Hydrogel and composition for hydrogel production

Abstract

To provide a hydrogel containing a polyphenol compound while having a sufficiently low content of residual monomers.SOLUTION: The present invention provides a hydrogel comprising a polymer matrix composed of a copolymer of a monofunctional monomer and a cross-linkable monomer, water, a polyhydric alcohol, and a polyphenol compound, where the polyhydric alcohol comprises linear and / or branched polyglycerine.SELECTED DRAWING: Figure 3

Description

[Technical field]

[0001] The present invention relates to a hydrogel and a composition for producing the hydrogel. [Background technology]

[0002] Polyphenol compounds have astringent and whitening properties, and when incorporated into a gel, a gel with skin conditioning properties is obtained. Polyphenol compounds are known to have an astringent effect that tightens the skin, as well as an antioxidant effect, and to have skin conditioning, skin protection, and whitening effects (Patent Document 1). For example, it has been reported that applying tannic acid, a type of polyphenol compound, to the skin suppresses the itching caused by atopic dermatitis (Non-Patent Document 1). By compounding a polyphenol compound with a hydrogel and applying it to the skin, it is expected that the effects of the polyphenol compound will be sustained while keeping the skin moist.

[0003] On the other hand, when a polyphenol compound is mixed with an aqueous solution of a monomer that constitutes the polymer matrix of a hydrogel and a hydrogel is produced by polymerization, the polymerization inhibitory effect of the polyphenol tends to leave unreacted monomers such as acrylamide that have skin irritation, limiting the use of the gel on the skin (Patent Document 2). This polymerization inhibitory effect of polyphenol is thought to be the result of the polyphenol compound releasing hydrogen radicals and terminating the radical chain reaction (Non-Patent Document 2).

[0004] It has been reported that mixing glycerin as a polymerization solvent reduces the inhibitory effect of polyphenol compounds and promotes polymerization (Non-Patent Document 3). In addition, a method has been reported in which a hydrogel that does not contain polyphenol compounds as a constituent is polymerized and then an aqueous solution of polyphenol compounds is absorbed (Non-Patent Document 4). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 2744572 [Patent Document 2] Patent No. 6663110 [Non-patent literature]

[0006] [Non-Patent Document 1] Journal of Investigative Dermatology (2010) 130, 1459-1463 [Non-Patent Document 2] Pharmacia, Vol. 36, No. 12, p. 1046 [Non-Patent Document 3] Macromolecular Bioscience (2022)22, 2100455 [Non-Patent Document 4] Macromolecules (2018)51,1696-1705 Summary of the Invention [Problem to be solved by the invention]

[0007] The gel of Non-Patent Document 3 still contains a large amount of residual monomers such as acrylamide, making it difficult to use on the skin. The manufacturing method of the gel of Non-Patent Document 4 increases the number of steps, making it complicated, and the gel becomes brittle due to swelling, making it less practical. An object of the present invention is to provide a hydrogel which contains a polyphenol compound and has a sufficiently small amount of residual monomers. [Means for solving the problem]

[0008] The present invention encompasses the embodiments described below. Section 1. A hydrogel comprising a polymer matrix made of a copolymer of a monofunctional monomer and a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol compound, A hydrogel, wherein the polyhydric alcohol comprises a linear and / or branched polyglycerol. Section 2. Item 2. The hydrogel according to item 1, wherein the degree of polymerization of the polyglycerin is 2 or more. Section 3. Item 3. The hydrogel according to item 1 or 2, wherein the monofunctional monomer is at least one selected from the group consisting of (meth)acrylamide-based monomers, (meth)acrylic acid ester-based monomers, and (meth)acrylic acid and / or a salt thereof. Section 4. Item 4. A gel sheet comprising the hydrogel according to any one of items 1 to 3. Section 5. Item 4. A biological electrode comprising the hydrogel according to any one of items 1 to 3. Section 6. 4. A medical external use material comprising a support and the hydrogel according to any one of items 1 to 3 provided on at least one surface of the support. Section 7. A composition for producing a hydrogel, comprising a monofunctional monomer, a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol, wherein the polyhydric alcohol comprises a linear and / or branched polyglycerin. [Brief description of the drawings]

[0009] [Figure 1] FIG. [Diagram 2] 1 is a schematic cross-sectional view of a medical topical agent applied to the skin. [Diagram 3] 1 is a graph showing the amount of residual monomer in each hydrogel of the Examples and Comparative Examples. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] As used herein, "(meth)acrylate" means acrylate and / or methacrylate, "(meth)acrylic acid" refers to acrylic acid and / or methacrylic acid, "(meth)acryloyl" refers to acryloyl and / or methacryloyl, and "(meth)acrylamide" refers to acrylamide and / or methacrylamide.

[0011] As used herein, a "sheet" refers to an article having a thickness of 200 μm or more, and a "film" refers to an article having a thickness of less than 200 μm.

[0012] In this specification, the term "comprise" is a concept that encompasses "consist essentially of" and "consist only of."

[0013] In the numerical ranges described in stages in this specification, the upper or lower limit of a certain numerical range can be arbitrarily combined with the upper or lower limit of another numerical range. In addition, in the numerical ranges described in this specification, the upper or lower limit of the numerical range may be replaced with a value shown in an example or a value that can be unambiguously derived from an example. Furthermore, in this specification, a numerical value connected with "~" means a numerical range that includes the numerical values ​​before and after "~" as the lower and upper limits.

[0014] Hereinafter, an embodiment of the present invention will be described in detail. <Hydrogel> According to one aspect of the present invention, there is provided a hydrogel comprising a polymer matrix composed of a copolymer of a monofunctional monomer and a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol, the polyhydric alcohol comprising a linear and / or branched polyglycerin. The hydrogel may be an adhesive hydrogel having adhesiveness to an adherend such as the skin.

[0015] (polymer matrix) First, the polymer matrix made of a copolymer of a monofunctional monomer and a crosslinkable monomer will be described. The monofunctional monomer can also be called a polymerizable monomer. The monofunctional monomer includes a monofunctional monomer having one ethylenically unsaturated group, and is not particularly limited. (Meth)acrylamide-based monomers, (meth)acrylic acid ester-based monomers, and (meth)acrylic acid or its salts are preferably used. These monofunctional monomers may be used alone or in combination of two or more.

[0016] Examples of (meth)acrylamide monomers include N,N-dialkyl(meth)acrylamides such as (meth)acrylamide, N,N-dimethyl(meth)acrylamide, and N,N-diethyl(meth)acrylamide; N-alkyl(meth)acrylamides such as N-isopropyl(meth)acrylamide, N-methyl(meth)acrylamide, N-ethyl(meth)acrylamide, and N-propyl(meth)acrylamide; N-hydroxyalkyl(meth)acrylamides such as N-hydroxyethyl(meth)acrylamide and N-hydroxymethyl(meth)acrylamide; cationic acrylamide compounds containing amino groups such as dimethylaminopropyl(meth)acrylamide; anionic monofunctional monomers containing sulfonic acid groups such as 4-acryloylmorpholine and tert-butylacrylamidosulfonic acid, or salts thereof; and derivatives thereof. These may be used alone or in combination of two or more.

[0017] Examples of the (meth)acrylic acid ester monomer include (meth)acrylic acid alkyl esters having an alkyl group with 1 to 18 carbon atoms, such as methyl (meth)acrylate, ethyl (meth)acrylate, n-propyl (meth)acrylate, isopropyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl (meth)acrylate, and tert-butyl (meth)acrylate; alkoxy group-containing (meth)acrylic acid esters such as 2-methoxyethyl (meth)acrylate, ethoxyethoxyethyl (meth)acrylate, and methoxypolyethylene glycol (meth)acrylate such as methoxytriethylene glycol (meth)acrylate; hydroxyalkyl (meth)acrylates (in which an aryl group may be bonded to the hydroxyalkyl group via an ether bond) such as 2-hydroxyethyl (meth)acrylate and 2-hydroxypropyl (meth)acrylate; glycerin mono(meth)acrylate; polyalkylene glycol mono(meth)acrylate such as polyethylene glycol mono(meth)acrylate and polyethylene glycol-polypropylene glycol copolymer; and (meth)acrylic acid esters having an aromatic ring such as benzyl (meth)acrylate. These may be used alone or in combination of two or more.

[0018] Examples of (meth)acrylic acid or a salt thereof include acrylic acid, methacrylic acid, sodium acrylate, potassium acrylate, potassium methacrylate, etc. These may be used alone or in combination of two or more.

[0019] The content of the structural unit derived from the monofunctional monomer in the hydrogel of the present invention is not particularly limited, but from the viewpoint of the shape retention and flexibility of the hydrogel, it is preferably within the range of 10 to 50 parts by mass, more preferably within the range of 15 to 45 parts by mass, relative to 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol, or relative to the total amount of the hydrogel. If the content is 10 parts by mass or more, the hydrogel has sufficient shape retention, which is preferable. Also, if the content is 50 parts by mass or less, there is little risk of the flexibility of the hydrogel being impaired.

[0020] The crosslinkable monomer is not particularly limited, but is preferably a compound having two or more polymerizable carbon-carbon double bonds in the molecule, such as divinylbenzene, divinyldiphenyl, N,N'-methylenebis(meth)acrylamide, ethylene glycol di(meth)acrylate, glycerin tri(meth)acrylate, polyethylene glycol di(meth)acrylate, polypropylene glycol di(meth)acrylate, polyglycerin di(meth)acrylate, etc. These may be used alone or in combination of two or more. In terms of high water solubility and formation of a uniform gel, the crosslinkable monomer preferably contains a diacrylamide derivative such as N,N'-methylenebis(meth)acrylamide. When the crosslinkable monomer contains a diacrylamide derivative, the amount of the diacrylamide derivative in the crosslinkable monomer is preferably 50% by mass or more, more preferably 60% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, or 100% by mass.

[0021] The content of the structural unit derived from the crosslinkable monomer in the hydrogel of the present invention is not particularly limited and varies depending on the type of monofunctional monomer and crosslinkable monomer used, but from the viewpoint of the shape stability and flexibility of the hydrogel, it is preferably within the range of 0.01 to 0.5 parts by mass, more preferably within the range of 0.01 to 0.1 parts by mass, relative to the total of 100 parts by mass of the polymer matrix, water, and polyhydric alcohol compound, or relative to the total amount of the hydrogel. If the content is 0.01 parts by mass or more, there is little concern about a decrease in shape stability due to low crosslink density. Also, if the content is 0.5 parts by mass or less, the gel is unlikely to become hard and brittle.

[0022] (water) The water content in the hydrogel of the present invention is not particularly limited, but in order to ensure suitable adhesive properties and electrical properties, it is preferably within the range of 10 to 60 parts by mass, more preferably 15 to 50 parts by mass, relative to the total 100 parts by mass of the polymer matrix, water, and polyhydric alcohol compound, or relative to the total amount of the hydrogel. When the water content is 10 parts by mass or more, the water content relative to the equilibrium water content of the hydrogel is not too low, and there is little risk of deterioration due to the hygroscopicity of the hydrogel. When the water content is 60 parts by mass or less, the water content relative to the equilibrium water content of the hydrogel is not too high, and there is little risk of deterioration due to drying of the hydrogel (for example, shrinkage, change in physical properties, etc.).

[0023] (Polyhydric alcohol) The polyhydric alcohol imparts moisture retention to the hydrogel, suppresses evaporation of water, and maintains the flexibility of the gel. The polyhydric alcohol contained in the hydrogel of the present invention includes linear polyglycerin, branched polyglycerin, or both.

[0024] In this specification, the term "linear polyglycerol" may also be referred to as glycerol having a linear structure, and includes, but is not limited to, polyglycerols that can be produced by a dehydration condensation reaction of glycerol or a polyaddition reaction of epichlorohydrin. An example of the linear polyglycerol is polyglycerol represented by the following formula (I). [ka] (n is an integer equal to or greater than 1.)

[0025] The degree of polymerization of the linear polyglycerol is not particularly limited, but is preferably 1-20, more preferably 2-10, and even more preferably 3-10. The number average molecular weight of the linear polyglycerol is preferably from 200 to 5,000 g / mol, and more preferably from 230 to 3,000 g / mol. The viscosity (40° C.) of the linear polyglycerol is preferably from 5,000 to 50,000 mPa·s, and more preferably from 8,000 to 30,000 mPa·s. The hydroxyl value of the linear polyglycerol is preferably from 500 to 2,000 KOHmg / g, and more preferably from 800 to 1,200 KOHmg / g.

[0026] As the linear polyglycerin, diglycerin, polyglycerin-3 (glycerin trimer), Unigly G series polyglycerin from NOF Corporation, polyglycerin from Sakamoto Yakuhin Kogyo Co., Ltd., and the like can be used.

[0027] The linear polyglycerol may be used alone or in combination of two or more kinds. When the hydrogel of the present invention contains linear polyglycerin, the content of linear polyglycerin in the hydrogel is preferably within the range of 5 to 80 parts by mass, more preferably within the range of 25 to 75 parts by mass, based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel, from the viewpoint of suppressing the residue of monomers such as acrylamide, which are components of the polymer matrix. If the content of linear polyglycerin is 20 parts by mass or more, it is preferable in that the residue of monomers, which are components of the polymer matrix, is more effectively suppressed. In addition, if the content is 80 parts by mass or less, it is preferable because the viscosity of the hydrogel composition is relatively low and easy to handle.

[0028] In this specification, "branched polyglycerol" can also be called glycerol having a branched structure, and means polyglycerol that can be produced by a polyaddition reaction of glycidol. An example of the branched polyglycerol is a branched polyglycerol represented by the following formula (II). Linear polyglycerols and modified products of linear polyglycerols (e.g., polyether-added (poly)glycerol, etc.) are not included in "branched polyglycerol". [ka]

[0029] In the branched polyglycerol, 50% or more of all the hydroxyl groups in the polyglycerol are preferably primary hydroxyl groups. The ratio of primary hydroxyl groups to all the hydroxyl groups contained in a specific compound is measured by a method for measuring nuclear magnetic resonance spectrum (NMR) for carbon atoms.

[0030] For example, the NMR spectrum for the carbon atoms of polyglycerol can be measured as follows. 500 mg of polyglycerin was dissolved in 2.8 mL of deuterium oxide, filtered, and then decoupled with a gate. 13 Obtain a C-NMR (125 MHz) spectrum. Note that the peak intensity indicates the presence of primary and secondary hydroxyl groups, which is proportional to the carbon number. 13 C chemical shifts are methylene carbons (CH 2 The peaks of the methine carbon (CHOH) are at around 63 ppm, and the methine carbon (CHOH) is at around 71 ppm. The abundance ratio of primary hydroxyl groups to secondary hydroxyl groups is calculated by analyzing the signal intensities of these groups. However, the methine carbon (CHOH) representing a secondary hydroxyl group overlaps with the peak of the methylene carbon adjacent to the methine carbon bonded to the methylene carbon representing the primary hydroxyl group, so the integral value of the methine carbon itself cannot be obtained. Therefore, the methylene carbon (CH 2 ) and calculate the integral value based on the signal intensity around 74 ppm.

[0031] The degree of polymerization of the branched polyglycerol is preferably 2 or more, more preferably 3 or more, more preferably 6 or more, even more preferably 10 or more, and particularly preferably 15 or more. A degree of polymerization of 3 or more is preferable in terms of the effect of suppressing polymerization inhibition. In addition, the upper limit of the degree of polymerization is not particularly limited, but is preferably 40 or less, more preferably 25 or less. In a preferred embodiment, the degree of polymerization of the branched polyglycerol is 6 to 40.

[0032] The number average molecular weight of the branched polyglycerol is preferably from 200 to 5,000 g / mol, and more preferably from 230 to 3,000 g / mol.

[0033] The viscosity (40° C.) of the branched polyglycerol is preferably from 5,000 to 50,000 mPa·s, and more preferably from 8,000 to 30,000 mPa·s.

[0034] The hydroxyl value of the branched polyglycerol is preferably 500 to 2,000 KOHmg / g, more preferably 800 to 1,200 KOHmg / g. The hydroxyl value can be calculated according to the 9th Edition of the Food Additives Standards "Testing Methods for Fats and Oils" or the Standard Fats and Oils Analysis Testing Method. The branched polyglycerol may be used alone or in combination of two or more kinds.

[0035] As the branched polyglycerol, the following products available from Daicel Corporation can be used. The viscosity is measured at 40° C. with an E-type viscometer at a rotation speed of 1 to 5 rpm depending on the viscosity.

[0036] Product name PGL03P: Number average molecular weight = 240 g / mol, viscosity (40°C) = 8,300 mPa·s, hydroxyl value = 1,100 to 1,200 KOHmg / g Product name PGL06: Number average molecular weight = 460g / mol, viscosity (40℃) = 23,000mPa·s, hydroxyl value = 900~1,000KOHmg / g Product name PGL10: Number average molecular weight = 660 g / mol, viscosity (40°C) = 27,900 mPa·s, hydroxyl value = 800-900 KOHmg / g Product name PGL10PSW: Number average molecular weight = 780 g / mol, viscosity (40°C) = 16,800 mPa·s, hydroxyl value = 805-855 KOHmg / g Product name PGL20PW: Number average molecular weight = 1,500 g / mol, viscosity (40°C) = 9,260 mPa·s, hydroxyl value = 695-755 KOHmg / g Product name PGLX: Number average molecular weight = 3,000 g / mol, Viscosity (40°C) = 8,500 mPa·s, Hydroxyl value = 675-715 KOHmg / g Product name PGLXPW: Number average molecular weight = 3,000 g / mol, Viscosity (40°C) = 19,800 mPa·s, Hydroxyl value = 650-750 KOHmg / g

[0037] When the hydrogel of the present invention contains a branched polyglycerin, the content of the branched polyglycerin in the hydrogel is not particularly limited, but from the viewpoint of suppressing the residue of monomers such as acrylamide, which are components of the polymer matrix, is preferably within the range of 5 to 80 parts by mass, more preferably within the range of 10 to 80 parts by mass, and more preferably within the range of 25 to 75 parts by mass, relative to the total amount of the polymer matrix, water, and polyhydric alcohol compound, which is 100 parts by mass in total, or relative to the total amount of the hydrogel. If the content of the branched polyglycerin is 5 parts by mass or more, it is preferable in that the residue of monomers, which are components of the polymer matrix, is more effectively suppressed. In addition, if the content is 80 parts by mass or less, it is preferable because the viscosity of the hydrogel composition is relatively low and easy to handle. From the viewpoint of suppressing the residue of monomers such as acrylamide, which are components of the polymer matrix, the total amount of linear and / or branched polyglycerol is preferably within a range of 5 to 80 parts by mass, more preferably within a range of 25 to 75 parts by mass, based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel.

[0038] In addition to the above, the polyhydric alcohol may further contain other polyhydric alcohols. As the other polyhydric alcohols, diols such as ethylene glycol, propylene glycol, butanediol, polyhydric alcohols such as glycerin, pentaerythritol, sorbitol, polyhydric alcohol condensates such as polyethylene glycol, polypropylene glycol, and polyhydric alcohol modified products such as polyoxyethylene glycerin can be used. These polyhydric alcohols may be used alone or in combination of two or more. The amount of the polyhydric alcohol other than linear and / or branched polyglycerol is preferably within a range of 0 to 60 parts by mass, more preferably within a range of 0 to 60 parts by mass, and more preferably within a range of 0 to 50 parts by mass, based on 100 parts by mass in total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel.

[0039] The total content of polyhydric alcohols in the hydrogel of the present invention (total content of linear polyglycerol, branched polyglycerol, and other polyhydric alcohols) is not particularly limited, but is preferably within the range of 30 to 80 parts by mass, more preferably within the range of 40 to 75 parts by mass, based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel. When the content of polyhydric alcohols is 30 parts by mass or more, the gel is less likely to dry, and the gel has good stability over time and flexibility, which is preferable. In addition, when the content is 80 parts by mass or less, bleeding out of polyhydric alcohols from the gel is suppressed, which is preferable. Alternatively, the total amount of polyhydric alcohols of the present invention is preferably within the range of 30 to 80% by mass, more preferably within the range of 40 to 75% by mass, based on the total amount of the hydrogel.

[0040] (Polyphenol compounds) In this specification, the polyphenol compound refers to a compound having multiple hydroxyl groups bonded to a benzene ring, and does not include the "polyhydric alcohol" used in the present invention.

[0041] Examples of polyphenol compounds include catechol, catechol derivatives (those in which a substituent other than hydrogen, such as an alkyl group, an aminoalkyl group, or a carboxyaminoalkyl group, is bonded to a carbon atom of the benzene ring other than the carbon to which the hydroxyl group of catechol is bonded, e.g., dopamine, 2,3-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, and 3,4-dihydroxyphenylalanine), gallic acid, gallic acid esters (propyl ester, isoamyl ester, octyl ester, dodecyl ester, and the like), pyrogallol, phloroglycine, catechin, epicatechin, gallocatechin, catechin gallate, gallocatechin gallate, and epicatechin gallate. Examples of tannins that may be used include, but are not limited to, epigallocatechin gallate, epigallocatechin, glucogallin, proanthocyanidin and its polymers, flavones (e.g., rutin, quercetin, quercetagin, quercetagetin, gossypetin, etc.), ellagic acid, penta-O-galloylglucose, tannic acid, gallotannin (tannin extracted from peony root), geraniin (tannins extracted from geranium herb, Mallotus japonicus, pomegranate skin, Chinese cornus, Japanese elm, etc.), condensed tannins (tannins extracted from persimmon tannin, cinnamon bark, ash tree, Japanese elm, etc.), tannins extracted from Quercus salicina bark, Quercus mizunara bark, and nuts of the same tree.

[0042] Tannic acid is not particularly limited, but examples thereof include hamameli tannin, persimmon tannin, tea tannin, Chinese gall tannin, gall tannin, myrobalan tannin, dividivi tannin, algarovilla tannin, valonia tannin, catechin tannin, etc. Tannic acid may be a single compound or a mixture of two or more compounds.

[0043] As the polyphenol compound, gallic acid esters and tannic acid are preferred, and tannic acid is more preferred.

[0044] The polyphenol compounds represented by the following formulas (1) to (6) are examples of the polyphenol compounds that can be used in the present invention. 1 , R 2 , R 3 , and R4 are each independently hydrogen or a hydrocarbon group having 1 to 8 carbon atoms. 1 , and R 2 are each independently hydrogen or a hydrocarbon group having 1 to 8 carbon atoms. 1 is hydroxy or OR 2 and R 2 is a hydrocarbon group having 1 to 15 carbon atoms, and in formula (6), R 1 , R 2 , and R 3 are each independently hydrogen, hydroxy, or a hydrocarbon group having 1 to 8 carbon atoms. In a preferred embodiment, each of the hydrocarbon groups in the formulas (1), (2), (4), and (6) is an alkyl group. The molecular weight of the condensed tannin of the formula (6) is, for example, 500 to 20,000. [ka]

[0045] The content of the polyphenol compound in the hydrogel of the present invention is not particularly limited, but is preferably within the range of 0.01 to 20 parts by mass, more preferably within the range of 0.1 to 10 parts by mass, and more preferably within the range of 1 to 5 parts by mass, based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel. If the content of the polyphenol compound is 0.1 parts by mass or more, it is preferable in terms of exerting the effects of the polyphenol compound, such as skin conditioning, skin protection, and / or skin whitening. In addition, if the content of the polyphenol compound is 20 parts by mass or less, it is preferable in terms of ease of production of the gel.

[0046] The polyphenol compounds in the hydrogel are not only dissolved in the hydrogel, but also bonded to the OH groups of the polyphenol compounds and the NH groups of the polymers that make up the gel. 2 This also includes polyphenols incorporated as part of the gel skeleton through hydrogen bonds with the groups.

[0047] Although the applicant does not wish to restrict the present invention to a specific hypothesis or theory, it is speculated that the mechanism by which linear and / or branched polyglycerol suppresses the inhibition of polymerization of monomers by polyphenol compounds is that the highly active phenolic OH group of polyphenol captures the radicals of the initiator to terminate the polymerization of monomers, while the OH group of polyglycerol forms a hydrogen bond with the OH group of polyphenol to cap the OH group of polyphenol, thereby suppressing the capture of radicals. Furthermore, since polyglycerol has more OH groups in one molecule than simple glycerol with a degree of polymerization of 1 and is structurally more likely to form associations, it is speculated that polyglycerol suppresses the inhibition of polymerization of monomers by polyphenol compounds more effectively than glycerol. In addition, even if the hydrogel-producing composition and hydrogel do not completely follow the above-mentioned mechanism, they are included within the technical scope of the present invention as long as they satisfy the requirements specified in the present invention.

[0048] (Water-soluble polymer) In order to enhance the adhesive strength, the hydrogel may contain an amphiphilic polymer such as polyacrylic acid and / or its salt, if necessary. Examples of such amphiphilic polymers include copolymers of acrylic acid and methacrylic acid, and polymers containing N-alkylsulfonic acid acrylamide as a structural unit. Any of these may be used alone, or multiple types may be used in combination.

[0049] (electrolyte) The hydrogel of the present invention may contain an electrolyte as necessary. By blending an electrolyte into the hydrogel, a conductive gel can be obtained. In addition, the addition of an electrolyte to the adhesive hydrogel improves ionic conductivity. The hydrogel to which conductivity has been imparted can be suitably used as a hydrogel for bioelectrodes such as an electrode for electrocardiogram measurement, an electrode for low-frequency therapeutic devices, and various earth electrodes. When used as such a hydrogel for bioelectrodes, the specific resistance of the hydrogel containing the electrolyte is preferably within the range of 0.01 to 100 kΩ·cm.

[0050] The electrolyte is not particularly limited, and examples thereof include alkali metal halides such as sodium halide (e.g., sodium chloride), lithium halide, and potassium halide; alkaline earth metal halides such as magnesium halide and calcium halide; other metal halides; hypochlorite, chlorite, chlorate, perchlorate, sulfate, carbonate, nitrate, and phosphate of various metals; inorganic salts such as ammonium salts and various complex salts; salts of monovalent organic carboxylic acids such as acetic acid, benzoic acid, and lactic acid; salts of polyvalent organic carboxylic acids such as tartaric acid; monovalent or divalent or higher salts of polyvalent carboxylic acids such as phthalic acid, succinic acid, adipic acid, and citric acid; metal salts of organic acids such as sulfonic acid and amino acids; organic ammonium salts; salts of polymer electrolytes with poly(meth)acrylic acid, polyvinylsulfonic acid, poly-tert-butylacrylamide sulfonic acid, polyallylamine, and polyethyleneimine;

[0051] The electrolyte may be a substance that is insoluble when the hydrogel is mixed, and dissolves in the hydrogel over time even if it is in a dispersed form during preparation of the mixed solution. Examples of such electrolytes include silicates, aluminates, metal oxides, hydroxides, etc. These may be used alone or in combination of two or more.

[0052] In the case of imparting electrical conductivity to the hydrogel of the present invention, the content of the electrolyte in the hydrogel is preferably within the range of 0.05 to 10 parts by mass, more preferably within the range of 0.1 to 5 parts by mass, based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel. A hydrogel containing water has inherent dielectric properties, and when combined with an electrode element to create an electrode, it has an electrical capacitance according to the thickness of the gel and the area of ​​the electrode element. However, the impedance (Z) of the electrode is greatly affected by the electrolyte concentration, particularly in the low-frequency region below 1 kHz. When the content of the electrolyte in the hydrogel is 0.001 parts by mass or more, the impedance can be reduced, making it suitable for electrical conductivity applications. Also, when the content is 10 parts by mass or less, the electrolyte can be dissolved uniformly in the hydrogel, and crystal precipitation inside the gel or inhibition of dissolution of other components is unlikely to occur.

[0053] The electrolyte may be used for purposes other than imparting electrical conductivity to the hydrogel. For example, an acid salt, a base salt, a polyfunctional salt, or a base such as sodium hydroxide may be added to adjust the pH of the hydrogel. The electrolyte may also be added to improve the moisture retention performance or impart antibacterial properties to the hydrogel.

[0054] (Other additives) The hydrogel may optionally contain other additives. Examples of other additives include preservatives, bactericides, antifungal agents, rust inhibitors, antioxidants, antifoaming agents, stabilizers, fragrances, surfactants, colorants, and medicinal ingredients (e.g., anti-inflammatory agents, vitamins, whitening agents, etc.). These additives may be used alone or in combination of two or more. These additives may be used within the range of 0.01 to 10 parts by mass based on 100 parts by mass of the total of the polymer matrix, water, and polyhydric alcohol compound, or based on the total amount of the hydrogel.

[0055] As described above, the hydrogel of the present invention uses linear and / or branched polyglycerin, which makes it possible to more effectively suppress the inhibitory effect of polyphenol compounds on monomer polymerization than conventional methods.

[0056] In the hydrogel of the present invention, the amount of unreacted residual monomer can be reduced. Among the monomers used in the hydrogel, the amount of crosslinkable monomer used is small and hardly remains, so the amount of unreacted residual monomer can be regarded as the total amount of unreacted monofunctional monomer. The amount of residual monomer in the hydrogel is not particularly limited, and the smaller the amount of residual monomer, the more preferable it is, for example, 1000 ppm or less, more preferably 500 ppm or less, more preferably 300 ppm or less, more preferably 100 ppm or less, more preferably 50 ppm or less.

[0057] The thickness of the hydrogel of the present invention is not particularly limited, but it may be in the form of a sheet having a thickness of 0.1 to 10 mm. The thickness is more preferably 0.3 to 5 mm. Such a sheet-shaped hydrogel having a thickness of 0.1 to 10 mm is excellent in flexibility and excellent in conformity to the surface of the skin of a living body.

[0058] <Hydrogel manufacturing method> The hydrogel of the present invention can be easily produced by a production method in which a hydrogel-producing composition containing a monofunctional monomer, a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol compound, the polyhydric alcohol containing at least one of a linear polyglycerin and a branched polyglycerin, is used to copolymerize the monofunctional monomer and the crosslinkable monomer in the hydrogel-producing composition. The hydrogel-producing composition can contain the above-mentioned water-soluble polymer, electrolyte, and / or various additives as necessary.

[0059] The hydrogel of the present invention can also be produced by a production method in which a polymer matrix formed in advance by, for example, polymerizing a monofunctional monomer and a crosslinkable monomer is impregnated with water, a polyhydric alcohol including linear and / or branched polyglycerol, and a polyphenol compound, and, as necessary, the above-mentioned water-soluble polymer, electrolyte, and / or various additives.

[0060] The polymerization of the monofunctional monomer and the crosslinkable monomer is preferably carried out in the presence of a polymerization initiator. For example, it is preferable to include a polymerization initiator in the composition for producing a hydrogel. The polymerization initiator is not particularly limited, and examples thereof include a thermal polymerization initiator and a photopolymerization initiator.

[0061] The thermal polymerization initiator is not particularly limited as long as it is cleaved by heat to generate radicals, and examples thereof include organic peroxides such as benzoyl peroxide; azo polymerization initiators such as azobiscyanovaleric acid, azobisisobutyronitrile, and azobisamidinopropane dihydrochloride; and persulfates such as potassium persulfate and ammonium persulfate. These thermal polymerization initiators may be used alone or in combination of two or more. If necessary, a redox initiator consisting of a reducing agent such as ferrous sulfate or pyrosulfite and a peroxide such as hydrogen peroxide, sodium thiosulfate, or peroxodisulfate may be used in combination with the thermal polymerization initiator.

[0062] The photopolymerization initiator is not particularly limited as long as it is cleaved by ultraviolet or visible light to generate radicals. Examples of the photopolymerization initiator include azo-based polymerization initiators such as 2,2'-azobis-N-(2-hydroxyethyl)propionamide and 2,2'-azobis(1-imino-1-pyrrolidino-2-methylpropane) dihydrochloride, α-hydroxyketones, α-aminoketones, benzyl methyl ketal, bisacylphosphine oxides, and metallocenes. More specifically, 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-propan-1-one (product name: Omnirad (registered trademark) 2959, manufactured by IGM Resins BV), 2-hydroxy-2-methyl-1-phenyl-propan-1-one (product name: Omnirad (registered trademark) 1173, manufactured by IGM Resins BV), and the like. BV), 1-hydroxy-cyclohexyl-phenyl-ketone (product name: Omnirad (registered trademark) 184, IGM Resins BV), 2-methyl-1-[(methylthio)phenyl]-2-morpholinopropan-1-one (product name: Omnirad (registered trademark) 907, IGM Resins BV), 2-benzyl-2-dimethylamino-1-(4-morpholinophenyl)-butan-1-one (product name: Omnirad (registered trademark) 369, IGM Resins BV). These photopolymerization initiators may be used alone or in combination of two or more.

[0063] The amount of the polymerization initiator used is preferably 0.01 to 1.0 parts by mass, more preferably 0.05 to 0.5 parts by mass, relative to 100 parts by mass of the total amount of the composition for producing a hydrogel (total amount of the obtained hydrogel). When the amount is 0.01 part by mass or more, the polymerization reaction proceeds sufficiently, and the amount of the monofunctional monomer and the crosslinkable monomer remaining in the obtained hydrogel can be reduced. When the amount is 1.0 part by mass or less, discoloration (yellowing) and odor caused by the polymerization initiator remaining in the obtained hydrogel can be prevented.

[0064] The method for polymerizing the monofunctional monomer and the crosslinkable monomer is not particularly limited, and examples thereof include a method of heating, irradiating, or irradiating a mixture (such as the above-mentioned hydrogel-producing composition) containing the monofunctional monomer and the crosslinkable monomer. Specifically, examples of the method include a method in which the mixture contains a thermal polymerization initiator as a polymerization initiator and polymerizes the monofunctional monomer and the crosslinkable monomer in the mixture by heating; a method in which the mixture contains a photopolymerization initiator as a polymerization initiator and polymerizes the monofunctional monomer and the crosslinkable monomer in the mixture by irradiating with light (ultraviolet or visible light); a method in which the mixture contains a thermal polymerization initiator and a photopolymerization initiator as polymerization initiators and polymerizes the monofunctional monomer and the crosslinkable monomer in the mixture by simultaneously irradiating with light and heating; and a method in which the mixture is irradiated with radiation such as an electron beam or gamma rays to polymerize the monofunctional monomer and the crosslinkable monomer in the mixture. In addition, when a redox initiator is used in combination as a thermal polymerization initiator, the reaction can be carried out without heating, but in order to reduce the amount of residual monomers or shorten the reaction time, it is preferable to heat the mixture even when a redox initiator is used in combination. As described above, it is also possible to irradiate the mixture with radiation to polymerize the monofunctional monomer and the crosslinkable monomer in the mixture, but since this requires special equipment for radiation irradiation, a method of heating or irradiating the mixture with light is preferable as a method of polymerizing the monofunctional monomer and the crosslinkable monomer in the mixture, and from the viewpoint of being able to obtain a gel with stable physical properties, a method of irradiating the mixture with light is more preferable.

[0065] When the mixture contains a photopolymerization initiator and is polymerized by ultraviolet irradiation, the cumulative dose of ultraviolet light is 1000 mJ / cm. 2 More preferably, it is equal to or greater than this. In addition, when producing the hydrogel of the present invention, the content of components other than the monofunctional monomer and the crosslinkable monomer (e.g., polyhydric alcohol, water, polyphenol compound, water-soluble polymer, electrolyte, other additives, etc.) relative to the total mass of the components used in producing the hydrogel (e.g., monofunctional monomer, crosslinkable monomer, polyhydric alcohol, water, polyphenol compound, water-soluble polymer, electrolyte, other additives, etc.) (or the total mass of the composition for producing the hydrogel) is equal to the content of components other than the structural units derived from the monofunctional monomer and crosslinkable monomer in the hydrogel of the present invention. In addition, the content of the monofunctional monomer and the crosslinkable monomer relative to the total mass of the components used in producing the hydrogel (or the total mass of the composition for producing the hydrogel) is equal to the content of the structural units derived from the monofunctional monomer and the crosslinkable monomer in the hydrogel of the present invention. For example, the content of the monofunctional monomer in the composition for producing the hydrogel is equal to the content of the structural units derived from the monofunctional monomer in the hydrogel of the present invention. The content of the crosslinkable monomer in the hydrogel-producing composition is equal to the content of the structural unit derived from the crosslinkable monomer in the hydrogel of the present invention. Furthermore, the total content of the monofunctional monomer and the crosslinkable monomer in the hydrogel-producing composition is equal to the content of the polymer matrix in the hydrogel of the present invention.

[0066] <Hydrogel sheet> The hydrogel of the present invention is prepared, for example, by gelling a liquid hydrogel-producing composition through polymerization and crosslinking, and therefore can be appropriately shaped according to the intended use.

[0067] 1 shows a cross section of one embodiment of a gel sheet containing a hydrogel according to the present invention. In the gel sheet 1 of this embodiment, a base film 3 and a top film 4 for protecting the hydrogel 2 are laminated on both sides of a sheet-like hydrogel 2. The thickness of the hydrogel 2 can be appropriately set depending on the application of the gel sheet 1, but for example, when the gel sheet 1 is used by adhering it to a living body, the thickness of the hydrogel 2 is preferably set within the range of 0.01 mm to 2.0 mm.

[0068] As the base film 3, for example, a resin film made of a resin such as polyester (e.g., polyethylene terephthalate (PET)), polyolefin (e.g., polypropylene), polystyrene, polyurethane, or the like, paper, or paper laminated with a resin film can be used. The surface of the base film 3 that comes into contact with the hydrogel 2 is preferably subjected to a release treatment such as silicone coating. That is, when the base film 3 is used as a release paper, a film obtained by subjecting the surface of a resin film made of a resin (e.g., polyester, polyolefin, polystyrene, or the like), paper, or paper laminated with the resin film to a release treatment can be suitably used as the base film 3. A biaxially oriented PET film, a biaxially oriented polypropylene (OPP) film, or the like is particularly preferred as the base film to be subjected to the release treatment. As a method of release treatment, silicone coating can be mentioned, and in particular, a baked-on silicone coating that crosslinks and hardens with heat or ultraviolet light is preferred.

[0069] Although it is possible to use a film made of the same material as the base film 3 as the top film 4, it is preferable to select a film made of a material that does not block light so as not to interfere with photopolymerization. Also, it is preferable not to use a film used as a backing material (lining material) as the top film 4. In particular, if there is a possibility that the film used as the backing material may deteriorate due to exposure to ultraviolet rays or the like, using the film used as the backing material as the top film 4 is not preferable, because the film used as the backing material will be located on the side directly exposed to ultraviolet rays.

[0070] In this embodiment, an intermediate substrate 5 made of woven or nonwoven fabric is embedded along the surface direction of the hydrogel 2 in order to improve the tear strength and handling of the hydrogel 2. The material of the woven or nonwoven fabric may be natural fibers such as cellulose, silk, or hemp, or synthetic fibers such as polyester, nylon, rayon, polyethylene, polypropylene, or polyurethane, or a blend of these fibers, and a binder may be used as necessary, and the material may be colored as necessary. The intermediate substrate 5 may be omitted.

[0071] The manufacturing method of the nonwoven fabric is not particularly limited, but examples thereof include a dry method, a wet method, a spunbond method, a meltblown method, an airlaid method, a chemical bond method, a thermal bond method, a needle punch method, and a hydroentanglement method. It is more preferable to adopt a manufacturing method according to the basis weight and material, and to have no unevenness in the basis weight, in order to control the position of the intermediate substrate 40. The woven fabric is also not particularly limited, and can be selected as appropriate, such as plain weave, tricot, or raschel.

[0072] The basis weight of the woven or nonwoven fabric is not particularly limited as long as it is a basis weight that can provide the desired physical properties as the intermediate substrate 5. For example, it is 10 to 40 g / m 2 It is preferable that the range is 10 to 28 g / m 2 It is more preferable that the basis weight is 10 g / m 2 If the weight is 40 g / m or more, the hydrogel 2 can be sufficiently reinforced, and unevenness in the weight per unit area is suppressed, so that the penetration of the liquid during the production of the hydrogel 2 becomes uniform, and the positional fluctuation of the intermediate substrate 5 is suppressed, which is preferable. 2 If the thickness is less than this, the intermediate base material 5 does not become too hard, and the hydrogel 2 has good conformability to the skin, which is preferable.

[0073] The thickness of the intermediate substrate 5 is preferably within a range of 0.05 to 2.0 mm. Also, 0.05 to 0.5 mm is more preferable, and 0.08 to 0.3 mm is particularly preferable. If it is 0.05 mm or more, the hydrogel 2 can be sufficiently reinforced and unevenness in basis weight is suppressed, so that the penetration of the liquid during the production of the hydrogel 2 becomes uniform and the positional fluctuation of the intermediate substrate 5 is suppressed, which is preferable. If it is 2.0 mm or less, the penetration of the liquid becomes good, which is preferable.

[0074] The method for producing the gel sheet 1 is not particularly limited, and the conditions vary depending on the composition of the hydrogel 2, the material and thickness of the intermediate substrate 5, etc. For example, a method in which the intermediate substrate 5 is held on the upper side of the base film 3 while a certain tension is applied to the intermediate substrate 5, a gel composition containing a mixture of the various components is poured onto the upper and lower sides of the intermediate substrate 5, a top film 4 is placed on top of the intermediate substrate 5, and the hydrogel 2 is crosslinked and cured by light irradiation and / or heat to obtain the gel sheet 1, a method in which two hydrogels with smooth surfaces are produced, and then the intermediate substrate 5 held under a certain tension is sandwiched between these hydrogels, and the base film 3 and the top film 4 are further laminated on both sides to obtain the gel sheet 1, and the like can be appropriately adopted.

[0075] <Uses of hydrogel> The hydrogel of the present invention as described above can provide the skin conditioning, skin protection, and / or whitening effects of polyphenol compounds to the skin, and can therefore be suitably used as a gel member to be attached to the surface of a living body in a living body electrode, or as a hydrogel for medical external materials to be attached to a living body, such as various adhesive tapes and wound dressings.

[0076] (Bioelectrodes) According to one aspect of the present invention, a biological electrode containing the hydrogel is provided. The biological electrode may be an electrode in which the hydrogel and an electrode made of a conductive material are laminated. The electrode may contain a conductive material. Examples of such materials include metals such as aluminum, stainless steel, copper, platinum, silver, a silver-silver chloride complex, gold, tin, titanium, nickel, and molybdenum, conductive carbon materials such as carbon black and graphite, and mixtures thereof.

[0077] The biological electrode of this embodiment can be used as a bioelectric potential measurement electrode used for electrocardiograms, electroencephalograms, nystagmus, electromyograms, etc., an electrical stimulation electrode used for transcutaneous electrical stimulation therapy (TENS), low-frequency treatment, etc., a counter electrode for an electric scalpel, an electrode for iontophoresis, or other medical electrodes.

[0078] (Medical topical materials) According to one aspect of the present invention, there is provided a medical topical material comprising a support and the above-mentioned hydrogel provided on at least one surface of the support. The medical topical material of this embodiment is produced by (i) applying the above-mentioned hydrogel-producing composition to one or both sides of a support and polymerizing and crosslinking the composition, (ii) directly attaching the above-mentioned hydrogel to one or both sides of a support, (iii) applying the hydrogel-producing composition onto release paper, polymerizing and crosslinking the composition, and attaching the composition to a support, or (iv) attaching the hydrogel attached to the release paper to a support. The hydrogel may be in the form of a sheet.

[0079] The support is not particularly limited as long as it is capable of holding the hydrogel. Specific examples include film or sheet-like supports used in bandages, adhesive dressings, or poultices, and these may be porous or non-porous.

[0080] The raw material of the support may be, for example, polyurethane, polyethylene, ethylene-vinyl acetate copolymer, ethylene-acrylic acid ester copolymer, polyvinyl chloride, unplasticized soft polyvinyl chloride (e.g., internal copolymer or blend system), polypropylene, nylon, polyester, silicone rubber, foamed polyethylene, foamed polyurethane, foamed ethylene-vinyl acetate copolymer, or other synthetic resin, or metals such as aluminum and copper, formed into a film or sheet. In addition, paper, nonwoven fabric, woven fabric, mesh fabric, or the like made of natural or synthetic fibers (e.g., regenerated cellulose (e.g., rayon), cellulose ester, or the like) may also be used, and a breathable or non-breathable substrate may be appropriately selected depending on the purpose. In addition, the above-mentioned films, metal films or sheets, woven fabric, or the like may be appropriately combined and laminated to form a laminate support. For example, examples of laminate supports include, but are not limited to, polyethylene-rayon laminated paper, PET and aluminum laminate, polyurethane and rayon laminate, and the like.

[0081] The thickness of the support which is a film or sheet (the total thickness in the case of a laminate) is not particularly limited, but can be, for example, 5 to 300 μm, and preferably 10 to 100 μm.

[0082] A surface treatment layer may be provided between the support and the hydrogel in order to enhance the adhesion between the support and the hydrogel. Specific examples of the surface treatment layer include physical surface treatments such as corona discharge treatment, plasma treatment, ozone treatment, ultraviolet irradiation treatment, and flame treatment, and surface treatments using coating agents such as silane coupling treatment, anchor coat, and primer coat, or combinations of these.

[0083] The surface of the support is subjected to a surface treatment, and the composition for producing a hydrogel is directly applied onto the resulting surface treatment layer and polymerized, thereby firmly adhering the support and the hydrogel. By providing a support to the medical topical material, the medical topical material can be used as a surgical tape.

[0084] An example of a medical topical material is shown in Figure 2. The medical topical material 6 comprises a support 7 and a hydrogel 8 provided in contact with one side of the support 7. The side of the hydrogel 8 opposite to the side in contact with the support 7 is attached to the skin 9 of a user of the medical topical material 6. As described above, a surface treatment layer may be provided between the support 7 and the hydrogel 8.

[0085] The hydrogels and medical topical materials of the above-mentioned embodiments can be suitably used as adhesives that are attached to the living body, such as surgical tapes to be attached to the living body, tapes for fixing catheters and infusion tubes / electrocardiogram electrodes / other sensors, poultices, wound dressings, tapes for fixing artificial anuses, etc., adhesives for fixing leads for electric therapy devices / magnetic therapy devices, and carrier / adhesive materials for transdermal absorption agents, or industrial adhesives for building materials / electronic materials, etc.

[0086] The disclosures of all patent applications and publications cited herein are hereby incorporated by reference in their entireties. The following examples are intended for illustrative purposes only and are not intended to limit the scope of the present invention in any way. Unless otherwise specified, reagents are commercially available or are obtained or prepared according to conventional techniques or procedures known in the art. EXAMPLES

[0087] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these. 1.Materials used MBAA: N,N'-methylenebisacrylamide PGL 06: Polyglycerin with branched structure, manufactured by Daicel Corporation, degree of polymerization 6, purity 100% PGL 10PSW R: Polyglycerin with branched structure, manufactured by Daicel Corporation, degree of polymerization 10, purity 95% PGL X: Polyglycerin with branched structure, manufactured by Daicel Corporation, degree of polymerization 40, purity 90% Diglycerin: Linear polyglycerin, manufactured by Sakamoto Pharmaceutical Co., Ltd., degree of polymerization 2, purity 95% PGL-S: Linear polyglycerin, manufactured by Sakamoto Pharmaceutical Co., Ltd., degree of polymerization 3, purity 100% Unigly G-6: Linear polyglycerin, NOF Corp., polymerization degree 6, purity 90% Polyglycerin #750: Linear polyglycerin, Polyglycerin #750, Sakamoto Pharmaceutical Co., Ltd., polymerization degree 10, purity 90% Glycerin 100% pure Omnirad 2959: Photoinitiator, 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-propan-1-one, IGM Resins BV Omnirad 1173: Photoinitiator, 2-hydroxy-2-methyl-1-phenylpropan-1-one

[0088] 2. Preparation of Gel Examples 1 to 15, Comparative Examples 1 to 2 Gels were produced using the compositions shown in Tables 1 and 2 according to the following procedure. Acrylamide or acrylic acid as a polymerizable monomer, N,N'-methylenebisacrylamide (MBAA) as a crosslinkable monomer, tannic acid (Fuji Chemical Industry Co., Ltd., product conforming to the Japanese Pharmacopoeia standard) as a polyphenol compound, glycerin or polyglycerin as a polyhydric alcohol, and water as a solvent were added to a plastic container, dissolved and stirred to obtain a composition for producing a hydrogel. Next, 1-[4-(2-hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-propan-1-one (manufactured by IGM Resins BV under the trade name Omnirad2959) or 2-hydroxy-2-methyl-1-phenylpropan-1-one (manufactured by IGM Resins BV under the trade name Omnirad1173) as a photopolymerization initiator was added to the mixture, and further dissolved by stirring. Next, the composition was poured into a silicone rubber mold (70 mm x 100 mm, thickness 1.0 mm) on a 30 μm thick biaxially oriented polyester film that had been siliconized and placed on glass, and then a 38 μm thick biaxially oriented polyester film that had been siliconized was placed on the mold so as to prevent air bubbles from being trapped, and then a quartz glass was placed on top to control the thickness. This was used for a peak intensity of 95 mW / cm 2 The gel was then irradiated with ultraviolet light from a UV lamp for 60 seconds, and removed from the mold to prepare a sample.

[0089] 3. Residual monomer amount measurement The amount of residual monomer in each of the samples obtained in the Examples and Comparative Examples was measured by the following method. The measurement results are shown in Tables 1 and 2. (1) Measurement of acrylamide monomer The measurement of residual acrylamide monomer was carried out as follows. Approximately 0.1 g of the sample was placed in a 10 mL centrifuge tube and weighed out. 3 PO 410 mL of aqueous solution / ethanol mixture (mixing volume ratio 9 / 1) was added using a whole pipette. After shaking well by hand, the mixture was left at room temperature for 24 hours to perform extraction. The centrifuge tube was then set in a tabletop centrifuge Model 4000 manufactured by Kubota Manufacturing Co., Ltd. and centrifuged for 20 minutes at a rotation speed of 3,000 rpm. The supernatant after centrifugation was filtered through a 0.45 μm aqueous chromatographic disk manufactured by GL Sciences Inc. and measured by high performance liquid chromatograph. The measurement conditions were as follows. Quantitative analysis was performed using the acrylamide monomer peak area from the obtained chromatogram. A calibration curve prepared in advance was used for quantification. Measurement equipment: Shimadzu Corporation HPLC LC-10A VP high performance liquid chromatograph Analytical column: Tosoh Corporation TSKgel-SCX 5μm (6.0mm ID1×150mm) Column temperature: 40℃ Pump and inlet temperature: Room temperature Sample injection volume: 20μL Mobile phase: 10mM H 3 PO 4 / Ethanol = 90 / 10 Flow rate: 1.0mL / min Detector wavelength: 210nm Analysis time: 7 minutes (2) Measurement of acrylic acid monomer The measurement of residual acrylic acid monomer was carried out as follows. Approximately 0.1 g of the sample was placed in a 10 mL centrifuge tube and weighed accurately. 10 mL of a 0.05% trifluoroacetic acid / acetonitrile mixture (mixed volume ratio 95 / 5) was poured into the centrifuge tube using a whole pipette. After shaking well by hand, the tube was left at room temperature for 24 hours to perform extraction. The centrifuge tube was then set in a tabletop centrifuge Model 4000 manufactured by Kubota Manufacturing Co., Ltd. and centrifuged for 20 minutes at a rotation speed of 3,000 rpm. The supernatant after centrifugation was filtered through a 0.45 μm aqueous chromatographic disk manufactured by GL Sciences Inc. and measured by a high-performance liquid chromatograph. The measurement conditions were as follows. Quantitative analysis was carried out using the acrylic acid monomer peak area from the obtained chromatogram. A calibration curve prepared in advance was used for quantitative analysis. Measurement equipment: Shimadzu Corporation HPLC LC-10A VP high performance liquid chromatograph Analytical column: Tosoh Corporation TSKgel ODS-80TSQA 5μm (4.6mm ID1×250mm) Column temperature: 40℃ Pump and inlet temperature: Room temperature Sample injection volume: 30 μL Mobile phase: 0.05% trifluoroacetic acid / acetonitrile = 95 / 5 Flow rate: 1.1mL / min Detector wavelength: 210nm Analysis time: 10 minutes

[0090] 4.Results In the sample of Example 1, the amount of residual acrylamide was as low as 60 ppm, whereas in the sample of Comparative Example 1, the amount of residual acrylamide was as high as 4400 ppm. In the sample of Example 3, in which the degree of polymerization of the branched polyglycerin was 40, the amount of residual acrylamide was even lower than that of the sample of Example 1. In the samples of Examples 4-7, which contain linear polyglycerin, the amount of residual acrylamide was the lowest when the degree of polymerization was 3, and when the degree of polymerization was higher than 3, the amount of residual acrylamide tended to increase as the degree of polymerization increased. In a comparison between Example 8 and Comparative Example 2, in which acrylic acid was used as the polymerizable monomer, the amount of residual acrylic acid in the gel of Example 8 was lower than that of Comparative Example 2. In comparison with the sample of Example 2, the samples of Examples 9-11 tended to have a higher amount of residual acrylamide as the amount of branched polyglycerin decreased. In comparison with the sample of Example 5, the samples of Examples 12 and 13 tended to have a higher amount of residual acrylamide as the amount of linear polyglycerin decreased. In Example 14, which contained a larger amount of tannic acid than the sample of Example 2, the amount of residual acrylamide was larger. [Explanation of symbols]

[0091] 1. Gel sheet 2. Hydrogel 3. Base film 4. Top film 5...Intermediate substrate 6. Medical topical materials 7...Support 8...Hydrogel for adhesives 9…Skin

[0092] [Table 1]

[0093] [Table 2]

Claims

1. A hydrogel comprising a polymer matrix made of a copolymer of a monofunctional monomer and a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol compound, A hydrogel, wherein the polyhydric alcohol comprises linear and / or branched polyglycerol.

2. The hydrogel according to claim 1 , wherein the degree of polymerization of the polyglycerin is 2 or more.

3. The hydrogel according to claim 1, wherein the monofunctional monomer is at least one selected from the group consisting of (meth)acrylamide-based monomers, (meth)acrylic acid ester-based monomers, and (meth)acrylic acid and / or a salt thereof.

4. A gel sheet comprising the hydrogel according to any one of claims 1 to 3.

5. A biological electrode comprising the hydrogel according to any one of claims 1 to 3.

6. A medical external use material comprising a support and the hydrogel according to any one of claims 1 to 3 provided on at least one surface of the support.

7. A composition for producing a hydrogel, comprising a monofunctional monomer, a crosslinkable monomer, water, a polyhydric alcohol, and a polyphenol, wherein the polyhydric alcohol comprises a linear and / or branched polyglycerin.

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