JPS6347470B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION BACKGROUND OF THE INVENTION Technical Field The present invention relates to a novel biological coating membrane. More specifically, the present invention relates to a biocoating membrane comprising a graft copolymer membrane of a water-soluble polymer and solubilized keratin. When skin is damaged by a wound, burn, etc., it is ideal to collect one's own skin from another site and transplant it for treatment. However, there are limits to the area and amount that can be collected, so when the affected area is large, an artificial covering membrane is usually used. The coating film of the present invention protects and protects such damaged skin.
used for treatment. Prior Art Conventional biological coating membranes for the above purpose include freeze-dried pig skin, nylon sheets, silicone gauze, silicone rubber membranes, membranes made by solidifying plasma, fibrin membranes, and oil-treated gauze. It was used. However, these have various problems in terms of compatibility with the affected area, water vapor permeability, and ability to prevent bacterial infection. Furthermore, recently, a coating film using collagen has been proposed (US Pat. No. 4,280,954). The collagen coating has excellent biocompatibility. However, collagen is antigenic and is not soluble in water. Atelocollagen is a type of collagen that has been treated to eliminate antigenicity, but it has the disadvantage that the membrane cannot be easily adjusted. That is, atelocollagen cannot be made into a highly concentrated aqueous solution, and does not dissolve in water unless the pH is around 3, so a neutralization operation is required afterwards. Furthermore, it is difficult to handle due to its high viscosity, and when insolubilizing it, it is difficult to control the crosslinking reaction. Moreover, it does not have good adhesion to the skin and is expensive. Purpose of the Invention Therefore, the purpose of the present invention is to provide a biological coating membrane that has excellent water vapor permeability (moisture permeability), conformability and adhesion to the skin, preventive effect against bacterial infection, etc., is inexpensive, and is easy to form. It's about doing. A further object of the present invention is to provide a biocoating membrane that is highly bioabsorbable and has no antigenicity. The biological coating membrane of the present invention that achieves the above object has a molecular weight of 500
It consists of a graft copolymer film of the above water-soluble polymer and solubilized keratin. Furthermore, the biocoating membrane of the present invention comprises the above-mentioned graft copolymer membrane and a biocompatible support membrane layer formed thereon. Furthermore, the biocoated membrane of the present invention includes the above-mentioned graft copolymer membrane layer, a biocompatible supporting membrane layer formed thereon,
It consists of a water permeation regulating layer formed on the support membrane layer or between the support membrane layer and the graft copolymer layer. Furthermore, in the biological coating membrane of the present invention, the graft copolymer membrane has a thickness of 5 to 1000 μm and a moisture permeability of 0.1 to 200 μm.
mg/cm ² ·hr and water absorption of 0.1 to 150 g/cm ² . Further, in the biological coating membrane of the present invention, the water-soluble polymer is selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivatives, and alginic acid. Furthermore, in the biological coating membrane of the present invention, the supporting membrane layer is made of a polymer selected from nylon, polypropylene, polyethylene, polyester, urethane, SBS, polyvinyl chloride, cellulose, acrylic, natural or synthetic rubber, and thermoplastic elastomer. It is formed. Furthermore, in the biological coating membrane of the present invention, the water permeation regulating layer is made of natural rubber, synthetic rubber, or thermoplastic elastomer, preferably silicone rubber, urethane rubber,
Made of SBS or EPDM. DETAILED DESCRIPTION OF THE INVENTION The biological coating membrane of the present invention is first composed of a graft copolymer membrane of a water-soluble polymer having a molecular weight of 500 or more and solubilized keratin. The above-mentioned solubilized keratin can be obtained by a method known per se, for example, the reduction method of O'Donell et al. (IJ
O′Donell et al Aust. J. Biol. Sci. Vol. 17, p. 973,
1964). That is, it is obtained by adding wool to a urea solution, treating with mercaptoethanol, then iodoacetic acid or chloroacetic acid, filtering, dialysis, and centrifugation. Alternatively, an oxidation method in which wool is treated with performic acid (S.Moore,
Journal of Biologi Chemistry, Volume 238, 235
Page, 1963). Preferable examples of the water-soluble polymers include polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivatives, and alginic acid. It is necessary that these polymers have a molecular weight of 500 or more, and a polymer having a molecular weight of 2,000 to 10,000 is preferable. A water-soluble polymer with a molecular weight smaller than 500 that is graft-polymerized with keratin retains antigenicity. The graft copolymers of the invention are prepared by methods known per se. For example, when the water-soluble polymer is polyethylene glycol, polypropylene glycol, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivative, alginic acid, etc., these water-soluble polymers are reacted with a coupling agent such as cyanuric chloride, and then the reaction is performed. A graft copolymer is obtained by coupling the product with solubilized keratin. Further, when the water-soluble polymer is polyvinyl alcohol, alginic acid, a water-soluble cellulose derivative, etc., the water-soluble polymer can be graft-copolymerized with solubilized keratin under irradiation with radiation. Furthermore, the above graft copolymer can also be obtained by reacting monomers such as acrylamide, acrylic acid, vinylpyrrolidone, etc. with solubilized keratin. Since the graft copolymer of the water-soluble polymer and solubilized keratin thus obtained is water-soluble, it is crosslinked to make it water-insoluble to prepare a coating film. Water-insoluble graft copolymers can be produced by various methods shown below. (1) Dissolve the water-soluble graft copolymer in water or a mixture of water and alcohol, put the solution in a dish and dry it, and then apply the resulting membrane to an aldehyde solution such as glutaraldehyde solution or formaldehyde solution, especially glutaraldehyde solution. Insolubilize by immersing in aldehyde solution. The water-soluble graft copolymer can be dissolved up to about 10% in water, but is preferably dissolved at a 5% concentration and dried in a dish. The film produced is 25%
After soaking in a glutaraldehyde solution of about 100 ml for 2 hours or more, washing with water and drying. Drying may be air drying or freeze drying. Distilled water can be used as water, but
If it is desired to produce a graft copolymer solution with a higher concentration, the solubility can be increased by adjusting the pH to the acidic or alkaline side. For example, in the case of a carboxymethyl keratin graft copolymer, the solubility becomes very high at pH 1 to 2 or pH 8 to 9. (2) Add an aldehyde solution, especially a glutaraldehyde solution, to the solution of the water-soluble graft copolymer and place the mixture in a dish to dry. It is desirable to add glutaraldehyde to a concentration of about 0.5%. (3) Dry the water-soluble graft copolymer solution in a dish, and slowly soak the resulting membrane in steam.
Stretched 1.5 to 5 times (preferably 2.5 to 4 times),
This state is maintained for 30 minutes or more, preferably 3 hours or more. (4) A solution of the water-soluble graft copolymer is placed in a dish and dried, and the resulting membrane is irradiated with gamma rays of 4 Mrad or more (preferably 6 to 10 Mrad) under deoxidized conditions or with ultraviolet rays under a nitrogen atmosphere. irradiate. (5) Add the aqueous solution of the water-soluble graft copolymer to a carboxylic acid, especially formic acid, trihaloacetic acid (e.g., trichloroacetic acid, tribromoacetic acid) or dihaloacetic acid (e.g., dichloroacetic acid, dibromoacetic acid) for about 50 minutes.
% and put the solution into a dish to dry. Although other carboxylic acids can also be used, the above carboxylic acids have high solubility and are particularly preferred. (6) The solubilized keratin obtained by cutting the crosslinked part of the keratin molecule is crosslinked again to make it insolubilized. That is, wool is reduced with tri-n-butylphosphine, formic acid is added to the wool, and the wool is treated with ultrasound. A coated membrane is obtained by forming a membrane from the supernatant after centrifugation. Alternatively, it can be obtained by reducing wool, adjusting the soluble portion to pH 5, dialyzing it, and then forming a cast film according to the method of O'Donell. (7) It can be obtained by dissolving a water-soluble graft copolymer in water or a mixture of water and alcohol, drying the solution, and treating the resulting membrane with hot water at 45°C or higher. (8) It can be obtained by dissolving a water-soluble graft copolymer in water or a mixture of water and alcohol, and heating and dehydrating the solution. Heating dehydration treatment is at 45℃
It is desirable to carry out the process at a temperature higher than that. By changing the degree of crosslinking in the above-mentioned insolubilization treatment, the degree of insolubilization of the graft copolymer membrane can adjust the degree of bioabsorption. The graft copolymer coating thus obtained preferably has a thickness of 5 to 1000 μm, a moisture permeability of 0.1 to 200 mg/cm ² ·hr and a water absorption of 0.1 to 150 g/cm ² . The above thickness of the graft copolymer film is necessary to maintain a certain level of strength and coating effect. Moisture permeability is necessary to prevent tissue destruction on the wound surface, and water absorption, which is expressed as the amount of water vapor that evaporates per unit time through a membrane with a unit area of close contact, is necessary to absorb and remove excess body fluid that has exuded. It is expressed as the amount of water absorbed per unit area of the membrane. The numerical values of the above-mentioned physical properties that the graft copolymer film should have are not necessarily critical, but in order to function as a coating film, it is necessary that they be within the above-mentioned numerical ranges, and It is appropriately selected within the range depending on the situation in which it is used. For example, in the early stages of a burn injury, body fluid exudates rapidly, so a graft copolymer film with high water absorption and moisture permeability is used to evaporate moisture and heat. The above-mentioned graft copolymer membrane can be used as a coating film by itself, but when long-term wound protection is required, a biocompatible support film can be used on top of the above-mentioned graft copolymer membrane. form a layer,
It is desirable to strengthen the membrane. The biocompatible support membrane layer does not need to be toxic or inflammatory to living organisms, and supports the gelatinized coating membrane by absorbing body fluids when used for a long period of time. Suitable materials for such a supporting membrane layer include nylon, polypropylene, polyethylene, polyester, urethane, SBS, polyvinyl chloride, cellulose, acrylic, various rubbers, and thermoplastic elastomers, including mesh, nonwoven fabric,
It is desirable that the membrane be in a form that allows living tissue to penetrate, such as woven fabric, velor, or sponge membrane. To form the support membrane layer on the graft copolymer, the support membrane is immersed in an aqueous graft copolymer solution, dried and then crosslinked with glutaraldehyde, or glutaraldehyde is added to the aqueous graft copolymer solution. Then, the support membrane is immersed in this and dried and crosslinked. If the support film is difficult to wet, plasma treatment is performed to make it hydrophilic. Furthermore, in the present invention, it is also desirable to form a water permeation regulating layer on the biocompatible support membrane layer or between the support membrane layer and the graft copolymer membrane layer. Preferred materials for the moisture permeation regulating layer include silicone rubber, urethane rubber, SBS, and EPDM.
This moisture permeation control layer has a moisture permeability of the entire coating film.
It is formed to have an amount of 0.1 to 200 mg/cm ² hr. Next, an example of manufacturing the coating film of the present invention will be shown. Production example (1) Preparation of solubilized keratin (Part 1) Add 95 ml of 8M urea solution adjusted to pH 7.4 with hydrochloric acid to 1.7 g of wool (Wool Top), and add 0.02 M of tris(hydroxymethyl)aminoethane to this mixture.
and 0.001 M of disodium ethylenediaminetetraacetic acid (EDTA-2Na), and after replacing with nitrogen gas, 1 ml of mercaptoethanol was added.
Adjust the pH to 10.3 with 5NKOH. Stir for 3 to 4 hours, add 2.68 g of iodoacetic acid, and adjust the pH to 8.5 with 5NKOH. After stirring overnight, it is filtered using Nutsutsue, and about 100 to 110 ml of the solution is dialyzed for 5 days. The dialyzed residue was centrifuged at 10,000 rpm for 1 hour, and the supernatant was lyophilized to yield 0.68 g of solubilized keratin.
(yield 40-60%). (Part 2) Add 3 ml of hydrogen peroxide solution dropwise to 27 ml of formic acid under cooling, and then stir at room temperature for 2 hours. 1.0 g of wool is soaked in the resulting performic acid solution. After leaving it in the dark for 24 hours, it is filtered using a glass filter (G ₃ ). Residue PH11 ammonia solution 150
ml and stir for 2 hours. PH10.3 with ammonia
After stirring for 24 hours, centrifugation is performed at 10,000 rpm for 1 hour, and the supernatant is freeze-dried to obtain solubilized keratin (yield: 40-50%). 2 Preparation of graft copolymer Preparation of polyethylene glycol-keratin graft copolymer (hereinafter referred to as PEG-SCMK) (1) Synthesis of cyanurated polyethylene glycol Dissolve 36.7 g (0.2 mol) of cyanuric chloride in 800 ml of anhydrous benzene. Add 20 g of anhydrous sodium carbonate and polyethylene glycol (single-terminated PEG manufactured by Union Carbide Co., Ltd.) to this solution.
Add 100 g (0.02 mol) of molecular weight 5000, and add 30
Stir at ℃ for 40 hours. After the reaction is completed, the anhydrous sodium carbonate is filtered out and petroleum ether 1.2-5
Let it sink again. Separate the precipitate and add benzene
Dissolve in 500-800ml, add petroleum ether and reprecipitate. This operation is repeated until cyanuric chloride is no longer confirmed by liquid chromatography, and the reaction product is dried under vacuum. (2) Synthesis of PEG-SCMK 3.0g of solubilized keratin extracted from wool and carboxymethylated was added to 0.1M borax solution (6N
Adjust the pH to 9.6 with KOH) Dissolve in 300 ml and cool to 5°C. To this solution, 10 g of cyanurated polyethylene glycol was slowly added over 30 minutes, and the mixture was stirred at 5°C for 6 hours. The reaction solution is dialyzed overnight to remove generated hydrogen chloride. Potassium dihydrogen phosphate as external dialysis fluid
A disodium hydrogen phosphate solution (PH7.1) and a Visking tube 30/20 (manufactured by Visking) are used as a dialysis membrane. Next, ammonium sulfate was added to the reaction solution at a concentration of 11 g/100 ml for salting out. Centrifuge the precipitate (8500 rpm,
1.5 hours) and then dialyzed and dissolved overnight. Water is used as the external dialysis fluid, and the one mentioned above is used as the dialysis membrane. After confirming that unreacted polyethylene glycol was removed, the dialysate was freeze-dried to produce the desired product (PEG-
SCMK). The yield was 49.8%. A cytotoxicity test was performed on a 0.5% solution of this product and the results were negative. 3 Preparation of biocoated membrane (1) Biocoated membrane composed of graft copolymer membrane (method a) Dissolve the PEG-SCMK obtained above in distilled water to make a 5% aqueous solution. This was dispensed into a Teflon dish at a volume of 0.16 ml/cm ² and air-dried to obtain a PEG-SCMK film with a thickness of about 50 to 60 μm. The membrane thus obtained is immersed in a 25% glutaraldehyde solution for 4 hours. Wash thoroughly with water to obtain the desired biological coating membrane. (Method b) Add a glutaraldehyde solution to a 5% PEG-SCMK solution to a concentration of about 0.5%, dispense the resulting solution into a Teflon dish at a concentration of 0.16 ml/cm ² , and air dry. (Method c) PEG-SCMK obtained in the same manner as Method a
The membrane is gently stretched 4 times in steam and held in that state for 3 hours. (Method d) PEG-SCMK obtained in the same manner as Method a
The membrane is irradiated with gamma rays for 6 hours under deoxidized conditions. Furthermore, using a 4W ultraviolet lamp under a nitrogen atmosphere,
UV rays are irradiated on one side for 3 hours from a distance of cm. (Method e) PEG-SCMK is dissolved in formic acid to make a 5% formic acid solution. Pour the solution into a Teflon dish at 0.16ml/
Dispense into cm ² and air dry. (F method) According to O'Donell's method, wool is reduced,
This soluble portion is adjusted to pH 5, dialyzed, and then cast into a membrane. (Method g) PEG-SCMK is dissolved in distilled water, and the aqueous solution is placed in a dish and air-dried. The obtained film was heated to 80℃
Soak it in warm water for 15 minutes, lift it up, and then dry it. (Method h) PEG-SCMK is dissolved in distilled water. Place this in a dish and dehydrate and dry at a temperature of 80℃. Table 1 shows the physical properties of the coating films obtained by the above methods (a method) to (h method).

[Table] Measurement method Water vapor permeability The test was conducted based on the Cupp method (JIS Z1504). However, to ensure that the water is always in contact with the membrane, a sponge with a thickness that is in contact with the membrane is placed in the container and distilled water is dispensed. Further, the storage conditions were a temperature of 37°C and a humidity of 45%. Water absorption After taking out the membrane that has been left in distilled water for more than 24 hours and removing the moisture on the surface, the temperature and humidity are 37℃ and humidity.
Leave it until it reaches a constant weight of 45%, then divide the weight difference before and after leaving it by the surface area. (2) Biocoated membrane consisting of a graft copolymer membrane layer and a biocompatible support membrane layer PEG-SCMK is dissolved in distilled water to make a 5% aqueous solution. Put this in a Teflon dish at 0.16ml/cm ²
Dispense so that Cut a piece of nylon mesh (NBC No. 330) into a Teflon plate size, place it gently on top and air dry. 25% of the obtained membrane
Soak in glutaraldehyde solution for 4 hours. Wash thoroughly with water. (3) A biocoating membrane consisting of a graft copolymer membrane layer, a biocompatible support membrane layer, and a water permeation regulating layer The graft copolymer membrane is produced in the same manner as in (2) above. Wash thoroughly with water and dry (air dry). The moisture permeation regulating layer may be of any type as long as it is a so-called silicone rubber film (dimethylpolysiloxane). Here, we use Toshiba Silicon YE3085 to fabricate a thin film.
(Thickness of 10 to 300 μm is acceptable) Here it is 100 μm. The support membrane layer is made of nylon mesh (NBC No.
330) was used. The support membrane layer may be bonded to the graft copolymer membrane in advance, or may be bonded to the silicone rubber layer first. The latter here. Apply a thin layer of silicone sealant (Dow 891) to the graft copolymer membrane and immediately
Adhere the silicone rubber membrane containing nylon mesh, apply a pasting load, and leave it alone. (Overnight) A composite membrane with sufficient bonding strength for practical use can be produced. Effects of the Invention The biocoating film of the present invention is composed of a graft copolymer film of a water-soluble polymer with a molecular weight of 500 or more and solubilized keratin, and has excellent conformability and adhesion to the skin without any foreign body reaction in the living body. ing. The graft copolymer membrane used in the present invention can be assimilated and absorbed by the living body depending on its preparation method, and has excellent adhesion to wounds and does not create gaps through which bacteria can invade. In addition, if it is absorbed into the body, there is no need to remove it.
Even if it is to be removed, it can be easily removed because it is softened. Furthermore, unlike gauze, it does not penetrate into the formed granulation, so it can be removed without damaging the wound. Furthermore, the biocoating membrane of the present invention has the feature of not having antigenicity even though it is made from protein, and therefore can be repeatedly applied to the wound surface. Furthermore, in the biocoating membrane of the present invention, the graft copolymer membrane has a thickness of 5 to 1000 μm and a moisture permeability of 0.1 to 200 mg/
cm ² ·hr and water absorption of 0.1 to 150 g/cm ² , and these physical properties are appropriately selected within the scope of the present invention depending on the state and location of the wound. For example, in the early stages of a burn, body fluid secretion is active, so a coating liquid with high water absorption and moisture permeability is selected.
In addition, when the wound is dry, a material with high water retention is selected and can be impregnated with a drug solution to promote the healing effect. In this case as well, destruction of tissue on the wound surface can be prevented by providing appropriate moisture permeability. Furthermore, since the biocoating membrane of the present invention does not allow bacteria to pass through, it is possible to maintain the wound in a sterile state, which is extremely useful for treatment. Furthermore, the biocoated membrane of the present invention is composed of a graft copolymer membrane layer of a water-soluble polymer with a molecular weight of 500 or more and soluble keratin, and a biocompatible support membrane layer formed thereon, which increases the physical strength of the membrane. has been reinforced. Furthermore, the biocoated membrane of the present invention includes a graft copolymer membrane layer of a water-soluble polymer having a molecular weight of 500 or more and solubilized keratin, and a biocompatible support membrane formed on the graft copolymer membrane layer. layer, and a moisture permeation regulating layer formed on the supporting membrane layer or between the supporting membrane layer and the graft copolymer membrane layer, and the permeability can be adjusted depending on the condition of the wound, the period of use, etc. It can be adjusted as appropriate. Next, the effects of the above-mentioned present invention will be specifically explained with reference to test examples. (1) Antigenicity test The antigenicity of the graft copolymer of the present invention was tested by the Schulzdale test method. In other words, 0.5W/V% test solution 2 to Guinea piglet (male 200-250g)
ml was administered three times every other day to establish sensitization. After one month, remove approximately 7 cm of the guinea pig's ileum and immediately place it in Ringerloch's solution aerated with O ₂ and clean the inside with a syringe. Cut out 3 cm of it and tie it with surgical silk thread. Place this in a Ringer's bath and pull both ends together so that slight pressure is applied. One end is attached to a recorder so that contractions can be recorded. The sample was prepared at a concentration of 1× in the Ringer bath.
10 ⁻⁵ g/ml and record ileal contractions. When the ileum contracts, there is an antigen-antibody reaction (+), and when it does not contract, there is no antigen-antibody reaction (-). The results are shown in Table 2.

[Table] From Table 2, solubilized keratin (A) and polyethylene glycol (Mn=300)-keratin graft copolymer (H) exhibit antigenicity, while other water-soluble polymer-keratin graft copolymers exhibit antigenicity. It is clear that it does not show gender. (2) Biocompatibility test Create a skin pocket under the skin on the back of a female guinea pig (approximately 200 g). After implanting a 1 cm x 1 cm sample, rinsing the skin together. After a certain period of time, the guinea pig's skin is cut and peeled off, and the condition of the sample is observed. The results are shown in Table 3.

[Table] From Table 3, it is clear that the biological coating membrane of the present invention does not exhibit any foreign body reaction when implanted subcutaneously, similar to the control. The degree of absorption into the body varies depending on the manufacturing method, but it is equal to or higher than the control. In addition, "absorption" means for several weeks or more,
This means that it ceases to function as a membrane when it is buried in a living body or kept in close contact with a wound.
For example, this refers to an extreme decrease in strength or partial melting. Granulation is one of the reactions that a living body exhibits when a foreign body is implanted, and is actively formed after implantation and disappears as the foreign body is assimilated and absorbed. If granulation remains, it will leave a scar, so it is desirable that it disappear as much as possible, but Table 2 shows that the coating film of the present invention is excellent in this respect as well. In addition, the thickness outside the range not shown in the table is 5 to 1000 μm, and the moisture permeability is 0.1 to 200.
Similar results were obtained for mg/cm ² ·hr and water absorption of 0.1 to 150 g/cm ² . (3) Bacterial permeability test agar 15.0g Sodium chloride 5.0g Papain decomposition product of soybean powder 5.0g Pancreatin decomposition product of casein 15.0g The coated membrane sample shown in Table 3 was placed on the TSA medium consisting of the above ingredients. Then, 1 ml of a Serratia marcescens suspension containing 10 ⁷ cells/ml was dispensed. After 3 hours, the bacterial solution was removed along with the membrane, and the medium was cultured at 31°C. After 24 hours, bacterial growth was observed, and no bacterial growth was observed in any of the membranes used. (4) Adhesion test Remove the full thickness of the skin from the back of the rat in a size of 2 x 2 cm. Place a sample large enough to cover this, cover it with gauze, and fix it to the living body with tape. After 72 hours, the adhesion force of this sample is measured. The measurement method is at a constant speed (20cm/
min) Pull one end of the sample in the vertical direction and measure the stress at that time. The results are shown in Table 4.

【table】

[Table] Table 4 shows that the biocoating film of the present invention, which is composed of a graft copolymer film layer and a biocompatible support film layer formed thereon, has appropriate adhesion to the skin.
It can be seen that it is excellent as an artificial coating film.

Claims (1)

[Scope of Claims] 1. A biological coating film comprising a graft copolymer film of a water-soluble polymer having a molecular weight of 500 or more and solubilized keratin. 2. Claim 1, wherein the water-soluble polymer is a polymer selected from polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivatives, and alginic acid.
Biological coating membrane described in Section 2. 3 The graft copolymer film has a thickness of 5 to 1000μ
m, moisture permeability 0.1 to 200 mg/cm ²・hr and water absorption 0.1
The biological coating membrane according to claim 1, which is a membrane having a weight of ~150 g/cm ² . 4. A biofilm layer consisting of a graft copolymer film layer of a water-soluble polymer having a molecular weight of 500 or more and solubilized keratin, and a biocompatible support film layer formed on the graft copolymer film layer. 5. The biological cover according to claim 4, wherein the water-soluble polymer is a polymer selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivatives, and alginic acid. Covering membrane. 6 The supporting membrane layer is made of nylon, polypropylene,
polyethylene, polyester, urethane, SBS,
The biological coating membrane according to claim 4, which is a polymer selected from polyvinyl chloride, cellulose, acrylic, natural or synthetic rubber, and thermoplastic elastomer. 7 A graft copolymer membrane layer of a water-soluble polymer having a molecular weight of 500 or more and solubilized keratin, a biocompatible support membrane layer formed on the graft copolymer membrane layer, and a biocompatible support membrane layer formed on the graft copolymer membrane layer, and a Or a biological coating membrane comprising a water permeation regulating layer formed between the support membrane layer and the graft copolymer membrane layer. 8. The biological cover according to claim 7, wherein the water-soluble polymer is a polymer selected from the group consisting of polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone, polyacrylamide, polyvinyl alcohol, water-soluble cellulose derivatives, and alginic acid. Covering membrane. 9 The supporting membrane layer is made of nylon, polypropylene,
polyethylene, polyester, urethane, SBS,
Claim 7 is made of a polymer selected from polyvinyl chloride, cellulose, acrylic, natural or synthetic rubber, thermoplastic elastomer.
Biological coating membrane described in Section 2. 10. The biological coating membrane according to claim 7, wherein the moisture permeation regulating layer is made of natural rubber, synthetic rubber, or thermoplastic elastomer. 11. The biological coating membrane according to claim 10, wherein the moisture permeation regulating layer is made of silicone rubber, urethane rubber, SBS, or EPDM.