table 3, it is seen that the gel-like composition based on chitosan hydrochloride and an aqueous solution of an organic acid (acetic, ascorbic, glycolic, lactic, citric, succinic) exhibits a prolonged antibacterial effect compared to the aqueous solution of the initial polymer of chitosan regardless of what chemical form it is located, i.e. as a polybase (-NH ₂ ) or as a polysalt (-NH ₃ ⁺ Cl ^- ). At the same time, it was experimentally determined that the maximum water-soluble concentration of the starting polymer is 4 wt.%. A higher concentration of both chitosan and chitosan hydrochloride leads to swelling of the polymer.

Group of examples 3-8. Anti-inflammatory effect.

Anti-inflammatory effect on the example of a gel-like composition of chitosan hydrochloride in an aqueous solution of ascorbic acid. Testing of samples is carried out on models in vitro (cell culture) and in vivo (in clinical practice).

Example 3. As test models in vitro, a culture of epithelial cells MA-104 is used (Scientific Research Institute of Cytology RAS, St. Petersburg). Cells are grown in an atmosphere of 5% CO ₂ at 37 ° C in a DMEM growth medium supplemented with 10% fetal calf serum (Gibco, USA) without antibiotics. Cells that have reached a monolayer are enzymatically disaggregated, washed in phosphate-buffered saline (PBS; Sigma, USA), resuspended in fresh medium and introduced into Petri dishes to a final concentration of 130-150 thousand cells in 1 ml of DMEM medium that does not contain ( negative control) or containing a sterile sample of a gel-like composition (7 μl per 1 ml of medium). The dynamics of changes in the concentration of IL-1β, IL-8 and TNF-α cytokines in growth media is monitored by enzyme-linked immunosorbent assay according to the instructions attached to the reagent kits manufactured by Vector-Best CJSC (Novosibirsk, Russian Federation).

The results of determining the production of cytokines culture MA-104 in response to contact with the gel-like composition are shown in table 4.

Table 4

Production of cytokines by the MA-104 epithelial cell culture in DMEM growth medium with or without the addition of a gel composition

Cytokine The concentration of cytokine in the growth medium, PG / ml No song added
in t, days With the addition of composition
in t, days 0.5 one 2 0.5 one 2 TNF-α 4.1 2.8 2.3 2.1 0 0 IL-8 0 6.0 636.0 0 28.0 702.0 IL-1β 5.2 139.5 12.4 14.8 189.9 26.8

From the data of table 4 it is seen that the gel-like composition on the 1st day reduces by 2 times, and on the 2nd day completely suppresses the secretion of the TNF-α cytokine, which is the main mediator of the inflammatory reaction; enhances the production of the cytokine IL-8, causing the migration of innate immunity cells into the focus of inflammation; increases the production of the cytokine IL-1β, stimulating the phagocytic activity of micro- and macrophages. Thus, in an in vitro experiment on the MA-104 epithelial cell culture model, the anti-inflammatory effect of the gel-like composition is revealed by suppressing the production of the anti-inflammatory cytokine TNF-α and stimulating innate immunity effector cells.

Example 4. In clinical practice, 15 patients suffering from mild chronic periodontitis are given a 10-day traditional complex therapy in conjunction with the application of a gel-like composition on the area of the papilla and marginal gum with a capture of 1-2 cm of the mucous membrane of the alveolar ridge and instillation in periodontal pockets . The duration of daily treatments is 15 minutes. The comparison group consists of 15 patients receiving traditional complex therapy without the use of a gel-like composition. The clinical condition of periodontal tissues is evaluated using the following indices: hygienic (IG), periodontal (PI), papillary-marginal-alveolar (RMA). The condition of the bone tissue of the interdental septa is evaluated according to intraoral radiography. An anti-inflammatory effect is defined as a reduction in the PMA index by the formula:

PE = 100 × [RMA (1) - RMA (2)] / RMA (1), (%),

where PE is anti-inflammatory effectiveness; PMA indices (1) and (2) refer to examination before and after therapy.

The results are shown in table 5.

Table 5

Index assessment of periodontal tissues in patients with mild chronic periodontitis before and after traditional therapy without and using a gel composition

Indicators Study group Comparison group Before therapy After therapy Before therapy After therapy PMA (%) 44.35 ± 2.15 6.37 ± 0.64 47.40 ± 2.46 20.15 ± 1.37 IG (points) 2.26 ± 0.50 1.18 ± 0.30 2.37 ± 0.40 1.20 ± 0.02 PI (points) 3.57 ± 0.10 2.53 ± 0.15 3.60 ± 0.43 2.95 ± 0.30 Effect (%) 85.6 57.5

From the data of table 5 it is seen that in the treatment of patients with mild chronic periodontitis, the anti-inflammatory effect is 1.5 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 5. The same as in example 4, but in the treatment of patients with chronic periodontitis of moderate severity.

Table 6

Index assessment of periodontal tissues in patients with moderate periodontitis before and after traditional therapy without and using a gel composition

Indicators Study group Comparison group Before therapy After therapy Before therapy After therapy PMA (%) 58.60 ± 4.29 8.40 ± 1.15 60.30 ± 4.19 24.70 ± 2.02 IG (points) 2.54 ± 0.40 1.24 ± 0.24 2.45 ± 0.45 1.20 ± 0.45 PI (points) 4.73 ± 0.20 3.63 ± 0.25 4.66 ± 0.45 3.61 ± 0.35 Effect (%) 85.7 59.0

From the data of table 6 it can be seen that in the treatment of patients with moderate periodontitis, the anti-inflammatory effect was 1.45 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 6. The same as in example 4, but in the treatment of patients with chronic catarrhal gingivitis.

Table 7

Index assessment of periodontal tissues in patients with chronic catarrhal gingivitis before and after traditional therapy without and using a gel composition

Indicators Study group Comparison group Before therapy After therapy Before therapy After therapy PMA (%) 28.30 ± 0.95 5.25 ± 0.09 27.70 ± 0.89 10.43 ± 0.25 IG (points) 2.15 ± 0.45 1.16 ± 0.10 2.10 ± 0.40 1.17 ± 0.23 PI (points) 2.05 ± 0.20 1.98 ± 0.17 2.14 ± 0.35 2.10 ± 0.20 Effect (%) 81.4 62.3

From the data of table 7 it is seen that in the treatment of patients with chronic catarrhal gingivitis, the anti-inflammatory effect was 1.3 times higher in the case of traditional therapy in combination with daily applications of a gel-like composition.

Example 7. A group of patients with exacerbation of chronic hypertrophic pharyngitis (10 people) undergoes traditional therapy - double cauterization of oropharyngeal lymphoid granules with a 10% solution of silver nitrate (lapis) with an interval of one day. In the second (experimental) group of patients with chronic hypertrophic pharyngitis (10 people), for 4 days, in addition to traditional therapy, the pharynx is daily treated with a gel-like composition (morning and evening) for 30-60 seconds. Hyperemia and the degree of infiltration of the granules of the oropharyngeal lymphoid tissue is assessed using a visual analogue scale (VAS) in scores from 0 to 5. The severity of the pain in the throat (pain, sensation of dryness, dryness, foreign body sensation in the throat) is assessed according to YOUR (0-10 points ) In this case, the absence of a sign is taken as 0, and for 5 and 10 (respectively) - its maximum severity. The results of applying the gel composition are presented in tables 8 and 9.

Table 8

The dynamics of changes in the intensity of pain in the throat during the treatment of chronic hypertrophic pharyngitis without and using a gel-like composition

Therapy The intensity of sore throat (according to YOUR, 0-10 points) Before therapy In t, days one 2 3 Traditional 8.1 ± 1.7 6.0 ± 0.8 5.2 ± 1.4 1.7 ± 1.5 Traditional + gel treatment 8.3 ± 1.5 1.9 ± 1.7 0 0

Table 9

The dynamics of the severity of hyperemia of the granules of the lymphoid tissue of the pharynx during the treatment of chronic hypertrophic pharyngitis without and using a gel-like composition

Therapy The severity of hyperemia of the granules of the lymphoid tissue of the pharynx
(according to YOUR, 0-5 points) Before treatment in t, days one 3 Traditional 4.5 ± 0.7 4.0 ± 1.2 2.4 ± 0.5 Traditional + gel treatment 4.7 ± 0.8 1.9 ± 0.7 1.0 ± 0.1

Based on the data shown in tables 8 and 9, it can be argued that the use of a gel-like composition in combination with traditional therapy of chronic hypertrophic pharyngitis provides a significantly higher analgesic effect and a more pronounced regression of symptoms of inflammation.

Example 8. 15 women suffering from vaginal dysbiosis undergo traditional therapy (metronidazole 500 mg orally 2 times a day for 7 days) in combination with the treatment of the vaginal mucosa with a gel composition in an amount of 1 ml 1 time in 2 days for 10 days. The comparison group consists of 15 women, also suffering from vaginal dysbiosis and receiving traditional treatment, but without the use of a gel-like composition. The effectiveness of the anti-inflammatory effect is evaluated according to patient complaints and the clinical picture. The results are shown in table 10.

Table 10

The dynamics of the relief of symptoms of vaginal dysbiosis during traditional therapy without and using a gel-like composition

Symptoms Study group
day Comparison group
day one 2 5 10 one 2 5 10 Itching and burning + ++ ++ + Discharge (white) + ++ ++ + Mucosal hyperemia + + +

The results presented in table 10 indicate the high efficiency of the use of a gel-like composition based on chitosan hydrochloride and a solution of ascorbic acid as an anti-inflammatory agent in combination with traditional therapy for vaginal dysbiosis.

The group of examples 9-10. Wound healing effect.

Testing the wound healing effect of samples of the gel-like composition is carried out in vivo in animal models. When working with experimental animals, they are guided by the order of the USSR Ministry of Health No. 755 of 08/12/1977 and the requirements of the European Convention for the Protection of Laboratory Animals. All manipulations with animals are carried out under ether anesthesia.

Example 9. The study of the wound healing effect of a gel-based composition based on chitosan hydrochloride and ascorbic acid is carried out on a model of sexually mature outbred white male mice with an average weight of 18-20 g. A standard wound is artificially modeled on the depilated back surface by resection of a 1 cm ² area of the dermal layer of the skin . In the experimental group of animals (10 pcs.), The gel-like composition is uniformly applied to the exposed wound surface. In the control group (10 pcs.) Wound healing occurs by primary intention without applying a gel-like composition. The course of the wound process is judged by the dynamics of reducing the area of the wound and its condition.

In FIG. 2 shows the dynamics of the wound healing process in laboratory animals (white mice) when using a gel-like composition based on chitosan hydrochloride and ascorbic acid (a-c) and in the control (g-e): freshly formed wound (a, d), wound condition by 3 -and (b, d) and the 14th day (c, f) of the experiment. It was found that when using a gel-like composition, wound healing occurs on average 1.7-2 times faster than in the control.

Example 10. The study of the wound healing effect of the gel-based composition based on chitosan hydrochloride and acetic acid is carried out on a model of sexually mature outbred female rats with an average weight of 300 g. Thermal burns of degree IIIB with an average area of 9.8 mm ^{2 are} modeled in the interscapular region. A scab formed on the 3rd day and pathologically changed tissues are removed by acute necrectomy. The control group of animals (15 rats) is left untreated, the rest (15 rats) are applied on a exposed wound surface gel-like composition.

It was found that when using a gel-like composition based on chitosan hydrochloride in an aqueous solution of acetic acid, an acceleration of the healing process of a burn wound of III degree is observed on average 1.6 times.

Example 11. Cosmetic action.

A small amount of a gel-like composition based on chitosan hydrochloride and a solution of lactic, glycolic or citric acid is applied to clean skin of the face, neck and hands with light circular movements. After 3-5 minutes, the composition is washed off with plenty of warm water. The procedure is repeated no more than 1-2 times a week. Cosmetic effects observed when using a gel-like composition based on chitosan salts are shown in Table 11.

Table 11

Cosmetic effect of a gel-like composition based on chitosan hydrochloride and organic acids

Composition Cosmetic effect Polymer Solvent Chitosan Hydrochloride Lactic acid Exfoliating
Brightening
Disinfectant
Lifting effect
Keratoplastic Glycolic acid Exfoliating
Disinfectant
Keratoplastic Lemon acid Brightening
Astringent
Refreshing
Keratoplastic
Disinfectant succinic acid Keratoplastic
Protective
Refreshing
Disinfectant

Thus, the use of a low molecular weight chitosan salt - chitosan hydrochloride in combination with various organic pharmacopoeial acids allows us to expand the spectrum of biological action and to obtain a composition that, depending on the selected acid, exhibits, in addition to antibacterial activity, anti-inflammatory, wound healing and cosmetic. Moreover, the resulting composition is non-toxic, easy to obtain, has a low cost and is available to a wide range of consumers.

Claims (1)

A gel-like biologically active composition for application to the skin, containing an active substance - chitosan hydrochloride and distilled water, characterized in that the composition further comprises an organic acid selected from the range: acetic, ascorbic, glycolic, lactic, citric, succinic; in the following ratio of starting components, wt.%:
chitosan hydrochloride 10-20 organic acid 1-10 distilled water rest

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