KR20070010572A - Method of manufacturing hydrogel for wound treatment using irradiation technology - Google Patents

Abstract

The present invention relates to a method for producing a hydrogel for wound treatment using a radiation technique, more specifically, a) after dissolving the biocompatible polymer and polyhydric alcohol in distilled water, by freezing and thawing the aqueous solution of the biocompatible polymer Forming a pre-hydrogel, b) coating an aqueous polyvinyl alcohol solution on a polymer film, a nonwoven fabric or a fiber, and drying the c) attaching the pre-hydration gel on the polyvinyl alcohol-coated polymer film, a nonwoven fabric or a fiber. It relates to a method of manufacturing a hydrogel for wound treatment using a radiation irradiation technique comprising the step of compressing and d) packaging the compressed hydrogel using a packaging material, and irradiating the radiation.

The hydrogel according to the present invention has a simple manufacturing method, absorbs the effluent properly while suppressing the amount of water evaporation, has excellent gel strength, and has an antibacterial function. In addition, by using irradiation technology, it satisfies both storage and sterilization at the same time, there is no problem of toxic residue because no initiator or crosslinking agent is used, it is easy to adhere to wound or skin, transparency of hydrogel, ease of handling, etc. By having the advantage of it can be usefully used for wound treatment or skin regeneration of burns, wounds and the like.

Description

Method for the preparation of hydrogels for wound dressing using radiation irradiation}

The present invention relates to a method for producing a hydrogel for wound treatment using a radiation irradiation technology, to freeze and thaw a biocompatible polymer and a polyhydric alcohol aqueous solution to form a pre-hydrogel, a polymer material to which the molded pre-hydrogel is adhered The present invention relates to a method for preparing a hydrogel for wound treatment by coating a polyvinyl alcohol aqueous solution capable of inducing effective adhesion between the preliminary hydrogels, adhering, compressing, and packaging the same, followed by irradiation and crosslinking.

In general, the wound healing process is divided into acute, restorative, and scar phases.

The first stage, the acute phase, is also called the extruder, where a series of reactions occur to remove tissue from damaged areas that have had tissues destroyed or incorporated foreign material. This is accompanied by inflammatory and coagulation reactions.

Restoration phase, also called proliferation phase, is the stage where new blood vessels are formed and damaged areas are increased and recovery of damaged areas occurs. In this period, active cell proliferation or active synthesis of intercellular substances collagen or proteoglycans in granulation tissue, which is a kind of connective tissue, is carried out, and epidermal cells acquire mobility and regenerate epidermal tissue by dividing and proliferating.

The third step, the scarring step, slows the proliferation of active cells as seen in the repair phase, and increases the physical strength of the damaged site as the collagen fibers cross-link. Finally, the vasculature also contracts and tissues other than the surrounding normal tissues are placed at the site of injury. By repeating the above steps, the wound is healed.

Wound treatments, such as venous stasis ulcers, pressure sores, surgical wounds, burn wounds, etc., are damaged and the skin is missing or significantly damaged. Mainly used. In addition to fiber dressings, non-woven fabrics or various synthetic products have been used in place.

In all cases a new granulation tissue must be created for the wound to heal, which is incompatible with necrotic tissue that is present on the wound and is unable to absorb wound secretions. Therefore, removal of necrotic tissue should be preceded in the wound healing process. As a method of removing necrotic tissue, there are enzymatic use and chemical treatment.

Enzyme application is usually used by soaking a solution of hypochlorite (alkaline hydrochlorite) in the dressing. However, if the dressing is dried and replaced or removed, it may not only damage the dry skin (eschar) of normal tissue, but also cause pain. Thus, the tissue is destroyed to separate necrotic tissue from the wound, but affect normal cells.

As an example of chemical treatment, creams are mainly used, which requires the use of a separate barrier cream to remove necrotic tissue and at the same time protect normal tissue.

Therefore, research on methods and techniques for easily removing necrotic tissue from wounds without touching normal tissues at the stage for wound healing is required.

In general, it is well known that the treatment of wounds is much faster than in a dry state when the wound is maintained in water [Rake BA, Appl. Nurs. Res . 1998, 11 , 174-182, efforts have been made to produce optimal hydrogels for wound healing.

The hydrogel is a material used for the purpose of burn treatment or skin regeneration that requires a constant wet state, and the hydrogel generally contains 60% or more moisture to be used for this purpose. In the case of severe burn treatment, the result is transplantation of tissue transplanted with autograft or in vitro culture of the patient's fibroblasts, which requires considerable time until the procedure is performed. Blocking must be preceded. At this time, the hydrogel is compatible with blood, body fluids and biological tissues can be used as a wound dressing. In addition, hydrogels can also be used in contact lenses and cartilage.

In order to produce a hydrogel that can be used for this purpose, the selection of a polymer capable of forming a hydrogel must be preceded. The polymer should have a three-dimensional network structure, including a hydrophilic functional group such as -carboxyl group (COOH), amide (CONH ₂ ),-amide group (CONH), sulfonic acid group (SO ₃ H), while absorbing water It should not be dissolved in. More specifically, the polymers that can be used in the hydrogel absorb water by capillary and osmotic phenomena due to the nature of the structure and contain water, and due to the covalent structure between the polymer chains as well as electrostatic and lipophilic interactions. It should be characterized by its insoluble in water.

Generally, the polymer used in the hydrogel is made of synthetic polymer, natural polymer or a mixture thereof, and the synthetic polymer is a hydrophilic synthetic polymer composed of polyvinyl alcohol, polyethylene oxide, polyhydroxyethyl methacrylate and polyvinylpyrrolidone. The natural polymer may be selected from the group consisting of gelatin, agar, alginate, collagen and chitosan.

The polyvinyl alcohol is a hydrophilic polymer that is suitable as a biomaterial, has excellent mechanical and thermal strength, and can be crosslinked by a physical method after several times of freezing and thawing, and is mainly used for preparing various hydrogels and membranes. Has been used.

The polyvinylpyrrolidone is a hydrophilic (water soluble) polymer and a biocompatible polymer, and has been widely used in plasma and other biomaterials for decades. Recently, research has been actively carried out as an alternative to glassy substances in the eye. In addition, since the polyvinylpyrrolidone contains oxygen and nitrogen in the unit structure, the polyvinylpyrrolidone can hydrogen bond with the water molecules, thereby forming a network structure. As a result, since it can contain a large amount of water, it is a suitable polymer for wound healing.

Chitosan is a generic term for deacetylation of chitin, and chitin is a shellfish such as crab and shrimp; Insects such as crickets and grasshoppers; Not only is it contained in mollusks such as squid in large quantities, it is the second most abundant natural polymer after cellulose contained in cell walls of higher plants such as strains and algae. These chitin or chitosan is bio-compatible, antimicrobial, biodegradable, etc. As the functionality is found, it is applied in a variety of fields and research is actively progressed. Chitosan inhibits the development of bacteria and fungi, and hemostatic action, and is generally known to have better medical efficacy than chitin. Such chitosan was insoluble in water and had limitations in application, but in recent years, efforts to develop water-soluble chitosan have been fruitful.

Methods of preparing such hydrogels include chemical methods and methods using irradiation technology. By irradiating radiation, rather than chemical method prepared by adding a chemical crosslinking agent or initiator, among them, there is no need to remove the chemical crosslinking agent or initiator, solve the toxicity problem due to the remaining of these substances, and can be combined with sterilization simultaneously with crosslinking. The use of radiation technology is attracting attention. In addition, the method using the irradiation technology has the advantage that not only do not apply heat in the cross-linking process, but also can be cross-linked even in the cooling state, and can freely adjust the physical properties only by adjusting the radiation dose without changing the composition.

US Patent No. 4,871,490 discloses a method for preparing a wound dressing using a radiation crosslinking method without using a chemical crosslinking agent. The production method is introduced to crosslink by irradiation with radiation after mixing agar and polyethylene oxide to polyvinylpyrrolidone. However, the polyvinylpyrrolidone hydrogel, which is used as a dressing for wound treatment because of no toxicity and excellent swelling of physical properties, has a higher adhesiveness than necessary, and its ductility and strength are weak so that it is torn during dressing or poly from wound after wound treatment. When the vinylpyrrolidone hydrogel dressing is removed, a portion of the wound may remain, which adversely affects burn treatment. In addition, since it is easy to dry after applying to the wound, it is difficult to remove from the wound, causing a secondary wound.

U. S. Patent No. 5,480, 717 discloses a method of preparing a hydrogel by casting polyvinylpyrrolidone aqueous solution onto a polymer film with an adhesive and irradiating with radiation. The polyvinylpyrrolidone used at this time shows the best physical properties when the molecular weight is 200,000-400,000, but when the molecular weight exceeds the above range, there is a problem in the production of a high concentration of aqueous solution, and the physical properties decrease again. have. In addition, the hydrogel prepared by this method has a high moisture content, but has a disadvantage in that the exudates are not well absorbed.

US Patent No. 6,022,330 discloses a technique for irradiating a nonwoven fabric and then graft copolymerizing N-isopropyl acrylamide to prevent the nonwoven fabric from sticking to the wound.

Furthermore, U.S. Patent No. 5,618,799 discloses a method of preparing a powder which can be applied to wound healing by mixing polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, methyl cellulose and the like with sucrose as a main component. However, since the hydrogel prepared by this method is applied to the wound in the form of a powder, there is a disadvantage that the wound healing effect is slow.

Therefore, the requirement of the hydrogel to satisfy the wound treatment should be able to absorb the body fluids, to prevent infection from bacteria, and to be easily removable to the wound or skin. In addition to good transparency and oxygen permeability, drug control, easy handling, storage and sterilization should be provided. Furthermore, less water evaporation of the hydrogel is required. This is because a great moisture evaporation decreases the hydrogel's properties and causes hardening, which is very likely to cause secondary wounds when attached to and removed from the wound. In order to prevent such evaporation of water, the polymer film (membrane) should be adhered to the hydrogel. However, until now, the development of a technology capable of inducing effective adhesion between the polymer film and the hydrogel has been insufficient.

Accordingly, the present inventors have found a method of manufacturing a hydrogel for wound treatment using a radiation irradiation technology that can obtain an excellent water vaporization effect by applying a polyvinyl alcohol aqueous solution to a polymer film or a nonwoven fabric to improve adhesion to the hydrogel. The invention has been completed.

It is an object of the present invention to provide a method for preparing a hydrogel for wound treatment using a radiation technique.

In order to achieve the above object, the present invention comprises the steps of a) dissolving the biocompatible polymer and polyhydric alcohol in distilled water, and then freezing and thawing the aqueous biocompatible polymer aqueous solution to form a pre-hydrogel; b) coating an aqueous polyvinyl alcohol solution on a polymer film, nonwoven fabric or fiber and drying; c) attaching the preliminary hydrogel onto the polyvinyl alcohol-coated polymer film, nonwoven fabric or fiber and compressing the adhesive; And d) packing the compressed hydrogel using a packaging material and irradiating the radiation.

EMBODIMENT OF THE INVENTION Hereinafter, one Embodiment of this invention is described in detail.

Step a) according to an embodiment of the present invention is a biocompatible polymer and a polyhydric alcohol is put in distilled water, dissolved by heating to prepare a homogeneous aqueous solution, poured into a mold or cast, and then frozen and thawed to form a pre-hydrated gel It's a step. The purpose of step 1) is to prepare starting materials for hydrogel preparation and ultimately to form a preliminary hydrogel through physical crosslinking by freezing and thawing.

Suitable polymers for the preparation of hydrogel according to one embodiment of the present invention can be any biocompatible polymer, preferably polyvinyl alcohol alone or polyvinyl alcohol in polyvinylpyrrolidone, polyethylene oxide, polyacrylic acid, gelatin , Aga, alginate, chitosan, and the like may be mixed and used, preferably polyvinyl alcohol alone. If the polyvinyl alcohol is mixed with the polyvinylpyrrolidone or the like, the polyvinyl alcohol content in these mixtures is preferably 40% by weight or more. If the content of polyvinyl alcohol is lower than 40% by weight, physical crosslinking by freezing and thawing cannot be obtained.

From the viewpoint of improving the potting power and flexibility of the hydrogel according to one embodiment of the present invention, a polyhydric alcohol may be mixed with the biocompatible polymer. However, polyhydric alcohols used in combination are required to have no toxicity to the living body. As the polyhydric alcohol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, hexylene glycol, sorbitol, mannitol, polyethylene glycol, and the like are preferable, and among these, glycerin may be more preferably used.

From the viewpoint of maintaining the preferred gel strength of the hydrogel according to one embodiment of the present invention, the content of the biocompatible polymer in the aqueous solution of step a) is preferably 10 to 35% by weight, the content of polyhydric alcohols relative to the total aqueous solution It is preferable that it is 1-20 weight%. If the content of the biocompatible polymer is less than 10% by weight it is not possible to maintain the gel strength enough to accommodate the drug to treat the wound. On the other hand, when it exceeds 35% by weight, it is difficult to dissolve in the aqueous solution. In addition, when the content of the polyhydric alcohol is less than 1% by weight, it may not be sufficiently improved the adhesion and flexibility. On the other hand, when it exceeds 20% by weight, it is not possible to maintain the gel strength enough to accommodate the drug.

From the viewpoint of maintaining the preferred gel strength of the hydrogel according to one embodiment of the present invention, the degree of polymerization of the polyvinyl alcohol is preferably 1,300 to 2,700, more preferably 1,500 to 2,500. If the polyvinyl alcohol has a degree of polymerization of 1,300 or less, gel strength enough to be used as a dressing cannot be obtained. On the other hand, when the degree of polymerization is 2,700 or more, it is difficult to prepare an aqueous solution by dissolving polyvinyl alcohol due to its high viscosity.

From the viewpoint of improving the physical properties of the hydrogel according to one embodiment of the present invention, the saponification degree of polyvinyl alcohol is preferably 85 to 99.9 mol%. The greater the degree of saponification, the better the physical properties of the hydrogel. On the other hand, if the saponification degree is less than 85 mol%, there is a disadvantage in that physical properties are lowered because it is not crystallized even when frozen.

Preparation of the hydrogel according to one embodiment of the present invention involves pouring or casting the polyvinyl alcohol / polyalcohol biocompatible polymer mixed aqueous solution into a mold (metal, polymer, ceramic, etc.), followed by freezing and thawing. By inducing physical crosslinking through freezing and thawing, a preliminary hydrogel having a thickness of 2 to 3 mm can be formed. In addition, a sheet of a biocompatible polymer aqueous solution may be formed with a coater, and frozen and thawed may form a preliminary hydrogel sheet. From the viewpoint of inducing preferable physical crosslinking of the hydrogel, the freezing temperature is preferably -150 to -15 ° C, more preferably -100 to -40 ° C. In addition, 5-50 degreeC is preferable and 20-30 degreeC of thawing temperature is more preferable. Freezing temperatures lower than −150 ° C. are not significantly different from freezing at higher temperatures to form physical crosslinks. On the other hand, the hydrogel is not frozen at a temperature higher than -15 ℃. In addition, a thawing temperature lower than 5 DEG C cannot secure an appropriate thawing time. On the other hand, thawing temperatures higher than 50 ° C. can weaken physical crosslinking.

In this case, the freezing time may be changed depending on the freezing temperature, usually 5 minutes to 1 hour is preferred. If less than 5 minutes effective freezing can not be achieved, if more than 1 hour it only takes more time for the hydrogel manufacturing process. Such freezing and thawing may be repeatedly performed to ensure stable physical crosslinking, preferably 1 to 10 times, and more preferably 1 to 5 times to form a physical crosslink.

Step b) according to an embodiment of the present invention is a step of coating and drying a polyvinyl alcohol aqueous solution on a coating layer of a polymer film, a nonwoven fabric or a fiber. The purpose of step 2) is to coat and dry the polyvinyl alcohol aqueous solution using the coating layer in order to suppress the drying of the hydrogel and to reinforce the strength of the hydrogel.

As the coating layer of the hydrogel according to one embodiment of the present invention, a polymer film, a nonwoven fabric or a fiber may be used. As the polymer film, polyurethane, silicone rubber, low density polyethylene, ultra low density polyethylene, ethylene vinyl acetate, plasticized polyvinyl chloride, or the like can be used. In addition, the nonwoven fabric may be a polypropylene nonwoven fabric, polyethylene nonwoven fabric, nylon nonwoven fabric, polyester nonwoven fabric, or the like.

From the viewpoint of improving the adhesion of the hydrogel to the polymer film, nonwoven fabric or fiber, the polyvinyl alcohol has a degree of polymerization of 500 to 2,700, a degree of saponification of 75 to 90 mol%, and a concentration of 5 to 30% by weight of the polyvinyl alcohol aqueous solution. Do. Moreover, it is preferable that it is 10-500 micrometers, and, as for the thickness of a coating layer, it is more preferable that it is 50-400 micrometers. If it is less than these ranges, the improvement of adhesive force is inadequate. On the other hand, when exceeding these ranges, as a result of reinforcing the gel strength of the hydrogel more than necessary and excessive adhesion, the hydrogel may be broken by weakening the flexibility.

Step c) according to an embodiment of the present invention is a step of attaching the pre-hydrogel prepared in step a) on the polyvinyl alcohol-coated polymer film, non-woven fabric or fiber prepared in step b) to compress. The purpose of step c) is to prevent bubbles from entering the interface between the polymer film and the hydrogel. Such compression can generally be carried out using a roller.

Step d) according to an embodiment of the present invention is a step of packaging the hydrogel compressed in step c) using a packaging material and finally irradiating with radiation. The purpose of step d) is to prevent contamination of the hydrogel with the epidermal layer and to safely store it for a long time, and to sterilize the crosslinking and hydrogel of the hydrogel polymer by irradiation.

The packaging material may be used without limitation as long as the packaging material is commonly used. For example, a polymer film such as polyethylene, polypropylene, polyvinyl chloride, nylon, polyester, or the like, or a laminate of aluminum foil or aluminum and a polymer film may be mentioned.

As the radiation used for the radiation treatment, gamma rays or electron beams are preferable, and gamma rays are more preferable among them. In this case, the irradiation dose of gamma rays is preferably 5 to 100 kGy, more preferably 25 to 50 kGy in consideration of the appropriate dose required for sterilization purposes of about 25 kGy. Excessive radiation doses in excess of 100 kGy result in reduced absorption and increased gel strength, while decreasing flexibility, making them easily broken. On the other hand, an irradiation dose smaller than 5 kGy cannot obtain a sterilization effect.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are merely to illustrate the present invention, but the content of the present invention is not limited by the examples.

< Example  1> Polyvinyl alcohol Hydrogel  Produce

Polyvinyl alcohol (polymerization degree 2400, saponification degree 99 mol%): glycerin = 70: 30 was mixed in the ratio of dissolved in distilled water to prepare a 25% by weight aqueous solution, and poured into the mold so that the thickness is 2 mm,- After freezing at 70 ° C. for 5 minutes, thawed at room temperature for 20 minutes to form a preliminary hydrogel. In order to attach the preliminary hydrogel separated from the mold to the polyurethane film, a polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution. The urethane film (15 μm) was applied to a thickness of 200 μm and dried at room temperature. The molded pre-hydrogel sheet was placed on the dried polyurethane film and pressed, and then packed in an aluminum laminate pack. Finally, gamma rays were irradiated with a radiation dose of 25 kGy to prepare hydrogels for wound treatment. As a result of the peeling test according to Experimental Example 1, the tear strength of the hydrogel was measured to be 64.7 g / cm 2.

< Example  2> Polyvinyl alcohol Hydrogel  Produce

Polyvinyl alcohol (polymerization degree 2400, saponification degree 99 mol%): glycerin = 70: 30 was mixed in the ratio of dissolved in distilled water to prepare a 25% by weight aqueous solution, and poured into the mold so that the thickness is 2 mm,- After freezing at 70 ° C. for 5 minutes, thawed at room temperature for 20 minutes to form a preliminary hydrogel. In order to attach the pre-hydrogel separated from the mold to the polypropylene nonwoven fabric, polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution, and then the aqueous solution was It was applied to a propylene nonwoven fabric (150 ㎛) to a thickness of 200 ㎛ dried at room temperature. The preformed hydrogel sheet was molded on the dried polypropylene nonwoven fabric, pressed, and then packed in an aluminum laminate pack. Finally, gamma rays were irradiated with a radiation dose of 25 kGy to prepare hydrogels for wound treatment. As a result of the peeling test according to Experimental Example 1, the tear strength of the hydrogel was measured to be 98.0 g / cm 2.

< Example  3> Polyvinyl alcohol Hydrogel  Produce

Polyvinyl alcohol (polymerization degree 2,400, saponification degree 99 mol%): polyvinylpyrrolidone (molecular weight 1,200,000): glycerin = 50: 20: 30 was mixed in a ratio of dissolved in distilled water to prepare an aqueous solution of 25% by weight, The aqueous solution was poured into a mold to have a thickness of 2 mm, frozen at −70 ° C. for 5 minutes, and thawed at room temperature for 20 minutes to form a prehydrate gel. In order to attach the preliminary hydrogel separated from the mold to the polyurethane film, polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution. It was applied to a polyurethane film (15 μm) to a thickness of 200 μm and dried at room temperature. The molded pre-hydrogel sheet was placed on the dried polyurethane film and pressed, and then packed in an aluminum laminate pack. Finally, gamma rays were irradiated with a radiation dose of 25 kGy to prepare hydrogels for wound treatment. As a result of the peeling test according to Experimental Example 1, the tear strength of the hydrogel was measured to be 60.2 g / cm 2.

< Example  4> Polyvinyl alcohol Hydrogel  Produce

Polyvinyl alcohol (polymerization degree 1700, saponification degree 99 mol%): glycerin = 70: 30 was mixed in a ratio of distilled water to prepare a 25% by weight aqueous solution, this aqueous solution was poured into a mold so that the thickness is 2 mm,- After freezing at 70 ° C. for 5 minutes, thawed at room temperature for 20 minutes to form a preliminary hydrogel. In order to attach the preliminary hydrogel separated from the mold to the polyurethane film, a polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution. The urethane film (15 μm) was applied to a thickness of 200 μm and dried at room temperature. The molded pre-hydrogel sheet was placed on the dried polyurethane film and pressed, and then packed in an aluminum laminate pack. Finally, gamma rays were irradiated with a radiation dose of 25 kGy to prepare hydrogels for wound treatment. As a result of the peeling test according to Experimental Example 1, the tear strength of the hydrogel was measured to be 67.2 g / cm 2.

< Example  5> Polyvinyl alcohol Hydrogel  Produce

Polyvinyl alcohol (polymerization degree 2400, saponification degree 99 mol%): gelatin: glycerin = 50: 20: 30 and mixed in a ratio of dissolved in distilled water to prepare a 25% by weight aqueous solution, the aqueous solution was molded to a thickness of 2 mm Poured in, frozen at -70 ℃ for 5 minutes, thawed at room temperature for 20 minutes to form a pre-hydrogel. In order to attach the preliminary hydrogel separated from the mold to the polyurethane film, a polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution. The urethane film (15 μm) was applied to a thickness of 200 μm and dried at room temperature. The molded pre-hydrogel sheet was placed on the dried polyurethane film and pressed, and then packed in an aluminum laminate pack. Finally, gamma rays were irradiated with a radiation dose of 25 kGy to prepare hydrogels for wound treatment. As a result of the peeling test according to Experimental Example 1, the tear strength of the hydrogel was measured to be 45 g / cm 2.

Experimental Example 1 Measurement of Change in Adhesion between Polyurethane Film and Hydrogel According to Kinds of Polyvinyl Alcohol

The polyvinyl alcohol hydrogels of Table 1 were prepared by varying the degree of polymerization and saponification of the polyvinyl alcohol used to bond the preliminary hydrogel formed by Example 1 to the polyurethane film. A peeling test for measuring tear strength was performed on the hydrogels a to f thus prepared. That is, the hydrogel sheet was cut to 1 cm in width, the polyurethane film and the end of the hydrogel (2 cm) were forcibly separated, and the force required to peel off was measured with a universal testing machine. The results are shown in Table 1 below.

Sample Name Types of Polyvinyl Alcohol Tear strength (g / ㎠) a Degree of polymerization 2,400, saponification degree 86 to 89 mol% 64.7 b Degree of polymerization 2,000, saponification degree 86-89 mol% 74.0 c Degree of polymerization 1,700, degree of saponification 86-89 mol% 97.2 d Degree of polymerization 500, saponification degree 86-89 mol% 2.0 e Degree of polymerization 500, saponification degree 99 mol% 1.9 f Degree of polymerization 1,700, degree of saponification: 99 mol% 1.9

From the results of Table 1, it can be seen that the polymerization degree and saponification degree of the preferred polyvinyl alcohol for improving the adhesion between the polyurethane film and the hydrogel are distributed in the range of 500-2700 and 75-90 mol%.

< Experimental Example  2> radiation On irradiation dose  According to the polyurethane film Hydrogel  Adhesion Change Measurement

Polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution, which was applied to a polyurethane film (15 μm) at a thickness of 200 μm, and room temperature. Dried at. On the dried polyurethane film, a pre-hydrated hydrogel sheet molded by Example 1 was placed and pressed to prepare a polyvinyl alcohol hydrogel of g ~ i, and then packaged in an aluminum laminate pack. Finally, gamma rays were irradiated with different irradiation doses (25, 50, 75 kGy) to samples g to i, and the peeling test was performed in the same manner as in Experimental Example 1. The results are shown in Table 2 below.

Sample Name Gamma Radiation Dose (kGy) Tear strength (g / ㎠) g 25 64.7 h 50 48.5 i 75 35.4

From the results in Table 2, it can be seen that the adhesion between the polyurethane film and the hydrogel is dependent on the gamma irradiation dose. In other words, it can be seen that the adhesion between the polyupetane film and the hydrogel is most preferable at a gamma irradiation dose of 25 kGy.

Experimental Example 3 Influence of Polyvinyl Alcohol Binder Thickness on Adhesion between Polyurethane Film and Hydrogel

 Polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25 wt% polyvinyl alcohol aqueous solution, and the aqueous solution was 150, 200, 300, and 500 on a polyurethane film (15 μm), respectively. It was applied to a thickness of μm and dried at room temperature. The hydrogel sheet formed in Example 1 was placed on the dried polyurethane film and pressed to prepare a polyvinyl alcohol hydrogel of j ~ o, and then packaged in an aluminum laminate pack. Finally, gamma rays of 25 kGy were irradiated to samples j to o, and a peeling test was conducted in the same manner as in Experimental Example 1. The results are shown in Table 3 below.

Sample Name Thickness of binder coating Tear strength (g / ㎠) j 5 μm 3.9 k 150 μm 60.2 l 200 μm 64.7 m 300 μm 53.0 n 500 μm 50.3 o 1000 μm 21.4

From the results in Table 3, it can be seen that the hydrogel according to the present invention is most preferably a thickness of the binder coating 200 ㎛.

Experimental Example 4 Influence of Polyurethane Film and Hydration Gel on Binder Concentration

Polyvinyl alcohol (polymerization degree 2,400, saponification degree 86 to 89 mol%) was dissolved in distilled water to prepare a 25, 20, 18.2, 14.3 wt% polyvinyl alcohol aqueous solution, and the aqueous solution was 200 on a polyurethane film (15 μm), respectively. It was applied to a thickness of μm and dried at room temperature. On the dried polyurethane film, a pre-hydrated hydrogel sheet formed in Example 1 was placed on the dried polyurethane film and compressed to prepare n-q polyvinyl alcohol hydrogel, and then packaged in an aluminum laminate pack. Finally, gamma rays of 25 kGy were irradiated, and a peeling test was conducted in the same manner as in Experimental Example 1. The results are shown in Table 4.

Sample Name Concentration of Polyvinyl Alcohol as Binder Tear strength (g / ㎠) p 25 wt% 64.7 q 20 wt% Z 60.3 r 18.2 wt% 58.7 s 14.3 wt% 53.1

From the results in Table 4, it can be seen that the concentration of polyvinyl alcohol as a binder affects the adhesion between the polyupetane film and the hydrogel. The most preferred concentration of polyvinyl alcohol is 25% by weight.

Experimental Example 5 Measurement of Swelling Degree

After irradiating gamma rays of 25, 50, 75 kGy finally to the hydrogel prepared in Example 1, the samples were cut into squares of 1 cm × 1 cm and immersed in distilled water or horse serum for 48 hours. Thereafter, water on the surface of the hydrogel was removed with cellulose paper to measure the swollen gel weight. The weighed hydrogel was placed in a vacuum oven and dried at 60 ° C. for 48 hours, and then dried gel weight was measured. The degree of swelling of the hydrogel was calculated by the following Equation 1, and the results are shown in Table 5.

Sample Name Gamma Radiation Dose (kGy) Swelling degree (%) Hose serum water t 25 270 1500 u 50 240 1400 v 75 200 1200

As shown in Table 5, as the gamma-irradiation amount increased to 25, 50, 75 kGy, the swelling degree of the hydrogel decreased, and the swelling degree was 5 to 6 times larger than that of the hose serum. From this, it can be seen that the hydrogel for wound treatment of the present invention can maintain an optimal moisture environment for the treatment of wounds when crosslinked by gamma irradiation of about 25 kGy, which is generally irradiated for sterilization.

The hydrogel according to the present invention has a simple manufacturing method, absorbs the effusion properly while suppressing the amount of water evaporation, has excellent gel strength, and has an antibacterial function that can prevent infection from bacteria. In addition, by using irradiation technology, it satisfies both storage and sterilization at the same time, there is no problem of toxic residue because no initiator or crosslinking agent is used, and it is easy to adhere to wounds and skin, transparency of hydrogel, ease of handling, etc. By having the advantage of it can be usefully used for wound treatment or skin regeneration of burns, wounds and the like.

Claims (13)

a) dissolving the biocompatible polymer and the polyhydric alcohol in distilled water, and then freezing and thawing the aqueous biocompatible polymer solution to form a pre-hydrated gel; b) coating an aqueous polyvinyl alcohol solution on a polymer film, nonwoven fabric or fiber and drying; c) attaching the preliminary hydrogel onto the polyvinyl alcohol-coated polymer film, nonwoven fabric or fiber and compressing the adhesive; And d) packaging the compressed hydrogel using a packaging material, and manufacturing a hydrogel for wound treatment using a radiation irradiation technique comprising the step of irradiating with radiation. The method of claim 1, wherein the biocompatible polymer is polyvinyl alcohol alone or polyvinyl alcohol from the group consisting of polyvinylpyrrolidone, polyethylene oxide, polyacrylic acid, gelatin, aga, alginate and chitosan. Method for producing a hydrogel for wound treatment using a radiation irradiation technology, characterized in that used in combination with at least one selected. The method of claim 1, wherein the content of the biocompatible polymer is a method for producing a hydrogel for wound treatment using a radiation irradiation technology, characterized in that 10 to 35% by weight based on the total aqueous solution. According to claim 2, wherein when the biocompatible polymer is a mixed polymer containing the polyvinyl alcohol, the content of the polyvinyl alcohol is wound using a radiation technique, characterized in that more than 40% by weight relative to the polyvinyl alcohol mixture solution Method for producing a therapeutic hydrogel. The method of claim 2, wherein the polyvinyl alcohol has a degree of polymerization of 1,300 to 2,700 and a degree of saponification of 85 to 99.9 mol%. The method of claim 1, wherein the polyhydric alcohol is at least one selected from the group consisting of glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, hexylene glycol, sorbitol, mannitol and polyethylene glycol Method for producing hydrogel for wound treatment using radiation technology. The method of claim 1, wherein the polyhydric alcohol content is 1 to 20% by weight based on the total aqueous solution of the method of producing a hydrogel for wound healing using a radiation technique. The method of claim 1, wherein the freezing is performed for 5 minutes to 1 hour at -150 ~ -15 ℃, the thawing is carried out at 5 ~ 50 ℃, repeatedly performing the freezing and thawing physically of the biocompatible polymer Method for producing a hydrogel for wound treatment using a radiation irradiation technology, characterized in that to form a bridge. The method of claim 1, wherein the polymer film is at least one selected from the group consisting of polyurethane, silicone rubber, low density polyethylene, high density polyethylene, ethylene vinyl acetate, and plasticized polyvinyl chloride. Method for preparing hydrogel for wound treatment. The method of claim 1, wherein the nonwoven fabric is at least one selected from the group consisting of a polypropylene nonwoven fabric, a polyethylene nonwoven fabric, a nylon nonwoven fabric, and a polyester nonwoven fabric. The method of claim 1, wherein the polyvinyl alcohol has a degree of polymerization of 500 to 2700 and a saponification degree of 75 to 90 mol%. The method of claim 1, wherein the concentration of the polyvinyl alcohol aqueous solution is 5 to 30% by weight, the thickness of the coating layer is a method for producing a hydrogel for wound treatment using a radiation irradiation technology, characterized in that 10 to 500 ㎛. The method of claim 1, wherein the radiation is gamma rays or electron beams, and the irradiation dose of the radiation is 5 ~ 100 kGy, the method of producing a hydrogel for wound treatment using a radiation irradiation technology.