JPH03289961A - Wound covering material - Google Patents

Abstract

PURPOSE:To improves simplicity, preserving ability, bacteria shielding ability, affinity with an organism, bleeding stopping ability, moisture content vaporization controllability by a method wherein after a small amount of methanol is absorbed in a spongelike sheet consisting of chitosan derivative and collagen, the spongelike sheet is mounted on a polyurethane film to dry the laminate. CONSTITUTION:20-80wt% ethylene oxide is contained and a random copolymer of tetrahydrofuran and ethylene oxide having average molecular amounts of 800-3000 is caused to react to diisocyanate. A chain is extended by using a chain extension agent, and two layers of a film formed of produced polyurethane resin and a porous sheet containing a chitosan derivative and a collagen derivative is formed. A chitosan derivative produced by chemically modifying chitosan, especially N-succinylated chitosan can be sufficiently used as a medical material. Further, by combining chitosan derivative, practical use is clinically carried out. This constitution provides adhesion, flexibility, durability, simplicity of handling, preserving ability, bacteria shielding ability, affinity with cell, bleeding stopping ability, excellent sewing ability, peeling ability from a wound surface, and beside moisture content vaporization controllability.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to wound dressings. More specifically, it is a wound made of two layers: a polyurethane resin film with excellent moisture permeability (hereinafter abbreviated as polyurethane film), and a bio-derived material sheet made of chitosan derivatives and collagen derivatives that are effective for the growth of tissue cells as artificial skin. Regarding covering materials.

[Conventional technology]

The main performance requirements for wound dressings are ■adhesion,
■Flexibility, ■Durability, ■Easy handling, ■Storability, ■
Bacterial blocking properties, ■ affinity with cells, ■ hemostatic properties, and ■ water evaporation control properties.

However, conventional wound dressing materials such as chitosan, collagen, chitosan-collagen composite materials, etc. have been used, but they have the disadvantage that even if they satisfy the required performance in some respects, they do not meet the requirements in other respects. was. (
(Unexamined Japanese Patent Publication No. 61-253065) (Problems to be Solved by the Invention) For example, sheets made only of biologically derived materials such as chitosan derivatives and collagen have low mechanical strength when wet, and as a result, some of them fail during use. It may crack or even fall out of the needle hole at the suture.

In addition, it is difficult to peel off the wound after use, and the wound surface may be damaged due to excessive force. In addition, a composite sheet of a bio-derived material sheet and a silicone film has poor moisture evaporation control properties, and there is a great risk that exudate will accumulate under the covering material. Although it is possible to make the film thinner to improve this, it lacks ease of handling.

[Purpose of the invention]

The purpose of the present invention is to solve the drawbacks of sheets made only of bio-derived materials and the drawbacks caused by using composite sheets. Namely, ■Adhesion, ■Flexibility, ■Durability, ■Ease of handling, ■Storability, ■Bacterial barrier properties, ■Compatibility with cells, ■Hemostasis, ■Moisture evaporation controllability, [phase] The purpose of the present invention is to provide a wound dressing material that satisfies all of the performance requirements for a wound dressing material, such as suturing properties and removability from the wound surface.

More specifically, in the initial stage of use of the wound dressing, a large amount of exudate is generated, and in order to improve this drainage (drainage of exudate), small mechanical holes are made in the composite sheet to prevent accumulation of exudate. After the wound dressing is used, the amount of exudate decreases and the hole closes as this fluid solidifies.Therefore, the composite sheet itself is required to have high moisture permeability.

Specifically, for example, in the case of a burn, the loss of water from the wound surface is 300 gHz O/m2-24 hrs for a first-degree burn, and 4300 gHz O/m2-24 hrs for a degree burn.

It is said to be 3400gHz O/m2・24hrs in ■degrees. (L. O. Lamke Burns.

3 P159-165) Conventionally, there is no material that satisfies flexibility, durability, and ease of handling, and also satisfies the above-mentioned moisture permeability. For example, the silicone resin film used for wound dressings has a rate of 1000 to 1700 gHzO/m2·24hrs, which does not have sufficient moisture permeability.

Chitosan is chitin that has been deacetylated by treatment with a concentrated alkali, and is a complex polysaccharide consisting of N-acetyl-D-glucosamine and D-glucosamine. Different ratios of D-glucosamine and D-glucosamine can be prepared.

Collagen derived from cow skin or pig skin is a major component of the connective tissue of living organisms, and is most suitable as a cell substrate, making it a material with extremely high biocompatibility. Also,
Collagen has relatively low antigenicity and is therefore widely used as a medical material.

Furthermore, these insoluble collagens (tropocollagen) are treated with proteolytic enzymes to remove the non-helical portions (telopeptides) at the molecular ends, and have extremely low antigenicity and are called atelocollagen. Atelocollagen has outstanding characteristics such as having the best biocompatibility among currently used medical materials due to its low antigenicity.

Chitosan-collagen composite materials are known to take advantage of the characteristics of chitosan and collagen and compensate for their respective drawbacks. (Japanese Unexamined Patent Publication No. 56-133344) However, chitosan is a polysaccharide that does not exist in living organisms and is obviously a foreign substance to living organisms, so if it is used as is in living organisms, a greater foreign body reaction will occur than with collagen. Therefore, it is difficult to apply chitosan alone as a medical material, and methods of improving biocompatibility by chemically modifying chitosan to obtain chitosan derivatives or by combining chitosan with collagen are being investigated.

It was discovered that chitosan derivatives obtained by chemically modifying chitosan, especially N-succinylated chitosan, can be used satisfactorily as medical materials, and furthermore, it was discovered that the combination of these chitosan derivatives and collagen could be used clinically. has been done.

From the above, adhesion, flexibility, durability, ease of handling,
The purpose of the present invention is to provide a wound dressing material that has preservability, bacteria-blocking properties, affinity with cells, hemostatic properties, good suturing properties, and peelability from the wound surface, and also has moisture evaporation control properties. .

[Means to solve the problem]

That is, the present invention uses, as a wound dressing material, a composite material in which a polyurethane film with excellent moisture permeability is used as a surface material, and a spongy sheet made of a chitosan derivative and collagen is laminated as a wound surface contact material. The gist is that a random copolymer of tetrahydrofuran and ethylene oxide containing 20 to 80% by weight of ethylene oxide units and having a number average molecular weight of 800 to 3,000 is reacted with a diisocyanate, and the chain is extended with a chain extender to obtain a polyurethane. The wound dressing has two layers: a resin film and a spongy sheet containing a chitosan derivative and collagen.

In the present invention, the ethylene oxide unit refers to the ratio of ethylene oxide to tetrahydrofuran and ethylene oxide expressed in weight percentage.

The polyurethane resin used in the polyurethane film of the present invention essentially contains a random copolymer of tetrahydrofuran (hereinafter abbreviated as TIF) and ethylene oxide (hereinafter abbreviated as EO) as a polyol component. This copolymer is ring-opened using water, ethylene glycol, short chain diol such as 1,4-butanediol as an initiator, and a mixture of THF and EO in the presence of a Lewis acid catalyst such as boron trifluoride ether complex. Synthesized by polymerization.

The content of EO units in the random copolymer of THF and EO is 20 to 80% by weight, preferably 30 to 70% by weight, in order to reduce swelling and deterioration of physical properties upon water absorption when polyurethane is used. %. More preferably, it is 40 to 60% by weight. The number average molecular weight of the random copolymer of THF and EO is 800 to 3,000. If the number average molecular weight is less than 800, the polyurethane film will be hard, and if it is more than 3,000, the adhesiveness will be high and swelling due to water absorption will increase. In order to obtain the best film properties, the number average molecular weight is preferably 1,000 to 2,500.

Further, if necessary, polytetramethylene ether glycol (hereinafter abbreviated as PTMG) may be mixed with the random copolymer of THF and EO.

In this case, the number average molecular weight of PTMGO to be added is 800.
~3,000, and the number average molecular weight of the polyol mixture is 800 to 3,000, and further 1,000 to 2,500 to obtain a polyurethane film with well-balanced physical properties.
It is preferable that

It should be noted that even if the aforementioned random copolymer of THF and EO contains a partial block copolymer structure generated during polymerization in the polyol chain, it does not go against the spirit of the present invention.

In addition to the above, THF (!: Copolymer with E○)
Adding EO to PTMG ring-opening polymerized with HF, or adding polyethylene glycol (hereinafter P
It is also possible to obtain a block copolymer by adding THF to (abbreviated as EG), but the polyurethane using these block copolymers contains a long chain of highly hydrophilic EO homopolymer in the structure, so it is difficult to obtain a block copolymer. Similarly to the case where PEG is mixed with polyurethane, swelling due to water absorption tends to increase significantly as the EO content in the total amount of polyurethane increases, which is a practical problem.

When the aforementioned random copolymer of THF and EO is used as the polyol component of polyurethane, it is surprising that THF
It has been found that, compared to block copolymers of and EO and combined systems of PTMG and PEG, it exhibits high moisture permeability despite the fact that the increase in water absorption due to an increase in the number of EO units is small.

In order to obtain the target polyurethane resin of the present invention, an excess of 7 equivalents of diisocyanate is added to the above specific polyol.
After reacting at 0 to 120°C to form a urethane prepolymer with isocyanate groups at the ends,
A method of chain extension using a chain extender at ~100°C is commonly used.

Here, the equivalent ratio of diisocyanate to polyol in the urethane prepolymer is usually 1.5 to 6:1, but in order to have both good physical properties and moisture permeability, it is 1.8 to 4.
The ratio is preferably 5:1.

The diisocyanate used in the present invention is 4.4'
- diphenylmethane diisocyanate.

2.4- and 2,6-dolylene diisocyanate, 1
．． Aromatic diisocyanates such as 5-naphthalene diisocyanate h, m- and P-phenylene diisocyanate Isophorone diisocyanate + 4. 4'-Dicyclohexylmethane diisocyanate, 1,4-cyclohexylene diisocyanate Examples include alicyclic diisocyanates such as hydrogenated products of tolylene diisocyanate, and aliphatic diisocyanates such as hexamethylene diisocyanate.

Among these, cycloaliphatic diisocyanates are preferred because they are non-yellowing and have good mechanical properties. These are usually used alone, but two or more types may be used in combination. Also,
Among the alicyclic diisocyanates, 4-4'-dicyclohexylmethane diisocyanate is most preferred in view of the balance between mechanical properties and moisture permeability of the film obtained.

Chain extenders used in the present invention include ethylene glycol, propylene glycol, diethylene glycol,
1.4~Low molecular diols such as butanediol and 1,6-hexanediol, aliphatic diamines such as ethylenediamine, 1,2-propanediamine, tetramethylenediamine and hexamethylenediamine, isophoronediamine, 4
．． 4'-dicyclohexylmethanediamine, 3.3'dimethyl-4,4'-dicyclohexylmethanediamine,
Examples include alicyclic diamines such as 1,4-cyclohexylene diamine, hydrous hydrazine, and water.

Among these, alicyclic diamines are preferred in terms of good stability of the polyurethane solution and good heat resistance of the resulting film, and can be used alone or in combination of two or more. Furthermore, the above-mentioned low-molecular-weight diols may be used in combination as long as the mechanical properties, heat resistance, etc. of the film are not significantly deteriorated. Among the alicyclic diamines, isophorone diamine is particularly preferred from the viewpoint of solution stability and balance of various physical properties of the film.

As the organic solvent used in the polyurethane synthesis of the present invention, solvents with strong dissolving power such as dimethylformamide, dimethylacetamide, and dimethyl sulfoxide can be used alone or in aromatic solvents such as toluene and xylene, and methyl ethyl ketone.

Ketone solvents such as acetone and cyclohexanone, acetate ester solvents such as ethyl acetate and butyl acetate, chlorine solvents such as dichloroethane, ether solvents such as tetrahydrofuran and dioxane, and alcohol solvents such as methanol and isopropanol. It can also be used singly or in combination with two or more selected ones.

The polyurethane resin obtained as described above preferably contains 15 to 60% by weight of ethylene oxide units based on the total amount of polyurethane, and if the ethylene oxide units are less than 15% by weight, the moisture permeability of the film is insufficient.
If it is more than 60% by weight, it is not preferable because dimensional changes and physical property deterioration due to swelling upon water absorption are large.

In addition, in the present invention, catalysts commonly used to promote urethanization reactions, such as tertiary amines such as triethylene diamine and organic tin compounds such as dibutyltin dilaurate, may be present if necessary during polyurethane synthesis.

Furthermore, in order to improve the durability of the polyurethane resin of the present invention, one or more of a hindered phenol antioxidant, a benzophenone or benzotriazole ultraviolet absorber, and a hindered amine stabilizer may be added in advance. Good too. In this case, each additive is added in an amount of 0.05 to 3% by weight based on the solid content of the polyurethane, but preferably 0.2 to 1% by weight in order to obtain a good effect with a small amount. In the polyurethane of the present invention, a hindered amine stabilizer is particularly effective and can reduce the decrease in physical properties against oxidative deterioration and hydrolysis during sterilization.

Regarding the membrane forming method, it is well known that a polyurethane membrane with high moisture permeability can be obtained by making it porous. Wet film forming method for extracting soluble substances (2) There is a method in which a water-in-oil emulsion of a polyurethane resin is applied onto a support and a porous film is obtained by heating and drying.

To obtain a non-porous film from a polyurethane resin solution, this solution is applied to a support or release paper, and dry film formation is performed by heating and drying. Stable moisture permeability can be obtained with good reproducibility, and even a single film can be used for practical purposes. A product with sufficient strength, elongation, and durability can be obtained.

Therefore, it is extremely useful as medical adhesive films, sanitary materials, and other moisture-permeable materials that do not allow the penetration of foreign substances.

The support used in dry film formation is not particularly limited, but it is desirable to use a release paper having a uniform thickness, which has an inverse correlation to the release properties of polyethylene or polypropylene films, fluorine-based films, or silicone-based films. The coating method is not particularly limited, but either a knife coater or a roll coater can be used. The drying temperature can be set arbitrarily depending on the capacity of the dryer, but it is necessary to select a temperature range that does not cause insufficient drying or rapid desolvation.

Preferably it is in the range of 60 to 130°C.

The thickness of the formed film is usually 10 to 200 μm, preferably 10 to 80 μm. If the thickness is less than 10 μm, pinholes are likely to form during coating, and the film is likely to block, making it difficult to handle. If the thickness is 80 μm or more, it tends to be difficult to obtain sufficient moisture permeability. Additionally, the film of the present invention is characterized in that the dependence of moisture permeability on film thickness is smaller than that of other urethane films.

The film of the present invention has a moisture permeability of 2,000 g/m"-24 hr or more, preferably 3,000 g/m"-24 hr or more at a thickness of 10 to 80 μm,
Measured according to JIS 20208), it has high moisture permeability. If it is less than this, it is not preferable because it causes stuffiness and discomfort when applied to the skin. In addition, the 100% modulus is 20 kg/cm" or more, preferably 30 kg/cm"
m” or more.100% modulus is 20kg/cm
If it is less than 2, the adhesiveness of the film is high, and the films tend to block each other. Moreover, if it exceeds 80 kg/cm'', flexibility tends to be poor and moisture permeability also tends to decrease.

The chitosan derivative, which is a component of the biologically derived material sheet comprising the chitosan derivative and collagen of the present invention, is obtained by succinylating chitosan.
-The chitosan used for the preparation of succinylated chitosan is
Any material obtained by deacetylating chitin with a concentrated alkali and soluble in acid can be used, provided that the degree of deacetylation is at least 45%. It is preferable to use one that is.

N-succinylated chitosan is prepared by reacting chitosan with a carboxylic acid anhydride to perform N-succinylation of chitosan, but by adding collagen to chitosan and then performing N-succinylation of chitosan. It can also be prepared. Furthermore, the N-acyl chitosan in the composite material of N-acyl chitosan and collagen is a chitosan derivative in which the amino group of chitosan is modified with a saturated or unsaturated fatty acid having 1 to 32 carbon atoms and/or a dicarboxylic acid having 2 to 8 carbon atoms. The N-acyl chitosan can also be N-acetyl chitosan or N-succinyl chitosan.

The collagen in the spongy sheet comprising a chitosan derivative and collagen of the present invention may be any type of atelocollagen with improved biocompatibility or a collagen derivative obtained by chemically processing collagen. I can do it. For example, succinylated collagen, which is made by treating collagen with succinic anhydride, has excellent antithrombotic properties, and methylated collagen, which is made by treating collagen with anhydrous methanol, has unique properties such as increasing the reaction with platelets. Therefore, medical materials suitable for purposes can be obtained according to their properties.

Chemical modification of collagen is carried out by reaction of collagen with various chemical reagents, but can also be carried out after mixing collagen with chitosan derivatives. When the reagent for chemically modifying collagen is a carboxylic anhydride, a composite material obtained by adding collagen to chitosan is reacted with the carboxylic anhydride to convert N-succinylation of chitosan and N-succinylation of collagen. You can also do both at the same time.

Chemical modification of collagen is mainly carried out on the amino groups or carboxyl groups of collagen.
00% (preferably 30 to 100%) of chemical modification is preferred.

The spongy sheet made of the chitosan derivative and collagen of the present invention contains chondroitin, chondroitin-4
- Further water retention can be imparted by adding sulfuric acid, dermatan sulfate, chondroitin-6-sulfate or hyaluronic acid. These mucopolysaccharides are contained in the skin and play an important role in retaining moisture.

Furthermore, by adding fibronectin or fibrin to the spongy sheet of the chitosan derivative and collagen of the present invention, repair of a wound can be promoted.

Furthermore, the reaction with blood can be controlled by adding heparin or protamine to the spongy sheet of the chitosan derivative and collagen of the present invention.

In order to develop new medical materials, it is necessary to improve their biocompatibility, and the chemical modifications and addition of biologically useful components described above serve the purpose in this respect.

The composite material of the present invention is produced by drying the chitosan derivative and collagen solution, dispersion, or gel described above, and the composite material solution or dispersion is applied to the surface of a substrate such as a glass plate. If the composite material is then dried, a film-like (sheet-like) or membrane-like material can be produced, and when the composite material is freeze-dried, a sponge-like sheet material can be produced.

The chitosan derivative and collagen sheet composite material of the present invention can be crosslinked by treatment with a bifunctional crosslinking agent or by irradiation, thereby improving the strength and water absorption of the material.

Any difunctional crosslinking agent for crosslinking the optical composite material can be used as long as it has two or more functional groups, but hexamethylene diisocyanate, glutaric Preferably, aldehydes or polyepoxy compounds are used. The polyepoxy compound used in the present invention is a hydrophilic crosslinking agent, such as diglycidyl ether of glycerol (degree of polymerization 1 to 3), polyglycidyl ether of polyol, especially glycerol diglycidyl ether, glycerol triglycidyl ether, diglycerol tetra Glycidyl ether and ethylene glycol glycidyl ether are preferred. After a mixture of a chitosan derivative and collagen is formed into a film, membrane, or sponge, the formed article is immersed in a solution of a crosslinking agent or irradiated with radiation, thereby causing a crosslinking reaction. As the radiation, any particle beam such as ultraviolet rays, gamma rays or alpha rays can be used, but it is preferable to use ultraviolet rays or gamma rays.

This wound dressing may be made to have an antibacterial effect by carrying an antibacterial agent thereon. Examples of methods for carrying an antibacterial agent include a method in which a predetermined amount of an antibacterial agent is dispersed in the biomaterial in advance to prepare a sheet of the biomaterial, and a method in which an antibacterial agent is loaded on a polyurethane film. A method of dispersing a predetermined amount of an antibacterial agent in the intermediate layer between a polyurethane film and a bio-derived material, for example, a method of dispersing a predetermined amount of an antibacterial agent in the same urethane resin as the polyurethane film to form a polyurethane film/antibacterial agent-dispersed polyurethane layer. /A three-layer structure made of bio-derived materials may also be used. As antibacterial agents, sulfa drugs, cephalosporins, penicillins, and nalidixic acid may be used.

The method for producing a composite sheet is usually to swell the surface of a polyurethane film with an organic solvent, such as an alcohol such as methanol, or another solvent, and then to swell it with a bio-derived material sheet and dry it. .

This composite sheet is used by applying the bio-derived material side to the wound surface. This material has excellent biocompatibility, so it adheres well to the wound surface, and since living cells do not excessively enter the mechanism, it can be removed after healing without damaging the wound surface. In particular, when skin grafting is required, an appropriate graft bed can be created.

Furthermore, the antibacterial agent contained in the polyurethane film, the biologically derived material, or the interlayer between the urethane film and the biologically derived material is gradually released, thereby preventing entry of bacteria from the outside and inhibiting infection of the wound surface.

〔Example〕

The present invention will be explained below with reference to examples, but the present invention is not limited to the contents of the examples.

<Production Examples 1 to 4> Production of THF-EO silane copolymer According to the recipe shown in Table 1, THF and EO were constantly mixed in an autoclave using ethylene glycol as an initiator, BF as an acid catalyst, and ethyl ether complex salt. Random copolymerization was carried out at pressure and 30°C. After polymerization, the acid catalyst in the product is neutralized with alkali, the precipitate is filtered, and the temperature is further heated at 100°C.
The water was dehydrated by bubbling with dry nitrogen.

The four types of THF-EO silane copolymers (hereinafter referred to as polyols) obtained, A, B, C, and D, were all colorless and transparent liquids, and their number average molecular weights and EO contents were as shown in Table 1.
It was as shown in

The number average molecular weight was calculated from OH value measurement, and the EO content was calculated from the amount charged.

<Production Examples 5 to 8> Production of polyurethane resin a) Production of polyurethane solution Using polyols A, B, C, and D shown in Table-1,
After reacting 4,4'-dicyclohexylmethane diisocyanate and each polyol in a flask at 100°C for 6 hours under dry nitrogen according to the recipe shown in Table 2 to obtain a urethane prepolymer having isocyanate groups at the terminals,
A chain extension reaction was carried out for 2 hours in a dimethylformamide solvent using isophorone diamine as a chain extender while maintaining the temperature at 30°C to obtain a colorless, transparent and viscous polyurethane solution with a polyurethane solid content concentration of 25 ht%. These temperatures 2
Each has a viscosity of 35,000 cps at 5°C.

20.0OOcps, 15,0OOcps, 16°00
It was 0 cps.

b) Preparation of polyurethane film The above polyurethane solution is diluted with methanol to a concentration of 1 wt%, and an antibacterial agent such as silver sulfadiazine, gentamicin, or polymyxin B is added to this methanol solution at a concentration of 0.01 wt% to 0.1 wt%. Mix in concentration range. This mixed solution was poured onto a glass plate provided with a spacer, stretched with a glass rod, and coated to a uniform thickness, and then dried at 80°C for a day and night to obtain a colorless and transparent polyurethane dry film. At this time, the thickness of the film was adjusted to about 30μ using a spacer.

In addition, when examining the difference in moisture permeability due to changes in film thickness, films with different thicknesses of 10 to 100 μm were separately produced. The obtained film was heated at 23°C for performance testing.
It was cured in a constant temperature and humidity room at 60% RH.

Production Example 9: Preparation of chitosan 200g of crushed red snow crab shell was mixed with 5% hydrochloric acid. After stirring for 5 hours at room temperature, the solution was filtered and the remaining solid was washed with water. This solid was placed in a 5% aqueous sodium hydroxide solution 21 and heated to 90°C for 2.5 hours with stirring, then the solution was filtered and the remaining solid was washed with water.

The chitin obtained here is 50% sodium hydroxide aqueous solution 2! After heating at 90°C for 2.5 hours with stirring, the solution was filtered, and the precipitated solids were thoroughly washed with water.
and dried at 95°C, with a degree of deacetylation of 99%.
41 g of chitosan was obtained.

<Production Example 10> Preparation of N-succinylchitosan Production Example 9
After dissolving 2 g of chitosan in 40 tnE of 8% acetic acid aqueous solution, this was diluted into 16 On/2 methanol. Separately, 1.4 g of succinic anhydride (corresponding to 0.98 mol per 1 mol of amine group of chitosan) was added to 5 ml of acetone.
The entire amount of the obtained acetone solution of succinic anhydride was added to the above chitosan solution, and the mixture was stirred overnight. After filtering the precipitate, it was dried to obtain 2 g of N-succinyl chitosan powder. The modification rate of amine groups in this N-succinyl chitosan was 35%.

Production Example 11 Preparation of Collagen Finely grind fresh calf dermis, and add 100 g of this fine powder.
was washed repeatedly with a 0.1M aqueous sodium acetate solution and then with water to obtain insoluble collagen.

Production Example 12> Preparation of Sponge 2.625 g of the aforementioned N-succinyl chitosan was dissolved in pyrogen-free water, and the pH was adjusted to 3 with IN hydrochloric acid to give 125 g.

1.125 g of the insoluble collagen obtained above was suspended in pyrogen-free water and adjusted to pH 3 with IN hydrochloric acid.
After mixing both solutions (25 g) and stirring well, dispense into trays and freeze-dry them into 100 mm x 100 mm x 2 pieces.
Twelve pieces of sponge of mm were obtained.

This sponge was neutralized in a mixture of methanol and dibasic sodium phosphate, and then immersed in methanol in which hexamethylene diisocyanate was dissolved to introduce crosslinking. This sponge was freeze-dried again and sterilized with styrene oxide gas to obtain a porous sheet of succinylated chitosan and insoluble collagen complex.

Production Example 13> Lamination of polyurethane film and sponge After absorbing a small amount of methanol into the spongy sheet made of the chitosan derivative and collagen obtained as described above, (b) of (Production Examples 5 to 8) ) A composite sheet was obtained by bonding and drying the 25 μm thick polyurethane film obtained in . Make a hole in this sheet using a kenzan,
Made into a porous composite sheet.

<Examples 1 to 3> After the bonded porous composite sheets obtained above were sterilized with ethylene oxide gas, they were subjected to the following tests.

A full-thickness defective side (35 mm in diameter) of the dorsal skin of a SP rat (6-8 weeks old) was surgically created, and a stainless steel ring with a diameter of 0.4 body diameter was sutured (16 stitches). The resulting composite sheet was applied, a moisturizing bat and absorbent cotton were placed on top of it, and it was bandaged with an aesthetic band. One week and two weeks later, bioadhesion and reconstruction of the dermal layer were examined histologically to confirm effectiveness.

The results are shown in Table 5, and it was found that all the materials had good healing effects and were suitable as wound dressings.

(Effects of the Invention) The wound dressing material of the present invention has excellent adhesion, flexibility, durability, ease of handling, preservability, bacterial barrier properties, affinity with living organisms, hemostasis, moisture evaporation control properties, etc., and is put to practical use. It is extremely excellent.

Out wish Man

Claims (2)

[Claims] (1) A polyurethane obtained by reacting a random copolymer of tetrahydrofuran and ethylene oxide containing 20 to 80% by weight of ethylene oxide units and having a number average molecular weight of 800 to 3,000 with a diisocyanate and extending the chain with a chain extender. A wound dressing material having two layers: a film made of resin and a porous sheet containing a chitosan derivative and a collagen derivative. (2) A wound dressing according to claim 1, in which an antibacterial agent is contained in a polyurethane resin film or a sheet containing a chitosan derivative and a collagen derivative.