JPH03206032A - Wound-covering material - Google Patents

Abstract

PURPOSE:To provide the subject wound-covering material consisting of a bio- compatible water-absorbing gel layer containing physiologically active substance of immune system and a water-permeation controlling layer laminated on the upper surface of the gel layer, capable of protecting the damaged skin under water-containing condition and effective in suppressing the pain and bacterial infection and promoting the epidemal regeneration. CONSTITUTION:The bacterial infection to the damaged skin such as wound or scald can be prevented by compounding a physiologically active substance of an immune system such as lysozyme hydrochloride to the gel layer of a wound-covering material consisting of (A) a bio-compatible water-absorbing gel layer containing preferably 50-500wt.% of water and composed of a matrix of a partially crosslinked polymer such as carboxymethylcellulose or a hydrogen bond-type polymer complex consisting of a poly(meth)acrylic acid and polyvinyl pyrrolidone, etc., and (B) a water-permeation controlling layer composed of polyurethane, etc., and laminated on the upper surface of the gel layer. The gel layer protects the wound softly in a water-containing state to suppress the pain and accumulates the exudate in the tissue to make a moist state and promote the cure of wound.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a novel wound dressing containing a physiologically active substance for the immune system. The dressing of the present invention is applied to damaged parts of the skin due to wounds, burns, etc., and protects the damaged parts in a hydrated state, suppresses pain, prevents bacterial infection, and promotes epidermal regeneration.

[Conventional technology]

As a wound protection dressing material for the purpose of protecting skin wounds and promoting healing, dry dressings (d
ry dressing) and wet dressing (wet dressing), which forms a moderately moist environment and allows rapid escape of epidermal cells, but the latter allows for rapid wound healing and prevents the wound surface from drying out. It is advantageous because it causes less necrosis and protects the wound surface.

Extensive burns or second-degree burns are susceptible to bacterial infection, which can lead to sepsis and shock, which can eventually become life-threatening.

Long-term administration of antibiotics is used to prevent infection, but in this case, bacteria develop drug resistance and bacterial replacement occurs.
As a result, it becomes infected with Durham-negative bacilli and fungi. On the other hand, many topical therapeutic agents emphasize antibacterial properties and permeability, with particular emphasis on Durham-negative rods such as Pseudomonas aeruginosa. The necessary conditions for a local treatment for burns are 1) strong antibacterial properties, 2) strong penetrating action that can act on bacteria under the skin of burns, 3) low tissue toxicity, and 4> analgesic effect. and 5) promoting epidermalization and granulation formation. Unfortunately, there is currently no local therapeutic agent that satisfies all of these conditions. Among the antibacterial agents currently in use, silver sulfadiazine has excellent antibacterial properties against Pseudomonas aeruginosa, and is commercially available in the form of a cream containing 1% silver sulfadiazine.

However, because it is cream-based, it soaks into the gauze bandage along with the exudate, leaving only about 21% remaining on the wound surface (Takehiko Oura, Emergency Medicine. 5, 1833).
(1981)).

In addition, as an alternative to this, a wound dressing made of animal tissue containing silver sulfadiazine (Japanese Patent Publication No. 59-2
03583) and a polyamino acid sponge containing silver sulfadiazine have been recently reported (Yoshimitsu Kuroyanagi et al., Journal of the Nichiga Kai. 7.526 (191!7)). However, these drugs also have the problem of bacterial resistance acquisition.

[Problem that the invention seeks to solve]

Absorbent dressings are said to heal quickly because the constituent gel-like material stores exudate inside, creating a hydrated state that allows epidermal cells to move freely over the moistened dermal surface. However, a humid environment is extremely unfavorable to bacterial infection.

Furthermore, since extensive burns and m-degree burns are susceptible to bacterial infection, a cream base containing an antibacterial agent is used to prevent infection. However, about 57% of this soaks into the gauze bandage along with the exudate, and only about 21% reaches the wound surface. In addition, cream-based products require complicated operations such as applying them to the wound surface every day. If the water-absorbing dressing could sustainably release antibacterial agents over a certain period of time, the wound surface would not be exposed to the outside, and there would be no need to apply it daily. Furthermore, when the wound dressing has a moisture permeation regulating layer, it not only controls moisture permeation but also prevents infection from the outside.

[Means for solving problems]

In order to achieve the above object, the present invention consists of the following configuration.

1) A wound covering comprising a biocompatible water-absorbing gel layer and a water permeation regulating layer laminated on the top surface of the gel layer, the gel layer containing a physiologically active substance for the immune system. Material.

2) The gel layer is made of carboxymethyl cellulose, poly
2. The wound dressing according to item 1, which is composed of a matrix of a partially crosslinked polymer selected from the group consisting of (meth)acrylamide, poly(meth)acrylic acid, and polyvinyl alcohol.

3) The wound according to item 1, wherein the gel layer is composed of a hydrogen-bonded polymer complex of poly(meth)acrylic acid and polyvinylpyrrolidone, hydroxypropyl cellulose, or succinylated atelocollagen and polyvinylpyrrolidone. Covering material.

Φ The wound dressing according to any one of items 1 to 3, wherein the physiologically active substance of the immune system is selected from lysozyme chloride, thymopoietin, or a fragment of thymopoietin.

5) The wound dressing according to any one of items 1 to 4, wherein the moisture permeation regulating layer is polyurethane or silicone.

6) 1 in which the gel layer contains 50 to 500% by weight of water
The wound dressing according to any one of items 5 to 5.

As described above, the wound dressing of the present invention is composed of two layers: a biocompatible water-absorbing gel layer and a water permeation regulating layer, and the gel layer contains a physiologically active substance for the immune system.

The biocompatible water-absorbing gel layer directly covers the wound surface to provide soft protection, suppress pain, protect the injured skin area under hydrated conditions, and prevent bacterial contamination. Furthermore, when the gel layer is applied to a wound surface, the constituent gel-like substances store exudate therein to create a moist state, allowing epidermal cells to move freely beneath the surface of the infiltrated dermis, thereby promoting healing.

The material constituting the gel layer includes a partially crosslinked polymer matrix selected from the group consisting of carboxymethyl cellulose, poly(meth)acrylamide, poly(meth)acrylic acid, and polyvinyl alcohol, and poly(meth)acrylic. A matrix composed of a hydrogen-bonded polymer complex of acid and polyvinylpyrrolidone, or hydroxypropyl cellulose, or succinylated atelocollagen and polyvinylpyrrolidone is used. Preferably, carboxymethylcellulose calcium salt, a complex of polyacrylic acid and polyvinylpyrrolidone, etc. are used.

Since the gel layer contains physiologically active substances for the immune system, bacterial infection on the wound surface is prevented, and if infection has already occurred, it is cured. Examples of physiologically active substances for the immune system used in the present invention include lysozyme chloride, which is an antibacterial agent for the innate immune system, and thymopoietin or a fragment thereof, which induces differentiation of T cells.

Lysozyme chloride is an enzyme that hydrolyzes the β-1.4 bond between N-acetylglucosamine and N-acetylmuramic acid of mucopolysaccharide or mucobebutide in cells. , 307)
It is widely distributed in animals and plants, and in mammals including humans, it is present in tears, nasal secretions, nasal cavities, sinus mucosa, saliva, white blood cells, plasma, etc., and destroys bacterial cell membranes in these areas. Lysozyme chloride has a wide variety of pharmacological actions, including antiviral, antibacterial, antiinflammatory, antiedema, hemostatic, tissue repair, and pus/mucosal decomposition.

Thymopoietin is a thymic factor extracted from bovine thymus, a protein with a molecular weight of 7000, and has a T lymphocyte differentiation effect. These thymic factors include thymosin and thymopoietin/tridecapeptide fragments, which are known to have effects on immune function.

A moisture permeation regulating layer is laminated on the upper surface of the water absorbent gel layer. When the wound dressing of the present invention is applied to a wound surface, this regulating layer regulates water evaporation to maintain an appropriate amount of water contained in the water-absorbing gel layer, and furthermore, bacteria can be absorbed from the outside into the dressing. This is to prevent intrusion. This moisture permeation regulating layer is composed of a film made of silicone, polyurethane, or the like.

The wound dressing of the present invention is made by soaking a matrix such as carboxymethyl cellulose in an aqueous solution of a physiologically active substance for the immune system, drying it, and then applying it on a Teflon sheet. , created by dry curing in an oven.

[For production]

The wound dressing material in the present invention has the following effects.

Partially crosslinked polymers selected from carboxymethylcellulose, poly(meth)acrylamide, poly(meth)acrylic acid and polyvinyl alcohol, or poly(meth)acrylic acid and polyvinylpyrrolidone or hydroxybrobyl cellulose or succinylated The biocompatible water-absorbing gel layer composed of a hydrogen-bonded polymer complex of atelocollagen and polyvinylpyrrolidone has water-retaining and water-absorbing properties.
It ensures adequate retention of exudate, has good adhesion to the wound surface, non-adhesiveness, and biocompatibility, and has a pain and cancer suppressing effect. Furthermore, by maintaining an appropriate biological environment with a high water content, healing, especially epidermal regeneration, is promoted, and the good adhesion to the wound surface suppresses the invasion of bacteria into the wound surface. By containing thymopoietin (2), which induces differentiation of T cells, it has the effect of inhibiting infection even on wound surfaces already contaminated with bacteria.

The moisture permeation control layer selected from the group consisting of silicone and polyurethane maintains proper moisture retention on the wound surface, ensuring the underlying polymer gel state and allowing moisture to pass through but not fungi. Due to its properties, it has the effect of preventing infection.

〔Example〕

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 A commercially available non-woven fabric made of carboxymethyl cellulose sodium salt (manufactured by Asahi Kasei Corporation) was mixed with 5% medical grade Silastic silicone (manufactured by Dow Corning).
The nonwoven fabric was immersed for 30 seconds in a hexane solution of
It was immersed in an aqueous solution of lysozyme chloride (L y Cfl ) for 10 seconds, left in a clean bench at room temperature, and sufficiently dried. Next, a hexane solution of 67% medical grade Silastic silicone was applied onto the Teflon sheet using a precision coating tool (applicator) to form a film. Immediately after coating, the above nonwoven fabric was placed on top of the wet layer and allowed to stand at room temperature for IO minutes, and then cured in the open at 60° C. for at least 1 hour. The moisture content of the wound dressing thus obtained was 192%.

Example 2 While thoroughly stirring a 1% aqueous solution of commercially available polyacrylic acid, 0.07% thymopoietin■ and tridecapeptide●
When the fragment (residues 29-41, TP13) is added and then a commercially available aqueous polyvinyl vidrine solution is slowly added dropwise, the solution begins to become cloudy and a hydrogen-bonded polymer complex is formed. Finally, polyvinyl vidrin was mixed with polyacrylic acid in equal amounts. This cloudy liquid was poured into a Teflon mold and air-dried. A polyurethane film (thickness: 28 mm) was pasted on one side of this matrix to produce a composite membrane. The moisture content of the wound dressing thus obtained was 78%.

Test example 1 Grafting test on rat skin defect wound w1st
After shaving the back of an ar-KY rat (weight 200 to 300 g), the back skin was treated with a peeling tool (dermatome).
Two wounds with a size of 20 x 20 mm and a depth of 15/1000 inch were created, and after the bleeding had stopped, a cloth soaked in saline was applied to each wound, and an elastic inside drape (storl-Drape ■ 3M (manufactured)
After covering it with water, it was fixed using elastic tape and raised for months with ad libitum water and feeding. Three days later, each animal was anesthetized and sacrificed.

Biopsies were taken from several locations on each wound surface, tissue specimens were prepared, and the tissues were observed under an optical microscope. As a result, in both Examples 1 and 2, no matrix was observed to fall off from the wound surface. Furthermore, compared to open wounds, the matrices of Examples 1 and 2 had weaker tissue reactions and faster epidermalization. In addition, LyC of the innate immune system
1 and the coating material to which TP13 of the cellular immune system was added showed a remarkable tendency to increase the growth of juvenile granulation.

〔Effect of the invention〕

As described above, in the present invention, the part that can come into contact with the wound part is made of a biocompatible water-absorbing gel-forming layer, the gel layer contains a physiologically active substance for the immune system, and the upper surface of the gel layer contains water. Since this is a wound dressing material characterized by a laminated permeation control layer, it can be applied to areas affected by diseases or wounds such as extensive burns, skin harvest wounds, skin abrasion wounds, and traumatic skin loss wounds. It has water vapor permeability and exudate absorbability, so it keeps the wound surface in an appropriate moist state and adheres closely to prevent bacterial infection and pain, and the contact area with the wound surface is biocompatible, so there is no foreign body reaction by living organisms. There is no possibility that the dressing will stick to the wound surface and cause bleeding or pain when removed, and in combination with keeping the wound surface under an appropriate moisturizing condition as described above, the wound area will heal. and regenerate cleanly without leaving any traces.

In addition, the wound-covering materials of the present invention are easily available and inexpensive, and the wound-covering material is economically superior. Furthermore, these characteristics are due to the fact that the biocompatible high water content gel forming layer is a matrix of partially crosslinked polymers based on carboxymethyl cellulose, poly(meth)acrylamide, poly(meth)acrylic acid, or polyvinyl alcohol, or poly(meth)acrylic acid. It is a hydrogen-bonded polymer complex of acrylic acid and polyvinylhydridone, hydroxypropylcellulose, or succinylated atelocollagen and polyvinylpyrrolidone, and it is even better if the moisture permeation control layer is silicone or polyurethane. Moreover, since both substances are stable against exudates, the coating material does not deteriorate due to exudates.

In addition, the present invention uses lysozyme chloride, which is an antibacterial agent of the innate immune system, and thymopoietin or a fragment of thymopoietin, which is a cellular immune system that induces differentiation of T cells, as an antibacterial agent, so the above substances themselves exist in the living body. Therefore, it has the advantage of being extremely weak in immunogenicity and easy to be applied clinically, and by including it in the wound dressing, it is possible to easily provide a wound dressing with excellent performance.

Claims (1)

[Scope of Claims] 1) Consists of a biocompatible water-absorbing gel layer and a water permeation regulating layer laminated on the top surface of the gel layer, and the gel layer contains a physiologically active substance for the immune system. A wound dressing characterized by: 2) The gel layer is made of carboxymethyl cellulose, poly(
The wound dressing according to claim 1, which is constituted by a matrix of a partially crosslinked polymer selected from the group consisting of meth)acrylamide, poly(meth)acrylic acid, and polyvinyl alcohol. 3) The wound according to claim 1, wherein the gel layer is composed of a hydrogen-bonded polymer complex of poly(meth)acrylic acid and polyvinylpyrrolidone, or hydroxypropylcellulose, or succinylated atelocollagen and polyvinylpyrrolidone. Covering material. 4) The wound dressing according to any one of claims 1 to 3, wherein the physiologically active substance of the immune system is selected from lysozyme chloride, thymopoietin or a fragment of thymopoietin. 5) The wound dressing according to any one of claims 1 to 4, wherein the moisture permeation regulating layer is made of polyurethane or silicone. 6) The wound dressing according to any one of claims 1 to 5, wherein the gel layer contains 50 to 500% by weight of water.