JP2006321792A - Water-bearing gel and its production method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a water-bearing gel characterized by good feeling of use thanks to low tackiness to an object, low irritation to skin, no free-liquid formation, simple composition and easy preparation. <P>SOLUTION: The invention provides (1) a composition for use in a water-bearing gel containing as its main components at least one compound (A) selected from the group consisting of a compound having a monovalent metal ion and a compound having a divalent metal ion, a (meth)acrylic polymer (B), water (C) and a cross-linking agent (D) reactive with a carboxy group, (2) the water-bearing gel obtainable from the composition, (3) a production method of the water-bearing gel and (4) a percutaneous absorption agent, a cooling sheet and cosmetics having the water-bearing gel. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a hydrogel body used for transdermally absorbable preparations, cosmetics, cooling sheets and the like, and a method for producing the same. More specifically, the present invention relates to a highly safe water-containing gel body having a very good usability because the tackiness is reduced by using a (meth) acrylic acid polymer, its production method and use.

  In recent years, water-containing gel bodies using acrylic polymers have been frequently used in percutaneous absorption preparations, cooling sheets, cosmetics and the like for medical use. Since generally used acrylic acid polymers have a high molecular weight, a gel body having elasticity and shape retention can be produced by using a carboxyl group as a crosslinking point and crosslinking with aluminum ions. However, since the acrylic acid-based polymer exhibits tackiness when dissolved in water, it causes stickiness more than necessary, and the usability is poor.

  On the other hand, when other water-soluble polymers are used, gels with extremely little tackiness (for example, agar) (Japanese Patent Laid-Open No. 2001-096145; Patent Document 1) can be used, and a conventional crosslinking system using an aluminum compound can be used. There were disadvantages such as not. Therefore, there has been a demand for a water-containing gel body having a reduced adhesiveness using a (meth) acrylic acid polymer that can use the same crosslinking system as that of the prior art.

JP 2001-096145 A

  The present invention solves the above-mentioned problems of the prior art, has a low adhesiveness to the adherend, good usability, little irritation to the skin, and does not produce a separating liquid, and is adjusted with a simple composition. Is to provide a water-containing gel body.

  In view of such circumstances, the present inventors use a polyacrylic acid partial neutralized product (acrylic acid-acrylate copolymer) or a polyacrylate, and a method for producing a hydrogel body with reduced adhesive strength. Was examined.

  First, a crosslinking agent was added to the acrylic acid-acrylate copolymer or polyacrylate at a high concentration. However, when crosslinked with a water-soluble epoxy compound or aluminum ions, the gel strength is not stable and unstable, or the gel body becomes turbid, resulting in poor transparency. In particular, a water-soluble epoxy compound is used as a crosslinking agent. If there was, there was concern about the effects of irritation on the skin caused by the residue.

  Next, the system is acidified, the polyacrylic acid partial neutralized product (acrylic acid-acrylate copolymer) or the dissociation of the salt in the polyacrylate is suppressed, and the polymer is shrunk to reduce the adhesiveness. Tried. Adhesion was certainly reduced by using this method, but a separating solution was produced over time, and in some cases, the pH of the gel body was remarkably lowered, which is a safety issue for applications applied to the human body. Occurred.

  Therefore, the present inventors added a compound containing a monovalent metal ion to a composition containing a (meth) acrylic acid polymer, and the metal ion contained therein contained a carboxyl of the (meth) acrylic acid polymer. The present invention was completed by finding that a water-containing gel showing excellent water retention ability can be produced by blocking the dissociation of the carboxyl group by ion-blocking the group, resulting in agglomeration (shrinking) of the polymer, and reduced adhesiveness. .

Since the gel body with reduced adhesiveness obtained by the present invention has excellent properties, it can be applied to various uses as described below.
(I) Pharmaceuticals: For example, transdermal absorption preparations, transmucosal absorption preparations, and the like.
(II) Medical device: For example, a cooling agent for the affected area at the time of fever, a wound healing agent, a therapeutic pad, a liquid absorbent for surgery, a dressing tape, a burn healing agent, and the like.
(III) Cosmetics, quasi drugs: for example, packs, suntan products, acne products, etc.

（式中、Ｒ¹及びＲ²はそれぞれ独立して水素原子またはメチル基を表し、ＭはＮＨ₄ ⁺またはアルカリ金属を表し、Ｘは不飽和単量体由来の２価の有機基を表す。）で示され、（１）／（２）＝１００／０〜０／１００（モル比）、かつ（１）及び（２）の総量／（３）＝１００／０〜１０／９０（モル比）である前記１に記載の含水ゲル体用組成物。
３．Ｍがナトリウムであり、前記繰り返し単位（１）及び（２）が、（１）／（２）＝０／１００〜１００／０（モル比）の範囲であり、前記繰り返し単位（３）を含まない前記２に記載の含水ゲル体用組成物。
４．１価の金属イオンを含有する化合物が塩化ナトリウムである前記１に記載の含水ゲル体用組成物。
５．さらに、多価アルコール（Ｅ）を含む前記１に記載の含水ゲル体用組成物。
６．前記カルボキシル基と反応する架橋剤（Ｄ）がアルミニウム化合物である前記１に記載の含水ゲル体用組成物。
７．（メタ）アクリル酸系重合体（Ｂ）がアクリル酸ナトリウム−Ｎ−ビニルアセトアミド共重合体である前記２に記載の含水ゲル体用組成物。
８．前記１〜７のいずれかに記載の含水ゲル体用組成物を用いて得られる含水ゲル体。
９．前記含水ゲル体中に含まれる水の含有量が５〜９８質量％である前記８に記載の含水ゲル体。
１０．前記１〜７のいずれかに記載の含水ゲル体用組成物を室温下に架橋させることを特徴とする含水ゲル体の製造方法。
１１．前記８または９に記載の含水ゲル体を用いた経皮吸収製剤。
１２．前記８または９に記載の含水ゲル体を用いた冷却シート。
１３．前記８または９に記載の含水ゲル体を用いた化粧料。 The present invention provides the following composition for a hydrogel body, a gel body, a percutaneous absorption preparation using the gel body, a cooling sheet, and a cosmetic.
1. At least one compound (A) selected from the group consisting of a compound containing a valent metal ion and a compound containing a divalent metal ion, a (meth) acrylic acid polymer (B), water ( C) and a crosslinking agent (D) that reacts with a carboxyl group.
2. The repeating unit of the (meth) acrylic acid polymer (B) has the general formulas (1), (2) and (3).

(In the formula, R ¹ and R ² each independently represents a hydrogen atom or a methyl group, M represents NH ₄ ⁺ or an alkali metal, and X represents a divalent organic group derived from an unsaturated monomer. ), (1) / (2) = 100/0 to 0/100 (molar ratio), and the total amount of (1) and (2) / (3) = 100/0 to 10/90 (molar ratio) 2) The composition for a hydrogel body according to 1 above.
3. M is sodium, the repeating units (1) and (2) are in the range of (1) / (2) = 0/100 to 100/0 (molar ratio), and include the repeating unit (3) 3. The composition for a hydrogel body according to 2 above.
4. The composition for a hydrogel body according to 1 above, wherein the compound containing a monovalent metal ion is sodium chloride.
5. Furthermore, the composition for hydrogel bodies of said 1 containing a polyhydric alcohol (E).
6). 2. The composition for hydrogel bodies according to 1 above, wherein the crosslinking agent (D) that reacts with the carboxyl group is an aluminum compound.
7). 3. The hydrogel composition according to 2, wherein the (meth) acrylic acid polymer (B) is a sodium acrylate-N-vinylacetamide copolymer.
8). A hydrogel body obtained using the composition for hydrogel bodies according to any one of 1 to 7 above.
9. The water-containing gel body according to 8, wherein the water-containing gel body contains 5 to 98% by mass of water.
10. A method for producing a water-containing gel, comprising cross-linking the composition for water-containing gel according to any one of 1 to 7 at room temperature.
11. A transdermally absorbable preparation using the hydrogel as described in 8 or 9 above.
12 10. A cooling sheet using the hydrogel body according to 8 or 9 above.
13. A cosmetic using the hydrogel body according to 8 or 9 above.

  The hydrogel body of the present invention has solved the problems of the prior art. The hydrogel body of the present invention has low adhesiveness to the adherend, good usability, little irritation to the skin, no separation liquid, simple composition, and easy adjustment.

  The composition for hydrogel bodies of the present invention comprises at least one compound (A) selected from the group consisting of compounds containing monovalent metal ions and / or divalent metal ions, (meth) acrylic acid heavy It is a composition for hydrous gel bodies composed mainly of a union (B), water (C) and a crosslinking agent (D) that reacts with a carboxyl group.

  The compound (A) containing a monovalent metal ion and / or a divalent metal ion used in the present invention is 0.001 to 10% by mass (hereinafter simply referred to as%) with respect to the total amount of the composition containing the components A to D. It is preferable to use within the range of 0.01) to 5%. If it is less than 0.001%, the gel body becomes highly sticky and the feeling of use may be deteriorated. On the other hand, if it exceeds 10%, the polymer is excessively aggregated, and as a result, a separating solution from the gel body may be formed, or the adhesiveness may become extremely low and the adhesion to the skin may be extremely inferior.

  Compounds containing monovalent metal ions include lithium, lithium oxide, butyl lithium, ethyl lithium, lithium bromide, lithium carbide, lithium iodide, lithium nitrate, lithium nitride, lithium sulfide, methyl lithium , Lithium sulfate, lithium chloride, lithium hydride, propyl lithium, lithium carbonate, lithium fluoride, lithium niobate, lithium peroxide, lithium hydroxide, lithium molybdate, lithium perchlorate, lithium acetate, lithium formate, tungstic acid Lithium, lithium hypochlorite, lithium acetate dihydrate, lithium iodide dihydrate, lithium hydrogen sulfate, lithium acetate dihydrate, lithium bromide monohydrate, lithium sulfate monohydrate, carbonic acid Dilithium, dilithium oxalate, dilithium sulfate, chromate Um dihydrate, lithium hydroxide monohydrate, lithium citrate tetrahydrate, lithium trihydrate perchlorate, and the like lithium hexafluorophosphate.

  In addition, sodium amide, sodium oxide, sodium azide, sodium acetate, sodium acetylide, sodium bromide, sodium formate, sodium iodide, sodium lactate, sodium methoxide, sodium nitrate, sodium sulfate, sulfide Sodium, sodium borate, metallic sodium, sodium bromate, sodium chloride, sodium hydride, sodium nitrite, sodium sulfite, sodium iodate, sodium phosphate, ecabet sodium, sodium butyrate, heparin sodium, sodium chlorate, citric acid Sodium oxide, sodium cyanate, sodium cyanide, sodium fluoride, sodium oleate, sodium oxalate, sodium peroxide, sodium silicate, sodium stannate Sodium, sodium-t-butoxide, sodium carbonate, suramin sodium, sodium benzoate, sodium chlorite, sodium chromate, sodium hydroxide, sodium selenate, sodium selenide, sodium laurate, inosinic acid (hereinafter referred to as IMP and Abbreviated.) Disodium, sodium alginate, sodium perborate, sodium persulfate, sodium phosphite, sodium rhodanide, disodium arsenate, sodium selenite, sodium ampenac, sodium tolmetine, sodium pyruvate, sodium saccharin , Sodium aluminate, sodium gluconate, sodium polysulfide, sodium stearate, sodium valproate, sodium iopodate, sodium bicarbonate, disodium carbonate, periodate Sodium, leviparin sodium, porfimer sodium, carmonam sodium, cefminox sodium, flomoxef sodium, cephalotin sodium, cefazolin sodium, latamoxef sodium, sodium glutamate, sodium molybdate, sodium percarbonate, perchloric acid Sodium, sodium salicylate, sodium thiosulfate, thiamylal sodium, triclofos sodium, sodium bicarbonate, sodium dichromate, sodium dichromate, sodium borofluoride, sodium acid sulfide disodium phosphate, beraprost sodium, cefotetan sodium , Ceftezol sodium, faropenem sodium, trisodium citrate, cefapirin sodium, ampicillin sodium, Cefoxitin sodium, cefsulodin sodium, cefuroxime sodium, dantrolene sodium, sodium antimonate, sodium dithionite, sodium propionate, sodium tungstate, sodium pyrosulfite, trisodium phosphate, sodium triphosphate, Dalteparin sodium, parnaparin sodium, danaparoid sodium, cefodizime sodium, carmellose sodium, iotaramate sodium, foscarnet sodium, sodium metasulfite, cefotaxime sodium, cefpyramid sodium, cyclamate sodium, diclofenac sodium, hydrogen Sodium borohydride, sodium hypochlorite, sodium thiocyanate, thiopental sodium, ticarcillin sodium Fosfomycin sodium, sodium arsenate, dibasic sodium phosphinate, sodium hyaluronate, imitrodast sodium, bucladecin sodium, sodium borohydride, sodium glucuronate, sodium aluminum sulfate, cefmetazole sodium, ceftizoxime Sodium, cloxacillin sodium, cyclamate sodium, fluorescein sodium, liothyronine sodium, loxoprofen sodium, piperacillin sodium, sodium hydrosulfite, sodium hypophosphite, sodium naphthionate, sodium permanganate, sodium pyrophosphate, fluvastatin Sodium, pravastatin sodium, rabeprazole sodium, sodium methacrylate, 5'-IMP dinato , Sodium amobarbital, sodium cefamandole, sodium cefoperazone, sodium ferrocyanide, sodium hydrogen sulfide, sodium metavanadate, sodium silicofluoride, sodium xanthate, sodium fluoroacetate, sodium lauryl sulfate, sodium cromoglycate, picosul Fate sodium, sodium fluoroacetate, sodium metabisulfite, sodium taurocholate, cerivastatin sodium, sodium acetate trihydrate, ceftriaxone sodium, carbenicillin sodium, cefbuperazone sodium, monosodium fumarate, levothyroxine sodium, dehydro Sodium acetate, sodium bisulfite, sulbenicillin sodium, sodium borate decahydrate, meta Sodium vanadate, sodium metaperiodate, sodium cholate hydrate, sodium sulfate decahydrate, sodium dodecyl sulfate, secobarbital sodium, robenzarit disodium, sodium deoxycholate, sodium nitroprusside, dicloxacillin sodium, phthalocyanine Sodium, sodium thioglycolate, disodium sulfate, sodium dihydronaphthalenidyl, gold sodium thiomalate, 2-biphenylol sodium, sodium cholate n hydrate, sodium stannate trihydrate, sodium sulfide nonahydrate , Edetate disodium calcium, epoprostenol sodium, ferrous sodium citrate, anhydrous sodium carbonate, sodium sulfite heptahydrate, sodium silicate aluminate, repose Sodium caffeine, disodium hydrogen arsenate, sodium saccharin dihydrate, dibasic sodium phosphate, sodium trichloroacetate, sodium tripolyphosphate, sodium peroxodisulfate, sodium bromfenac hydrate, sodium molybdate dihydrate Japanese, basic sodium phosphate, tribasic sodium phosphate, sodium trifluoroacetate, tetrasodium pyrophosphate, sodium chromate tetrahydrate, sodium succinate hexahydrate, sodium dihydrogen citrate, stearyl fumarate Sodium phosphate, sodium antimony tartrate, sodium cyanoborohydride, sodium dihydrogen phosphate, sodium plasterone sulfate, sodium selenite pentahydrate, sodium dipicrylamine, sodium hexametaphosphate, sodium perborate Umum tetrahydrate, sodium tetrahydroborate, sodium acyl β-alanine, disodium hydrogen phosphate, sodium perchlorate monohydrate, (+)-sodium pantothenate, sodium metasilicate (anhydrous), tetrafluoroborate Sodium sulfate, sodium sulfanilate dihydrate, sodium cellulose sulfate, pantoprazole sodium hydrate, chondroitin sulfate sodium, disodium methylarsonate, sodium hexafluorosilicate, sodium riboflavin phosphate, sodium dextran sulfate sulfur, phosphoric acid Trisodium dodecahydrate, disodium 5′-guanylate, disodium 5′-inosinate, sodium dextran sulfate sulfur 18, sodium sulfobromophthalein, disodium cytidylate, laur Sodium sulfonic acid salt, sodium betamethasone phosphate, sodium polystyrene sulfonate, sodium prednisolone phosphate, sodium pentachlorophenol, sodium dichloroisocyanurate, sodium dexamethasone phosphate, sodium estramustine phosphate, sodium prednisolone succinate, fumarate Sodium hydrogen oxyhydrogen, sodium hexacyanoferrate (II), sodium 1-dodecane sulfonate, sodium dihydrogen phosphate dihydrate, sodium carbazochrome sulfonate, sodium hydrocortisone phosphate, sodium 2-hydroxypropanoate, sodium pyrophosphate Hydrate, disodium dihydrogen pyrophosphate, sodium triacetoxyborohydride, hydrocortisone sodium succinate, dibasic Sodium phosphate dodecahydrate, colistin sodium methanesulfonate, sodium dodecylbenzenesulfonate, chloramphenicol sodium succinate, sodium 2-hydroxypropionate, sodium (Z) -9-octadecenoate, 2-hydroxysuccinate Disodium acid, sodium cyclohexylsulfamate, flavin adenine dinucleotide sodium, uridine-5′-diphosphate disodium, sodium diphenylamine-4-sulfonate, sodium methylprednisolone succinate, inosine 5′-monophosphate sodium salt, Inosine-5′-disodium phosphate, sodium N-cyclohexylsulfamate, cytidine 5′-disodium phosphate, guanosine-5′-disodium phosphate, (E) -2 1-sodium butenedioate, dexamethasone sodium metasulfobenzoate, 2,4-dichlorophenoxyacetic acid sodium salt, sodium (2,4-dichlorophenoxy) acetate, disodium 1,5-naphthalenedisulfonate, pentachlorophenol, sodium Salt (industrial), sodium 4- (2,4-dichloro-m-toluoyl) -1,3-dimethylpyrazole-5-olate, sodium 2-methyl-4-chlorophenoxyacetate, (4-chloro-2- Methylphenoxy) sodium acetate, sodium [(4-chloro-2-methylphenyl) oxy] acetate, hydrogenated coconut oil fatty acid sodium glycerol sulfate, sodium 5-ethyl-5,8-dihydro-8-oxofuro [3,2-b ] [1,8] naphthyridine-7-carboxylate 2-hydroxy-1,2,3-propanetricarboxylic acid trisodium salt, 1-phenylazo-2-naphthol-4 ′, 6-disulfonic acid disodium salt, 1- (p-sodiosulfophenylazo) -2-hydroxynaphthalene -6-sulfonic acid sodium, 6-hydroxy-5-[(4-sulfophenyl) azo] -2-naphthalenesulfonic acid disodium, 2-hydroxy (1,1'-azobisnaphthalene) -3,4 ', Trisodium 6-trisulfonate, (+)-N-[(R) -2,4-dihydroxy-3,3-dimethylbutyryl] -β-alanine sodium, 4-[(2,4-dimethylphenyl) Azo] -3-hydroxy-2,7-naphthalenedisulfonate, (+)-3-[[(R) -2,4-dihydroxy-3,3-dimethyl Styryl] amino] propionate, and the like [methyl (2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl -1H- pyrazol-4-yl) amino] Sodium methanesulfonate.

  In addition, as a compound containing potassium, potassium alum, potassium oxide, potassium bromide, potassium iodide, potassium nitrate, potassium sulfate, potassium sulfide, potassium acetate, potassium bromate, potassium chloride, potassium nitrite, potassium sulfite, potassium arsenate , Potassium iodate, potassium hydride, potassium t-butoxide, potassium carbonate, potassium chlorate, potassium cyanate, potassium cyanide, potassium fluoride, potassium oxalate, potassium silicate, potassium arsenite, potassium stannate, chromic acid Potassium, potassium hydroxide, potassium phosphate, potassium sorbate, potassium bisulfate, potassium selenate, potassium persulfate, potassium rhodanide, losartan potassium, potassium selenite, potassium tellurite, warfarin potassium, periodate Potassium, gluconate, canrenoate, potassium perchlorate, potassium thiosulfate, potassium dichromate, potassium borofluoride, potassium dichromate, potassium molybdate, potassium pyrosulfite, potassium aspartate, potassium pemirolast , Potassium hypochlorite, potassium thiocyanate, potassium clavulanate, potassium aluminum sulfate, potassium cyanide sulfate, potassium borohydride, potassium hypophosphite, potassium metaphosphate, potassium permanganate, potassium pyrophosphate, potassium ferricyanide, Potassium ferrocyanide, potassium silicofluoride, potassium hydrogen sulfate, potassium metavanadate, potassium xanthate, potassium hydrogen oxalate, dipotassium chlorazepate, potassium selenocyanate, dioxalate Potassium, fluorosilicate, potassium stannate trihydrate, potassium hydrogen carbonate, potassium peroxodisulfate, potassium aluminum sulfate, tetrapotassium pyrophosphate, potassium benzylpenicillin, potassium (methylsulfinyl) methanide, potassium dihydrogen phosphate, Dipotassium hydrogen phosphate, dipotassium glycyrrhizinate, potassium tetrafluoroborate, potassium guaiacol sulfonate, potassium hexafluorosilicate, potassium aluminum sulfate dodecahydrate, o-ethyl potassium dithiocarbonate, potassium hexacyanoiron (III) , Phenoxymethylpenicillin potassium, potassium (2E, 4E) -2,4-hexadienoate, and the like.

  In addition, examples of the compound containing rubidium include rubidium oxide, rubidium bromide, rubidium iodide, rubidium sulfate, rubidium chloride, rubidium fluoride, rubidium acetate, rubidium hydrogen sulfate, and zirconium bicarbonate. , Cesium cyanide, cesium oxide, cesium bromide, cesium iodide, cesium nitrate, cesium sulfate, cesium chloride, cesium carbonate, cesium fluoride, cesium carbonate, cesium oxalate, dicesium sulfate, dicesium L-tartrate, hydroxide Examples include, but are not limited to, cesium monohydrate, cesium trifluoroacetate, 1-cesium 2,3-dihydroxybutanedioate, 1-cesium hydrogen 2,3-dihydroxybutanedioate, and the like. Among these, sodium chloride and potassium chloride, particularly sodium chloride is preferable from the viewpoint of safety and stability of the compound.

  In addition, as a compound containing a divalent metal ion, as a compound containing beryllium, beryllium oxide, beryllium bromide, beryllium carbide, beryllium iodide, beryllium nitrate, beryllium nitride, beryllium sulfide, beryllium chloride, beryllium fluoride, Examples thereof include beryllium silicate, beryllium distearate, beryllium sulfate tetrahydrate, acetylacetone beryllium salt, and magnesium-containing compounds include magnesium oxide, magnesium orotate, arylmagnesium, magnesium acetate, magnesium boride, and magnesium bromide. , Magnesium carbide, magnesium iodide, magnesium nitrate, magnesium nitride, magnesium sulfate, magnesium sulfide, magnesium (powder), magnesium chloride, magnesium carbonate, salt Magnesium oxide, magnesium citrate, magnesium fluoride, magnesium silicate, magnesium silicide, magnesium hydroxide, magnesium phosphide, magnesium orotate, magnesium nitrate (II), magnesium stearate, magnesium perchlorate, magnesium myristate, Magnesium oxalate, magnesium hydrogen carbonate, magnesium silicofluoride, magnesium fluorosilicate, phenyl magnesium bromide, magnesium nitrate hexahydrate, phthalocyanine magnesium, magnesium acetate tetrahydrate, magnesium benzoate trihydrate, magnesium magnesium carbonate , Magnesium chromate pentahydrate, Magnesium hexafluorosilicate, Magnesium aluminate metasilicate, Bismuth magnesium aluminate silicate, Al hydroxide Examples include minium magnesium carbonate hydrate.

Moreover, as a compound containing calcium, calcium carbide, calcium oxide, calcium bromide, calcium carbide, calcium cyanamide, calcium iodide, calcium lactate, calcium nitrate, calcium nitride, calcium sulfate, calcium sulfide, calcium acetate, calcium chloride, Calcium nitrite, calcium sulfite, calcium arsenate, calcium hydride, calcium arsenate, calcium iodate, calcium carbonate, calcium chlorate, calcium fluoride, calcium oxalate, calcium peroxide, calcium silicate, calcium silicide, cyanide Calcium phosphide, calcium arsenite, heparin calcium, calcium chlorite, calcium chromate, calcium hydroxide, calcium phosphate, calcium phosphite, folinate calcium Calcium gluconate, calcium stearate, calcium aspartate, calcium hypochlorite, fosfomycin calcium, calcium metasilicate, calcium thiocyanate, calcium hypophosphite, calcium pantothenate, calcium permanganate, calcium fenoprofen, calcium chloride dihydrate Japanese, calcium carbonate, polycarbophil calcium, mupirocin calcium hydrate, calcium hydrogen phosphate, calcium glycerophosphate, calcium diiodostearate, precipitated calcium carbonate, disodium calcium edetate, atorvastatin calcium hydrate, (+) -Calcium pantothenate, calcium paraaminosalicylate, calcium tocopherol succinate, calcium sulfonate polystyrene (+)-Pantothenic acid calcium salt (2: 1), calcium aluminoparaaminosalicylate, 3-hydroxy-4-[(4-methyl-2-sulfophenyl) azo] -2-naphthalenecarboxylic acid calcium salt, etc. Examples of the compound containing barium include barium oxide, barium azide, barium acetate, barium bromide, barium iodide, barium nitrate, barium nitride, barium sulfate, barium sulfide, barium formate, barium lactate, barium chloride, Barium sulfite, barium carbonate, barium chlorate, barium fluoride, barium peroxide, barium cyanide, barium chromate, barium hydroxide, barium titanate, barium selenate, barium phosphate, barium nitrate (II), selenium selenium Barium oxide, barium manganate, barium oxalate , Barium stearate, barium perchlorate, barium thiosulfate, barium hypochlorite, barium permanganate, barium chloranilate, barium chloride dihydrate, barium diacetate, barium bromide dihydrate, dipropion Barium oxalate, barium chlorate monohydrate, barium hydroxide octahydrate, barium thiocyanate dihydrate, barium thiosulfate monohydrate, acetylacetone barium dihydrate, etc. Not a thing.
In the following (B), the polymer in which M is an alkali metal is not included in the compound (A) here.

  The (meth) acrylate polymer (B) used in the hydrogel composition of the present invention is 0.5 to 30% by mass based on the total amount of the composition containing the components (A) to (D). It is preferable to use in the range of 2-20 mass%. When the amount is less than 0.5% by mass, the strength of the gel body is remarkably reduced, and as a result, oozing from the support or skin residue of the gel may occur. If it exceeds 30% by mass, the viscosity of the sol at the time of molding will increase, and coating and mixing of other components may become difficult.

（式中、Ｒ¹及びＲ²はそれぞれ独立して水素原子またはメチル基を表し、ＭはＮＨ₄ ⁺またはアルカリ金属を表し、Ｘは不飽和単量体由来の２価の有機基を表す。）で示され、（１）／（２）＝１００／０〜０／１００（モル比）、かつ（１）及び（２）の総量／（３）＝１００／０〜１０／９０（モル比）であることが好ましい。 The (meth) acrylic acid polymer of component (B) has a repeating unit represented by general formulas (1), (2) and (3).

(In the formula, R ¹ and R ² each independently represents a hydrogen atom or a methyl group, M represents NH ₄ ⁺ or an alkali metal, and X represents a divalent organic group derived from an unsaturated monomer. ), (1) / (2) = 100/0 to 0/100 (molar ratio), and the total amount of (1) and (2) / (3) = 100/0 to 10/90 (molar ratio) ) Is preferable.

  Specific examples of the component (B) include acrylic acid or methacrylic acid sodium salt, alkali metal salt such as potassium salt, homopolymer such as ammonium salt, acrylic acid or methacrylic acid sodium salt, potassium salt and the like. Examples of the alkali metal salt, ammonium salt and acrylic acid copolymer, acrylic acid or methacrylic acid sodium salt, potassium salt alkali metal salt, ammonium salt and methacrylic acid copolymer, etc. be able to.

  Of all the unsaturated monomers used for the component (B), unsaturated monomers other than acrylic acid may be used as long as the range is up to 90 mol%.

  Examples of unsaturated monomers other than acrylic acid include maleic acid, maleic anhydride, fumaric acid, crotonic acid, itaconic acid, vinyl sulfonic acid, styrene sulfonic acid, 2- (meth) acrylamide-2-methylpropane Hydrophilic unsaturated monomers containing acid groups such as sulfonic acid, 2- (meth) acryloylethanesulfonic acid, 2- (meth) acryloylpropanesulfonic acid, and salts thereof; N-vinylacetamide, N-methyl-N- Vinylacetamide, acrylamide, methacrylamide, N-ethyl (meth) acrylamide, Nn-propyl (meth) acrylamide, N-isopropyl (meth) acrylamide, N, N-dimethyl (meth) acrylamide, 2-hydroxyethyl (meth) ) Acrylate, 2-hydroxypropyl (meth) acrylate Nonionic hydrophilic unsaturated monomers such as methoxypolyethylene glycol (meth) acrylate, polyethylene glycol mono (meth) acrylate, vinylpyridine, N-vinylpyrrolidone, N-acryloylpiperidine, N-acryloylpyrrolidine; N-dimethylaminoethyl (meth) acrylate, N, N-diethylaminoethyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylate, N, N-dimethylaminopropyl (meth) acrylamide and quaternary salts thereof, etc. A cationic hydrophilic unsaturated monomer, styrene, vinyl chloride, butadiene, isobutene, ethylene, propylene, stearyl (meth) acrylate, lauryl (meth) acrylate, etc., and one kind selected from these groups It can be used or two or more kinds. Moreover, you may use the unsaturated monomer which forms a hydrophilic resin by hydrolysis of a functional group like methyl (meth) acrylate, ethyl (meth) acrylate, vinyl acetate.

  Among these, N-vinylacetamide, N-methyl-N-vinylacetamide, N-vinylpyrrolidone, methoxypolyethylene glycol (meth) acrylate, N, N-dimethylaminoethyl (meth) acrylate, and acrylamide are particularly preferable.

  Examples of the polymerization method of the unsaturated monomer used for the component (B) include (a) a method using a radical polymerization initiator, (b) a method using radiation, (c) a method using electron beams, and (d) light. Although known methods such as ultraviolet polymerization using a sensitizer can be mentioned, in order to obtain a high-performance acrylic acid polymer, (a) polymerization using a radical polymerization initiator is preferred.

  Examples of the polymerization method (a) include in-frame polymerization, hydrogel polymer fragmentation, various aqueous solution polymerizations such as polymerization under pressure, reverse phase suspension polymerization, and reverse phase emulsion polymerization. Although known polymerization methods such as precipitation polymerization and bulk polymerization can be exemplified, reverse phase suspension polymerization or aqueous solution polymerization is particularly preferred. In the polymerization, the distinction between continuous, semi-batch, and batch and the distinction between reduced pressure, increased pressure, and normal pressure are not particularly limited.

  In the polymerization, bulk polymerization or precipitation polymerization may be used, but it is preferable to perform polymerization as a solution from the viewpoint of performance and ease of polymerization control. The polymerization solvent is not particularly limited as long as it is a liquid in which an unsaturated monomer is dissolved, and examples thereof include water, methanol, ethanol, acetone, dimethylformamide, dimethyl sulfoxide, and the like, but water or an aqueous solvent is particularly preferable. . In addition, the concentration at which the unsaturated monomer is polymerized as a solution is not particularly limited and may exceed the saturated concentration. However, from the viewpoints of various physical properties and reduction of residual monomers, the concentration is usually 20% by mass to the saturated concentration. , Preferably it is the range of 25-50 mass%. In the polymerization, a hydrophilic polymer such as a chain transfer agent, starch, cellulose or a derivative thereof, polyvinyl alcohol, or a crosslinked poly-N-vinylacetamide may be added to the unsaturated monomer. The amount used thereof is usually 5 parts by mass or less for the former and 50 parts by mass or less for the latter. Chain transfer agents include hypophosphorous acid such as hypophosphorous acid and sodium hypophosphite, sulfur-containing compounds such as thioacetic acid, thioglycolic acid and mercaptoethanol, disulfides, and halides such as carbon tetrachloride. And phosphorous acids such as phosphorous acid and sodium phosphite.

  Examples of the radical polymerization initiator used for such polymerization include persulfates such as potassium persulfate, ammonium persulfate, and sodium persulfate; organic peroxides such as t-butyl hydroperoxide and cumene hydroperoxide; Hydrogen; azo compounds such as 2,2′-azobis (2-amidinopropane) dihydrochloride; other known polymerization initiators such as chlorite, hypochlorite, ceric salt, permanganate Among these, one or more selected from the group consisting of persulfates, hydrogen peroxide, and azo compounds are preferable. In addition, when an oxidizing radical polymerization initiator is used, a reducing agent such as sulfurous acid (hydrogen) salt, iron, or L-ascorbic acid may be used in combination. When an azo polymerization initiator is used, ultraviolet rays are used in combination. You can do it. These radical polymerization initiators may be added to the polymerization system all at once or sequentially, but the amount used is usually 0.001 to 2 mol%, preferably 0.01 to 1 mol%.

  Water (C) is added to increase the solubility of the (meth) acrylic acid polymer and to increase the viscosity, and the addition amount is 5 to 98% by mass. When the water content is less than 5% by mass, the solubility of the (meth) acrylic acid polymer is deteriorated and the thickening effect is reduced, so that the polymer remains on the release paper or the applied skin surface. There may be a so-called “glue remaining” phenomenon or a so-called “back-through” phenomenon in which the gel body escapes from the support. On the other hand, if it exceeds 98% by mass, the strength of the gel body is remarkably reduced. As a result, the shape-retaining property is reduced and oozing from the support or gel residue may occur.

  The composition for a hydrogel body of the present invention is added with a crosslinking agent (D) that reacts with a carboxyl group in order to maintain the shape retention of the resulting gel body and to prevent “glue residue”. Examples of the reaction with the carboxyl group include ionic bond and covalent bond.

  A crosslinking agent is added in 0.01-20 mass% with respect to the composition for hydrous gel bodies, More preferably, the range of 0.1-10 mass% is good. When the addition amount is less than 0.01% by mass, the crosslinking may be insufficient and stringing may occur in the base. If it exceeds 20% by mass, the gel strength becomes unstable and unstable, or the gel body becomes turbid, resulting in poor transparency. In particular, in the case of an epoxy compound, there are concerns about the effects of toxicity and stability due to unreacted substances. .

As the crosslinking agent, an aluminum compound is particularly preferable.
Examples of the aluminum compound include aluminum chloride, potassium alum, ammonium alum, aluminum nitrate, aluminum sulfate, EDTA-aluminum, aluminum hydroxide / sodium bicarbonate coprecipitate (for example, “Kumlite” from Kyowa Chemical Industry Co., Ltd.), Synthetic aluminum silicate, aluminum stearate, aluminum allantoate, synthetic hydrotalcite (for example, “Alkamak”, “Alkamizer”, “Kyoward”, etc., Kyowa Chemical Industry Co., Ltd.)), alumina hydroxide and magnesium hydroxide ( For example, “Sanarmin” from Kyowa Chemical Industry Co., Ltd.), aluminum hydroxide (eg “Dry Aluminum Hydroxide Gel S-100, Low Water Content Type” from Kyowa Chemical Industry Co., Ltd.), aluminum acetate, dihydroxyaluminum Minoacetate (eg, “Glycinal SG, PG or SA” from Kyowa Chemical Industry Co., Ltd.), kaolin, synthetic hydrotalcite, magnesium aluminate metasilicate (eg, “Noiselin” from Toyama Chemical Co., Ltd.) And magnesium aluminate silicate. These aluminum compounds may be water-soluble or sparingly soluble. These aluminum compounds can be used alone or in combination of two or more.

  Other crosslinking agents can also be added. Examples thereof include inorganic acid salts such as calcium, tin, iron, magnesium, manganese, zinc and barium (for example, calcium chloride, magnesium chloride, iron alum, ferric sulfate, magnesium sulfate, EDTA-calcium, EDTA- Magnesium, stannous chloride, calcium carbonate, calcium phosphate, calcium hydrogen phosphate, magnesium carbonate, barium sulfate, magnesium silicate, magnesium stearate, magnesium citrate), hydroxides (eg, calcium hydroxide, barium hydroxide, Magnesium hydroxide (for example, “Kisuma” of Kyowa Chemical Industry Co., Ltd.), ferric hydroxide, stannous hydroxide, etc.), oxide (for example, magnesium oxide (for example, Kyowa Chemical Industry Co., Ltd.) “Kyowa mug” “Mugsarat” etc.)), formaldehyde, e Examples include epoxy compounds such as lenglycol diglycidyl ether, glycerin diglycidyl ether, polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether, and polypropylene glycol diglycidyl ether. These crosslinking agents can be used alone or in combination. Can be used.

  It is preferable that the composition for hydrogel bodies of this invention contains a polyhydric alcohol (E). The polyhydric alcohol is blended for the purpose of enhancing the solubility and activity of the drug in the adhesive for patch and improving the transferability to the skin. Polyhydric alcohols include ethylene glycol, propylene glycol, 1,3-butylene glycol, ethylene glycol monobutyl ether, diethylene glycol, triethylene glycol, 1,4-butylene glycol (dihydric alcohol), glycerin, trioxyisobutane (trihydric alcohol) ), Erythritol, pentaerythritol (tetrahydric alcohol), xylit, adnit (pentahydric alcohol), allozulcit, sorbitol, sorbitol liquid, mannitol (hexahydric alcohol), polyglycerin, dipropylene glycol, etc. Absent. Among these, glycerin is particularly preferable from the viewpoint of safety and affinity with a (meth) acrylic acid polymer. A polyhydric alcohol may be used independently and may be used 2 or more types.

  The polyhydric alcohol is added in a range of up to 90% by mass, and more preferably in a range of up to 60% by mass with respect to the total amount of the composition for hydrogel body. When the addition amount exceeds 90% by mass, the thickening effect due to the (meth) acrylic acid polymer is hardly exhibited, and sufficient shape retention may be difficult to obtain.

  Moreover, solvents other than polyhydric alcohols can also be added to the composition for hydrous gel bodies of the present invention. Examples of these solvents include monohydric alcohols such as methanol, ethanol, propanol, benzyl alcohol, phenethyl alcohol, isopropyl alcohol, isobutyl alcohol, hexyl alcohol, 2-ethylhexanol, cyclohexanol, octyl alcohol, butanol and pentanol, In addition to water-miscible organic solvents such as acetone, methyl ethyl ketone and other ketones, cellosolve, dioxane, dimethylformamide, N-methylpyrrolidone and dimethyl sulfoxide, organic solvents that are not miscible with water, such as ethyl acetate and crotamiton.

  Furthermore, as a speed control agent for the crosslinking reaction, metal ions such as tartaric acid, citric acid, lactic acid, glycolic acid, malic acid, salicylic acid, fumaric acid, methanesulfonic acid, maleic acid, acetic acid, sodium EDTA-2, urea, triethylamine, ammonia, etc. On the other hand, inorganic acids such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, hydrobromic acid, etc. can be used in addition to organic acids, organic acid salts, organic bases and the like having chelate or coordination ability.

  The polymer for water-containing gel body of the present invention can be added with other polymers for the purpose of improving the shape retention and adhesiveness of the gel body obtained. These polymers include polyvinylpyrrolidone, carboxyvinyl polymer which is cross-linked polyacrylic acid, vinylpyrrolidone-ethyl acrylate copolymer, and N-vinylacetamide-sodium acrylate copolymer. Examples thereof include polymers, N-vinylacetamide homopolymers, polyvinylsulfonic acid, N-vinylacetamide cross-linked products, polyitaconic acid, hydroxypropylcellulose, hydroxypropylmethylcellulose and the like. Among these, N-vinylacetamide-sodium acrylate copolymer is particularly preferable from the viewpoint of improving adhesion to the skin. In the N-vinylacetamide-sodium acrylate copolymer, the molar ratio of N-vinylacetamide to sodium acrylate is preferably in the range of 99.9: 0.1 to 50:50, more preferably 95.0: 5 to 50. : 50 is good.

  These polymers are added in a range of up to 20% by weight, more preferably up to 10% by weight, based on the total amount of the hydrogel composition. When the addition amount exceeds 20% by mass, the gel body becomes too hard, and the feeling of adhesion with the skin may deteriorate.

  There are many drugs that can be administered using the gel bodies of the present invention. For example, (a) corticosteroids: for example, hydrocortisone, prednisone, beclomethasone pyropionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate, etc.

(B) Anti-inflammatory analgesic: for example, salicylic acid, glycol salicylate, methyl salicylate, 1-menthol, camphor, sulindac, trimethine sodium, naproxen, fenbufen, piroxicam, triamcinolone, hydrocortisone acetate, indomethacin, ketoprofen, acetaminophen, mefenamic acid Flufenamic acid, ibufenac, loxoprofen, thiaprofen, pranoprofen, fenbufen, diclofenac, diclofenac sodium, alclofenac, lornoxicam, mepranoprofen, oxyphenbutazone, ibuprofen, felbinac, ketorolac, vermoprofen, nabumetone, naproxen , Flurbiprofen, fluocinonide, clobetasol propionate, OX-2 inhibitors (celecoxib, rofecoxib, Barekokishibu, parecoxib, Baredekokishibu, ethoxy drag, nimesulide, etc. meloxicam) such,

(C) Antifungal agents: for example, clotrimazole, econazole nitrate, omoconazole nitrate, thioconazole nitrate, ketoconazole nitrate, miconazole nitrate, isoconazole nitrate, tolnaftate, sulconazole nitrate, pyrrolnitrin, pimafucin, undecylenic acid, salicylic acid, siccanin, nystatin , Nornaphthate, exalamide, phenyliodoundecinoate, thianthol, ciclopirox olamine, haloprozin, tricomycin, variotin, pentamycin, amphotericin B, etc.

(D) Antihistamine: for example, antibiotics such as tetracycline hydrochloride, diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole, chloramphenicol, diphenhydramine, chlorpheniramine maleate, etc.
(E) hypnotic sedative: for example, phenobarbital, amobarbital, cyclobarbital, lorazepam, haloperidol, etc.
(F) Tranquilizer: For example, fluphenazine, theoridazine, diazepam, flunitrazepam, chlorpromazine, etc.
(G) Antihypertensive agents: for example, clonidine, clinidine hydrochloride, pindolol, propranol, propranol hydrochloride, bufuranol, indenolol, bucmolol, nifedipine, etc.

(H) Antihypertensive diuretics: For example, hydrothiazide, cyclopenthiazide, etc.
(I) Antibiotics: for example, penicillin, tetracycline, oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc.
(J) Anesthetic agents: for example, lidocaine, benzocaine, ethyl aminobenzoate, dibucaine, etc.
(K) Antibacterial substances: for example, benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc.

(L) Vitamin preparations: For example, vitamin A, ergocalciferol, cholecalciferol, octotiamine, riboflavin butyrate, etc.
(M) Antiepileptic agents: for example, nitrazepam, meprobamate, clonazepam, etc.
(N) coronary vasodilator: for example, nitroglycerin, nitroglycol, isosorbidinitrate, erythritol tetranitrate, pentaerythritol tetranitrate, propatyl nitrate, etc.
(O) antihistamine: for example, diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole, etc.

(P) Antitussives: for example, dextromethorphan, terbutaline, ephedrine,
Such as ephedrine hydrochloride,
(Q) Sex hormones: For example, progesterone, estradiol, etc.
(R) antidepressant: for example, doxepin
(S) Angina treatment agent: antiperspirants such as diethylamide and camphor, nitroglycerin, isosorbide nitrate, etc.
(T) narcotic analgesics: morphine hydrochloride, ethyl morphine hydrochloride, morphine sulfate, cocaine hydrochloride, pethidine hydrochloride, codeine phosphate, dihydrocodeine phosphate, fentanyl citrate, sufentanil, meperidine hydrochloride, etc.

(U) Herbal medicines: buckwheat, euhi, onji, gadget, chamomile, caroten, licorice, kyoukyo, kyounin, gou, trash, saikachi, psycho, saishin, shizenshi, shouma, senega, sojutsu, sohakuhi, choji, chimney, tokonto, nanjitsu , Baimo, Bakumondo, Hange, Beaked Jutsu, Hiyos, Bowhou, Maou, etc.

(V) Others: 5-Fluorouracil, dihydroergotamine, fentanyl, desmopressin, digoxin, metoclopramide, domperidone, scopolamine, scopolamine hydrobromide, and other veterinary drugs, hypnotics, cardiovascular drugs, brain metabolism stimulants, Bactericides, enzyme preparations, enzyme inhibitors, biopharmaceuticals (polypeptides), keratosis treatments, narcotics, antineoplastic agents, general anesthetics, anti-anxiety agents, asthma / nasal allergy agents, anti-parkinsonian agents, chemotherapy Agent, anthelmintic agent, antiprotozoal agent, hemostatic agent, cardiotonic agent, stimulant / stimulant agent, addictive addiction agent, Chinese medicine, radiopharmaceutical, urogenital and anal agent, hypoglycemic agent, antiulcer agent, hair agent, Examples include sequestering agents, antiperspirants, tranquilizers, anti-sham blood agents, anti-rheumatics, anti-gout agents and anticoagulants. But it is not limited. These drugs can be used in combination of two or more as required, and the compounding ratio of the drug is 0.01 to 30% by mass, preferably 2 to 20% by mass with respect to the total mass of the adhesive for a patch. It is preferable to adjust.

  The drug can be included after solution stage (or gel suspension stage) or after aging for cross-linking reaction. The preferred method depends on the initial objectives for the drug's physical properties, site of administration and release rate.

  In addition, auxiliary agents that promote the absorption of these drugs can be added. Examples of adjuvants include ethyl alcohol, isopropyl alcohol, butanol, 1,3 butanediol, propylene glycol, polyethylene glycol # 400, glycerin, crotamiton, benzyl alcohol, phenylethyl alcohol, propylene carbonate, hexyl decanol, propanol, salicylic acid , Allantoin, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, lanolin, azone, 1-geranyl azasilroheptan-2-one (GACH), fatty acid dialkyrolamide, salicylic acid, salicylic acid Derivatives, keratin softeners such as urea and sulfur, humectants such as pyrrolidone carboxylic acid, propylene glycol monooleate, polyoxy Surfactants such as ethylene sorbitan monostearate, sorbitan monostearate, glycerol monostearate, esters such as isopropyl myristate, diethyl sebacate, higher alcohols such as oleyl alcohol, stearyl alcohol, lauryl alcohol, stearic acid, Terpenes such as hexanoic acid, nonanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, oleic acid, linoleic acid, menthol, menthone, limonene, pinene, piperiton, terpinene, terpinolene, terpinolol, carbeol Compounds and surfactants, allantoin, dimethyl sulfoxide, dimethylacetamide, dimethylformamide, diisopropyl adipate, diethyl sebacate, ethyl Auxiliary agents such as urate, lanolin, azone, etc., as well as other refreshing agents such as menthol and camphor, almond oil, olive oil, camellia oil, persic oil, mint oil, sesame oil, soybean oil, mink oil, cottonseed oil, corn Oil, safflower oil, coconut oil, eucalyptus oil, castor oil, liquid components such as liquid paraffin, petrolatum, squalene, squalane, lanolin, gelling agent such as carboxyvinyl polymer, neutralizing agent such as diisopropanolamine, etc. More than one type can be blended. In consideration of skin irritation and the like, these blending amounts are desirably 0.1 to 5 parts by mass with respect to 100 parts by mass of the drug.

The composition for a hydrogel body of the present invention is a gel for the purpose of expressing more of its characteristics, or for the purpose of improving processing / moldability and quality, and improving the dispersibility and stability of the drug in the gel body. Those selected according to the purpose can be further arbitrarily blended to such an extent that the performance of the above is not impaired. Such additives include:
(1) Wetting agent: For example, glycerin, propylene glycol, sorbit, 1,3-butylene glycol, dl-pyrrolidone carboxylic acid, sodium lactate, etc.
(2) Astringents: for example, citric acid, tartaric acid, lactic acid, aluminum chloride, aluminum sulfate, allantochlorohydroxyaluminum, allantoindihydroxyaluminum, aluminum phenolsulfonic acid, zinc paraphenolsulfonic acid, zinc sulfate, aluminum chlorohydroxide, etc.
(3) Moisturizer: for example, glycerol, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerol, polyethylene glycol, dipropylene glycol and other polyhydric alcohols, sodium lactate and other NMF components, hyaluronic acid, collagen, Water-soluble polymers such as mucopolysaccharides and chondroitin sulfate,

(4) Thickeners: eg gum arabic, tragacanth gum, locust bean gum, guar gum, echo gum, karaya gum, agar, starch, carrageenan, alginic acid, alginates (eg sodium alginate), propylene glycol alginate, dextran, dextrin, amylose, Natural polymers such as gelatin, collagen, pullulan, pectin, amylopectin, starch, amylopectin sodium semiglycolate, chitin, albumin, casein, polyglutamic acid, polyaspartic acid, methylcellulose, ethylcellulose, propylcellulose, ethylmethylcellulose, hydroxyethylcellulose, Hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethyl starch, al Semi-synthetic polymers such as lithium metal carboxymethyl cellulose, alkali metal cellulose sulfate, cellulose graft polymer, crosslinked gelatin, cellulose acetate phthalate, starch-acrylic acid graft polymerization, phthalic anhydride modified gelatin, succinic acid modified gelatin, polyvinyl alcohol , Polyvinyl pyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, vinyl pyrrolidone-ethyl acrylate copolymer, vinyl pyrrolidone-styrene copolymer, vinyl pyrrolidone-vinyl acetate copolymer, vinyl acetate- (meth) acrylic acid copolymer , Polyvinyl acetate-crotonic acid copolymer, N-vinylacetamide-sodium acrylate copolymer, and other N-vinylacetamide copolymers, polyvinylsulfonic acid, N-vinyl Acetamide crosslinked product, polyitaconic acid, polyhydroxyethyl acrylate, polyacrylamide, styrene - maleic acid anhydride copolymer, acrylamide - such as the synthesis of polymers such as acrylic acid copolymers,

(5) Tackifying substances: For example, adhesive substances such as silicone rubber, polyisoprene rubber, styrene-block copolymer rubber, acrylic rubber, natural rubber, etc.
(6) Antidiarrheal: For example, camphor, thymol, menthol, polyoxyethylene lauryl ether, antihistamine, ethyl aminobenzoate, etc.
(7) Keratin softening release agent: for example, sulfur, thioxolone, selenium sulfide, salicylic acid, resorcin, etc.
(8) Anti-fouling substances: for example, chili powder, red pepper essence, etc.
(9) Powder raw materials: For example, montmorillolite, anhydrous silicic acid, stone kou, carbon black, diatomaceous earth, bengara, calcium carbonate, hydrotalcite, talc, glass, kaolin, bentonite, metal soap, aerosil, mica titanium, Bismuth oxychloride, fish scale foil, zinc white, titanium dioxide, etc.

(10) Oily raw materials: For example, almond oil, olive oil, hydrogenated oil, camellia oil, castor oil, owl oil, coconut oil, beeswax, whale wax, lanolin, carnauba wax, candelilla wax, liquid paraffin, petrolatum, microcrystalline wax, Ceresin, squalene, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, oleic acid, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, octyldodecanol, cholesterol, hexyldecanol, white sterol, cetyl lactate, isopropyl myristate , Hexyl laurate, myristyl myristate, isopropyl palmitate, octyldodecanol myristate, butyl stearate, cacao oil, tree wax, jojoba oil, gray Pseed oil, avocado oil, mink oil, egg yolk oil, beeswax, whale wax, lanolin, carnauba wax, candelilla wax, liquid paraffin, ceresin wax, paraffin wax, behenic acid, isopropyl adipate, octyldodecyl myristate, octyl oleate Dodecyl, cholesterol oleate, etc.

(11) Surfactant: For example, lauryl sulfate ester salt, polyoxyethylene alkyl ether sulfate, alkyl benzene sulfonate, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkyl phenyl ether phosphate, N-acyl amino acid salt, Anionic surfactants such as sodium stearate, potassium palmitate, sodium cetyl sulfate, sodium lauryl sulfate, triethanolamine palmitate, sodium polyoxyethylene lauryl phosphate, sodium acylglutamate, surfactin, benzalkonium chloride, benzethonium chloride , Cationic surfactants such as stearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, Amphoteric surfactants such as rudiaminoethylglycine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, lauryldimethylaminoacetic acid betaine, lecithin, polyol fatty acid ester, glyceryl monostearate, lipophilic mono Glycerin oleate, ethylene glycol monostearate, propylene glycol monostearate, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene alkylphenol ether, polyoxyethylene sorbitol fatty acid Esters, N-acyl amino acid esters, sucrose fatty acid esters, fatty acid alkylolamides, polyoxyethylenated sterols Non-ionic surfactants such as alcohol, polyoxyethylenated lanolin, polyoxyethylene hydrogenated castor oil,

(12) Colorant: For example, yellow iron oxide, red iron oxide, black iron oxide, ultramarine, carbon black, chromium hydroxide, chromium oxide, tar dye, lake, red No. 2, red No. 3, red No. 102, red No. 201 Yellow No. 4, Yellow No. 5, Blue No. 1, Blue No. 2, etc.

(13) Fragrance: For example, palm oil, orange oil, pepper oil, jasmine oil, cedar oil, ginger oil, terpin oil, orange flower oil, rose oil, eucalyptus oil, lime oil, lemon oil, Japanese mint oil, rose Vegetable fragrances such as mary oil, animal fragrances such as musk, reibiko, kairikou and rysenkou, hydrocarbon fragrances such as bromostyrol, pinene and limonene, alcoholic fragrances such as benzyl alcohol and l-menthol, ethyl acetate and salicylic acid Esters such as methyl, aldehydes such as benzaldehyde and salicylaldehyde, ketones such as camphor, muscone, musk ketone and l-menton, ethers such as safrole, phenols such as thymol , Lactone fragrances, acid fragrances such as phenylacetic acid, nitrogen such as indole Such as compound-based perfume,

(14) UV blocker: for example, ASL-24, Cyasorb UV-9, benzophenone series such as Uvinul M-40, benzoic acid series such as Salol, azole series such as Tinuvin P, nitrile series such as Uvinul N-35, Urea such as Ancor UA, Neo Heliopan Give tan F, 2-hydroxy-4-methoxybenzophenone, octyldimethylparaaminobenzoate, paraamino acids such as ethylhexylparamethoxycynamate, salicylic acid, benzofuran, coumarin, azole, etc. ,

(15) Antiseptic fungicides: for example, acids such as benzoic acid, salicylic acid, dehydroacetic acid, sorbic acid, boric acid and their salts, phenol, chlorocresol, chlorxylenol, isopropylmethylphenol, resorcin, orthophenylphenol, paraoxybenzoic acid Phenols such as ester, phenoxyethanol, thymol, hinokitiol, thioxolone, halogenated bisphenols such as hexachlorophene, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, trichlorocarbanilide, halocarban, monoethanol Amide compounds such as amides, quaternary ammonium compounds such as benzalkonium chloride, alkylisoquinolinium bromide, benzethonium chloride, cetylpyridinium chloride, lauryl di (a Aminoethyl) amphoteric surface active agents such as glycine, 2-pyridine thiol-1-oxide zinc salt, gluconate, chlorhexidine, thiram, N- trichloromethylthio-4-cyclohexene-1,2-dicarboximide, etc. chlorobutanol,

(16) Antioxidant: For example, nordihydroguaiaretic acid, guaiac fat, propyl gallate, butylhydroxyanisole, dibutylhydroxytoluene (BHT), tocopherol (vitamin E), 2,2′-methylenebis (4-methyl) -6-tert-butyl) phenol, etc.

(17) Chelating agent: for example, edetate, pyrophosphate, hexametaphosphate, citric acid, tartaric acid, gluconic acid, etc.
(18) UV scattering agent: For example, titanium oxide, kaolin, talc, etc.
(19) pH adjuster: for example, sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonia, aqueous ammonia, triethanolamine, dimethylamine, diethylamine, trimethylamine, triethylamine, triisopropanolamine, triphosphate Sodium, disodium hydrogen phosphate, dipotassium hydrogen phosphate, monoethanolamine, diethanolamine, diisopropanolamine, polyethanolamine, and other alkali metal hydroxides, alkaline earth metal hydroxides, primary and secondary Or tertiary alkylamines or alkalis such as primary, secondary or tertiary alkanolamines, and acids such as citric acid, tartaric acid, lactic acid, glycolic acid, hydrochloric acid, nitric acid, malic acid, phosphoric acid, etc. Other, acidic or al Polymers exhibiting retentivity are also used, such as alginic acid, polyglutamic acid, polyaspartic acid, starch-acrylic acid graft polymer, polyacrylic acid, polyvinyl acetate-crotonic acid copolymer, vinyl acetate- (meth) acrylic acid copolymer. A polymer, a vinyl acetate-crotonic acid copolymer, polyvinyl sulfonic acid, polyitaconic acid, a styrene-maleic anhydride copolymer, an acrylamide-acrylic acid copolymer, and the like are exemplified, but not limited thereto.

  In addition, stabilizers, fillers, preservatives, plasticizers, softeners, anti-degradation agents, etc. can be added, and these additives can be optionally added within a range that does not affect the properties of the resulting adhesive for patches. .

  The water-containing gel body of the present invention is directly mixed with various raw materials and then poured into an appropriate mold in a sol state, where it is crosslinked and molded, or the crosslinked gel is directly used with an appropriate molding machine, tableting machine, etc. It is prepared into various molded products. The mixing of the raw materials can be performed by appropriately selecting and using, for example, a kneader, a kneader, a kneader ruder, an azimuth homomixer, a planetary mixer, a double planetary mixer, and the like.

  In order to form a hydrogel body into a sheet, paper, wood, metal, glass fiber, cloth (nel, woven fabric, non-woven fabric, etc.), synthetic resin (polyurethane, ethylene vinyl acetate copolymer, polyvinyl chloride, polyester (for example, Polyethylene terephthalate), polyolefins (eg, polyethylene, polypropylene, etc.), polyamides (eg, nylon 6, nylon 66, etc.), polyvinylidene chloride, polytetrafluoroethylene, etc., metal foils such as aluminum, rubber or cellulose derivatives and plastics with these Appropriate amount of water-containing gel can be applied to one or both sides of a molded product such as a laminated film with a film, sheet (foil), or tape, etc. Easy storage of the resulting sheet-like water-containing gel In order to make The release sheet treated by other appropriate method is stuck, or the surface not coated with hydrous gel is treated with silicon or other suitable method to make the release surface, and the gel is applied It is desirable to wind or overlap the sheet so that it overlaps the non-exposed surface, and polyethylene film, polypropylene film, release paper, cellophane, polyvinyl chloride, polyester, etc. are used as the release sheet.

  Examples of the composition for hydrogel bodies of the present invention will be described below, but the present invention is not limited to these examples. In addition, a part shows a mass part.

Example 1:
Formula:
Acrylic acid / sodium acrylate (50/50 (molar ratio)) copolymer 4 parts Glycerin 30 parts Aluminum hydroxide 0.4 parts Water 63.4 parts Sodium chloride 2 parts Tartaric acid 0.2 parts

  Based on the above formulation, an acrylic acid / sodium acrylate copolymer (“Viscomate NP-700”: Showa Denko Co., Ltd.), aluminum hydroxide (“dry hydroxylation”) was added to a mixture of water, tartaric acid and sodium chloride. Aluminum gel (S-100) ”: Kyowa Chemical Industry Co., Ltd.) and a glycerin dispersion were gradually added and kneaded until uniform. The obtained sol was molded and sealed, and then aged at about 20 ° C. for 3 days. Then, the gel was removed from the container, and when the gel was touched with a finger, it stretched, had a strong repulsive force, had a low stickiness, and did not cling to the finger. On the other hand, the obtained sol was poured into a mold having a thickness of 1.0 mm and a size of 10 × 20 cm and aged at 20 ° C. for 3 days. The support was made of a gum tape, and the gel body was coated on the adhesive surface of the gum tape. After the obtained gel body was exposed at 25 ° C. and relative humidity 60% for 24 hours, it was subjected to an inclination angle of 30 using a C140 type tester of Yoshimitsu Seiki Co., Ltd. according to the tack test method of JIS Z0237. The degree of ball tack was 8.

Example 2:
Formula:
Sodium polyacrylate aqueous solution 20 parts Glycerin 35 parts Potassium chloride 0.25 parts Aluminum hydroxide 0.4 parts Tartaric acid 1.6 parts Purified water 42.75 parts

  In the above formula, water, tartaric acid, sodium polyacrylate aqueous solution ("Viscomate SL-104Y": Showa Denko KK) and potassium chloride were mixed with aluminum hydroxide ("dried aluminum hydroxide gel (low water content product). ) ”: Kyowa Chemical Industry Co., Ltd.) and a glycerin dispersion were added all at once and kneaded until uniform. The obtained sol was molded and sealed, and then aged at about 20 ° C. for 3 days. Then, the gel was removed from the container, and when the gel was touched with a finger, it stretched, had a strong repulsive force, had a low stickiness, and did not cling to the finger.

Example 3:
Formula:
Acrylic acid / sodium acrylate (50/50 (molar ratio)) copolymer 4 parts Sodium phosphate 0.5 parts Magnesium chloride 1 part Purified water 64.4 parts Glycerin 29.5 parts Aluminum hydroxide 0.4 parts Tartaric acid 0.2 parts

  In the above formulation, acrylic acid / sodium acrylate copolymer, glycerin and aluminum hydroxide ("dried aluminum hydroxide gel (S-100)": Kyowa) in a mixed solution of sodium phosphate, magnesium chloride, tartaric acid and purified water Chemical Industry Co., Ltd.) was added and kneaded until uniform. The obtained sol was molded and sealed, and then aged at about 20 ° C. for 3 days. Then, the gel was removed from the container, and when the gel was touched with a finger, it stretched, had a strong repulsive force, had a low stickiness, and did not cling to the finger.

Example 4:
Formula:
N-vinylacetamide / sodium acrylate (55/45 (molar ratio)) copolymer
28 parts Citric acid 0.5 part Synthetic hydrotalcite 0.9 part Ammonium alum 0.1 part Aluminum oxide 19.0 parts Lithium chloride 9.5 parts 1,3-butanediol 10 parts N-vinylacetamide crosslinked 1 part Purified water 31 parts

  In the above formulation, N-vinylacetamide / sodium acrylate copolymer, synthetic hydrotalcite (“Alkamak”: Kyowa Chemical Industry Co., Ltd.), ammonium alum in a mixture of citric acid, lithium chloride and purified water Then, a mixed solution of aluminum oxide, N-vinylacetamide crosslinked product and 1,3-butanediol was gradually added and kneaded. The obtained sol was molded and sealed, and then aged at about 20 ° C. for 3 days. Then, the gel was removed from the container, and when the gel was touched with a finger, it stretched, had a strong repulsive force, had a low stickiness, and did not cling to the finger.

Example 5:
Formula:
Sodium acrylate / potassium methacrylate = 50/50 (molar ratio)
Copolymer 0.5 part Sorbitol polyglycidyl ether 0.05 part Potassium chloride 0.005 part Calcium chloride 0.005 part Sodium carboxymethylcellulose 5.5 parts Purified water 93.445 parts

  In the above-mentioned formulation, potassium acrylate / calcium chloride, sorbitol polyglycidyl ether (“Denacol EX-614B”: Nagase Kasei Kogyo Co., Ltd.) and purified water mixed solution with sodium acrylate / potassium methacrylate copolymer and carboxymethylcellulose Sodium was added all at once and kneaded well until uniform. The obtained sol was molded and sealed, and then aged at about 20 ° C. for 3 days. Then, the gel was removed from the container, and when the gel was touched with a finger, it stretched, had a strong repulsive force, had a low stickiness, and did not cling to the finger.

Comparative Example 1:
Formula:
Acrylic acid / sodium acrylate (50/50 (molar ratio)) copolymer 4 parts Glycerin 30 parts Aluminum hydroxide 0.4 parts Purified water 65.4 parts Tartaric acid 0.2 parts

  In the above formulation, an acrylic acid / sodium acrylate copolymer ("Viscomate NP-700": Showa Denko KK), aluminum hydroxide ("dried aluminum hydroxide gel (S- 100) ”: Kyowa Chemical Industry Co., Ltd.) and a glycerin dispersion were gradually added and kneaded until uniform. After the obtained sol was molded and sealed and aged at about 20 ° C. for 3 days, the gel was stretched when removed from the container and touched with a finger, but the force to return was weak, and the gel was clinging to the finger. On the other hand, the obtained sol was poured into a mold having a thickness of 1.0 mm and a size of 10 × 20 cm and aged at 25 ° C. for 3 days. The support was made of a gum tape, and the gel body was coated on the adhesive surface of the gum tape. After the obtained gel body was exposed at 25 ° C. and relative humidity 60% for 24 hours, it was subjected to an inclination angle of 30 using a C140 type tester of Yoshimitsu Seiki Co., Ltd. according to the tack test method of JIS Z0237. The ball tack value of the degree was 18.

Comparative Example 2:
Formula:
N-vinylacetamide / sodium acrylate (55/45 (molar ratio))
Copolymer 28 parts Citric acid 0.5 part Synthetic hydrotalcite 0.9 part Ammonium alum 0.1 part Aluminum oxide 19.0 parts 1,3-butanediol 10 parts N-vinylacetamide crosslinked 1 part Purified water 40.5 parts

In the above formulation, N-vinylacetamide / sodium acrylate copolymer, synthetic hydrotalcite (“Alkamak”: Kyowa Chemical Industry Co., Ltd.), ammonium alum, aluminum oxide and A mixed solution of N-vinylacetamide crosslinked product and 1,3-butanediol was gradually added and kneaded. After the obtained sol was molded and sealed and aged at about 20 ° C. for 3 days, the gel was stretched when removed from the container and touched with a finger, but the force to return was weak, and the gel was clinging to the finger.

Claims (13)

  At least one compound (A) selected from the group consisting of a compound containing a monovalent metal ion and a compound containing a divalent metal ion, a (meth) acrylic acid polymer (B), water (C) And a crosslinking agent (D) that reacts with a carboxyl group. The repeating unit of the (meth) acrylic acid polymer (B) has the general formulas (1), (2) and (3).

(In the formula, R ¹ and R ² each independently represents a hydrogen atom or a methyl group, M represents NH ₄ ⁺ or an alkali metal, and X represents a divalent organic group derived from an unsaturated monomer. ), (1) / (2) = 100/0 to 0/100 (molar ratio), and the total amount of (1) and (2) / (3) = 100/0 to 10/90 (molar ratio) The composition for hydrogel bodies according to claim 1.   M is sodium, the repeating units (1) and (2) are in the range of (1) / (2) = 0/100 to 100/0 (molar ratio), and include the repeating unit (3) The composition for hydrogel bodies according to claim 2, which is not present.   The composition for hydrogel bodies according to claim 1, wherein the compound containing a monovalent metal ion is sodium chloride.   Furthermore, the composition for hydrous gel bodies of Claim 1 containing a polyhydric alcohol (E).   The composition for hydrous gel according to claim 1, wherein the crosslinking agent (D) that reacts with the carboxyl group is an aluminum compound.   The composition for a hydrogel body according to claim 2, wherein the (meth) acrylic acid polymer (B) is a sodium acrylate-N-vinylacetamide copolymer.   A water-containing gel obtained by using the composition for water-containing gel according to any one of claims 1 to 7.   The water-containing gel body according to claim 8, wherein a content of water contained in the water-containing gel body is 5 to 98 mass%.   A method for producing a hydrogel body, comprising cross-linking the composition for hydrogel body according to claim 1 at room temperature.   A transdermally absorbable preparation using the hydrogel body according to claim 8 or 9.   A cooling sheet using the hydrogel body according to claim 8 or 9. Cosmetics using the water-containing gel body according to claim 8 or 9.