WO2014065772A1 - Agent for healing wounds of various etiologies and method for the use thereof - Google Patents

Abstract

1. Subject matter of the invention: Chitoplast-derma and a method for the use of a composition thereof as a wound dressing. 2. Field of use: Medicine and the chemical and pharmaceutical industry; the invention can be used as a therapeutic agent for healing wounds of various etiologies and 2^nd and 3^rd degree burns, preventing scarring, stopping bleeding (haemostasis) etc. 3. Essence of the invention: The use of chitosan, a natural polymer, to create a hydrogel composition containing chitosan and/or chitosan derivatives, particularly chitosan iodide, glycerin, sodium hydroxide, acetic acid, biologically active substances, silver nanoparticles, and water. 4. Technical result: The creation of the optimum micro environment for wound healing, a high capacity for absorbing wound exudate, an absence of pyrogenic, antigenic and toxic activity, the capacity for creating a broad range of surgical dressings for healing wounds of various etiologies and agents for stopping bleeding.

Description

 MEANS FOR TREATMENT OF RAS OF VARIOUS ETHIOLOGY

 AND METHOD OF ITS APPLICATION

The invention relates to the field of medicine and the pharmaceutical industry, and can be used as a therapeutic agent for the treatment of wounds of various etiologies, II and III degree burns, prevention of scarring, hemostasis (hemostasis), etc.

 Known helium preparation that contains synthetic polymers (Pat. 2157243 RU, IPC A 61L 15/22. Hydrogel composition and dressings from it for the treatment of wounds of various etiologies / Valuev L.I. et al .; applicant and patentee A. Pishchurov. N. - 3.N ° 991 13730/14; declaring 01.07.1999; publ. 10.10.2000), the disadvantage of which is the use of toxic monomers in its manufacture, namely acrylamide; stratification and destruction during storage, poor adhesion with a wound, as well as the inability to use this composition to form a wound cover and other methods of treating wounds without the use of auxiliary materials (linings).

Also known are helium preparations that contain polymers, collagen, gelatin, alginate, chitosan alone or in a composition alone with other and auxiliary substances, in particular gentamicin (Pat. 2252787 CI RU, IPC A61L15 / 28. Method for producing artificial skin matrix / Bolshakov I.N. et al .; applicant and patent holder of GOU VPO Krasnoyarsk State Medical Academy of the Ministry of Health of the Russian Federation (RU). - 3. JY ° 2003136466/15; filed on December 6, 2003; published on May 27, 2005). Such compositions are characterized by a sufficiently high biocompatibility, but in the case of the presence of collagen in them or other proteins may cause an immunological reaction, and in the case of molecular crosslinking may contain residues of a toxic crosslinking agent.

 The closest analogue of the proposed invention is a helium preparation, which contains a colloidal solution of chitosan, gentamicin and a number of auxiliary substances and methods for its use (Pat. UA 84369, IPC A61K 31/7036. A therapeutic agent based on chitosan with a bactericidal and wound healing effect, use and method treatment / Khotsenko O. A.; applicant and patentee Khotsenko O. A. - 3. jY "a200705863; claimed. 05.25.2007; publ. 10.10.2008).

 The disadvantage is that this composition can be used exclusively as an ointment to accelerate wound healing.

 The basis of the invention is the task of creating a chitoplast -derm and methods of using it as a wound cover for the treatment of wounds of various etiologies, which would have the properties of an improved qualitative and quantitative composition of biological materials that have adhesion to the skin, high biological activity, which ensures the creation of an optimal microenvironment for wound healing, high ability to absorb wound exudate, the absence of pyrogenic, antigenic and toxic effects, the ability to create I have a wide range of dressings for the treatment of wounds of various etiologies, means to stop bleeding.

 The use of chitosan - a natural polymer in the invention is due to the presence of a number of unique abilities, such as non-toxicity, elasticity, biocompatibility, biodegradability with the creation of safe monomers, the ability to model surfaces with complex relief.

Chitoplast-dermis is a hydrogel composition that contains chitosan and / or chitosan derivatives, actually chitosan iodide, glycerin. sodium hydroxide, acetic acid, biologically active substances, silver nanoparticles, water in the following ratio (% May):

 Chitosan / Chitosan Iodide - 2-5

 Glycerin - 0.1-10

Sodium hydroxide - 0, 1 - 5

Acetic acid - 0.5 - 1

Biologically active substances - 0.1 - 5

Silver Nanoparticles / Silver Iodide - 0.1 - 0.5

Water is the rest.

This composition contains an aqueous colloid in which the polymer absorbs water or an aqueous buffer solution (acetic acid solution). A hydrogel is formed by self-organization of the polymer chains of chitosan when the pH of the solution is changed, which is achieved by the addition of sodium hydroxide. The concentration of sodium hydroxide affects the functional properties of the hydrogel, including its ability to absorb wound fluid, fill the wound cavity. The degree of deacetylation and molecular weight of chitosan are important. In the claimed composition, chitosan has a deacetylation degree of more than 80%, and a molecular weight of 200 to 500 kDA.

The hydrogel composition is obtained by dissolving the polymer in a weak solution of acetic acid, followed by raising the pH to 7-7.5 and saturating with glycerol, biologically active substances and / or silver nanoparticles. Silver nanoparticles are obtained by treating a 1% solution of silver nitrate with water-extractive substances of oak bark for 24-48 hours. Include nanoparticles in the hydrogel in the form of a colloidal solution. The composition of the initial solutions for obtaining chitoplapsterderma is presented in Table 1. Table 1

The composition of the initial solutions to obtain chitoplast-dermis

The invention also relates to the use of these compositions as wound dressings with antibacterial and wound healing effects.

 Chitoplast - dermis (composition 1 and 2) can be used as an independent medical form by placing a tube in a sterile dish (figure 1). After applying the gel to the surface of the defect, a porous film with a thickness of 0.5 -5 mm is formed within 7-10 minutes.

The biological activity of chitoplast-dermis was evaluated by antimicrobial activity and ability to influence the course of the wound process. Data regarding antibacterial activity are given in table. 2, 3. Efficacy demonstrated in laboratory rats. table 2

The sensitivity of clinical strains of microorganisms to

 antibiotics and chitoplast -derma

Table 3

The sensitivity of clinical strains of microorganisms to

 antibiotics and chitoplast -derma

A comparative analysis indicates that the healing of wounds treated with chitoplastderma is -. occurs faster by 2-3 days and without complications (Fig.2-5).

Chitoplast-dermis (composition 3) can be used to form a transparent film wound cover by irrigation on a glass or Teflon lining. The formed film is treated with a solution of sodium hydroxide 1-5% for 30-120 minutes And a mixture of distilled water and glycerol 1: 1 for 30-120 minutes The time and concentration of sodium hydroxide affect the rate of lysis of the film on the wound surface. Non-toxic film forms during lysis of the film. glycosamine, which can be used in the biosynthesis of aminopolysaccharides of the body. Gradual lysis of the film eliminates additional injury to the wound during dressings. The transparency of the film makes it possible to observe the course of the wound process without removing the coating. The film adheres well to the wound (Fig.6).

 On exudating wounds, a perforated film can be used (as an aid) (hole diameter 3-5 m, perforation area 10%).

 By freeze drying (removing water by evaporating ice) or by freezing - gelation (Fig. 7), porous sponges (Fig. 8) can be obtained from the starting compositions 1-3 to stop bleeding and absorb exudate. Sponges obtained by the method of freezing - gelling can be used as a carrier of saline or drugs in the wet state. The release of drugs is accompanied by the absorption of exudate and toxins.

 Composition 4 is suitable for the formation of granules by the dropwise addition of a solution of chitosan to a solution of sodium hydroxide (Fig. 9, 10). The obtained granules are washed with water and freeze-dried. Granules can be used as a sorption material, and material to stop bleeding.

 These modifications do not cause changes in chitosan molecules, as evidenced by infrared spectroscopy (for example, granules), and therefore do not impair the biological properties of the material.

 By combining chitoplast-dermis 1 or 2 (the lower layer, which is adjacent to the wound) and films based on composition 3 (upper layer), a two-layer wound coating can be obtained.

By combining xerogel 1-2, dried to a film state (lower layer), a perforated film based on composition 3 (upper layer) and chitosan iodide (inner layer) you can get a three-layer coating.

 By combining xerogel 1-2, dried to a film state (lower layer), a perforated film based on composition 3 (reinforcing inner layer), chitosan iodide (binding inner layer), sponge (upper layer), a four-layer wound cover can be obtained.

 Chitoplast-derm compositions as a wound cover can be used in the treatment of wounds with varying degrees of exudation, ensuring the creation of an optimal microenvironment for wound healing, high absorption capabilities for wound exudate, and the absence of pyrogenic, antigenic and toxic effects, which prevents the penetration of microorganisms.

Claims

CLAIM 1. Chitoplast-dermis for the treatment of wounds of various etiologies, which contains chitosan derivatives and auxiliary substances, which differs in that the chitoplast-dermis has hydrogel properties and additionally contains a natural polymer - chitosan iodide glycerin, sodium hydroxide, acetic acid, biologically active substances, nanoparticles silver, water in the following ratio of components (May.%):  Chitosan iodide - 2-5  Glycerin - 0.1-10  Sodium hydroxide - 0, 1 -5  Acetic acid - 0.5-1  Biologically active substances - 0.1-5  Silver nanoparticles - 0.1-0.5  Water is the rest.  2. The method of using chitoplast - dermis according to claim 1, as a wound dressing with antibacterial and wound healing effects, which is characterized in that a hydrogel composition is applied to the prepared defect surface to form a porous film from 0.5 to 5 mm thick, and a multilayer coating is obtained by forming films with different degrees of drying, perforation, the number of biologically active substances that lay one on top of the other. 3. The method of using the chitoplast-dermis according to claim 2, characterized in that to stop bleeding, absorb exudate and toxins from the chitoplast-dermis, they form a macroporous sponge-like structure by freeze drying. 4. The method of using chitoplast-dermis according to claim 2, characterized in that the chitoplast-dermis form spherical fanules with a diameter of 0.5 mm to 5 mm by adding sodium hydroxide.