RU8607U1 - SPONGE "HITOSKIN - SUPER" - Google Patents

Abstract

1. A sponge for the treatment of wound surfaces in the form of a porous elastic body made of collagen-containing material, in the volume of which an active principle is distributed, 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 builder, and the active principle contains superoxide dismutase. 2. The sponge according to claim 1, characterized in that the active principle contains a mixture of superoxide dismutase with antibiotics and antiseptics.

Description

HITOSKIN SUPER SPONGE

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 No. 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 relatively low wound healing activity, caused either by partial destruction of collagen molecules due to 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 ( 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 with the subsequent introduction of structure-forming agents - polyethylene glycol or formaldehyde, as well as antibiotics - gentamicin or lycomycin. (Pat. RF No. 2034572, 1995, class A 61 L 15/44).

MKHAL 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 structural sponge and whose material ensures its high performance properties, in particular the combination of gas permeability and elasticity with softening and wound healing characteristics.

This task is achieved in that the sponge based on collagen-containing material in the volume of which the active principle is distributed is made of a mixture of collagen fibrils and chitosan fibers, moreover, collagen fibrils are fixed in space using a mesh structure based on chitosan molecules and a structurant, and the active principle contains superoxmdismutase (SOD).

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 best characteristics are achieved when the active principle contains a mixture of SOD with antibiotics and antiseptics, for example, furatsilin, chlorhexidine derivatives, levomycetin, etc. substances. The content of antiseptics is usually 0.01 -1.0% dry. weight

SOD can be administered both in free form and in liposomal form. As superoxide dismutase, SOD is ingested from human blood or cattle or from a genetically engineered strain of microorganisms. The optimal content of SOD in the sponge is from 0.1 to 10% dry. weight.

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-particles of SOD, 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, SOD, antibiotics and antiseptics are added, after which a structurant is introduced, after which the solution is subjected to freeze drying.

In the process of obtaining from chitosan and collagen, fibers 1 are formed, characterized by a developed surface on which particles 3 and 4 are mainly sorbed. The structure-forming agent interacts with the fibers, forming a network stabilizing structure 2, which makes it difficult to desorb particles 3 and 4 from the spongy mass.

Weighed portions of chitosan and collagen are dissolved in acetic acid, then antiseptics and SOD are added, after which a structural agent is added, mixed thoroughly and subjected to freeze drying.

In the course of the process, fibrils 1 are formed from collagen, characterized by a developed surface, on which particles 3 and 4 are mainly sorbed in the future. 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 sponge masses.

sponges 2. At the same time, 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; the complex of SOD and collagen fibrils is easily processed by the patient’s fibroblasts into the connective tissue, while SOD additionally stimulates the immune activity of cells. 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.

It is necessary to apply a new sponge on the pus and actively exuding wounds, on average 1 time per day, removing the remnants of the old one with rinsing with a disinfectant solution, for example, 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.

Compared to other sponges, this sponge, which received the code name “HITOSKIN-SUPER, turned out to be most effective for the initial stage of treatment of complicated purulent wounds.

The industrial applicability of the proposed solution is illustrated by the following examples.

Example 1. Obtaining a sponge "HITOSKIN-SUPEJ.

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 and the analysis was performed against distilled water with a periodic change of water until the RP of the dialyzed mixture exceeds 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% glutaraldehyde solution was introduced into the prepared mixture with stirring, and the resulting solution was poured into plastic cuvettes 7 x 12 cm in size. The cuvettes with material were frozen in a freeze-drying chamber until - and then subjected to freeze-drying.

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

Example 2. The use of sponges "HITOSKIN-SUPBR

Sponges “HITOSKIN-SUPER were examined in the dermatological clinic of St. Petersburg State Medical University. Acad. I.P. Pavlova in 1996-97. on the example of 65 patients, including 24 people with venous trophic ulcers, 11 patients with chronic ulcerative pyoderma, 5 patients with Mortarella syndrome, 2 patients with obliterating entertariitis, 3 pain

ny with post-burn ulcers of the thigh and lower legs, 2 patients with ulcerative necrotic homerrhagic vasculitis, 18 people with banal pyococcal ecgims and rupees ..

All patients received general 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.

For irregular geometric shapes and large areas of ulcers (14 cases), the method of “vintage application of pieces of sponge 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 HITOSKINSUPER sponges 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 vasodilator therapy.

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

The tests showed the industrial applicability of new sponges with superoxide dismutase, called “HITOSKIN-SUPER.

Claims (2)

1. A sponge for the treatment of wound surfaces in the form of a porous elastic body made of collagen-containing material, in the volume of which an active principle is distributed, 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 structurant, and the active principle contains superoxide dismutase. 2. The sponge according to claim 1, characterized in that the active principle contains a mixture of superoxide dismutase with antibiotics and antiseptics.