RU2193896C2 - Covering for wounds - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: covering for wounds contains, wt.%: polysaccharide of plant origin, 2-95; medicinal product, up to 0.5; rubber latex, the balance. The covering could be designed as a monolayer film. The innovation favors to prolong the action of medicinal preparations that leads to higher atraumaticity of therapy, especially in case of burn and vast trophic lesions of skin. EFFECT: higher efficiency of therapy. 9 cl, 12 ex

Description

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

 Known coating for wounds containing a composition made of chitosan and collagen crosslinked with glutaraldehyde or hyoxal, and containing antiseptic drugs or anesthetics (RU, A1, 96124444).

However, the use of cross-linked collagen makes this coating hard and poorly soluble, which complicates the supply of biologically active additives to the wound surface and does not provide a sufficient degree of vapor permeability. This coating has a vapor permeability of not more than 0.5 mg / cm ² / h, while the vapor permeability of healthy skin is 1.4 mg / cm ² / h (B.K. Gavrilyuk et al. Cell culture and tissue reconstruction (using the example skin), Academy of Sciences of the USSR, National Center for Scientific Research, IBP, Pushchino, 1988, p. 10). In addition, such a coating is opaque, as it contains cross-linked collagen, which makes it difficult to monitor the state of the wound.

 A known film made from a mixture of collagen and natural rubber latex (RU, C1 1251528) and intended for the cultivation of animal cells. This film is monolayer and homogeneous in structure. However, it does not have the necessary degree of adhesion to fresh and wet wounds and cannot be used as a coating for wounds.

 Known coating for wounds in the form of a monolayer homogeneous film made of a mixture of latex fluororubber and polysaccharides of plant origin (RU, C1 2091082).

 Such a film is transparent, elastic and adheres well enough to the surface of the wound. However, often in the event of various complications or to prevent complications, additional treatment of the affected skin with drugs having a bactericidal, or antiseptic, or anesthetic, or other necessary effect is required. These substances quickly decompose in wound exudate, which requires frequent coating changes. Frequent change of the wound cover, in turn, causes additional injury to the wound surface.

 The technical problem to which the invention is directed is to expand the arsenal of monolayer, homogeneous, transparent films suitable for use as a coating for wounds.

 Another task is to prolong the action of drugs.

 Another challenge is to increase the non-invasiveness of wound healing.

 The tasks are solved in that a coating for wounds is proposed, including rubber latex and a polysaccharide of plant origin, which according to the invention additionally contains a drug.

 As a medicine, the coating contains a substance suitable for external and / or internal use.

 The coating contains the drug in an amount providing its therapeutic effect.

 As a medicine, the coating contains at least one component selected from the group comprising antimicrobial agents, anesthetics, vitamins, skin regeneration promoting substances, proteolytic substances, or a mixture of these substances.

 As an antimicrobial agent, the coating contains, for example, antibiotics or antiseptics.

 As an antibiotic, the coating contains, for example, lincomycin or gentamicin.

 As an antiseptic, the coating contains, for example, miramistin, or chlorhexidine, or dioxidine, or colloidal silver, or a silver salt.

 As a vitamin, the coating contains, for example, ascorbic acid or aevit.

 As a substance affecting cell regeneration, the coating contains, for example, methyluracil.

 As a proteolytic substance, the coating contains, for example, trypsin or chemotrypsin.

 As the rubber, the coating contains, for example, natural rubber, or fluororubber, or siloxane (silicone) rubber, or butyl rubber, or styrene rubber, or polyisobutylene, or other rubber suitable for medical or food use, capable of forming latex.

 As a plant-derived polysaccharide, the coating contains at least one polysaccharide selected from the group consisting of water-soluble cellulose derivatives, pectins, carrageenans, alginic acid salts, agar-agar and its derivatives, gel-forming vegetable resins.

 Most preferably, as a plant-derived polysaccharide, the coating comprises a mixture of at least one salt of alginic acid with methyl cellulose, or carboxymethyl cellulose, or carrageenan, taken in any ratio.

 The proposed coating as a plant polysaccharide may also contain a mixture of at least one salt of alginic acid with pectin and at least one component selected from the group consisting of methyl cellulose, carboxymethyl cellulose and carrageenan, taken in any ratio. As a gelling vegetable resin, the coating contains, for example, gum arabic, xanthan gum, tragacanth.

Mentioned components of the coating contains the following ratio of components, wt.%:
Polysaccharide - 2-95
Medicinal product in effective quantity - Up to 0.5
Latex Rubber - Else
The proposed coating is made in the form of a monolayer film.

 The essence of the invention lies in the fact that experimentally it was found that the introduction of a medicinal product in a mass of up to 0.5% by weight of the main film-forming components, on the one hand, practically does not worsen physical and mechanical properties (strength, elasticity, vapor permeability, wound adhesion ) films, and, on the other hand, allows access to the drug necessary for treating a wound for at least the time of interaction of the polysaccharide component of the coating with the wound exudate.

 When a film containing a drug is applied to the wound, the polysaccharide component of the film interacts with the wound exudate (with partial dissolution of the polysaccharide) and, accordingly, the drug is gradually released and its direct effect on the wound surface. This, on the one hand, increases the exposure time of the drug to the wound surface and, on the other hand, eliminates the need to remove the coating material for periodic application of an antibiotic or other necessary substance to the wound surface.

To obtain the proposed films take known substances:
Latex of a copolymer of trifluorochlorethylene with vinyldenfluoride or a copolymer of hexafluoropropylene with vinyldenfluoride (grades SKF-32 and SKF-26 TU 6-05-65-137, Krivo-Chepetsk), which are medical rubbers;
Latex of natural rubber, for example, Revertex T type - "Handbook rubber", M .: Chemistry, 1971, p. 21, 200.

 Latex of polyisobutylene - "Handbook of rubber", M .: Chemistry, 1971, p. 186, 190.

 SKT siloxane rubber latex - "Handbook of rubber worker", M .: Chemistry, 1971, p. 137.

Water-soluble methyl cellulose grade MTs-100, or MTs-400, obtained according to TU-6-55-221-137-93 (Research Institute "Polymersynthesis", Vladimir),
or water-soluble methyl cellulose, M0262 - Reference "Reagents for biochemistry and research in the field of natural sciences" SIGMA, 1999, p. 694.

 Carboxymethyl cellulose. C5672 - Reference "Reagents for Biochemistry and Research in the Field of Natural Sciences" SIGMA, 1999, p. 22.

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

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

 Xantangam (GUM XANTHAN), G1253 - Reference book "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, p. 526.

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

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

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

 Acceptable Medicines - Russian Drug Register. M, 1999.

 The proposed coating is obtained, for example, as follows.

 An aqueous polysaccharide solution is prepared, for example, methyl cellulose, or a mixture of polysaccharides. Then, rubber latex (with a dry matter concentration of 15-60%) is introduced into this solution, previously freed from coagulated particles by sequential filtering through nylon filters with cells of 1.0, 0.5, 0.2, and 0.1 mm.

 Take the calculated amount of rubber latex, an aqueous solution of plant polysaride and mix thoroughly until a homogeneous mass is obtained. Then, the desired drug is introduced into this mass, and the mixture is again thoroughly mixed. The mixture is poured into cups or glass plates with a layer, the thickness of which is calculated depending on the concentration of dry matter in the film, and dried at room temperature until a dry film is obtained.

 The coating is cut into sheets of the desired size and shape, hermetically sealed under vacuum in a double sealed package and sterilized with gamma radiation at a dose of 2.5 Mrad. This method of obtaining and packaging the coating allows you to maintain the activity of the drug 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 production and application of coatings for wounds.

 Example 1. To obtain the proposed coating took 2 l of water, in which 10 g of carboxymethyl cellulose was dissolved, 1 l of fluororubber rubber latex (grade SKF-26) containing 300 g / l of dry matter and 50 ml of 0.1% as a medicine Miramistin, which has an antiseptic effect (Register of Medicinal Products of Russia, Moscow, 1999, p. 626).

 First, a mixture of an aqueous solution of carboxymethyl cellulose and previously freed from coagulated particles by successive filtering through nylon filters with cells of 1.0, 0.5, 0.2, and 0.1 mm rubber latex was thoroughly mixed until a homogeneous homogeneous mass was obtained. Then this mass was thoroughly mixed with a solution of miramistin and again filtered through a nylon filter with 0.2 and 0.1 mm cells. The mixture was poured onto glass plates and dried in air at room temperature until an elastic and transparent film with a thickness of 100 ± 10 microns was obtained. Then the film was hermetically sealed under vacuum, for example, in a plastic film and sterilized with gamma radiation at a dose of 2.5 Mrad. The miramistin activity was tested in a freshly prepared coating and after 6 and 12 months of storage of the coating (in a dark place at room temperature) to inhibit the growth of Escherichia coli (E. Coli) and Staphylococcus aureus (Staphylococcus aureus) using the disc technique, as described in the well-known methodological manual "Method for determining the antibiotic sensitivity of microorganisms by disk diffusion." M., Ministry of Health, 1984. At the same time, the disks were cut from the coating.

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

 When a film is applied to a wet wound, a polysaccharide component of a film of this thickness interacts with exudate with partial dissolution for 30-48 hours and all this time miramistin acts 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 coating was obtained in the same manner as described in example 1, except that 10 g of methyl cellulose, 5 g of sodium alginate, 1 l of natural rubber latex containing 300 g of dry matter, and 40 mg of gentamicin were taken on 2 l of water. sulfate in the form of a solution for injection (Russian Drugs Register, Moscow, 1999. p. 324).

 The activity of gentamicin was tested in a freshly prepared coating and after 6 and 12 months of storage of the coating (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 coating in a dark, dry and cool place, the activity of gentamicin practically does not decrease for at least a year.

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

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

 Example 3. The proposed coating was obtained as described in example 1, except that 4 g of water was taken 40 g of methyl cellulose, 20 g of calcium alginate, 10 g of carrageenan type II (C1138), 1 l of latex siloxane rubber SKT, containing 300 g of dry matter, and 0.05 g of silver nitrate in the form of an aqueous solution (10 ml) (Medicines, Handbook, Krasnoyarsk, "Grotesque", 1993, p. 300).

 The bacteriostatic activity of the freshly prepared coating was checked and after 6 and 12 months of storage of the coating (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 coating in a dark, dry and cool place, the bacteriostatic activity of the coating does not change. When a film is applied to a wet wound, the polysaccharide component of the film with a thickness of 100 microns dissolves under the action of exudate within 30-48 hours, and all this time silver nitrate acts on the wound.

 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 4. The proposed coating was obtained as described in example 1, except that 4 g of water was taken 40 g of carboxymethyl cellulose, 10 g of pectin. 10 g of sodium alginate, 10 g of type II carrageenan (C1138) 1 l of polyisobutylene latex containing 300 g of dry matter, and 100 mg of lidocaine (10 ml of a 1% solution) (Russian Drug Register, Moscow, 1999, p. 568 )

 The anesthetic activity of the freshly prepared coating was checked and after 3 months of storage of the coating (in a dark place at room temperature) by subjective sensation (pain relief) of burn patients. It was found that when the coating is stored in a dark, dry and cool place, the anesthetic activity of the coating does not deteriorate for at least one year.

 When applying a film to a wet wound, the anesthetic acts on the wound for 30-48 hours, and the analgesic effect is maintained all this time.

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

 Example 5. The proposed coating was also obtained as described in example 4, except that 50 mg of dioxidine (5 ml of a 1% solution) was additionally taken as a medicine (Russian Drug Register, Moscow, 1999. p. 392 )

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

 The antimicrobial activity of the freshly prepared coating was checked, and after 3 months of storage of the coating (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 coating retained its anesthetic and antimicrobial properties.

 With a coating thickness of 100 microns, the anesthetic and antimicrobial effects last for 48 hours.

 Example 6. The proposed coating was obtained in the same manner as described in example 4, except that 0.1 g of gum arabic was taken instead of pectin, and 5 g of methyluracil was taken as a medicine (Russian Drug Register, Moscow, 1999, p. 608).

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

 Known 5% methyluracil ointment ("A 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, moreover, makes it difficult to observe the wound.

 If the proposed coating with a thickness of 100 microns is used for the treatment of trophic wounds, the therapeutic effect of methyluracil on the wound continues for the entire time the coating is on the wound.

 In the case of treatment of trophic ulcers, the coating is replaced (depending on the state of the wound) once every 4-7 days. At the same time, methyluracil ointment must be applied daily and daily to dress the patient.

 Using the proposed coating containing methyluracil can reduce the healing time of trophic wounds by 25-30% compared with a coating that does not contain methyluracil (prototype).

 Example 7. The proposed coating was obtained in the same manner as described in example 1, with the exception that 2 ml of an injection solution of Aevita was taken as a medicine (Russian Drug Register, Moscow, 1999, p. 134).

 Aevit is a means of stimulating the healing process.

 When using a coating with a thickness of 100 microns, aevit acts on the wound for 30-48 hours.

 The use of coatings containing aevit for treating trophic wounds made it possible to accelerate wound epithelization by 25-30% compared with the use of coatings (prototype) that did not contain aevit.

 Example 8. The proposed coating was obtained in the same manner as described in example 1, except that 0.5 g of ascorbic acid solution was taken as a medicine (Russian Drug Register. Moscow, 1999, p. 189).

 Ascorbic acid is also a means of stimulating the wound healing process.

 When using a coating with a thickness of 100 microns, ascorbic acid acts on the wound for 30-48 hours.

 The use of coatings containing ascorbic acid for the treatment of trophic lesions of the skin stimulates the growth of fibroblasts of the connective tissue of the dermis by 15-25% compared with the use of coatings (prototype) that do not contain this drug.

 Example 9. The proposed coating 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 medicine (Medicines, Reference, Krasnoyarsk. "Grotesque", 1993, p .488).

 Chymotrypsin is a wound cleanser.

 A 100 micron thick chymotrypsin coating acts on the wound for 30-48 hours. Treatment of the wound with a solution of chymotrypsin has an effect only for 2-3 hours.

 The use of coatings containing chymotrypsin for the treatment of trophic wounds allows the wound cleansing process to be carried out compared to the use of coatings not containing this drug.

 Example 10. To obtain the proposed coating took 1 l of water, in which 10 g of carboxymethyl cellulose was dissolved, 1 l of an aqueous 0.5% agarose solution, 1 l of butyl rubber latex containing 300 g / l of dry matter and 50 ml as a drug 0.1% miramistin, which has an antiseptic effect, and 0.3 g of ascorbic acid in the form of an aqueous solution.

 First, a mixture of an aqueous solution of carboxymethyl cellulose, agarose and previously freed from coagulated particles by successive straining through nylon filters with cells of 1.0, 0.5, 0.2 and 0.1 mm butyl rubber latex was thoroughly mixed until a homogeneous homogeneous mass was obtained. Then this mass was thoroughly mixed with a solution of miramistin and a solution of ascorbic acid and again filtered through a nylon filter with 0.2 and 0.1 mm cells. The resulting mixture was poured onto glass plates and dried in air at room temperature until an elastic and transparent film with a thickness of 100 ± 10 microns was obtained. Then the film was hermetically sealed under vacuum, for example, in a plastic film and sterilized by gamma radiation. Miromistin activity was checked as described in Example 1.

 It was found that when the coating is stored in a dark, dry and cool place, the activity of miramistin is practically not reduced for at least a year.

 When applying a film to a wet wound, a polysaccharide component of a film of this thickness interacts with exudate with partial dissolution for 30-48 hours, and all this time miramistin and ascorbic acid act on the wound.

 The film was used to treat long-term non-healing wounds caused by mechanical damage to the skin.

 The combined effect of miramistin and ascorbic acid ensured wound healing within 12 days.

 Example 11. The proposed coating was obtained in the same manner as described in example 10, except that 40 g of methyl cellulose, 10 g of calcium alginate, 10 g of type II carrageenan (C1138), 0.1 g of gum arabic, 0, 1 g of xanthan gum, 1 l of SKT siloxane rubber latex containing 300 g of dry matter, 0.3 g of trypsin in the form of an aqueous solution and 0.1 g of gentamicin.

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

 When applying a film to a wet wound, gentamicin and trypsin act on the wound for 30-48 hours.

 The film was used to treat burn wounds of the 2nd degree.

 The combined effect of gentamicin and trypsin ensured that the wound was cleaned and completely healed within 14 days.

 Example 12. The proposed coating was obtained as described in example 1, except that 4 g of water was taken 40 g of carboxymethyl cellulose, 10 g of pectin, 10 g of sodium alginate, 1.0 g of tragacanth, 1 l of polyisobutylene latex containing 300 g of dry matter, 0.05 g of colloidal silver and 5.0 g of an aqueous solution of methyluracil.

 The film was used to treat trophic ulcers.

 The combined effect of silver and methyluracil provided complete healing of the wound within 20 days.

 Thus, the proposed coating allowed to expand the arsenal of monolayer, homogeneous, transparent films that adhere well to the wound and are suitable for use as a coating for wounds.

 The use of the proposed coating allows you to prolong the action of drugs, including anesthetics and antimicrobial agents, and thereby increase the non-invasiveness of treatment, which is especially important in the treatment of burns and extensive trophic skin lesions.

Claims (9)

1. Coating for wounds in the form of a monolayer film, including rubber, taken in the form of latex, and a polysaccharide of plant origin, characterized in that it further comprises at least one medicinal substance, preferably intended for the treatment of wounds and selected from the group including antimicrobial substances , anesthetics, vitamins, substances that promote skin regeneration, proteolytic substances in the following ratio of components, wt. %:
Polysaccharide - 2.0-95.0
Medicinal substance - Up to 0.5
Rubber - Other
2. The coating according to claim 1, characterized in that it contains antibiotics or antiseptics as an antimicrobial substance.  3. The coating according to claim 1, characterized in that as the rubber it contains latex-forming rubber, suitable for medical or food use and non-toxic to animal cells, selected from the group comprising natural rubber, or fluororubber, or siloxane rubber, or butyl rubber, or styrene rubber, or polyisobutylene.  4. The coating according to claim 1, characterized in that as a polysaccharide of vegetable origin, it contains at least one polysaccharide selected from the group comprising water-soluble cellulose derivatives, pectins, carrageenans, alginic acid salts, agar-agar and its gel-forming derivatives vegetable resins.  5. The coating according to claim 4, characterized in that as a gelling vegetable resin, it contains at least one component selected from the group consisting of gum arabic, xanthan gum, tragacanth.  6. The coating according to claim 2, characterized in that it contains lincomycin or gentamicin as an antibiotic.  7. The coating according to claim 2, characterized in that it contains miramistin, or chlorhexidine, or dioxidine, or colloidal silver or a silver salt as an antiseptic.  8. The coating according to claim 1, characterized in that it contains ascorbic acid or aevit as a vitamin.  9. The coating according to claim 1, characterized in that as a substance affecting the regeneration of cells, it contains methyluracil.  10. The coating according to claim 1, characterized in that it contains trypsin or chemotrypsin as a proteolytic substance.