JPH0728908B2 - Wound cover material - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a wound cover material that has excellent adhesion to living tissue and that stably maintains a wound healing effect even after long-term use.

[Prior Art and its Problems] As a healing method for burns such as burns and wounds due to traumatic skin defects, ointments, ribanol gauze and the like have already been put into practical use and widely used. In recent years, freeze-dried pig skin, collagen short fiber sheet, regenerated cellulose, polyurethane foam, silicone rubber and the like have also been used. However, these have poor adhesion to the wound surface, or although they adhere to each other, they have the drawback that they dissolve during use and sufficient performance cannot be maintained.

On the other hand, it has long been known that gelatin has a hemostatic effect, and many wound healing materials based on gelatin are also known. For example, Japanese Patent Publication No. 31-4644 and Japanese Patent Publication No. 40-
Japanese Patent Publication No. 9431 discloses a method for producing spongy hemostatic gelatin, which comprises, as a main material, unmodified gelatin or a mixture of this and methyl cellulose, which is foamed and dehydrated by adding a foaming promoting aid. However, since gelatin is easily dissolved in blood or body fluid, the spongy hemostatic gelatin obtained by the above method has a drawback that it is dissolved by bleeding blood or body fluid infiltration when applied to the wound surface. .

In order to solve the above-mentioned problem of solubility of gelatin, there is provided a method in which an aldehyde is allowed to act to cross-link and foam gelatin molecules to suppress the dissolution of gelatin. However, in this method, the type and amount of cross-linking agent,
There is a large difference in the properties of the modified gelatin obtained depending on the crosslinking conditions and the like, and it is not possible to stably obtain the one having practically satisfactory performance.

On the other hand, fibronectin is known as a new physiologically active substance. In wounds such as burns or trauma, fibronectin is considered to have an action of repairing damaged tissue and removing colloidal cell debris and bacteria flowing out from the damaged tissue into blood, and the wound reduces fibronectin in plasma, After that, it is known to recover to a normal value.
Therefore, it has been attempted to normalize the blood level by administration of exogenous fibronectin, but even if the blood level of fibronectin is normalized, the reticuloendothelial function is not improved and the wound is healed early. It has not been done.

[Means for Solving Problems] The present invention relates to a wound cover material that maintains excellent wound healing effect for a long period of time by using together gelatin and fibronectin, the solubility of which is suppressed by crosslinking.

That is, the present invention relates to a system comprising 5 to 35% by weight of gelatin and 95 to 65% by weight of water, and 0.005 to 5.0% by weight of gelatin.
0.05 for sodium lauryl sulfate and gelatin
The present invention relates to a wound covering material obtained by adding glycidyl ethers of glycidyl group / g gelatin, mixing and agitating the mixture in a temperature range of 30 to 60 ° C., and supporting or impregnating fibronectin in a gelatin foam.

In the present invention, general gelatin used for medical purposes can be used as it is. Their jelly strength is
Those having 100 bloom or more, particularly 150 to 300 bloom are preferable. Gelatin prepared by any of the acid treatment method and the alkali treatment method can be used, but the alkali treatment method is preferably used.

Examples of the glycidyl ethers include ethylene propylene glycol diglycidyl ether, glycerol polyglycidyl ether, diglycerol polyglycidyl ether, polyglycerol polyglycidyl ether, sorbitol polyglycidyl ether, and ethylene glycol diglycidyl ether. Ethylene glycol diglycidyl ether is preferable because stable crosslinking can be efficiently obtained.

As fibronectin, commercially available fibronectin that can be used for medical purposes can be used, but fibronectin purified from human plasma by utilizing its affinity for gelatin is preferable.

Next, a method for manufacturing the wound cover material of the present invention will be described.

Gelatin and water are mixed in a ratio of 5:95 to 35:05 (% by weight). If the amount of gelatin is less than 5% by weight, the pore size of the foam becomes extremely uneven and the foam becomes very soft, which is not preferable. On the other hand, when the gelatin content exceeds 35% by weight, the pores of the foam become extremely small and the foam becomes extremely hard, which is not preferable. After leaving the mixture at room temperature for 4 hours or more, 30 ~ 70
C., preferably 35 to 45.degree. C., and gently stirred to dissolve gelatin. Subsequently, glycidyl ethers are added while keeping the heating state, and then sodium lauryl sulfate is added. Sodium lauryl sulfate may be added at the same time as the glycidyl ethers, or after a few minutes (2-
5 minutes later) may be added. The addition amount of glycidyl ethers is preferably in the range of 0.05 to 5 mmole glycidyl group / g gelatin. When the glycidyl ethers are less than 0.05m mole glycidyl group / g gelatin, the obtained gelatin foam has a small pore diameter, a low porosity, and an extremely low wet strength. Addition amount of glycidyl ethers is 5m mole
When it exceeds glycidyl groups / g gelatin, the obtained gelatin foam has a large variation in the pore diameter and the hardness is large, and the adhesion of the wound cover material to the wound surface is poor. The mixture is usually reacted by stirring. The tank or stirring blade used for stirring is not particularly limited, but it is preferable to perform stirring at high speed using a stirring blade having a large stirring effect. The reaction time is preferably 20 seconds to 5 minutes, particularly 30 seconds to 2 minutes. When the reaction time is less than 20 seconds, the crosslinking is insufficient, and the obtained wound cover material is easily dissolved in blood, body fluid, etc., and a stable healing effect cannot be maintained. If the reaction time exceeds 5 minutes, the viscosity of the reaction product increases, foaming becomes insufficient, and the adhesion to the wound surface decreases.

The gelatin foam prepared as described above is poured into a molding machine according to a conventional method and freeze-dried. The concentration of fibronectin is 1-1000μ on the surface of the obtained gelatin foam.
A physiological saline solution of fibronectin in the range of g / ml is supplied by a syringe to carry 0.01 to 100 μg of fibronectin per unit area (1 cm ² ) of the surface of gelatin foam. Alternatively, the gelatin foam is immersed in the physiological saline solution of fibronectin, and impregnated with 0.01 to 100 μg of fibronectin per unit area near the surface of the gelatin foam.

The wound cover material of the present invention can also be used as a composite comprising a film-shaped or mesh-shaped synthetic polymer material layer. When it is not a composite, it can be used by applying it to a wound site by an appropriate method and covering the outer surface with another material such as gauze. But,
The wound cover material of the present invention is particularly advantageous for use as a composite in general.

As the synthetic polymer material used for forming the complex, a material which covers the wound area and has appropriate water vapor permeability and oxygen permeability, for example, a water vapor transmission rate of about 0.3 to 1 mg / cm ² / hr can be used. In addition, any substance may be used as long as it has an infection-preventing effect that prevents the invasion of bacteria from the outside, and further has the effect of preventing the outflow of body fluid, but it is a relatively porous synthetic material such as polyethylene or polypropylene. The use of polymeric materials is preferred, these being used as films or meshes.

The present invention will be described in detail below with reference to examples.

Example Production of Wound Cover Material 7.5 g of gelatin (E-170 manufactured by Miyagi Chemical Co., Ltd.) was added to 5 g of distilled water.
After adding 0 g and leaving it at room temperature for 4 hours, it was heated to 40 ° C. and stirred to dissolve. Next, 0.598 g of ethylene glycol diglycidyl ether as a cross-linking agent and 0.25 g of sodium lauryl sulfate as a foaming agent were added, and the mixture was stirred at a rotation speed of 18500 rpm for 1 minute. The foamed viscous product produced was quickly poured into a 50 × 50 × 1 mm size molding machine and subsequently rapidly freeze-dried. It was found that the obtained gelatin foam was immersed in physiological saline at 37 ° C for 24 hours, but no weight loss was observed, and it did not elute. Tensile strength is 10 kg / cm ² and tensile elongation is 10
%, The flexural modulus was 564 kg / cm ² . On the surface of this gelatin foam, a physiological saline solution having a concentration of 1 μg / ml of fibronectin was added by a syringe to obtain a gelatin foam surface 1c.
1 μg of fibronectin was loaded per m ² .

The fibronectin-supported gelatin foam was applied to the surface of a polyethylene porous film having a thickness of 50 μm and an average pore diameter of 2.3 μ to a thickness of 100 to 300 μm to manufacture a wound cover material.

Evaluation of Wound Healing Effect (No. 1) Male Wister rats (9 weeks old, weight 300-350 g) were depilated on the back and anesthetized, and then 2.5 × 5 cm using a dermatome
Wounds were made on the back. The wound cover material of the example was attached to the wound site, the wound surface was observed after 3, 7, 10, 14, 17, and 21 days, and the change of the wound cover material itself was observed. The results are shown in Table 1.

Evaluation of wound healing effect (Part 2) A glass rod with a tip of 2 cm in diameter was immersed in saline solution at 80 ° C,
After the temperature of the glass rod itself was raised to 80 ° C., the glass rod was taken out and quickly pressed against the dehaired back of the rat for 10 seconds. The blisters generated at the burn site were peeled off after 2 hours, a wound cover material was attached to the burn surface, and the same observation as above was performed. The results are shown in Table 1.

Comparative Example A gelatin foam was produced in the same manner as in Example except that ethylene glycol diglycidyl ether was not added. When the obtained gelatin foam was immersed in physiological saline at 37 ° C. for 24 hours, it almost dissolved. The tensile strength was 7.8 kg / cm ² , the tensile elongation was 9%, and the flexural modulus was 575 kg / cm ² . This gelatin foam was applied to the same porous film as in Example to a thickness of about the same to manufacture a wound cover material.

Using the obtained wound cover material, the wound healing effect was evaluated in the same manner as in Examples. The results are shown in Table 1.

In addition, in order to compare the wound healing effect, Table 1 also shows the effect of the natural healing of the wound in addition to the evaluation results of Examples and Comparative Examples.

[Effects of the Invention] The wound cover material of the present invention is appropriately crosslinked and foamed, has excellent adhesion to the wound surface, and is hardly dissolved in blood or body fluid. Further, since fibronectin is present in the vicinity of the surface of the wound cover material, a stable wound healing effect is maintained for a long period of time.

Claims (4)

[Claims] 1. A system consisting of 5 to 35% by weight of gelatin and 95 to 65% by weight of water, 0.005 to 5.0% by weight of sodium lauryl sulfate and 0.05 to 5 m of gelatin.
A wound cover material obtained by adding fibronectin to a gelatin foam obtained by adding glycidyl ethers of glycidyl group / g gelatin and mixing and stirring in a temperature range of 30 to 60 ° C. 2. The wound cover material according to claim 1, wherein the glycidyl ethers are ethylene glycol diglycidyl ether. 3. The wound cover material according to claim 1, wherein fibronectin is supported on the surface of gelatin foam. 4. The wound cover material according to claim 1, wherein fibronectin is impregnated near the surface of the gelatin foam.