JP2001212170A - Wound cover material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a wound cover material capable of accelerating tissue cell proliferation and arterialization in a state holding the surface of a wound to proper wet environment in the whole of a wound healing process even if adapted to a wound part much in the amount of an exudate to realize the acceleration of early and efficient treatment and having no fear increasing a pain at a time of the replacement of the wound cover material or damaging the regenerated skin or the like. SOLUTION: This wound cover material is constituted by laminating a nonwoven fabric layer and a sponge layer containing a crosslinked hyaluronic acid and crosslinked alginic acid both of which are crosslinked by an epoxy compound and contains an antibacterial agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a novel wound dressing. More specifically, the wound dressing material of the present invention is applied to a wound part that exudes a large amount of wound fluid when stopping or treating a wound part such as a burn, a pressure sore, a skin ulcer, an abrasion, or a cut, thereby protecting the wound part. At the same time, cells having a tissue repair function are infiltrated into the cells to promote wound healing.

[0002]

2. Description of the Related Art Conventionally, as a method of stopping or treating a wound such as a burn, a pressure sore, a skin ulcer, an abrasion, or a cut, a therapeutic agent is applied to the wound, and then a gauze or cotton wool is applied thereon. There have been proposed many methods for protecting a wound by covering the wound with a wound dressing material.

When gauze is directly applied to a wound, exudate from the wound is directly absorbed by the gauze.
The absorption capacity of the gauze is not very high and exudate accumulation occurs. This storage, on the contrary, promotes the generation of bacteria and makes early healing difficult. In particular, in a wound part where the exudate from the wound is large, the ointment or cream of the therapeutic agent mixes with the exudate to form a muddy state. Therefore, the wound dressing must be replaced frequently and the ointment or cream must be reapplied. Further, if the wound dressing is changed frequently, the amount of medicine to be used increases, and there is a problem that the pain of the patient when changing the wound dressing increases. In addition, these conventional wound dressings have low antibacterial properties and, when protecting the wound for a very short time, even if they can be easily separated from the wound, In the case of peeling after coating for a long time, it is often peeled off integrally with the granulation, and the blood clot is exposed again, causing unpleasant pain and rebleeding, etc. Has disadvantages. Therefore, when the rebleeding wound portion is repeatedly covered with the same wound dressing material again and the final healing is performed, scars easily remain on the wound portion after healing, which is not preferable in cosmetic surgery. There were problems such as.

[0004] As alternatives to these, wound dressing materials made of artificial materials such as silicone gauze and silicone rubber film sheets, and wounds made of biological materials such as freeze-dried pork skin, chitin nonwoven fabric, collagen film, and polyamino acid sponge can be used. Coatings are also known. However, among these, the wound dressing made of an artificial material leaves various problems in terms of adhesion to a wound portion, water vapor permeability, and the like. On the other hand, wound dressings made of biological materials have characteristics such as biocompatibility, but many of them have antigenicity and also have drawbacks such as cell infection and deterioration due to exudate.

Further, from the viewpoint of good affinity with the wound site and promotion of healing, materials derived from living organisms, such as hyaluronic acid and alginic acid, have been taken up in the medical field such as wound dressing. Have been. However, hyaluronic acid is not only highly biocompatible and highly biodegradable, but also can promote the proliferation and angiogenesis of fibroblasts and help heal wounds, When applied, uncrosslinked hyaluronic acid has a short remaining period and is a device for obtaining good retention in the wound, i.e., it is present in the wound for a necessary period, and disappears from the tissue as the defective tissue is healed. It has long been desired to obtain a substance suitable for the purpose of progressing. Alginic acid extracted from seaweed is a natural polymer having mannuronic acid and guluronic acid as constituent units, and its metal salt has a hemostatic effect,
Although a wound dressing made of alginate has been put to practical use because it has an analgesic effect and further has a mucosal protective effect, there has been a problem that the calcium salt of alginic acid has cytotoxicity.

[0006]

The wound healing process when a living body is damaged with a tissue defect generally includes a stage I (inflammatory stage), a stage II (granulation and reepithelialization stage), and a stage III.
Phase (matrix formation and reconstitution phase).
In stage I, platelets are aggregated and activated at the bleeding site where blood vessels are destroyed due to tissue damage, and various physiologically active substances including multiple cell growth factors are released together with the formation of thrombus and contribute to healing Has been recognized. II
In the phase, vascular endothelial cells, fibroblasts, epidermal cells, and the like cooperate to cause granulation, and these cells further contribute to granulation by producing factors that promote the proliferation of surrounding cells. In stage III, granulation tissue is absorbed and fibroblasts and new blood vessels that have excessively proliferated are reduced, and are replaced by collagen fibers and elastic fibers to complete healing. Thus, there are various aspects in the process of wound healing.

As described above, it is thought that the type of cell and cell growth factor which play a major role in the process of wound healing changes every moment, and that it is controlled in a complicated manner, and eventually heads for convergence. Can be

[0008] However, hyaluronic acid and alginic acid used in the conventional wound dressing materials are used alone, and exhibit different and unique effects in certain aspects of the wound healing process. Was not able to exert an effect in the whole wound healing process.

Further, the method can be applied to a wound with a large amount of exudate to absorb a considerable amount of exudate exuding from the wound, and to remove water contained in the exudate at a desired rate. There was a strong need to provide a wound dressing that could be transferred through the dressing to the exterior surface of the wound dressing and evaporate this moisture into the surrounding environment, thereby extending the useful life of the wound dressing. . Therefore,
An object of the present invention is a biomaterial which can be applied to a wound part with a large amount of exudate and promotes proliferation of tissue cells and angiogenesis in the whole process of wound healing while keeping the wound part in an appropriate moist environment. To provide a wound dressing material that can promote early and efficient treatment by applying to a wound site, and that does not cause pain when replacing the wound dressing material or damage the regenerated skin, etc. It is in.

[0010]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, completed the present invention. The present invention is as follows. (1) A wound dressing comprising a nonwoven fabric layer and a sponge layer containing crosslinked hyaluronic acid and crosslinked alginic acid crosslinked with an epoxy compound. (2) The wound dressing according to the above (1), wherein the basis weight of the nonwoven fabric layer is 30 to 300 g / m ² . (3) The wound dressing according to the above (1) or (2), wherein the sponge layer containing the crosslinked hyaluronic acid and the crosslinked alginic acid crosslinked with the epoxy compound contains 1 to 20% by weight of uncrosslinked hyaluronic acid and / or uncrosslinked alginic acid. (4) In the sponge layer containing a crosslinked hyaluronic acid and a crosslinked alginic acid crosslinked with an epoxy compound, the content of the crosslinked hyaluronic acid is 10 to 80% by weight, and the content of the crosslinked alginic acid is 20 to 90% by weight. The wound dressing according to any one of claims 1 to 3. (5) The wound dressing according to any one of (1) to (4) above, which contains an antibacterial agent.

[0011]

DETAILED DESCRIPTION OF THE INVENTION The present invention is applied to a wound with a large amount of exudate, absorbs a large amount of wound exudate released from the wound, and evaporates water contained therein into the surrounding environment. Accordingly, it is an object of the present invention to provide a wound dressing that can reduce the frequency of replacing the wound dressing and at the same time realizes early and efficient treatment promotion.

The wound dressing directly covers and protects the wound, softens the wound, provides an appropriate moist environment, and prevents bacterial contamination. Furthermore, the wound dressing is made of a cell-infiltrating material, and when applied to the wound site, macrophages, neutrophils and other inflammatory cells infiltrate and fibroblasts infiltrate at an early stage. It is preferable that the dermal-like connective tissue is constructed to promote the healing of the wound, and the material is eventually absorbed by the wound surface and disappears with the healing of the wound. A sponge layer containing hyaluronic acid and alginic acid, which are biological materials, is suitable as a material for promoting such cell invasion.

[0013] Hyaluronic acid and alginic acid are biomaterials and themselves have the effect of promoting wound healing.
Moreover, when these biomaterials are applied to a wound, they are decomposed and absorbed over time. Therefore, a wound dressing using a matrix composed of these biomaterials can not only promote healing, but also does not require peeling or the like at the time of replacement.
There is no risk of adversely affecting the healing wound.

[0014] Hyaluronic acid provides a highly hydrated microenvironment to the wound during the wound healing process. It is known that, in such a microenvironment, adhesion and detachment of a cell membrane and a substrate when various cells move through a wound is controlled, and cell healing is facilitated, so that wound healing is promoted. ing.

[0015] Thus, hyaluronic acid is not only very biocompatible and biodegradable, but also
Although it can promote the proliferation and angiogenesis of fibroblasts and assist wound healing, hyaluronic acid is of biological origin and therefore has a high affinity for cell tissues, but uncrosslinked hyaluronic acid has hyalonase and the like in vivo. Easily decomposed and absorbed by enzymes. When using it there,
It is necessary to introduce cross-links by some means to enhance physical properties. However, the introduction of cross-linking greatly reduces the affinity of hyaluronic acid for cells and tissues before introduction, and tends to prevent cell invasion. That is, it is difficult to achieve both enhancement of physical properties and improvement of biological performance such as affinity for cells and tissues.

On the other hand, alginic acid is usually obtained by boiling seaweed with a dilute sodium carbonate solution. Alginic acid sodium salt is usually dissolved in exudate, so that alginic acid sodium salt is usually used. Alginate fibers, woven fabrics, knitted fabrics, alginate films and the like have been used as calcium alginate salts that are hardly soluble in exudates. However, since the calcium salt of alginic acid is cytotoxic, it is necessary to minimize the amount of calcium salt used.

As a result of extensive studies by the present inventors, a wound dressing comprising a nonwoven fabric layer and a sponge layer containing a crosslinked hyaluronic acid and a crosslinked alginic acid crosslinked with an epoxy compound,
It can absorb a significant amount of exudate oozing from the wound surface and transfer the moisture contained in the exudate through the wound dressing to the outer surface of the wound dressing within the desired rate. Evaporation into the surrounding environment can extend the useful life of the wound dressing, while applying a sponge layer of biomaterial to the wound site to promote wound healing and release after healing The present invention has also been found to be easy.

One object of the wound dressing of the present invention is to absorb a large amount of exudate released from the wound when applied to a wound with a large amount of exudate, and to contain the exudate contained in the exudate. The transfer of moisture present within the desired rate through the wound dressing to the exterior surface of the wound dressing, evaporating this water into the surrounding environment, and maintaining the wound in a reasonably moist environment. In order to achieve this object, it is preferable to use a nonwoven fabric composed of hydrophobic fibers and superabsorbent fibers.

As the hydrophobic fibers used in the present invention, synthetic fibers such as polyester, nylon, acryl, polypropylene and polyethylene are preferable. As the highly absorbent fiber, wood pulp, natural fiber of cotton, rayon, regenerated fiber of cupra, semi-synthetic fiber such as acetate, and the like are used. Particularly, the hydrophobic fiber and the superabsorbent fiber are 6: 4 by weight.
When used in a ratio of 8: 2, the hydrophobic fibers receive water from the highly absorbent fibers that have absorbed the exudate, and serve to evaporate the water in the outer air layer, which is particularly preferable. The thickness of the fiber constituting the nonwoven fabric layer composed of the hydrophobic fiber and the highly absorbent fiber is about 0.3 to 5 denier (d), preferably 0.5 to 3 denier (d).
It is desirably about d.

The nonwoven fabric can be prepared by a known method, for example, the following method. A wet process in which a short fiber layer (web) is made with water, impregnated with resin, and dried and hardened, just as paper is made. A dry method in which a web is made mechanically without using water and bonded with resin or adhesive fibers. A needle punch method in which a web of the same type as the dry type is pierced with a pierced needle to mechanically entangle the fibers. Spunlace method in which fibers are entangled with a high-pressure water stream on a web of the same type as the dry type. A web with a uniform thickness by arranging a large number of continuous yarns in all directions like a spider web while simultaneously blowing out the melted raw resin from many small holes (nozzles) before forming fibers Spunbonding method, where yarns are naturally and mechanically attached to each other.

The above-mentioned nonwoven fabric layer can also be formed by any of these known methods,
Alternatively, these methods can be used in combination, but depending on the production method, a direction in which the fiber is easily stretched and a direction in which the nonwoven fabric is difficult to stretch can be formed. Since the nonwoven fabric layer used in the present invention needs to have elasticity, a nonwoven fabric layer having a relatively large elongation is used. The elongation is length 60cm width 6cm
Cm when a load of 1500g is hung on a non-woven fabric
The extension is expressed as a percentage of the original length, and the nonwoven fabric used in the present invention is preferably 30 to 200%,
More preferably, the content is 40 to 150%.

The thickness of the nonwoven fabric layer composed of the hydrophobic fiber and the highly absorbent fiber is preferably about 1 to 20 mm, more preferably about 1 to 10 mm in consideration of flexibility, durability, workability, absorbability, and the like. Is desirable. The basis weight of the nonwoven fabric layer composed of the hydrophobic fiber and the superabsorbent fiber is preferably from 30 to 300 g / m ² from the viewpoint of the retention of exudate,
More preferably, those having 50 to 200 g / m ² are suitable.

When a nonwoven fabric layer composed of only hydrophobic fibers is further laminated on one or both sides of the nonwoven fabric layer composed of hydrophobic fibers and superabsorbent fibers, a nonwoven fabric layer composed of the hydrophobic fibers and superabsorbent fibers is formed. There is an advantage that, at the same time as suppressing fluffing, the adhesiveness of the nonwoven fabric layer composed of the hydrophobic fiber and the highly absorbent fiber can be further improved. Examples of the fiber material of the nonwoven fabric layer composed of only hydrophobic fibers include polyester, polypropylene, polyethylene, nylon, and thermoplastic elastomer. Among these hydrophobic fiber materials, a thermoplastic elastomer is a preferable material as a wound dressing material because it exhibits rubber elasticity at room temperature and is highly elastic. Among the thermoplastic elastomers, polyolefin-based, polyurethane-based, and polyester-based elastomers are particularly preferred because they are soft and rich in elasticity.
As these hydrophobic fiber materials, commercially available products or improved products thereof can be used.

The thickness of the fibers constituting the nonwoven fabric layer composed of only hydrophobic fibers is preferably about 0.3 to 5 d, more preferably about 0.5 to 3 d.

The basis weight of the nonwoven fabric layer composed of only hydrophobic fibers is preferably 5 to 100 g / m ² .

Another object of the present invention is to provide a wound dressing capable of sustaining the effect of promoting wound healing for a long period of time. By using a crosslinked hyaluronic acid and a crosslinked alginic acid crosslinked with an epoxy compound for the sponge layer of the wound dressing according to the present invention, it is possible to achieve both the enhancement of the physical properties of the above hyaluronic acid and the improvement of biological performance. At the same time, the cytotoxicity caused by the calcium salt of alginic acid is reduced, and the effect of promoting wound healing can be maintained for a long time. That is, when the carboxyl groups of hyaluronic acid are cross-linked with an epoxy compound, a cross-linked hyaluronic acid that is strong and has high enzyme decomposability can be obtained without affecting the basic structure of hyaluronic acid. When the cross-linked hyaluronic acid is decomposed by the enzyme again, the hyaluronic acid is regenerated and effectively acts on the wound healing, so that a highly safe wound dressing material having a long-term healing promoting effect can be obtained. Further, by cross-linking alginic acid with an epoxy compound, the healing effect can be maintained for a long time without being easily dissolved by the exudate even if the calcium salt is minimized. Further, since the sponge layer containing the crosslinked hyaluronic acid and crosslinked alginic acid of the biomaterial comes into contact with the wound site, it not only promotes the healing of the wound site, but also damages the wound site when removing the wound dressing of the present invention. Nothing.

In the sponge layer of the wound dressing according to the present invention, the cross-linked hyaluronic acid and the cross-linked alginic acid may be composed in an arbitrary ratio, but the content of the cross-linked hyaluronic acid is 10 to 80% by weight, It is preferable to use a sponge layer having a content of alginic acid of 20 to 90% by weight. Furthermore, when 1 to 20% by weight of uncrosslinked hyaluronic acid and / or uncrosslinked alginic acid is added to a sponge layer composed of crosslinked hyaluronic acid and crosslinked alginic acid, the hyaluronic acid is applied immediately after the wound dressing material is applied to a wound. as well as/
Or, it is particularly preferable because the effect of alginic acid is exerted.

As the hyaluronic acid to be crosslinked, for example, those having a molecular weight of preferably 500,000 to 3,000,000, more preferably 1.8 to 2.2 million are used. As the crosslinking agent, a water-soluble polyfunctional epoxy compound can be used. As the polyfunctional epoxy compound, for example,
Ethylene glycol diglycidyl ether, diethylene glycol diglycidyl ether, triethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, dipropylene glycol diglycidyl ether, tripropylene glycol diglycidyl ether, glycerol diglycidyl ether, glycerol triglycidyl ether, trimethylol Examples thereof include propane triglycidyl ether, sorbitol polyglycidyl ether, diglycidyl succinate, and diglycidyl adipate.

The crosslinking reaction is generally carried out at 0.2 to 2.0% by weight of hyaluronic acid, preferably at 0.5 to 1% by weight.
An aqueous solution is prepared and the pH of the solution is 4-7, preferably about 5
After adjusting to ~ 6, a reaction in which the epoxy compound is added so as to be about 1 / 5,000 to 1 mol, preferably about 5 / 5,000 to 1/5 mol with respect to the repeating unit of hyaluronic acid. It can be performed using a liquid. As the solvent, in addition to the above-mentioned water, an alcohol-water system can be used.

The reaction temperature may be, for example, about 20 to 80 ° C., preferably about 40 to 60 ° C., and the reaction time is preferably 2 to 10 hours, more preferably 4 to 6 hours.

The degree of cross-linking of hyaluronic acid is determined by the type, ratio, and reaction conditions of the epoxy compound used in the cross-linking reaction. The degree of cross-linking determines the biodegradability, water content, and hydrolysis rate of hyaluronic acid after molding. Therefore, the degree of cross-linking should be appropriately selected according to the application site of the wound dressing and the purpose of use.

On the other hand, as the alginic acid to be crosslinked, alkali salts of alginic acid, for example, sodium, potassium, ammonium salts of alginic acid are used. Further, as the crosslinking agent, the same polyfunctional epoxy compound as used for crosslinking of hyaluronic acid can be used.

The crosslinking reaction is generally carried out at 0.2 to 5.0% by weight of alginic acid, preferably at 0.5 to 3% by weight.
An aqueous solution is prepared and the pH of the solution is 4-7, preferably about 5
After adjusting to ~ 6, the reaction can be carried out using a reaction solution in which the epoxy compound is added in an amount of 1/20 to 2 mol, preferably about 1/10 to 1 mol, based on the repeating unit of alginic acid. it can. As the solvent, in addition to the above-mentioned water, an alcohol-water system can be used.

The reaction temperature may be, for example, about 20 to 80 ° C., preferably about 40 to 60 ° C., and the reaction time is preferably 2 to 10 hours, more preferably 4 to 6 hours.

The degree of cross-linking of alginic acid is determined by the type, proportion, and reaction conditions of the epoxy compound used in the cross-linking reaction. The degree of cross-linking changes the biodegradability, water content, and hydrolysis rate of alginic acid after molding. Therefore, the degree of crosslinking should be appropriately selected according to the application site of the wound dressing and the purpose of use.

Generally, the degree of cross-linking of hyaluronic acid and alginic acid is such that about 5 to 30% by weight of hyaluronic acid and / or alginic acid remains after being implanted in a living body (for example, subcutaneously of Wistar rats) and allowed to stand for one week. Is preferred.

The biomaterial used in the present invention needs to have good contact with the wound, and for that purpose, a sponge-like material is particularly preferable.

The sponge-like biomaterial may be a mixed sponge layer formed by mixing a solution containing cross-linked hyaluronic acid and a solution containing cross-linked alginic acid and freeze-drying the mixture. A sponge layer containing a sponge and a sponge layer containing a crosslinked alginic acid may be laminated.

As a method of forming the sponge layer of the present invention,
Generally, a solution composed of a biomaterial is stored at -20 ° C to -10C.
0 ° C., preferably −40 ° C. to −80 ° C. in a freezer, freeze-freeze and vacuum dry, or freeze-dry in a freeze dryer.
It is obtained by gradually freezing at 0 to -50 ° C and drying under vacuum. For example, when preparing a mixed sponge layer containing cross-linked hyaluronic acid and cross-linked alginic acid, after mixing a solution containing cross-linked hyaluronic acid and a solution containing cross-linked alginic acid, −20 ° C. to −100 ° C., preferably −40 ° C. to −100 ° C. 8
It may be manufactured by quenching and freeze-drying in a freezer at 0 ° C. and freeze-drying, or may be manufactured by gradually freezing to −30 to −50 ° C. in a freeze dryer and vacuum drying. . Also, when laminating a sponge layer containing crosslinked hyaluronic acid and a sponge layer containing crosslinked alginic acid, first inject a solution containing crosslinked hyaluronic acid into a molding container, and then inject a solution containing crosslinked alginic acid thereover, -20 ° C ~-
100 ° C., preferably may be produced by quenching and freeze-drying in a freezer at −40 to −80 ° C., or after gradually freezing to −30 to −50 ° C. in a freeze dryer,
It may be manufactured by vacuum drying.

When the sponge layer containing cross-linked hyaluronic acid and cross-linked alginic acid contains uncross-linked hyaluronic acid and / or uncross-linked alginic acid, each uncross-linked solution is mixed with the cross-linked solution and freeze-dried. Can be Examples of the method for forming the sponge layer include the freeze-drying method as described above, but are not limited thereto, and those skilled in the art can employ an appropriate method.

The thickness of the sponge layer made of a biomaterial may be arbitrarily set according to the purpose of use of the wound dressing material and the site to which the wound material is applied.
m, more preferably about 2 to 10 mm. When a sponge layer containing cross-linked hyaluronic acid and a sponge layer containing cross-linked alginic acid are laminated, the sum of the thicknesses is 1 to 20 m.
m, more preferably about 2 to 10 mm.

The thickness of the sponge layer containing the crosslinked hyaluronic acid and the thickness of the sponge layer containing the crosslinked alginic acid are arbitrarily set by changing the concentration and ratio of the solution containing the crosslinked hyaluronic acid and the solution containing the crosslinked alginic acid to be poured into the molding container. You can do it.

As a method of laminating the sponge layer composed of the above-mentioned biomaterial and the nonwoven fabric layer, any known method may be used. When the sponge layer containing crosslinked hyaluronic acid and crosslinked alginic acid is prepared, the sponge layer is laminated with the nonwoven fabric layer. Is preferred. For example, it can be obtained by first putting a solution containing cross-linked hyaluronic acid and cross-linked alginic acid into a container of an arbitrary shape, placing a nonwoven fabric layer thereon, and freeze-drying.

Since the present wound dressing has a problem that the antibacterial effect is not exerted at the wound site, any of the constituent members of the nonwoven fabric layer and the sponge layer made of a biomaterial, or all of the constituent members, are used. It is preferable to mix an antibacterial agent into the constituent members. As the antibacterial agent, any antibacterial agent such as a sulfa drug, penicillin, nalidixin, silver sulfadiazine, polymyxin sulfate, and gentamicin sulfate can be used, but the most preferable is
The use of silver sulfadiazine, which has a broad antibacterial spectrum and makes resistant bacteria less likely to appear. The antimicrobial content is
The type of the drug, the purpose of use and the site of application of the wound dressing may be determined, but when silver sulfadiazine is used, the content or applied amount of the wound dressing is 20 to 500 μm.
g / cm ² , preferably 30 to 400 μg / cm ² . With such a content, the growth of bacteria on the wound surface can be suppressed, and at the same time, the growth of cells inside the wound dressing that has absorbed the exudate can be effectively suppressed. The wound dressing is bandage-shaped or several cm
Any shape such as a pat from a corner to several tens cm square can be used, and it can be appropriately selected and used depending on the degree and depth of the wound, the area of the wound surface, and the like.

[0045]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but the effects of the present invention will be specifically described. However, the present invention is not limited to the following Examples.

Example 1 Production of a Wound Dressing Material Production of a Nonwoven Fabric Layer A nonwoven fabric layer composed of a hydrophobic fiber and a high-absorbency fiber was prepared by mixing a polyester fiber having an average fineness of 1.5 d and a rayon fiber having a mean size of 2.0 d by 70 by weight. After mixing at a ratio of 30, an extremely thin fiber layer (web) is made, and the webs are superimposed so that the basis weight is 100 g / m ^2, and the web layer is pierced with a pierced needle. The fibers were mechanically entangled with each other (needle punch method). Next, a hydrophobic polyester-based thermoplastic elastomer (trade name: Perprene, manufactured by Toyobo Co., Ltd.) was bonded to both surfaces of the nonwoven fabric layer by a spun bond method so that the total weight of the nonwoven fabric layer was 140 g / m ² . . Manufacture of cross-linked hyaluronic acid One of the 2 million molecular weight hyaluronic acid produced by fermentation
Ethylene glycol diglycidyl ether as a crosslinking agent was added to a 1% by weight aqueous solution (pH = 6) so as to be 1/10 mol of the molecular weight of the repeating unit of hyaluronic acid. Next, the mixture was allowed to stand in a dryer set at 50 ° C. for 5 hours to perform an intermolecular crosslinking reaction. Production of cross-linked alginic acid Commercially available sodium alginate (Wako Pure Chemical Industries, Ltd.)
Of ethylene glycol diglycidyl ether as a cross-linking agent was added to a 2% by weight aqueous solution (pH = 6) of the formula (1) in an amount of 1 mol based on the molecular weight of the repeating unit of alginic acid.
Next, the mixture was allowed to stand in a dryer set at 50 ° C. for 5 hours to perform an intermolecular crosslinking reaction. Production of Wound Dressing Material 4 cc of a 1% by weight aqueous solution of uncrosslinked hyaluronic acid was placed in a circular polystyrene container having a diameter of 50 mm and a height of 20 mm.
8 cc of the aqueous cross-linked hyaluronic acid solution prepared in 1), 8 cc of the aqueous cross-linked alginic acid solution prepared in 1), and 1 mg of silver sulfadiazine were sufficiently mixed and added. The above nonwoven fabric layer was cut into a circular shape having a diameter of 50 mm and mounted thereon. This polystyrene container was frozen at −40 ° C., and then dried under vacuum to produce a wound covering material containing a spongy biomaterial.

Example 2 Production of wound dressing Production of cross-linked hyaluronic acid One of hyaluronic acid having a molecular weight of 2,000,000 produced by the fermentation method
Ethylene glycol diglycidyl ether as a cross-linking agent was added to a 1% by weight aqueous solution (pH = 6) so as to be 1/100 mol based on the molecular weight of the repeating unit of hyaluronic acid. Next, the mixture was allowed to stand in a dryer set at 50 ° C. for 5 hours to perform an intermolecular crosslinking reaction. Production of cross-linked alginic acid Commercially available sodium alginate (Wako Pure Chemical Industries, Ltd.)
Of ethylene glycol diglycidyl ether as a cross-linking agent was added to a 2% by weight aqueous solution (pH = 6) of the formula (1) in an amount of 1 mol based on the molecular weight of the repeating unit of alginic acid.
Next, the mixture was allowed to stand in a dryer set at 50 ° C. for 5 hours to perform an intermolecular crosslinking reaction. Manufacture of wound dressing Crosslinked hyaluronic acid aqueous solution 12c manufactured in a circular polystyrene container having an inner diameter of 50 mm and a height of 20 mm
c, 1 mg of silver sulfadiazine was added, followed by 8 cc of the cross-linked alginate aqueous solution prepared above. On top of that, the nonwoven fabric layer produced in Example 1 was cut into a circular shape with a straight diameter of 50 mm and placed. This polystyrene container was frozen at −40 ° C., and then dried under vacuum to produce a wound covering material containing a spongy biomaterial.

Comparative Example 1 A wound dressing material for a control experiment A circular polystyrene container having an inner diameter of 50 mm and a height of 20 mm was charged with 20 cc of a 1% by weight aqueous solution of hyaluronic acid having a molecular weight of 2,000,000 prepared by a fermentation method. Next, the polystyrene container was placed in a freeze dryer, frozen at -40 ° C, and vacuum-dried to prepare a sponge-like wound dressing.

Comparative Example 2 Wound Dressing Material for Control Experiment 10 cc of a 2% by weight aqueous solution of commercially available sodium alginate (Wako Pure Chemical Industries, Ltd.) was injected into a circular polystyrene container having an inner diameter of 50 mm and a height of 20 mm. Next, the polystyrene container was placed in a freeze dryer, frozen at -40 ° C, and vacuum-dried to prepare a sponge-like wound dressing.

Example 3 Animal Experiment The wound dressings obtained in Examples 1 and 2 and Comparative Examples 1 and 2 were sterilized with ethylene oxide gas, and then subjected to the following experiment. That is, under anesthesia, the backs of Japanese white rabbits (3 months old) were shaved, disinfected with isodine,
A 0 mm circular full-thickness skin defect wound was created on both backs of a rabbit, the right back was applied with the wound dressing according to the present invention manufactured in Example 1 or 2, and the left back was used as a comparative example as a control experiment. The wound dressing for control experiment prepared in 1 or 2 was applied, and gauze was applied thereon and fixed with an elastic adhesive tape.

One week later, the dressing was removed under anesthesia, the condition of the wound surface was observed, and the area around the wound was disinfected with isodine.
The wound dressing according to the present invention and a wound dressing for control experiments were applied. Thereafter, a new wound dressing material was replaced every week, and the state of the wound was observed over time.

When the wound dressing according to the present invention was applied, almost all of the hyaluronic acid and / or alginic acid was decomposed and absorbed when removed in one week.

On the right back to which the wound dressing according to the present invention is applied, the wound surface is kept in a moderately moist environment, the formation of granulation tissue and the shrinkage from around the wound are promoted, and the wound dressing is applied.
At the week, the diameter of the skin defect wound was about 10 mm.

On the other hand, on the left back to which the wound dressing for control experiment consisting only of the hyaluronic acid or alginate sponge layer was applied, the diameter of the skin defect wound was about 20 mm at 3 weeks after the application of the wound dressing.

As described above, the wound dressing according to the present invention exhibited a healing-promoting effect as compared with the wound dressing for control experiments using only hyaluronic acid or alginic acid.

[0056]

As described above, the wound dressing according to the present invention has the following effects. Since the wound dressing material is laminated with a nonwoven fabric layer composed of a hydrophobic fiber and a highly absorbent fiber, even when a large amount of exudate is released from the wound, the exudate is absorbed and contained therein. The wound can be constantly kept in a moderately moist environment because the moisture that has been evaporated can be evaporated into the surrounding environment. Hyaluronic acid and alginic acid used in the present wound dressing are biomaterials each having an effect of promoting the healing of skin defects, but by combining these biomaterials, furthermore, in the whole process of wound healing, The effect is that the healing can be promoted very quickly and efficiently. By crosslinking hyaluronic acid and alginic acid with an epoxy compound, the effect of promoting wound healing can be maintained for a long time. Hyaluronic acid and alginic acid are biomaterials that are degraded and absorbed over time when applied to a wound surface. Therefore,
Wound dressings using matrices of these biomaterials not only provide enhanced healing, but also do not require long-term replacement. Even if it is replaced, there is an effect that there is no damage to the new tissue and no pain. By adding an antibacterial agent, the proliferation of bacteria is suppressed, and a further excellent healing promoting effect can be obtained.

Continued on the front page F term (reference) 4C076 AA75 AA77 AA82 BB31 CC19 CC31 EE10A EE12A EE24A EE26A EE36 EE37 FF70 4C081 AA12 BA12 BA13 BA14 CA021 CA071 CA161 CA231 CD021 CD042 CD082 CE01 DA05 DB03 DC04

Claims (5)

[Claims] 1. A wound dressing comprising a nonwoven fabric layer and a sponge layer containing a crosslinked hyaluronic acid and a crosslinked alginic acid crosslinked with an epoxy compound. 2. The nonwoven fabric layer has a basis weight of 30 to 300 g / m.
^2. The wound dressing according to claim 1, which is ² . 3. The wound according to claim 1, wherein the sponge layer containing the crosslinked hyaluronic acid and the crosslinked alginic acid crosslinked with the epoxy compound contains 1 to 20% by weight of uncrosslinked hyaluronic acid and / or uncrosslinked alginic acid. Coating material. 4. A sponge layer containing cross-linked hyaluronic acid and cross-linked alginic acid cross-linked with an epoxy compound,
The content of cross-linked hyaluronic acid is 10 to 80% by weight,
The wound dressing according to any one of claims 1 to 3, wherein the content of the crosslinked alginic acid is 20 to 90% by weight. 5. The wound dressing according to claim 1, further comprising an antibacterial agent.