RU2468129C2 - Biopolymeric fibre, composition of forming solution for its obtaining, method of forming solution preparation, linen of biomedical purpose, biological bandage and method of wound treatment - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: composition of forming solution for formation of biopolymeric fibres includes polyethylene oxide, chitosan, organic acid and water. Or composition of forming solution for formation of biopolymeric fibres includes chitosan, water and component, selected from polyethylene oxide, polyvinyl alcohol or polyvinylpyrrolidone. Chitosan with molecular weight 30-40 kDa and polyethylene oxide with molecular weight 2000-8000 kDa are used. Composition additionally contains cellulose diacetate and biologically active substances. Method of forming solution preparation includes mixing of components in powder-like state and their dissolution with mixing to homogenous state. Linen of biomedical purpose, formed from biopolymer chitosan-based fibres, in order to obtain from it bandage for wound treatment, is subjected to swelling in physiological solution or distilled water. Additionally linen of biomedical purpose is subjected to thermal processing, after which it is placed into distilled water or physiological solution for swelling. Or linen is additionally processed with alkaline reagent, with further washing with distilled water, after which it is placed into distilled water for swelling. For wound treatment linen of biomedical purpose is applied on wound in form of biological bandage.

EFFECT: invention makes it possible to obtain biopolymer fibre with application of optimal compositions of textile composition based on chitosan and non-toxic polymer for stable electroformation of defect-free fibres, methods of modification of linen of biomedical purpose for obtaining bandage in form of wound covering are ecologically clean and economical.

2 tbl, 73 ex, 5 dwg

Description

The group of inventions relates to chemical and biochemical technology, in particular to methods for producing solutions for forming biopolymer fibers from chitosan, to producing biopolymer fibers and non-woven fibrous-porous materials from chitosan by electrospinning, as well as to medicine, specifically to new biological dressings based on chitosan intended for the treatment of wounds of various etiologies (burns of the II-IIIAB degree, donor sites, long-term non-healing wounds, trophic ulcers, pressure sores and other skin defects moat), which allows to accelerate the healing process, create an optimal environment for regeneration, protect the wound from the occurrence of the infectious process and trauma, and prevent the formation of gross scars. The group of inventions can be used in the chemical, biochemical and cosmetic industries, biology, medicine, pharmacology, as well as in research practice in these areas.

Amino polysaccharide of animal origin, chitosan, obtained from chitin of arthropod shells, is characterized by a number of valuable properties: non-toxic, completely loses antigenicity in the process of production, has high sorption ability, is compatible with most drugs, has antibacterial and antifungal effects, is biocompatible with human tissues, affects regeneration processes of damaged skin, biodegradable by the natural metabolic pathway, etc. An important feature of chitosan is The preservation, and in some cases, the improvement of these useful qualities in molded products based on it, is ongoing.

Chitosan is widely used in biotechnology, pharmacology and is the main component of many new medicinal, cosmetic and other drugs. Biocompatibility with living tissues, closeness in functional qualities to the components of the dermis in vivo, bioinertness, biodegradability, biocidal and other properties of chitosan determine the prospects of developing new materials for medical and biological purposes based on it.

The chitosan macromolecule has a hetero chain structure and is constructed from units of residues of D-glucosamine (mainly) and N-acetyl-D-glucosamine linked by β-1,4-glycosidic bonds. Currently, the term chitosan is usually called a copolymer with a degree of deacetylation (the number of units of D-glucosamine) above ~ 75 mol.% [Chitin and chitosan: Preparation, properties and application / Ed. K.G.Skryabin, G.A. Vikhoreva, V.P. Varlamova. M .: Science. 2002. 368 p.]. The structural formula of the chitosan macromolecule is given below, the n-x index corresponds to the degree of chitosan deacetylation.

и степени деацетилирования (СД) [Holme H.K., Hagen A., Dornish М. // Chitosan Per os: from Dietary Supplement to Drug Carrier. Grottammare: Atec. 2001. P.153-163; Куликов С.Н., Чирков С.Н., Ильина А.В. и др. // Прикладная биохимия и микробиология. 2006. Т. 42. №2. С.224-228; Шиповская А.Б., Фомина В.И., Казмичева О.Ф. и др. // Высокомолек. соед. 2007. Т.49Б. №12. С.2195-2199]. Например, высокомолекулярный хитозан со средневязкостной молекулярной массой

не растворим в воде и растворим в водных растворах органических и одноосновных неорганических кислот. Образцы низкомолекулярного хитозана с

и СД≥70 мольн.% хорошо растворяются в воде. С увеличением СД до 85 мольн.% усиливается антибактериальное действие полимера [Герасименко Д.В., Авдиенко И.Д., Банникова Г.Е. и др. // Прикладная биохимия и микробиология. 2004. Т.40. №3. С.301-306; Герасименко Д.В., Авдиенко И.Д., Банникова Г.Е. и др. // Современные перспективы в исследовании хитина и хитозана: Матер, седьмой Международ. конф. М.: Изд-во ВНИРО. 2003. С.233-238], повышается селективность полимерного материала [Агеев Е.П., Вихорева Г.А., Матушкина Н.Н. и др. // Высокомолек. соед. 2000. Т.42А. №2. С.333-339] и др. В медицине, фармакологии, косметологии целесообразнее использовать образцы хитозана в широком диапазоне молекулярных масс и со степенью ацетилирования СД≥80 мольн.%.It is noted that almost all the functional properties of chitosan depend on its molecular parameters, in particular molecular weight

and degrees of deacetylation (DM) [Holme HK, Hagen A., Dornish M. // Chitosan Per os: from Dietary Supplement to Drug Carrier. Grottammare: Atec. 2001. P.153-163; Kulikov S.N., Chirkov S.N., Ilyina A.V. et al. // Applied Biochemistry and Microbiology. 2006.V. 42. No. 2. S.224-228; Shipovskaya A.B., Fomina V.I., Kazmicheva O.F. et al. // High Molecule. conn. 2007.V.49B. No. 12. S.2195-2199]. For example, high molecular weight chitosan with a medium viscosity molecular weight

insoluble in water and soluble in aqueous solutions of organic and monobasic inorganic acids. Samples of low molecular weight chitosan with

and DM ≥70 mol% are well soluble in water. With an increase in DM to 85 mol%, the antibacterial effect of the polymer is enhanced [Gerasimenko D.V., Avdienko I.D., Bannikova G.E. et al. // Applied Biochemistry and Microbiology. 2004.V. 40. Number 3. S.301-306; Gerasimenko D.V., Avdienko I.D., Bannikova G.E. and others // Modern prospects in the study of chitin and chitosan: Mater, Seventh International. conf. M .: Publishing house VNIRO. 2003. S.233-238], increases the selectivity of the polymer material [Ageev EP, Vikhoreva GA, Matushkina NN et al. // High Molecule. conn. 2000. T. 42A. No. 2. S.333-339] and others. In medicine, pharmacology, cosmetology, it is more expedient to use chitosan samples in a wide range of molecular weights and with a degree of acetylation of DM ≥80 mol%.

Currently, one of the promising directions for the processing of chitosan into biomedical materials is the production on its basis of fibers with diameters from nano- (nm) to micrometers (μm), as well as non-woven fibrous-porous materials with nanoscale pores.

To date, the only high-performance and industry-approved method for producing polymer nanofibers and submicron diameter fibers is the electrodynamic method (electroforming). The method is based on the process of formation of thin polymer jets under the influence of an electric field of high tension, followed by drying of the jet and settling in the form of a fiber uniform in length. The use of nanofibers for the creation of non-woven materials for biomedical purposes is due to a number of unique properties inherent in the fibers of nanoscopic and submicron diameters, including a large specific surface area and ultra-small pore size. It is known that the small pore size promotes the filtration of nanosized particles already on the surface of the material, and also prevents the diffusion of the liquid in the pores of the material, effectively holding it inside. On the other hand, when using a non-woven material with nanoscale pores and the inclusion of drugs, precise dosing and targeted delivery of the drug to damaged tissues can be carried out. These properties are necessary in the clinical practice of using non-woven fibrous-porous material for improved absorption of the wound, reliable biological protection of the wound surface at the stage of restoration of the epithelium, creating the effect of a controlled effect on the regeneration processes, etc.

The known composition of the solution for forming fibers from chitosan electrodynamically, including chitosan in a concentration of C = 6-8 wt.% And trifluoroacetic acid or chitosan C = 8 wt.% And a mixture of trifluoroacetic acid with dichloromethane in a ratio of 90: 10-70: 30 [Ohkawa K., Cha D., Kim H. et al. // Macromolec. Rapid Communic. 2004. V.25. P.1600-1605. DOI: 10.1002 / marc. 200400253]. The electrospun fiber obtained from solutions of chitosan in trifluoroacetic acid is characterized by a diameter of d = 330-610 nm, and from solutions of chitosan in a mixture of trifluoroacetic acid with dichloromethane, d = 200-660 nm.

The disadvantage is the use of aggressive solvents - trifluoroacetic acid and dichloromethane, a small amount of which inevitably remains in the finished fiber. Trifluoroacetic acid has a strong acidity and quickly penetrates tissues, causing severe burns to the skin, eyes, mucous membranes, etc. Inhalation of trifluoroacetic acid vapor causes pulmonary edema. Dichloromethane is very volatile, it is metabolized in the body to carbon monoxide, which can cause acute poisoning. Prolonged integumentary contact with dichloromethane can cause its accumulation in fatty tissues and lead to burns. With prolonged work with dichloromethane, liver damage and neuropathy are possible. The maximum concentration limit of dichloromethane in the working area is 50 mg / m ³ , in the water of water bodies not more than 7.5 mg / l. A significant disadvantage is the instability of the electroforming process.

Known compositions of molding solutions for the electroforming of fibers from chitosan, including chitosan with DM = 56-65 mol.% At a concentration of C = 7 wt.% And acetic acid concentration C _K = 90% [Geng X., Kwon Oh-H., Jang J. // Biomaterials. 2005. V.26. P.5427-5432. DOI: 10.1016 / j.biomaterials.2005.01.06] or chitosan with CD-75-85 mol.% At a concentration of C = 3-5 wt.% And acetic acid C _K = 80-90% [Vrieze De S., Westbroek P., Camp TV, Langenhove Van L. // J. Mater. Sci. 2007. V.42. P.8029-8034. DOI: 10.1007 / s10853-006-1485-6]. The average diameter of the resulting electro-spun fiber is ~ 130 nm and 50-100 nm, respectively.

до 398 кДа), а также снижение концентрации уксусной кислоты (например, с C_K=90% до 80%) приводит к получению волокон с большим количеством дефектов.The disadvantage is the use of chitosan with a low degree of deacetylation, which limits the use of fiber in medical practice. In addition, a concentration of acetic acid close to glacial acetic acid is used, which is environmentally and economically not feasible. A significant drawback is also the instability of the process of electroforming fiber: a slight increase in the concentration of chitosan in solution (for example, from 7 wt.% To 8 wt.%) Or medium viscosity molecular weight of chitosan (for example, with

to 398 kDa), as well as a decrease in the concentration of acetic acid (for example, with C _K = 90% to 80%) leads to the production of fibers with a large number of defects.

и СД=75-99.5 мольн.%. Полученные волокна перерабатывают в иглопробивной нетканый материал и изготовляют салфетки или тампоны.A method for producing chitosan fibers of linear density 0.52-1.0 Tex from a solution of polymer C = 3-4 wt.% In 2% acetic acid by the method of wet molding in a precipitation bath containing 2% NaOH and 10% Na ₂ SO ₄ , followed by die drawing from -45 to + 90% and plasticizing drawing from 20 to 110% [Illarionova E.L., Kalinina T.N., Chufarovskaya T.I., Khokhlova V.A. // Chem. fiber. 1995. No. 6. S.18-22]. In this case, chitosan is used with

and SD = 75-99.5 mol.%. The resulting fibers are processed into needle-punched non-woven material and wipes or tampons are made.

Disadvantages: the method of wet molding into a precipitation bath and, accordingly, the low productivity of the process, the need for die and platification drawing. The goal - obtaining fiber from chitosan by the electrostatic method - was not set in the method.

The possibility of their modification, including by mixing chitosan with other polymers, contributes to the expansion of the areas and effectiveness of the use of chitosan-containing materials of medical and biological purposes. The most promising are mixtures of chitosan with biologically inert artificial multi-purpose polymers (used in medicine, pharmacology, cosmetology, etc.): polyethylene oxide [Alekseev V.L., Kelberg E.A., Bronnikov S.V., Evmenenko G. BUT. // High Molecule. conn. 2001.V. 43A. No. 10. P.1856-1860], polyvinyl alcohol [Mukhina V.R., Pastukhova N.V., Semchikov Yu.D. et al. // High Molecule. conn. 2001.V. 43A. No. 10. S.1797-1804; Vnuchkin A.A. // Abstract. Cand. chemical sciences. SPb. 2009], polyvinylpyrrolidone [RF Patent No. 2247555, IPC A61K 7/48, A61K 31/14, A61K 31/722, A61P31 / 04; RF patent No. 2379025, IPC A61K 9/06, A61K 31/79, A61K 31/722], cellulose diacetate [Du J., Hsieh Y.-L. // Cellulose. 2009. V.16. P.247-260. DOI: 10.1007 / s10570-008-9266-9] and others.

Mixed chitosan-containing materials can be obtained in the form of electrospun fibers and non-woven fibrous-porous canvases from a common molding solution obtained by mixing an aqueous acid solution of chitosan and an aqueous solution of an auxiliary polymer. The addition of a second polymer component to the molding solution of chitosan leads to a stable and reproducible electrospinning and to obtain fiber with virtually no defects.

и 1300 кДа, степенью деацетилирования СД=77-78 мольн.% и поливиниловый спирт в соотношении компонентов 70:30-30:70 с общей концентрацией полимера в растворе С_П=1-4.5 мас.%, муравьиную кислоту или 0.2 М уксусную кислоту [Ohkawa К., Cha D., Kim H. et al. // Macromolec. Rapid Communic. 2004. V.25. P.1600-1605. DOI: 10.1002/marc.200400253]. Хитозан растворяют в растворе кислоты, поливиниловый спирт - в воде, затем осуществляют смешение растворов в заданном соотношении компонентов. Волокна, полученные из раствора смеси хитозан: поливиниловый спирт = 70:30, характеризуются большим количеством дефектов в виде утолщений и капель. Волокна, полученные из раствора смеси хитозан: поливиниловый спирт = 50:50 с использованием хитозана с в муравьиной кислоте имеют диаметр d=80-170 нм, из раствора смеси хитозан:поливиниловый спирт = 30:70-d=110-220 нм. Волокна, полученные из раствора смеси хитозан: поливиниловый спирт = 50:50 с использованием хитозана с

в муравьиной или 0.2 М уксусной кислоте характеризуются d=120-270 нм.A known composition of the molding solution for producing chitosan-containing fiber by the method of electrodynamic molding, including chitosan with

and 1300 kDa, the degree of deacetylation of SD = 77-78 mol.% and polyvinyl alcohol in the ratio of components 70: 30-30: 70 with a total polymer concentration in the solution With _P = 1-4.5 wt.%, formic acid or 0.2 M acetic acid [Ohkawa K., Cha D., Kim H. et al. // Macromolec. Rapid Communic. 2004. V.25. P.1600-1605. DOI: 10.1002 / marc. 200400253]. Chitosan is dissolved in an acid solution, polyvinyl alcohol in water, then the solutions are mixed in a given ratio of components. Fibers obtained from a solution of a mixture of chitosan: polyvinyl alcohol = 70:30 are characterized by a large number of defects in the form of thickenings and drops. Fibers obtained from a solution of a mixture of chitosan: polyvinyl alcohol = 50:50 using chitosan with in formic acid have a diameter of d = 80-170 nm, from a solution of a mixture of chitosan: polyvinyl alcohol = 30: 70-d = 110-220 nm. Fibers obtained from a solution of a mixture of chitosan: polyvinyl alcohol = 50:50 using chitosan with

in formic or 0.2 M acetic acid are characterized by d = 120-270 nm.

The disadvantage is the low degree of chitosan deacetylation, the use of formic acid (which is unacceptable when obtaining biomedical materials). In addition, stable spinning of defect-free fiber is observed only from solutions of chitosan: polyvinyl alcohol mixtures with a high content of the second polymer component (> 50%). In this connection, the main fiber content is polyvinyl alcohol, which, unlike chitosan, is not a biologically active polymer and does not exhibit antibacterial, reparative, and other properties.

A significant part of the literature and patent sources relates to the process of electroforming, properties and morphology of bicomponent nanofibers from mixtures of chitosan with polyethylene oxide in different proportions of components.

Known compositions for electroforming chitosan-containing fiber from solutions of mixtures of chitosan with polyethylene oxide in relatively dilute acetic acid. For example, from solutions of chitosan: polyethylene oxide = 50:50 or 67:33 mixtures with a total polymer concentration of C _P = 4-6 wt.% In 2% acetic acid, fibers with a diameter of 80-180 nm are obtained [Duan B., Dong S., Yuan X., Yao K. // J. Biomater. Sci. Polymer Edn. 2004. V.15. No. 6. P.797-811], from solutions of chitosan: polyethylene oxide = 25:75 mixtures with a total polymer concentration of C _P = 5 wt.% In 3% acetic acid, fibers with a core-shell structure and d = 340-495 nm [Zhang J.-F., Yang D.-Z., Xu F. et al. // Macromolec. 2009. V.42. Number 14. P.5278-5284. DOI: 10.1021 / ma900657y]. Nanofibers from solutions of chitosan: polyethylene oxide mixtures with a total polymer concentration of C _P = 2.2-3 wt.% In 0.5 M acetic acid are obtained only when the ratio of polymer components in the mixture is 60:40 [Bhattarai N., Edmondson D., Veiseh O. et al . // Biomaterials. 2005. V.26. P.6176-6184. DOI: 10.1016 / j.biomaterials.2005.03.0.0]. To obtain a nanofiber from solutions of chitosan: polyethylene oxide = 90:10 mixtures in 0.5 M acetic acid, a surfactant (Triton X-100 ™ in an amount of 0.3%) and a co-solvent (dimethyl sulfoxide in an amount of 10%) are added to the system.

The disadvantage of all compositions, with the exception of the composition of chitosan: polyethylene oxide = 90:10, is the low content of chitosan in the molding solution. Obtaining nanofibers from a solution of a mixture of chitosan: polyethylene oxide in a component ratio of 90:10 requires the additional introduction of a nonionic surfactant and dimethyl sulfoxide. All this significantly reduces the biocompatibility, biodegradability and other useful properties of electro-spun fiber.

Also known are compositions for electroforming a chitosan-containing nanofiber from solutions of mixtures of chitosan with polyethylene oxide in concentrated acetic or formic acid.

The known composition of the spinning solution for forming nanofibers with d = 60-145 nm, including chitosan and polyethylene oxide or N-carboxyethylchitosan and polyethylene oxide in a ratio of 50:50 components with a total polymer concentration in the solution With _P = 1.7-2 wt.%, Acetic acid concentration With _K = 85% or formic acid With _K = 85% [Penchev H., Paneva D., Manolova N., Rashkov I. // Macromolec. Biosci. 2009. No9. P.884-894. DOI: 10.1002 / mabi.200900003].

The disadvantages are the low content of chitosan and the low total concentration of polymers in the molding solution, which is not economically feasible. The content of chitosan biopolymer in the finished fiber is also small.

A known composition of the molding solution, including chitosan and polyethylene oxide in a ratio of components of 62.5: 37.5-30: 70 with a total polymer concentration of C _P = 2.5-4 wt.%, Acetic acid With _K = 32-45%, from which the fiber is formed with d = 100-180 nm [Klossner RR, Queen HA, Coughlin AJ, Krause WE // Biomacromolec. 2008. V.9. No. 10. P.2947-2953]. In this case, chitosan is used with diabetes = 75-85 mol%. Chitosan is dissolved in acetic acid With _K = 80-90%, polyethylene oxide in water (the preparation time for homogeneous solutions of individual polymers is 24-72 hours), then the resulting solutions are mixed in a given ratio of components. The effect of chitosan content in the molding solution on the diameter of the electro-spun composite fiber was also noted. Thus, finer fibers are obtained by electrospinning from solutions of mixtures of chitosan: polyethylene oxide with a high content of chitosan.

The disadvantage is that the solution and the electro-spun fiber contain a relatively small amount of biocompatible polymer, a relatively low degree of deacetylation of the chitosan used, as well as the length and multi-stage process of obtaining the molding solution. The task of obtaining fibers from aqueous solutions of water-soluble chitosan in the method was not posed.

There are a number of patents describing a method for producing fibers from chitinchitosan and multicomponent composite fibers from a mixture of chitosan with other natural and synthetic polymers, as well as non-woven fibrous-porous material based on them.

A known method of electroforming nanofibers from solutions of chitinchitosan in N-methylmorpholine oxide, hexafluoro-2-propanol, hydrated hexafluoroacetone and formic acid [Patent KR 2005 / 10-0032656 A].

The disadvantage is the use of aggressive and technologically unsuitable solvents.

A method is known biocomposite electrospinning nanofibers from a mixture of chitosan or oligohitozana with alginic acid in a ratio of chitosan components (oligohitozan): alginic acid in the finished fiber, 20: 80-1: 99, using as polymers and oligomer aqueous solutions of acetic solvent (C = 1% _K ), hydrochloric (With _K = 1-5%), etc. acids [Patent WO 2007/093805 A1, IPC A61L 15/28; C08J 5/18; D01F 8/18].

Disadvantages: the maximum content of chitosan aminopolysaccharide in dry fiber does not exceed 80%, the inability to obtain a biocomposite fiber from aqueous polymer solutions.

Known methods for producing the electrostatic method of composite nanofibers and non-woven material based on them from mixtures of chitosan with synthetic polymers: polyamides [Patent KR 2007 / 10-0749966 B1; Patent CN 2009 / 10-1502759 A], polyesters (for example, polyethylene terephthalate) [Patent KR 2006 / 10-0652496 B1].

The main disadvantage is the use of aggressive solvents (hexafluoroisopropanol, formic acid, etc.) to dissolve the synthetic polymer.

A known method for producing non-woven fibrous functional material containing a synthetic polymer polylactide, biopolymers of chitosan, peptide, zein, gelatin, collagen [JP patent 2008/38271 A]. A method is described for producing a biodegradable composite nonwoven material from nanofibers containing, wt%: chitosan 0-50, polylactide and polyglycolide 49.9-99.9, anti-inflammatory and antibacterial drugs 0.1-25 [Patent CN 2009 / 10-1491689 A]. A known method for producing fibrous scaffold for biomedical purposes, including macromolecules of synthetic polymers - polylactide, polyglycolide, copolymers of polylactide and polyglycolide, polyhydroxybutyrate, polyhydroxyvaleriate, biopolymers - chitosan, chitin, alginic acid, collagen and gentauron 200, 10 and 200 gelatin, 10 and 200 gelatin 2 IPC A61L 27/14, A61L 27/20, A61L 27/40]. An electrostatic method is described for the production of a nonwoven material containing chitosan, a biodegradable natural polymer (collagen, gelatin, polyglutamic acid, silk, cellulose, alginic acid, hyaluronic acid), a biodegradable synthetic polymer (polyethylene oxide, polyvinyl alcohol polyhydroxybutyric acid, polyhydroxybutyric acid, copolymers of polylactide with polyglycolide, polycaprolactone, polyester, polyanhydride) and cell growth factor [Patent KR 2008 / 10-0104932 B1]. Electro-spun amorphous pharmaceutical compositions are described for the manufacture of stable solid dispersions of an amorphous form of a drug in polymer nanofibers, consisting of a water- or non-water-soluble fiber-forming polymer, or combinations thereof and particles of a drug substance, in particular chitosan and its derivatives, polyethylene oxide, polyvinyl acetate, polyvinylpyrrolidone, polyvinyl alcohol, hyaluronic acid, alginate, carrageenan, cellulose derivatives (Na-carboxymethyl cellulose, m ethyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, cellulose acetate phthalate), non-crystalline cellulose, starch and its derivatives (such as hydroxyethyl starch, sodium starch glycolate, polychloramide, starch, from Rohm Pharma), poly-alpha-hydroxy acids, poly-alpha-amino acids and their copolymers, polyorthoesters, polyphosphazines or polyphosphoesters [RF Patent No. 23 31411, IPC A61K 9/48, A61K 9/20, A61K 9/52, A61K 9/22].

The main disadvantages of these compositions are their multicomponent composition, a large number of auxiliary (s) polymer (s), complex structural organization and high cost.

There are also patents describing the compositions of molding solutions for forming two- and three-component composite chitosan-containing fibers with a relatively high chitosan content, methods for producing and compositions of these fibers and non-woven fibrous-porous materials based on them, including chitosan and additionally polyethylene oxide and / or other inert synthetic and natural polymers.

Known methods for producing three-component composite fibers with d = 50-500 nm and the composition of the spinning solutions for their formation. For example, a method is proposed for producing a composite nanofiber containing chitosan: serine: polyethylene oxide in a ratio of components of 66:17:17 [JP Patent 2008/163520 A]. Describes a method for producing non-woven fibrous material from nanofibers containing, wt.%: Chitosan 10-90 and a mixture of polyethylene oxide with polyvinyl alcohol, the rest [Patent CN 2004/1569254 A]. The ratio of polyethylene oxide: polyvinyl alcohol varies from 90:10 to 10:90. The molding is carried out from solutions with a total polymer concentration of C _P = 4-8 wt.% In acetic acid with an electric field voltage of 5-30 kV, a volume flow of 0.1-0.5 ml / h, and an interelectrode distance of 5-25 cm.

The main disadvantage of these methods and compositions is the maximum chitosan content in the electro-spun fiber does not exceed 90%.

There is a method of producing a two-component chitosan-containing fiber with d = 60-120 nm and a chitosan content of up to 96.3% by electroforming solutions of a mixture of chitosan with polyethylene oxide or polyvinyl alcohol in trifluoroacetic acid or other trihalo-carboxylic acids [Patent WO 2009/011944 A2, IPC D01D 6/02 5/00, C12N 0/00]. In this case, chitosan is used with DM = 72-83 mol%. The resulting material is additionally treated with a crosslinking agent - glutaraldehyde.

The disadvantages of the method are the use of aggressive carcinogenic solvents, which excludes the use of the resulting material in medicine, pharmacology, etc .; additional processing using toxic glutaraldehyde, which leads to the formation of crosslinks between glutaraldehyde, chitosan and polyethylene oxide or polyvinyl alcohol, accompanied by the loss of water solubility, biodegradability and elasticity of the fiber and the material as a whole. The goal - the production of nanofibers from aqueous solutions of mixtures of chitosan with polyethylene oxide or polyvinyl alcohol - was not set in the method.

Also known are methods of producing chitosan-containing artificial fibers having antibacterial activity against Staphylococcus aureus. Streptococcus salivarius, Pseudomonas aeruginosa, biocompatibility and biodegradability, from chitin by grinding chitin, deacetylation to chitosan with DM = 91 mol.% Or more, xanthogenation and wet molding [RF Patent No. 2258102, IPC D01F 4/00] ,0101 4/00 as well as from chitosan by grinding chitosan, adding NaOH solution, carrying out chitosan mercerization followed by xanthogenization, wet forming chitosan from viscose obtained, finishing and drying [RF Patent No. 2278188, IPC D01F 4/00, С08В 9/00]. The resulting fiber contains 10-100 wt.% Chitosan, has a thickness of 16.6-17.2 tex, strength 105-125 mN / tex, elongation at break 11-13%.

The disadvantage is the length and complexity of the method; micron diameter, high strength and low elastic properties of the fiber. The task of obtaining chitosan-containing nanofibers with antibacterial activity by the method of electrostatic molding to obtain a therapeutic coating for wounds in the method was not posed.

Meanwhile, the use of electrospun non-woven fibrous-porous materials from chitosan fibers with nano- and submicron diameters as wound dressings or other biological dressings is extremely promising. This is due to both the valuable healing functions of the chitosan aminopolysaccharide and the unique special properties of electrospun fibers and materials based on them, determined by the small size (diameter) of the nanofiber, the absence of extended defects, the high specific surface of the material, etc. However, to date, the use of non-woven fabric from Chitosan nanofibers are not known in clinical practice.

The relevance of the development and improvement of wound dressings is dictated by the tasks of modern surgery and the low efficiency of traditional dressings. In medicine, the problem of obtaining artificial materials with physico-chemical and biological properties close to the properties of the skin, which can be used as wound coverings, has long been a problem.

The conditions ensuring optimal wound healing are: moisture of the wound surface, sufficient oxygen tension in the wound tissues, the absence of excess wound exudate, prevention of secondary infection, protection against external traumatic effects and heat loss.

Based on this, the requirements for modern dressings are formulated. The role of the dressing is not only to protect the wound from the external environment and mechanical trauma, its purpose is to actively influence the wound process by creating the best conditions for healing and the necessary dosage of drugs, as well as a favorable microclimate achieved by optimal vapor and gas permeability and timely drainage exudate. In addition, the dressing should be well modeled on the wound, fit snugly against the wound surface, have sufficient elasticity and mechanical strength, be non-traumatic, not have toxic and local irritating effects, have no antigenic and pyrogenic properties, be resistant to sterilization, comfortable to wear, comfortable in the application and removal, long-term operation on the wound, have a long shelf life. The wound coverings used for this purpose must meet the following requirements: isolate the wound from infection, protect it from drying out, effectively remove excess wound exudate and its toxic components, provide a moist environment, gas exchange, constant temperature around the wound, reduce heat transfer, and have certain antibacterial properties create an optimal environment for regeneration and epithelization, prevent trauma to the wound, loss of heat, protein and tissue fluid, protect the wound from contamination macroparticles, provide the opportunity to be carriers for drugs. Biomaterials used to create wound coverings must be sufficiently strong and flexible, resistant to sterilization, convenient for use by the patient and medical staff, biocompatible with dermal tissues, as well as biodegradable [Shapovalov SG // FAR Mindex Practitioner. 2008. No8. S.38-46].

However, none of the currently available biocoatings fully satisfy surgeons. All this poses the task of developing a new generation of materials for solving surgical problems that can not only perform protective functions (closing the wound from external infection, antibacterial effects, dosed sorption of wound exudate, etc.), but also contribute to the development of repair processes up to the complete epithelization of the damaged surface . In addition, one of the properties of new biocoatings should be their effective effect on the wound, which will reduce the number of painful dressings and significantly increase the interval between them.

Currently, most successfully solve this problem, coatings made in the form of sheets or films from a mixture of synthetic polymers and polymers of biological origin, since coatings made only from synthetic polymers, for example monocomponent polyurethane [US Patent No. 2871218, IPC C08G 18/66; C08G 18/76; C08G 18/00] or multicomponent mixtures of polyurethane and polyallyl ether [German Federal Patent No. 34098558], have good physical and mechanical properties, are quite durable, water- and vapor-permeable, but have only a protective function and are not capable of stimulating regeneration processes. On the other hand, coatings made only of biopolymers, for example monocomponent collagen [US Patent No. 4578067, A61L 15/32; A61L 15/16; A61F 13/16; A61L 15/00] or multicomponent from a mixture of gelatin and chitosan [US Patent No. 4572906, A61L 26/00; C08L 5/08; C08L 89/06; A61F 13/00; A61K 31/70; A61K 37/00; C09D 3/04], a mixture of collagen, chitosan and glycosaminoglycans [Patent WO 88/10123, IPC A61L 27/00; A61L 27/26; A61L 27/34; C08L 89/06; C12N 5/00; A61L 27/00; C08L 89/00; C12N 5/00; A61L 15/04], they stimulate regeneration processes well, but have low physical and mechanical properties: brittle in a dry and fragile in a wet state, quickly decompose by enzymes in biological fluids of the wound, which leads to the loss of protective functions.

There are many known samples of wound dressings that differ in chemical composition. Of the wide range of polymer wound coatings that currently exists, biodegradable polysaccharide coatings, which can be useful both in the early stages of wound healing and later ones, are the most suitable for all medical and biological requirements. The general properties of biocompatible polysaccharide materials (including chitosan) are their hydrophilicity, which determines their high adsorption capacity (up to 5000%), good wound adhesion, lack of toxicity and irritating effect, as well as hemostatic properties. Their stimulating effect on the healing processes of wounds and burns was noted, which contributes to the more rapid development of granulation tissue, acceleration of epithelization. The presence of polysaccharide materials on the wound favorably affects the repair processes at all stages of the wound treatment. The main problem of obtaining coatings from natural polysaccharides is the achievement of good mechanical strength of the coating and stability on the wound. The development of biodegradable polymer coatings with high sorbing ability and various absorption times is currently the most relevant area in the field of creating effective biological dressings for treating wounds.

Currently, biological materials based on the aminopolysaccharide of chitin and its deacetylated derivative of chitosan are widely studied to solve the above problem.

In recent years, preparations based on chitosan and its compositions with other natural, artificial or synthetic polymers are used in powdered form in regenerative medicine [RF Patent No. 2086247, IPC A61K 35/70; Alekseev A.A., Feofilova E.P., Tereshina V.M. et al. // Combustiology. 2002. No4. http://burn.ru/all/number/show/?id=3493] or gel-like dermatoprotective agents [RF Patent No. 2258515, IPC A61K 31/722, A61K 31/355, A61K 9/08, A61P 17/02] perforated film coatings for the treatment of wounds [RF Patent No. 2219954, IPC A61L 15/28], hydrocolloid application coatings [RF Patent No. 2219955, IPC A61L 15/32, A61L 15/22, A61P 17/02], sponge-type coatings [ RF Patent No. 2240830, IPC A61L 15/44], biological compositions [RF Patent No. 2108114, IPC A61L 15/28], hydrogel dressings [RF Patent No. 2270646, IPC A61F 13/02, A61L 15/22, A61L 15 / 44, A61L 15/60] and others. Moreover, materials with a fibrous structure are marked higher e kinetic characteristics, as well as improved biological properties.

Chitosan coatings are air- and vapor-permeable, inhibit invasion from the outside of microorganisms, create an optimal microclimate in the wound, and promote cell growth and proliferation in the wound. Chitosan, in addition to stimulating proliferation in the first stages of the wound healing process, is very useful in the final phase of healing - restructuring of the scar. Its presence in the wound helps to avoid the formation of gross scars.

A dressing is known, one of the variants of which contains chitosan and is made in the form of an elastic perforated film [RF Application No. 99100105/14, IPC A61L 15/26, A61L 15/28, A61L 15/64].

The disadvantages are: layering and, as a result, the impossibility of complete congruency with the wound surface, the removal of the wound discharge by absorbing the dressing of the dressing, which leads to the inevitability of a frequent change of dressings.

Also known is a biologically active polymer sorbent film created on the basis of chitosan [Kildeeva N.R., Vikhoreva T.A., Larionova A.S., Galbraich L.S. // Modern approaches to the development of effective suture materials and polymer implants: Mater. III international Conf. M. 1998. 130-131 S.], containing the enzyme trypsin and modified with a cross-linking reagent - sodium dodecyl sulfate, which also exhibits antimicrobial properties.

The disadvantages are: poor simulations on the wound, low strength of the dressing in the wet state, which creates the likelihood of the wound being discharged from the dressing into the wound zone, and the presence of a reagent toxic to the human body - sodium dodecyl sulfate.

Known polymer film on the wound based on chitosan, having a thickness of 5-50 μm, modified with a cross-linking agent - epichlorohydrin, which may also contain 0-20% polyvinyl alcohol or polyethylene glycol and antibacterial or antiseptic substances [Patent WO 2001/0141820 A1, IPC A61L 15 / 28; A61L 15/16].

Disadvantages: relatively low adsorption capacity of the film, fast biodegradation of the film in the wound environment, which makes it difficult to clean the wound, because wound discharge adsorbed by the film and biodegradation products remain in the wound, complete removal of the film is possible only when used on relatively dry wounds.

Known dressing, which is a perforated film and containing chitosan in the form of salts of organic acids (acetic, succinic or glycolic), glutaraldehyde, polyvinyl alcohol and a biologically active additive in the form of CO ₂ extracts of medicinal plants [RF Patent 2219954, IPC A61L 15/28 ].

Disadvantages of the dressing: insufficient congruency with the wound surface, low adsorption capacity, limited vapor permeability, the inability to timely remove excess wound discharge due to perforation in the form of holes or notches. In the case of the use of medicinal plants (for example, yarrow, sea buckthorn, plantain, eucalyptus, wormwood, St. John's wort, coriander) as a biologically active additive of CO ₂ -extracts, the likelihood of developing allergic reactions increases. The disadvantages are also the complex composition of the dressing, the inclusion of toxic glutaraldehyde, low elastic properties due to the increase in crosslinking between glutaraldehyde, chitosan and polyvinyl alcohol.

Known biological composition for the treatment of wounds "Collachite" containing chitosan, glutaraldehyde and antiseptic drugs - synthetic or herbal origin, which is biodegradable [RF Patent No. 2108114, IPC A61L 15/28]. The composition "Collachite" can be made in the form of a film or sponge.

The disadvantages are: high adhesion to the wound surface, the inability to use at all stages of the wound process, the need for frequent dressings, fragmentation of the dressing as a result of lysis of the dressing with an increase in the exposure time of the dressing on the wound, difficulties in dressing associated with the adhesion of dressings to the wound. If there is even a moderate amount of wound in the wound, lysis of the coating is noted during the first days of its use and the formation of a gel-like mass on the wound surface, which required replacement of the coating and the need to control its integrity. In addition, toxic glutaraldehyde is used to obtain the dressing.

Sponge dressings are known for treating wounds from a mixture of gelatin, chitosan and formaldehyde [Chinese Patent No. 1097980], cellulose and chitosan [Japanese Application No. 0376029], collagen and chitosan [Patent WO No. 8504133, IPC A01N 25/10; A61F 13/00; A61F 2/10; A61K 47/00; A61K 9/00; A61K 9/22; A61K 9/70; A61L 15/00; A61L 15/32; A61L 15/44; A61L 15/64; A61L 17/00; A61L 27/24; A61L 27/56; A61L 27/58; С08Н 1/00; C08L 89/00; C08L 89/06; C09H 1/00].

The main disadvantages of these sponges are low hygroscopicity, high density, relatively low wound healing activity, caused either by partial destruction of the biodegradable components of the sponge dressing, or by the adhesion of the sponge to the wound and poor oxygen supply to the repair zone. Often, antibacterial agents (usually furatsilin and gentamicin) are introduced into their composition. However, these substances are present in excess and often cause allergic reactions.

A serious drawback of many dressings is their adhesion to the wound, as a result of which the dressings become painful, and most importantly, injuries to regenerating tissues occur. Many of the positive properties of dressings are reduced due to damage caused by removing the dressing adhered to the healing wound [Turner T.D., Schmidt R.J., Harding K.G. Advances in wound management. London: John Wiley & Sons, 1986. C.23-29]. Adhesion of a dressing to a wound occurs for various reasons. In most cases, “bonding” of the coating to the wound surface occurs. The role of "glue" is performed by exudate, which forms a scab when dried. The strength of such a compound depends on the chemical nature of the polymer in the dressing.

Collagen-chitosan spongy wound coverings are also known [Certificate for utility model of the Russian Federation No. 8608 U1, IPC A61L 15/44], which are sponges for treating wound surfaces in the form of a porous elastic body made from a mixture of collagen fibrils and chitosan fibers, and the fibrils are fixed in space using a network structure based on chitosan molecules and a structure-forming agent containing a biologically active substance or its mixture with antibiotics or antiseptics.

Disadvantages: when using these wound dressings, the wound exudate is rapidly absorbed and the sponge swells. The sponge gradually completely “sticks” to the surface of the wound, turning into a crust. With abundant exudation, the sponge must be changed 1 time per day. Frequent change of dressings makes dressings painful, leads to disruption of wound epithelialization, which injures the young epithelium, lengthens the duration of treatment and often contributes to the formation of rough scars.

In addition, common disadvantages for all spongy coatings are: the ability of thick layers of the sponge to soak in wound exudate and play the role of a substrate for the microbial flora of the wound. The large pore diameter of the sponge promotes the germination of granulations and the traumatic removal of the coating from the surface of the wounds.

Regardless of the etiology and pathogenesis of wounds, the principles of external treatment of skin defects are general and include: cleansing of necrotic masses, antiseptic treatment, stimulation of growth of granulations and the process of epithelization, mechanical protection of wounds. However, there are many ways to treat wounds.

Traditionally, lotions, wet-drying dressings, ointments, emulsions, suspensions of various medicines are used for this purpose. However, these drugs are poorly tolerated by patients, especially with large areas of damage, high soreness of wounds, frequent change of dressings (wet dressings dry to the bottom of the ulcer, ointment - prevent gas exchange on the surface of the wound, poorly absorb wound exudate). Therefore, at present, preference is given to wound coverings, which include a medicinal substance.

A known method of treating wounds [RF Patent No. 2108078, IPC A61F 13/02, A61F 13/54, A61L 15/00] by applying over the wound a perforated film dressing made of a polyethylene film with Breitman complex powder applied on its surface in the form of a mixture talc, cephalolexin, streptomycin, erythromycin, terramycin, tetracycline, vibromycin, synthomycin, neomycin, kanamycin, nystatin, dactarin, canesten and rivanol. Dressings are carried out as necessary after 24, 48 and 72 hours. Treatment is carried out until the wounds are completely healed.

Disadvantages: the presence in the dressing material of a large number of different types of antibiotics increases the frequency of allergic reactions, and the plastic film has neither barrier nor sorption properties and performs only the function of a mechanical barrier and is foreign to wound tissues.

A known method of treating wounds [RF Patent No. 2265454, IPC A61K 47/36], which consists in applying a perforated multicomposite film to the wounds, which contains (wt.%): Polyvinyl alcohol 9.8-19.8, chitosan 78.3-89.4, anesthetic 0.1 -0.2, an antibacterial substance in the form of an antibiotic of the aminoglycoside series, for example gentamicin, 0.5-2.0.

The disadvantages of this method are that the applied dressing has a low mechanical strength, since it does not contain binding components. In addition, it contains a large amount of polyvinyl alcohol, which is not a biologically active polymer and, partially dissolving in wound exudate, often has a locally irritating effect.

A known method of treating wounds [RF Patent No. 2386436, IPC A61K 31/14], which consists in applying a multicomposite dressing to the wound, which is a combination of a gel based on a mixture of water-soluble polysaccharides and a film containing at least fluoro rubber latex and a polysaccharide of plant origin, which is applied over the gel. The dressing is changed every 2-4 days until the wound is completely epithelized. If necessary, before applying the dressing material, debrizing is carried out - the wound toilet, which includes cleaning the wound of microorganisms, dead tissue, blood and its clots, causing a phagocytic inflammatory reaction. As a gel, take the hydrogel according to RF patent No. 2180856, IPC A61L 15/28 or RF patent No. 2194535, IPC A61L 15/28, mainly containing a water-soluble cellulose derivative, salt of alginic acid, carrageenan or pectin, or a mixture thereof, water and an antiseptic. As a film, a monolayer film is taken according to the patent of the Russian Federation No. 2193896, IPC A61L 15/28, mainly containing fluorine rubber latex, a water-soluble cellulose derivative or a salt of alginic acid, or carrageenan, or pectin, or a mixture thereof and an antiseptic.

The disadvantages of this method are the complexity and complexity of the application, especially with extensive wound defects, insufficient absorption of the wound, lack of opportunities to expand the range of therapeutic effects on the wound by including additional drugs, which narrows the possibilities of using the method in various fields of surgery.

и 900 кДа. Сформованное волокно имеет диаметр d~80-400 нм. Получение волокна с d~80-200 нм осуществляют из формовочных растворов, содержащих хитозан в количестве более 75 мас.% от общей массы полимера в растворе. При этом отмечается, что воспроизводимое электроформование бездефектного волокна наблюдается при содержании хитозана в смеси не менее 80-85 мас.% от общей массы полимера в исходном формовочном растворе. Электропряденое волокно, полученное из раствора смеси хитозан: полиэтиленоксид = 95:5 и 90:10 характеризуется большим количеством дефектов, для снижения которых формование волокна проводят при T=40 и 70°С.The closest in composition to the claimed aqueous acidic solution for forming biopolymer fibers from chitosan and the method for its preparation is a solution containing chitosan and polyethylene oxide with a total polymer concentration C _P = 1.33-4.4 wt.%, Acetic acid concentration C _K = 50-90 % [Desai K., Kit K., Li J., Zivanovic S. // Biomacromolec. 2008. V.9. Number 3. P.1000-1006]. Chitosan and polyethylene oxide are separately dissolved in acetic acid, the resulting solutions are mixed in the ratio of the components 95: 5, 90:10, 75:25, 50:50 and the fiber is formed by the electrodynamic method at room temperature. Chitosan with a degree of acetylation of SD = 67-83 mol.% Is used (for obtaining a defect-free fiber, the most optimal is SD = 70 mol.%), Polyethylene oxide with a weight average molecular weight

and 900 kDa. The formed fiber has a diameter of d ~ 80-400 nm. Obtaining fibers with d ~ 80-200 nm is carried out from molding solutions containing chitosan in an amount of more than 75 wt.% Of the total polymer mass in solution. It is noted that the reproducible electroforming of a defect-free fiber is observed when the chitosan content in the mixture is at least 80-85 wt.% Of the total polymer mass in the initial molding solution. Electro-spun fiber obtained from a solution of a mixture of chitosan: polyethylene oxide = 95: 5 and 90:10 is characterized by a large number of defects, to reduce which the fiber is formed at T = 40 and 70 ° C.

Disadvantages: the use of chitosan with a relatively low degree of deacetylation, which limits the biomedical use of fiber; the use of polyethylene oxide with a relatively low molecular weight; low concentration of a polymeric substance (a mixture of chitosan and polyethylene oxide) in the molding solution, which reduces the productivity of the electroforming process; a relatively low (less than 90%) content of a biocompatible chitosan polymer in a solution suitable for stable electrospinning, and, accordingly, in the finished fiber; the need to use elevated temperature to obtain electrospun fiber with a chitosan content of more than 90%, which is economically and environmentally unfeasible.

The closest in composition to the claimed aqueous solution for forming biopolymer fibers from chitosan and the method for its preparation is a solution containing water-soluble chitosan and polyethylene oxide or oligochitosan and polyethylene oxide with a total polymer concentration C _P = 5 wt.%, Deionized water [Zhang J.-F , Yang D.-Z., Xu F. et al. // Macromolec. 2009. V.42. Number 14. P.5278-5284. DOI: 10.1021 / ma900657y]. Water-soluble chitosan, oligochitosan and polyethylene oxide are dissolved in deionized water, the resulting solutions are mixed in the ratio of components of water-soluble chitosan: polyethylene oxide = 75:25, 50:50 and 25:75, oligochitosan: polyethylene oxide = 25:75 and the fiber is formed by the electrodynamic method at T = 70 ° C. A fiber formed from an aqueous solution of a mixture of oligochitosan with polyethylene oxide has a diameter of d ~ 600 nm, and water-soluble chitosan with polyethylene oxide has a diameter of d ~ 145-220 nm. Used polyethylene oxide

Disadvantages: the relatively low content of chitosan in the solution and, accordingly, in the finished fiber, the need for an electroforming process at elevated temperature, the relatively large diameter of the oligochitosan-containing fiber.

и СД=75 мольн.%, полиэтиленоксид с

до 400 кДа. Получаемое волокно имеет диаметр d=10-250 нм. Максимально достигаемое содержание хитозана в бикомпонентом волокне 90.3 мас.%. Получаемый в процессе электропрядения материал представляет собой композитный материал, состоящий из синтетического субстрата (спанбонд с поверхностной плотностью 17 г/м²) и слоя хитозансодержащих нановолокон с поверхностной плотностью 0.05-100 г/м².Closest to the claimed electrospinning biopolymer fiber from chitosan, non-woven fibrous-porous fabric from chitosan and a method for producing it is a method for producing nanofibers by electrospinning polymer matrices prepared on the basis of a chitosan biopolymer mixed with an auxiliary non-toxic polymer polyethylene oxide, characterized in that chitosan is forming dissolved in acetic acid concentration C _K = 50-90% for 12-24 hours and is heated to a temperature T = 35-50 ° C, then the resulting sol p is mixed with previously (separately) obtained at T = 35-50 ° C an aqueous solution of polyethylene oxide and placed in an electrostatic field between the forming and collecting electrodes at an electric field voltage of 60-75 kV, interelectrode distance of 10-20 cm [Patent WO 2009/049565 A2, IPC D01D 5/00; D01D 5/06; D01F 4/00; D01F 9/00]. It uses chitosan with

and DM = 75 mol.%, polyethylene oxide with

up to 400 kDa. The resulting fiber has a diameter of d = 10-250 nm. The maximum achievable chitosan content in the bicomponent fiber is 90.3 wt.%. The material obtained during electrospinning is a composite material consisting of a synthetic substrate (spunbond with a surface density of 17 g / m ² ) and a layer of chitosan-containing nanofibers with a surface density of 0.05-100 g / m ² .

The disadvantages of the method: the duration and increased temperature of the preparation of the molding solution; the use of chitosan samples with a relatively low degree of deacetylation and polyethylene oxide with a relatively low molecular weight. A significant drawback is the use of chitosan samples in a relatively narrow molecular weight range and with a low degree of deacetylation, as well as the low (90.3% or less) content of the biocompatible chitosan polymer in the finished fiber. The relatively high content in the finished nanofiber of an auxiliary polymer of synthetic origin (polyethylene oxide) reduces biocompatibility, bacteriostatic, biodegradability and other valuable qualities of electro-spun fiber and non-woven material, which limits its use in biomedicine, pharmacology, etc. The goal - obtaining nanofibers and non-woven fibrous-porous fabric from aqueous solutions of chitosan with an auxiliary non-toxic polymer - was not set.

No solutions have been found to the use of non-woven fibrous-porous materials from electrospun polymer fibers, in particular from chitosan nanofibers, as wound dressings and biological dressings for treating wounds of various etiologies in clinical conditions in the patent and scientific literature.

The invention is aimed at solving the following problems:

- obtaining electrospun biopolymer fibers from chitosan and non-woven fibrous-porous fabric based on them using chitosan with a high degree of deacetylation and in a wide range of molecular weight;

- obtaining electrospun biopolymer fibers from chitosan and non-woven fibrous-porous fabric based on them with a chitosan content in the finished product of more than 90.3 wt.% from aqueous acid solutions of chitosan with an auxiliary non-toxic polymer using not only aqueous solutions to dissolve chitosan and an auxiliary non-toxic polymer acetic acid, but also aqueous solutions of natural organic acids (or their derivatives) for multi-purpose use (used in medicine, pharmacology, cosmetology, etc.) - Imon, lactic, ascorbic, succinic, but also including biologically active substances - hemostatic, antiseptic, antimicrobial agents, local anesthetics, proteolytic enzymes, etc. in order to give the finished product the additional therapeutic effect.;

- obtaining electrospun biopolymer fibers from chitosan and a nonwoven fibrous-porous fabric based on them with a chitosan content in the finished product of more than 75 wt.% from aqueous solutions of water-soluble chitosan with an auxiliary non-toxic polymer with the inclusion of biologically active substances - hemostatic, antiseptic, antimicrobial agents, local anesthetics, proteolytic enzymes, etc., as well as using aqueous solutions of aminocaproic and tranexamic amino acids to dissolve chitosan, are REGARD hemostatic drugs, in order to give the finished product the additional therapeutic effect;

- increasing the elasticity of the non-woven fibrous-porous fabric based on electrospun biopolymer fibers from chitosan;

- the creation of a biological dressing in the form of a wound cover from a non-woven fibrous-porous fabric of biomedical purpose from electro-spun chitosan fibers for the treatment of wounds of various etiologies (burns of the II-IIIAB degree, donor sites, long-term non-healing wounds, trophic ulcers, pressure sores and other skin defects), allowing to accelerate the healing process, create optimal conditions for the uncomplicated course of the wound process and regeneration, protect the wound from microbial invasion and trauma, and prevent the formation of s rough scars;

- the creation of a biological dressing in the form of a wound cover from a non-woven fibrous-porous fabric of biomedical purpose from electro-spun chitosan fibers with enhanced therapeutic capabilities, with a prolonged therapeutic effect due to the metered delivery of biologically active medicinal substances to the zone of planned exposure. As a dietary supplement, the dressing may contain a proteolytic enzyme, an antimicrobial, antiseptic, hemostatic or analgesic drug;

- the development of an effective method of treating wounds of various etiologies, taking into account the objective state of the wound and the stage of its healing, using a biological dressing, which is a healing wound cover from a non-woven fibrous-porous web of biomedical use, obtained from electrospun nanofibers of chitosan.

The technical result that can be obtained by implementing a group of inventions.

1. Obtaining electrospun biopolymer defect-free fibers and non-woven fibrous-porous fabric based on them:

- from chitosan with a high degree of deacetylation (DM ≥80 mol.%) and in a wide range of molecular weight;

- with a minimum amount of auxiliary non-toxic polymer, in particular, from aqueous-acid solutions of chitosan when the chitosan content in the finished product reaches more than 90.3 wt.%, from aqueous solutions of chitosan when the chitosan content in the finished product reaches more than 75 wt.%;

- using multipurpose aqueous solutions of natural organic acids (or their derivatives) for the dissolution of chitosan and auxiliary non-toxic polymer (used, for example, in medicine, pharmacology, cosmetology, etc.) - lemon, milk, ascorbic, succinic, aminocaproic and tranexamic;

- with the inclusion of biologically active substances - hemostatic, antiseptic, antimicrobial agents, local anesthetics, proteolytic enzymes, etc., in order to give the finished product an additional therapeutic effect.

2. Achieving an optimal and economically viable method of mixing and dissolving the components of the dope solution used for electroforming fiber.

3. The choice of the optimal composition of the spinning composition based on chitosan for the stable electrospinning of defect-free fibers of nano- and submicron size and non-woven fibrous-porous fabric of different surface density.

4. Development of an optimal environmentally friendly and economically feasible method of modifying a non-woven fibrous-porous fabric to obtain a material with improved elastic properties while ensuring sufficient strength for use of the material in medical applications.

5. The creation of a biological dressing in the form of a wound cover from a non-woven fibrous-porous fabric of biomedical purpose, obtained from electrospun fibers of chitosan, providing:

- maximum plasticity and complete congruence of the biological dressing with the wound surface;

- a high degree of atraumatic;

- a given antibacterial effect;

- improved absorption of the wound and retention of the wound within the coating;

- regenerative effect on the wound with simultaneous bioresorption of the wound cover under the action of the wound discharge;

- targeted delivery of drugs to damaged tissues;

- prolonged and uniform healing effect on the wound;

- the possibility of a long stay on the wound until the complete restoration of the lost skin with the achievement of healing due to a single application of the drug;

- uncomplicated course of the wound process and regeneration in the treatment of burns of the II-IIIAB degree, donor sites, long-term non-healing wounds, trophic ulcers, pressure sores and other skin defects.

6. Development of a method for treating wounds of various etiologies, including a wound toilet and applying the biological dressing described above, which allows the dressing to remain on the wound for a long time, in some cases until the lost skin is completely restored with healing achieved by a single application of the drug.

The problem is achieved in that the composition of the molding solution for forming biopolymer fibers includes chitosan, polyethylene oxide, organic acid, water, while chitosan is used with a molecular weight of 30-500 kDa, a degree of deacetylation of 80-95 mol.% With a ratio of components, wt.% : chitosan - 2.0-7.0, polyethylene oxide - 0.012-0.4, organic acid - 2.5-70, water - the rest. Polyethylene oxide is used with a molecular weight of 2000-8000 kDa. Acetic acid of 50-80% concentration, or citric acid of 10-50% concentration, or lactic acid of 5-30% concentration, or ascorbic acid of 10-30% concentration, or succinic acid are used as organic acid. acid of 5-10% concentration, or aminocaproic acid of 3-6% concentration, or tranexamic acid of 2.5-5% concentration. The composition additionally contains cellulose diacetate in an amount of 0.051-0.09 wt.%.

The composition may contain additives of biologically active substances in an amount of 0.4-0.55 wt.%, While biologically active substances of local anesthetic action (for example, novocaine, lidocaine) or antibacterial and bacteriostatic actions (azithromycin, erythromycin, clarithromycin and other).

Another variant of the composition of the molding solution for forming biopolymer fibers includes chitosan, polyethylene oxide, water, while chitosan is used with a molecular weight of 30-40 kDa with a ratio of components, wt.%: Chitosan - 5.71-6.89, polyethylene oxide - 0.069-0.6, water - the rest . Polyethylene oxide is used with a molecular weight of 2000-8000 kDa. The composition may contain additives of biologically active substances in an amount of 0.1-1.25 wt.%, While biologically active substances of antiseptic, disinfecting and anti-inflammatory effects (e.g. protargol), or proteolytic effects (chymotrypsin, chymopsin, collagenase), or hemostatic action (thrombin, ferrocryl, aminocaproic or tranexamic acid), or local anesthetic action (novocaine, lidocaine), or antibacterial and bacteriostatic action (furagin, fusi yn-Na et al.).

The composition of the molding solution for forming biopolymer fibers includes chitosan, polyvinyl alcohol or polyvinylpyrrolidone, water, while chitosan is used with a molecular weight of 30-40 kDa at a ratio of components, wt.%: Chitosan - 6.0-7.14, polyvinyl alcohol or polyvinylpyrrolidone - 1.43-1.92 water is the rest.

A method of preparing a molding solution in which a molding solution of a chitosan biopolymer with an auxiliary polymer or auxiliary polymers is prepared by mixing the polymers in a powder state, followed by their dissolution in a solvent on a magnetic stirrer until a homogeneous state for 2-8 hours depending on the molecular weight and polymer concentration , type and concentration of organic acid.

A biopolymer fiber comprising chitosan in the form of an organic acid salt and polyethylene oxide, while chitosan is used with a molecular weight of 30-500 kDa, a degree of deacetylation of 80-95 mol.% With a ratio of components, wt.%: Chitosan in the form of an organic acid salt - 90.7- 99.75, polyethylene oxide - the rest. Polyethylene oxide is used with a molecular weight of 2000-8000 kDa. As a salt of chitosan and an organic acid, chitosan acetate, or chitosan citrate, or chitosan lactate, or chitosan ascorbate, or chitosan succinate, or chitosan aminocapriate, or chitosan tranexamate are used. The biopolymer fiber additionally contains cellulose diacetate in an amount of 4.0-7.3 wt.%

Biopolymer fiber contains additives of biologically active substances in an amount of 6.2-8.3 wt.%, While biologically active substances of local anesthetic action or antibacterial and bacteriostatic effects that are stable in an acidic environment are used as additives.

Another version of the biopolymer fiber includes chitosan and polyethylene oxide, or polyvinyl alcohol, or polyvinylpyrrolidone, while chitosan is used with a molecular weight of 30-40 kDa with a ratio of components, wt.%: Chitosan - 75.8-99, polyethylene oxide - the rest. Polyethylene oxide is used with a molecular weight of 2000-8000 kDa.

Biopolymer fiber contains additives of biologically active substances in an amount of 1.4-14.9 wt.%, While biologically active substances of antiseptic, disinfecting and anti-inflammatory action, or proteolytic effect, or hemostatic effect, or local anesthetic action, or antibacterial and bacteriostatic action are used as additives.

A biomedical canvas, which is a non-woven fibrous-porous material formed from biopolymer fibers of chitosan or a salt of chitosan and an organic acid, 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 , breaking load at uniaxial tension 0.61-33.6 N, elongation at break 6.0-16.4%, degree of sorption of water vapor 55-110 wt.% and vapor 0.5N hydrochloric acid 450-1500 wt.%, the degree of sorption of physiological solution 600-800 wt.% and distillers water of 450-650 wt.%, while using chitosan with a molecular weight of 30-500 kDa, the degree of deacetylation of 80-95 mol.%.

A method of modifying a web of biomedical use, according to which the web is further subjected to swelling in physiological saline or distilled water at a temperature of 20-25 ° C for 2-3 minutes to a degree of sorption of physiological saline by a cloth of at least 600-800 wt.%, Distilled water of at least 450-650 wt.%, While providing a value of the relative elongation of the web at break of at least 35%. The canvas is additionally subjected to heat treatment at a temperature of 80-150 ° C for 15-30 minutes, placed in distilled water or saline for 2-3 minutes to a degree of swelling of the canvas 700-1100 wt.%, While providing the value of the relative elongation of the canvas at break not less than 35%. The canvas is further treated with an alkaline reagent for 1 h, followed by washing with distilled water until a neutral pH is reached. As an alkaline reagent, use 1 N sodium hydroxide solution or triethanolamine or ethyl alcohol. After washing, the web is placed in distilled water to a degree of swelling of the web of at least 200-410 wt.%, While providing a value of the relative elongation of the canvas at break of at least 35%.

A biological dressing for the treatment of wounds of various etiologies in the form of a wound dressing, which is a non-woven fibrous-porous fabric of biomedical purpose, formed from electro-spun biopolymer fibers of chitosan or a salt of chitosan and an organic acid, using chitosan with a molecular weight of 30-500 kDa, a degree of deacetylation of 80 -95 mol.%.

A method for treating wounds of various etiologies, including a wound toilet and applying a biological dressing to it, using the biological dressing described above.

The method is as follows.

1. Preparation of the molding solution. An air-dry sample of chitosan is mixed with an air-dry sample of an auxiliary polymer or auxiliary polymers, poured with a solvent (an aqueous solution of acid of a given concentration or water), and stirred on a magnetic stirrer at room temperature and normal atmospheric pressure for τ = 2-8 hours until homogeneous state and filtered through a nitrocellulose filter with a pore diameter of 0.45 μm. If necessary, at the last stage of homogenization, a biologically active substance is introduced into the solution in the form of a molecular or dispersed solution. The solution is stored under static conditions at room temperature, the storage time of the solution is not more than 4-5 days.

2. Electroforming of biopolymer fibers from chitosan and non-woven fibrous-porous fabric based on them. The resulting molding solution is placed in a single-capillary spinning cell - a 20 g steel needle with a flat tip - electrospinning plants. A positive electrode of a direct current source with a supplied voltage of U = 10-40 kV is connected to the cell. The molding solution is supplied by a metering micropump. A collecting electrode-collector in the form of a rotating cylinder with a rotation speed of up to 1500 rpm or a stationary flat metal plate is grounded. The needle of the spinning cell is located perpendicular to the axis of rotation of the drum or the plane of the plate at a distance L = 8-40 cm.The volumetric flow rate of the spinning solution, controlled by a micropump, is 0 = 2.5-10 ml / h. The jet of spinning solution formed under the influence of an electric field settles on the collector electrode and cures in the form of air-dry fibers. Over time, a non-woven fibrous-porous fabric with a random or ordered arrangement of fibers forms on the collector electrode.

3. Physico-chemical modification of the non-woven fibrous-porous fabric from electrospun biopolymer chitosan fibers. The canvas is kept in distilled water or physiological saline (0.9% NaCl) in a chemical vessel of any type at a temperature of 20-25 ° C and normal atmospheric pressure for 2-3 minutes. The canvas is kept in a heating cabinet at a temperature of 80-150 ° C for 15-30 minutes, then in distilled water for 2-3 minutes.

4. Chemical modification of non-woven fibrous-porous fabric from electrospun biopolymer chitosan fibers. The canvas is kept in a solution of caustic soda (C _NaOH = 1 H), or triethanolamine (With _TEA ≤60%), or ethyl alcohol (With _ES ≤70%) for 1 hour with a bath module of 1:10 in a chemical vessel of any type at temperature 20-25 ° C and normal atmospheric pressure. Then the canvas is washed with distilled water to a neutral pH = 7.0-7.5 and placed in distilled water for 3-5 minutes.

5. Assessment of the biocompatibility of the non-woven fibrous-porous fabric from electrospun biopolymer chitosan fibers. The canvas is modified, sterilized and used as a matrix for the cultivation of epithelial-like or epithelial cells.

6. Clinical studies of a biological dressing in the form of a wound cover from a non-woven fibrous-porous web of biomedical use from electro-spun chitosan fibers.

A biological dressing for treating wounds is made of a non-woven fibrous-porous web of biomedical use from electro-spun chitosan fibers and is a healing wound dressing with a number of unique characteristics: improved absorption of the wound and its retention inside the coating, accurate dosage of the drug and its targeted delivery to damaged tissues, antibacterial action and regenerative effect, the property gradually dissolves on its own no under the action of wound.

Before applying the biological dressing, the wound is carefully treated with antiseptic solutions. If necessary, a wound toilet is carried out, including cleaning it of excess wound exudate, dead tissue, blood clots that have fallen into the wound of particles. Then, using tweezers, the wound cover is transferred to the wound, cut out in accordance with its configuration and fixed on top with a gauze bandage. The coatings change as they get wet by the wound, on average after 3-4 days, while only wet areas of the coating are removed from the wound surface and replaced with new ones corresponding in size to the removed areas. If the coatings do not get wet, they are not removed until the wounds are completely epithelized. If the coatings are used as temporary closure of wounds in the area of deep burns after necrectomy, they are removed as the wounds are prepared for autodermoplasty.

и степенью деацетилирования 80-95 мольн.%; полиэтиленоксид с

; поливиниловый спирт, поливинилпирролидон, диацетат целлюлозы; органические кислоты, раствор едкого натра и триэтаноламина квалификации х.ч.; дистиллированную воду, этиловый спирт, физиологический раствор и биологически активные вещества медицинской степени чистоты. Физико-химическая характеристика полимеров представлена в таблице 1. Фармакологические свойства органических кислот и биологически активных веществ приведены в таблице 2.When solving the problems set in the invention, chitosan with a molecular weight is used

and a degree of deacetylation of 80-95 mol.%; polyethylene oxide with

; polyvinyl alcohol, polyvinylpyrrolidone, cellulose diacetate; organic acids, solution of caustic soda and triethanolamine qualification of chemically pure; distilled water, ethyl alcohol, physiological saline and biologically active substances of medical purity. Physico-chemical characteristics of the polymers are presented in table 1. The pharmacological properties of organic acids and biologically active substances are shown in table 2.

The viscosity (η, Pa · s) of the molding solutions was determined on rotational viscometers: an automatic Rheotest RN 4.1 viscometer (Germany) with a cylinder-to-cylinder working unit (Н2, S1 measuring systems) in the shear stress range τ = 2-160 Pa, Brookfield LVDV- II + (Brookfield Engineering, USA) with a cylinder-to-cylinder working unit (measuring system SC4-31) in the range τ = 0.082-1.02 Pa. The electrical conductivity (æ, mS / cm) of the molding solutions was measured on an Anion-4120 conductometer (Russia).

The linear speed of fiber formation was determined by the formula

where Q is the volumetric flow rate, C _P is the polymer concentration, d is the fiber diameter, ρ _W and ρ _P are the polymer and solvent densities, respectively.

The fiber diameter (d, nm) was measured using a Tescan MIRA LMU scanning electron microscope (Czech Republic). The surface density (δ, g / m ² ) of the nonwoven fabric was determined by weighing a rectangular flap with an area of 200 cm ² on an Ohaus analytical balance (weighing accuracy ± 0.001 g).

The sorption process was characterized by the degree of sorption (α, wt.%), Which was calculated by the formula: α = (mm ₀ ) · 100% / m ₀ , where m and m ₀ are the masses of the swollen and initial, respectively, non-woven fibrous-porous fabric . Saline solution (0.9% NaCl), distilled water, and water vapor and a pair of medium formed by 0.5 N hydrochloric acid were used as the sorbate (the latter was chosen as a medium simulating wound exudate).

Elastic-plastic properties were determined according to the Material test i130 “Static tensile test of non-woven fabric” on a Tira Test 28005 uniaxial tensile testing machine (Germany) with a loading cell of 100 N and a traverse speed of 10-50 mm / min. Breaking load (F, N) and elongation were determined at break. The elongation at break (ε,%) was calculated taking into account the initial length of the sample taken for testing, and expressed as a percentage.

To test the biocompatibility of a non-woven fibrous-porous web made of electro-spun biopolymer chitosan fibers, test transfects used a transformed macaque kidney embryonic epithelial cell line (MA-104) from the collection of the Scientific Research Institute of Cytology RAS (St. Petersburg) and human dermal fibroblasts. Fibroblasts were isolated during cultivation by spontaneous migration of cells from skin fragments obtained from healthy donors during plastic surgeries. Cell cultures were grown in DMEM growth medium supplemented with 10% cattle fetal serum for 1-7 days in a CO ₂ incubator at T = 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 Tescan MIRA LMU scanning electron microscope (Czech Republic). The monolayer of cell culture was disaggregated and separated from the nonwoven fibrous-porous fabric by enzymatically treating the monolayer with a mixture of 0.25% trypsin solution with 0.2% solution of versene in a 1: 1 ratio at T = 37 ° C.

The invention is illustrated by examples of specific performance and illustrations, where:

figure 1 shows a micrograph of biopolymer fibers of the composition of chitosan acetate: polyethylene oxide = 99: 1 (wt.%), obtained by scanning electron microscopy;

figure 2 shows a photograph of a non-woven fibrous-porous fabric of biopolymer fibers of the composition of chitosan acetate: polyethylene oxide = 99: 1 (wt.%);

figure 3 is a micrograph of biopolymer fibers of the composition chitosan: polyethylene oxide = 95: 5 (wt.%) obtained by scanning electron microscopy;

figure 4 presents a monolayer of cell culture of embryonic epithelium MA-104 after 1 day of cultivation on a non-woven fibrous-porous fabric of biopolymer fibers of the composition chitosan: polyethylene oxide = 99: 1 (wt.%);

figure 5 - the result of exposure to trypsin on a monolayer of cell culture MA-104 grown on a non-woven fibrous-porous fabric from biopolymer fibers of the composition chitosan: polyethylene oxide = 99: 1 (wt.%).

The group of examples 1-6. The effect of the concentration of acetic acid on the physicochemical characteristics of the molding solution, the parameters of the electrospinning process, and the characteristics of biopolymer fibers from chitosan acetate.

смешивают с воздушно-сухой навеской 0.03 г полиэтиленоксида

, заливают 96.88 г водного раствора уксусной кислоты С_К=50% и растворяют перемешиванием на магнитной мешалке в течение τ=6-8 час. Состав формовочного раствора, мас.%:Example 1. Prepare a molding solution with a total polymer concentration of C _P = 3.12 wt.% In acetic acid concentration C _to = 50%. Air-dry hitch 3.09 g chitosan

mixed with air-dry weight 0.03 g of polyethylene oxide

, fill in 96.88 g of an aqueous solution of acetic acid With _K = 50% and dissolve by stirring on a magnetic stirrer for τ = 6-8 hours. The composition of the molding solution, wt.%:

chitosan - 3.09,

polyethylene oxide - 0.03,

acetic acid - 50,

water is the rest.

Characterization of the molding solution: viscosity η = 1.62-1.82 Pa · s, electrical conductivity æ = 2.8 mS / cm.

The solution is filtered, fed into the spinning cell of the electroforming unit and formed into a flat electrode at a voltage of U = 20-25 kV, interelectrode distance L = 25 cm, volumetric flow rate Q = 5-7 ml / h.

Electrospun fibers have a diameter of d = 200-260 nm, there is a small number of defects in the form of spindle-shaped thickenings. Chitosan in the formed fiber is in the salt form of chitosan acetate, a salt of chitosan and acetic acid. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Example 2 is carried out analogously to example 1. The difference was in the use of acetic acid concentration With _K = 70%. The composition of the molding solution, wt.%:

chitosan - 3.09,

polyethylene oxide - 0.03,

acetic acid - 70,

water is the rest.

Physico-chemical characteristics of the molding solution: viscosity η = 2.20-2.28 Pa · s, electrical conductivity æ = 1.2 mS / cm. The parameters of the electroforming process: flat electrode, voltage U = 20-25 kV, interelectrode distance L = 25 cm, volumetric flow Q = 5-7 ml / h. Characteristics of electro-spun fibers: diameter d = 150-200 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Example 3 was carried out analogously to example 1. The difference was in the use of acetic acid concentration With _K = 80%. The composition of the molding solution, wt.%:

chitosan - 3.09,

polyethylene oxide - 0.03,

acetic acid - 80,

water is the rest.

Physico-chemical characteristics of the molding solution: η = 2.20-2.28 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 18-20 kV, L = 20 cM, Q = 2.5 ml / h. Characteristics of electro-spun fibers: d = 150-200 nm, there are no defects on the fiber. During prolonged electrospinning, drying of the molding solution at the exit of the spinning cell is observed. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Example 4 is carried out analogously to example 1. The difference is that when mixing air-dry polymer weights, 3.105 g of chitosan and 0.015 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 3.105,

polyethylene oxide - 0.015,

acetic acid - 50,

water is the rest.

Characterization of the molding solution: η = 1.38-1.66 Pa · s, æ = 2.7 mS / cm. Electroforming parameters: flat electrode, U = 20-25 kV, L = 25 cm, Q = 5-7 ml / h. Characteristics of electro-spun fibers: d = 200-250 nm, defects in the form of spindle-shaped thickenings are noted. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

Example 5 is carried out analogously to example 2. The difference is that when mixing air-dry polymer weights, 3.105 g of chitosan and 0.015 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 3.105,

polyethylene oxide - 0.015,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.38-1.66 Pa · s, æ = 2.7 mS / cm. Electroforming parameters: flat electrode, U = 20-25 kV, L = 25 cm, Q = 5-7 ml / h. Characteristics of electro-spun fibers: d = 150-200 nm, there are no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

Example 6 is carried out analogously to example 3. The difference is that when mixing air-dry polymer weights, 3.105 g of chitosan and 0.015 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 3.105,

polyethylene oxide - 0.015,

acetic acid - 80,

water is the rest.

Characterization of the molding solution: η = 1.02-1.06 Pa · s, æ = 1.8 mS / cm. Electroforming parameters: flat electrode, U = 20 kV, L = 20 cm, Q = 3 ml / h. Characteristics of electro-spun fibers: d = 150-200 nm, there are no defects on the fiber. During prolonged electrospinning, drying of the molding solution at the exit of the spinning cell is observed. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

From examples 1-6 it can be seen that the concentration of acetic acid With _K = 70% is the most optimal for the electroforming of biopolymer fibers from chitosan.

The group of examples 7-17. The formation of biopolymer fibers and non-woven fibrous-porous fabric from solutions of chitosan with an auxiliary polymer in acetic acid With _K = 70%; the influence of the molecular weight of chitosan and polyethylene oxide on the physicochemical characteristics of the molding solution, the parameters of the electrospinning process, and the characteristics of biopolymer fibers from chitosan acetate.

, общая концентрация полимера в формовочном растворе С_П=4.323 мас.%, при смешении воздушно-сухих навесок полимеров используют 4.28 г хитозана и 0.043 г полиэтиленоксида. Состав формовочного раствора, мас.%:Example 7 is performed analogously to example 2. The difference was that they use a sample of chitosan with

, the total concentration of the polymer in the molding solution With _P = 4.323 wt.%, when mixing air-dry weights of polymers, 4.28 g of chitosan and 0.043 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 4.28,

polyethylene oxide - 0.043,

acetic acid - 70,

water is the rest.

Physico-chemical characteristics of the molding solution: η = 1.13 Pa · s, æ = 1.5 mS / cm. Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1200-1500 rpm, U = 30-35 kV, L = 15-40 cm, Q = 3-6 ml / h. Characterization of electro-spun fibers: d = 200-500 nm, there are no defects on the fiber (Fig. 1). The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Over time, a non-woven fibrous-porous fabric is formed on the collector electrode with a random or ordered arrangement of fibers from chitosan acetate and a surface density of 5-25 g / m ² (Fig. 2), which easily simulates a surface with a complex relief.

, общая концентрация полимера в формовочном растворе С_П=3.03 мас.%, при смешении воздушно-сухих навесок полимеров используют 3.0 г хитозана и 0.03 г полиэтиленоксида. Состав формовочного раствора, мас.%:Example 8 is performed analogously to example 2. Difference: use chitosan with

, the total concentration of the polymer in the molding solution With _P = 3.03 wt.%, when mixing air-dry weights of polymers using 3.0 g of chitosan and 0.03 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.03,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.2 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 20-30 kV, L = 15-20 cm, Q = 3-6 ml / h. Characterization of electro-spun fibers: d = 300-500 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric of biopolymer fibers of chitosan acetate δ = 5-25 g / m ² .

. Состав формовочного раствора, мас.%:Example 9 is performed analogously to example 8. Difference: use polyethylene oxide with

. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.03,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.02-1.08 Pa · s, æ = 1.4 mS / cm. Electroforming parameters: flat electrode, U = 10 kV, L = 8-12 cm, Q = 2.5-5 ml / h. Characteristics of electro-spun fibers: d = 50-250 nm, there are minor defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

, общая концентрация полимера в формовочном растворе С_П=2.02 мас.%, при смешении воздушно-сухих навесок полимеров используют 2.0 г хитозана и 0.02 г полиэтиленоксида. Состав формовочного раствора, мас.%:Example 10 is performed analogously to example 2. Difference: use chitosan with

, the total concentration of the polymer in the molding solution With _P = 2.02 wt.%, when mixing air-dry weights of polymers using 2.0 g of chitosan and 0.02 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 2.0,

polyethylene oxide - 0.02,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.17-1.34 Pa · s, æ = 1.0 mS / cm. Electroforming parameters: flat electrode, U = 30 kV, L = 20 cm, Q = 2-6 ml / h. Characteristics of electro-spun fibers: d = 150-200 nm, there are minor defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 11 is carried out analogously to example 7. The difference is that the total concentration of the polymer in the molding solution With _P = 4.201 wt.%, When mixing air-dry weights of polymers using 4.18 g of chitosan and 0.021 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 4.18,

polyethylene oxide - 0.021,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 0.48-0.54 Pa · s, æ = 2.3 mS / cm. Electroforming parameters: flat electrode, U = 25-40 kV, L = 15-40 cm, Q = 3-6 ml / h. Characterization of electro-spun fibers: d = 70-200 nm, there are no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 12 is carried out analogously to example 7. The difference is that the total concentration of the polymer in the molding solution With _P = 4.633 wt.%, 4.61 g of chitosan and 0.023 g of polyethylene oxide are used when mixing air-dry polymer weights. The composition of the molding solution, wt.%:

chitosan - 4.61,

polyethylene oxide - 0.023,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 3.1 Pa · s, æ = 2.2 mS / cm. Electroforming parameters: flat electrode, U = 25-40 kV, L = 15-40 cm, Q = 3-6 ml / h. Characterization of electro-spun fibers: d = 70-200 nm, there are no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 13 is carried out analogously to example 8. Difference: the total concentration of the polymer in the molding solution With _P = 3.015 wt.%, When mixing air-dry weights of polymers using 3.0 g of chitosan and 0.015 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.015,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.32-1.34 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 12.5 kV, L = 20 cm, Q = 2.5 ml / h. Characterization of electro-spun fibers: d = 300-500 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

. Состав формовочного раствора, мас.%:Example 14 is performed analogously to example 13. The difference was that they use polyethylene oxide with

. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.015,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.7-1.8 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 10-25 kV, L = 10-20 cm, Q = 2.5-5 ml / h. Characteristics of electro-spun fibers: d = 100-500 nm, there are minor defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.5,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 15 is carried out analogously to example 7. Difference: the total concentration of the polymer in the molding solution With _P = 4.19 wt.%, When mixing air-dry weights of polymers, 4.18 g of chitosan and 0.01 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 4.18,

polyethylene oxide - 0.01,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 0.24-0.40 Pa · s, æ = 2.4 mS / cm. Electroforming parameters: flat electrode, U = 25-40 kV, L = 15-40 cm, Q = 3-6 ml / h; unstable fiber forming. Characteristics of electro-spun fibers: d = 170-600 nm, there are defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.75,

polyethylene oxide - the rest.

Example 16 is carried out analogously to example 7. Difference: the total concentration of the polymer in the molding solution With _P = 4.812 wt.%, When mixing air-dry weights of polymers 4.80 g of chitosan and 0.012 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 4.80,

polyethylene oxide - 0.012,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 2.97 Pa · s, æ = 2.3 mS / cm. Electroforming parameters: flat electrode, U = 25-40 kV, L = 15-40 cm, Q = 3-6 ml / h. Characteristics of electro-spun fibers: d = 170-600 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.75,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

, общая концентрация полимера в формовочном растворе С_П=3.03 мас.%, при смешении воздушно-сухих навесок полимеров используют 3.0 г хитозана и 0.03 г полиэтиленоксида. Состав формовочного раствора, мас.%:Example 17 is performed analogously to example 8. The difference is that they use polyethylene oxide with

, the total concentration of the polymer in the molding solution With _P = 3.03 wt.%, when mixing air-dry weights of polymers using 3.0 g of chitosan and 0.03 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.03,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.17-1.32 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 10-25 kV, L = 10-20 cm, 0 = 1-5 ml / h; unstable fiber forming. Characterization of electro-spun fibers: d = 50-95 nm, multiple defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.9,

polyethylene oxide - the rest.

Group of examples 18-20. The effect of the concentration of chitosan in the molding solution on the physicochemical characteristics of the molding solution, the parameters of the electroforming process, the characteristics of biopolymer fibers from chitosan acetate and non-woven fibrous-porous fabric based on them.

Example 18 is carried out analogously to example 7. The difference is that the total concentration of the polymer in the molding solution With _P = 3.03 wt.%, When mixing air-dry weighed polymers using 3.0 g of chitosan and 0.03 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 3.0,

polyethylene oxide - 0.03,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 0.24 Pa · s, æ = 1.2 mS / cm. Electroforming parameters: flat electrode, U = 30 kV, L = 20 cm, Q = 6 ml / h, linear speed of fiber formation V = 1130 m / s. Characteristics of electro-spun fibers: d = 190 ± 10 nm, there are no defects on the fiber and fiber structure of the non-woven fiber-porous fabric. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Example 19 was carried out analogously to example 18. Differences: the total concentration of the polymer in the molding solution With _P = 6.06 wt.%, When mixing air-dry weighed samples of polymers using 6.0 g of chitosan and 0.06 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 6.0,

polyethylene oxide - 0.06,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 0.8 Pa · s, æ = 1.5 mS / cm. Electroforming parameters: flat electrode, U = 30 kV, L = 20 cm, Q = 6 ml / h, V = 1080 m / s. Characterization of electro-spun fibers: d = 160 ± 10 nm, there are no defects on the fiber and fiber structure of the non-woven fiber-porous fabric. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

Example 20 is carried out analogously to example 18. Differences: the total concentration of the polymer in the molding solution With _P = 7.07 wt.%, When mixing air-dry weights of polymers using 7.0 g of chitosan and 0.07 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 7.0,

polyethylene oxide - 0.07,

acetic acid - 70,

water is the rest.

Characterization of the molding solution: η = 1.8 Pa · s, æ = 2.5 mS / cm. Electroforming parameters: flat electrode, U = 30 kV, L = 20 cm, Q = 6 ml / h, V = 845 m / s. Characteristics of electro-spun fibers: d = 360 ± 20 nm, there are no defects on the fiber and fiber structure of the non-woven fiber-porous fabric. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 99.0,

polyethylene oxide - the rest.

A group of examples 21-27. The influence of the storage time of the molding solution on the rheological parameters of the system and the characteristics of electrospun biopolymer fibers from chitosan acetate.

Example 21 was carried out analogously to example 7, but using a flat electrode and a molding solution stored under static conditions for 1 day. Characterization of the molding solution: η = 0.86 Pa · s, æ = 1.5 mS / cm. Characteristics of electro-spun fibers: d = 300-320 nm, there are no defects on the fiber and fibrous structure of the non-woven fibrous-porous fabric.

Example 22 was performed analogously to example 21, but using a molding solution stored under static conditions for 2 days. Characterization of the molding solution: η = 0.75 Pa · s, æ = 1.5 mS / cm. Characterization of electro-spun fibers: d = 150-170 nm, there are no defects on the fiber and fibrous structure.

Example 23 was carried out analogously to example 21, but using a molding solution stored under static conditions for 3 days. Characterization of the molding solution: η = 0.70 Pa · s, æ = 1.5 mS / cm. Characteristics of electro-spun fibers: d = 120-140 nm, there are no defects on the fiber and fibrous structure.

Example 24 was carried out analogously to example 21, but using a molding solution stored under static conditions for 4 days. Characterization of the molding solution: η = 0.65 Pa · s, æ = 1.5 mS / cm. Characterization of electro-spun fibers: d ~ 90 nm, minor defects appear on the fiber and fibrous structure.

Example 25 was performed analogously to example 21, but using a molding solution stored under static conditions for 5 days. Characterization of the molding solution: η = 0.61 Pa · s, æ = 1.5 mS / cm. Characterization of electro-spun fibers: d ~ 80 nm, defects on the fiber and fibrous structure in the form of thickenings.

Example 26 was performed analogously to example 21, but using a molding solution stored under static conditions for 6 days. Characterization of the molding solution: η = 0.56 Pa · s, æ = 1.5 mS / cm. Characterization of electro-spun fibers: d ~ 80 nm, defects on the fiber in the form of thickenings and drops.

Example 27 was performed analogously to example 21, but using a molding solution stored under static conditions for 8 days. Characterization of the molding solution: η = 0.52 Pa · s, æ = 1.5 mS / cm. Unstable electroforming, turning into a spray of a solution in the form of drops. Characterization of electro-spun fibers: d ~ 80 nm, a significant number of defects on the fiber in the form of thickenings and drops.

Examples 28, 29. The formation of biopolymer fibers and non-woven fibrous-porous fabric from molding solutions of chitosan with a bicomponent modifier (for example, biopolymer fibers from chitosan acetate).

Example 28 was carried out analogously to example 7. The difference was that cellulose diacetate was additionally added to the molding solution, the total polymer concentration in the molding solution was C _P = 4.51 wt.%, When mixing air-dry polymer weights, 4.09 g of chitosan and 0.33 g of polyethylene oxide were used and 0.09 g of cellulose diacetate. The composition of the molding solution, wt.%:

chitosan - 4.28,

polyethylene oxide - 0.33,

cellulose diacetate - 0.09,

acetic acid - 70,

water is the rest.

Electroforming parameters: a rotating electrode-cylinder with D = 8 cm and a rotation speed of 300-600 rpm, U = 30 kV, L = 30 cm, Q = 5 ml / h. Characterization of electro-spun fibers: d = 300-500 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 90.7,

cellulose diacetate - 7.3,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 29 was carried out analogously to example 28. The difference is that the total concentration of the polymer in the molding solution With _P = 5.126 wt.%, 4.87 g of chitosan, 0.205 g of polyethylene oxide and 0.051 g of cellulose diacetate are used when mixing air-dry polymer weights. The composition of the molding solution, wt.%:

chitosan - 4.87,

polyethylene oxide - 0.205,

cellulose diacetate - 0.051,

acetic acid - 70,

water is the rest.

Electroforming parameters: a rotating electrode-cylinder with D = 8 cm and a rotation speed of 300-600 rpm, U = 30 kV, L = 30 cm, Q = 5 ml / h. Characterization of electro-spun fibers: d = 300-500 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan acetate - 95.5,

cellulose diacetate - 4.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

).The group of examples 30-33. The formation of biopolymer fibers from solutions of chitosan with an auxiliary polymer in other organic acids (for example, a sample of chitosan with

)

Example 30 is carried out analogously to example 7. The difference is that citric acid with a concentration of C _K = 10-50% is used, the total concentration of the polymer in the molding solution is C _P = 4.44 wt.%, 4.13 g of chitosan are used for mixing air-dry polymer weights 0.31 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 4.44,

polyethylene oxide - 0.31,

citric acid - 10-50,

water is the rest.

Electroforming parameters: flat electrode, U = 30 kV, L = 20 cm, Q = 5 ml / h. The diameter of electrospun biopolymer fibers is d = 140-900 nm. Chitosan in the formed fiber is in the salt form of chitosan citrate - a salt of chitosan and citric acid. The composition of the biopolymer fiber, wt.%:

chitosan citrate - 93.0,

polyethylene oxide - the rest.

и молочную кислоту концентрации С_К=5-30%, общая концентрация полимера в формовочном растворе С_П=3.86 мас.%. Состав формовочного раствора, мас.%:Example 31 is performed analogously to example 7. Difference: use polyethylene oxide with

and lactic acid concentration With _K = 5-30%, the total polymer concentration in the molding solution With _P = 3.86 wt.%. The composition of the molding solution, wt.%:

chitosan - 3.67,

polyethylene oxide - 0.19,

lactic acid - 5-30,

water is the rest.

Electroforming parameters: flat electrode, U = 25 kV, L = 35 cm, Q = 4 ml / h. The diameter of electrospun biopolymer fibers is d = 200-840 nm. Chitosan in the spun fiber is in the salt form of chitosan lactate, a salt of chitosan and lactic acid. The composition of the biopolymer fiber, wt.%:

chitosan lactate - 95.0,

polyethylene oxide - the rest.

Example 32 was carried out analogously to example 31. Difference: ascorbic acid of a concentration of C _K = 10-30% was used, the total polymer concentration in the molding solution was C _P = 3.406 wt.%. The composition of the molding solution, wt.%:

chitosan - 3.27,

polyethylene oxide - 0.136,

ascorbic acid - 10-30,

water is the rest.

Electroforming parameters: flat electrode, U = 25 kV, L = 25 cm, Q = 4 ml / h. The diameter of electrospun biopolymer fibers is d = 1000-1750 nm. During molding, the fibers fit into ordered spiral structures. Chitosan in the formed fiber is in the salt form of chitosan ascorbate, a salt of chitosan and ascorbic acid. The composition of the biopolymer fiber, wt.%:

chitosan ascorbate - 96.0,

polyethylene oxide - the rest.

Example 33 is carried out analogously to example 31. Difference: succinic acid is used with a concentration of C _K = 5-10%, the total polymer concentration in the molding solution is C _P = 3.86 wt.%. The composition of the molding solution, wt.%:

chitosan - 3.67,

polyethylene oxide - 0.19,

succinic acid - 5-10,

water is the rest.

Electroforming parameters: flat electrode, U = 20 kV, L = 25 cm, Q = 5 ml / h. The diameter of electrospun biopolymer fibers is d = 350-600 nm. Chitosan in the spun fiber is in the salt form of chitosan succinate, a salt of chitosan and succinic acid. The composition of the biopolymer fiber, wt.%:

chitosan succinate - 95.0,

polyethylene oxide - the rest.

The group of examples 34-41. Formation of biopolymer fibers and non-woven fibrous-porous fabric from aqueous solutions of water-soluble chitosan.

смешивают с воздушно-сухой навеской 0.44 г полиэтиленоксида

, заливают 95.12 г дистиллированной воды и растворяют перемешиванием на магнитной мешалке в течение τ=2-5 час. Состав формовочного раствора, мас.%:Example 34. Prepare a molding solution with a total polymer concentration of C _P = 4.88 wt.%. Air-dry weight 4.44 g of chitosan

mixed with air-dry weight 0.44 g of polyethylene oxide

95.12 g of distilled water is poured and dissolved by stirring on a magnetic stirrer for τ = 2-5 hours. The composition of the molding solution, wt.%:

chitosan - 4.44,

polyethylene oxide - 0.44,

water is the rest.

Physico-chemical characteristics of the molding solution: η = 2.25 Pa · s, æ = 11.2 mS / cm, the ratio of the components of chitosan: polyethylene oxide = 90: 10. Further procedures are carried out analogously to example 1. Electroforming parameters: flat electrode, U = 25-35 kV, L = 20-30 cm, Q = 2.5-6 ml / h. The fiber is not molded.

Example 35 was carried out analogously to example 34. The difference was that the total polymer concentration in the molding solution was C _P = 6.4 wt.%, 5.8 g of chitosan and 0.6 g of polyethylene oxide were used when mixing air-dry polymer weights. The composition of the molding solution, wt.%:

chitosan - 5.8,

polyethylene oxide - 0.6,

water is the rest.

Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1200-1500 rpm, U = 30-40 kV, L = 30 cm, Q = 6 ml / h. Characteristics of electro-spun fibers: d = 180-320 nm, there are no defects on the fiber and fiber structure of the non-woven fiber-porous fabric. The composition of the biopolymer fiber, wt.%:

chitosan - 90.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 36 is carried out analogously to example 34. The difference is that the total concentration of the polymer in the molding solution With _P = 5.99 wt.%, When mixing air-dry weights of polymers using 5.71 g of chitosan and 0.28 g of polyethylene oxide. The composition of the molding solution, wt.%:

chitosan - 5.71,

polyethylene oxide - 0.28,

water is the rest.

Characterization of the molding solution: η = 1.65 Pa · s, æ = 10.5 mS / cm. Electroforming parameters: flat electrode, U = 30-35 kV, L = 25-30 cm, Q = 2.5-4 ml / h, unstable molding. Characteristics of electro-spun fibers: d = 200-600 nm, defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan - 95.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 37 was carried out analogously to example 34. Difference: the total concentration of the polymer in the molding solution With _P = 6.9 wt.%, When mixing air-dry weights of polymers, 6.55 g of chitosan and 0.35 g of polyethylene oxide are used. The composition of the molding solution, wt.%:

chitosan - 6.55,

polyethylene oxide - 0.35,

water is the rest.

Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1200-1500 rpm, U = 30-40 kV, L = 30 cm, Q = 6 ml / h. The characteristic of electro-spun fibers: d = 220-320 nm, there are no defects on the fiber and the fibrous structure of the non-woven fibrous-porous fabric (Fig. 3). The composition of the biopolymer fiber, wt.%:

chitosan - 95.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

. Состав формовочного раствора, мас.%:Example 38 was carried out analogously to example 34. Difference: the total concentration of the polymer in the molding solution With _P = 6.96 wt.%, When mixing air-dry weights of polymers using 6.89 g of chitosan and 0.069 g of polyethylene oxide with

. The composition of the molding solution, wt.%:

chitosan - 6.89,

polyethylene oxide - 0.069,

water is the rest.

Characterization of the molding solution: η = 1.95 Pa · s, æ = 15.4 mS / cm. Electroforming parameters: flat electrode, U = 30-35 kV, L = 25-30 cm, Q = 2.5-4 ml / h, unstable molding. Characterization of electro-spun fibers: d = 200-600 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%:

chitosan - 99.0,

polyethylene oxide - the rest.

Example 39 is carried out analogously to example 34. The difference is that polyvinyl alcohol is used as an auxiliary polymer, the total polymer concentration in the molding solution is C _P = 8.12 wt.%, When mixing air-dry polymer weights, 6.25 g of chitosan and 1.87 g of polyvinyl alcohol are used . The composition of the molding solution, wt.%:

chitosan - 6.25,

polyvinyl alcohol - 1.87,

water is the rest.

Characterization of the molding solution: η = 2.26 Pa · s, æ = 11.5 mS / cm. Electroforming parameters: flat electrode, U = 10-40 kV, L = 20-35 cm, Q = 3-10 ml / h. The diameter of electro-spun fibers d = 170-250 nm. The composition of the biopolymer fiber, wt.%:

chitosan - 77.0,

polyvinyl alcohol - the rest.

Example 40 is carried out analogously to example 39. The difference is that the total concentration of the polymer in the molding solution With _P = 8.57 wt.%, When mixing air-dry weights of polymers using 7.14 g of chitosan and 1.43 g of polyvinyl alcohol. The composition of the molding solution, wt.%:

chitosan - 7.14,

polyvinyl alcohol - 1.43,

water is the rest.

Characterization of the molding solution: η = 2.3 Pa · s, æ = 13.6 mS / cm. Electroforming parameters: flat electrode, U = 10-40 kV, L = 20-35 cm, Q = 3-10 ml / h. The diameter of electro-spun fibers d = 150-300 nm. The composition of the biopolymer fiber, wt.%:

chitosan - 83.0,

polyvinyl alcohol - the rest.

Example 41 was carried out analogously to example 34. Difference: polyvinylpyrrolidone was used as an auxiliary polymer, the total polymer concentration in the molding solution was C _P = 7.92 wt.%, 6.0 g of chitosan and 1.92 g of polyvinylpyrrolidone were used when mixing air-dry polymer weights. The composition of the molding solution, wt.%:

chitosan - 6.0,

polyvinylpyrrolidone - 1.92,

water is the rest.

Characterization of the molding solution: η = 3.15 Pa · s, æ = 10.0 mS / cm. Electroforming parameters: flat electrode, U = 10-40 kV, L = 20-35 cm, Q = 5-10 ml / h. The diameter of electrospun fibers d = 90-150 nm. The composition of the biopolymer fiber, wt.%:

chitosan - 75.8,

polyvinylpyrrolidone - the rest.

).Examples 42, 43. The formation of biopolymer fibers and non-woven fibrous-porous fabric from solutions of chitosan with an auxiliary polymer in organic acids for medical purposes (for example, a sample of chitosan with

)

или 5000 кДа. Состав формовочного раствора, мас.%:Example 42 is carried out analogously to example 35. The difference is that aminocaproic acid is used with a concentration of C _K = 3-6%, the total polymer concentration in the molding solution is C _P = 5.3 wt.%, 5.0 g of chitosan are used for mixing air-dry polymer weights and 0.3 g polyethylene oxide s

or 5000 kDa. The composition of the molding solution, wt.%:

chitosan - 5.0,

polyethylene oxide - 0.3,

aminocaproic acid - 3-6,

water is the rest.

Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1500 rpm, U = 20 kV, L = 30 cm, Q = 4 ml / h. Characteristics of electro-spun fibers: d = 250-400 nm, no defects on the fiber. Chitosan in the formed fiber is in the salt form of chitosan aminocapriate, a salt of chitosan and aminocaproic acid. The composition of the biopolymer fiber, wt.%:

chitosan aminocapriate - 94.0,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

или 5000 кДа. Состав формовочного раствора, мас.%:Example 43 is performed analogously to example 35, the total concentration of the polymer in the molding solution With _P = 6.4 wt.%. Difference: using tranexamic acid with a concentration of C _K = 2.5-5%, when mixing air-dry weights of polymers, 6.0 g of chitosan and 0.4 g of polyethylene oxide are used with

or 5000 kDa. The composition of the molding solution, wt.%:

chitosan - 6.0,

polyethylene oxide - 0.4,

tranexamic acid - 2.5-5,

water is the rest.

Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1500 rpm, U = 35-40 kV, L = 30 cm, Q = 5 ml / h. Characteristics of electro-spun fibers: d = 350-500 nm, no defects on the fiber. Chitosan in the formed fiber is in the salt form of chitosan tranexamate - a salt of chitosan and tranexamic acid. The composition of the biopolymer fiber, wt.%:

chitosan tranexamate - 93.7,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

).Group of examples 44-49. The formation of biopolymer fibers and non-woven fibrous-porous fabric from chitosan with the addition of biologically active substances (for example, samples of chitosan with

)

Example 44 was carried out analogously to example 35. Three compositions were prepared, differing in the amount of biologically active substance with antiseptic, disinfectant and anti-inflammatory effects, namely protorgol. The difference from example 35 is that the total concentration of the molding solution With _P = 7.64-8.39 wt.%, When mixing air-dry weights of polymers, 6.7 g of chitosan, 0.44 g of polyethylene oxide are used and additional protargol is added in an amount of 0.5 g for one composition, for another composition of 0.7 g and for the third 1.25 g. The composition of the molding solution, wt.%:

chitosan - 6.7,

polyethylene oxide - 0.44,

protargol - 0.5, or 0.7, or 1.25,

water is the rest.

The fiber was obtained from the above three compositions. Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1500 rpm, U = 20 kV, L = 25 cm, Q = 4 ml / h. Characteristics of electro-spun fibers: d = 150-300 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan - 79.9-87.7,

protargol - 6.6-14.9,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 45 was carried out analogously to example 44. Four compositions were prepared, differing in the number of biologically active substances of proteolotic action, namely chymotrypsin. Difference from example 44: additionally administer chymotrypsin in an amount of 0.1 g for one composition, 0.3 g for another, 0.7 g for the third and 1.25 g for the fourth. Composition of the molding solution, wt.%:

chitosan - 6.7,

polyethylene oxide - 0.44,

chymotrypsin - 0.1, or 0.3, or 0.7, or 1.25,

water is the rest.

Fiber was obtained from the four formulations described above. Characteristics of electro-spun fibers: d = 130-280 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan - 79.9-92.5,

chymotrypsin - 1.4-14.9,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 46 is carried out analogously to example 45. Difference: four formulations were prepared, differing in the amount of biologically active substance with a hemostatic effect, namely thrombin. The composition of the molding solution, wt.%:

chitosan - 6.7,

polyethylene oxide - 0.44,

thrombin - 0.1, or 0.3, or 0.7, or 1.25,

water is the rest.

Fiber was obtained from the four formulations described above. Characteristics of electro-spun fibers: d = 130-280 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan - 79.9-92.5,

thrombin - 1.4-14.9,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 47 was carried out analogously to example 35. Three compositions were prepared, differing in the amount of biologically active substance of local anesthetic action, namely novocaine. The difference from example 35: the total concentration of the molding solution With _P = 7.84-8.66 wt.%, A weight of 6.6 g of chitosan is mixed with a weight of 0.34 g of polyethylene oxide and novocaine is additionally added in an amount of 0.4 g for one composition, 0.78 g for another and 1.2 for the third g. The composition of the molding solution, wt.%:

chitosan - 6.6,

polyethylene oxide - 0.34,

novocaine - 0.4, or 0.78, or 1.2,

water is the rest.

The fiber was obtained from the above three compositions. Electroforming parameters: cylinder with a diameter of D = 8 cm and a rotation speed of 1500 rpm, U = 35-40 kV, L = 30 cm, Q = 6 ml / h. Characteristics of electro-spun fibers: d = 150-250 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan - 81.0-89.9,

novocaine - 5.5-14.7,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 48 was carried out analogously to example 47. Difference: three compositions were prepared, differing in the amount of biologically active substance with antibacterial and bacteriostatic effects, namely fusidine-Na. The composition of the molding solution, wt.%:

chitosan - 6.6,

polyethylene oxide - 0.34,

fusidin-Na - 0.4, or 0.78, or 1.2,

water is the rest.

The fiber was obtained from the above three compositions. Characteristics of electro-spun fibers: d = 140-260 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan-81.0-89.9,

fusidin-Na - 5.5-14.7,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

. Было приготовлено три состава, отличающихся количеством биологически активного вещества местноанестезирующего действия, а именно лидокаина. Отличие от примера 19 в том, что общая концентрация формовочного раствора С_П=6.46-6.61 мас.%, дополнительно вводят лидокаин в количестве для одного состава 0.4 г, для другого состава 0.48 г и для третьего 0.55 г, в качестве растворителя используют уксусную кислоту концентрации C_K=50%, или 70%, или 80%. Состав формовочного раствора, мас.%:Example 49 is performed analogously to example 19, while using chitosan with

. Three formulations were prepared, differing in the amount of biologically active substance of local anesthetic action, namely lidocaine. The difference from example 19 is that the total concentration of the molding solution With _P = 6.46-6.61 wt.%, Additionally enter lidocaine in an amount of 0.4 g for one composition, 0.48 g for another composition and 0.55 g for the third, acetic acid is used as a solvent concentration C _K = 50%, or 70%, or 80%. The composition of the molding solution, wt.%:

chitosan - 6.0,

polyethylene oxide - 0.06,

lidocaine - 0.4, or 0.48, or 0.55,

acetic acid - 50, or 70, or 80,

water is the rest.

The fiber was obtained from the above three compositions. Characteristics of electro-spun fibers: d = 150-250 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan acetate - 90.8-92.9,

lidocaine - 6.2-8.3,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

Example 50 was carried out analogously to example 49. Difference: three compositions were prepared, differing in the amount of biologically active substance with antibacterial and bacteriostatic effects, namely erythromycin. The composition of the molding solution, wt.%:

chitosan - 6.0,

polyethylene oxide - 0.06,

erythromycin - 0.4, or 0.48, or 0.55,

acetic acid - 50, or 70, or 80,

water is the rest.

The fiber was obtained from the above three compositions. Characteristics of electro-spun fibers: d = 120-250 nm, no defects on the fiber. The composition of the biopolymer fiber, wt.%, The following:

chitosan acetate - 90.8-92.9,

azithromycin - 6.2-8.3,

polyethylene oxide - the rest.

The surface density of the non-woven fibrous-porous fabric δ = 5-25 g / m ² .

The group of examples 51-58. Elastic-plastic and sorption characteristics of a non-woven fibrous-porous material formed from biopolymer fibers of chitosan or a salt of chitosan and an organic acid.

и полиэтиленоксида

, сформованный на вращающийся электрод-цилиндр с диаметром D=60 мм и скоростью вращения 1000 об/мин, с содержанием хитозана 99.0 мас.% и поверхностной плотностью δ=5 г/м² характеризуется: разрывной нагрузкой в направлении преимущественной ориентации волокон в материале F₁=4.3 Н; разрывной нагрузкой в направлении, перпендикулярном преимущественной ориентации волокон в материале, F₂=0.7 Н; относительным удлинением в направлении преимущественной ориентации волокон в материале ε₁=6.0%; относительным удлинением в направлении, перпендикулярном преимущественной ориентации волокон в материале, ε₂=9.5%; степенью сорбции паров воды α₁=70 мас.%; степенью сорбции паров 0.5 Н соляной кислоты α₂=1400 мас.%; степенью сорбции физиологического раствора (0.9% NaCl) α₃=~800 мас.%; степенью сорбции дистиллированной воды α₄=~650 мас.%.Example 51. Non-woven fibrous-porous material (biomedical web) from biopolymer fibers of chitosan acetate

and polyethylene oxide

formed on a rotating electrode-cylinder with a diameter of D = 60 mm and a rotation speed of 1000 rpm, with a chitosan content of 99.0 wt.% and a surface density of δ = 5 g / m ^{2 is} characterized by: breaking load in the direction of the predominant orientation of the fibers in the material F ₁ = 4.3 N; breaking load in the direction perpendicular to the preferred orientation of the fibers in the material, F ₂ = 0.7 N; relative elongation in the direction of the preferred orientation of the fibers in the material ε ₁ = 6.0%; relative elongation in the direction perpendicular to the preferred orientation of the fibers in the material, ε ₂ = 9.5%; the degree of sorption of water vapor α ₁ = 70 wt.%; the degree of sorption of vapors of 0.5 N hydrochloric acid α ₂ = 1400 wt.%; the degree of sorption of physiological saline (0.9% NaCl) α ₃ = ~ 800 wt.%; the degree of sorption of distilled water α ₄ = ~ 650 wt.%.

Example 52 is carried out analogously to example 51. Difference: the sample has a surface density of δ = 10 g / m ² . Sample characteristic: F ₁ = 13.3 H, F ₂ = 1.8 H, ε ₁ = 7.1%, ε ₂ = 8.6%, α ₁ = 90 wt.%, Α ₂ = 1500 wt.%.

Example 53 is carried out analogously to example 51. Difference: the sample has a surface density of δ = 14.5 g / m ² and is molded into a cylinder with a diameter of D = 60 mm with a rotation speed of 600 rpm. Sample characteristic: F ₁ = 23.3 H, F ₂ = 3.9 H, ε ₁ = 10.2%, ε ₂ = 16.4%, α ₁ = 110 wt.%, Α ₂ = 450 wt.%.

Example 54 is performed analogously to example 53, but the sample is molded onto a cylinder D = 25 mm. Sample characteristic: F ₁ = 28.9 N, F ₂ = 5.7 H, ε ₁ = 4.5%, ε ₂ = 13.5%.

Example 55 is carried out analogously to example 53, but the sample is molded onto a flat stationary electrode. Specimen characteristic: breaking load at uniaxial tension of 2.6 N, elongation at break of 13.1%.

Example 56 is performed analogously to example 51. Difference: the sample has a surface density of δ = 25.3 g / m ² . Sample characteristic: F ₁ = 33.6 H, F ₂ = 4.1 N, ε ₁ = 7.1%, ε ₂ = 11.6%, α ₁ = 55 wt.%, Α ₂ = 1400 wt.%; α ₃ = ~ 600 wt.%; α ₄ = ~ 450 wt.%.

, полиэтиленоксида

и диацетата целлюлозы с соотношением компонентов хитозан:полиэтиленоксид:диацетат целлюлозы = 96:3:1 и поверхностной плотностью δ=10.6 г/м². Характеристика образца: разрывная нагрузка при одноосном растяжении 12.4 Н, относительное удлинение при разрыве 8.3%.Example 57 was carried out analogously to example 55. The difference was that they use a non-woven fibrous-porous material from biopolymer fibers of chitosan acetate

polyethylene oxide

and cellulose diacetate with a ratio of chitosan: polyethylene oxide: cellulose diacetate = 96: 3: 1 and a surface density of δ = 10.6 g / m ² . Specimen characteristic: breaking load at uniaxial tension 12.4 N, elongation at break 8.3%.

с содержанием хитозана 95.0 мас.% и поверхностной плотностью δ=10.0 г/м². Характеристика образца: F₁=3.72 Н, F₂=0.61 H, ε₁=4.7%, ε₂=14%.Example 58 is carried out analogously to example 55. The difference is that they use a non-woven fibrous-porous material from biopolymer fibers of chitosan

with a chitosan content of 95.0 wt.% and a surface density of δ = 10.0 g / m ² . Sample characteristic: F ₁ = 3.72 N, F ₂ = 0.61 H, ε ₁ = 4.7%, ε ₂ = 14%.

Group of examples 59-64. The effect of physico-chemical modification of a non-woven fibrous-porous fabric from biopolymer fibers of chitosan or a salt of chitosan and an organic acid on the elastic-plastic properties of the material (for example, a non-woven fibrous-porous fabric from biopolymer fibers of chitosan acetate).

Example 59. A non-woven fibrous-porous material (biomedical web) from biopolymer fibers of chitosan acetate, obtained according to example 51, is kept in saline for 2-3 minutes until the degree of sorption is reached α ₃ = ~ 800 wt.%. The modified web is subjected to uniaxial tension on a tensile testing machine. The value of the breaking load in the direction of the preferred orientation of the fibers in the material is F ₁ = 1.8 N, the value of the relative elongation in the direction of the preferred orientation of the fibers in the material is ε ₁ = 35.6%.

Example 60 was carried out analogously to example 59. The difference was that the web was incubated in distilled water for 2-3 minutes until the degree of sorption was reached α ₄ = ~ 650 wt.%. Elastic-plastic characteristics of the modified web: F ₁ = 1.8 N, ε ₁ = 40.4%.

Example 61 was carried out analogously to example 59. The difference consisted in the use of biomedical fabrics from biopolymer fibers of chitosan acetate obtained in example 56. The degree of sorption of 0.9% NaCl is α ₃ = ~ 600 wt.%. Elastic-plastic characteristics of the modified web: F ₁ = 16.3 N, ε ₁ = 40%.

Example 62 was carried out analogously to example 61. The difference was in the use of distilled water as a sorption medium. The characteristic of the modified web: α ₄ = ~ 450 wt.%, F ₁ = 13.2 H, ε ₁ = 35%.

Example 63. A biomedical canvas made from biopolymer fibers of chitosan acetate, obtained according to example 51, is kept in a heating cabinet at T = 80-150 ° C for 15-30 minutes. The modified web is placed in distilled water for 2-3 minutes. The characteristic of the modified web: α ₄ = ~ 1000-1100 wt.%, F ₁ = 3.4 H, ε ₁ = 45%.

Example 64 was performed analogously to example 63. The difference consisted in the use of a biomedical web from biopolymer fibers of chitosan acetate obtained in example 56. Characteristic of the modified web: α ₄ = ~ 700-750 wt.%, F ₁ = 20.5 N, ε ₁ = 37.7 %

The group of examples 65-69. The effect of chemical modification of a nonwoven fabric from biopolymer fibers of chitosan or a salt of chitosan and an organic acid on the elastic-plastic properties of the material (for example, a nonwoven fibrous-porous fabric from biopolymer fibers of chitosan acetate).

Example 65. A biomedical web from biopolymer fibers of chitosan acetate obtained in Example 51 is kept in a solution of triethanolamine (With _TEA ≤60%) for 1 h. The modified web is washed with distilled water to pH = 7.0-7.5, placed in distilled water on 3-5 minutes to achieve the degree of sorption α ₄ = ~ 400-410 wt.% And subjected to uniaxial tension on a tensile testing machine. Elastic-plastic characteristics of the modified web: F ₁ = 2.0 H, ε ₁ = 41.9%.

Example 66 was performed analogously to example 65. The difference was that a sodium hydroxide solution (C _NaOH = 1 N) was used as a modifying reagent. The characteristic of the modified web: (α ₄ = ~ 300-360 wt.%, F ₁ = 1.8 N, ε ₁ = 35.6%.

Example 67 is carried out analogously to example 65. The difference is that ethanol is used as the modifying reagent (With _ES ≤70%). The characteristic of the modified web: α ₄ = ~ 350-400 wt.%, F ₁ = 2.7 N, ε ₁ = 40.2%.

Example 68 was performed analogously to example 65. The difference is that a biomedical web from biopolymer fibers of chitosan acetate obtained according to example 56 is used. Characteristic of the modified web: α ₄ = ~ 200-250 wt.%, F ₁ = 13.2 N, ε ₁ = 39.2%.

Example 69 was performed analogously to example 66. The difference was the use of a biomedical web of biopolymer fibers of chitosan acetate obtained in example 56. Characteristic of the modified web: α ₄ = ~ 250-280 wt.%, F ₁ = 15.5 N, ε ₁ = 36.4 %

Examples 70-72. Cultivation of epithelial-like MA-104 cells and human skin fibroblasts on a non-woven fibrous-porous fabric of biopolymer chitosan fibers.

Example 70. Use a non-woven fibrous-porous fabric from biopolymer chitosan fibers obtained in example 51 and modified in example 67. The cloth is sterilized, placed in a sterile Petri dish, filled with growth medium with the addition of 10% cattle fetal serum and a suspension of MA cells is introduced -104 at a concentration of 3 · 10 ⁵ cells / cm ² . Cultivation is carried out in a CO ₂ incubator in an atmosphere of 5% CO ₂ at T = 37 ° C. The formation of a complete monolayer of cells is observed after 1 day. cultivation (figure 4). When the web with the monolayer of the culture of embryonic epithelium MA-104 grown on them is moved to another Petri dish, the viability of the cells and their ability to further adhesion and proliferation are preserved.

Example 71. A monolayer of cell culture of MA-104 embryonic epithelium is disaggregated and separated from the non-woven fibrous-porous web by enzymatic treatment with a mixture of 0.25% trypsin solution with 0.2% solution versen in a 1: 1 ratio at T = 37 ° C (Fig. 5).

Example 72 is performed analogously to example 70. The difference is that normal fibroblasts isolated from human skin are used in a concentration of not less than 1 million in 1 ml. The formation of a complete monolayer of cells is observed in the period from 5 to 7 days.

Examples 70-72 show the high biocompatibility of a non-woven fibrous-porous fabric from electrospun biopolymer chitosan fibers with dermal and epithelial cells, which allows positive recommendations for its use in medicine, pharmacology, cosmetology, etc.

Example 73. The use of a biological dressing of a non-woven fibrous-porous fabric, formed from biopolymer fibers of chitosan or a salt of chitosan and an organic acid, for the treatment of wounds of various etiologies.

Clinical studies of a biological dressing in the form of a wound cover from a non-woven fibrous-porous web of biomedical use from electro-spun fibers of chitosan or a salt of chitosan and an organic acid and a method for treating wounds of various etiologies using this dressing were carried out in the Municipal Clinical Hospital No. 7 of the city of Saratov on volunteer patients in the treatment of II-IIIAB degree burns, donor sites, long-term non-healing wounds, trophic ulcers, pressure sores and other skin defects according to GOST R 52379-2005 "Good clinical practice."

The clinical study included 59 patients. Moreover, the created biological dressing in the form of a wound dressing from a nonwoven fibrous-porous web of biomedical use from electro-spun fibers of chitosan or a salt of chitosan and organic acid was used to treat II-IIIA degree burns in 15 people, residual long-term healing wounds in 18, and donor wounds in 8, trophic ulcers in 5, bedsores in 3, as a temporary closure of wounds in the area of deep burns after necrectomy in order to prepare them for autodermoplasty in 5, for the treatment of wounds closed by autodermografts in 5. Pl the area of burn wounds, for the treatment of which a biological dressing was used, ranged from 0.5 to 15% of the body surface.

Evaluation of the effectiveness of wound dressings was carried out on the basis of clinical observations. Control over the course of the wound process was carried out on the basis of clinical data (color and nature of the exudate, relief of signs of inflammation, time of appearance of granulations, formation of the epithelial layer), the timing of completion of epithelization, and the duration of individual phases. The subjective sensations of the patient (soreness, burning, itching) were also evaluated, side effects were revealed, the usability of the dressings was evaluated.

Clinical studies have shown that wound coverings based on a non-woven fibrous-porous web of biomedical use made of electro-spun fibers of chitosan or a salt of chitosan and an organic acid are easily modeled on the surface of wounds and adhere tightly to the wound surface due to their high plasticity, they sorb excess wound excess well. Their pronounced stimulating effect on the regenerative processes in wounds was noted. The use of developed wound coverings promotes earlier regeneration of the upper layer of the skin and quick self-healing of superficial wounds, the growth of granulation tissue and accelerated preparation of wounds for transplant autoderm grafts in the deep wound area, stimulates marginal and islet epithelization in the treatment of long-term non-healing wounds, reduces blood loss in the donor area wounds.

Coatings can be on the wound for a long time, atraumatic, and also easily peel off as the wound epithelializes, which allows the dressing to be performed painlessly and without trauma to the underlying wound tissue. In some cases, the complete restoration of the lost skin is achieved through a single application of the coating. These properties of the developed biological dressings can protect wounds from infection, prevent additional trauma to the newly formed epithelium, significantly reduce the number and frequency of dressings, the number of anesthetic benefits, and reduce plasma loss in the area of extensive wounds, which reduces the need for protein fluids to be transfused.

Created wound coverings are well tolerated by patients, do not cause allergic reactions even with prolonged exposure to the wound surface. The application of wound dressing is not accompanied by painful sensations in the patient. After applying the bandage, all patients noted a decrease in discomfort and pain, which allowed to reduce the dose of pain medication. Side effects when applying wound dressings were not observed. In all observations, there were no cases of suppuration and complicated course of the wound process.

Thus, wound dressings based on non-woven fibrous-porous tissue of a biomedical purpose from electrospun chitosan fibers provide optimal conditions for regeneration and uncomplicated course of the wound process, have a stimulating effect on regenerative processes in wounds of various etiologies, and contribute to timely epithelization of wounds, which can significantly accelerate the process healing, protect the wound from the occurrence of the infectious process and trauma, reduce the patient's treatment time and to prevent the formation of rough scars.

The developed biological dressing has a number of unique characteristics in comparison with well-known compositions of the same purpose: improved consumer properties, well tolerated by patients, reduces the consumption of dressings and expensive medications, convenient in use, which allows it to be used to provide medical care to patients with wounds of various etiologies, including in extreme conditions.

The use of the created biological dressing is an effective way to treat wounds of various etiologies depending on the objective condition of the wound and the stage of its healing and can be recommended for the treatment of II-IIIAB degree burns, donor sites, long-term non-healing wounds, trophic ulcers, pressure sores and other skin defects.

Thus, the invention for the first time defines compositions and methods for preparing molding solutions of chitosan and auxiliary polymer or chitosan and auxiliary polymers for electroforming nanofibers and submicron diameter fibers from chitosan or a salt of chitosan and an organic acid, as well as a nonwoven fibrous-porous fabric based on them:

- with a low content of auxiliary polymer: polyethylene oxide in an amount of 0.012-0.4 wt.% when using acid-soluble samples of chitosan, polyethylene oxide in an amount of 0.069-0.6 wt.%, polyvinyl alcohol or polyvinylpyrrolidone in an amount of 1.43-1.92 wt.% when using water-soluble samples of chitosan;

- with a low content of auxiliary polymers: polyethylene oxide in an amount of 0.012-0.4 wt.% and cellulose diacetate in an amount of 0.051-0.09 wt.%;

- with the use of organic acids for multi-purpose use in medicine, pharmacology, cosmetology, food industry, etc.: acetic, citric, lactic, ascorbic, succinic, aminocaproic, tranexamic.

- with the addition of biologically active substances: hemostatic, antiseptic, antimicrobial drugs, local anesthetics, proteolytic enzymes, etc.

For the first time, electrospun biopolymer nano- and microfibers from chitosan or a salt of chitosan and an organic acid were obtained, as well as samples of a nonwoven fibrous-porous fabric based on them with a surface density of 5-25 g / m ² :

- with a low content of auxiliary polymer: polyethylene oxide in an amount of 0.25-9.3 wt.% when using acid-soluble samples of chitosan, polyethylene oxide in an amount of 1.0-24.2 wt.% when using water-soluble samples of chitosan,

- with a low content of auxiliary polymers: polyethylene oxide in an amount of 0.25-9.3 wt.% and cellulose diacetate in an amount of 4.0-7.3 wt.%;

- using organic acids for multi-purpose use, many of which are used as medicines;

- with the addition of biologically active substances that give the finished product an additional therapeutic effect.

Methods have been developed for modifying a non-woven fibrous-porous fabric from electro-spun biopolymer fibers of chitosan or a salt of chitosan and an organic acid, which make it possible to obtain a fabric with high elastic properties and with sufficient strength for use in medical practice. Modification methods are simple to implement, environmentally friendly and economically viable.

Based on the obtained highly elastic, non-toxic, biocompatible and biodegradable non-woven fibrous-porous fabric from electro-spun biopolymer fibers of chitosan or a salt of chitosan and an organic acid, a biological dressing has been created and a method has been developed for treating wounds of various etiologies using this dressing depending on the objective state of the wound and the stage of its healing. . As a biologically active additive, the dressing may contain a proteolytic enzyme, an antimicrobial, antiseptic, hemostatic or analgesic drug.

The dressing is a healing wound dressing and has a number of unique characteristics, due to its own properties of the canvas:

- maximum ductility and elasticity;

- complete congruence with the surface of the wound;

- a high degree of atraumatic;

- improved absorption of the wound;

- the property of holding the wound discharge within the coating;

- exposure to a wound with a regenerative effect;

- moderate antibacterial effect;

- non-allergenic;

- providing gas exchange of the wound surface;

- property gradually dissolves independently under the action of a wound discharge;

- accurate dosing of the medicinal product in the dressing;

- targeted drug delivery to damaged tissues;

- prolonged therapeutic effect on the wound;

- uniform therapeutic effect on the wound throughout its area;

- the possibility of a long stay on the wound, in some cases until the complete restoration of the lost skin with the achievement of healing due to a single application of the drug;

- lack of need for frequent dressings, a significant reduction in soreness and frequency of dressings;

- ease of use.

The stimulating effect of wound dressing is also due to the introduction of biologically active substances in tissues that stimulate regeneration and create a structural basis for epithelization, vascular sprouting and growth of granulation tissue. Moreover, the coating structure provides favorable conditions for the migration of cells and the formation of their monolayers.

Thus, a biological dressing in the form of a wound cover made of a non-woven fibrous-porous fabric of biomedical purpose from electro-spun nanofibers of chitosan or a salt of chitosan and an organic acid provides conditions that are optimal for healing on the wound surface, which leads to a reduction in the treatment time, as well as improved functional and cosmetic treatment results by reducing the possibility of scar formation.

Table 1. Physicochemical Characterization of Polymers Polymer Manufacturer Characteristics

, кДа

kDa

kDa SD, mol.% Chitosan ZOA "Bioprogress", Schelkovo 38 - 80.0 87 - 83.6 200 - 82.0 280 - 82.8 480 - 84.1 Laboratory sample, Saratov 220 - 93.4 280 - 88.7 Polyethylene oxide Sigma-Aldrich, USA - 2000 - - 5000 - - 8000 - Polyvinyl alcohol Sigma-Aldrich, USA - 130 - Polyvinylpyrrolidone LLC "Orgpolymersynthesis Spb" TU 9365-002-46270704-2001, Izv. Number 5 Cellulose diacetate Khimvolokno LLC, Vladimir 70 - CA * = 55 * CA is the degree of acetylation.

Table 2. Pharmacological properties of organic acids and biologically active substances Substance / preparation Appointment Acids Lemon Regulation of energy metabolism in cells, antioxidant effect Dairy Regulation of metabolic processes, antimicrobial and antiseptic effects Ascorbic (Vitamin C) Regulation of redox processes, carbohydrate metabolism, blood coagulation, tissue regeneration; participation in the synthesis of collagen and procollagen; antioxidant effect Amber Stimulation of metabolic processes in cells, antioxidant effect Aminocaproic Hemostatic effect Tranexam Hemostatic effect, fibrinolysin inhibitor Biologically active substances Protorgol, povidone-iodine, chlorhexidine, etc. Antiseptic, disinfectant and anti-inflammatory effect Novocaine, lidocaine, trimecaine, prilocaine, etc. Local anesthetizing effect: decrease or complete suppression of the excitability of sensitive nerve endings in dermal and other tissues Furagin, fusidin-Na, azithromycin, erythromycin, clarithromycin, etc. Antibacterial and bacteriostatic effect against Staphylococcus spp., Nocardia asteroides, Clostridia spp., Neisseria meningitidis, Neisseria gonorrhoeae, Streptococcus spp. and etc. Chymotrypsin, chymopsin, collagenase, protease C, etc. Proteolytic effect: splitting of necrotic tissue (without affecting living tissue), thinning viscous secrets and exudates Thrombin, ferrocryl, etc. Hemostatic effect

Claims (21)

1. The composition of the molding solution for forming biopolymer fibers, including chitosan, polyethylene oxide, organic acid, water, characterized in that 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, with a ratio of components, wt.%:
chitosan 2.0-7.0 polyethylene oxide 0.012-0.4 organic acid 2,5-70 water rest 2. The composition according to claim 1, characterized in that the organic acid used is acetic acid of 50-80% concentration or citric acid of 10-50% concentration or lactic acid of 5-30% concentration or ascorbic acid 10 -30% concentration or succinic acid of 5-10% concentration or aminocaproic acid of 3-6% concentration or tranexamic acid of 2.5-5% concentration. 3. The composition according to claim 1, characterized in that it further comprises cellulose diacetate in an amount of 0.051-0.09 wt.%. 4. The composition according to claim 1, characterized in that it additionally contains additives of biologically active substances in an amount of 0.4-0.55 wt.%, While biologically active substances of local anesthetic or antibacterial and bacteriostatic, stable in an acidic environment, are used as additives actions. 5. The composition of the molding solution for forming biopolymer fibers, including chitosan, polyethylene oxide, water, characterized in that chitosan is used with a molecular weight of 30-40 kDa, polyethylene oxide is used with a molecular weight of 2000-8000 kDa, with a ratio of components, wt.%:
chitosan 5.71-6.89 polyethylene oxide 0.069-0.6 water rest 6. The composition according to claim 5, characterized in that it contains additives of biologically active substances in an amount of 0.1-1.25 wt.%, While biologically active substances of antiseptic, disinfectant, anti-inflammatory or local anesthetic or antibacterial are used as additives bacteriostatic or proteolytic or hemostatic action. 7. The composition of the molding solution for forming biopolymer fibers, including chitosan, water, characterized in that it additionally contains polyvinyl alcohol or polyvinylpyrrolidone, while chitosan is used with a molecular weight of 30-40 kDa, with a ratio of components, wt.%:
chitosan 6.0-7.14 polyvinyl alcohol or polyvinylpyrrolidone 1.43-1.92 water rest 8. A method of preparing a molding solution of a composition according to claims 1-4, 5, 7, comprising 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 with their subsequent dissolution in an appropriate solvent on a magnetic stirrer until a homogeneous state for 2-8 hours 9. A biopolymer fiber comprising chitosan in the form of an organic acid salt and polyethylene oxide, characterized in that 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, at a ratio components, wt.%:
chitosan as an organic acid salt 90.7-99.75 polyethylene oxide rest 10. The biopolymer fiber according to claim 9, characterized in that chitosan acetate or chitosan citrate or chitosan lactate or chitosan ascorbate or chitosan succinate or chitosan aminocapriate or chitosan tranexamate are used as the chitosan salt and organic acid. 11. Biopolymer fiber according to claim 9, characterized in that it further comprises cellulose diacetate in an amount of 4.0-7.3 wt.%. 12. The biopolymer fiber according to claim 9, characterized in that it additionally contains additives of biologically active substances in an amount of 6.2-8.3 wt.%, While biologically active substances of local anesthetic or antibacterial and stable in an acidic environment are used as additives bacteriostatic action. 13. Biopolymer fiber, including chitosan and polyethylene oxide or polyvinyl alcohol or polyvinylpyrrolidone, characterized in that chitosan is used with a molecular weight of 30-40 kDa, polyethylene oxide is used with a molecular weight of 2000-8000 kDa, with a ratio of components, wt.%:
chitosan 75.8-99 polyethylene oxide rest 14. The biopolymer fiber according to item 13, characterized in that it additionally contains additives of biologically active substances in an amount of 1.4-14.9 wt.%, While biologically active substances of antiseptic, disinfectant, anti-inflammatory or local anesthetic or antibacterial and bacteriostatic or proteolytic or hemostatic effects. 15. A biomedical canvas, which is a non-woven fibrous-porous material formed from biopolymer fibers according to any one of claims 9-14, 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 , tensile strength with uniaxial tension of 0.61-33.6 N, elongation at break of 6.0-16.4%, the degree of sorption of water vapor 55-110 wt.% and vapor 0.5 N hydrochloric acid 450-1500 wt. %, the degree of sorption of physiological saline 600-800 wt.% and distilled water 450-650 wt.%, while Use chitosan with a molecular weight of 30-500 kDa, a deacetylation degree of 80-95 mol.%. 16. A method of modifying a web of biomedical use according to claim 15, characterized in that the web is further subjected to swelling in physiological saline or distilled water at a temperature of 20-25 ° C for 2-3 minutes to a degree of sorption of physiological saline by a cloth of at least 600-800 wt.%, distilled water of at least 450-650 wt.%, while providing a value of the relative elongation of the canvas at break of at least 35%. 17. The method of modifying a web of biomedical use according to claim 15, characterized in that the web is further subjected to heat treatment at a temperature of 80-150 ° C for 15-30 minutes, after which the web is additionally placed in distilled water or physiological saline to a degree of swelling of the web 700 -1100 wt.%, While providing a value of the relative elongation of the web at break of at least 35%. 18. The method for modifying a web of biomedical use according to claim 15, characterized in that the web is additionally treated with an alkaline reagent for 1 hour, followed by washing with distilled water until a neutral pH is reached, after washing, the web is placed in distilled water to a degree of swelling of the web of at least 200 -410 wt.%, While providing a value of the relative elongation of the web at break of at least 35%. 19. The method of modifying the web according to claim 18, characterized in that a 1 N sodium hydroxide solution or triethanolamine or ethyl alcohol is used as the alkaline reagent. 20. A biological dressing for the treatment of wounds of various etiologies in the form of a wound dressing, including chitosan, characterized in that it is a non-woven fibrous-porous fabric of biomedical purpose, formed from electrospun biopolymer fibers of chitosan or a salt of chitosan and an organic acid according to any one of claims 9- 14, using chitosan with a molecular weight of 30-500 kDa, a degree of deacetylation of 80-95 mol.%. 21. A method of treating wounds of various etiologies, including a wound toilet and applying a biological dressing to it, characterized in that the biological dressing according to claim 20 is used.

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