RU8608U1 - WOUND COVER "HITOSKIN" - Google Patents

Abstract

1. A wound cover for the treatment of wound surfaces in the form of a porous elastic sponge made of collagen-containing material, characterized in that it is made of a mixture of collagen fibrils and chitosan fibers, the fibrils being fixed in space using a mesh structure based on chitosan molecules and a structure-forming agent. 2. The coating according to claim 1, characterized in that an active principle containing a biologically active substance or its mixture with antibiotics and antiseptics is placed in its mass.

Description

MKIAY5 / 44

WOUND COVER “HITOSKIN

The utility model relates to the field of medicine, namely to new devices designed for the treatment of wound surfaces.

It is known to use for healing wounds chemical-pharmaceutical and other drugs in various dosage forms, for example, in the form of ointments, suspensions, plasters, lotions, etc. forms (US Pat. No. 5169630, 1992, class AB L 7/48 and No. 5324508, 1994, class A61 K 45/05; Pat. RF No. 2007180, 1994, class A61 L 35/78, pat. RF 2028158, class A61 L 15/38).

The main problem arising from their use is the optimal combination of bactericidal and wound healing characteristics with gas permeability and high performance characteristics (coating strength, ease of separation from the wound surface, etc.).

One of the most promising dosage forms for treating wounds is a collagen sponge or dressing, on which the active principle is applied. It is known, in particular, the use for the treatment of wounds of porous collagen sponges (ed. St. USSR No. 561564, 1965, class A61 K 37-00), a mixture of gelatin, chitosan and formaldehyde (US Pat. China No. 1097980, 1995, class. A61 L 14/44), gelatin and formaldehyde with antibiotic additives (US Pat. RF No. 2033149, 1995, class A 61 L 15/44), cellulose and chitosan (Japanese accent application No. 0376029, 1990, class A61 L 15 / 44), collagen and chitosan (US Pat. PCT No. 8504413, 1986, CL C08 L 89/09).

The main disadvantages of these sponges are the relatively low wound healing activity, caused either by partial destruction of collagen molecules due to the nonconservation of their native conformation after crosslinking with formaldehyde or other bifunctional agents such as glutaraldehyde and its analogues, or sticking of the sponge to the wound and poor oxygen supply to the zone for pure collagen sponges) ..

The prototype of the proposed solution is a sponge, characterized by a more developed surface of the base fibers due to their execution from a mixture of collagen with hydroxyappatite in the ratio of components, (mass.) 1-10: 1, followed by the introduction of surfactants - polyethylene glycol or formaldehyde, as well as antibiotics - gentamicin or lycomycin . (Pat. RF No. 2034572,1995, class A 61 L 15/44).

The disadvantages of such a sponge are the presence in some cases of allergic reactions, as well as low sorption ability, which practically excludes the inclusion of wound healing preparations of protein origin with an enhanced wound healing effect.

The challenge facing the authors is to create a sponge structure and material which ensures its high performance properties, in particular the combination of gas permeability and elasticity with softening and wound healing characteristics.

This task is achieved by the fact that the sponge based on collagen-containing material was made from a mixture of collagen fibrils and chitosan fibers, and collagen fibrils are fixed in space using a mesh structure based on chitosan molecules and a structure former.

As a builder, formaldehyde, glutaraldehyde and its derivatives are used. For greater elasticity, ammonium and the like are additionally introduced. compounds as a gelling agent ..

The sponge can be independently used for medicinal purposes, as well as a matrix for introducing into the wound various preparations previously placed in the volume of the sponge.

Better characteristics are achieved when an active principle is added to the sponge containing biologically active substances (BAS), for example, having immunomodulating properties, as well as antibiotics and antiseptics, for example, furatsilin, chlorhexidine derivatives, levomycetin, etc. substances.

The content of antiseptics is usually 0.01-1.0% dry. weight of biologically active substances can be introduced both in free form and in liposomal form. Various enzymes, polysaccharides, proteins, etc. can be used as biologically active substances. substances.

A general view of the sponge of the claimed type is shown in FIG. 1, which shows 1- collagen fibrils, 2- mesh structure of chitosan and collagen macromolecules crosslinked by a structure-forming agent, for example, derivatives of glutaraldehyde, 3- biologically active substances, for example, in the form of liposomal vesicles, 4- particles of antibiotics and antiseptics.

The sponge is prepared as follows. . Samples of chitosan and collagen are dissolved in acetic acid, biologically active substances, antibiotics and antiseptics are added, after which a structurant is introduced and the solution is freeze-dried.

In the course of production from chitosan and collagen, fibers 1 are formed, characterized by a developed surface, on which particles 3 and 4 are mainly sorbed. The structure former interacts with the fibers, forming a network stabilizing structure 2, which makes it difficult to desorb particles 3 and 4 from the spongy mass and prolong its action. Weighed portions of chitosan and collagen are dissolved in acetic acid, then antibiotics, antiseptics and biologically active substances are introduced, after which the structurant is added, mixed thoroughly and subjected to freeze drying.

In the process, fibrils 1 are formed from collagen, characterized by a developed surface, on which particles 3 and 4 are mainly adsorbed. The structure former interacts with fibers and fibrils 1, forming a network stabilizing structure 2, prolonging the desorption of particles 3 and 4 from the spongy mass .

The sponge is used by applying its soft (least dense) surface to the wound surface and fixing it with a bandage if necessary. In this case, the wound exudate is rapidly absorbed and the hydrophilic internal structure swells.

sponges 2. In this case, the permeability of structure 2 increases and particles 3 and 4 gradually diffuse into the affected tissue area.

During contact with the wound, chitosan stimulates repair processes and provides favorable conditions for the speedy healing of wounds, biologically active substances 3 and collagen 1 fibrils are easily processed by the patient's fibroblasts into connective tissue, while biologically active substances additionally stimulate immune and other cell activity. Gradually, the sponge fully adheres to the surface of the wound, turning into a crust. After epithelialization of the wound, the sponge drops off on its own.

On purulent and actively exudating wounds, it is necessary to apply a new sponge on average 1 time per day, removing the remnants of the old washing off with a disinfectant solution, for example, a 3% peroxide solution.

After the surface of the wound is completely cleansed, the sponge is applied on an ongoing basis, up to its separation from the wound.

The experiments on the practical use of the sponge showed its high efficiency for the treatment of burn and wound surfaces of the skin. The terms of wound healing compared with conventional methods are reduced by an average of 1-2 weeks.

The useful applicability of the claimed solution is illustrated by the following examples.

Example 1. Obtaining a sponge “HITOSKIN model.

Zg of dry freeze-dried collagen was cut into small pieces and dissolved in 150 ml of 3N acetic acid. In parallel, 3g of chitosan in granules was dissolved in 150 ml of 2% acetic acid. The solutions were mixed and placed in a dialysis bag. Dialysis was performed against distilled water with a periodic change of water until the pH of the dialyzed mixture did not exceed 5.4. Next, the polymer solution was transferred into a flask, and 0.04 g of SOD and 0.06 ml of a 20% solution of gibbitan (chlorhexidine bigluconate) were added to the solution with stirring.

6 ml of a 1.25% solution of glutaraldehyde was introduced into the prepared mixture with stirring, and the resulting solution was poured into plastic cuvettes 7x12 cm in size.

Porous sponges containing SOD in an amount of 0.6% by dry weight or 0.1 mg / sq. Cm were obtained. The density of the coating was 0.05 - 0.01 g / cm3. Water absorption capacity of 3000 - 8000%.

Example 2. The receipt of the sponge "HITOSKIN model 2.

In 300 ml of 2% acetic acid was dissolved 3 g of freeze-dried collagen and 3g of chitosan in granules. After dissolution, excess acetic acid is removed before the formation of collagen fibrils begins. Then, 15 ml of a suspension of liposomes with beta-carotene were introduced into the polymer solution; 0.06 ml of a 20% solution of chlorhexidine bigluconate and 0.006 ml of polysept. After stirring, the solution was poured into the cuvettes with a layer thickness of 8-12 mm and, after gel formation, was freeze-dried.

The dry product was cut into plates of predetermined sizes, packaged and labeled. Sponge is mainly used to treat ulcerative skin lesions.

Example 3. Obtaining a sponge "HITOSKIP model 3.

In 300 ml of 2% acetic acid was dissolved 3 g of freeze-dried collagen and 3g of chitosan. After dissolution, excess acetic acid is removed before the formation of collagen fibrils begins. 15 ml of a suspension of beta-carotene liposomes were introduced into the polymer solution; 0.018 g of furatsilin and 0.06 g of gentamicin. After stirring, the solution was poured into the cuvettes with a layer 6–8 mm thick. After the gel was formed, it was brought into contact with a 1-4% glutaraldehyde solution for 24 hours and lyophilized.

The dry product was cut into plates of specified sizes, packaged and stamped.

Example 4. The use of sponges “HITOSKIP

Sponges “HITOSKIN were examined at the dermatological clinic of St. Petersburg State Medical University. Acad. I.P. Pavlova in 1996-97. for example, 88 patients, including 41 people with venous trophic ulcers, 11 patients with chronic ulcerative pyoderma, 7 patients with Mortarella syndrome, 2 patients with obliterating entertariitis, 5 patients with post-burn ulcers of the thigh and lower legs, 4 patients with ulcerative necrotic homerrhagic vasculitis, 18 people with banal pyococcal ectims and rupees ..

All patients received symptomatic therapy. Sponges were used for external therapy for 1.5-3 months.

The bottom of the ulcers was previously cleaned of pus, fibrin, and necrotic masses using wet-drying dressings, then a sponge was placed on the ulcer so that its edges grasp the skin surrounding the ulcer by 5-6 mm. The sponge was lightly pressed to the bottom of the ulcer and fixed with a hygroscopic gauze bandage.

With irregular geometric shapes and large areas of ulcers (14 cases), the method of “vintage application of sponge pieces on the entire surface of the ulcer was used. Dressings were carried out daily, washing off the remains of the sponge with 3% hydrogen peroxide solution. The experiments showed that already on the third day of applying the sponges, active granulations appeared, the edges of the ulcers became gentle, and the edge epithelization began. After the onset of active marginal epithelization, the sponge was not removed.

Healing in the absence of trophic disorders was observed within 1.5-3 weeks depending on the area. It was shown that the use of sponges “HITOSKIN model is most effective for stimulating processes in sluggish ulcers, as well as in patients with pyococcal and post-burn ulcers, where 100% cure is observed. In patients whose ulcers are caused by trophic disturbances, the use of sponges improves the condition of the ulcer in 100% of cases, stimulates granulation, reduces the depth and area of the ulcer, and in 70% of cases, the effect of clinical healing of the ulcers was achieved within 3 months of the general vasodilating therapy.

The use of sponges “HITOSKIN models 2 and 3 are most effective for stimulating the existing granulation of the ulcer bottom and enhancing marginal epithelization.

Almost all patients tolerated external sponge therapy well, noted a decrease in discomfort.

The tests showed the industrial applicability of new wound dressings in the form of sponges, called “HITOSKIN.

Claims (2)

1. A wound cover for the treatment of wound surfaces in the form of a porous elastic sponge from a collagen-containing material, characterized in that it is made from a mixture of collagen fibrils and chitosan fibers, the fibrils being fixed in space using a mesh structure based on chitosan molecules and a structure-forming agent. 2. The coating according to claim 1, characterized in that in its mass is placed an active principle containing a biologically active substance or its mixture with antibiotics and antiseptics.