WO2006112533A1

WO2006112533A1 - Water-containing gel form and production method thereof

Info

Publication number: WO2006112533A1
Application number: PCT/JP2006/308496
Authority: WO
Inventors: Tetsuya Ishii; Manabu Kanayama
Original assignee: Showa Denko K.K.
Priority date: 2005-04-18
Filing date: 2006-04-18
Publication date: 2006-10-26

Abstract

Provides a water-containing gel form which exhibits reduced stickiness to the attached material, good sence of use and low irritation to skin, forms no syneresis liquid, has simple composition and is easily prepared. Further, provides a method to adjust arbitrarily crosslinking speed on production of a water-containing gel form using a (meth)acrylic acid-based polymer. (1) a composition for water-containing gel form comprising at least one kind of compound (D) selected from the group consisting of compounds containing a monovalent or divalent metal ion, and a (meth)acrylic acid-based polymer (A), water (C) and a crosslinker (B), which reacts with carboxyl groups, as major components, (2) a water-containing gel form obtained from the composition, (3) a production method of the water-containing gel form and (4) a transdermal formulation, cooling sheet and cosmetics using the water-containing gel form. A production method of a water-containing gel form, wherein crosslinking speed of the (meth)acrylic acid-based polymer is adjusted by adding at least one kind of metal salt (component D') selected from the group consisting of metal salts containing a monovalent or divalent metal ion when the (meth)acrylic acid-based polymer (component A) is crosslinked by mixing with an aluminum-containing compound (component B') and water (component C).

Description

DESCRIPTION

WATER - CONTAINING GEL FORM AND PRODUCTION METHOD THEREOF

Cross-Reference to related applications

This application is an application filed under 35 U. S . C. §111 (a) claiming benefit pursuant to 35 U. S .C. §119 (e) of the filing dates of Provisional Application Nos . 60/675098 and 60/734314 filed April 27, 2005, and November 8, 2005, respectively, pursuant to U. S. C. §111 (b) .

Field of the invention

This invention relates to a water-containing gel form used in transdermal formulation, cosmetics, cooling sheet or the like and a production method thereof. More specifically, it relates to a water-containing gel form with reduced stickiness, very excellent sence of use and high safety by comprising a (meth) acrylic acid-based polymer, a production method and use thereof . Furthermore, the present invention relates to a method for controlling crosslinking speed on production of the water-containing gel form comprising the (meta) acrylic acid-based polymer based on that the crosslinking speed is altered by adding a metal salt to a raw material composition.

Background art

In recent years, a water-containing gel form comprising an acrylic acid-based polymer has been often used in transdermal formulation for medical use, cooling sheet, cosmetics and the like. Because the acrylic acid-based polymer generally used has high molecular weight, a gel form having elasticity and shape-retaining property can be produced by crosslinking carboxyl groups, which serve as crosslinking points, with aluminum ion. However, the acrylic acid-based polymer exhibits stickiness when it is dissolved in water, causing excessive stickiness and bad sence of use. On the other hand, other water-soluble polymers have deficiency such that the gel exhibits extremely low stickiness (for example, agar) (Japanese published unexamined application 2001-96145; Patent document 1) or that conventional crosslinking system using an aluminum compound cannot be used. Accordingly, there has been demand for a water-containing gel form with reduced stickiness comprising a (meth) acrylic acid-based polymer wherein the conventional crosslinking system can be used. Such water-containing gel form is generally produced by being ionically crosslinked polymer such as sodium polyacrylate, poly(acrylic acid), acrylic acid-sodium acrylate copolymer with an aluminum compound (Japanese published unexamined application H8-104631; Patent document 2; Japanese published unexamined application 2002-275056; Patent document 3) .

Generally, an aluminum compound with poor solubility in water is used. This is because use of a highly water-soluble aluminum compound promotes crosslinking of the gel at once causing inhomogeneous crosslinking.

Moreover, in some cases, too high crosslinking speed causes inconvenience in production. Accordingly, there has been generally used a method wherein an aluminum compound with poor solubility in water is gradually dissolved by using an acid to undergo crosslinking. As acids, there have been used organic acids, particularly hydroxycarboxylic acids having both a hydroxyl group and a carboxyl group in a molecule such as lactic acid and tartaric acid (Japanese published unexamined application S60-226808; Patent document 4) .

Patent document 1; Japanese published unexamined application 2001-096145

Patent document 2; Japanese published unexamined application H8-104631 Patent document 3; Japanese published unexamined application 2002-275056

Patent document 4; Japanese published unexamined application S60-226808 DISCLOSURE OF THE INVENTION

It has been desired to solve the above-mentioned problems of the conventional techniques and to provide a water-containing gel form which exhibits low stickiness to an attached object, good sence of use and low irritation to skin, forms no syneresis liquid, is simple in composition and can be easily prepared.

Furthermore, when gel is produced under the conditions disclosed in Patent documents 2 to 4, the crosslinking speed is difficult to adjust and in most cases, crosslinking occurs too fast or too slowly. If crosslinking occurs too fast, the gel is rapidly cured, and coating and molding become difficult. On the other hand, if crosslinking occurs too slowly, for example, when the gel is coated on supporting nonwoven fabric, it penetrates from the fabric, or curing takes longer period,- which reduces productivity. As means for solving these problems, there has been adopted a method for retarding the progress of crosslinking, wherein crosslinking is retarded by trapping aluminum temporarily by adding a chelating agent such as disodium ethylenediaminetetraacetate or tetrasodium ethylenediaminetetraacetate dihydrate. However, this method extremely retards crosslinking and poses a lot of restrictions such as effects on other raw materials, toxicity in application to human body and inability of accelerating crosslinking.

Alternatively, there has been a method for retarding dissolution of aluminum ion, wherein production (kneading) of a water-containing gel form is carried out at low temperature, but this method also has problems of extremely slow crosslinking and rising production cost. On the other hand, for promoting crosslinking there has been a method wherein gel is heated after molding, but this method has problems such that productivity decreases, introduction of thermally unstable compounds is difficult and the gel becomes inhomogeneous as water evaporates. In such circumstances, there has also been desired to solve the problems of conventional techniques and to provide a method to control crosslinking speed of a

(meth) acrylic acid-based polymer which is very simple in composition, causes no problem of toxicity and can be applied to the same production process as that used conventionally. Considering the above-mentioned circumstances, the present inventors investigated production method of a water-containing gel form with reduced stickiness by using a poly(acrylic acid) partial salt (acrylic acid-acrylate salt copolymer) or polyacrylate salt.

First, they tried that a crosslinker in a high concentration was added to an acrylic acid-acrylate salt copolymer or polyacrylate salt. However, in the case where crosslinking was performed with a water-soluble epoxy compound or aluminum ion, the gel strength was unstable or the gel form exhibited poor transparency due to turbidity. Moreover, particularly when a water-soluble epoxy compound was used as the crosslinker, effects of residual material on skin such as irritation were feared.

Next, they tried that the system was made acidic to reduce stickiness by shrinking the polymer due to suppression of salt dissociation of the poly (acrylic acid) partial salt (acrylic acid-acrylate salt copolymer) or polyacrylate salt . Indeed, stickiness was reducedby this method, but syneresis liquid was gradually formed and in some cases the pH of the gel form significantly decreased, causing a problem of safety in use for human body.

Then, the present inventors found that addition of a compound comprising monovalent metal ion to a composition comprising a (meth) acrylic acid-based polymer suppresses dissociation of carboxyl groups in the (meth) acrylic acid-based polymer due to ion-blocking by the metal ion, causing aggregation (shrinkage) of the polymer and providing water-containing gel with reduced stickiness and excellent water-holding ability and they accomplished the present invention.

Moreover, during investigation on preparation of gel forms by crosslinking of a polyacrylate salt with an aluminum-containing compound, the present inventors found that crosslinking speed can be arbitrarily adjusted by adding at least one kind of metal salt selected from the group consisting of metal salts comprising a monovalent or divalent metal ion, and they examined effects of various metal salts on the crosslinking speed to accomplish the present invention.

The present invention provides a composition for a water-containing gel form, a production method thereof, the gel form and transdermal formulation, cooling sheet and cosmetics using the gel form described below. 1. A composition for a water-containing gel form comprising at least one kind of compound (component D) selected from the group consisting of compounds comprising a monovalent or divalent metal ion, and a (meth) acrylic

acid-based polymer (component A) , water (component C) and a crosslinker which reacts with carboxyl groups (component

B) . 2. The composition for water-containing gel form according to 1, wherein the repeating units of the (meth) acrylic

acid-based polymer (component A) are represented by general formulae (1) , (2) and (3) :

-CH₂C (R¹) (COOM) - (1) -CH₂C (R²) (COOH) - (2)

-X- (3)

(In the formulae, each of R¹ and R² represents independently a hydrogen atom or a methyl group, M represents NH₄ ⁺ or an alkali metal and X represents a divalent organic group derived from an unsaturated monomer), the molar ratio of (I)/ (2) ranges from 100/0 to 0/100 and the molar ratio of total amount of (1) and (2) to (3) ranges from 100/0 to 10/90.

3. The composition for water-containing gel form according to 2, wherein M is sodium, the molar ratio of the repeating

units (1) and (2'), (I)/ (2), is in a range from 0/100 to

100/0 and the repeating unit (3) is not contained.

4. The composition for water-containing gel form according

to 1, wherein the compound comprising a monovalent metal ion is sodium chloride.

5. The composition for water-containing gel form according to 1, which further comprises a polyol (component E) . 6. The composition for water-containing gel form according to 1, wherein the crosslinker which reacts with carboxyl groups (component B) is an aluminum compound. 7. The composition for water-containing gel form according to 2, wherein the (meth) acrylic acid-based polymer (component A) is sodium acrylate-JW-vinylacetamide copolymer.

8. A water-containing gel form prepared by using the composition for water-containing gel form according to 1.

9. A production method of a water-containing gel form, wherein the composition for water-containing gel form according to 1 is crosslinked at room temperature.

10. A production method of a water-containing gel form, wherein, on crosslink.ing of the (meth) acrylic acid-based polymer (component A) by mixing with an aluminum compound

(component B^f ) and water (component C), the crosslinking speed of the (meth) acrylic acid-based polymer is adjusted by adding at lea-st one kind of metal salt (component D' ) selected from the group consisting of metal salts comprising a monovalent or divalent metal ion.

11. The production method^'of a water-containing gel form according to 10, wherein the metal salt (component D') is dissolved in water in advance and then added. 12. The production method of a water-containing gel form according to 10, wherein the metal salt (component D' ) is

added at a temperature ranging from 0°C to 40°C.

13. The production method of a water-containing gel form according to 10, wherein the (meth) acrylic acid-based polymer comprises repeating units represented by general formulae (1), (2) and (3) : -CH₂C (R¹) (COOM) - (1)

-CH₂C (R²) (COOH) - (2)

-X- (3)

(In the formulae, each of R¹ and R² represents independently a hydrogen atom or a methyl group, M represents NH₄ ⁺ or an alkali metal and X represents a divalent organic group derived from an unsaturated monomer) , the molar ratio of (I)/ (2) ranges from 100/0 to 0/100 and the molar ratio of total amount of (1) and (2) to (3) ranges from 100/0 to 10/90. 14. The production method of a water-containing gel form according to 13/ wherein the (meth) acrylic acid-based polymer (component A) is sodium acrylate-N-vinylacetamide copolymer . 15. The production method of the water-containing gel form according to 13, wherein M is sodium, the molar ratio of the repeating units (1) and (2) , (1) / (2) , is in a range from 0/100 to 100/0 and the repeating unit (3) is not contained. 16. The production method of a water-containing gel form according to 10, wherein the mean particle diameter (d50) of the (meth) acrylic acid-based polymer (component A) is in a range from 30 to 250 μm.

17. The production method of a water-containing gel form according to 10, wherein the metal salt (component D' ) is sodium chloride.

18. The production method of a water-containing gel form according to 10, wherein the metal salt (component D') is magnesium chloride. 19. The production method of a water-containing gel form according to 10, wherein the composition further comprises a polyol (component E) .

20. The production method of a water-containing gel form according to 19, wherein the metal salt (component D' ) is dispersed in the polyol (component E) in advance and then added.

21. A water-containing gel form obtained by the production method of the water-containing gel form according to 10. 22. The water-containing gel form according to 8 or 21, wherein the water content therein is in a range from 5 to 98% by weight.

23. A transdermal formulation using the water-containing gel form according to 8 or 21.

24. A cooling sheet using the water-containing gel form according to 8 or 21.

25.. Cosmetics using the water-containing gel form according to 8 or 21. Effects of the invention

The water-containing gel form of the present invention solves the problems of conventional technique. The water-containing gel form of the present invention exhibits reduced stickiness, good sence of use and low irritation to skin, and it does not form syneresis liquid. It is simple in composition and easily prepared.

The present invention enables adjusting arbitrarily crosslinking speed and preparing gel desired for each purpose. Furthermore, the water-containing gel form of the present invention is very simple in composition/ has no problem of toxicity and is applicable to the same production process as that used conventionally. Best mode for carrying out the invention

(Composition for water-containing gel form) The composition for water-containing gel form of the present invention comprises at least one kind of compound (component D) selected from the group consisting of compounds comprising a monovalent or divalent metal ion, a (meth) acrylic acid-based polymer (component A), water (component C) and a crosslinker (component B) which reacts with carboxyl groups as major components. (Component D)

The content of the compound comprising a monovalent or divalent metal ion used in the present invention (component D) is preferably in a range from 0.001 to 10% by weight (% by weight is simply represented as % hereafter), more preferably in a range from 0.01 to 5%, of the total amount of the composition comprising components A to D. If it is less than 0.001%, the gel form sometimes exhibits high stickiness and bad sence of use. When it is more than 10%, the polymer sometimes excessively aggregates causing formation of syneresis liquid or the gel form exhibits very poor adhesion to' skin due to extremely low stickiness. Among compounds containing a monovalent metal ion, as lithium-containing compounds there may be mentioned "lithium oxide, butyllithium, ^' ethyllithium, lithium bromide, lithium carbide, lithium iodide, lithium nitrate, lithium nitride, lithium sulfide, methyllithium, lithium sulfate, lithium chloride, lithium hydride, propyllithium, lithium carbonate, lithium fluoride, lithium niobate, lithium peroxide, lithium hydroxide, lithium molybdate, lithium perchlorate, lithium acetate, lithium formate, lithium tungstate, lithium hypochlorite, lithium acetate dehydrate anhydrate, lithium iodide dihydrate, lithium hydrogensulfate, lithium acetate dihydrate, lithium bromide monohydrate, lithium sulfate monohydrate, dilithium carbonate, dilithium oxalate, dilithium sulfate, lithium chromate dihydrate, lithium hydroxide monohydrate, lithium citrate tetrahydrate, lithium perchlorate trihydrate and lithium hexafluorophosphate . As sodium-containing compounds, there may be mentioned sodium azide, sodium amide, sodium oxide, sodium acetate, sodium acetylide, sodium bromide, sodium formate, sodium iodide, sodium lactate, sodium methoxide, sodium nitrate, sodium sulfate, sodium sulfide, sodium borate, sodium metal, sodium bromate, sodium chloride, sodium hydride, sodium nitrite, 'sodium sulfite, sodium iodate, sodium phosphate, ecabet sodium, sodium valerate, heparin sodium salt, sodium chlorate, sodium citrate, sodium cyanate, sodium cyanide, sodium fluoride, sodium oleate, sodium oxalate, sodium peroxide, sodium silicate, sodium stannate, sodium t-butoxide, sodium carbonate, suramin sodium salt, sodium benzoate, sodium chlorite, sodium chromate, sodium hydroxide, sodium selenate, sodium selenide, sodium laurate, disodium inosinate (abbreviated as IMP hereafter), sodium alginate, sodium perborate, sodium persulfate, sodium phosphite, sodium rhodanide (sodium thiocyanate) , disodium arsenate, sodium selenite, amfenac sodium, tolmetin sodium, sodium pyruvate, saccharin sodium salt, sodium aluminate, sodium gluconate, sodium polysulfide, sodium stearate, sodium valproate, sodium iopodate, sodium bicarbonate (sodium hydrogen carbonate) , disodium carbonate, sodium periodate, reviparin sodium, porphimer sodium, carumonam sodium, cefminox sodium, flomoxef sodium, cefalotin sodium, cefazolin sodium, latamoxef sodium, sodium glutamate, sodium molybdate, sodium percarbonate, sodium perchlorate, sodium salicylate, sodium thiosulfate, thiamylal sodium, triclofos sodium, sodium dichromate, sodium borofluoride, acidic sodium sulfide, disodium phosphate, beraprost sodium, cefotetan sodium, ceftezol sodium, faropenem sodium, trisodium citrate, cephapirin sodium, ampicillin sodium, cefoxitin sodium, cefsulodin sodium, cefuroxime sodium, dantrolen sodium, sodium antimonate,^' sodium propionate, sodium tungstate, sodium pyrosulfite, trisodium phosphate, sodium triphosphate, sodium hydrosulfite, dalteparin sodium, parnaparin sodium, danaparoid sodium, cefodizime sodium, carmellose sodium, sodium iotalamate, foscarnet sodium, sodium metasulfite, cefotaxime sodium, cefpiramide sodium, sodium cyclohexyl sulfamate (sodium cyclamate), diclofenac sodium, sodium borohydride, sodium hypochlorite, thiopental sodium, ticarcillin sodium, phosphomycin sodium, sodium arsenate, sodium phosphinate dibasic ( sodium hypophosphite) , sodium hyarulonate, imitrodast sodium, bucladesin sodium, sodium glucronate, aluminum sodium sulfate, cefmetazole sodium, ceftizoxime sodium, cloxacillin sodium, fluorescein sodium salt, liothyronine sodium, loxoprofen sodium, piperacillin sodium, sodium hydrosulfite, sodium naphthionate, sodium permanganate, sodium pyrophosphate, fluvastatin sodium, pravastatin sodium, rabeprazole sodium, sodium methacrylate, 5'-IMP disodium salt, amobarbital sodium, cefamandol sodium, cefoperazone sodium, sodium ferrocyanide (sodium hexacyanoferrate ( II) , ) sodium hydrogensulfide/ sodium metavanadate, sodium silicofluoride sodium hexafluorosilicate) , sodium xanthogenate, sodium lauryl sulfate ( sodium dodecyl sulfate), sodium cromoglycate, sodium picosulfate, sodium fluoroacetate, sodium metabisulfite, sodium taurocholate, cerivastatin sodium, sodium acetate trihydrate, ceftriaxone sodium, carbenicillin sodium, cefbuperazone sodium, sodium hydrogen fumarate, levothyroxine sodium, sodium dehydroacetate, sodium hydrogensulfite, sulbenicillin sodium, sodium borate decahydrate, sodium metavanadate, sodium metaperiodate, sodium cholate hydrate, sodium sul fate decahydrate, secobarbital sodium, lobenzarit disodium, sodium deoxycholate, sodium nitroprusside, dicloxacillin sodium, sodium phthalocyanine, sodium thioglycolate, disodium sulfate, sodium dihydronaphthalenidyl, sodium aurothiomalate, 2-biphenylol sodium salt, sodium cholate n-hydrate, sodium stannate trihydrate, sodium sulfide nonahydrate, disodium calcium edetate, epoprostenol sodium, sodium iron (II) citrate, anhydrous sodium carbonate, sodium sulfite heptahydrate, sodium silicoaluminate, sodium benzoate-caffeine, disodium hydrogenarsenate, saccharin disodium salt dihydrate, sodium phosphate dibasic, sodium trichloroacetate, sodium tripolyphosphate, sodium peroxobisulfate/ bromphenac sodium hydrate, sodium molybdate dihydrate, sodium phosphate basic, sodium phosphate tribasic, sodium trifluoroacetate, tetrasodium pyrophosphate, sodium chro^'mate tetrahydrate, sodium succinate hexahydrate, sodium dihydrogen citrate, sodium stearyl fumarate, antimony sodium tartrate, sodium cyanoborohydride, sodium dihydrogenphosphate, sodium prasterone sulfate, sodium selenite pentahydrate, dipicrylamine sodium salt, sodium hexametaphosphate, sodium perborate tetrahydrate, sodium tetrahydroborate, acyl D-alanine sodium salt, disodium hydrogenphosphate, sodium perchlorate monohydrate, sodium (+) -pantothenate, sodium metasilicate (anhydrous), sodium tetrafluoroborate, sodium sulfanylate dihydrate, sodium cellulose sulfate, pantoprazole sodium hydrate, chondroitin sulfate sodium salt, disodium methylarsonate, sodium riboflavin phosphate, dextran sulfate sodium sulfur, trisodium phosphate dodecahydrate, disodium 5 ' -guanylate, disodium 5 ' -inosinate, dextran sulfate sodium sulfur 18, sulfobromophthalein sodium salt, disodium 5 ' -citidilate, sodium laurylsulfonate, betamethasone sodium phosphate, sodium polystyrenesulfonate, prednisolone sodium phosphate, sodium pentachloxophenolate, sodium dichloroisocyanurate, dexamethasone sodium phosphate, estramustine phosphate sodium, prednisolone sodium succinate, sodium hydrogen fumarate, sodium 1-dodecanesulfonate, sodium dihydrogenphoshate dihydrate, carbazochrome sodium sulfonate, hydrocortisone sodium phosphate, sodium 2-hydroxypropanoate, sodium pyrophosphate decahydrate, disodium dihydrogenpyrophosphate, sodium triacetoxyborohydride, hydrocortisone sodium succinate, sodium dihydrogenphosphate dodecahydrate, colistin sodiummethanesulfonate, sodium dodecylbenzenesulfonate, chloramphenicol sodium succinate, sodium 2-hydroxypropionate, disodium 2-hydroxysuccinate, sodium ( Z) -9-octadecenoate, sodium cyclohexylsulfaminate, flavin adenine dinucleotide sodium salt, disodium uridine 5 ' -diphosphate, sodium diphenylamine-4-sulfonate, methylprednisolone sodium succinate, sodium inosine 5 ' -monophosphate, disodium inosine 5 ' -diphosphate, sodium iV-cyclohexylsufaminate, disodium citidine 5 ' -phosphate, disodium guanosine 5 ' -phosphate, sodium hydrogen ( E) -2-butenedioate, dexamethasone sodium m-sulfobenzoate, sodium (2, 4-dichlorophenoxy) acetate, disodium 1, 5-naphthalenedisulfonate, sodium pentachlorophenolate (technical grade) , sodium

4- (2, 4-dichloro-τπ-toluoyl) -1, 3-dimethylpyrazol-5-olate, sodium ( 4-chloro-2-methylphenoxy) acetate, hardened coconut-oil fatty acid glyceryl ester sulfate sodium salt, sodium 5-ethyl-5, 8-dihydro-8-oxofuro [ 3 , 2-b] [1,8] naphthyridine

-7-carboxylate, trisodium

2-hydroxy-l, 2, 3-propanetricarboxylate, disodium l-phenylazo-2-naphthol-4 ' , 6-disulf onate, sodium 1- (p-sodiosulfophenylazo) -2-hydroxynaphthalene-6-sulf o nate, disodium

6-hydroxy-5- [ ( 4-sulf ophenyl ) azo] -2-naphthalenesulf onat e, trisodium

2-hydroxy- ( 1 , 1 ' -azobisnaphthalene ) -3, 4 ' , 6-trisulfonate, (+ ) -IV- [(R) -2, 4-dihydroxy-3, 3-dimethylbutyryl ] D-alanine sodium salt, sodium

4- [ (2 , 4-dimethylphenyl) azo] -3-hydroxy-2 , 7-naphthalened isulfonate, sodium

( + ) -3- [ [ (R) -2, 4-dihydroxy-3, 3-dimethylbutyryl] amino]pr opionate and sodium

[methyl (2, 3-dihydro-l, 5-dimethyl-3-oxo-2-phenyl-lJf-pyr azol-4-yl) amino] methanesulfonate .

As potassium-containing compounds, there may be mentioned 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, potassium chromate, potassium hydroxide, potassium phosphate, potassium sorbinate, potassium bisulfate, potassium selenate, potassium persulfate, potassium rhodanide (potassium thiocyanate ) , losartan potassium, potassium selenite, potassium tellurite, warfarin potassium, potassium periodate, potassium gluconate, potassium canrenoate, potassium perchlorate, potassium thiosulfate, potassium dichromate, potassium borofluoride, potassium molybdate, potassium pyrosulfite, potassium aspartate, pemirolast potassium, potassium hypochlorite, potassium clavulanate, aluminum potassium sulfate, potassium borohydrite, potassium hypophosphite, potassium metaphosphate, potassium permanganate, potassium pyrophosphate, potassium ferricyanide, potassium ferrocyanide, potassium silicofluoride (potassium fluorosilicate, potassium hexafluorosilicate) , potassium hydrogensulfate, potassium metavanadate, potassium xanthσgenate (potassium o-ethyldithiocarbonate ) , potassium hydrogenoxalate, dipotassium clorazepate, potassium selenocyanate, dipotassium oxalate, , potassium stannate trihydrate, potassium hydrogencarbonate, potassium peroxobisulfate, tetrapotassium pyrophosphate, benzylpenicilline potassium salt, potassium (methylsulfinyl ) methanide, potassium dihydrogenphosphate, dipotassium hydrogenphosphate, glycyrrhizic acid dipotassium salt, potassium tetrafluoroborate, potassium guiacolsulfonate, aluminum potassium sulfate dodecahydrate, potassium hexacyanoferrate (III) , phenoxymethylpenicillin potassium salt and potassium {2E, AE) -2, 4-hexadienoate . As rubidium-containing compounds, there may be mentioned rubidium oxide, rubidium bromide, rubidium iodide, rubidium sulfate, rubidium chloride, rubidium fluoride, rubidium acetate, rubidium hydrogensulfate, dirubidium carbonate. As cesium-containing compounds, there may be mentioned cesium cyanide, cesium oxide, cesium bromide, cesium iodide, cesium nitrate, cesium sulfate, cesium chloride, cesium carbonate, cesium fluoride, dicesium carbonate, dicesium oxalate, dicesium sulfate, dicesium L-tartrate, cesium hydroxide monohydrate, cesium trifluoroacetate and sodium hydrogen 2 , 3-dihydroxybutanedioate . The compound containing monovalent metal ion is not limited to those listed here. Among these, from the viewpoints of safety and stability of compounds, it is preferably sodium chloride or potassium chloride, in particular sodium chloride.

Among compounds containing divalent metal ion, as beryllium-containing compounds, there may be mentioned beryllium oxide, beryllium bromide, beryllium carbide, beryllium iodide, beryllium nitrate, beryllium nitride, beryllium sulfide, beryllium chloride, beryllium fluoride, beryllium silicate, beryllium distearate, beryllium sulfate tetrahydrate and beryllium acetylacetonate . As magnesium-containing compounds, there may be mentioned magnesium oxide, magnesium orotate, arylmagnesium, magnesium acetate, magnesium boronide, magnesium bromide, magnesium carbide, magnesium iodide, magnesium nitrate, magnesium nitride, magnesium sulfate, magnesium sulfide, magnesium (powder) , magnesium chloride, magnesium carbonate, magnesium chlorate, magnesium citrate, magnesium fluoride, magnesium silicate, magnesium silanide, magnesium hydroxide, magnesium phosphoride, magnesium orothinate, magnesium (II) nitrate, magnesium stearate, magnesium perchlorate, magnesium myristate, magnesium oxalate, magnesium hydrogencarbonate, magnesium silicσfluoride, magnesium fluorosilicate, phenylmagnesium bromide, magnesium nitrate hexahydrate, phthalocyanin magnesium, magnesium acetate tetrahydrate, magnesium benzoate trihydr^'ate, calcium magnesium carbonate, magnesium chromate pentahydrate, magnesium hexaf luorosilicate, magnesium metaaluminosilicate, bismuth magnesium aluminosilicate and aluminum magnesium hydroxide carbonate hydrate. As calcium-containing compounds, there may be mentioned calcium carbide, calcium oxide, calcium bromide, 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 iodate, calcium carbonate, calcium chlorate, calcium fluoride, calcium oxalate, calcium peroxide, calcium silicate, calcium silanide, calcium cyanide, calcium arsenite, heparin calcium salt, calcium chlorite, calcium chromate, calcium hydroxide, calcium phosphate, calcium phosphoride, calcium folinate, calcium gluconate, calcium stearate, calcium aspartate, calcium hypochlorite, phosphomycin calcium salt, calcium metasilicate, calcium thiocyanate, calcium hypophosphite, calcium panthotenate, calcium permanganate, phenoproϋen calcium, calcium' chloride dihydrate, calcium magnesium carbonate, polycarbofil calcium, mupirocin calcium salt hydrate, calcium hydrogenphosphate, calcium glycerophosphate, calcium diiodostearate, precipitated calcium carbonate, calcium disodium edetate, atorvastatin calcium salt hydrate, calcium (+ ) -panthotenate, calcium p-aminosalycilate, calcium tocopherol succinate, calcium polystyrenesulfonate, (+ ) -panthotenic acid calcium salt (2:1), calcium alumino-p-aminosalicylate and calcium 3-hydroxy-4- [ ( 4-methyl-2-sulfophenyl ) azo] -2-naphthalen ecarboxylate . As barium-containing compounds, there may be mentioned 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 (II) nitrate, barium selenite, barium manganate, barium oxalate, barium stearate, barium perchlorate, barium thiosulfate, barium hypochlorite, barium permanganate, chloranilic acid barium salt, barium chloride dihydrate, barium diacetate, barium bromide dihydrate, barium dipropionate, barium chlorate monohydrate, barium hydroxide octahydrate, barium thiocyanate dihydrate, barium thiosulfate monohydrate and barium acetylacetonate dihydrate, although the compound containing divalent metal ^'ion is not limited to these. (Component A)

The content of the (meth) acrylate salt polymer (component A) used in the water-containing gel form of the

present invention is preferably in a range from 0.5 to 30% by weight, more preferably in a range from 2 to 20% by weight of the total amount of composition comprising components

A to D. When it is less than 0.5% by weight, the gel strength is too low, and as a result oozing out from a supporting body or remaining of the gel on skin sometimes takes place. When it is more than 30% by weight, the viscosity of sol during molding increases, and coating or mixing with other components may become difficult.

The repeating units of the (meth) acrylic acid-based polymer, component A, are represented by general formulae (1) , (2) and (3) .

-CH₂C (R¹) (COOM- (1)

-CH₂C (R²) (COOH) - (2)

-X- (3)

(In the formulae, each of R¹ and R² represents independently a hydrogen atom or a methyl group, M represents NH^⁺ or an

alkali metal and X represents a divalent organic group

derived from an unsaturated monomer) Preferably the molar

ratio of (I)/ (2) is 100/0 to 0/100 and the molar ratio of

total amount of (1) and (2^') to (3) is 100/0 to 10/90. Wherein, the polymer in which M is alkali metal is not included in component D.

As specific examples of component A, there may be mentioned single-component polymer of acrylic acid or methacrylic acid, alkali metal salts such as sodium salt and potassium salt and ammonium salt thereof, copolymer of alkali metal salts such as sodium salt and potassium salt or ammonium salt of acrylic acid or methacrylic acid and acrylic acid, and copolymer of alkali metal salts such as sodium salt and potassium salt or ammonium salt of acrylic acid or methacrylic acid and methacrylic acid. Among these, the case wherein M is sodium salt is preferred. An unsaturated monomer other than acrylic acid-related compounds may be used in a range up to 90 mol% of the total amount of unsaturated monomers used as the component A.

As unsaturated monomers other than acrylic acid-related compounds, there may be mentioned, for example, acidic group-containing hydrophilic unsaturated monomers such as' maleic acid, maleic anhydride, fumaric acid, crotonic acid, itaconic acid, vinylsulfonic acid, styrenesulfonic acid, 2- (meth) acrylamido-2-methylpropanesulfonic acid, 2- (meth) acryloylethanesulfonic acid and

2- (rαeth) acryloylpropanesulfonic acid or salts thereof; non-ionic hydrophilic unsaturated monomers such as ΛJ-vinylacetamide, Λf-methyl-N-vinylacetamide, acrylamide, methacrylamide, N-ethyl (meth) acrylamide, Λf-n-propyl (meth) acrylamide, N-isopropyl (meth) acrylamide,

N, AT-dimethyl (meth) acrylamide, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, methoxypolyethylene glycol (meth) acrylate, polyethylene glycol mono (meth) acrylate, vinylpyridine, W-vinylpyrrolidone, .W-acryloylpiperidine and N-acryloylpyrrolidine; cationic hydrophilic unsaturated monomers such as

(meth) acrylate,

(meth) acrylate , iV^N-dimethylaminopropyl (meth) acrylate

N,N-dimethylaminopropyl (meth) acrylamide and quaternary salts thereof, styrene, vinyl chloride, butadiene, isobutene, ethylene, propylene, stearyl (meth) acrylate and lauryl (meth) acrylate . One kind or two or more kinds of monomers selected from these groups may be used. Further, one may use unsaturated monomers with which hydrophilic resin is formed by hydrolysis of a functional group such as methyl (meth) acrylate, ethyl (meth) acrylate and vinyl acetate.

Among these, A7-vinylacetamide, iV-methyl-N-vinylacetamide, AJ-vinylpyrrolidone, methoxypoly (ethylene glycol) (meth) acrylate, AJ,AJ-dimethylaminoethyl (meth) acrylate or acrylamide is particularly preferred.

In the present invention, a preferred polymer as component A is sodium acrylate-AJ-vinylacetamide copolymer . As polymerization method of the above-mentioned unsaturated monomers used for the component (A) , for example, there may be mentioned known polymerization methods such as (a) polymerization with a radical polymerization initiator, (b) radiation-induced polymerization, (c) electron radiation polymerization and (d) ultraviolet-ray polymerization with a photosensitizer . To obtain an acrylate polymer with high performance, (a) polymerization with a radical polymerization initiator is preferred. As polymerization method (a), for example, there may be mentioned known polymerization methods such as frame polymerization, segmentation of water-containing gel-like polymer, aqueous solution polymerization such as polymerization under pressurized conditions, reversed phase suspension polymerization, reversed phase emulsion polymerization, precipitation polymerization and bulk polymerization. Reversed phase suspension polymerization or aqueous solution polymerization is preferred. Further, the system and pressure on polymerization are not particularly limited; polymerization can be carried out in a continuous, semi-batch or batch system under a reduced, positive or normal pressure. Polymerization can be carried out by bulk polymerization or precipitation polymerization, but it is preferably carried out in solution phase from the viewpoint of performance and easiness of controlling polymerization. The solvent used in polymerization is not particularly limited as long as it is a liquid in which the unsaturated monomers are dissolved. There may be mentioned, for example, water, methanol, ethanol, acetone, dimethylformamide and dimethylsulfoxide . In particular, water or aqueous solvent is preferred. The concentration of the unsaturated monomers in solution on polymerization is not particularly limited. Although it may exceeds the saturation concentration, from the viewpoint of various physical properties and reducing remaining monomers, it is usually from 20% by weight to the saturation concentration, preferably from 25 to 50% by weight. On polymerization, a chain transfer agent or hydrophilic polymer such as starch or cellulose or derivatives thereof, polyvinylalcohol and crosslinked poly-N-vinylacetamide may be added to the unsaturated monomer. The amount of such additive is usually 5 parts by weight or less for the former and 50 parts by weight or less for the latter. As the chain transfer agent, there may be mentioned hypophosphites such as hypophosphorous acid and sodium hypophosphite, sulfur-containing compounds such as thioacetic acid, thioglycolic acid and mercaptoethanol, disulfides, halogenated compounds such as carbon tetrachloride, phosphites such as phosphorous acid and sodium phosphite. As the radical initiator used for polymerization, one can use known initiators including persulfates such as potassium persulfate, ammonium persulfate and sodium persulfate; organic peroxides such as t-butyl hydrogenperoxide and cumene hydroperoxide; azo compounds such as 2, 2' -azobis (2-amidinopropane) dihydrochloride; chlorites, hypochlorites, cerium(IV) salts and permanganates. Among these, it is preferred to use one kind or two or more kinds of compounds selected from the group consisting of persulfates, hydrogen peroxide and azo compounds. Further, when an oxidizing radical polymerization initiator is used, reducing agents such as (hydrogen) sulfites, iron and L-ascorbic acid may be used together. When an azo-type initiator is used, ultraviolet-ray may be irradiated. Such a radical initiator may be added to polymerization system either at once or successively. Its amount is usually 0.001 to 2 mol%, preferably 0.01 to 1 mol%, of the amount of unsaturated monomer. (Component B)

The water-containing gel form of the present invention comprises a crosslinker which reacts with carboxyl groups (component B) in order to maintain shape-retaining property of the obtained gel and to prohibit "adhesive deposit" . The reaction with carboxyl groups includes formation of ionic bonds or- covalent bonds.

The content of the crosslinker is in a range from 0.01 to 20% by weight, preferably in a range from 0.1 to 10% by weight, of the total amount of composition for water-containing gel form. When it is less than 0.01% by weight, crosslinking is sometimes insufficient causing stringiness on substrate. When it is more than 20% by weight, the gel strength is not constant and the gel may be unstable or the gel exhibits poor transparency due to turbidity. Particularly, in the case of epoxy compounds, toxicity and effects on stability due to unreacted material are feared.

As the crosslinker, aluminum compounds are particularly preferred.

The aluminum compounds include aluminum chloride, potassium alum, ammonium alum, aluminum nitrate, aluminum sulfate, EDTA-Al, aluminum hydroxide-sodium hydrogencarbonate coprecipitate (for example, Kyowa Chemical Industry Co., Ltd., Kumulite™) , synthetic alurαinosilicate, aluminum stearate, aluminum allantoinate, synthetic hydrotalcite (for example, Kyowa Chemical Industry Co., Ltd., ALMCAMAC™, ALCAMIZER™ and KYOWAAD™) , aluminum magnesium hydroxide (for example, Kyowa Chemical Industry Co., Ltd., Sanalmin™) , aluminum hydroxide (for example, Kyowa Chemical Industry Co ., Ltd., dried aluminum hydroxide gel S-IOO, low water type) , aluminum acetate, dihydroxyaluminum aminoacetate (for ^■ example, Kyowa Chemical Industry Co., Ltd., Glycinal™ SG, PG or SA) , kaolin, magnesium metaaluminosilicate (for example, Toyama Chemical Co ., Ltd., Neusilin™) , magnesium aluminosilicate and the like. These aluminum compounds may be water soluble or scarcely soluble to water. One kind or two or more kinds of these aluminum compounds may be us ed .

Other crosslinkers may be used. As examples of such agents, there may be mentioned salts of an inorganic acid with calcium, tin, iron, magnesium, manganese, zinc, barium or the like (for example, calcium chloride, magnesium chloride, iron alum, iron (III) sulfate, magnesium sulfate, EDTA-Ca, EDTA-Mg, tin (II) chloride, calcium carbonate, calcium phosphate, calcium hydrogenphosphate, magnesium carbonate, barium sulfate, magnesium silicate, magnesium stearate and magnesium citrate), hydroxides (for example, calcium hydroxide, barium hydroxide, magnesium hydroxide (for example, Kyowa Chemical Industry Co., Ltd., KISUMA™) , iron (III) hydroxide, tin(II) hydroxide), oxides (for example, magnesium oxide (for example, Kyowa Chemical Industry Co ., Ltd., Kyowamag™ and MAGSARAT™) ) , formaldehyde, epoxy compounds such as ethylene glycol diglycidyl ether, glycerine diglycidyl ether, polyethylene glycol diglycidyl ether, propylene glycol diglycidyl ether and polypropylene glycol diglycidyl ether. One kind or two or more kinds of these crosslinkers can be used. (Component C)

Water (component C) is added for increasing solubility of (meth) acrylic acid-based polymer and for thickening. Its amount is in a range from 5 to 98% by weight, preferably from 8 to 95% by weight. If the water content is less than 5% by weight, because solubility of (meth) acrylic acid-based polymer is reduced and thickening effect decreases, there sometimes occurs "adhesive-deposit", a phenomenon that polymer is left on releasing paper or applied skin surface, or "strike-through", a phenomenon that polymer slips out of the supporting material. On the other hand, if the amount is more than 98% by weight, the gel strength significantly decreases and as a result the gel form sometimes ooze out from the supporting material or remains on skin due to reduced shape-retaining ability.

(Component E)

The composition for water-containing gel form of the present invention preferably comprises a polyol

(component E) depending on necessity. The polyol is added to enhance solubility and activity of a drug in an adhesive for patch and to improve its transferability to skin. As polyols, there may be mentioned diols such as ethylene glycol, propylene glycol, 1 , 3-butanediol, ethylene glycol monobutyl ether,' diethylene glycol, triethylene glycol and 1, 4-butanediol, triols such as glycerine and isobutanetriol, tetraols such as erythritol and pentaerythritol, pentaols such as xylitol and adonitol, hexaols such as allodulcitol, sorbitol, sorbitol liquid and mannitol, polyglycerine, dipropylene glycol and the like, although it is not limited thereto. Among these, glycerine is particularly preferred on points of safety and affinity with (meth) acrylic acid-based polymer.

Polyols may be used singly or as a mixture of two or more. The polyol is added at 90% by weight or less, preferably 60% by weight or less, of the total amount of the composition for water-containing gel form. If the amount is more than 90% by weight, thickening effect of the (meth) acrylic acid-based polymer is difficult to be realized and the shape-retaining ability may become insufficient .

The composition for water-containing gel form of the present invention may also comprise solvent other than polyols. As examples of such solvent, there may be mentioned monools such as methanol, ethanol, propanol, benzyl alcohol, phenethyl alcohol, isopropyl alcohol, isobutyl alcohol, hexyl alcohol, 2-ethylhexanol, cyclohexanol, octyl alcohol, butanol and pentanol, ketones such as ' acetone and methyl ethyl ketone, water-miscible organic solvents such as cellosolve, dioxane, dimethylformamide, iV-methylpyrrolidone and dimethyl sulfoxide and organic solvents immiscible with water such as ethyl acetate and crotamiton.

Further, as an agent for adjusting crosslinking speed, there may be used organic acids, organic acid salts or organic bases, which can chelate or coordinate to metal ions, such as tartaric acid, citric acid, lactic acid, glycolic acid, malic acid, salicylic acid, fumaric acid, methanesulfonic acid, maleic acid, acetic acid, EDTA-2Na, urea, triethylamine and ammonia as well as inorganic acids such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid and hydrobromic acid.

The composition for water-containing gel form of the present invention may comprise other polymers for improving shape-retaining ability or adhesion of the obtained gel form. As such polymers, there may be mentioned polyvinylpyrrolidone, carboxyvinyl polymer, which is crosslinked poly(acrylic acid), vinylpyrrolidone-ethyl acrylate copolymer, W-vinylacetamide-based copolymer such as .W-vinylacetamide-sodium acrylate copolymer, s^'ingle-component polymer of N-vinylacetamide, poly (vinylsulfonic acid), crosslinked iV-vinylacetamide polymer, poly ( itaconic acid), hydroxypropylcellulose and hydroxypropylmethylcellulose . Among these, W-vinylacetamide-sodium acrylate copolymer is preferred in the point of improving adhesion to skin. In I\J-vinylacetamide-sodiuiα acrylate copolymer, the molar ratio of N-vinylacetamide to sodium acrylate is preferably in a range from 99.9:0.1 to 50:50, more preferably in a range from 95.0:5 to 50:50.

These polymers may be added at an amount of 20% by weight or less, preferably 10% by weight or less, to the total amount of the composition for water-containing gel form. If the content is more than 20% by weight, the gel form becomes too hard and feeling of adhesion to skin may be deteriorated.

(Production method of a water-containing gel form) The above-mentioned water-containing gel form can be prepared by crosslinking the composition for water-containing gel form described above at room temperature .

In the production method of the water-containing gel form relating to the present invention, at least one kind of metal salt (component D') selected from the group consisting of metal salts comprising a monovalent or divalent metal ion is added when (meth) acrylic acid-based polymer (component A) is crosslinked by mixing with an aluminum-containing compound (component B' ) and water (component C) .

By adding component D' in this way, the crosslinking speed can be adjusted arbitrarily.

Although the reason is not unambiguously clarified, the present inventors deduce the following mechanism of adjustment of crosslinking speed by adding metal salts. In the case where crosslinking is accelerated, it is considered that the concentration of carboxylate increases by the presence of metal ion and as a result formation of ionic bonds between aluminum ion and

(meth) acrylic acid-based polymer is accelerated. Salts containing a monovalent ion, particularly sodium salts, exhibit strong tendency of acceleration. For this reason, sodium salt is preferred as component D' . On the other hand, in cases wherein crosslinking is retarded, it is considered that the carboxyl groups in (meth) acrylic acid-based polymer forms ionic bonds with the metal ion in the added metal salt faster than with aluminum ion, which suppresses formation of ionic bonds between carboxyl groups in (meth) acrylic acid-based polymer and aluminum ion. Subsequently, crosslinking of the polymer with aluminum ion is likely to proceed via substitution of the metal ion with aluminum ion. Here, if the ionization tendency of the metal is larger that of aluminum, substitution of the ions is likely to occur more easily. Metal salts containing a divalent metal ion, particularly calcium salts tend to retard crosslinking. This is likely because calcium ion forms ionic bonds with carboxyl groups in (meth) acrylic acid-based polymer faster than aluminum ion, causing aggregation of the polymer molecules and decrease of the gel strength.

Component A used in the present invention is as described above. In order to improve the precision of adjustment of crosslinking speed by adding metal salts, the mean particle diameter (d50) of (meth) acrylic acid-based polymer (component A) is preferably 30 to 250

/im, more preferably 50 to 150 jUm. If the mean particle size is 30 flm or less, the polymer dissolves in water too quickly and the reaction of the polymer with the metal ion proceeds inhomogeneously, while if it is 250 μm or more, dissolution in water is too slow resulting difficulty in controlling the crosslinking speed of the (meth) acrylic acid-based polymer. Aluminum compounds (component B' ) used here are aluminum compounds among the crosslinkers described above. (Component B)

The aluminum compound is added in the amount in a range from 0.01 to 20% by weight, more preferably in a range from 0.1 to 10% by weight, of the total amount of components A , B' , C and D' . If the amount is less than the above-mentioned lower limit, crosslinking is insufficient causing stringiness on supporting material. If the amount is more than the above-mentioned upper limit, the gel strength is unstable or the gel form exhibits poor transparency due to turbidity. Moreover, as mentioned above, other crosslinkers may be added together with the aluminum compounds. When such a crosslinker other than the aluminum compounds is used, the crosslinker is added in the amount of preferably 10% by weight or less, more preferably 5% by weight or less, of the total amount of composition .

Component C is as described above. Component D' is used here are metal salts which are listed in above Component D but contain neither metal oxide nor organic compound.

The amount of component D' added is in a range from 0.01 to 15% by weight, preferably in a range from 0.1 to 10% by weight of the total amount of components A, B' , C and D' .

Particularly, when component A contains COOM groups and the amount of metal salt is adjusted based on the molar amount of COOM group, crosslinking speed can be adjusted more efficiently.

When a monovalent metal salt is added, the molar ratio of monovalent ion to COOM group in the (meth) acrylic acid-based polymer is preferably [COOM] / [monovalent metal ion] = 0.01 to 60.0, more preferably [COOM] / [monovalent metal ion] = 0.1 to 40.0. If this ratio is more than 60.0, effect of the added metal ion may be hardly attained. If it is less than 0.01, the gel tends to form syneresis liquid after crosslinking or desired properties may not be obtained, for example, the pH of gel form is altered or adhesion is reduced.

If a divalent metal salt is added, the molar ratio of divalent ion to COOM group in the (meth) acrylic acid-based polymer is preferably [COOM] / [divalent metal ion] = 0.01 to 50.0, more preferably [COOM] / [divalent metal ion] = 0.1 to 30.0. In the case where two or more kinds of the monovalent metal salts or two or more kinds of the divalent metal salts are used together, they can be added at amounts in the above-mentioned range. When the monovalent salt and the divalent metal salt are used together, they can be added at amounts such that [COOM] /[sum of monovalent and divalent metal ions] = 0.01 to 50.0, as in the case of the divalent metal salts.

On adjusting crosslinking speed, when crosslinking is accelerated with a monovalent salt, the more it is added, the faster the crosslinking proceeds. When crosslinking is retarded with a divalent salt, the more it is added, the more the crosslinking is slowed. Thus, depending on the desired crosslinking speed, one can vary charge of a metal salt or adjust the amount to be added.

The amount of the (meth) acrylic acid-based polymer (component A) added in the composition is in the range described above .

Preferred (meth) acrylic acid-based polymer mixture used in the method of adjusting cross liking speed in the present invention, depending on necessity, comprises a polyol (component E), which is as described above. Moreover, the metal salt (component D' ) may be dispersed in the polyol in advance and then added.

Further, the above-mentioned agent for adjusting crosslinking speed may be used.

In the method of adjusting crosslinking in the present invention, other polymers may be added to the (meth) acrylic acid-based polymer to improve shape-retaining ability or adhesion. As such polymers, there may be mentioned those described above. (Preparation method) In the method for adjusting crosslinking speed of (meth) acrylic acid-based polymer relating to the present invention, at least one kind of metal salt (component D' ) containing a monovalent or divalent metal ion is added to a mixture comprising the (meth) acrylic acid-based polymer (component A), the aluminum-containing compound (component B')_/ water (component C) and optional components such as the polyols described above.

It is preferred that metal salt (component D') is dissolved in water in advance. Alternatively, when the composition comprises a polyol, the metal salt may be dispersed in the polyol (component E) and then added.

Metal salt (component D' ) is added at a temperature from 0 to 40⁰C, preferably from 5 to 40°C, if necessary, with stirring. In this temperature range, crosslinking speed can be adjusted easily.

The water content contained in the water-containing gel form thus obtained is desirably 5 to 98% by weight, preferably 10 to 95% by weight. Gel forms with water content in this range exhibit high shape-retaining ability and high gel strength and therefore they are suitable for use in transdermal formulations, cooling sheet, cosmetics and the like.

Specifically, the gel form. can be applied to the following use.

(I) Pharmaceuticals: for example, transdermal formulations and transmucosal formulations;

(II) Medical goods: for example, coolant for feverish affected part, wound-curing medicine, treating pad, liquid-absorbing agent for surgery, dressing tape and medicine for burns .

(III) Cosmetics and quasi-drugs: for example, pack goods, suntan goods and acne-care goods. A lot of pharmaceuticals can be administrated by using gel forms of the present invention. For example, (a) corticosteroids: such as hydrocortisone, prednisone, beclomethasone propionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate and chlobetasol propionate;

(b) antiphlogistic analgesic: such as salicylic acid, glycol salicylate, methyl salicylate, 1-menthol, camphor, sulindac, tolmetin sodium, naproxen, fenbufen, piroxicam, triamcinolone, hydrocortisone acetate, indometacin, ketoprofen, acetaminophen, mefenamic acid, flufenamic acid, ibufenac, loxoprofen, tiaprofen, pranoprofen, fenbufen, diclofenac, diclofenac sodium, alclofenac, lornoxicam, mepranoprofen, oxyfenbutazon, ibuprofen, felbinac, ketorolac, bermoprofen, nabumeton, naproxen, flurbiprofen, fluocinonide, clobetasol propionate and COX-2 inhibitor (celecoxib, rofecoxib, valecoxib, parecoxib, valedecoxib, etodolac, nimesulide, meloxicam) ;

(c) antifungal agents: such as clotrimazole, econazole nitrate, omoconazole nitrate, tioconazole nitrate, ketoconazole nitrate, miconazole nitrate, isoconazole nitrate, tolnaftate, sulconazole nitrate, pyrrolnitrin, pimafucin, undecylenic acid, salicylic acid, siccanin, nystatin, nornaphtate, exalamide, phenyl iodoundecynoate, thianthol, ciclopirox olamine, haloprogin, trichomycin, variotin, pentamycin and amphotericin B;

(d) antihistamines: such as antibiotics such as tetracycline hydrochloride, diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole and chloramphenicol, diphenhydramine and chlorpheniramine maleate;

(e) hypnotics and sedatives: such as phenobarbital, amobarbital, cyclobarbital, lorazepam and haloperidol;

(f) tranquilizers: such as fluphenazine, thioridazine, diazepam, flunitrazepam and chlorpromazine;

(g) antihypertensive agents: such as clonidine, clonidine hydrochloride, pindolol, propranol, propranol hydrochloride, bupranol, indenolol, bucumolol and nifedipine;

(h) hypotensive diuretics: such as hydrothiazide and cyclopentiazide ; (i) antibiotics: such as penicillin, tetracycline, oxytetracycline, fradiomycin sulfate, erythromycin and chloramphenicol ;

(j) anesthetics: such as lidocaine, benzocaine, ethyl aminobenzoate and dibucaine; ( k) - antibacterial agents: such as benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine and clotrimazole;

(1) vitamins: such as vitamin A, ergocalciferol, cholecalciferol, octotiamine and riboflavin butyrate; (m) antiepileptic : such as nitrazepam, meprobamate and clonazepam;

(n) coronary vasodilators: such as nitroglycerine, nitroglycerin, isosorbide dinitrate, erythritol nitrate, pentaerythritol tetranitrate and propatylnitrate; (o) antihistamines: such as diphenhydramine hydrochloride, chlorpheniramine' and diphenylimidazole;

(p) antitussives: such as dextrometorphane, terbutaline, ephedrine and ephedrine hydrochloride;

(q) sex hormones: such as progesterone and estradiol; (r) antidepressant: such as doxepin; (s) therapeutic agents for stenocardia: such as diethylamide, antiperspirants such as camphor, nitroglycerine and isosorbide nitrate; (t) narcotic analgesic: such as morphine hydrochloride, ethylmorphine hydrochloride, morphine sulfate, cocaine hydrochloride, petidine hydrochloride, codeine phosphate, dihydrocodeine phosphate, fentanyl citrate, sufentanil and meperidine hydrochloride; (u) herbal medicines: such as Phellodendron bark, cherry bark extract, Polygala root, Curcuma zedoaria, Matricaria chamomilla, Trichosanthis Semen, Glycyrrhizae Radix, Platycodon grandiflorum, Armeniacae Semen, Bezoar Bovis, Schizandrae Fructus, Gleditsia japonica, Bupleuri Radix, Asiasari Radix, Plantaginis Semen, Cimicifugae Rhizoma, Senegae Radix, Atractylodis Lanceae, Mori Cortex, Caryophylli Flos, Aurantii Nobilis Pericarpium, Ipecacuanhae Radix, Nandina domestica seed, Pulsatilla chinensis, Ophiopogonis Tuber, Pinelliae Tuber, Atractyrodis Rhizoma, Hyoscyamus niger L.,

Saponshinikoviae Radix and Ephedrae Herba; and (v) others: such as 5-fluorouracil, dihydroergotamine, fentanyl, desmopressin, digoxin, metocloprarαide, domperidone, scopolamine, scopolamine hydrobromide as well as medicals for animals, hypnotics, cardiovascular treatment agents, cerebral metabolism improvers, sterilizers, enzymatic medicines, enzyme inhibitors, biological medicines (polypeptides), treatment agents for keratosis, narcotics, anti-malignant tumor, general anesthetics, antianxiety agents, medicines for asthma or nasal allergy, antiparkinsonism drug, chemotherapy agents, vermicides, antiprotozoal agents, hemostatic, cardiotonic drugs, analeptics, stimulants, medicines for addiction, Chinese medicines, radioactive medicals, medicines for urinogenital organs or anus, hypoglycemic agents, antiulcer agents, hair-dressing agents, metal ion blocking agents, antiperspirants, tranquilizers, anticoagulants, antirheumatics and gout suppressants, although it is not limited to these. Further, two or more kinds of these drugs can be used together, if necessary. The blending ratio of drug is 0.01 to 30% by weight, preferably 2 to 20% by weight, of the total mass of the above-mentioned adhesive for patch. ^■ Drugs can be incorporated either at the stage of solution (or sta'ge of gel suspension) or after aging for crosslinking reaction. The suitable method depends on the physical properties of drug, desired purpose for administration site and releasing rate. Further, auxiliary agents enhancing absorption of these drugs can be added. As examples of auxiliary agent, there may be mentioned keratolytics such as ethyl alcohol, isopropyl alcohol, butanol, 1 , 3-butanediol, propylene glycol, polyethylene glycol #400, glycerine, crotamiton, benzyl alcohol, phenylethyl alcohol, propylene carbonate, hexyldodecanol, propanol, salicylic acid, allantoin, dimethylsulfoxide, dimethylacetamide, dimethylformamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, lanolin, Azone, l-geranylazacycloheptan-2-one (GACH) , fatty acid dialkylolamide, salicylic acid, salicylic acid derivatives, urea and sulfur, humectants such as pyrrolidonecarboxylic acid, surfactants such as propylene glycol monooleate, polyoxyethylenesorbitan monostearate, sorbitan monostearate and glycerine monostearate, esters such as isopropyl myristate and diethyl sebacate, higher alcohols such as oleyl alcohol, stearyl alcohol and lauryl alcohol, fatty acids such as stearic acid, hexanoic acid, nonanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, oleic acid and linoleic acid, terpenoids such as menthol, menthone, limonene, pinene, piperitone, terpinene, terpinolene, terpinolol and carveol, surfactant, coagents such as allantoin, dimethylsulfoxide, dimethylacetamide, dimethylformamide, diisopropyl adipate, diethyl sebacate, ethyl laurate, lanolin and Azone . If necessary, one can also add one or more kinds of other components including refrigerants such as menthol and camphor, oils such as almond oil, olive oil, camellia oil, persic oil, peppermint oil, sesame oil, soybean oil, mink oil, cottonseed oil, corn oil, safflower oil, coconut oil, eucalyptus oil, castor oil, liquid paraffin, vaseline, squalene, squalane and lanolin, gelating agents such as carboxyvinyl polymer, neutralizing agents such as diisopropanolamine and the like. The blending ratio of these auxiliary agents is preferably 0.1 to 5 parts by weight for 100 parts by weight of the drug, considering irritation to skin.

To enhance its characteristics, to improve processing, moldability, and quality or to improve dispersion and stability of drugs in the gel form, the composition for water-containing gel form of the present invention can further comprise additives selected arbitrarily depending on purposes to the extent such that the performance of gel is not deteriorated. As such additives, there may be mentioned:

(1) moistening agents: for example, glycerine, propylene glycol, sorbitol, 1, 3-butanediol, dl-pyrrolidonecarboxylic acid and sodium lactate; (2) astringents: for example, citric acid, tartaric acid, lactic acid, aluminum chloride, aluminum sulfate, aluminum allantoin chloride hydroxide, aluminum allantoin dihydroxide, aluminum phenolsulfonate, zinc p-phenolsulfonate, zinc sulfate and aluminum chloride hydroxide;

(3) humectants : for example, polyols such as glycerine, propylene glycol, 1 , 3-butanediol, sorbitol, polyglycerine, polyethylene glycol and dipropylene glycol, NMF components such as sodium lactate, water-soluble polymers such as hyarulonic acid, collagen, mucopolysaccharides, and chondroitin sulfate;

(4) thickening agents: for example, naturally occurring polymers such as gum arabic, tragacanth, locust bean gum, gum guar, xanthan gum, karaya gum, agar, starch, carrageenan, alginic acid, alginate salts (for example, sodium alginate), propylene glycol alginate, dextran, dextrin, amylose, gelatin, collagen, pullulan, pectin, amylopectin, amylopectin sodium semiglycolate, chitin, albumin and casein, semi-synthetic polymers such as poly (glutamic acid), poly (aspartic acid), methylcellulose, ethylcellulose, propylcellulose, ethylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethy1cellulose, carboxymethyl starch, carboxymethylcellulose alkali metal salt, cellulose sulfate alkali metal salt, graft-polymerized cellulose, crosslinked gelatin, cellulose acetate phthalate, starch-acrylic acid graft polymer, gelatin modified with phthalic anhydride and gelatin modified with succinic acid and synthetic polymers such as polyvinyl alcohol, polyvinylpyrrolidone, poly (vinyl methyl ether), carboxyvinyl polymer, vinylpyrrolidone-ethyl acrylate copolymer, vinylpyrrolidone-styrene copolymer, vinylpyrrolidone-vinyl acetate copolymer, vinyl acetate- (meth) acrylic acid copolymer, vinyl acetate-crotonic acid copolymer, N-vinylacetamide-based copolymers such as N-vinylacetamide-sodium acrylate, poly (vinylsulfonic acid), crosslinked N-vinylacetamide polymer, poly (itaconic acid), poly (hydroxyethyl acrylate) , polyacrylamide, styrene-maleic anhydride copolymer and acrylamide-acrylic acid copolymer;

(5) adhesion agents: for example, adhesives such as silicone rubber, polyisoprene rubber, styrene block-copolymer ^'rubber, acrylate rubber and natural rubber;

(6) antipruritic: for example, camphor, thymol, menthol, polyoxyethylene lauryl ether, antihistamines and ethyl aminobenzoate;

(7) keratolytic: for example, sulfur, thioxolone, selenium sulfide, salicylic acid and resorcinol;

(8) agents for prohibiting mistakenly eat: for example, cayenne powder and cayenne essence;

(9) powdery materials: for example, montmorillonite, silicic acid anhydride, gypsum, carbon black, diatomite, red ocher, calcium carbonate, hydrotalcite, talc, quartz, kaolin, bentonite, metal soap, aerosol, mica-titanium, oxychlorobismuth, dew pearl, zinc flower and titanium dioxide;

(10) oils: for example, sweet almond oil, olive oil, hardened oil, camellia oil, castor oil, Japan wax, coconut oil, bees wax, spermaceti, lanolin, carnauba wax, candelilla wax, liquid paraffin, vaseline, 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 rαyristate, hexyl laurate, myristyl myristate, isopropyl palmitate, octyldodecanol myristic acid ester, butyl stearate, cacao oil, Japan wax, jojoba oil, grape seed oil, avocado oil, mink oil, egg yolk oil, ceresin wax, paraffin wax, behenic acid, isopropyl adipate, octyldodecyl myristate, octyldodecyl oleate and cholesteryl oleate; (11) surfactants: for example, anionic surfactants such as lauryl sulfate salt, polyoxyethylene alkyl ether sulfate salt, alkylbenzenesulfonate salts, polyoxyethylene alkyl ether phosphate, polyoxyethylene alkylphenyl ether phosphate, IV-acyl amino acid salts, sodium stearate, potassium palmitate, cetyl sodium sulfate, lauryl sodium sulfate, triethanolammonium palmitate, polyoxyethylene lauryl sodium phosphate, sodium acylglutamate and surfactin, cationic surfactants such as benzalkonium chloride, benzethonium chloride, stearyltrimethylammonium chloride, distearyldimethylammonium chloride and stearyldimethylbenzylammonium chloride, amphoteric surfactants such as alkyldiaminoethylglycine hydrochloride,

2-alkyl-iV-carboxymethyl-i\J^'-hydroxyethylimidazolinium betaine, lauryldimethylaminooacetate betaine and lecithin, non-ionic surfactants such as polyol fatty acid esters, glyceryl monostearate, lipophilic glyceryl monooleate, ethylene glycol monostearate, propylene glycol monostearate, sorbitan fatty acid esters, polyoxyethylenesorbitan fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylenesorbitol fatty acid esters, ΛJ-acylamino acid esters, sucrose fatty acid esters, fatty acid alkylolamide, polyoxyethylene-derivatized sterol, polyoxyethylene-derivatized lanolin and polyoxyethylene-derivatized hardened castor oil/

(12) colorants: for example, yellow iron oxide, red ocher, black iron oxide, indigo, carbon black, chromium hydroxide, chromium oxide, tar pigment, lake, Red#2, Red#3, Red#102, Red#201, Yellow#4, Yellow#5, Blue#l and Blue#2 :

(13) perfumes: for example, vegetable perfumes such as mustard oil, orange oil, pepper oil, jasmine oil, cedar oil, iris oil, turpentine, bitter orange blossom oil, rose oil, eucalyptus oil, lime oil, lemon oil, Japanese peppermint oil and rosemary oil, animal perfumes such as musk, civetone, castoreum and ambergris, hydrocarbon perfumes such as bromostyrol, pinene and limonene, alcoholic perfumes such as benzyl alcohol and 1-menthol, ester-type perfumes such as ethyl acetate and methyl salicylate, aldehyde-type perfumes such as benzaldehyde and salicylaldehyde, ketone-type perfumes such as camphor, muscone, musk ketone and 1-menthone, etheral perfumes such as safrole, phenolic perfumes such as thymol, lactone-type perfumes, acid-type perfumes such as phenylacetic acid and nitrogen-compound perfumes such as indole;

(14) ultraviolet-ray blockers : for example, benzophenone derivatives such as ASL-24 and Cyasorb UV-9 and Uvinul M-40, benzoic acid derivatives such as Salol, azols such as Tinuvin P, nitriles such as Uvinul N-35, urea derivatives such as Ancour UA, p-amino acid-type compounds such as Neo Heliopan Give tan F, 2-hydroxy-4-methoxybenzophenone, octyl dimethyl-p-aminobenzoate, ethylhexyl p-methoxycinnamate, salicylic acid derivatives, benzofuran derivatives, coumarin derivatives and azol-type compounds;

(15) antiseptic germicides: for example, acids such as benzoic acid, salicylic acid, dehydroacetic acid, sorbic acid and boric acid and salts thereof, phenols such as phenol, chlorocresol, chloroxylenol , isopropylmethylphenol, resorcinol, o-phenylphenol, p-hydroxybenzoate esters, phenoxyethanol, thymol, hinokitiol and thioxolone, halogenated bisphenols such as hexachlorophene and 2, 4 , 4 ' -trichloro-2 ' -hydroxydiphenyl ether, amide compounds such as trichlorocarbanilide, halocarban and undecylenylmonoethanolamide, quaternary ammonium salts such as benzalkonium chloride, alkylisoquinolinium bromide, benzethonium chloride and cetylpyridinium chloride, amphoteric surfactants such as lauryldi (aminoethyl) glycine, 2-pyridinethiol-l-oxide zinc, gluconic acid, chlorhexidine, thiram, I\7-trichloromethylthio-4-cyclohexene-l , 2-dicarboximide and chlorobutanol ;

(16) antioxidant: for example, nordihydroguaiaretic acid, guaiac gum, propyl gallate, butylhydroxyanisol, dibutylhydroxytoluene (BHT), tocopherol (vitamin E) and 2,2' -methylenebis ( 4-methy1-6- t-butyl ) phenol; (17) chelating agents: for example, edetates, pyrophosphates, hexametaphosphates, citric acid, tartaric acid and gluconic acid;

(18) ultraviolet-ray scattering agents: for example, titanium dioxide, kaolin and talc; (19) pH adjusters: for example, bases including alkali metal hydroxides, alkaline earth metal hydroxides, primary, secondary or tertiary alkylarαines or primary, secondary or tertiary alkanolamines such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonia, aqueous ammonia, triethanolamine,^' dimethylamine, diethylamine, trimethylamine, triethylamine, triisopropanolamine, trisodium phosphate, disodium hydrogenphosphate, dipotassium hydrogenphosphate, monoethanolamine, diethanolamine, diisopropanolamine and polyethanolamine, further, acids such as citric acid, tartaric acid, lactic acid, glycolic acid, hydrochloric acid, nitric acid, malic acid and phosphoric acid as well as acidic or basic macromolecules such as alginic acid, poly ( glutamic acid) , poly (aspartic acid), starch-acrylic acid graft-polymer, poly(acrylic acid), poly(vinyl acetate-crotonic acid), vinyl acetate- (meth) acrylic acid copolymer, vinyl acetate-crotonic acid copolymer, poly (vinylsulfonic acid), poly (itaconic acid), styrene-maleic anhydride copolymer and acrylamide-acrylic acid copolymer, although not limited thereto.

Besides these, additives such as stabilizers, fillers, preservatives, plasticizers, softeners and antidegradants can be arbitrarily added in an amount such that characteristics of adhesive for patch are not affected thereby.

The water-containing gel forms of the present invention can be prepared as various shaped materials by either a method wherein a mixture of raw materials in sol state is directly poured into a suitable frame and crosslinked to form therein or a method wherein crosslinked gel is directly formed using a suitable forming apparatus or tablet maker. Mixing of raw materials can be carried out with an appropriate apparatus selected from, for example, kneader, cokneader, kneader ruder, agihomomixer, planetary mixer and double planetary mixer.

To form a water-containing gel form as sheet, a suitable amount of the water-containing gel form is coated on one side or both sides of supporting materials such as paper, woods, metal, glass fiber, fabrics (flannel, woven fabric, unwoven fabric etc.) , synthetic resins (polyurethane, ethylene-vinyl acetate copolymer, poly (vinyl chloride) , polyester (for example, polyethylene terephthalate) polyolefin (for example, polyethylene and polypropylene) , polyamide (for example, Nylon-6 and Nylon-66) , poly ( vinylidene chloride) and polytetraf luoroethylene) , metal foil such as aluminum, rubber or cellulose derivatives or formed materials thereof such as laminated films with plastic films, sheet (foil) or tape. For easy preservation of the obtained sheet-like water-containing gel form, it is desirable that releasing paper, which is treated with silicone or another suitable method, is adhered to the surface coated with the water-containing gel form or that the surface uncoated with the water-containing gel form is treated with silicone or another suitable method to provide a releasing surface, the sheet being wound or piled so that the releasing surface is placed on top of the uncoated surface. As the releasing sheet, polyethylene film, polypropylene film, releasing paper, cellophane, poly(vinyl chloride) and polyester are used. Examples

The composition for water-containing gel form of the present invention will be explained with examples, although the present invention is not limited thereto. In the examples, "part" represents "part by weight". Example Al:

Formulation : acrylic acid/sodium acrylate (50/50 (molar ratio)) copolymer 4 parts glycerine 30 parts aluminum hydroxide 0.4 part water 63.4 parts sodium chloride 2 parts tartaric acid 0.2 part

According to the above formulation, a liquid dispersion of acrylic acid/sodium acrylate copolymer (VISCOMATE™

NP-700: Showa Denko K.K.)and aluminum hydroxide (Dried aluminum hydroxide gel (S-100) : Kyowa Chemical Industry Co., Ltd.) in glycerine was gradually added to a mixture of water, tartaric acid and sodium chloride. The mixture was stirred until it became homogeneous. The obtained sol

was formed, sealed hermetically and aged at about 20°C for

3 days. When the gel form was taken from the container and touched with fingers, it stretched, exhibited strong elasticity and low stickiness, and did not cling to fingers .

On the other hand, the obtained sol was poured into a frame

with a thickness of 1.0 mm and a dimension of 10 x 20 cm and aged at 20°C for 3 days. Here, packing tape was used as the supporting material wherein the adhesion surface of the packing tape was coated with the gel form. After the obtained gel form was exposed at 25°C with a relative humidity of 60% for 24 hr, the tack test was carried out according to JIS Z0237 tack test method with a tester (C140: Yoshimitsu Seiki Corp.) . The ball tack value was 8 at a tilt angle of 30 degree. Example A2 :

Formulation : sodium polyacrylate aqueous solution 20 parts glycerine 35 parts potassium chloride 0.25 part aluminum hydroxide 0.4 part tartaric acid 1.6 parts purified water 42.75 parts

According to the above formulation, a liquid dispersion of aluminum hydroxide (Dried aluminum hydroxide gel (low-water type) : Kyowa Chemical Industry Co., Ltd.) in glycerine was added at once to a mixture of water, tartaric acid, sodium polyacrylate aqueous solution (VISCOMATE™ SL-104Y: Showa Denko K. K.) and potassium chloride. The mixture was kneaded until it became homogeneous. The obtained sol was formed, sealed hermetically and aged at about 20°C for 3 days. When the gel form was taken from the container and touched with fingers, it stretched, exhibited strong elasticity and low stickiness, and did not cling to fingers. Example A3:

Formulation : acrylic acid/sodium acrylate (50/50 (molar ratio)) copolymer 4 parts sodium phosphate 0.5 part magnesium chloride 1 part purified water 64.4 parts glycerine 29.5 parts aluminum hydroxide 0.4 part tartaric acid 0.2 part

According to the above formulation, acrylic acid/sodium acrylate copolymer, glycerine and aluminum hydroxide (Dried aluminum hydroxide gel (S-100) : Kyowa Chemical Industry Co., Ltd.) were added to a mixture of sodium phosphate, magnesium chloride, tartaric acid and water. The mixture was kneaded until it became homogeneous. The obtained sol was formed, sealed hermetically and aged at about 20°C for 3 days. When the gel form was taken from the container and touched with fingers, it stretched, exhibited strong elasticity and low stickiness, and did not cling to fingers. Example A4 : Formulation:

W-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

IλJ-vinylacetamide crosslinked materiall part purified water 31 parts

According to the above formulation, a liquid mixture of W-vinylacetamide/ sodium acrylate copolymer, synthetic hydrotalcite (ALCAMAC™: Kyowa Chemical Industry Co., Ltd.), ammonium alum, aluminum oxide, -V-vinylacetamide crosslinked material and 1 , 3-butanediol was gradually added to a mixture of citric acid, lithium chloride and purified water. The mixture was kneaded. The obtained sol was formed, sealed hermetically and aged at about 20⁰C for 3 days . When the gel form was taken from the container and touched with fingers, it stretched, exhibited strong elasticity and low stickiness, and did not cling to fingers . Example A5 : Formulation: 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

According to the above formulation, sodium acrylate/potassium methacrylate copolymer and sodium carboxymethylcellulose were added at once to a liquid mixture of potassium chloride, calcium chloride, sorbitol polyglycidyl ether (DENACOL™ EX-614B: Nagase Chemtex Corporation) and purified water. The mixture was well kneaded until it became homogeneous . The obtained sol was formed, sealed hermetically and aged at about 20⁰C for 3 days. When the gel form was taken from the container and touched with fingers, it stretched, exhibited strong elasticity and low stickiness, and did not cling to fingers.

Comparative example Al: Formulation : acrylic acid/sodium acrylate (50/50 (molar ratio)) copolymer 4 parts glycerine 30 parts aluminum hydroxide 0.4 part purified water 65.4 parts tartaric acid 0.2 part

According to the above formulation, a liquid dispersion of acrylic acid/sodium acrylate copolymer (VISCOMATE™ NP-700: Showa Denko K.K.), aluminum hydroxide (Dried aluminum hydroxide gel (S-100) : Kyowa Chemical Industry Co., Ltd.) in glycerine was gradulally added to a mixture of purified water and tartaric acid. The mixture was kneaded until it became homogeneous . The obtained sol was formed, sealed hermetically and aged at about 20⁰C for 3 days. When the gel form was taken from the container and touched with fingers, it stretched but the restoring force was weak and the gel clung to fingers . On the other hand, the obtained sol was poured into a frame with a thickness of 1.0 mm and a dimension of 10 x 20 cm and aged at 25°C for 3 days. Here, packing tape was used as the supporting material wherein the adhesion surface of the packing tape was coated with the gel form. After the obtained gel form was exposed at 25°C with a relative humidity of 60% for 24 hr, the tack test was carried out according to JIS Z0237 tack test method with a tester (C140: Yoshimitsu Seiki Corp.) . The ball tack value was 18 at a tilt angle of 30 degree.

Comparative example A2 : Formulation

W-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 IV-vinylacetamide crosslinked material 1 part purified water 40.5 parts

According to the above formulation, a liquid mixture of IV-vinylacetamide/ sodium acrylate copolymer, synthetic hydrotalcite (ALCAMAC™: Kyowa Chemical Industry Co., Ltd.), ammonium alum, aluminum oxide, N-vinylacetamide crosslinked material and 1 , 3-butanediol was gradually added to a mixture of citric acid and purified water. The mixture was kneaded. The obtained sol was formed, sealed hermetically and aged at about 20⁰C for 3 days. When the gel form was taken from the container and touched with fingers, it stretched but the restoring force was weak and the gel clung to fingers .

Next, adjustment of crosslinking speed was evaluated in the following example B and comparative example B. Methods for measuring crosslinking speed

Crosslinking speeds were determined with gel strength as a parameter. The gel strength was measured with a digital force gauge (Nidec-Shimpo Corp. : DFG-O.2K) and its test stand, based on the principle of card tension meter.

The sensory pole (made of aluminum) was a cylindrical column with a diameter of 10 mm and a height of 12 mm. The transfer distance was 30 mm and the transfer speed was 5 mm/sec. The gel was poured into a resin sample tube in its sol state and the measurement was carried out with n

Here, the relationship between observed values of this measurement and a sensory test with finger touch is shown in Table 1. Table 1. The relationship between the measured values of gel strength and representation in the sensory test

Examples Bl to B3 and comparative examples Bl and B2 : Adjustment of crosslinking speed with sodium chloride

(Composition)

Each compostion was prepared as shown in Table 2.

Table 2 Composition Unit:part by weight

polymer 1: acrylic acid/sodium acrylate (50/50 (molar ratio) copolymer (VISCOMATE™ NP-700: Showa Denko K. K.)

polymer 2: IV-vinylacetamide/sodium acrylate (90/10

(weight ratio) ) copolymer Al (OH) 3: aluminum hydroxide (Dried aluminum hydroxide gel

(S-IOO) : Kyowa Chemical Industry Co., Ltd.) (Formulation)

A liquid dispersion of polymer and aluminum hydroxide in glycerine was gradually added to a mixed aqueous solution of tartaric acid and sodium chloride to attain the composition shown in Table 2. The mixture was kneaded until it became homogeneous.

(Results

The resuls are shown in- Table 3 Table 3. Gel strength and gelation speed Unit: gf

In the table, the gelation speed is the increment of gel strength per day (gf/day) , that is, the value obtained by subtracting the gel sterngth at 0 day from the gel strength at 1 day. It is clearly indicated that the gelation speed is higher for the samples with sodium chloride added.

Examples B4 to B6 and comparative example B3 : Adjustment of crosslinking speed with potassium chloride (Composition)

The composition is listed in Table 4. Here, comparative example Bl is the same as comparative example Bl described above .

Table 4. Composition Unit: part by weight

polymer 1: acrylic acid/sodium acrylate (50/50 (molar ratio)) copolymer (VISCOMATE™ NP-700: Showa Denko K. K.) polymer 3: Itf-methyl-N-vinylacetamide/ammonium acrylate

(30/70 (weight ratio)) copolymer

1,3-BD: 1, 3-butanediol

Al(OH)₃: aluminum hydroxide (Dried aluminum hydroxide gel

(S-IOO): Kyowa Chemical Industry Co., Ltd.)

(Formulation)

A liquid dispersion of polymer and aluminum hydroxide in glycerine/1, 3-butanediol was gradually added to a mixed aqueous solution of tartaric acid and potassium chloride. The resultant mixure was kneaded until it became homogeneous .

(Results)

The results are listed in Table 5. It indicates that the gelation speed is higher for the samples with potassium chloride added.

Table 5. Gel strength and gelation speed Unit: gf

Examples B7 to B9 and comparative example B4 :

Adjustmet of crosslinking speed with calcium chloride ( Formulation)

The composition is listed in Table 6. Here, comparative example Bl is the same as comparative example Bl decsribed above .

polymer 1: acrylic acid/sodium acrylate (50/50 (molar ratio)) copolymer (VISCOMATE™ NP-700: Showa Denko K. K.) polymer 4 : iV-vinylacetamide/sodium acrylate

(60/40 (weight ratio)) copolymer

PG: propylene glycol

Al(OH)₃: aluminum hydroxide (Dried aluminum hydroxide gel

(S-IOO): Kyowa Chemical Industry Co., Ltd.)

Glycinal : dihydroxyaluminum aminoacetate (Glycinal™:

Kyowa Chemical Industry Co., Ltd.)

(Formulation)

A liquid dispersion of polymer and aluminum hydroxide or Glycinal in glycerine/propylene glycol was added gradually to a mixed aquoues solution of tartaric acid and calcium, chloride to attain the composition shown in Table 6. The resultant mixture was kneaded until it became homogeneous . (Results)

The results are shown in Table 7. For the samples with calcium chloride added, the initial gelation speed is very low (that is, easily shaped), and gelation proceeds at later stage.

Table 7.GeI strength and gelation speed Unit: gf

Examples BlO to B12 and comparative example B5 : Adjustment of crosslinking speed with magnesium chloride (Composition)

The composition is listed in Table 8. Here, comparative example Bl is the same as comparative example Bl descrived above .

Table 8. Composition Unit: part by weight

polymer 1: acrylic acid/sodium acrylate ( 50/50 (weight

ratio)) copolymer (VISCOMATE™ NP-700: Showa Denko K. K.) polymer 5: N-vinylacetamide/methacrylic acid/potassium acrylate (30/20/50 (mass ratio)) copolymer Al(OH)₃: aluminum hydroxide (Dried aluminum hydroxide gel (S-IOO) : Kyowa Chemical Industry Co., Ltd.)

(Formulation)

A liquid dispersion of polymer and aluminum hydroxide

or Glycinal in glycerine was added to a mixed aqueous

solution of tartaric acid and calcium chloride to attain

the composition shown in Table 8. The resultant mixture

was kneaded until it became homogeneous.

(Results) The results are lited in Table 9. For the samples with magnesium chloride added, the initial gelation speed is very low (that is, easily shaped) and gelation proceeds at later stage.

Table 9. Gel strength and gelation speed Unit :gf

Claims

1. A composition for a water-containing gel form comprising at least one kind of compound (component D) selected from the group consisting of compounds comprising a monovalent or divalent metal ion, and a (meth) acrylic acid-based polymer (component A) , water (component C) and a crosslinker which reacts with carboxyl groups (component B) .

2. The composition for water-containing gel form according to claim 1, wherein the repeating units of the

(meth) acrylic acid-based polymer (component A) are represented by general formulae (1) , (2) and (3) : -CH₂C (R¹) (COOM) - (1)

-CH₂C (R²) (COOH) - (2) -X- ^' (3)

(wherein, each of R¹ and R² represents independently a hydrogen atom or a methyl group, M represents NH₄ ⁺ or an alkali metal and X represents divalent organic group derived from an unsaturated monomer) , the molar ratio of (1) / (2) ranges from 100/0 to 0/100 and the molar ratio of total amount of ^'(1) and (2) to (3) ranges from 100/0 to 10/90.

3. The composition for water-containing gel form according to claim 2, wherein M is sodium, the molar ratio of the repeating units (1) and (2), (I)/ (2), is in a range from 0/100 to 100/0 and the repeating unit (3) is not contained.

4. The composition for water-containing gel form according to claim 1, wherein the compound comprising a monovalent metal ion is sodium chloride.

5. The composition for water-containing gel form according to claim 1, which further comprises polyol (component E) .

6. The composition for water-containing gel form according to claim 1, wherein the crosslinker which reacts with carboxyl groups (component B) is an aluminum compound.

7. The composition for water-containing gel form according to claim 2, wherein the (meth) acrylic acid-based polymer (component A) is sodium acrylate-N-vinylacetamide copolymer .

8. A water-containing gel form prepared by using the composition for water-containing gel form according to claim 1.

9. A production method of a water-containing gel form, wherein the composition for water-containing gel form according to claim 1 is crosslinked at room temperature.

10. A production method of a water-containing gel form, wherein, on crosslinking of the (meth) acrylic acid-based polymer (component A) by mixing with aluminum compound

(component B') and water (component C), the crosslinking speed of the (meth) acrylic acid-based polymer is adjusted

by adding at least one kind of metal salt (component D' )

selected from the group consisting of metal salts comprising a monovalent or divalent metal ion.

11. The production method of a water-containing gel form according to claim 10, wherein the metal salt (component

D' ) is dissolved in water in advance and then added.

12. The production method of a water-containing gel form according to claim 10, wherein the metal salt (component

D') is added at a temperature ranging from 0°C to 40°C.

13. The production method of a water-containing gel form according to claim 10, wherein the (meth) acrylic

acid-based polymer comprises repeating units represented by general formulae (1), (2) and (3) : -CH₂C (R¹) (COOM)- (1)

-CH₂C (R²) (COOH) - (2)

-X- (3)

(wherein, each of R¹ and R² represents independently a

hydrogen atom or a methyl group, M represents NH₄ ⁺ or an

alkali metal and X represents a divalent organic group derived from an unsaturated monomer) , the molar ratio of

(I)/ (2) ranges from 100/0 to 0/100 and the molar ratio of

total amount of (1) and (2) to (3) ranges from 100/0 to

10/90.

14. The production method of a water-containing gel form according to claim 13, wherein the (meth) acrylic acid-based polymer (component A) is sodium acrylate-N-vinylacetamide copolymer .

15. The production method of a water-containing gel form according to claim 13, wherein M is sodium, the molar ratio of the repeating units (1) and (2) , (1) / (2) , is in a range from 0/100 to 100/0 and repeating unit (3) is not contained.

16. The production method of a water-containing gel form according to claim 10, wherein the mean particle diameter

(d50) of the (meth) acrylic acid-based polymer (component A) is in a range from 30 to 250 μm.

17. The production method of a water-containing gel form according to claim 10, wherein the metal salt (component D') is sodium chloride.

18. The production method of a water-containing gel form according to claim 10, wherein the metal salt (component D') is magnesium chloride.

19. The production method of a water-containing gel form according to claim 10, wherein the composition further comprises a poly^'ol (component E) .

20. The production method of a water-containing gel form according to claim 19, wherein the metal salt (component D') is dispersed in the polyol (component E) in advance and then added.

21. A water-containing gel form obtained by the production method of a water-containing gel form according to claim 10.

22. The water-containing gel form according to claim 8 or 21, wherein the water content therein is in a range from 5 to 98% by weight .

23. A transdermal formulation using the water-containing gel form according to claim 8 or 21.

24. A cooling sheet using the water-containing gel form according to claim 8 or 21.

25. Cosmetics using the water-containing gel form according to claim 8 or 21.