JP3612138B2 - PVA hydrogel laminate and method for producing the same - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a polyvinyl alcohol (hereinafter abbreviated as PVA) hydrogel useful as a biocompatible material such as a wound dressing, and particularly relates to a novel laminate formed by laminating a plurality of PVA hydrogel layers.
[0002]
[Prior art]
PVA hydrogel that has been crosslinked by irradiating PVA aqueous solution with radiation is transparent, heat resistant, and excellent in chemical resistance, gas permeability, and bacteria resistance, so it is expected as a biocompatible material such as wound dressing Has been.
[0003]
As a method of obtaining a PVA hydrogel, in JP-A-4-358521, is irradiated with an electron beam to the PVA aqueous solution and dried to obtain a film, then as a method for performing immersion treatment method to further increase the strength of the gel, medical Instrumental Vol. 62, pp. 285-289 (1992), there is known a method of irradiating a PVA aqueous solution dried and heat-treated.
However, the PVA hydrogel obtained by these methods is a single layer.
[0004]
[Problems to be solved by the invention]
When PVA hydrogel is used as, for example, a wound dressing, it has various characteristics such as adjustment of the strength of the entire gel and control of the diffusion time of the drug to be introduced into the gel according to the application location and application. Although changes are required, there is a problem that conventional single layer PVA hydrogels cannot easily cope with these changes.
[0005]
[Means for Solving the Problems]
The present inventors are a laminate of a plurality of hydrogel layers, comprising polyvinylpyrrolidone (hereinafter abbreviated as PVP), methyl vinyl ether maleic anhydride copolymer (hereinafter abbreviated as VEMA) and isobutylene maleic anhydride copolymer. A step of irradiating a first polyvinyl alcohol aqueous solution, which may contain a polymer selected from a coalescence (hereinafter abbreviated as IBMA), to obtain a first hydrogel layer;
Applying a second aqueous polyvinyl alcohol solution, which may contain a polymer selected from PVP, VEMA and IBMA, onto the first hydrogel layer; and
A step of irradiating the coated second polyvinyl alcohol aqueous solution with radiation to obtain a second hydrogel layer
It has been found that a hydrogel laminate characterized in that it is produced by a method comprising:
[0006]
DETAILED DESCRIPTION OF THE INVENTION
The PVA aqueous solution used in the practice of the present invention preferably contains PVA as an essential component, and further includes any one of PVP, VEMA, and IBMA, or a combination thereof, because it can impart adhesiveness to the hydrogel.
[0007]
The PVA used preferably has a saponification degree of 78 to 100 mol% and an average polymerization degree of 1,000 or more, and has a saponification degree of 97 mol% or more and an average polymerization degree of 1,500 to 2,000. It is more preferable that The PVP used preferably has a weight average molecular weight of 20,000 to 150,000, and more preferably 25,000 to 120,000. VEMA preferably has a weight average molecular weight of 200,000 to 900,000, more preferably 800,000 or more, and IBMA has a weight average molecular weight of 10,000 to 1,000,000. The thing of 30,000-500,000 is more preferable.
[0008]
When PVP is contained, the blending ratio (weight ratio) of PVA and PVP is preferably 2: 8 to 8: 2 from the viewpoint of imparting flexibility. Further, from the viewpoint of imparting tackiness, the blending ratio (weight ratio) of PVA and PVP, VEMA and / or IBMA is preferably 1: 9 to 9: 1, and preferably 2: 8 to 8: 2. More preferred.
[0009]
The concentration of these PVA aqueous solutions is preferably 5 to 50% by weight and more preferably 10 to 40% by weight in order to maintain a certain amount of water after irradiation.
[0010]
In order to impart flexibility, a water-soluble plasticizer such as glycerin, polyglycerin, PEG, DPG, or macrogol may be added to the PVA aqueous solution.
[0011]
Moreover, in order to provide adhesiveness, you may add polyacrylic acid, its sodium salt, its ester, cyclodextrin, pectin, etc. to PVA aqueous solution.
[0012]
In addition, humectants, colorants, antibacterial agents and pharmacologically active substances may be added to the PVA aqueous solution. Moreover, you may add after irradiation.
[0013]
The hydrogel layer according to the present invention is obtained by irradiating radiation after coating the PVA aqueous solution to a certain thickness.
[0014]
The thickness of the coating is not particularly limited, but is preferably 10 μm or more in order to develop adhesiveness.
[0015]
Examples of radiation include γ-rays, electron beams, and X-rays. In particular, an electron beam is preferable because of easy control of absorbed dose and irradiation depth.
[0016]
The absorbed dose of radiation is preferably 20 to 100 kGy, more preferably 20 to 60 kGy. However, when a layer having a low crosslinking density is produced, the absorbed dose is preferably 10 kGy or more, more preferably 15 kGy or more, and further preferably 20 kGy or more.
[0017]
Irradiation may be any of γ-rays, X-rays, and electron beams. However, since the dose rate of electron beams is 500 times higher than that of γ-rays, a product can be produced in a short time. For this reason, since continuous production is possible, when producing hydrogel industrially in large quantities, it is desirable to use an electron beam. Further, since the electron beam can be irradiated in a short time, it does not induce deterioration due to oxidation or the like on the irradiated object, which is preferable irradiation. The dose required to make the hydrogel depends on the mixing ratio of PVA and other materials, but the preferred dose is 20-80 kGy. If it is 10 kGy or less, sufficient strength cannot be obtained because of insufficient crosslinking. If it is 90 kGy or more, the cross-linking is excessive and the adhesiveness is lowered. The predetermined dose for obtaining the hydrogel may be performed by irradiation at a high dose rate at one time, or any method of batch irradiation performed in several times. Gamma ray irradiation is advantageous for obtaining a thick hydrogel because of its high permeability. At this time, the dose may be the same as that of the electron beam.
[0018]
The hydrogel layered product concerning the present invention is obtained by repeating the process of irradiating with radiation after further applying the PVA aqueous solution on the already formed PVA hydrogel layer.
[0019]
Here, in all hydrogel layers, PVA aqueous solutions that differ in any or all of components, compounding ratios, concentrations, etc. may be used, and in some hydrogel layers, the same PVA aqueous solution may be used. Alternatively, the same PVA aqueous solution may be used in all hydrogel layers.
[0020]
Moreover, you may produce the PVA hydrogel laminated body from which a crosslinking degree and thickness differ between layers by changing irradiation dose or the thickness of coating. When the irradiation dose is increased, the degree of cross-linking increases and a PVA hydrogel with higher strength can be obtained.
[0021]
In some cases, various non-woven fabrics, films and the like may be sandwiched between the respective layers, and support layers such as various non-woven fabrics, films and foams may be provided. PVA nonwoven fabric, PVA film, and polypropylene nonwoven fabric are preferable as the nonwoven fabric and film used between the layers, and the polyurethane film, polyurethane foam, PVA nonwoven fabric, PVA film, PP nonwoven fabric, and polyurethane film are used as the film and foam used for the support. Alternatively, a composite support of polyurethane foam and PVA nonwoven fabric, PVA film or PP nonwoven fabric may be used.
[0022]
【The invention's effect】
According to the PVA hydrogel laminate obtained by the present invention, it is very easy to cope with changes in strength, flexibility, drug release rate, etc., depending on the application and application location.
[0023]
【Example】
Step 1: Preparation of various aqueous PVA solutions 20 grams of PVA with a saponification degree of 98.5% and a polymerization degree of 1700 and 80 grams of water are placed in a 300 cc glass Erlenmeyer flask and heated for 20 minutes using an autoclave at 121 ° C. PVA was dissolved to prepare a first PVA aqueous solution. Further, 20 grams of the same PVA, 20 grams of VEMA having a weight average molecular weight of 900,000, and 60 grams of water were placed in a 300 cc glass Erlenmeyer flask, and a second aqueous PVA solution was prepared in the same procedure as described above.
Step 2: Preparation of hydrogel laminate The PVA aqueous solution is coated on a polyurethane film support, the first PVA aqueous solution is applied to a thickness of 250 μm, and 20 kGy of electron beam is irradiated from the upper surface at a time. A first hydrogel layer was formed on the polyurethane film. Next, the first PVA aqueous solution is further coated on the first hydrogel layer to a thickness of 250 μm, and the irradiation amount of the electron beam from the upper surface is increased to 40 kGy, so that the second hydrogel layer is It was formed on the hydrogel layer. Similarly, the second PVA aqueous solution is applied on the second hydrogel layer to a thickness of 250 μm, and an electron beam of 60 kGy is irradiated at once from the upper surface to form the third hydrogel layer on the second hydrogel layer. A hydrogel layer was formed.
The laminate thus produced is shown in FIG. In the obtained laminate, the layers were firmly bonded and physically integrated.
[Brief description of the drawings]
FIG. 1 is a hydrogel laminate produced according to an example.
[Explanation of symbols]
1: Polyurethane film support 2: First hydrogel layer 3: Second hydrogel layer 4: Third hydrogel layer

Claims (9)

A laminate of a plurality of hydrogel layers,
Polyvinylpyrrolidone, the first aqueous solution of polyvinyl alcohol may contain a polymer selected from methyl vinyl ether-maleic anhydride copolymer and an isobutylene-maleic anhydride copolymer, radiation to obtain a first hydrogel layer The step of:
A step of applying a second polyvinyl alcohol aqueous solution, which may contain a polymer selected from polyvinyl pyrrolidone, methyl vinyl ether maleic anhydride copolymer and isobutylene maleic anhydride copolymer, onto the first hydrogel layer. ;and
A step of irradiating the coated second polyvinyl alcohol aqueous solution with radiation to obtain a second hydrogel layer
The hydrogel laminated body manufactured by the method containing this . The hydrogel laminate according to claim 1, wherein each hydrogel layer is obtained from a polyvinyl alcohol aqueous solution different from those of other hydrogel layers. The hydrogel laminate according to claim 1, wherein each hydrogel layer is obtained from the same aqueous polyvinyl alcohol solution. The hydrogel laminate according to claim 1, wherein at least two of the hydrogel layers are obtained from the same aqueous polyvinyl alcohol solution. The hydrogel laminate according to claim 1, wherein the absorbed dose of radiation is the same in all the formed hydrogel layers. The hydrogel laminate according to claim 1, wherein the absorbed dose of radiation is different in all formed hydrogel layers. The hydrogel laminate according to claim 1, wherein the absorbed dose of radiation is the same in any of a plurality of formed hydrogel layers. Irradiation to obtain a first hydrogel layer in a first polyvinyl alcohol aqueous solution which may contain a polymer selected from polyvinyl pyrrolidone, methyl vinyl ether maleic anhydride copolymer and isobutylene maleic anhydride copolymer The step of:
Polyvinylpyrrolidone, the second polyvinyl alcohol solution may contain a polymer selected from methyl vinyl ether-maleic anhydride copolymer and an isobutylene-maleic anhydride copolymer, the step of applying the first hydrogel layer And a step of irradiating the coated second polyvinyl alcohol aqueous solution with radiation in order to obtain a second hydrogel layer. The method for producing a hydrogel laminate according to claim 8, wherein the second polyvinyl alcohol aqueous solution is the same as or different from the first polyvinyl alcohol aqueous solution.

Images