KR100612374B1 - Hydrogels for Wound Dressings Containing Covering Layer to Prevent Water Loss and Its Preparation - Google Patents

Abstract

The present invention relates to a hydrogel for wound treatment containing a moisture release prevention layer and a method of manufacturing the same, and more particularly, to an aqueous solution containing a biocompatible polymer and a moisture release prevention layer composed of an EVA, EVOH, VLDPE film or polyurethane film. A hydrogel for treating wounds and a method for producing the same, which has an advantage of being able to adequately absorb the effusion without a great amount of water evaporation and having excellent gel strength, which can be useful for treating wounds or wounds such as burns and wounds or for skin regeneration. There is this.

Hydrogel, EVA (ethylene vinylacetate copolymer), EVOH (ethylene-vinylalcohol copolymer), VLDPE (very low density polyethylene), polyurethane, biocompatible polymer, radiation

Description

Hydration gel for wound treatment containing a moisture release prevention layer and a method for manufacturing the same {Hydrogels for Wound Dressings Containing Covering Layer to Prevent Water Loss and Its Preparation}             

1 is a schematic diagram of a hydrogel manufacturing method of the present invention,

2 is a schematic diagram of a cut or a fine hole of Table 1 of the present invention,

3 is a schematic view of a drying apparatus measuring the degree of water evaporation in the hydrogel of the present invention,

4 is a result of measuring the water evaporation degree of the hydrogel that does not contain the film or film of the present invention,

5 is a result of measuring the water evaporation degree of the hydrogel containing the EVA film of the present invention,

6 is a result of measuring the degree of moisture evaporation of the hydrogel containing the EVOH film of the present invention,

7 is a result of measuring the water evaporation degree of the hydrogel containing the VLDPE film of the present invention,

8 is a result of measuring the water evaporation degree of the hydrogel containing the polyurethane membrane of the present invention.

The present invention relates to a hydrogel for wound treatment containing a moisture release prevention layer and a method for manufacturing the same, and more particularly, an aqueous solution containing a biocompatible polymer, an ethylene vinylacetate copolymer (EVA), and an ethylene vinyl alcohol aerial. The present invention relates to a hydrogel for wound healing containing an ethylene vinylalcohol copolymer (EVOH), a very low density polyethylene (VLDPE) film or a polyurethane film, and a method for preparing the wound gel.

Hydrogels are materials used for the purpose of burn treatment or skin regeneration that require a constant wet state, and usually contain 80% or more of moisture to achieve the above 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 usually requires considerable time before performing this procedure. have. At this time, the wound dressing to prevent infection of the affected area prior to the procedure, it is possible to prevent the infection of the affected area by introducing a hydrogel having excellent affinity with blood, body fluids and biological tissues.

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 in order to function properly moisture, carboxyl group (-COOH), amide group (-CONH ₂ ), amide group (-CONH-), sulfonic acid group (-SO ₃ H) Absorption of water, including hydrophilic functional groups, should not dissolve in water. That is, the polymer that can be used in the hydrogel absorbs water by capillary and osmotic phenomena due to the characteristics of the structure, and contains water, and due to the covalent structure between the polymer chains as well as electrostatic and lipophilic interactions, It must have characteristics that do not dissolve.

Generally, the polymer used in the hydrogel is made of a synthetic polymer, a natural polymer or a mixture thereof.

The synthetic polymer may be selected from the group of hydrophilic synthetic polymers consisting of polyvinylpyrrolidone, polyethylene oxide, polyhydroxyethyl methacrylate and polyvinyl alcohol, and natural polymers are gelatin, agar, alginate, carrageenan and chitosan. It may be selected from the group consisting of.

U.S. Patent No. 4,226,232 discloses a method for preparing a hydrogel for wound treatment by graft reaction of acrironitrile on starch, but the manufacturing method is complicated and there are many problems in removing impurities.

EP-A-0207022 discloses a composition consisting of hygroscopic particles and thickeners, but this technique is suitable for wounds such as ulcers in which exudates are excessively discharged, but the drying rate is too high when necrotic tissue is to be removed. There is a problem that can give trauma or stress the patient because it is fast.

U. S. Patent No. 5,480, 717 discloses a method of preparing a crosslinked hydrophilic hydrogel by applying a hydrophilic aqueous solution on a polymer film and irradiating with radiation. However, the patent has the advantage of being able to effectively remove wound secretions by using a hydrophilic hydrogel, while the disadvantage is difficult to apply to ulcers or deep wounds.

U. S. Patent No. 6,022, 330 discloses a technique in which a nonwoven fabric does not stick to a wound by irradiating the nonwoven fabric and then graft copolymerizing N-isopropylacrylamide.

U.S. Patent No. 5,618,799 has prepared a powder which can be applied to wound healing by mixing polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acid, methylcellulose and the like with sucrose as a main ingredient. It is disadvantageous because the wound healing effect is slow.

In addition, the Republic of Korea Patent No. 349020, the application of the gel formed by the interaction of the polyvinylpyrrolidone and chitosan derivatives for wound packing, wound dressing, drug delivery dressing, cosmetic face mask, cosmetic wrap dressing It is starting. This technique also has the advantage of manufacturing a pack using a hydrogel having excellent properties, but has a disadvantage that the base and a variety of additives mixed with the hydrogel pack agent. In particular, the face mask is made of a dry film and has the disadvantage of exerting its effect in a state where the skin is wet with water.

Hydration gel for wound treatment such as implantable therapeutic acrylamide copolymer hydrogel having a moisture content of at least 80% and elastic deformation in Korea Patent Registration No. 347520, Publication No. 2004-0012816, Publication No. 2004-0022575, etc. Is disclosed.

On the other hand, the present inventors have disclosed a hydrogel for wound treatment containing polyvinylpyrrolidone, chitosan, polyethylene oxide or sodium alginate in Patent No. 333317, Patent No. 440239 for wound treatment containing a urethane membrane A method for preparing a hydrogel has been disclosed, and Patent Publication No. 2004-0051130 discloses a method for preparing a hydrogel for wound treatment containing sodium carboxymethyl cellulose, sodium alginate and polyol.

Hydrogels are also prepared by chemical methods and methods using radiation. Since the chemical method of manufacturing by adding a chemical crosslinking agent or initiator has secondary problems of removing these chemical crosslinking agents or initiators and toxic residues, the use of radiation which has the advantage of combining both crosslinking and sterilization at the same time is spotlighted. Is getting.

Moreover, the radiation use method does not need to apply heat in the crosslinking process, crosslinking is possible even in a cooling state, and has the advantage of freely controlling physical properties without changing the composition only by controlling the radiation dose.

U. S. Patent No. 5,389, 376 discloses a method for preparing a wound dressing using a radiation crosslinking method without using such a chemical crosslinking agent. The production method describes that polyvinylpyrrolidone is mixed with agar and polyethylene oxide and irradiated with radiation to crosslink. The patent takes advantage of the characteristics of the crosslinking method of radiation, that is, the ability to simultaneously promote crosslinking and sterilization. Although agar was added to the polyvinylpyrrolidone aqueous solution to reduce the deformation of the hydrogel in the drying process, the strength of the hydrogel was low when the polyvinylpyrrolidone and agar were mixed, and the compatibility was not good. Tends to be weak and torn.

U. S. Patent No. 5,480, 717 discloses a hydrogel prepared by casting polyvinylpyrrolidone aqueous solution onto an adhesive polymer film and irradiating the same. However, while the strength of the hydrogel prepared in the present invention is weak, the adhesiveness is too strong, there was a disadvantage that the polyvinylpyrrolidone remains when preparing the hydrogel from the wound.

Japanese Patent Application Laid-Open No. 9-267453 (US Pat. No. 5,846,214) discloses a technique of improving physical properties by using polyvinyl alcohol as a base material and placing another laminating agent thereon. However, since the product is manufactured simply by irradiation, there is a limit to the improvement of physical properties, and since the form cannot be kept in the packaging without irradiation, the process is not carried out in the final product without mold irradiation. The hydrogel is present together, there was a disadvantage to use a separate antimicrobial agent for long-term use in the affected area.

The conditions under which hydrogels are best suited for the purpose of treating burns, wounds, must absorb body fluids, prevent infection from bacteria, and facilitate attachment to wounds or skin. In addition, transparency and oxygen permeability should be good, drug control should be possible, handling should be easy, storage and sterilization should be possible. In addition, the hydrogel should not evaporate to a degree that degrades the physical properties of the hydrogel and its functionality as a dressing for wound treatment while being applied to the wound site.

Since the hydrogel contains 80% or more water, the moisture of the hydrogel begins to evaporate when exposed to air at a body temperature of 37 ℃. The hydrogel is evaporated after 12 hours or more at a temperature of 37 ℃, the moisture is evaporated and dried hydrogel is no longer available for wound treatment. Therefore, the hydrogel basically absorbs water, while maintaining the mechanical properties and shape while drying, it is necessary to properly control the gel strength and swelling.

The present inventors have endeavored to prepare hydrogels that can be effectively used to treat wounds, wounds, and the like and to regenerate the skin, and as a result, a living body selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, carrageenan, or mixtures thereof A hydrogel was prepared by applying an aqueous solution of a suitable polymer onto an EVA, EVOH VLDPE film or polyurethane membrane to form a prehydrate gel with the polymer suitable for this purpose and optimum molecular weight conditions, and irradiating with an appropriate radiation dose to form a crosslinked hydrogel. By confirming that the hydrogel of the present invention can be suitably used for wound treatment, the present invention has been completed.

An object of the present invention, while absorbing water, while maintaining the mechanical properties and shape while drying, and prevents the release of water, the hydrogel for wound healing containing a moisture release prevention layer that can properly control the gel strength and swelling and the preparation thereof It is to provide a method.

In order to achieve the above object, the present invention is an aqueous solution comprising a biocompatible polymer and ethylene vinyl acetate copolymer (Ethylene Vinylacetate Copolymer; EVA), ethylene vinyl alcohol copolymer (Ethylene Vinylalcohol Copolymer; EVOH), ultra low density polyethylene (Very) Provided is a hydrogel for wound treatment containing a moisture release prevention layer composed of a Low Density Polyethylene (VLDPE) film or a polyurethane film.

Such biocompatible polymers are in particular polyvinylpyrrolidone (PVP) or carrageenan.

Hereinafter, the present invention will be described in detail.

In order to obtain the excellent performance hydrogel of the present invention, selection of a suitable polymer and a polymer having an optimal molecular weight must be preceded. This is because, in the case of polymers having a high molecular weight, when the components are not compatible with each other, phase separation may occur, resulting in deterioration of final physical properties.

Therefore, as the polymer that satisfies the above conditions, the polymer that can be used in the preparation of the hydrogel according to the present invention can be any biocompatible polymer, preferably polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) , Synthetic polymers selected from the group consisting of polyethylene oxide (PEO) and polyacrylic acid, or natural polymers selected from the group consisting of gelatin, agar, alginate, chitosan and carrageenan It may be used, more preferably, the aqueous solution is to use polyvinylpyrrolidone, carrageenan. It is also desirable to add polyhydric alcohols to the biocompatible polymers selected above for the purpose of increasing adhesion and flexibility. The polyhydric alcohol is preferably polyethylene glycol.

Polyvinylpyrrolidone is a water soluble and biocompatibility polymer and has been widely used for decades as blood fluids and other biomaterials. 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 structure, it is able to hydrogen bond with water molecules and can form a network structure through this, so that it may contain a large amount of moisture for wound healing purposes. Suitable polymers.

The optimum molecular weight of the selected polymer is preferably 200,000 to 1,300,000, more preferably 360,000 to 1,300,000 in the case of the polyvinylpyrrolidone.

In this case, when the molecular weight is 200,000 or less, particularly 40,000 or less, it is easy to prepare an aqueous solution because the viscosity of the polymer solution is low, but the gelation rate and gel strength, which are physical properties, are low, and therefore, are not suitable for use as a hydrogel for wound treatment. On the other hand, when the molecular weight exceeds 1,300,000, when mixed with other polymers, there is a problem in that it is difficult to produce a uniform hydrogel due to poor compatibility with the materials.

Carrageenan, used as a natural polymer, is a complex polysaccharide extracted from red algae that grows in clean waters and is used as a dispersant, emulsion stabilizer, swelling agent, thickener, binder, dietary fiber, anti-crystal, and gelling agent in food applications. In addition to food, the polymer is expected to be used in medicine, cosmetics, and other fields. In general, carrageenan is an anionic polymer with sulfuric acid groups showing strong hydrophilicity, and kappa-, κ-, lambda-, lambda-, and iota-, ι depending on the content and position of the sulfate group. -), Mu- (mu-, μ-), kappa-furcellaran (κ-furcellaran) form is divided into a single or mixed form is commercialized. Usually, three kinds of carrageenan of kappa-, lambda-, and iota-type are mainly used. One of the characteristics of these carrageenan is that it is easily gelled by cations and has excellent film forming ability. In particular, the carrageenan used in the present invention is preferably kappa-carrageenan in which gelation is best among the three kinds of carrageenan in consideration of its gelling properties. The molecular structure of kappa-carrageenan is shown in equation (1).

(1)

(One)

Like polyvinylpyrrolidone, polyalcohol is a water-soluble polymer that is harmless to the human body and has excellent biocompatibility. The polyhydric alcohol has a property of softening the hydrogel in a hydrogel dressing of the present invention and having a high moisture protection effect. Suitable polyhydric alcohols for the preparation of hydrogel can be used by mixing one or two or more of ethylene glycol, propylene glycol, 1,3-butylene glycol, hexylene glycol, glycerin, polyethylene glycol, polypropylene glycol, sorbitol, mannitol. It is preferable that the molecular weight of polyethyleneglycol in the said polyhydric alcohol is 200-600, and it is preferable that polypropylene glycol is 200-450. Polyhydric alcohol having a higher molecular weight is in a solid phase, when mixed with other polymers, it is difficult to prepare a uniform hydrogel due to poor compatibility with materials.

(2)

(2)

In the present invention, the aqueous solution is to prepare a biocompatible polymer aqueous solution selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, carrageenan or a mixture thereof.

In the case of solutions prepared by mixing them, it is 1 to 37% by weight of polyvinylpyrrolidone with respect to the total weight, and 0.1 to 10% by weight of carrageenan can be mixed therein.

At this time, when the carrageenan increases to 10% by weight or more of the total weight of the aqueous solution, the viscosity increases, which makes it difficult to dissolve. In addition, 1 to 10% by weight of polyethylene glycol can be further mixed with respect to the total aqueous solution. At this time, when the polyethylene glycol is more than 10% by weight of the total aqueous solution weight it is not possible to obtain a gel strength that can be used as a dressing.

 When preparing the aqueous solution of the polyvinylpyrrolidone, carrageenan and polyethylene glycol, the weight of the total aqueous solution is preferably 5 to 40% by weight, most preferably 10 to 25% by weight.

At this time, when the hydrogel is prepared with an aqueous solution of 5% by weight or less, it is not possible to obtain a gel strength that can be used as a dressing, and more than 25% by weight of the polymer aqueous solution is too large to make a sheet.

EVA, EVOH, VLDPE forming the moisture release prevention layer according to the present invention will be described in detail.

EVA (Ethylene Vinyl Acetate copolymer) is a copolymer resin of ethylene and vinyl acetate. Due to its excellent transparency, flexibility and low temperature brittleness, raw materials for shoe materials, agricultural films, and laminating films are also used, and are attracting attention as PVC substitutes. Vinyl acetate is hydrophilic, and as the vinyl acetate content of EVA increases, the hydrophilicity increases. Because of its hydrophilicity, it has excellent adhesion with hydrogel and can suppress water evaporation. EVA containing 3 to 35% by weight vinyl acetate is suitable.

 EVOH (Ethylene Vinyl Alcohol) is a copolymerized thermoplastic resin of ethylene (ethylene) and vinyl alcohol (vinyl alcohol). EVOH is used as a food packaging material because it can block the passage of inorganic gases such as oxygen, carbon dioxide gas, and organic gases such as aromatic components of food. In addition, it has excellent chemical resistance and excellent surface gloss. Vinyl alcohol has hydrophilicity. As the vinyl alcohol content of EVOH increases, hydrophilicity increases. It is hydrophilic and has excellent adhesiveness with hydrogel and has moisture control ability.

Polyethylene is the first commercially available polyolefin-based material of ethylene polymer, which is very low density polyethylene (VLDPE), linear low density polyethylene (LLDPE), low density polyethylene (LDPE), Medium density polyethylene (MDLE), high density polyethylene (HDPE), and the like. In general, polyethylene has good water barrier properties, chemical resistance and low cost, and gas permeability. In particular, the VLDPE (ultra low density polyethylene) has a high cold resistance and has good thermal adhesiveness, and is widely used as a thermal adhesive packaging material when laminating with other packaging materials. In addition, the ultra low density polyethylene is a material suitable for preventing water evaporation of the hydrogel due to its excellent impact resistance, very high oxygen permeability, and low moisture permeability.

The present invention also provides a method for producing a hydrogel for wound treatment.

Specifically, 1) preparing polyvinylpyrrolidone, carrageenan and polyethylene glycol in distilled water, heating and stirring to prepare an aqueous solution (step 1);

2) laying the EVA, EVOH, VLDPE film or polyurethane film on the tray (step 2);

3) applying the aqueous solution of step 1 on the EVA, EVOH, VLDPE film or polyurethane film of step 2 and left at room temperature to form a prehydrate gel (step 3);

4) packing the preliminary hydrogel of step 3 (step 4); And

5) It provides a method for producing a hydrogel for wound treatment containing a moisture release prevention layer consisting of a step (step 5) of irradiating and sterilizing the packaged gel of step 4 with radiation.

The aqueous solution of step 1 is to prepare a biocompatible polymer aqueous solution selected from the group consisting of polyvinylpyrrolidone, carrageenan and polyethylene glycol or mixtures thereof.

In the case of a solution prepared by mixing them, it is 1 to 37% by weight of polyvinylpyrrolidone with respect to the total weight, and 0.1 to 10% by weight of carrageenan can be mixed therein. At this time, when the carrageenan increases to 10% by weight or more of the total weight of the aqueous solution, the viscosity increases, which makes it difficult to dissolve.

In addition, 1 to 10% by weight of polyethylene glycol can be further mixed with respect to the total aqueous solution. At this time, when the polyethylene glycol is more than 10% by weight of the total aqueous solution weight it is not possible to obtain a gel strength that can be used as a dressing.

When preparing the aqueous solution of the polyvinylpyrrolidone, carrageenan and polyethylene glycol, the weight of the total aqueous solution is preferably 5 to 40% by weight, most preferably 10 to 25% by weight.

At this time, when the hydrogel is prepared with an aqueous solution of 5% by weight or less, it is not possible to obtain a gel strength that can be used as a dressing, and more than 25% by weight of the polymer aqueous solution is too large to make a sheet.

Step 2 is to lay the EVA, EVOH, VLDPE film or polyurethane film on the tray. The cover layer is used to increase the air permeability by using an EVA, EVOH, VLDPE film having a thickness of 10 ~ 500 ㎛, or fine cut with a knife on these films or to form micropores. Polyurethane membranes do not need to be physically formed with knives or secondary pores because they can form appropriate micropores depending on the processing process.

The tray may use trays of various diameters, heights and shapes, and the like, and by using various trays, a hydrogel having a desired shape and size may be manufactured.

Step 3 is poured into the tray of the step 2 of the aqueous solution containing the polyvinyl foryridone, carrageenan and polyethylene glycol obtained in step 1 in the EVA, EVOH, VLDPE film or polyurethane film and the aqueous solution of 40 ℃ or less, in particular at room temperature The pregel is formed by maintaining the temperature. When the temperature of the aqueous solution obtained in step 1 is lowered to 40 ℃ or less solidified by the characteristics of carrageenan preliminary hydrogel is formed.

Step 4 is a step of packing the preliminary hydrogel of step 3. Conventional packaging materials may be used for packaging, and for example, polymer films such as polyethylene, polypropylene, polyvinyl chloride, nylon, polyester, or aluminum foil or laminates of aluminum and polymer films may be used.

In step 5, irradiation is a step capable of crosslinking and sterilizing the aqueous solution, preferably gamma rays or electron beams.

At this time, the preferable irradiation dose is 5-100 kGy, and the preferable irradiation dose is 25-50 kGy in consideration that the appropriate dose normally required for sterilization purpose is about 25 kGy. On the other hand, when an excessive dose of 100 kGy or more is irradiated, the gel strength increases, but the swelling property decreases and the flexibility decreases, making it easily broken.

The hydrogel of the present invention shows an average gelation rate of 30 to 50%, an average swelling of 5,000 to 8,000%, and a gel strength value of 80 to 540 g · cm. At this time, the hydrogel contains EVA, EVOH, VLDPE film or polyurethane film, thereby greatly improving the gel strength.

In addition, the degree of water evaporation of the hydrogel can be controlled by the hydrogel containing EVA, EVOH, VLDPE film or polyurethane film.

Therefore, the hydrogel of the present invention can be obtained by a simple manufacturing process, and has excellent gel strength by physical crosslinking including carrageenan, and contains EVA, EVOH, VLDPE film or polyurethane membrane, and does not have a large amount of water evaporation. By absorbing suitably and using radiation irradiation, both storage and sterilization can be satisfied simultaneously. In addition, due to the inherent viscosity of the hydrogel, it is easy to adhere to wounds and skin, and the final hydrogel obtained by applying a colorless polymer solution completely dissolved in water is transparent so that the state of the wound can be observed without removing the hydrogel dressing from the wound. It has advantages

Hereinafter, the present invention will be described in more detail by the following examples.

However, the following examples are provided to illustrate the present invention, and the content of the present invention is not limited by the following examples.

< Example  1>

Polyvinylpyrrolidone Of Carrageenan Of Polyethylene glycol Hydrogel  1, manufacture

 6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

 The prepared aqueous solution was poured into a tray and left at room temperature to form a gel and packaged, and then irradiated with a gamma ray of 25 kGy to prepare a hydrogel 1 by the same process as in FIG. 1.

< Example  2>

Polyvinylpyrrolidone, carrageenan and polyethylene glycol hydrogels containing EVA films  2, manufacturing

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

EVA film having a vinyl acetate content of 12% by weight was laid on a tray, and the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and irradiated with a gamma ray of 25 kGy to prepare hydrogel 2.

< Example  3>

Polyvinylpyrrolidone, carrageenan and polyethylene glycol hydrogels containing EVA films  3, manufacturing

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

Each of the three sheaths of Table 1 was cut out on the EVA film for drying rate control.

EVA film having a vinyl acetate content of 12% by weight was laid on a tray, and the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and irradiated with a gamma ray of 25 kGy to prepare hydrogel 3.

One 2 3 width 2 mm 2 mm 2 mm interval 2 mm 2 mm 10 mm Line spacing 8 mm 16 mm 16 mm

The cut marks of Table 1 are shown in FIG.

< Example  4>

Polyvinylpyrrolidone, carrageenan and polyethylene glycol hydrogels containing EVOH films  4, Manufacture

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

An EVOH (32 mol%) film was placed on a tray, and the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and irradiated with a gamma ray of 25 kGy to prepare a hydrogel 4.

< Example  5>

Polyvinylpyrrolidone, carrageenan and polyethylene glycol hydrogels containing EVOH films  5, Manufacture

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

Each of the three sheaths of Table 1 was cut out in the EVOH film for drying rate control.

The EVOH film was laid on a tray, the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and then irradiated with a gamma ray of 25 kGy to prepare hydrogel 5.

< Example  6>

Polyvinylpyrrolidone, carrageenan and polyethylene glycol hydrogels containing VLDPE films  6, manufacturing

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

VLDPE (density 0.88 g / cm ³ , melt index 0.8) film was laid on a tray, and the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, packaged, and irradiated with a gamma ray of 25 kGy to hydrate gel 6 Was prepared.

< Example  7>

VLDPE (density 0.88 g / cm ³ , melt index 0.8) polyvinylpyrrolidone containing film , Carrageenan  And Polyethylene glycol Hydrogel  7, manufacturing

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

Each of the three sheaths of Table 1 was cut out on the VLDPE film for drying rate control.

The VLDPE film was laid on a tray, the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and then irradiated with a gamma ray of 25 kGy to prepare a hydrogel 7.

< Example  8>

Containing polyurethane membrane Polyvinylpyrrolidone , Carrageenan  And Polyethylene glycol  Preparation of Hydrogel 8

6 wt% of PVP having a molecular weight of 1,300,000, 2 wt% of carrageenan, and 1 wt% of PEG having a molecular weight of 400 were mixed in distilled water and dissolved at 90 ° C.

Polyurethane film was laid on a tray, and the aqueous solution was poured to a height of 3 mm, left at room temperature to form a gel, and then packaged, and then irradiated with a gamma ray of 25 kGy to prepare a hydrogel 8.

< Experimental Example  1>

Hydrogel Gelation rate  Measure

The package of the hydrogels prepared in Examples 1 to 8 was taken out and taken out, immersed in distilled water for 48 hours to dissolve the uncrosslinked portions, and the undissolved portions were put in a vacuum oven and dried at 37 ° C. for 48 hours and then dried. By measuring the weight, the gel content of the hydrogel was calculated by Equation 1.

The gelation rate of the hydrogels prepared in Examples 1 to 8 was 30 to 50% on average.

< Experimental Example  2>

Hydrogel Swelling degree  Measure

After removing the packaging of the hydrogel prepared in Examples 1 to 8 and immersed in distilled water for 48 hours, water on the surface of the hydrogel was wiped off and the swollen gel weight was measured. The weighed hydrogel was placed in a vacuum oven, dried at 37 ° C. for 48 hours, and the dried gel weight was measured to calculate the degree of swelling of the hydrogel by Equation 2.

The swelling degree of the hydrogels prepared in Examples 1 to 8 was 5,000 to 8,000% on average.

< Experimental Example  3>

Hydrogel Gel strength  Measure

Opening and taking out the packaging of the hydrogels prepared in Examples 1, 2, 4, 6, and 8 to make a specimen having a thickness of 2 mm and a width of 20 cm ² to measure the gel strength of the hydrogel using a texture analyzer (Texture-Analyzer) Gel strength was calculated by the equation (3). The results are shown in Table 2.

  Gel strength (gcm) = (weighted force when destroyed) x (length increased when destroyed)

Example 1 Example 2 Example 4 Example 6 Example 8 Gel strength (gcm) 80 430 310 540 380

As shown in the results of Table 2, the gel strength of the hydrogels of Examples 2, 4, 6, and 8 containing EVA, EVOH, VLDPE film or polyurethane membrane was greater than that of the hydrogel of Example 1 without the membrane. Seemed. When the hydrogel contained a film or film, it was confirmed that the physical properties were improved.

< Experimental Example  4>

EVA, EVOH , VLDPE  Film or polyurethane film Hydrogel  Effect on moisture evaporation

The effect of EVA, EVOH, VLDPE film or polyurethane film on the hydrogel was measured by comparing the degree of water evaporation of the hydrogel containing and not the EVA, EVOH, VLDPE film or polyurethane membrane.

The package of the hydrogels prepared in Examples 1 to 8 was opened and taken out, and the degree of moisture evaporation of the hydrogels was measured using the drying apparatus of FIG. 3.

The temperature of the water contained in the drying apparatus of FIG. 3 was fixed at 37 ° C., and the humidity inside the drying apparatus was 60 to 80% due to evaporation of water. The hydrogel placed on the mesh of the drying apparatus is the bottom surface is the vaporized water vapor and the upper surface is in contact with the air.

Degree of water evaporation of the hydrogel was calculated by the following equation (4).

Figure 4 shows the degree of water evaporation of the hydrogel of Example 1 containing no membrane. Moisture evaporates rapidly up to the first 5 hours, and after 20 hours all the moisture contained in the hydrogel evaporates.

FIG. 5 shows the water evaporation degree of the hydrogel of Example 2 containing EVA film and Example 3 in which three sheaths of Table 1 were placed on the EVA film, and the hydrogel of Example 2 was subjected to 60 hours. Only% moisture was evaporated. Hydrogel with a sheath as shown in Table 1 of Example 3 60% after 60 hours, hydrogel with a sheath as shown in Table 2 2% 28% after 60 hours, with a sheath as shown in Table 3 After 60 hours, 12% of the water evaporated.

FIG. 6 shows the water evaporation degree of the hydrogel of Example 4 containing EVOH film and Example 5 in which three kinds of sheaths of Table 1 were cut on the EVOH film. Only% moisture was evaporated. Hydrogel with a sheath as shown in Table 1 of Example 5 was 77% after 60 hours, and hydrogel with a sheath as shown in Table 2 at 2% was 58% after 60 hours and with a sheath as shown in Table 3 at Table 1. After 60 hours, 35% of the water evaporated.

FIG. 7 shows the water evaporation degree of the hydrogel of Example 6 containing VLDPE film and the hydrogel of Example 7 in which three sheaths of Table 1 were cut on the VLDPE film. Only% moisture was evaporated. Hydrogel gel with a sheath as shown in Table 1 of Example 7 50% after 60 hours, the hydrogel with a sheath as shown in Table 2 2 20% after 60 hours, a hydrogel with a sheath as shown in Table 3 After 60 hours, 7% of the water evaporated.

FIG. 8 shows the water evaporation degree of the hydrogel of Example 8 containing a polyurethane membrane . In the hydrogel of Example 8, 40% of the water was evaporated after 60 hours.

From the above results, the hydrogel of the present invention contained water for about 20 hours, but containing EVA, EVOH VLDPE film or polyurethane film cover material, hydrogel containing 86-98% water even after 60 hours. Could be prepared. In addition, it was possible to control the evaporation of water of the hydrogel by giving a sheath as shown in Table 1, at this time it was possible to prepare a hydrogel containing 23 to 93% water even after 60 hours.

The present invention having the above-described configuration is simple in its manufacturing process, contains EVA, EVOH VLDPE film or polyurethane film cover material, absorbs the effluent appropriately without a great amount of water evaporation, and has excellent gel strength. In addition, it not only has an antibacterial function to prevent infection from bacteria, but also satisfies storage and sterilization simultaneously by using irradiation. Moreover, since no residual initiator or crosslinking agent is used, there is no problem of toxic residue, and it is easy to adhere to wounds and skin, and has advantages such as transparency and ease of handling, so as to treat wounds and wounds or to regenerate skin. It can be usefully used.

In addition, according to the manufacturing method of the present invention, because the tray is used, it is possible to easily prepare a hydrogel having various shapes, sizes, and thicknesses.

Claims (12)

A biocompatible polymer aqueous solution containing polyvinylpyrrolidone and carrageenan was prepared on a water release prevention layer consisting of ethylene vinyl acetate copolymer (EVA), ethylene vinyl alcohol copolymer (EVOH), ultra low density polyethylene (VLDPE) film, or polyurethane film. Hydrogel for wound treatment formed by application to a wound. delete The hydrogel for wound treatment according to claim 1, wherein the biocompatible polymer aqueous solution further comprises polyethylene glycol. The hydrogel of claim 1, wherein the polyvinylpyrrolidone has a molecular weight of 200,000-1,300,000. 4. The hydrogel for wound treatment according to claim 3, wherein the polyethylene glycol has a molecular weight of 200 to 600. The hydrogel of claim 1, wherein the carrageenan is kappa-carrageenan. The method of claim 1, wherein the aqueous solution further comprises 1 to 37% by weight of polyvinylpyrrolidone and 0.1 to 10% by weight of a carrageenan biocompatible polymer, or 1-10% by weight of polyethylene glycol with the biocompatible polymer. Hydrogel for wound treatment, characterized in that. 1) preparing a mixture of polyvinylpyrrolidone and carrageenan, or the mixture and polyethylene glycol in distilled water, followed by heating and stirring to prepare an aqueous solution (step 1); 2) ethylene vinyl acetate copolymer (EVA), ethylene vinyl alcohol copolymer (EVOH), ultra low density polyethylene (VLDPE) film or polyurethane membrane on a tray (step 2); 3) applying the aqueous solution of step 1 on the EVA, EVOH, VLDPE film or polyurethane film of step 2 and left at room temperature to form a prehydrate gel (step 3); 4) packing the preliminary hydrogel of step 3 (step 4); And 5) A method for producing a hydrogel for wound treatment containing a moisture release preventing layer comprising a step (step 5) of irradiating, crosslinking and sterilizing the packaged gel of step 4 with radiation. 9. The method of claim 8, wherein the thickness of the film of step 2 is 10 ~ 500 ㎛ method of producing a hydrogel for wound treatment. 10. The method of claim 8 or 9, wherein a cut or fine pores are formed on the film to increase air permeability. 9. The method of claim 8, wherein the radiation irradiated in step 5 is gamma rays or electron beams. The method of manufacturing a hydrogel for wound treatment according to claim 8 or 11, wherein the radiation dose of the radiation is 5 to 100 kGy.

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