RU2180856C1 - Agent for wound healing - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: invention proposes an agent for wounds healing containing the following components, wt.-%: water-soluble derivative of cellulose, 0.9-15.0; water-soluble polysaccharide of vegetable origin forming polyanions in solution, 0.1- 15.0; alginic acid water-soluble salt, biological active supplement taken in the amount providing therapeutic effect and water, the balance. Agent is made as gel with viscosity 250 centipoises, not less. The prepared gel shows the enhanced strength, it forms elastic, porous, gas- and steam-permeable coating in contact with wound surface being without use of additional bandages. EFFECT: improved and valuable medicinal properties of agent. 13 cl, 9 ex

Description

 The present invention relates to medicine and is intended primarily for use in surgical practice for closing and treating wounds, burns, trophic ulcers.

 A known composition for the treatment of wounds containing (in wt.%) 0.2-1.5 collagen, 0.002-0.05 sulfated glycosaminoglycans, 0.05-2.5 water-soluble cellulose derivatives, the rest is water (RU, C1, 2092156) .

 This composition is made in the form of a solution that drains easily from the wound surface, which requires frequent application to the wound. So in the treatment of trophic ulcers, the solution is applied daily 3 times a day (see patent specification RU, C1, 2092156). In addition, this composition can cause allergic reactions, as it contains protein - collagen.

 The technical problem to which the invention is directed is to expand the arsenal of agents for the treatment of burns, weeping and lacerations, as well as trophic skin lesions.

 Another task is to create a tool that adheres well to the wet surface of the wound and forms a vapor-permeable coating on it.

 Another objective is to reduce the possibility of an allergic reaction.

 And another task is to prolong the action of drugs and increase the non-invasiveness of wound healing.

 The tasks are solved in that a wound treatment product is provided comprising a water-soluble cellulose derivative and water, which according to the invention further comprises a water-soluble plant-derived polysaccharide containing anionic groups and forming polyanions in solution, and a drug and / or biologically active additive.

 As a water-soluble plant-derived polysaccharide containing anionic groups and forming polyanions in a solution, the product contains at least one component selected from the group consisting of alginic acid, a water-soluble salt of alginic acid, carrageenan, fucoidin, zosterin, gum arabic, xanthangum, tragacanth and peck or their mixture in any combinations and ratios.

 As a medicinal substance, the agent contains at least one component selected from the group consisting of antibiotics, antiseptic substances, anesthetics, or a mixture of these substances.

 As a biologically active additive, the product contains vitamins, substances that affect cell regeneration, proteolytic substances, plant extracts, or a mixture of these substances.

The tool contains the following ratio of components, wt.%:
the sum of the water-soluble derivative of cellulose and the water-soluble polysaccharide of plant origin containing anionic groups and forming polyanions in the solution is 1.0-17.0;
a drug substance and / or dietary supplement in an amount sufficient to provide a therapeutic effect;
water is the rest.

The sum of the water-soluble derivative of cellulose and the water-soluble polysaccharide of plant origin containing anionic groups and forming polyanions in the solution is 1.0-17.0;
drug substance and / or biologically active additive - up to 10.0;
water is the rest.

 The tool can be made in the form of a gel with a viscosity of at least 250 cps.

 As a water-soluble cellulose derivative, the agent of the invention comprises methyl cellulose, or carboxymethyl cellulose, or a mixture thereof.

The tool may contain the following ratio of components, wt.%:
water soluble cellulose derivative -1.0-15.0;
alginic acid or its salts - 0.1-15.0;
drug substance and / or dietary supplement in an amount sufficient to provide a therapeutic effect;
water is the rest.

The tool may contain the following ratio of components, wt.%:
water-soluble cellulose derivative - 1.0-15.0;
carrageenan, or fucoidin, or zosterin, or gum arabic, or xanthan gum, or tragacanth or pectin - 0.03-15.0;
drug substance and / or dietary supplement in an amount sufficient to provide a therapeutic effect;
water is the rest.

The tool may contain the following ratio of components, wt.%:
Water-soluble cellulose derivative - 1.0-15.0
Alginic acid or its salts - 0.1-15.0
Carrageenan - 0.03-15.0
Pectin - 0.03-15.0
Fucoidin - 0.03-15.0
Zosterin - 0.03-15.0
Gum Arabic - 0.03-15.0
Xanthangam - 0.03-15.0
Tragacanth - 0.03-15.0
Drug substance and / or dietary supplement in an amount sufficient to provide a therapeutic effect
Water - The rest.

 Moreover, as an antibiotic, the product contains, for example, lincomycin or gentamicin, as an antiseptic, it contains, for example, miramistin, or chlorhexidine, or dioxidine, or colloidal silver, or a silver salt, as a vitamin, for example, ascorbic acid or aevit, as a substance affecting cell regeneration, it contains, for example, methyluracil or mummy; as a proteolytic substance, it contains, for example, trypsin or chemotrypsin.

 As a plant extract, the product contains, for example, sea buckthorn oil or plantaglucid.

The essence of the invention lies in the fact that experimentally it was possible to select a composition of substances that form a gel that remains sufficiently plastic (semi-liquid, but not spreading) at a temperature of from 0 ^o C to 50 ^o C for a sufficiently long time, well filling in lacerations and deep wounds, Adhesive to a wet wound and forming, in interaction with the wound exudate and air, an elastic, spongy, well vapor permeable coating that does not require additional dressings. In addition, it was found that this gel is a good tool for prolonging the action of drugs. When applying the proposed tool to a wet wound, the cation exitate proteins of the wound surface exudate interact with the anion exchangers (polyanions) of the proposed tool and the air, resulting in an elastic, spongy, well vapor permeable coating (a denser elastic part from the side of the air and a semi-liquid gel from the side of the wound surface) under which the regeneration and epithelization of the wound surface and the gradual exfoliation of the coating occur. Allergic reactions to water-soluble polysaccharides of plant origin are not described in the literature. Due to the fact that from the side of the wound surface the agent remains in the form of a semi-liquid gel for a long time, medicinal substances enclosed in the gel act on the wound for the entire time the agent is on the damaged area of the skin. This allows you to reduce the frequency of treatment of wounds with medicinal substances and thereby increase the non-invasiveness of treatment.

 The ability of alginic acid and its salts, carrageenan, fucoidin, zosterin, pectin and similar polysaccharides to form polyanions in a solution is known (see Yu.A. Ovchinnikov. Bioorganic chemistry.- M .: Education, 1987, p. 498.

To obtain the proposed funds take known substances:
Water-soluble methyl cellulose - grade МЦ-100, or МЦ-400, obtained according to TU-6-55-221-137-93 (Research Institute "Polymersynthesis", Vladimir),
or water-soluble methyl cellulose, M6385, M0262 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 694).

 Carboxymethyl cellulose, C5678 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 22).

 Pectin, P9135 (from citrus) (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 790).

 Gum arabic (GUM ARABIC), G9752 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 526).

 Xantangam (GUM XANTHAN), G1253 (Reference "Reagents for Biochemistry and Research in the Field of Natural Sciences" SIGMA, 1999, p. 526).

 Tragacanth (TRAGACANTH), G1128 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 526).

 Carrageenan (Carrageenan), C1138 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 225).

 Sodium alginate, A2158 (Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, S. 81).

 Calcium Alginate (Thomas, S. "Use of calcium alginate dressing", Pharm. J., 1985, 235, p. 188).

 Fucoidin, F5631 (Reference "Reagents for Biochemistry and Research in the Field of Natural Sciences" SIGMA, 1999, p. 465).

 Acceptable medicines (Register of medicines of Russia. - M., 1999).

The proposed coating is obtained, for example, as follows:
preparing an aqueous solution of methyl cellulose, or carboxymethyl cellulose, or a mixture of these components. Then, the calculated amount of alginic acid, or a water-soluble salt of alginic acid, or carrageenan, or fucoidin, or zosterol, or pectin, or a mixture thereof in any combinations and ratios, is introduced with constant stirring, and at the same time, the desired drug substance is introduced. The mixture is Packed in pre-prepared bottles or tubes and sterilized, for example, by gamma radiation at a dose of 2.5 Mrad, or by autoclaving for 1 h at a temperature of 112 ^o C and a pressure of 0.5 ATM. This method of preparation and packaging of the product allows you to maintain the activity of the drug substance enclosed in it (subject to the temperature and light conditions) for almost the entire period guaranteed by the manufacturer of the drug.

 We give examples of specific receipt and use of the proposed funds for the treatment of wounds.

 Example 1

 To obtain the proposed means for treating wounds, 1 liter of water was taken in which 50 g of carboxymethyl cellulose was dissolved, 1.5 g of sodium alginate and a drug substance, which was taken as 15 ml of 0.1% miramistin, which had an antiseptic effect (Drug Register Russia. - M., 1999, p. 626).

The resulting mass was Packed in sterile tubes, sterilized by autoclaving for 1 h at a temperature of 112 ^o C and a pressure of 0.5 ATM and stored until use at room temperature for 1 year.

 The resulting tool is a plastic gel, extracted from the tube with pressure.

 The gel was applied to a cleaned wet wound and covered with it the entire wound surface. After a few minutes of interaction of the gel with the wound exudate and the air, an elastic, transparent coating was formed in the first 1-2 days, which turned into a porous spongy mass in two days, which did not require additional fixation, and which peeled off from the wound as it was epithelized.

 The miramistin activity was tested in a freshly prepared gel and after 6 and 12 months of storage of the gel (in a dark place at room temperature) to inhibit the growth of Escherichia coli (E. Coli) and Staphylococcus aureus (Staphylococcus aureus) using a disc technique, as described in the well-known methodological manual "A method for determining the antibiotic sensitivity of microorganisms by the method of disk diffusion." - M .: Ministry of Health, 1984. Moreover, the disks were cut out of the gel.

 It was found that when storing the gel in a dark, dry and cool place, the activity of miramistin practically does not decrease for at least a year.

 When the gel is applied to a wet wound, an elastic coating forms, which remains semi-liquid on the side of the wound, and due to this, miramistin acts on the wound for the entire time the coating is on the wound.

 From the side of the air, the gel is compacted and as a result there is no need to fix the gel on the wound.

 If the wound is moistened with a solution of miramistin, and then closed with a dressing, the drug has a therapeutic effect for 4-6 hours.

 Example 2

 The proposed drug was obtained in the same manner as described in example 1, except that 30 g of methyl cellulose, 0.5 g of pectin were taken per 1 liter of water, and 13 mg of gentamicin sulfate was taken as a drug for injection (Drug Register Russia.- M., 1999, p. 324).

 The activity of gentamicin was tested in a freshly prepared coating and after 6 and 12 months of storage of the gel (in a dark place at room temperature) to inhibit the growth of Escherichia coli (E. Coli) and Staphylococcus aureus (Staphylococcus aureus) using the aforementioned disc technique.

 It was found that when storing the gel in a dark, dry and cool place, the activity of gentamicin practically does not decrease for at least a year.

 When applying the gel to a wet wound, gentamicin acts on it for 30-48 hours.

 When washing a wound with a gentamicin solution, the therapeutic effect lasts 3-4 hours.

 Example 3

 The proposed tool was obtained in the same manner as described in example 1, except that 30 g of methyl cellulose, 1.2 g of sodium alginate, 1 g of carrageenan and 20 mg of lidocaine (2 ml of a 1% solution) were taken per 1 liter of water ( The register of medicines of Russia.- M., 1999, p. 568).

 The anesthetic activity of the freshly prepared gel was checked and after 3 months of storage (in a dark place at room temperature) according to the subjective sensation (pain relief) of burn patients.

 It was found that when storing the gel in a dark, dry and cool place, the anesthetic activity of the coating does not deteriorate for at least one year.

 When applying the gel to a wet wound, the anesthetic acts on the wound for 20-24 hours, and the analgesic effect is maintained all this time.

 If the wound is moistened with an anesthetic solution, and then covered with a dressing, then the analgesic effect lasts only for 1-2 hours.

 Example 4

 The proposed tool was obtained in the same manner as described in example 3, except that 60 g of carboxymethyl cellulose, 5 g of pectin, 15 g of sodium alginate, 5 g of carrageenan were taken per 2 l of water, and 10 mg of antiseptic dioxidine was additionally administered as a drug substance (1 ml of a 1% solution) (Register of medicines of Russia.- M., 1999, p. 392).

 The anesthetic activity of the freshly prepared gel was checked and after 3 months of storage (in a dark place at room temperature) according to the subjective sensation of burn patients.

 The antimicrobial activity of the freshly prepared gel was checked and after 3 months of storage (in a dark place at room temperature) to inhibit the growth of E. coli (E. Coli) and Staphylococcus aureus (Staphylococcus aureus) using the aforementioned disc technique.

 It was found that during 3 months of storage, the product retained its anesthetic and antimicrobial properties.

 When applying such a gel to a wound, the anesthetic effect lasts for 20-24 hours, and the antimicrobial effect continues throughout the entire time the agent is on the wound.

 Example 5

 The proposed tool was obtained in the same manner as described in example 1, except that 70 grams of methylcellulose, 6 grams of pectin, 10 grams of calcium alginate, 5 grams of carrageenan and 2 grams of methyluracil were taken per 2 liters of water (Russian Drug Register. - M ., 1999, p. 608).

 Methyluracil is a means of stimulating the healing process of a wound.

 Known 5% methyluracil ointment ("Quick reference to the recipe". - M.: Medicine, 1974, S. 220), also used to accelerate the healing of trophic wounds.

 The ointment applied to the wound must be covered with a protective, for example, gauze dressing, which itself is a traumatic factor and, in addition, makes it difficult to observe the wound.

 In the case of treatment of long-term non-healing trophic ulcers, the gel coating is destroyed after 7-10 days of being on the wound and throughout this time methyluracil acts on the affected area. In the case of the use of methyluracil ointment, it must be applied daily and daily to dress the patient.

 Using the proposed gel containing methyluracil can reduce the healing time of trophic wounds by 25-30% compared with the use of methyluracil ointment.

 The product obtained as described in examples 1-5, depending on the concentration of gelling agents, is a less or more dense plastic gel that fits well on the wound, fills all its bumps well, adheres well to it and does not require additional fixation. The coating formed on the wound is transparent during the first two days, which allows you to monitor the condition of the wound. Then the outer part of the coating is compacted and a porous spongy mass is formed, which exfoliates from the wound as it heals or is destroyed after 7-10 days.

 Example 6

 The proposed tool was obtained in the same manner as described in example 5, except that 1.5 ml of an injection solution of the Aevita drug was administered as a medicinal substance (Russian Drug Register. - M., 1999, p. 134).

 Aevit is a means of stimulating the healing process.

 When a gel is applied to a trophic ulcer, aevit acts on it for the entire time the coating is on the affected area of the skin. The use of gel containing aevit for the treatment of trophic ulcers allowed to accelerate wound epithelization by 25-30% compared with the treatment of ulcers with an aevit solution.

 Example 7

 The proposed tool was obtained in the same manner as described in example 2, except that as a medicine took 0.05 g of silver nitrate in the form of an aqueous solution (10 ml) (Medicines. Handbook. Krasnoyarsk: Grotesk, 1993, p . 300).

 The bacteriostatic activity of the freshly prepared product was checked and after 6 and 12 months of storage (in a dark place at room temperature) to inhibit the growth of E. coli (E. Coli) and Staphylococcus aureus (Staphylococcus aureus) using the aforementioned disc technique.

 It was found that when storing the product in a dark, dry and cool place, the bacteriostatic activity of the gel does not change. When a gel is applied to a trophic ulcer, silver nitrate acts on it during the entire time the coating is on the affected area of the skin.

 Thus, the use of coatings containing an antimicrobial agent for the treatment of trophic wounds allows faster cleaning of the wound from microorganisms and less injury to the patient.

 Example 8

 The proposed tool was obtained in the same manner as described in example 3, except that 0.5 g of ascorbic acid solution was taken as the medicinal substance (Russian Drug Register. - M., 1999, p. 189).

 As well as methyluracil, ascorbic acid is a stimulant of the wound healing process and is often used to treat trophic ulcers.

 When a gel is applied to a trophic ulcer, ascorbic acid acts on it during the entire time the coating is on the affected area of the skin.

 The use of a gel containing ascorbic acid for the treatment of trophic wounds stimulates the growth of fibroblasts of the dermis connective tissue and accelerates wound epithelization by 25-30% compared with the treatment of ulcers with ascorbic acid solution.

 Example 9

 The proposed tool was obtained in the same manner as described in example 1, except that 0.5 g of chymotrypsin (as a solution) was administered as a drug (Medicines. Handbook. Krasnoyarsk: Grotesque, 1993, p. 488).

 Chymotrypsin is a wound cleanser.

 When a gel containing chymotrypsin is applied to a trophic ulcer that needs to be cleaned, it acts on the affected area for 30-48 hours. Treatment of the ulcer with a solution of chymotrypsin has an effect only for 2-3 hours.

 The use of coatings containing chymotrypsin for the treatment of trophic lesions of the skin allows the wound cleansing process to be carried out in comparison with the use of coatings not containing this drug.

 The proposed tool was used in the treatment of burns - 10 cases, trophic dry and weeping ulcers - 85 cases, lacerated animal bites - 2 cases and injuries sustained in road accidents - 2 cases.

 Thus, the proposed tool expands the arsenal of adhesives that are well adhering to a fresh and wetting wound, suitable for treating wounds and forming an elastic vapor-permeable coating directly on the wound, prolonging the effect of the drug substance contained therein. The use of such a tool does not require additional fixation, for example, with a gauze bandage. In addition, the proposed tool does not cause allergic reactions, since it does not contain protein substances, and increases the non-invasiveness of treatment, since it can be on the affected area of the skin for 7-10 days and provide the effect of the drug substance contained in it.

 The present invention can also be used in cosmetology for the healing of facial skin treated with a laser. In this case, the gel forms a coating that exfoliates as the laser-treated skin regenerates.

Claims (10)

 1. A means for treating wounds containing a water-soluble derivative of cellulose, a derivative of alginic acid, a biologically active substance and water, characterized in that it further comprises at least one component selected from the group consisting of carrageenan, fucoidin, zosterin, gum arabic, xanthan gum, tragacanth and pectin or their mixture in any combinations and ratios, and its water-soluble salt as a derivative of alginic acid.  2. The tool according to p. 1, characterized in that as a biologically active substance it contains at least one component selected from the group comprising antibiotics, antiseptic substances, anesthetics, vitamins, substances that affect cell regeneration, proteolytic substances, plant extracts or a mixture of these substances. 3. The tool according to p. 1, characterized in that it contains the following ratio of components, wt. %:
Water-soluble cellulose derivative - 1.0-15.0
Water-soluble salt of alginic acid - 0.1-15.0
Carrageenan, or fucoidin, or zosterin, or pectin, or gum arabic, or xanthan gum, or tragacanth - 0.03-15.0
Biologically active substance - An amount sufficient to provide a therapeutic effect
Water - Else
4. The tool according to paragraphs. 1 and 3, characterized in that it contains the following ratio of components, wt. %:
Water-soluble cellulose derivative - 1.0-15.0
Water-soluble salt of alginic acid - 0.1-15.0
Carrageenan, or fucoidin, or zosterin, or pectin, or gum arabic, or xanthan gum, or tragacanth - 0.03-15.0
Biologically active substance - Up to 10.0
Water - Else
5. The tool according to p. 4, characterized in that it contains the following ratio of components, wt. %:
Water-soluble cellulose derivative - 1.0-15.0
Water-soluble salt of alginic acid - 0.1-15.0
Carrageenan - 0.03-15.0
Pectin - 0.03-15.0
Gum Arabic - 0.03-15.0
Biologically active substance - An amount sufficient to provide a therapeutic effect
Water - Else
6. The tool according to any one of paragraphs. 1-5, characterized in that as a water-soluble derivative of cellulose, it contains methyl cellulose, or carboxymethyl cellulose, or a mixture thereof.  7. The tool according to any one of paragraphs. 1-6, characterized in that it is made in the form of a gel with a viscosity of at least 250 cps.  8. The tool according to p. 2, characterized in that as an antibiotic it contains, for example, lincomycin or gentamicin.  9. The tool according to p. 2, characterized in that as an antiseptic it contains, for example, miramistin, or chlorhexidine, or dioxidine, or colloidal silver, or a silver salt.  10. The tool according to p. 2, characterized in that it contains, for example, ascorbic acid or aevit as a vitamin.  11. The tool according to p. 2, characterized in that as a substance affecting the regeneration of cells, it contains, for example, methyluracil or mummy.  12. The tool according to p. 2, characterized in that as a proteolytic substance it contains, for example, trypsin or chymotrypsin.  13. The tool according to p. 2, characterized in that as a plant extract it contains, for example, sea buckthorn oil or plantaglucid.