EA033876B1 - Pharmaceutical composition with homeostatic and wound-healing effect - Google Patents

Abstract

The invention represents a pharmaceutical composition in the form of a sterile powder for topical use with a homeostatic and wound-healing effect, the composition comprising a carboxylated derivative of a glucopyranose-based polymer as the main active substance in the form of a sterile powder for topical use with a homeostatic and wound-healing effect, comprising a carboxylated derivative of a glucopyranose-based polymer as the main active substance mixed with other components based on 100 kg of a mixture: 0.1-90 kg of the carboxylated derivative of a glucopyranose-based polymer, 0.1-30 kg of epsilon-acetylaminocaproic acid, epsilon-aminocaproic acid or a mixture thereof, 0.1-10 kg of protamine, 0.1-5 kg of dipyridamole, 0.1-5 kg of papaverine, 0.1-5 kg of bendazole. The composition can be used for quick cessation of venous and arterial bleeding of a traumatic nature (gun-shot wounds and the like) and for the activation of wound regeneration, including post-operative wounds, burns, abdominal wounds, traumatic wounds including gun-shot wounds. The invention can be used in pharmaceutics, surgery, A&E and first medical aid.

Description

Technical field

The invention relates to pharmacy and urgent medicine, surgery, and in particular to topically applied powder compositions for the rapid stopping of bleeding in humans and animals.

Terminology

A pharmaceutical composition with a hemostatic effect is a mixture of several substances, including several biological active hemostatic and wound healing, as well as several auxiliary and form-forming substances in the form of a sterile powder for topical use, which can also be used to accelerate wound healing, stop bleeding as with capillary, venous, and arterial bleeding due to the ability to quickly swell in the wound and tampon it. An analogue of the proposed tool is the drug Celox (Celox), which is able to absorb blood from the wound and turn into a gel, thereby closing open bleeding.

The carboxylated derivative of the glucopyranose polymer is [C6H7O2 (OH) 3 _-x (OR-COOH) _x ] _n , where x = 0.05-3, R = -CH ₂ -; —CO — CH ₂ —CH ₂ -; -CO-CH = CH- and others) is a derivative of a glucopyranose polymer in which carboxylation of glucose residues is carried out by introducing a carboxyl group (-COOH) by alkylation or acylation of hydroxyl glucose residues (glucopyranose); glucopyranose monomers are interconnected by 1,4-glycosidic bonds. Modification of alcohol hydroxyls of glucopyranose can be carried out with varying degrees of substitution (x = 0.08-3) by carboxylation (carboxycellulose or carboxy starch). For the carboxylation of polysaccharides, maleic, succinic, phthalic and other anhydrides of di- and polycarboxylic acids can be used, and for alkylation, substances such as monochloroacetic acid (carboxymethyl cellulose or carboxymethyl starch are formed in this case).

Cellulose is one of the most common natural polymers of a polysaccharide nature, the main component of the cell walls of plants, which determines the mechanical strength and elasticity of plant tissues. Cellulose macromolecules are constructed from elementary units of D-glucose connected by 1,4-glycosidic bonds in linear unbranched chains. The average degree of polymerization of cellulose (the number of glycosidic residues) varies over a wide range - from several hundred (for viscose fiber pulp it is 300-500) to 10-14 thousand (for cotton fiber and bast fibers). Cellulose has a complex supramolecular structure. The primary element is a microfibril, consisting of several hundred macromolecules and having the form of a spiral (thickness 35-100, length 500-600 nm and above).

Carboxymethyl cellulose - (CMC, cellulose glycolic acid, [C ^ O ^ OHy-TOCH ^ OOHXE, where x = 0.08-1.5) is a cellulose derivative in which cellulose is carboxylated by introducing a carboxylmethyl group (-CH2-COOH) via covalent bond with hydroxyl groups of glucose monomers. Na-carboxymethyl cellulose is used as a plasticizer, thickener, and resorbent. As a thickening agent, it is a part of toothpaste, food products, cosmetics, medicines.

Carboxypropyl cellulose is a CPC, a cellulose derivative in which carboxylation of cellulose is carried out by introducing a carboxypropyl group (—CH ₂ —CH ₂ —CH ₂ —COOH) through a covalent bond with the hydroxyl groups of glucose monomers. It is used in tablet coatings and as a prolonging excipient in the production of various dosage forms of drugs.

Carboxymethyl starch - (CMS) is a modified starch, ether starch, water-soluble anionic polymer. It is odorless, non-toxic, linear in form with a degree of substitution of more than 0.2 or more, soluble in water. Formula [C ₆ H ₇ O ₂ (OH) ₂ OCH ₂ COONa. It can be used as an emulsifier, thickener, dispersant, stabilizer, adhesive, film-forming agent, which are widely used in oil, textile, chemical, tobacco, paper, construction, food, pharmaceutical and other industries. Its sodium salt, also known as (CMS-Na), is commonly used. It is a white or yellow powder, without taste and smell, non-toxic, easily absorbs moisture. Soluble in alcohol, ether, chloroform and other organic solvents.

Epsilon-aminocaproic acid - (6-aminohexanoic acid or ε-aminocaproic acid) is a hemostatic drug that inhibits the conversion of profibrinolysin to fibrinolysin.

Epsilon-acetyl-aminocaproic acid - Acetyl-6-aminocaproic acid in the form of a sodium salt is used as a medicine called acetamin. A feature of the action of Acemine is the ability to cleanse wounds from necrotic masses, reduce exudation, accelerate epithelization and tissue regeneration. Acemin is used to treat long-term non-healing wounds, burns, as well as closed fractures, especially with prolonged bone non-healing, to accelerate the formation of a postoperative scar.

The protamine base is a low molecular weight (4-12 kD) basic nuclear protein; in many animals, along with histones, it is contained in sperm, and in some (for example, in fish) it is completely

- 1,033,876 places histones; the presence of protamine protects DNA from the action of nucleases and gives chromatin a compact form. It is an antagonist of heparin and enhances blood coagulation.

Activators of cyclic adenosine monophosphate accumulation - substances that increase the accumulation in the cell of cyclic adenosine monophosphate (cAMP), as a rule, these are activators of adenylate cyclase (papaverine, bendazole) or phosphodiesterase inhibitors (dipyridamole).

Cyclic adenosine monophosphate (cAMP) is a secondary messenger of cells involved in conducting intracellular signals. The 3,5- (phosphate) adenosine molecule is formed by the action of adenylate cyclase (APC) on adenosine triphosphate.

The main element of the cyclase system is adenylate cyclase, associated with the cell membrane and forming the receptor-G-protein / GTP: ACC complex. G-proteins interact with ACC. As a result, the function of cAMP-dependent protein kinases (A1 and A2) changes and the concentration of cAMP in the cAMP cell is a key factor in the negative regulation of the ICC function, activates protein kinase A, remains in the form of secondary messengers when the cell is stimulated with cytokines, hormones, mitogens and antigens. With an increased content of cAMP in mast cells, their response to signals causing degranulation weakens. The content of cAMP in the cell changes both in the early stages of ICC activation (recognition and reception of activators, changes in the state of the cell membrane, activation of kinase, phospholipid, calmodulin and coactivation signaling pathways), as well as in its later stages (cytokine synthesis, proliferation). cAMP has a positive effect on the maturation and differentiation of macrophages, on their cytotoxic activity. The activity of the cAMP signaling pathway regulates the expression of c-fos and c-jun genes, factor AP-1, the conduct of co-stimulatory signals by increasing the activity of transcription factors CREB, CREM, ATF. The negative regulation of the cAMP-dependent signaling pathway is carried out by the enzyme phosphodiesterase, which destroys cAMP. Phosphodiesterases of types 3 and 4 function in lymphocytes.

Dipyridamole - dipiridamole, 2,6-bis [bis- (3-hydroxyethylamino) -4,8-di-H-piperidino-pyrimido- (5,4d) pyrimidine.

Papaverine - 1- (3,4-dimethoxybenzyl) -6,7-dimethoxyisoquinoline.

Bendazole - 2- (phenylmethyl) -S-benzimidazole.

State of the art

Cellulose derivative preparations.

Due to the presence of hydroxyl groups in elementary macromolecules, cellulose is easily esterified and alkylated; these reactions are widely used in industry to produce cellulose ethers and esters. Many cellulose derivatives are able to form elastic films, which determines their use in the production of various medicines.

For the preparation processes using high quality reverse osmosis water (including for medical purposes), several grades of cellulose acetate membranes (MGA series) are produced, which have a selectivity of sodium chloride from 70 to 90%. Ultracellulose membranes (pore sizes from 5 to 50 nm) based on cellulose acetate are used to purify and concentrate proteins, enzymes, and antibiotics. Microfiltration membranes (pore sizes from 100 to 1000 nm) are used in microbiological, biological and physicochemical analyzes, for cleaning microorganism solutions of drugs, sterilizing filtration, electrophoretic separation of blood serum proteins and other high molecular weight compounds.

The use of cellulose acetate (AC) for microencapsulation of low and high molecular weight drugs is promising. Typically, polymer microcapsules are of the order of tens or hundreds of microns, and the membrane thickness is hundredths or tenths of a micron. Microencapsulated drugs (microcapsule size less than 20 microns) are introduced into ointment bases, used to prepare syrups and other liquid dosage forms. Microencapsulation is used in the preparation of injectable mixtures in the form of suspensions of microcapsules for intramuscular and subcutaneous administration with controlled release.

The use of cellulose acetate for microencapsulation of drugs allowed to obtain microcapsules with a release rate of the drug, depending on the size of the microcapsule.

Cellulose acetates are used as a polymer permeable membrane for the immobilization of enzymes (glucooxidase, invertase, esterase, etc.), as well as polyenzyme systems (glucose oxidase and catalase, glucose oxidase and peroxidase). Using cellulose triacetate, fibrous immobilized enzymes were obtained.

In the production of tablets, AC is used to create a film that protects the medicinal substance from the effects of the external environment, and also as a binding and granulating substance.

Water-soluble AC is used to coat tablets of various drugs (glucose, terpinghydrate, aspen, ascofen, amidopyrine, etc.) and serves as a protective coating, providing a prolonged action of the drug.

The film-forming properties of methyl cellulose (MC) make it possible to use it as a protective coating for medicinal substances for enteral or topical use. By dissolving

- 2 033876 or suspension of medicinal substances for various purposes in a solution of MC with a polymer concentration of up to 60%, single-dose drugs in the form of films with a thickness of 0.05-1 mm were obtained.

From methylhydroxypropyl cellulose (MGPC), film coatings are prepared for gastro-soluble solid dosage forms.

Phthalyl, acetylphthalyl, acetylsuccinyl - cellulose derivatives (manufactured by Japanese companies) are widely used in the manufacture of medicines. The shell of tablets of such polymers does not dissolve in the stomach (pH 1.4) and protects the drug from the harmful effects of the contents of the stomach. Once in the intestines (pH 6.7-7.4), the tablet shell dissolves, which allows the drug to quickly absorb into the blood.

Sodium salt of carboxymethyl cellulose (Na-CMC) can be used as a protective shell for suppositories intended for use in places with a hot climate. Tablets with good appearance and satisfactory strength and disintegration characteristics in the body are usually obtained using (1-8)% Na-CMC solutions. The CMC aluminum salt in the form of a 1-5% aqueous solution is used for the manufacture of rapidly disintegrating vaginal tablets.

Films of Na-CMC have a pronounced stimulating effect on reparative processes in infected skin wounds, accelerate the formation and maturation of granulation tissue, and actively influence fibrillogenesis processes. An effective tool for the treatment of long-term non-healing radiation burns is an ointment, which is a Na-CMC gel containing an anti-inflammatory substance - fodomos. Ointments based on Na-CMC are used as light-protective, coating and cooling pastes. Bactericidal fluids containing Na-CMC form water-washable films and can be used to treat external wounds.

Pure methyl cellulose hydrogels are used as a drying ointment or wet dressing, as well as protective ointments when working with organic solvents and aggressive media. For the treatment of skin diseases, burns and local anesthesia, MC-based ointments containing anesthetics, antibiotics, silver salts, mercury, zinc, etc. are used.

For the treatment of wounds and burns, the use of monocarboxyl cellulose (MCC) in the form of a sedimentation-resistant aqueous suspension, which forms a film on a drying wound surface, has been proposed. This form of MCC can be considered as a biomaterial that combines the properties of a wound cover and a therapeutic agent that stimulates healing. Acceleration of healing of burns with the help of MCC is 35%. The range of therapeutic effects of the suspension can be significantly expanded by introducing biologically active substances into its composition.

Since the pharmacological action of many drugs is determined by the presence of the corresponding chemical groups in their composition, a new approach to the synthesis of drug polymers using the chemical properties of cellulose derivatives has been implemented. The prescribed character of the pharmacological action is given to the polymer by introducing the corresponding chemical groups into the polymer chain.

The prolonged action of drugs can also be achieved by attaching them to the polymer matrix with a relatively labile covalent bond, in particular ester or amide. To obtain such derivatives, the drug fixation reaction is carried out with carboxymethyl cellulose chloride.

Modified starches.

Starches can be modified in several ways in order to change their technological and physico-chemical properties.

When heated with acid or as a result of enzymatic hydrolysis, long starch chains are broken down into simpler molecules with the formation of low molecular weight water-soluble dextrins (dextrin, polydextrin and maltodextrin). Dextrins can be crosslinked so that the chains form a loop. Cyclodextrins are substances used as solubilizers of hormones and fat-soluble vitamins.

Starches pregluteinize (pre-gelatinized) by high temperature extrusion to obtain instant gelatinization preparation. Known oxidized starch obtained in reaction with sodium hypochlorite, characterized by the formation of transparent and low viscosity solutions. The introduction of a carboxymethyl group makes starch less prone to degradation at high temperature and by bacteria. Carboxymethylated starch is also called starch glycolate.

Carboxymethyl groups increase the wettability and solubility of starch; therefore, it is often used as a disintegrant of tablet dosage forms.

The introduction of longer carbon chains (carboxyethyl or carboxypropyl) reduces the tendency of starch to recrystallize. This fact is important for increasing the durability of pharmaceutical gels.

Starches can be esterified with acetic acid. Acetylated starch is an excellent film former.

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Known pharmaceutical composition (US Patent 5773033 Autologous isolated and purified fibrinogen with biocompatible anionic or cationic chitosan polymer), which is a chitosan / fibrinogen containing hemostatic agents. Agents containing fibrinogen and chitosan have been patented, having strong hemostatic properties and are applicable in urgent cases to stop bleeding from damaged vessels. Chitosan and fibrinogen are applied to the tissue base and, when bleeding occurs, similar tissue is applied to the wound, thereby stopping bleeding.

The disadvantage of this invention is the presence of an expensive protein of fibrinogen from donated blood in a lyophilized form. In addition, chitosan and its salts have a very limited degree of swelling and the onset of action. Such compositions cannot be used to urgently stop heavy gunshot, including abdominal, bleeding due to the onset of action after 15-20 minutes. After this period of time with arterial bleeding, the patient loses more than 50% of the blood and dies. In addition, these compositions are not able to activate tissue regeneration like cAMP activators.

These disadvantages are eliminated by the use of carboxylated starch and cellulose derivatives in the form of salts with coagulation activators (aminocaproic acid and protamine) and tissue regeneration activators (papaverine, bendazole and dipyridamole). The low cost of these products, the formation of salts between them and the carboxypolysaccharide carrier during swelling, the high swelling rate and a high percentage of liquid uptake make it possible to use this composition in the form of a powder when introduced into the wound to stop urgent, including arterial bleeding.

Disclosure of Invention

The aim of the invention is the creation of a pharmaceutical composition with hemostatic and wound healing effects, capable of exerting a quick effect in emergency cases of rupture of blood vessels, including gunshot and including arterial bleeding when applied topically in the form of a sterile powder.

This goal is achieved by creating a pharmaceutical composition in the form of a sterile powder for topical application with a hemostatic and wound healing effect containing, as the main active substance, a carboxylated derivative of the glucopyranose polymer in a mixture with other components per 100 kg of a mixture of 0.1-90 kg of a carboxylated derivative of a polymer glucopyranoses, 0.1-30 kg of epsilon-acetyl-aminocaproic, epsilonaminocaproic acid or a mixture thereof, 0.1-10 kg of protamine, 0.1-5 kg of dipyridamole, 0.1-5 kg of pa Averina 0.1-5 kg bendazol.

Further differences of the present invention are that carboxymethyl cellulose is used as a carboxylated derivative of glucopyranose polymer, carboxypropyl cellulose is used as a carboxylated glucopyranose derivative, succinyl cellulose is used as a carboxylated glucopyromatic polymer and carboxymecopyrroxypropyl derivative is used. succinyl starch is used as the glucopyranose polymer; a mixture of carboxymethyl cellulose, carboxypropyl cellulose, succinyl cellulose, carboxymethyl starch and succinyl starch is used as the carboxylated derivative of the glucopyranose polymer.

The chemical structure of the carboxylated glucopyranose polymer [CeH'zO ^ OHh ^ OR-COOH) ^, where x = 0.05-3, R are the carboxyl-containing substituents -CH ₂ -; -CO-CH ₂ CH ₂ -; -CO-CH = CH- and others)

Embodiments of the invention

Example 1. Obtaining a pharmaceutical composition Gemma.

0.1-90 kg of carboxy starch (for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof) are added to the mixer, 0.1-30 kg of epsilon-acetyl-aminocaproic acid, 0.1-10 kg of protamine, 0.1-5 kg of papaverine, 0.1-5 kg of bendazole, 0.1-5 kg of dipyridamole, mix until completely homogeneous, pack 1-30 g in aluminum bags or glass vials. Vials

- 4 033876 are corked with rubber stoppers and rolled with aluminum caps, and aluminum bags are sealed on a packaging machine. Vials and bags are autoclaved under standard sterilization conditions (120 ° C, 30 min).

Example 2. Obtaining a pharmaceutical composition Carbox.

0.1-90 kg of carboxycellulose (for example, succinyl cellulose, maleinyl cellulose, carboxymethyl cellulose or a mixture thereof) are added to the mixer, 0.1-30 kg of epsilon-aminocaproic acid, 0.1-1 kg of protamine, 0.1-5 kg of papaverine are added , 0.1-5 kg of bendazole, 0.1-5 kg of dipyridamole, mix until completely homogeneous, pack 1-30 g in aluminum bags or glass vials. The bottles are corked with rubber stoppers and rolled with aluminum caps, and the aluminum bags are sealed on a packaging machine. Vials and bags are autoclaved under standard sterilization conditions (120 ° C, 30 min).

Example 3. Obtaining a pharmaceutical composition Carbox / Gemma.

0.1-90 kg of carboxycellulose (for example, succinyl cellulose, maleinyl cellulose, carboxymethyl cellulose or a mixture thereof) is added to the mixer, 0.1-90 kg of carboxy starch (for example, succinyl starch, maleinyl starch, carboxymethyl starch or a mixture thereof) is added, 0.1-30 kg of epsilon-aminocaproic acid, 0.1-1 kg of protamine, 0.1-5 kg of papaverine, 0.1-5 kg of bendazole, 0.1-5 kg of dipyridamole, mix until completely uniform, packaged in 1-30 g in aluminum bags or glass bottles. The bottles are corked with rubber stoppers and rolled with aluminum caps, and the aluminum bags are sealed on a packaging machine. Vials and bags are autoclaved under standard sterilization conditions (120 ° C, 30 min).

Example 4. The effect of the drug Carbox and Gemma on the coagulation time.

The most difficult type of surgical pathology are injuries and injuries of the abdomen, accompanied by heavy bleeding. In this regard, the provision of reliable hemostasis is one of the most pressing problems of modern surgery.

As a result of the studies, the bleeding time was established under the conditions of using modern hemostops. The following application preparations were used as materials for experimental studies: hemostatic collagen sponge (GGK), Hemostop, Celox, and experimental Carbox and Gemma preparations. The experiment was performed on 60 Wistar rats. In an acute experiment, a median laparotomy was performed under anesthesia, and standard liver and spleen injuries were modeled. A hemostatic agent comparable to its size was poured onto the wound area. Simultaneously with the modeling of wounds using a stopwatch, the bleeding time began. Thus, it was found that all experimental materials have hemostatic activity, significantly shortening the bleeding time, with the exception of the experiment with Hemostop material, whose indicators are close to control. The bleeding time from liver injury in the conditions of using Carbox and Gemma materials decreased by 62.7-68.9% relative to the control and by 37.2-43.8% relative to HHC. The shortening of the time to stop bleeding from a standard spleen injury was maximum when testing Carbox and Gemma materials and was 2.23-2.45 times (p <0.001) less than the control and 1.81-1.89 times (p <0, 05) relative to GGC. Indicators of bleeding time for HHC material contributed to a decrease in the time for stopping bleeding from liver injury by 34.0–40.4% and from spleen injury by 19.6–26.2% relative to the control.

Example 5. The rate of resorption of Carbox and Gemma.

One of the most important indicators of hemostatic drugs is their biological inertness and complete controlled biodegradation. Accordingly, as a result of in vitro studies, the rate of resorption of modern hemostatic materials Carbox and Gemma was established. Materials for the study were hemostatic application tools: hemostatic collagen sponge, Cellox, Hemostop, as well as new materials on Carbox and Gemma. The study was carried out in vitro under experimental conditions: a sample of hemostatic material weighing 1 g was placed in a volumetric tube containing 5 ml of distilled water. The tube was placed in a thermostat with a constant temperature of 37 ° C. The results of the biological degradation rate of each hemostatic material were evaluated on days 1, 3, 7, and 14. The test hemostatic tube was removed from the thermostat and a visual descriptive evaluation of the hemostatic agent was performed. The studied hemostop was removed from the experimental medium and dried. Subsequently, repeated weighing of the studied hemostop was performed. The difference in the mass of the hemostop before the experimental study and after its implementation, expressed as a percentage, reflected the rate of resorption of the studied drug. Studying in an experiment in vitro the rate of degradation of hemostatic agents showed that all the studied samples of materials were resorbed. High resorptive activity was observed in the hemostatic composition Gemma - 100% (P <0.001), the resorption rate was 97.83% (P <0.001), the maximum resorptive activity was observed in the GHS and Carbox (CMC) preparations. The lowest rates of degradation were observed in the study of the Hemostop material, the resorption of which is 10 times less relative to the Celox materials (42.3% (P <0.05)) amounted to 10.34% (P <0.05).

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Example 6. The study of the sorption activity of Carbox and Gemma.

As a result of the study, the sorption properties of modern application hemostops Carbox and Gemma were evaluated. The samples of the following hemostops were studied: hemostatic collagen sponge, Celox, Gemostop, Carbox and Gemma. In the course of the experiment, the mass of distilled water was determined, which is able to be absorbed by the experimental sample of the studied materials of standard equal mass (1 g). The degree of complete saturation of the studied agent was determined visually by a change in the spatial properties of the material — swelling. The time of complete saturation of the application preparations was fixed using a stopwatch. To assess the sorption activity of the studied samples of materials, their hygroscopicity was determined using the following formula hygroscopicity (ml / g) = m ₁ / m ₂ , where: m ₁ is the volume (mass) of water absorbed by the material (ml); m ₂ is the mass (g) of material. For a comprehensive assessment of the sorption properties of the application materials, we used a sorption indicator (SP), which is the volume of liquid that 1 g of a material sample can absorb for 1 s of the SP (mlkhs / g) = hygroscopicity / t, where t is the time of complete saturation of the material (from). The data obtained were processed statistically with the calculation of average values, average errors of the mean and significance of differences using Student and Mann-Whitney criteria (with respect to the hemostatic collagen sponge). The error of the statistical hypothesis was p <0.05. Thus, a relatively high sorption activity was demonstrated by a hemostatic collagen sponge having hygroscopicity of 69.41 ± 1.65 ml / g and a sorption index of 15.1 ± 0.95 mlhc / g. The hygroscopic results of the Carbox and Gemma materials were 70.31 ± 1.71 ml / g (p <0.05) and 49.1 ± 0.31 ml / g (p <0.05), and the sorption index was 17.4 ± 1.11 mlhs / g (p <0.05) and 11.7 ± 1.12 mlhs / g (p <0.05), respectively. The minimum sorption properties were noted in the hemostops Celox and Hemostop, the hygroscopicity of which was 5.63 ± 1.21 ml / g and 6.11 ± 1.16 ml / g, and the sorption index was 1.23 ± 0.11 mlhs / g and 1 10 ± 0.04 mlhc / g, respectively.

Example 7. Determination of the effect of the compositions Carbox and Gemma on tissue regeneration. The study of the healing properties of the compositions was carried out on male Vistar white rats.

In 38 animals that were anesthetized with diethyl ether for 2–4 min, a 2 by 2 cm skin area was cut out on the dorsal side of the body, behind the right shoulder blade. The skin was taken with tweezers, it was pulled back, a piece of skin was cut off with a size of 2 cm, wound depth 2 mm , the average area of the wound was 4 ± 1.0 cm ² . The resulting wounds of a polygonal shape were intensively bleeding. Then the animals of the first and second groups (10 in each) were applied to the wound Carbox and Gemma. The wounds of rats of the 3rd group were treated with Celox, the 4th group of 8 animals was the control group, the wounds of these animals were not treated. The preparations were applied so that the formed gels covered the entire surface of the wound and capture a small fragment around the wound. BF-6 glue was applied on top of the gel, dried and the animals were released into cells. After 3, 6, 9, 11, and 13 days from the start of the experiment (before the healing of wounds in animals of all groups), a planimetric study was carried out, which made it possible to judge the features of reparative processes. The measurement of the area of the wounds was carried out in this way: on the celluloid film that was applied to the wound, its contours were applied, after which the area of the wound surface was determined using graph paper. The results of the first series of experiments (see table) showed that, under the influence of the Carbox and Gemma compositions, wound healing at all stages of the study was significantly accelerated. The effectiveness of the carboxy composition was statistically higher than that of the Gemma and Celox compositions.

Rat skin wound healing in rats under the influence of Carbox and Gemma compositions

A drug The foundation η The wound area * (S) during the observation, cm ² (M ± W) 1-3 days 3-6 days 6-9 days 9-11 days 11-13 days Carbox Carboxycellulose 10 4.0 + 0.7 1.1 ± 0.4 0.2 ± 0.1 - - Gem Carboxy starch 10 4.2 ± 0.9 2.0 ± 0.4 0.7 ± 0.2 0.4 ± 0.1 Coelox Chitosan 10 4.1 ± 1.0 3.2 ± 0.3 2.4 ± 0.3 1.0 ± 0.3 0.3 ± 0.1 The control - 8 4.0 ± 0.6 3.6 ± 0.6 2.6 ± 0.6 1.5 ± 0.5 0.5 ± 0.2

* P <0.05

As can be seen from the table, in fact, wounds in animals were healed 2 times faster, the wounds of which were treated with the Carbox composition (from 13 to 6 days), while the effectiveness of the control sample

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Celox was no different from control. Wound epithelization was initiated already on the second day after application of the composition.

Claims (7)

CLAIM 1. A pharmaceutical composition in the form of a topical powder with a hemostatic and wound healing effect, containing as its main active ingredient a polysaccharide, characterized in that for its production as a polysaccharide a carboxylated derivative of the glucopyranose polymer is used in a mixture with other components per 100 kg of mixture 0.1-90 kg carboxylated derivative of glucopyranose polymer, 0.1-30 kg of epsilon-acetyl-aminocaproic acid, epsilon-aminocaproic acid or mixtures thereof, 0.1-10 kg of protamine, 0.1-5 kg of dipyridamole, 0.1-5 kg papaverine, 0.1-5 kg of bendazole. 2. The composition according to claim 1, where carboxymethyl cellulose is used as the carboxylated derivative of the glucopyranose polymer. 3. The composition according to claim 1, where carboxypropyl cellulose is used as the carboxylated derivative of the glucopyranose polymer. 4. The composition according to claim 1, where succinyl cellulose is used as the carboxylated derivative of the glucopyranose polymer. 5. The composition according to claim 1, where carboxymethyl starch is used as the carboxylated derivative of the glucopyranose polymer. 6. The composition according to claim 1, where succinyl starch is used as the carboxylated derivative of the glucopyranose polymer. 7. The composition according to claim 1, where as a carboxylated derivative of a glucopyranose polymer, a mixture of carboxymethyl cellulose, carboxypropyl cellulose, succinyl cellulose, carboxymethyl starch, succinyl starch is used. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2