RU2736061C1 - Method of producing biocomposite based on airgel of bacterial cellulose having haemostatic properties - Google Patents

Abstract

FIELD: biotechnology; medicine.

SUBSTANCE: invention refers to biotechnology and medicine, namely to a method for producing a biocomposite based on airgel of bacterial cellulose having haemostasis properties. Method comprises producing a gel film of bacterial cellulose by culturing a strain of bacteria Gluconacetobacter sucrofermentans VKPM V-11267 in static conditions on a medium with molasses, separation of obtained gel film of bacterial cellulose from culture medium and its cleaning, mechanical grinding of purified gel film of bacterial cellulose for 10 minutes, production of hydrogel a) bacterial cellulose-chitosan in ratios of 80:20 by mixing 2 % chitosan solution in 1 % acetic acid, bacterial cellulose hydrogel, 25 % glutaric aldehyde, with addition of sodium fusidine in combination with one or more additional components, or b) bacterial cellulose:chitosan:gelatine:transglutaminase in ratio of 5:5:15:5 respectively, with addition of sodium fusidine in combination with one or more additional components, wherein the additional components are selected from physiologically active polyphenolic compounds - dehydroquercetin or resveratrol, low-molecular peptides - tinrostyma, and/or coagulation factors - thrombin or transglutaminase, obtaining airgel by freezing in a low-temperature refrigerator for a day and then performing lyophilic drying.

EFFECT: invention provides wider range of wound coatings based on airgel of bacterial cellulose with enhanced haemostatic properties and antimicrobial action.

1 cl, 16 ex

Description

The invention relates to the field of biotechnology and medicine, and in particular to a method for producing a biocomposite based on a bacterial cellulose airgel, used, for example, as a wound covering with antibacterial and hemostatic properties.

Modern dressings are aimed not only at preventing the spread of wound infection, but also at improving the process of wound healing and stopping bleeding, especially in extreme situations. Depending on the type of wound and the phase of healing, the dressing requires different therapeutic and pharmacological functions. Dressings should maintain moisture in the wound, diffuse gases, remove excess exudate, protect the wound from microorganisms, provide mechanical protection, provide easy and painless wound removal, be flexible, cost effective, and free of side effects.

The market for dressings has grown significantly over the past 10 years, but only a few of these dressings have all the necessary properties to protect and heal wounds. Natural polymers are of particular interest due to their high absorption and swelling capacity, non-cytotoxicity; in addition, various active compounds can be immobilized in these polymers. Natural polymers are also a suitable matrix for enzyme immobilization and functionalization.

Quite a lot of various coatings are known for treating wounds and stopping bleeding, in which drugs are applied to a natural base or synthetic material.

It is also known a wound covering, which has a pronounced hemostatic effect, based on chitosan and fibrin monomer used as an active substance. In order to give the sponge antiseptic and antibacterial effects, antiseptics (up to 3%) and broad-spectrum antibiotics (up to 10%) of the total mass of the mixture can be added to the base solution (RU 2618896, IPC A61K 9/18, A61L 15/28, A61L 15/32, A61L 15/20, A61L 15/44, A61P 7/04, publ. 05.11.2017).

The disadvantage of this solution is the lack of specific antiseptic agents and antibiotics, which make it possible to give the resulting composite antibacterial properties.

Also known is a wound dressing containing sodium alginate as a base and ferrous sulfate as an active substance. This invention provides an expansion of the range of hemostatic sponges with a pronounced hemostatic effect and the exclusion of a direct adverse effect of the active substance on the wound surface and surrounding tissues due to the pharmacological form of the sponge (RU 2627855 IPC A61K 33/26, A61K 31/715, A61K 31/717, A61K 31/722, A61K 31/197, A61P 7/04, publ. 08/14/2017).

Known wound dressing based on a collagen-chitosan complex for the restoration of skin defects in the form of a sponge, gel, colloidal solution, film. The use of the proposed wound covering for the closure of planar wound defects allows to improve the qualitative and quantitative characteristics of the restored wound skin defects of the cicatricial and pericarcular zones, leads to a complete restoration of the epidermal-dermal complex corresponding to healthy skin (RU 2254145 IPC A61L15 / 28, A61L15 / 32, A61L26 / 00, publ. 20.06.2005).

The disadvantage of the claimed solution is that the composite lacks pronounced hemostatic properties that prevent bleeding, as well as narrow functionality.

The closest technical solution to the claimed one is a wound covering with a hemostatic effect, containing bacterial cellulose, synthesized using a symbiotic culture of Medusomyces gisevii Sa-12 in the form of a sponge, containing up to 10% hemostatic and up to 3% antimicrobial agents in relation to bacterial cellulose. As a hemostatic component it contains fibrin monomer, thrombin, blood coagulation factors VIII and IX, iron salt of polyacrylic acid, for example, feracryl. As an antimicrobial component, it contains dioxidine or chlorhexidine, or silver, or Dr. Chistoteloff's solution, broad-spectrum antibiotics, for example, cefipime or azithromycin (RU 2624242, IPC A31L 15/18, A61L 15/44, A61L 15/28, A61F 13/00, publ. 03.07.2017).

The disadvantage of the known solution is the use of a symbiotic culture of variable composition, the absence of regenerative properties in the wound dressing, and the use of broad-spectrum antibiotics of cefipime or azithromycin as an antimicrobial component, the effectiveness of which has been proven for oral administration.

The technical result of the claimed invention is to expand the range of wound dressings based on bacterial cellulose airgel with enhanced hemostatic properties and antimicrobial action.

The essence of the invention lies in the fact that the method of obtaining a biocomposite based on a bacterial cellulose airgel with hemostatic properties consists in obtaining a gel film of bacterial cellulose by cultivating a bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses, separating the obtained gel films of bacterial cellulose from the culture medium and its purification, mechanical grinding of the purified gel film of bacterial cellulose for 10 min to obtain a hydromodule with a ratio of 1: 3, obtaining a hydrogel of bacterial cellulose-chitosan in a ratio of 80:20 by mixing a 2% solution of chitosan in 1% acetic acid, bacterial cellulose hydrogel, 25% glutaraldehyde. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for a day, then freeze-dried. Also, an airgel is obtained bacterial cellulose: chitosan: gelatin: transglutaminase in a ratio of 5: 5: 15: 5, respectively, and the addition of sodium fusidine, physiologically active compounds of polyphenolic nature in the form of dehydroquarcetin or resveratrol, low molecular weight peptides (tinrostim), blood coagulation factors such as thrombin, transglutaminase.

The bacterial strain Gluconacetobacter sucrofermentans H-110 was isolated at the Department of Biotechnology of the Mordovian State University from Kombucha with subsequent selection based on natural selection. The culture was identified to species by analysis of genes encoding 16S rRNA at FGUP GosNIIGenetics. The bacterial strain Gluconacetobacter sucrofermentans H-110 was deposited in the All-Russian Collection of Industrial Microorganisms (VKPM) under registration number: B-11267. The bacterial strain is not zoopathogenic, phytopathogenic and is not dangerous for other reasons.

The method for producing bacterial cellulose is described in the applicant's inventions (RU 2536973, IPC C12N 1/20, publ. 27.12.2014, RU 2536257, IPC C12N 1/20, publ. 20.12.2014).

The claimed invention uses the antibiotic fusidin sodium, the effectiveness of which has been proven for external use, in particular in the treatment of systemic and local staphylococcal infections of the skin and soft tissues.

Fusidic acid has bacteriostatic, and in high doses, bactericidal activity mainly against gram-positive bacteria. The mechanism of action is associated with the rapid suppression of protein synthesis in microorganisms. It is produced by the fungi Fusidium coccineum and is the only representative of the fusidan class used in clinical practice. Fusidic acid is most active against staphylococci and streptococci. Gram-negative bacteria are overwhelmingly resistant to fusidic acid (Salmonella spp., Proteus spp., Escherichia coli). The spectrum of antimicrobial activity of fusidic acid is narrow, because within the same genus, different types of microorganisms can have different sensitivity to the drug. Pharmacological profile of fusidic acid: good tolerability, low level of resistance and no cross-resistance with other antibiotics, as well as the possibility of stepwise therapy for wider application, especially in infections caused by S. aureus.

Chitosan - a natural biopolymer, polysaccharide, a product of chitin deacetylation, is an object of study and is actively used in practical medicine due to its unique physicochemical, biological, ecological and physiological properties, namely: biocompatibility, biodegradability, stability in the natural environment, lack of toxicity, high biological activity, economic availability. Antiviral, antibacterial activity of chitosan was established, immunostimulating, adjuvant, adaptogenic, antihypoxic, cholestric, radioprotective, hemostatic action was confirmed. The physicochemical and biological properties of this polymer make it possible to consider chitosan and its derivatives as a promising raw material for the production of drugs with various pharmacotherapeutic actions. Chitosan has a large number of hydrogen bonds, which determine its ability to bind a large number of organic water-soluble substances.

Dihydroquercetin (DHQA) belongs to the group of phenolic compounds with high antioxidant activity. DHAQ inhibits the processes of lipid peroxidation of cell membranes, prevents the damaging action of free radicals, slows down the premature aging of cells and the development of various diseases. For the manifestation of the antioxidant effect, DHAQ is introduced into various ointments. In medical practice, DHAQ is used as an anti-inflammatory, anti-radiation, oncoprotective agent. Helps maintain the functions of the immune system, has an antitoxic effect. Possesses gastroprotective activity: stimulates the processes of regeneration of the mucous membranes.

Resveratrol is a natural biologically active substance from the group of polyphenols, isolated from dark grapes and grape seeds, which has proven anticarcinogenic, hepatoprotective and anti-inflammatory properties. Resveratrol, an antioxidant substance in grapes, has cardioprotective properties, enhances postnecrotic regeneration of cardiomyocytes, increases high-density lipoprotein levels, and reduces blood fibrinogen concentration and platelet aggregation.

Low molecular weight peptides contained in various organs and tissues of a macroorganism are called cytomedins. The role of these peptides in the body is to regulate the functions of homeostasis, and they themselves have antioxidant, anticarcinogenic, immunomodulatory and other biologically active properties. One such compound is tinrostim.

The method of producing a biocomposite based on bacterial cellulose airgel with hemostatic properties is carried out as follows.

Example 1. Get a gel film of bacterial cellulose by cultivating the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and 0.06% sodium fusidin and 0.03% thrombin are introduced. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 2. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and 0.06% sodium fusidin, 0.03% thrombin and 0.1% resveratrol are introduced. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 3. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidin, 0.03% thrombin and 2% dehydroquartsetin. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 4. Get a gel film of bacterial cellulose by cultivating the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove the cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified bacterial cellulose gel film is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and 0.06% sodium fusidine, 0.03% thrombin and 0.1% tinrostim are introduced. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 5. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidin and 10% traglutaminase solution. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 6. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and 0.06% sodium fusidin, 10% transglutaminase solution and 0.1% resveratrol are introduced. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 7. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidin, 10% transglutaminase solution and 2% dehydroquartsetin. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 8. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidin, 10% transglutaminase solution and 0.1%) tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 9. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidine, 0.03%) thrombin, OD% resveratrol and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 10. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidine, 0.03%) thrombin, 2% dehydroquarcetin and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 11. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and 0.06% sodium fusidine, 10% transglutaminase solution, 0.1% resveratrol and 0.1% tinrostim are introduced. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 12. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a composite "bacterial cellulose-chitosan" in a ratio of 80:20, a 2% solution of chitosan in 1% acetic acid, a hydrogel of bacterial cellulose, 25% glutaraldehyde (2%, v / v) are mixed and make 0.06% sodium fusidine, 10% transglutaminase solution, 2% dehydroquartsetin and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 13. Get a gel film of bacterial cellulose by cultivating the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a hydrogel in a ratio of 5: 5: 15: 5, mix 2% chitosan solution in 1% acetic acid, 10% gelatin solution, 20% transglutaminase solution and bacterial cellulose hydrogel and add 0.06% fusidin sodium, 0.1% resveratrol and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 14. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a hydrogel in a ratio of 5: 5: 15: 5, mix 2% chitosan solution in 1% acetic acid, 10% gelatin solution, 20% transglutaminase solution and bacterial cellulose hydrogel and add 0.06% fusidine sodium, 2% dehydroquarcetin and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 15. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a hydrogel in a ratio of 5: 5: 15: 5, mix 2% chitosan solution in 1% acetic acid, 10% gelatin solution, 20% transglutaminase solution and bacterial cellulose hydrogel and add 0.06% fusidine sodium, 0.1% resveratrol, 0.03% thrombin and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

Example 16. Get a gel film of bacterial cellulose by culturing the bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses. To remove cells and components of the culture medium, the resulting bacterial gel film is purified. Mechanical grinding of the purified gel-film of bacterial cellulose is carried out to obtain a hydromodule with a ratio of 1: 3.

To obtain a hydrogel in a ratio of 5: 5: 15: 5, mix 2% chitosan solution in 1% acetic acid, 10% gelatin solution, 20% transglutaminase solution and bacterial cellulose hydrogel and add 0.06% fusidin sodium, 2% dehydroquartsetin, 0.03% thrombin and 0.1% tinrostim. In order to obtain aerogels, the obtained sample is frozen in a low-temperature refrigerator for 24 hours, then freeze-dried.

The antibacterial properties of the claimed biocomposite are determined by a method based on the ability of antibiotic substances to diffuse in agar media and form zones in which microorganisms sensitive to these antibiotics do not develop. The bacteria Staphylococcus aureus 209 R are used as a test microorganism. A biocomposite disc with an antibiotic is placed in the center of a Petri dish inoculated with a test culture. The antibacterial properties of the obtained biocomposites are judged by the diameter of the growth inhibition zones of the test culture. The zone of no growth of the test culture when using biocomposites obtained on the basis of aerogels of bacterial cellulose, chitosan and sodium fusidin, as well as physiologically active compounds of polyphenolic nature (dehydroquartzin, resveratrol),

low molecular weight peptides (tinrostim), blood coagulation factors (thrombin, transglutaminase) is 23.3 ± 2.1 mm.

Thus, a biocomposite based on bacterial cellulose airgel has been developed, which has the ability to stop bleeding, containing chitosan as a hemostatic agent and antimicrobial agent, fusidic acid as an enhancer of antimicrobial action, physiologically active polyphenolic compounds (dehydroquartzin, resveratrol),

low molecular weight peptides (tinrostim). The resulting biocomposite based on a hydrogel of bacterial cellulose has high antibiotic activity against Staphylococcus aureus bacteria, hemostatic properties and can be used in medicine as wound dressings.

Claims (1)

A method of obtaining a biocomposite based on a bacterial cellulose airgel with hemostatic properties, which consists in obtaining a gel film of bacterial cellulose by cultivating a bacterial strain Gluconacetobacter sucrofermentans VKPM B-11267 under static conditions on a medium with molasses, separating the obtained gel film of bacterial cellulose from the culture medium and its purification, mechanical grinding of the purified gel film of bacterial cellulose for 10 min, obtaining a hydrogel a) bacterial cellulose-chitosan in a ratio of 80:20 by mixing a 2% solution of chitosan in 1% acetic acid, bacterial cellulose hydrogel, 25 % glutaraldehyde, with the addition of sodium fusidin in combination with one or more additional components, or b) bacterial cellulose: chitosan: gelatin: transglutaminase in a ratio of 5: 5: 15: 5, respectively, with the addition of sodium fusidine in combination with one or more additional components, and complement The individual components are selected from physiologically active polyphenolic compounds - dehydroquartzin or resveratrol, low molecular weight peptides - tinrostim, and / or blood coagulation factors - thrombin or transglutaminase, obtaining an airgel by freezing in a low-temperature refrigerator for a day and then freeze drying.