RU12971U1 - SPONGE - Google Patents

Abstract

1. A sponge for the treatment of wound surfaces in the form of a porous elastic body 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 interleukin-1 beta. 2. The sponge according to claim 1, characterized in that the active principle contains a mixture of interleukin-1 beta with antibiotics and antiseptics. Sponge according to claims 1 and 2, characterized in that interleukin-1 beta is in liposomal form.

Description

MKHAL 15/44

The utility model relates to the field of medicine, namely to new devices and dosage forms intended for the treatment of wound and burn 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. US L 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 L 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. In particular, it is known to 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. 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 is the relatively low wound healing activity, caused either by partial destruction of collagen molecules due to the nonconservation of their native conformation after

SPONGE

crosslinking with formaldehyde or other bifunctional agents such as glutaraldehyde and its analogues, or sticking a sponge on a wound and poor oxygen supply to the repair area (typical for purely collagen sponges) ..

The prototype of the claimed technical 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 structure-forming agents - polyethylene glycol or formaldehyde, as well as antibiotics - gentamicin or lycomycin. (Pat. RF No. 2034572, 1995, class A61 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 that have an increased wound-healing effect.

The challenge facing the authors is to create a sponge whose structure and material ensures its high performance properties, in particular the combination of gas permeability and elasticity with softening and wound healing characteristics, which provide greater efficiency in the treatment of burns of various occurrences, prickles, and chronic sluggish infected wounds.

This task is achieved by the fact 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, and collagen fibrils are fixed in space using a network structure based on chitosan molecules and a structurant, and the active principle contains the endogenous mediator of the body's defense reactions is interleukin-1 beta.

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

The best characteristics are achieved when the active principle contains a mixture of interleukin-1 beta with antibiotics and antiseptics, for example, furacilin, chlorhexidine derivatives, levomycetin, etc. substances.

Interleukin-1 beta (IL-1) can be administered both in free form and in liposome form.

A general view of the sponge of the claimed type is shown in FIG. 1, which shows: I - collagen fibrils,

2-mesh structure of macromolecules of chitosan and collagen crosslinked by a structure-forming agent, for example, derivatives of glutaraldehyde,

3-particles of IL-1, 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, then antiseptics and beta-carotene are introduced (the latter is usually in liposomal form), after which a 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 or burn surface, fixing it with a bandage if necessary. In this case, the wound exudate is rapidly absorbed and the hydrophilic internal structure of the sponge 2 swells. At the same time, the permeability of structure 2 increases and particles 3 and 4 gradually diffuse into the affected tissue zone. During contact with the wound, chitosan stimulates repair processes and provides favorable conditions for the speedy healing of wounds, a complex of IL-1 particles and collagen fibrils is easily processed by the patient’s fibroblasts into connective tissue, while IL-1 additionally stimulates 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 old ones 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 chronic sluggish infected wounds. The terms of wound healing compared with conventional methods are reduced by an average of 1-2 weeks.

Compared with other sponges, this sponge, which received the code name HITOSKIN-PL, was most effective for the treatment of chronic sluggish purulent wounds.

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

Example 1. Obtaining sponge CHITOSKIN-IL1 model A. 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, 10 ml of a sterile IL-1 solution (1 mg / ml) was introduced into the polymer solution; A. About ml of a 20% solution of chlorhexidine bigluconate and 0.006 ml of polysept. After stirring, the solution was poured into cuvettes with a layer 8–12 mm thick and, after gel formation, was freeze-dried.

The dry product was cut into plates of predetermined sizes, packaged and labeled. The sponge is used mainly for pressure sores and sluggish conditions for burns.

Example 2. Obtaining sponge HITOSKPP-IL1 model B. In 300 W of 2% acetic acid, 3 g of freeze-dried collagen and 3g of chitosan were dissolved. After dissolution, excess acetic acid is removed before the formation of collagen fibrils begins. 10 ivui sterile IL-1 solution was 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

gel formation it was brought into contact with a 1-4% solution of glutaraldehyde for 24 hours and subjected to lyophilization.

The dry product was cut into plates of predetermined sizes, packaged and labeled. The sponge is used mainly for the treatment of surgical sluggish infected wounds.

Example 3. The use of CHITOS-IL1

HITOSK1Y1-ILG sponges were examined at the dermatological clinic of St. Petersburg State Medical University. Acad. I.P. Pavlova in 1996-97. for example, 22 patients with post-burn ulcers of the thigh and lower legs, 7 patients with surgical sluggish infected wounds, 5 patients with pressure sores.

All patients received general symptomatic therapy. Sponges were used for external therapy for about 5-3 months.

The bottom of the wounds was previously cleaned of pus, fibrin, necrotic masses, then a sponge was placed on the ulcer so that its edges 5-6 mm grasped the skin surrounding the wound. 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 (8 cases), the method of vintage application of sponge pieces to 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 granules appeared .. gs, the edges of the ulcers became gentle, the marginal epithelization began. After the onset of active marginal epithelization, it was not removed. Healing in the absence of trophic disorders was observed within 2-3 weeks B, depending on the area.

It has been shown that the use of HITOSKIP-PLG sponges is most effective D. To achieve active granulation of the bottom of the ulcers. Almost all patients tolerated external sponge therapy well, noted a decrease in discomfort. The duration of treatment was reduced by 7-12 days, depending on the pathology.

Claims (3)

1. A sponge for the treatment of wound surfaces in the form of a porous elastic body 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 interleukin-1 beta.  2. The sponge according to claim 1, characterized in that the active principle contains a mixture of interleukin-1 beta with antibiotics and antiseptics. 3. Sponge according to claims 1 and 2, characterized in that interleukin-1 beta is in liposomal form.