METHOD FOR MANUFACTURING CATAPLASM, AND METHOD FOR SUPPRESSING CRYSTAL DEPOSITION OF l-MENTHOL IN CATAPLASM

Abstract

To provide a method for suppressing crystal deposition of l-menthol in a cataplasm.SOLUTION: A method for manufacturing a cataplasm equipped with a support layer, an adhesive layer laminated on the support layer, and a release liner provided on an opposite face of the support layer with respect to the adhesive layer includes the steps of: obtaining an adhesive composition containing drug, water, gelatin, l-menthol, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion and magnesium aluminometasilicate; and spreading the adhesive composition on the release liner or the support layer, and laminating the support layer or the release liner on the composition, wherein a content of methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is 1.5 mass% to 20 mass%, a content of magnesium aluminometasilicate is 0.25 mass% to 0.45 mass%, and a content of gelatin is 1 mass% to 3 mass%, based on the total mass of the adhesive layer.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing a cataplasm and a method for inhibiting the precipitation of 1-menthol crystals in a cataplasm. [Background technology]

[0002] A cataplasm is a type of adhesive patch produced by spreading a drug-containing adhesive layer on a support layer such as cloth, and the adhesive layer generally has a high moisture content. To achieve a high moisture content in the adhesive layer and ensure excellent shape retention and cohesion, the adhesive layer contains a water-soluble polymer such as gelatin, polyacrylic acid, neutralized polyacrylic acid, or polyvinyl alcohol. Furthermore, a cataplasm containing a cooling agent such as l-menthol can provide a cooling sensation upon use and exhibit pain-relieving and cooling effects (e.g., Patent Documents 1 and 2).

[0003] It is known that l-menthol-containing poultices may have a problem in that l-menthol crystals may precipitate in the adhesive layer. To solve this problem, for example, Patent Document 3 discloses that the content of menthol in a water-containing gel composition is set to a specific amount, and one or more selected from silica and talc are blended into the water-containing gel composition to suppress menthol precipitation. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2020-132637 [Patent Document 2] Japanese Patent Application Publication No. 2019-81755 [Patent Document 3] Japanese Patent Publication No. 2022-75038 Summary of the Invention [Problem to be solved by the invention]

[0005] In the process of developing a cataplasm in which l-menthol crystal precipitation is inhibited, the present inventors have found that in addition to l-menthol crystal precipitation, other problems may occur, such as uneven spreading during spreading, components of the adhesive layer seeping out from the backing layer after spreading, insufficient adhesion and liner releasability, and pain when removing the cataplasm after application to the skin.

[0006] The present invention has been made in consideration of the problems of the above-mentioned prior art, and aims to provide a cataplasm that inhibits precipitation of l-menthol crystals, spreads evenly, has excellent adhesion and liner releasability, inhibits bleeding, and reduces pain when removed. [Means for solving the problem]

[0007] As a result of extensive research conducted by the present inventors to achieve the above-mentioned object, they have found that a cataplasm in which precipitation of l-menthol crystals is inhibited can be obtained by adjusting the content of methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion within a predetermined range in an adhesive layer containing water, gelatin, l-menthol, methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate.

[0008] However, even though the content of methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion was within the specified range, new issues arose, such as unevenness when spreading the adhesive layer, components of the adhesive layer seeping into the support layer after spreading, insufficient adhesion and liner removability, and pain when removing the patch.

[0009] As a result of intensive research into the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by adjusting the blending amounts of magnesium aluminometasilicate and gelatin, among the components contained in the poultice of the present invention, to a predetermined range, and have thus completed the present invention.

[0010] That is, the present invention relates to the following [1] to [6]. [1] A cataplasm comprising a support layer, an adhesive layer laminated on the support layer, and a release liner provided on the surface of the adhesive layer opposite the support layer, wherein the adhesive layer contains a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate, and the content of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is 1.5% to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% to 0.45% by mass, and the content of the gelatin is 1% to 3% by mass, based on the total mass of the adhesive layer. [2] The poultice according to [1], wherein the adhesive layer further contains at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid. [3] A method for producing a cataplasm comprising a support layer, an adhesive layer laminated on the support layer, and a release liner provided on the surface of the adhesive layer opposite the support layer, the method comprising the steps of obtaining an adhesive composition containing a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion and magnesium aluminometasilicate, and spreading the adhesive composition on the release liner or support layer and laminating the support layer or release liner thereon, wherein the content of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is 1.5% by mass to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% by mass to 0.45% by mass, and the content of the gelatin is 1% by mass to 3% by mass, based on the total mass of the adhesive layer. [4] The method according to [3], wherein the pressure-sensitive adhesive composition further contains at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid. [5] A method for suppressing the precipitation of crystals of l-menthol in a cataplasm comprising a support layer, an adhesive layer laminated on the support layer, and a release liner provided on the surface of the adhesive layer opposite the support layer, the method comprising the steps of obtaining an adhesive composition containing a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion and magnesium aluminometasilicate, and spreading the adhesive composition on a release liner or support layer and laminating the support layer or release liner thereon, wherein the content of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is 1.5% by mass to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% by mass to 0.45% by mass, and the content of gelatin is 1% by mass to 3% by mass, based on the total mass of the adhesive layer. [6] The method according to [5], wherein the pressure-sensitive adhesive composition further contains at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a cataplasm that inhibits precipitation of l-menthol crystals, spreads evenly, has excellent adhesion and liner releasability, inhibits bleeding, and reduces pain when removed. DETAILED DESCRIPTION OF THE INVENTION

[0012] Preferred embodiments of the present invention will be described in detail below.

[0013] A poultice according to a first embodiment of the present invention comprises a support layer, an adhesive layer laminated on the support layer, and a release liner provided on the surface of the adhesive layer opposite the support layer, wherein the adhesive layer contains a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate, and the content of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is 1.5% by mass to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% by mass to 0.45% by mass, and the content of the gelatin is 1% by mass to 3% by mass, based on the total mass of the adhesive layer.

[0014] The support layer may be any layer capable of supporting a water-containing pressure-sensitive adhesive layer, and those well known to those skilled in the art can be used. Examples of the support layer include woven fabric (including knitted fabric), nonwoven fabric, resin film, foam sheet, and paper. When woven fabric, nonwoven fabric, or resin film is used as the support layer, examples of the material include polyolefins such as polyethylene, polypropylene, and polybutylene, polyesters such as polyethylene terephthalate, rayon, polyurethane, and cotton, and these may be used alone or in combination of two or more, and may be a single layer or a laminate. Polyester is more preferred as the material for the support layer.

[0015] The support layer is preferably a nonwoven fabric or a woven fabric, and particularly preferably a nonwoven fabric or a woven fabric having a predetermined elongation recovery rate (elongation elastic modulus). In this specification, "elongation recovery rate" refers to a value measured according to JIS L1096:2010, and refers to "elongation elastic modulus at constant load" or "elongation elastic modulus at constant rate elongation." For example, "50% elongation recovery rate" refers to the elongation elastic modulus when elongated to an elongation rate of 50% (constant rate elongation), and "load at 50% elongation" refers to the load (constant load) required to elongate to an elongation rate of 50%. Using a nonwoven fabric or woven fabric having a predetermined elongation recovery rate is preferable because, when applied to a moving part such as a joint, the support layer expands and contracts in response to the movement of the application site.

[0016] When the support layer is a nonwoven fabric, the recovery rate of the nonwoven fabric at 50% elongation is, for example, 60 to 99%, preferably 65 to 95%, and more preferably 70 to 90%. The load at 50% elongation of the nonwoven fabric is, for example, 1 to 6 N / 50 mm in the longitudinal direction (long axis direction) and 0.1 to 3 N / 50 mm in the transverse direction (short axis direction). The basis weight of the support layer is, for example, 80 to 150 g / m 2 and 90 to 120 g / m 2 Preferably, the thickness of the support layer is 0.5 to 2 mm, for example. The basis weight and thickness of the support layer are measured in accordance with the standard JIS L1906:2000. The bending resistance of the support layer (the bending resistance is measured by Method A (45° cantilever method) of JIS L1096:2010) can be, for example, 20 to 40 mm in the longitudinal direction (long axis direction) and 10 to 35 mm in the transverse direction (short axis direction), and is preferably 25 to 35 mm in the longitudinal direction (long axis direction) and 15 to 30 mm in the transverse direction (short axis direction).

[0017] The knitted fabric used as the support layer also includes knitted fabrics obtained by gathering stitches by circular knitting, warp knitting, weft knitting, etc. Knitted fabrics made from one or a combination of two or more materials such as polyester, nylon, polypropylene, and rayon are preferred, and among these, knitted fabrics made from polyethylene terephthalate, which has little interaction with drugs, are more preferred.

[0018] In particular, when the support layer is a woven fabric, the 50% elongation recovery rate of the woven fabric is, for example, 60 to 99%, preferably 65 to 95%, and more preferably 70 to 90%. The load at 50% elongation is, for example, 1 to 5 N / 25 mm in the longitudinal direction (long axis direction) and preferably 0.1 to 3 N / 25 mm in the transverse direction (short axis direction). The bending resistance of the support layer can be, for example, 10 to 30 mm in the longitudinal direction (long axis direction) and 10 to 30 mm in the transverse direction (short axis direction), and is preferably 15 to 25 mm in the longitudinal direction (long axis direction) and 15 to 25 mm in the transverse direction (short axis direction).

[0019] The thickness of the woven fabric as the support layer is preferably 0.5 to 2 mm.

[0020] In particular, fabrics with a basis weight of 80 to 150 g / m 2 When the polyethylene terephthalate woven fabric is used, the water contained in the adhesive is less likely to seep through the mesh of the woven fabric during spreading, and the anchoring property between the woven fabric and the adhesive is more excellent.

[0021] Furthermore, the polyethylene terephthalate woven fabric preferably has a longitudinal (longitudinal) modulus of 2 to 12 N / 50 mm and a transverse (short-axis) modulus of 2 to 8 N / 50 mm (modulus measurement method is in accordance with JIS L1018:1999). If the modulus is lower than 2 N / 50 mm, the woven fabric may stretch when the adhesive is spread, causing the adhesive to seep into the mesh, resulting in a decrease in functionality as a cataplasm. If the modulus is higher than 12 N / 50 mm (longitudinal) or 8 N / 50 mm (transverse), the cataplasm may have poor stretchability and may not be able to follow the expansion of the skin when applied to a moving part.

[0022] The material of the release liner is not particularly limited, and liners made of materials generally known to those skilled in the art can be used. When a woven fabric, nonwoven fabric, knitted fabric, or resin film is used as the support layer, examples of the material of the release liner include polyethylene, polypropylene, polybutylene, polyethylene terephthalate, rayon, polyurethane, and paper, and these materials may be used alone or in combination of two or more. The material of the release liner is preferably polypropylene film.

[0023] The adhesive layer contains a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate.

[0024] The drug is not particularly limited as long as it is a drug that can be absorbed transdermally. Examples of the drug include non-steroidal anti-inflammatory drugs such as indomethacin, felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate, and ketoprofen, or esters thereof, antihistamines such as diphenhydramine, analgesics such as aspirin, acetaminophen, ibuprofen, and loxoprofen sodium, local anesthetics such as lidocaine, muscle relaxants such as suxamethonium chloride, antifungal agents such as clotrimazole, antihypertensives such as clonidine, vasodilators such as nitroglycerin and isosorbide dinitrate, vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octotiamine, and riboflavin butyrate, prostaglandins, scopolamine, fentanyl, capsicum extract, and vanillylamide nonylate. Some drugs exist as two optical isomers, R- and S-isomers. The drug used in this embodiment may be either one of the optical isomers or a mixture of the two optical isomers in any ratio. The drug may be in the form of a pharmaceutically acceptable salt, and examples of the pharmaceutically acceptable salt include inorganic base salts such as sodium salts, potassium salts, and calcium salts; organic base salts such as amine salts such as monoethanolamine and diethanolamine; inorganic acid salts such as hydrochloride, nitrate, and phosphate; and organic acid salts such as acetate, lactate, benzenesulfonate, and citrate.

[0025] The content of the drug in the adhesive layer may be an amount that allows the drug to exert its medicinal effect and varies depending on the type of drug, for example, 0.5% to 1.5% by mass for indomethacin, 0.5% to 1.5% by mass for diclofenac sodium, 0.1% to 1% by mass for ketoprofen, 0.5% to 1.5% by mass for felbinac, and 0.1% to 1% by mass for flurbiprofen.

[0026] The water content in the pressure-sensitive adhesive layer can be 30% to 70% by mass, or may be 30% to 60% by mass, or 35% to 52% by mass, based on the total mass of the pressure-sensitive adhesive layer.

[0027] The gelatin content in the adhesive layer is 1 to 3% by mass, preferably 1.25 to 3% by mass, and more preferably 1.5 to 3% by mass, based on the total mass of the adhesive layer.

[0028] The content of l-menthol in the adhesive layer can be 0.5% by mass to 3% by mass, preferably 1% by mass to 2% by mass, and more preferably 1% by mass to 1.5% by mass, based on the total mass of the adhesive layer.

[0029] Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is an emulsion (aqueous emulsion) in which methyl acrylate-2-ethylhexyl acrylate copolymer resin is dispersed in water. The content of methyl acrylate-2-ethylhexyl acrylate copolymer resin in the emulsion can be 55% to 65% by mass based on the total mass of the emulsion. The emulsion may contain an emulsifier, such as polyoxyethylene nonylphenyl ether. The content of the emulsifier can be 1% to 5% by mass based on the total mass of the emulsion. The content of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion in the pressure-sensitive adhesive layer is 1.5 to 20% by mass (equivalent to 0.825 to 13% by mass of the methyl acrylate-2-ethylhexyl acrylate copolymer resin), preferably 2 to 19% by mass (equivalent to 1.1 to 12.35% by mass of the methyl acrylate-2-ethylhexyl acrylate copolymer resin) or 3 to 20% by mass (equivalent to 1.65 to 13% by mass of the methyl acrylate-2-ethylhexyl acrylate copolymer resin), and more preferably 3 to 18% by mass (equivalent to 1.65 to 11.7% by mass of the methyl acrylate-2-ethylhexyl acrylate copolymer resin). Commercially available methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsions include, for example, Nikasol TS-620 (trade name, manufactured by Nippon Carbide Industries Co., Ltd.) and BPW HW-2 (trade name, manufactured by Toyochem Co., Ltd.).

[0030] The content of magnesium aluminometasilicate in the adhesive layer is 0.25% by mass to 0.45% by mass, preferably 0.25% by mass to 0.43% by mass, and more preferably 0.28% by mass to 0.4% by mass, based on the total mass of the adhesive layer.

[0031] The ratio of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion content to the magnesium aluminometasilicate content in the pressure-sensitive adhesive layer is preferably 3.3:1 to 80:1 (equivalent to 1.815:1 to 52:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin), more preferably 5.4:1 to 76:1 (equivalent to 2.97:1 to 49.4:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin) or 6.6:1 to 80:1 (equivalent to 3.63:1 to 52:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin), and even more preferably 7.5:1 to 72:1 (equivalent to 4.125:1 to 46.8:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin). The ratio of the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion content to the gelatin content in the pressure-sensitive adhesive layer is preferably 0.5:1 to 20:1 (equivalent to 0.275:1 to 13:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin), more preferably 0.75:1 to 16:1 (equivalent to 0.4125:1 to 10.4:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin) or 1:1 to 20:1 (equivalent to 0.55:1 to 13:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin), and even more preferably 1:1 to 12:1 (equivalent to 0.55:1 to 7.8:1 as methyl acrylate-2-ethylhexyl acrylate copolymer resin).

[0032] The adhesive layer may contain, as other components, water-soluble polymers (excluding gelatin; the same applies hereinafter), cooling agents (excluding l-menthol; the same applies hereinafter), adhesion enhancers (excluding methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion; the same applies hereinafter), solubilizers, crosslinkers (excluding magnesium aluminometasilicate; the same applies hereinafter), fillers, humectants, stabilizers, preservatives, chelating agents, colorants, flavoring agents, pH adjusters, etc. In one embodiment of the present invention, the adhesive layer preferably does not contain propylene glycol.

[0033] Examples of adhesion enhancers include acrylic ester copolymers such as aminoalkyl methacrylate copolymer E. When the adhesive layer contains an adhesion enhancer, the content thereof is preferably 0.1% by mass to 1.0% by mass based on the total mass of the adhesive layer. The adhesive layer preferably does not contain any adhesion enhancers other than the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion.

[0034] The water-soluble polymer is not particularly limited as long as it can retain moisture in the adhesive layer, and those generally known to those skilled in the art can be used. Examples of water-soluble polymers include polyacrylic acid, neutralized polyacrylic acid, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, hydroxypropyl cellulose, sodium carboxymethylcellulose (carmellose sodium), methylcellulose, and carrageenan. A single water-soluble polymer may be used, or two or more may be used in combination. The neutralized polyacrylic acid may be a fully neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. Examples of the neutralized polyacrylic acid include polyacrylic acid salts, such as sodium salts, potassium salts, calcium salts, and ammonium salts. The partially neutralized polyacrylic acid is a polymer chain in which structural units derived from acrylic acid and structural units derived from acrylic acid salts are present in any ratio. It is preferable to use a partially neutralized polyacrylic acid in which 50 mol% of the carboxy groups in a polymer chain are neutralized. The water-soluble polymer preferably contains at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid, and more preferably contains polyacrylic acid and neutralized polyacrylic acid. When the pressure-sensitive adhesive layer contains a water-soluble polymer, the content thereof is preferably 3% by mass to 15% by mass, more preferably 5% by mass to 13% by mass, and even more preferably 7% by mass to 11% by mass, based on the total mass of the pressure-sensitive adhesive layer. When the pressure-sensitive adhesive layer contains polyacrylic acid, the content thereof is preferably 1% by mass to 5% by mass, more preferably 2% by mass to 5% by mass, and even more preferably 2.5% by mass to 4.5% by mass, based on the total mass of the pressure-sensitive adhesive layer. When the pressure-sensitive adhesive layer contains neutralized polyacrylic acid, the content thereof is preferably 1% by mass to 5% by mass, more preferably 1.5% by mass to 4.5% by mass, and even more preferably 2% by mass to 4% by mass, based on the total mass of the pressure-sensitive adhesive layer.When the pressure-sensitive adhesive layer contains polyvinyl alcohol, the content thereof is preferably 1% by mass to 5% by mass, more preferably 1% by mass to 4% by mass, and even more preferably 1.5% by mass to 3.5% by mass, based on the total mass of the pressure-sensitive adhesive layer.

[0035] Examples of the refreshing agent include thymol, l-isopulegol, and peppermint oil. One refreshing agent may be used alone, or two or more refreshing agents may be used in combination. When the pressure-sensitive adhesive layer contains a refreshing agent, the content thereof is preferably 1% by mass to 1.5% by mass based on the total mass of the pressure-sensitive adhesive layer.

[0036] The solubilizing agent is not particularly limited as long as it can dissolve the drug, and examples thereof include surfactants such as crotamiton; N-methylpyrrolidone; polyalkylene glycols such as polyethylene glycol (PEG) and polybutylene glycol; oxyalkylene fatty acid esters such as polyethylene glycol monostearate; polyoxyalkylene sorbitan fatty acid esters such as polysorbate 80; sorbitan fatty acid esters such as sorbitan monooleate; and polyoxyethylene hydrogenated castor oil. These solubilizing agents may be used alone or in combination of two or more. When the adhesive layer contains a solubilizing agent, the content thereof is preferably 0.1% to 3% by mass, more preferably 0.2% to 1% by mass, and even more preferably 0.3% to 0.7% by mass, based on the total mass of the adhesive layer.

[0037] The crosslinking agent is a component for adjusting the degree of progress of the crosslinking reaction between neutralized polyacrylic acids and between the neutralized polyacrylic acid and optionally added polyacrylic acid, and a crosslinking agent commonly used in poultices can be used. Examples of crosslinking agents include aluminum compounds. When the adhesive layer contains a crosslinking agent, the content thereof is preferably 0.05% by mass to 1% by mass, more preferably 0.1% by mass to 0.7% by mass, and even more preferably 0.2% by mass to 0.5% by mass, based on the total mass of the adhesive layer. When the content of the crosslinking agent is within this range, a poulticet with better skin conformability can be obtained. It is preferable that the adhesive layer does not contain any crosslinking agent other than magnesium aluminometasilicate.

[0038] Examples of the filler include inorganic fillers such as silicic anhydride, titanium oxide, synthetic aluminum silicate, kaolin, talc, bentonite, magnesium aluminometasilicate, etc., and the filler may be one of these or a combination of two or more of them. When the pressure-sensitive adhesive layer contains a filler, the content thereof is preferably 0.1% by mass to 1.5% by mass, more preferably 0.2% by mass to 1% by mass, and even more preferably 0.3% by mass to 0.7% by mass, based on the total mass of the pressure-sensitive adhesive layer.

[0039] The humectant is not particularly limited as long as it can suppress evaporation of water from the pressure-sensitive adhesive layer over time. Examples of humectants include polyhydric alcohols such as glycerin, sorbitol, ethylene glycol, 1,4-butanediol, polyethylene glycol, and liquid paraffin. These humectants may be used alone or in combination of two or more. The humectant preferably contains at least one selected from the group consisting of glycerin and sorbitol, and more preferably contains glycerin and sorbitol. When the pressure-sensitive adhesive layer contains a humectant, the content thereof is preferably 15% to 45% by mass, more preferably 20% to 40% by mass, and even more preferably 25% to 35% by mass, based on the total mass of the pressure-sensitive adhesive layer.

[0040] Examples of stabilizers include oxybenzone, dibutylhydroxytoluene (BHT), sodium edetate, UV absorbers (e.g., dibenzoylmethane derivatives), etc. When the pressure-sensitive adhesive layer contains a stabilizer, the content thereof is preferably 0.05% by mass to 1% by mass, more preferably 0.1% by mass to 0.6% by mass, and even more preferably 0.2% by mass to 0.6% by mass, based on the total mass of the pressure-sensitive adhesive layer.

[0041] Examples of preservatives include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, 1,2-pentanediol, benzoic acid and its salts, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, 4-isopropyl-3-methylphenol, 2-isopropyl-5-methylphenol, phenol, hinokitiol, cresol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, chlorobutanol, benzalkonium chloride, and benzethonium chloride. These preservatives may be used alone or in combination of two or more. When the adhesive layer contains a preservative, the content thereof is preferably 0.01% by mass to 1% by mass, more preferably 0.05% by mass to 0.5% by mass, and even more preferably 0.1% by mass to 0.2% by mass, based on the total mass of the adhesive layer.

[0042] Examples of chelating agents include edetic acid (also known as ethylenediaminetetraacetic acid, EDTA) or salts thereof, ascorbic acid, pyrophosphate, hexametaphosphate, gluconate, etc. These chelating agents may be used alone or in combination of two or more. A more specific example of an edetate is sodium edetate. When the adhesive layer contains a chelating agent, the content thereof is preferably 0.05% by mass to 1% by mass, more preferably 0.1% by mass to 0.6% by mass, and even more preferably 0.2% by mass to 0.6% by mass, based on the total mass of the adhesive layer.

[0043] The total mass of the adhesive layer is 200 g / m 2 ~1000g / m 2 It can be 400g / m 2 ~1000g / m 2 400 g / m 2 ~650g / m 2 Preferably, it is 400 g / m 2 ~650g / m 2 When the total mass of the adhesive layer is within the above range, the thickness of the entire poultice can be reduced, the poultice can easily conform to the skin, and the difference in level with the peripheral edge when applied is reduced, so that the poultice tends to be less likely to peel off.

[0044] The pH of the adhesive layer is preferably 4 to 8, and more preferably 4.5 to 6. A pH of 4 or higher reduces skin irritation, while a pH of 8 or lower improves the moldability and shape retention of the poultice. In particular, when the backing layer is a woven fabric, particularly a knitted fabric, bleeding may occur during the formation of the adhesive layer, but a pH of 5 to 6.5 tends to suppress bleeding. The pH can be measured, for example, according to the pH measurement method in the general test methods of the Japanese Pharmacopoeia, using a glass composite electrode and diluting a sample 20 times with purified water.

[0045] The cataplasm can be produced, for example, by mixing a drug, water, gelatin, l-menthol, a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion, magnesium aluminometasilicate, and, if necessary, the optional components described above, to obtain an adhesive composition, spreading the adhesive composition uniformly on a release liner, and laminating a backing layer thereon. Alternatively, the cataplasm may be produced by spreading the adhesive composition uniformly on a backing layer, and laminating a release liner thereon. [Example]

[0046] The components of the compositions shown in Examples and Comparative Examples of Tables 1 to 4 (the numerical values of each component in the table represent mass %) were mixed to prepare an adhesive composition. Next, the obtained adhesive composition was uniformly spread on a release liner (a polypropylene film) so that the mass of the adhesive layer per unit area was 500 g / m 2 and a support layer (a non-woven fabric made of polyethylene terephthalate, basis weight: 100 g / m 2 ) was laminated thereon, and then cut into a size of 140 cm 2 (10 cm × 14 cm) to obtain a patch. A methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion was Nikkazol TS-620 (trade name, manufactured by Nippon Carbide Industries Co., Inc.). Also, concentrated glycerin and D-sorbitol solution were those listed in the Japanese Pharmacopoeia (The Eighteenth Revised Japanese Pharmacopoeia). For each patch, l-menthol precipitation, unevenness during spreading, bleeding, liner curl, liner peelability, initial adhesiveness, adhesiveness over time, pain during peeling, and remaining adhesive layer were evaluated by the following methods respectively.

[0047] <Unevenness during spreading> The adhesive layer during spreading was observed and evaluated according to the following evaluation scores. A score of 2 or more was judged as acceptable. 2. The surface and thickness are uniform over the entire surface of the adhesive layer (area: 90% or more) and there is no unevenness in spreading 1. In a part of the adhesive layer (area: exceeding 10%), the surface and / or thickness are not uniform, and unevenness in spreading is confirmed

[0048] All of the following evaluations were performed on the patches that were sealed in an aluminum packaging bag, left standing at 25°C for 10 days or more, up to 15 days at most, and then taken out from the packaging bag.

[0049] <l-menthol precipitation> The surface of the adhesive layer of the patch was visually observed, and the presence or absence of crystal precipitation of l-menthol was evaluated according to the following criteria. Ten patches were evaluated, and the average value of the scores was used as the evaluation result. A score (average value) of 2.0 or more was judged as acceptable. 2. No precipitation 1. Precipitation

[0050] <bleeding> The area of ​​the portion where the components of the adhesive layer had seeped into the backing layer was measured and evaluated according to the following evaluation score: Five to 20 patches were evaluated, and the average score was used as the evaluation result, with a score (average value) of 5.0 or more being judged as acceptable. 5.No bleeding 4. Slight bleeding (area: less than 10%) 3. Slight bleeding (area: 10% to less than 20%) 2. Excessive seepage (area: 20% to less than 30%) 1. There is a considerable amount of seepage (area: 30% or more)

[0051] <Liner misalignment> The degree of misalignment between the adhesive layer of the cataplasm and the release liner was scored according to the following criteria: Five to 20 cataplasms were evaluated, and the average score was used as the evaluation result. A score (average value) of 4.0 or more was judged to be acceptable. 4. No liner misalignment (less than 0.5mm) 3. Almost no liner misalignment (misalignment between 0.5mm and 1.5mm) 2. Clear liner misalignment (misalignment of 1.5mm or more) 1. Measurement impossible (liner layer fell off during testing)

[0052] <Liner releasability> The ease of peeling the release liner from the cataplasm was scored according to the following criteria. Evaluation was performed on 5 to 20 cataplasms, and the average score was used as the evaluation result. A score (average value) of 3.0 or more was judged to be acceptable. 5. Very easy to peel off 4.Slightly easy to peel off 3.Acceptable peelability 2. Somewhat difficult to peel off 1. Very difficult to peel off

[0053] <Initial adhesion> The release liner was peeled off from the patch and applied to the elbows of 5 to 20 subjects. After bending the elbows 40 times, the adhesiveness of the adhesive layer to the skin was scored according to the following criteria. The average score of the 5 to 20 subjects was used as the evaluation result, and a score (average) of 5.0 or higher was considered acceptable. 6. No peeling 5. Peeling of the edge (less than 1 / 4) 4. Peeling of 1 / 4 or more but less than 1 / 3 3. Peeling of 1 / 3 or more but less than 1 / 2 Peeling of 2.5 or more 1. Falling off

[0054] <Adhesion over time> The release liner was peeled off from the patch and applied to the elbows of 5 to 20 subjects, and the adhesive layer's adhesion to the skin was scored according to the following criteria after 4 hours and 6 hours. The average score of the 5 to 20 subjects was used as the evaluation result, and a score (average) of 5.0 or higher was considered acceptable. 6. No peeling 5. Peeling of the edge (less than 1 / 4) 4. Peeling of 1 / 4 or more but less than 1 / 3 3. Peeling of 1 / 3 or more but less than 1 / 2 Peeling of 2.5 or more 1. Falling off

[0055] <Pain when peeling> In the above-mentioned adhesion test over time, the patch was removed from the subject's elbow after 6 hours of application, and the pain experienced when removing the patch was scored according to the following criteria. The average score of 5 to 20 subjects was used as the evaluation result, and a score (average) of 3.0 or higher was considered acceptable. 4. None 3. Slightly (not noticeable) 2. Slightly 1. Quite likely

[0056] <Remaining adhesive layer> In the above-mentioned peeling pain test, the proportion of the adhesive layer remaining on the skin (area basis) after peeling the patch was scored according to the following criteria. The average score of 5 to 20 subjects was used as the evaluation result, and a score (average) of 3.0 or more was judged to be acceptable. 4. None 3. Slightly remaining (less than 1 / 10) 2. Somewhat remaining (more than 1 / 10 but less than 1 / 5) 1. A lot remains (more than 1 / 5)

[0057] The results are summarized in Tables 1 to 4. In the tables, A indicates that the acceptable conditions in the above evaluation are met, and B indicates that the acceptable conditions are not met. [Table 1]

[0058] As is clear from the results shown in Table 1, it was confirmed that in the cataplasm containing less than 1.5% by mass of methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (Comparative Example 1), l-menthol crystals precipitated and the liner releasability was insufficient. On the other hand, in the cataplasms containing 3.0% to 25% by mass of methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (Comparative Examples 2 to 6), although l-menthol crystal precipitation was suppressed, other problems arose, such as insufficient liner releasability, adhesion, bleeding, or pain upon removal.

[0059] [Table 2]

[0060] As is clear from the results shown in Table 2, the patches containing less than 0.25% by mass or more than 0.45% by mass of magnesium aluminometasilicate (Comparative Examples 7, 8, 11, 12 and 15) and the patches containing less than 1% by mass or more than 3% by mass of gelatin (Comparative Examples 7 to 15) were found to be insufficient in at least one respect: unevenness during spreading, adhesion, bleeding, and liner releasability.

[0061] [Table 3]

[0062] [Table 4]

[0063] As is clear from the results shown in Tables 3 and 4, the cataplasms of the present invention (Examples 1 to 8 and 14 to 18) were confirmed to be excellent in all evaluation items.

[0064] Furthermore, poultices (Examples 9 to 12) were produced in the same manner as in Example 4, except that diclofenac sodium (1.0% by mass), ketoprofen (0.3% by mass), felbinac (0.7% by mass), or flurbiprofen (0.33% by mass) was used instead of indomethacin, and the poultices were evaluated. All of the poultices of Examples 9 to 12 showed good results in all evaluation items.

[0065] A cataplasm (Example 13) was produced in the same manner as in Example 4, except that BPW HW-2 (trade name, manufactured by Toyochem Co., Ltd.) was used as the methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion instead of Nikasol TS-620 (trade name, manufactured by Nippon Carbide Industries Co., Ltd.), and the cataplasm was evaluated. The cataplasm of Example 13 showed good results in all evaluation items.

Claims

1. a support layer; a pressure-sensitive adhesive layer laminated on the support layer; a release liner provided on the surface of the pressure-sensitive adhesive layer opposite to the support layer; A method for producing a poultice comprising: a step of obtaining a pressure-sensitive adhesive composition containing a drug, water, gelatin, 1-menthol, a methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate; a step of spreading the PSA composition on a release liner or a support layer, and laminating a support layer or a release liner thereon, the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion is 1.5% by mass to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% by mass to 0.45% by mass, and the content of the gelatin is 1% by mass to 3% by mass, based on the total mass of the pressure-sensitive adhesive layer; A method for manufacturing a poultice.

2. The method according to claim 1, wherein the pressure-sensitive adhesive composition further comprises at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid.

3. a support layer; a pressure-sensitive adhesive layer laminated on the support layer; a release liner provided on the surface of the pressure-sensitive adhesive layer opposite to the support layer; A method for suppressing crystal precipitation of 1-menthol in a cataplasm comprising: a step of obtaining a pressure-sensitive adhesive composition containing a drug, water, gelatin, 1-menthol, a methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion, and magnesium aluminometasilicate; a step of spreading the PSA composition on a release liner or a support layer, and laminating a support layer or a release liner thereon, the content of the methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion is 1.5% by mass to 20% by mass, the content of the magnesium aluminometasilicate is 0.25% by mass to 0.45% by mass, and the content of the gelatin is 1% by mass to 3% by mass, based on the total mass of the pressure-sensitive adhesive layer; method.

4. The method according to claim 3, wherein the pressure-sensitive adhesive composition further comprises at least one selected from the group consisting of polyacrylic acid and neutralized polyacrylic acid.

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