Patches

Abstract

[Problem] To provide a hydrous transdermal patch in which the stability of glycol salicylate and the adhesive strength and degree of crosslinking of a formulation have been improved. [Solution] Provided is a hydrous transdermal patch comprising a support body, an adhesive layer provided on the support body, and a release liner attached to the adhesive layer. The adhesive layer contains a) glycol salicylate, b) an alkyl (meth)acrylic acid ester copolymer, c) a partially neutralized poly(acrylic acid), d) a water-soluble polymer compound including carmellose sodium, e) a wetting agent including glycerin, f) a crosslinking agent, g) hydrochloric acid and h) water. The blending quantity of glycerin in the adhesive layer is more than 15 times and not more than 18 times the blending quantity of glycol salicylate on a mass basis.

Description

[Technical Field]

[0001] The present invention relates to an aqueous patch, and more particularly to an aqueous patch that has good adhesive strength despite being aqueous, has good stability of the glycol salicylate contained therein, and has an appropriate degree of crosslinking. [Background technology]

[0002] Patches using a water-containing adhesive base, commonly referred to as "cataplasms" (referred to herein as aqueous patches), are a type of patch that comprises a paste layer (adhesive layer) containing an active ingredient such as a drug on a support such as a nonwoven fabric. Because patches use a water-containing adhesive base for the paste layer, they cause little skin irritation but have weak adhesive strength, and in particular, as the water in the paste layer evaporates, the adhesive strength decreases over time, making them prone to peeling from the skin. To solve these problems, a known technique involves blending an emulsion (also called emulsion) base in which an acrylic acid alkyl ester copolymer, known as one of the components that make up non-aqueous (also called hydrophobic or lipophilic) adhesives, is dispersed into the plaster layer (adhesive layer) of an aqueous adhesive patch.

[0003] For example, Patent Document 1 discloses a patch (comparison product) in which 1% of a methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion (trade name Nikazol TS-620, Nippon Carbide Industries Co., Ltd.) is blended into a cataplasm base (plaster). Patent Document 2 discloses an aqueous topical patch that contains, relative to the total composition for an aqueous topical patch, 0.01% by mass to 10.0% by mass of a water-dispersible surfactant and 5.0% by mass to 10% by mass of a methyl acrylate-2-ethylhexyl acrylate copolymer, with the aim of providing an aqueous topical patch that exhibits adhesive strength and re-adhesive strength when applied for extended periods of time, inhibits hardening and loss of flexibility due to moisture loss, and inhibits rupture of the support when removed. Patent Document 3 discloses a catalyzed patch that has sufficient adhesive strength even when the water content of the patch decreases over time, and contains a partially neutralized polyacrylic acid, a methyl acrylate-2-ethylhexyl acrylate copolymer in an amount 2.5 to 10 times the neutralized product by mass (5 to 25% by mass based on the plaster), and polyacrylic acid. Patent Document 4 discloses a cataplasm containing poly(methyl acrylate / 2-ethylhexyl acrylate) and a surfactant such as a polyethylene glycol fatty acid ester, with the aim of providing a cataplasm that allows the release liner to be peeled off with less force. Patent Document 5 discloses that a cooling / heating sheet was obtained using an adhesive composition containing 1.5 wt % of an acrylic resin emulsion (trade name: Nikazol TS-620) and 6.2 wt % of sodium polyacrylate. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 9-208462 [Patent Document 2] Patent No. 5650684 specification [Patent Document 3] Patent No. 5921779 specification [Patent Document 4] International Publication No. 2016 / 104227 [Patent Document 5] Japanese Patent Application Laid-Open No. 2002-104957 Summary of the Invention [Problem to be solved by the invention]

[0005] As mentioned above, it is known that acrylic acid alkyl ester copolymers, such as methyl acrylate-2-ethylhexyl acrylate copolymer, can be incorporated into the adhesive layer to enhance the adhesive durability of aqueous patches. However, glycol salicylate has issues with its drug stability in aqueous solvents, meaning that the drug stability and adhesive strength of aqueous patches containing glycol salicylate have not yet been fully satisfactory. [Means for solving the problem]

[0006] As a result of intensive research into solving the above-mentioned problems, the inventors have discovered that the above-mentioned problems can be solved by adjusting the pH of the adhesive (plaster base), in particular by incorporating hydrochloric acid as an essential ingredient for pH adjustment, in order to achieve both improved stability of glycol salicylate in aqueous patches, improved adhesiveness of the preparation, and an appropriate degree of crosslinking, and have thus completed the present invention.

[0007] That is, the present invention provides a water-containing patch comprising a backing, a pressure-sensitive adhesive layer provided on the backing, and a release liner attached to the pressure-sensitive adhesive layer, The pressure-sensitive adhesive layer essentially contains the following components a) to h): a) glycol salicylate, b) (meth)acrylic acid alkyl ester copolymer, c) partially neutralized polyacrylic acid, d) a water-soluble polymer compound containing carmellose sodium; e) a humectant including glycerin; f) a crosslinking agent; g) hydrochloric acid, and h) water; and, the amount of glycerin in the pressure-sensitive adhesive layer is more than 15 times and not more than 18 times the amount of glycol salicylate, by mass; This relates to a water-containing patch.

[0008] Furthermore, the present invention provides the following embodiments. 1) The aqueous patch, wherein the pH value of the pressure-sensitive adhesive layer is 4.00 to 4.85. 2) When the total mass of the pressure-sensitive adhesive layer is 100% by mass, the pressure-sensitive adhesive layer a) 0.1 to 30% by mass of glycol salicylate, b) 0.1 to 5% by mass of an (meth)acrylic acid alkyl ester copolymer, c) 3.5 to 4.5% by mass of a partially neutralized polyacrylic acid, d) 2.0 to 30% by mass of a water-soluble polymer compound containing sodium carboxymethylcellulose, e) 30 to 70% by mass of a wetting agent containing glycerin, f) 0.01 to 6.0% by mass of a crosslinking agent, g) 0.1 to 1.5% by mass of hydrochloric acid, h) 10 to 90% by mass of water, and is formulated in the following proportions. 3) The aqueous patch, wherein the degree of swelling of the pressure-sensitive adhesive layer, calculated as the ratio of the weight of the pressure-sensitive adhesive layer after 24-hour immersion and standing to the weight of the pressure-sensitive adhesive layer before immersion and standing in purified water, is less than 50. 4) Storage conditions: The reduction rate (%) of the residual rate (%) of glycol salicylate before and after storage at 60°C for 2 weeks is less than 5%. As an example of a preferred embodiment of the present invention, the following can be cited. (i) In the pressure-sensitive adhesive layer, the total blending amount of the partially neutralized polyacrylic acid and sodium carboxymethylcellulose is within 7% by mass based on the total mass of the pressure-sensitive adhesive layer, and the blending amount of the partially neutralized polyacrylic acid is 3.5% by mass or more, and the blending amount of sodium carboxymethylcellulose is 2.0% by mass or more. (ii) The (meth)acrylic acid alkyl ester is a copolymer of a monomer mixture composed of monomer A and monomer B, wherein monomer A is a monomer that forms a polymer having a glass transition temperature (Tg) of 270 K or higher when homopolymerized, and monomer B is a monomer that forms a polymer having a glass transition temperature (Tg) of 220 K or lower when homopolymerized. (iii) The aforementioned aqueous patch, wherein the partially neutralized polyacrylic acid has a degree of neutralization of 30% to 65%, and a 0.2% by mass aqueous solution thereof has a viscosity of 450 to 650 mPa·s. (iv) The aforementioned hydrous adhesive patch, wherein the carmellose sodium has a viscosity of 1,000 to 3,000 mPa·s in a 1% by mass aqueous solution and a degree of ester substitution of 0.60 to 0.95. (v) The aqueous patch, wherein the crosslinking agent is a poorly soluble aluminum compound. (vi) The aqueous adhesive patch, wherein the adhesive layer is formed from an adhesive layer-forming composition containing the components a) to h) and having a viscosity of 90 to 250 Pa·s. (vii) the pressure-sensitive adhesive layer further i) Sodium edetate hydrate as a chelating agent The aqueous patch comprising: [Effects of the Invention]

[0009] According to the present invention, by incorporating hydrochloric acid into the adhesive layer of an aqueous patch containing glycol salicylate in the adhesive layer, it is possible to provide an aqueous patch in which the active ingredient glycol salicylate is stable over time, the adhesive strength of the preparation is high, and the degree of crosslinking is good. Furthermore, the present invention can provide a hydrous patch that can maintain adhesive strength even after the water in the adhesive layer has evaporated, has low skin irritation, low inter-substrate adhesion, and is reapplicable to the skin. DETAILED DESCRIPTION OF THE INVENTION

[0010] As described above, the present inventors have discovered that in aqueous patches, particularly aqueous patches in which a non-aqueous adhesive base is incorporated into the paste layer (adhesive layer) of an aqueous patch, the pH of the adhesive (paste) can be adjusted by incorporating hydrochloric acid, an inorganic acid, into the adhesive layer; specifically, by shifting the pH value of the adhesive layer from the neutral side to the acidic side, the stability of the drug (glycol salicylate) in the presence of water can be improved. Particularly surprisingly, the inventors have discovered that the incorporation of hydrochloric acid not only improves drug stability but also improves both the degree of crosslinking and adhesive strength, which are hardly sufficient when other acids are used. The constitution of the aqueous patch of the present invention will be explained below.

[0011] The aqueous patch of the present invention (hereinafter also simply referred to as "patch") comprises a backing, an adhesive layer provided on the backing, and a release liner attached to the adhesive layer. The shape of the above-mentioned patch, particularly the preparation portion consisting of the support and the adhesive layer provided on the support, is not particularly limited, and various shapes can be selected according to the application site, such as a square (square, rectangle, etc.), quadrilateral (trapezoid, rhombus, etc.), polygon, circle, ellipse, semicircle, triangle, crescent, and shapes combining these. The area of the patch (particularly the above-mentioned preparation portion) can be determined appropriately, for example, in consideration of the amount of active ingredient to be blended in the adhesive layer, and can be, for example, 2 to 300 cm. 2 The range can be:

[0012] [Adhesive layer] The adhesive layer in the aqueous patch of the present invention essentially contains a) glycol salicylate, b) (meth)acrylic acid alkyl ester copolymer, c) partially neutralized polyacrylic acid, d) water-soluble polymer containing carmellose sodium, e) humectant containing glycerin, f) crosslinker, g) hydrochloric acid, and h) water. The aqueous adhesive patch of the present invention is characterized in that, in addition to the hydrophilic acrylic adhesive described below, i.e., c) partially neutralized polyacrylic acid, b) an alkyl (meth)acrylate copolymer, which generally constitutes a non-aqueous acrylic adhesive, is blended into the aqueous adhesive layer. Generally, hydrophilic acrylic adhesives such as polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, and N-vinylacetamide-sodium acrylate copolymer resin are widely used as adhesives for the adhesive layer (plaster layer) of aqueous adhesive patches. From the viewpoint of high affinity with the above-mentioned hydrophilic acrylic adhesives and ability to be kneaded uniformly, acrylic and methacrylic emulsion-type adhesives are preferably used as non-aqueous adhesives to be blended into the aqueous adhesive layer of aqueous adhesive patches. In this specification, the term "(meth)acrylic acid alkyl ester copolymer" is intended to include both alkyl esters of acrylic acid and alkyl esters of methacrylic acid, and the term "acrylic pressure-sensitive adhesive" is intended to include both acrylic pressure-sensitive adhesives and methacrylic pressure-sensitive adhesives.

[0013] <a)サリチル酸グリコール> The adhesive layer in the aqueous patch of the present invention contains glycol salicylate (also called ethylene glycol salicylate) as an active ingredient. In addition to glycol salicylate, other non-steroidal anti-inflammatory agents such as felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, ibuprofen, or esters thereof; antihistamines such as diphenhydramine, chlorpheniramine, or the like; analgesics such as aspirin, acetaminophen, ibuprofen, or loxoprofen sodium, or local anesthetics such as lidocaine, dibucaine, or the like, may also be used as needed. antifungal agents such as clotrimazole; antihypertensive agents such as clonidine; vasodilators such as nitroglycerin and isosorbide dinitrate; vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin, and riboflavin butyrate, prostaglandins; scopolamine, fentanyl, capsicum extract, vanillylamide nonylate, capsaicin, dl-camphor, and the like may be used in combination.

[0014] The amount of glycol salicylate, and when other active ingredients are contained, the total amount of glycol salicylate and the other active ingredients can be determined appropriately depending on the type of the other active ingredients, and can be, for example, from 0.1% by mass to 30% by mass, or from 0.5% by mass to 15% by mass, based on the total mass of the adhesive layer of the aqueous patch.

[0015] <b)(メタ)アクリル酸アルキルエステル系共重合体> The (meth)acrylic acid alkyl ester copolymer (non-aqueous adhesive base) that constitutes non-aqueous acrylic adhesives is a copolymer composed of the following components: a (meth)alkyl ester monomer having 2 to 9 carbon atoms that, when homopolymerized, forms a polymer with a glass transition temperature (Tg) of -55°C (218K) or lower as the component that exerts adhesive strength; a monomer that, when homopolymerized, forms a polymer with a Tg of 8 to 165°C (281 to 438K) as the component that improves cohesive strength; and, if necessary, a monomer having functional groups that can act as crosslinking points, such as carboxyl groups or hydroxyl groups (examples of the monomers are listed in Table 1).

[0016] [Table 1]

[0017] Homopolymers made by polymerizing only monomers that exhibit adhesive strength are said to have high adhesive strength but weak mechanical strength, so copolymers that have improved mechanical strength by copolymerization with monomers that improve cohesive strength are generally used as adhesives. As listed as monomers that exhibit adhesive strength in Table 1 above, in the present invention, monomers with higher adhesive strength are used, such as butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, and isononyl acrylate, which have a Tg of 220 K or less when homopolymerized (homopolymer). Of these, 2-ethylhexyl acrylate, which has a proven track record of use as a pharmaceutical additive and has high adhesive strength (low Tg of the homopolymer), can be preferably used. Furthermore, examples of monomers that improve cohesive strength (Tg of the homopolymer is 270 K or higher) include the monomers listed in Table 1, and among these, in the present invention, methyl acrylate is preferred because it has high mechanical strength and does not significantly reduce adhesiveness (Tg of the homopolymer is relatively low).

[0018] As mentioned in the prior art, a commercially available acrylic acid alkyl ester copolymer used in patches is Nikazol (registered trademark) TS-620 (methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion) manufactured by Nippon Carbide Corp. Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is listed in the Pharmaceutical Excipients Standards.

[0019] In the adhesive layer of the aqueous patch of the present invention, the amount of the (meth)acrylic acid alkyl ester copolymer (in the case of an emulsion, the amount converted to solid content) can be, for example, from 0.1% by mass to 5% by mass, from 0.5% by mass to 4.5% by mass, or from 1.0% by mass to 4.5% by mass, based on the total mass of the adhesive layer of the aqueous patch. The blending ratio with the acrylic hydrophilic adhesive described below can be, for example, a mass ratio of acrylic acid alkyl ester copolymer:acrylic hydrophilic adhesive = 1.5:1 to 1:10, 1.5:1 to 1:5, or 1.5:1 to 1:1.

[0020] <c)ポリアクリル酸部分中和物> The adhesive layer of the aqueous patch of the present invention contains a partially neutralized polyacrylic acid as an acrylic hydrophilic adhesive. If necessary, the pressure-sensitive adhesive layer may contain an acrylic hydrophilic pressure-sensitive adhesive other than a partially neutralized polyacrylic acid. Examples of the acrylic hydrophilic pressure-sensitive adhesive generally include water-soluble (meth)acrylic polymers. Water-soluble (meth)acrylic polymers are polymers obtained by polymerizing a (meth)acryloyl group-containing monomer having a water-soluble functional group (hydrophilic group), and exhibit adhesive properties when incorporated into the pressure-sensitive adhesive layer together with water. Examples of water-soluble (meth)acrylic polymers include the aforementioned partially neutralized polyacrylic acid, homopolymers such as polyacrylic acid, and copolymers such as N-vinylacetamide-sodium acrylate copolymer resins.

[0021] The partially neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. In other words, in this specification, the term "partially neutralized polyacrylic acid" encompasses not only a neutralized product in which some of the acid groups of polyacrylic acid are neutralized, but also a neutralized product in which all of the acid groups of polyacrylic acid are neutralized. The partially neutralized polyacrylic acid refers to a polyacrylic acid salt, and examples of such salts include sodium salt, potassium salt, calcium salt, and ammonium salt. Examples include Viscomate NP-800 (manufactured by Showa Denko K.K.).

[0022] In a preferred embodiment, the partially neutralized polyacrylic acid used in the present invention has a degree of neutralization of 30% to 65%. Furthermore, it is preferable to use a partially neutralized polyacrylic acid having a viscosity of 450 to 650 mPa s at 20°C when the partially neutralized polyacrylic acid is dissolved in a 0.2% by mass aqueous solution. By using a partially neutralized polyacrylic acid, particularly one having such a degree of neutralization and viscosity, the adhesiveness to the skin can be enhanced when the composition absorbs water, and crosslinking with the crosslinking agent can be further promoted, thereby preventing dissolution when the composition absorbs water.

[0023] The compounding amount of the above-mentioned partially neutralized polyacrylic acid, and the total compounding amount of the partially neutralized polyacrylic acid and other acrylic-based hydrophilic pressure-sensitive adhesives when other acrylic-based hydrophilic pressure-sensitive adhesives are included, can be, for example, 0.1% by mass or more and 10% by mass or less, 1% by mass or more and 8% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the aqueous pressure-sensitive adhesive. For example, the compounding amount of the above-mentioned partially neutralized polyacrylic acid can be 3.5% by mass or more and 4.5% by mass or less based on the total mass of the pressure-sensitive adhesive layer.

[0024] <d) Water-soluble polymer compound> As the above-mentioned water-soluble polymer compound, the pressure-sensitive adhesive layer in the pressure-sensitive adhesive of the present invention essentially contains sodium carboxymethylcellulose (carboxymethylcellulose sodium). By using sodium carboxymethylcellulose, the shape retention of the preparation can be better maintained, and it has thixotropy and can further reduce the pain during peeling. In a preferred embodiment, the sodium carboxymethylcellulose used in the present invention can have a viscosity of 1,000 to 3,000 mPa·s at 20°C in its 1% by mass aqueous solution. Also, sodium carboxymethylcellulose preferably has an ester substitution degree of 0.60 to 0.95.

[0025] Moreover, a water-soluble polymer compound other than sodium carboxymethylcellulose may be contained. Examples thereof include gelatin, agar, polyvinyl alcohol (including partially saponified products), polyvinylpyrrolidone, propylene carbonate, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, sodium alginate, maleic anhydride copolymer, and carrageenan. These can be used in combination with sodium carboxymethylcellulose by appropriately combining one or more of them.

[0026] The amount of the water-soluble polymer compound can usually be in the range of, for example, 1.0% by mass or more and 30% by mass or less, 2.0% by mass or more and 30% by mass or less, 2.5% by mass or more and 20% by mass or less, or 3.0% by mass or more and 10% by mass or less, based on the total mass of the adhesive layer of the aqueous patch. Furthermore, for example, the amount of carmellose sodium blended can be 2.0% by mass or more and 3.5% by mass or less, based on the total mass of the adhesive layer.

[0027] <e)グリセリンを含む湿潤剤> The adhesive layer of the aqueous patch of the present invention contains a humectant (also called a moisturizer) to inhibit evaporation of water over time. As the above-mentioned wetting agent, glycerin is blended as an essential ingredient in the adhesive layer of the patch of the present invention. Furthermore, a humectant other than glycerin may be blended, examples of which include polyhydric alcohols such as D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,4-butanediol, maltitol, xylitol, etc. These may be used alone or in appropriate combinations of two or more together with glycerin.

[0028] The amount of the humectant blended can usually be in the range of, for example, 30% by mass or more and 70% by mass or less, 40% by mass or more and 60% by mass or less, 40% by mass or more and 50% by mass or less, or 45% by mass or more and 55% by mass or less, based on the total mass of the adhesive layer of the aqueous patch. In the present invention, the amount of glycerin in the adhesive layer is more than 15 times and not more than 18 times the amount of glycol salicylate (a) by mass, e.g., 15.5 to 18.0 times, 16.0 to 17.9 times, 16.5 to 17.9 times, 16.7 to 17.9 times, 17.0 to 17.9 times, 17.5 to 17.9 times, or 15.5 to 17 times. If the amount of glycerin is too low, the adhesive may have insufficient moisture retention, resulting in the adhesive's tendency to volatilize. Furthermore, if the amount of glycerin is too high, the drug may become less stable. On the other hand, if the amount of drug (glycol salicylate) is increased too much to improve stability, safety issues may arise.

[0029] <f)架橋剤> The crosslinking agent to be incorporated into the adhesive layer of the aqueous patch of the present invention may be a polyvalent metal salt, particularly a polyvalent metal compound containing aluminum. Examples include hydroxides such as aluminum hydroxide and magnesium alumina hydroxide; normal salts or basic salts of inorganic or organic acids such as aluminum chloride, aluminum sulfate, potassium aluminum sulfate, aluminum glycinate (dihydroxyaluminum aminoacetal), dihydroxyaluminum aminoacetate, synthetic aluminum silicate, dried aluminum hydroxide gel, kaolin, and aluminum stearate; double salts such as aluminum alum; aluminates such as sodium aluminate; inorganic aluminum complex salts and organic aluminum chelate compounds; and polyvalent metal compounds such as synthetic hydrotalcite, magnesium aluminosilicate, and magnesium aluminometasilicate, which may be used alone or in combination of two or more. Among these, it is preferable to use dihydroxyaluminum aminoacetate, which is a poorly soluble aluminum compound, synthetic aluminum silicate, and dried aluminum hydroxide gel.

[0030] The blending amount of the crosslinking agent may be appropriately selected in consideration of the degree of crosslinking that can contribute to the residue of the adhesive on the skin and the adhesiveness. Based on the total mass of the adhesive layer of the aqueous patch, for example, it can be in the range of 0.01% by mass or more and 6.0% by mass or less, 0.01% by mass or more and 4.0% by mass or less, or 0.01% by mass or more and 2.0% by mass or less.

[0031] <g) Hydrochloric acid> The adhesive layer of the aqueous patch of the present invention is characterized by containing hydrochloric acid. The blending amount of hydrochloric acid can be, for example, in the range of 0.1% by mass or more and 1.5% by mass or less based on the total mass of the adhesive layer of the aqueous patch. In addition, if only other acids such as the acids listed in <organic acids> described later and inorganic acids other than hydrochloric acid are blended without blending hydrochloric acid, it becomes difficult to obtain both appropriate crosslinkability and good adhesiveness. For example, when tartaric acid is used, good adhesiveness cannot be obtained. When phosphoric acid is used, it may result in inferior results compared to the case of using hydrochloric acid from the viewpoints of the stability of salicylic acid glycol and the expression of appropriate crosslinkability. In order to obtain an equivalent effect to the case of using hydrochloric acid in terms of stability, a larger blending amount may be required. Although it is preferable not to add phosphoric acid, it can be added within the limit that does not affect the effects of the present invention, particularly the degree of crosslinking.

[0032] <h) Water> As described above, the aqueous patch of the present invention contains water (moisture) in the adhesive layer. In this specification, the "water" contained in the adhesive layer includes not only water separately added as water when forming the adhesive layer, but also water contained in the form of an emulsion or an aqueous solution. The blending amount of water is not particularly limited, but based on the total mass of the adhesive layer of the aqueous patch, for example, it can be in the range of 10% by mass or more and 90% by mass or less, 15% by mass or more and 70% by mass or less, or 20% by mass or more and 50% by mass or less. Note that this moisture blending amount is the value at the time of preparing the patch or before applying the patch. If water volatilizes from the adhesive layer over time during application, this is not the case.

[0033] <i)キレート剤> The adhesive layer of the aqueous patch of the present invention may contain a chelating agent to control the viscosity of the paste during production. Examples of chelating agents include sodium edetate (ethylenediaminetetraacetic acid disodium salt). The amount of the chelating agent can usually be in the range of, for example, 0.01 to 1% by mass, or 0.1 to 0.3% by mass, based on the total mass of the adhesive layer of the aqueous patch.

[0034] <Organic solvents> The adhesive layer of the aqueous patch of the present invention may contain an organic solvent as a component that can assist in dissolving the active ingredient such as a drug (i.e., function as a solubilizing agent) and prevent the active ingredient from precipitating from the adhesive layer. Examples of such organic solvents (solubilizing agents) include crotamiton, N-methyl-2-pyrrolidone, polyalkylene glycols such as macrogol 400 (polyethylene glycol) and polybutylene glycol, polyvinyl alcohol, fatty acid esters such as diethyl adipate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, and oleyl oleate, polyoxyalkylene fatty acid esters, sorbitan esters, polyhydric alcohols such as 1,3-butanediol, dimethylformamide, and dimethyl sulfoxide. These can be used alone or in combination of two or more.

[0035] When an organic solvent is used, the amount of the organic solvent may be, for example, 0.1% by mass or more and 20% by mass or less, based on the total mass of the adhesive layer of the aqueous patch.

[0036] <Organic acid> The adhesive layer of the aqueous patch of the present invention may contain an organic acid, such as tartaric acid, citric acid, lactic acid, gluconic acid, glycolic acid, malic acid, fumaric acid, methanesulfonic acid, maleic acid, or acetic acid, which may be used alone or in combination of two or more. When using an organic acid, its blending amount can be, for example, in the range of 0.1% by mass or more and 5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the aqueous pressure-sensitive adhesive sheet. By using an organic acid in such a blending amount range, it is expected that problems such as insufficient crosslinkability, dissolution of the pressure-sensitive adhesive, and stickiness can be suppressed, while on the other hand, problems such as the crosslinking reaction proceeding too far and the paste becoming too hard to be manufactured can be suppressed.

[0037] <Surfactant> A surfactant can also be incorporated into the pressure-sensitive adhesive layer of the aqueous pressure-sensitive adhesive of the present invention. Examples of such surfactants include polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol dioleate, polypropylene glycol dioleate; sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan monoesquioleate, and ethylene oxide adducts thereof; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan triisostearate; polyoxyethylene alkyl ethers such as polyoxyethylene dodecyl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyalkylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethylhexyl ether, polyoxyethylene isodecyl ether; polyoxyethylene alkylphenol ethers such as polyoxyethylene styrenated phenyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene distyrenated phenyl ether, polyoxyethylene tribenzylphenyl ether; glycerin fatty acid esters such as glycerin monostearate, glycerin monooleate; and nonionic surfactants such as polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, and lecithin.These can be used alone or in appropriate combination of two or more kinds. When these surfactants are used, the blending amount can be in the range of, for example, 0.001% by mass or more and 10% by mass or less, 0.01% by mass or more and 5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch.

[0038] <Other optional components> In the pressure-sensitive adhesive layer of the water-containing patch of the present invention, as other optional components, antioxidants such as dibutylhydroxytoluene (BHT), inorganic powders such as calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, calcium sulfate, ultraviolet absorbers such as benzoylmethane derivatives, coloring agents, fragrances, preservatives, etc., which are generally blended in the pressure-sensitive adhesive layer of conventional water-containing patches (poultices) or non-water-containing patches (tape agents), can be blended. When these optional components are used, they can be used alone or in combination of two or more kinds, usually in the range of 0.01% by mass or more and 1% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the water-containing patch.

[0039] [Support] Examples of the support used in the aqueous adhesive of the present invention include flexible supports such as films, non-woven fabrics, Japanese paper, cotton fabrics, knitted fabrics, woven fabrics, and laminate composites of non-woven fabrics and films. These supports are preferably made of a flexible material that can adhere to the skin and follow the movement of the skin, and a material that can suppress the occurrence of skin irritation and the like after long-term application. Examples of the materials of these supports include those containing polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon / polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, ether polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene rubber, ethylene-vinyl acetate copolymer, cellophane, etc. as essential components.

[0040] In addition, supports such as fabrics can be colored with a colorant to a skin tone such as skin color, thereby reducing the difference from the skin color during application. In terms of being able to easily show through the skin tone under the application, a form of a plastic film with excellent transparency can be adopted.

[0041] The thickness of the support is usually about 5 μm to 1 mm. When the support is a cloth, its thickness is preferably 50 μm to 1 mm, more preferably 100 to 800 μm, and still more preferably 200 to 700 μm. When the support is a plastic film, its thickness is preferably 10 to 300 μm, more preferably 12 to 200 μm, and still more preferably 15 to 150 μm. When the thickness of the support is extremely thin, about 5 μm to 30 μm, it is preferable to provide a peelable carrier film layer on the surface opposite to the adhesive layer formed on the support, as it improves the handleability as an adhesive. However, if the thickness of the support is less than 5 μm, the strength and handleability of the adhesive patch will decrease, making it difficult to attach to the skin, and it may be torn by contact with other members, etc., or peeled off from the skin in a short time by contact with water such as bathing. Also, if the thickness of the support is too large (exceeding 1 mm), the adhesive patch will be less likely to follow the movement of the skin, and it will be easier to form a cause for peeling at the edge of the adhesive patch, so there is a risk of peeling off from the skin in a short time or an increase in discomfort during attachment. In the case where the support is a film, for the purpose of improving the anchoring property between the adhesive and the support, the surface of one side or both sides of the support may be treated by sandblasting, corona treatment, or the like. Also, in order to make it easier to take out from the packaging material, unevenness may be provided on one side or both sides of the support by a method other than sandblasting.

[0042] [Release Liner] The release liner (also referred to as a release layer or release paper) used in the aqueous adhesive patch of the present invention is preferably a material in which drugs, etc. in the adhesive layer are less likely to be absorbed or adsorbed, and those commonly used in the technical field of adhesive patches can be used. For example, plastic films such as polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unstretched, stretched, etc.), polyethylene, polyurethane, polyvinyl chloride, polystyrene; papers such as high-quality paper, glassine paper, parchment paper, kraft paper, and synthetic paper; release-processed papers obtained by coating the above plastic films, papers or synthetic papers, synthetic fibers, etc. with a release agent having release performance such as silicone resin or fluororesin; aluminum foil; laminated processed papers obtained by laminating these films and sheets in various ways, and laminated release-processed papers obtained by coating the laminated processed papers with a release agent, etc., colorless or colored sheets can be mentioned. Note that the release liner can also be provided with unevenness so as to be easily taken out from the packaging material. The thickness of these release liners is not particularly limited, but is usually in the range of 10 μm to 1 mm, for example, 20 μm to 500 μm, preferably 40 μm to 200 μm. In addition, when peeling the adhesive layer from the release liner, it is desirable that the peeling force is within a specific range. This is because if the peeling force of the adhesive layer from the release liner is too weak, when the adhesive in the packaging material is taken out and the adhesive is caught on the packaging material, the adhesive layer (i.e., the adhesive) may shift and peel off from the release liner. Also, if the peeling force of the adhesive layer (adhesive) from the release liner is too strong, there is a risk that the handling property during use will deteriorate. The peeling force of the adhesive layer from the release liner depends on the type of release liner used, but can be, for example, 0.01 N / 15 mm to 0.5 N / 15 mm.

[0043] [Manufacturing method of aqueous adhesive] The aqueous adhesive of the present invention can be manufactured using a conventionally known method. For example, as an example, it can be manufactured through the following steps (i) or (ii). (i) A step of coating a support with an adhesive layer-forming composition to form an adhesive layer, and a step of bonding the adhesive layer formed on the support to a release liner. (ii) A step of applying an adhesive layer-forming composition onto a release liner to form an adhesive layer, and a step of laminating the adhesive layer formed on the release liner with a support. The thickness of the adhesive layer is not particularly limited, but is usually 10 μm to 1000 μm, for example, about 20 μm to 800 μm.

[0044] The adhesive layer-forming composition is a semi-solid composition containing various components included in the aforementioned adhesive layer: glycol salicylate (among others, active ingredients), (meth)acrylic acid alkyl ester copolymer, partially neutralized polyacrylic acid (among others, acrylic hydrophilic adhesive), water-soluble polymer compound containing sodium carboxymethylcellulose, wetting agent containing glycerin, crosslinking agent, hydrochloric acid, and water, and further may contain a chelating agent, organic solvent, organic acid, surfactant, and furthermore other optional components as desired. From the viewpoint of operability during production, the adhesive layer-forming composition preferably has a viscosity of 90 to 250 Pa·s, 100 to 250 Pa·s, more preferably 130 to 250 Pa·s at 20°C to 30°C. When the viscosity is less than 90 Pa·s, there is a risk of the paste leaking through when a knitted fabric or woven fabric is used as the support. When the viscosity exceeds 250 Pa·s, it becomes difficult to spread.

[0045] [pH value of the adhesive layer in the aqueous adhesive patch] In the aqueous adhesive patch of the present invention, the pH value of its adhesive layer is preferably on the acidic side (less than 6.0), and can be 3.5 or more and less than 6.0, for example, 4.00 to 4.85, preferably 4.40 to 4.80, more preferably 4.50 to 4.80. By controlling the pH value of the adhesive layer within a suitable range, the stability of glycol salicylate can be made good, and furthermore, an aqueous adhesive patch excellent in the productivity of the adhesive patch can be obtained, such as the coating property (spreadability) of the adhesive being improved. The pH value of the adhesive layer can be measured, for example, in accordance with the pH measurement method of the Japanese Pharmacopoeia general test method at a temperature of 20 to 25°C.

[0046] In some cases, the pH value of a solution obtained by diluting an adhesive (paste) with water may be regarded as the pH value of the adhesive layer (for example, International Publication No. 2016 / 104226). As a specific procedure, the release liner is peeled off from the prepared patch, the adhesive is scraped off from the exposed adhesive layer using a spatula or the like, purified water is added to the collected adhesive, and a uniform solution is prepared by diluting it, for example, 20-fold. The obtained solution is kept at room temperature (25.0 ± 0.2°C), the glass composite electrode of a calibrated pH meter is inserted into the solution, and the pH value is measured.

[0047] <Degree of swelling> When the adhesive layer (adhesive layer-forming composition) of the present invention is immersed and allowed to stand in purified water for 24 hours, it is preferable that the degree of swelling of the adhesive layer, calculated as the ratio of the weight of the adhesive layer after 24 hours of immersion and standing to the weight of the adhesive layer before immersion and standing, is less than 50. The procedure for measuring and calculating the degree of swelling is, for example, as follows: The hydroadhesive patch and the support are cut into a predetermined size, and their weights are measured with the liner peeled off for the hydroadhesive patch (initial hydroadhesive patch (liner-peeled) weight, initial support weight). Then, these are immersed and allowed to stand in purified water for 24 hours, and their weights after 24 hours of immersion and standing are measured respectively (weight of the hydroadhesive patch (liner-peeled) after standing in purified water, weight of the support after standing in purified water), and the degree of swelling can be calculated according to the following formula. Degree of swelling of the adhesive layer = (weight of the hydroadhesive patch (liner-peeled) after standing in purified water - weight of the support after standing in purified water) / (initial weight of the hydroadhesive patch (liner-peeled) - initial weight of the support) By setting the degree of swelling of the adhesive layer to less than 50, the shape retention of the adhesive layer can be maintained, and a hydroadhesive patch can be provided that suppresses the risk of the adhesive layer remaining on the skin after peeling.

Examples

[0048] The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

[0049] <Preparation of the patch> The patches (preparations) of the Examples, Comparative Examples, and Production Examples were produced according to the following procedures.

[0050] Example 1: 1.5 parts by mass of polyvinyl alcohol was dissolved in purified water (aqueous phase). Next, 1 part by mass of Macrogol 400 was added to 1.25 parts by mass of ethylene glycol salicylate and 1 part by mass of L-menthol and dissolved (oil phase). Furthermore, 4 parts by mass of partially neutralized polyacrylic acid (degree of neutralization: 35%, viscosity: when made into a 0.2% by mass aqueous solution, the viscosity at 20°C was 547 mPa·s), 3 parts by mass of carmellose sodium (degree of ester substitution: 0.82, viscosity: when made into a 1% by mass aqueous solution, the viscosity at 20°C was 1,840 mPa·s), and 0.25 parts by mass of dihydroxyaluminum aminoacetate were uniformly dispersed in 22 parts by mass of concentrated glycerin (glycerin phase). The aqueous phase, 7 parts by mass of a methyl acrylate-2-ethylhexyl acrylate copolymer emulsion, 0.20 parts by mass of sodium edetate hydrate, 30 parts by mass of a 70% D-sorbitol aqueous solution, and 0.9 parts by mass of hydrochloric acid diluted with purified water (the remainder) were added to a mixer in this order and uniformly dispersed or dissolved. The oil phase and glycerin phase were then added to the mixture in this order and kneaded uniformly. Furthermore, 1 part by mass of lactic acid was added, and the mixture was kneaded uniformly under degassing conditions to obtain a pressure-sensitive adhesive layer-forming composition of Example 1. The resulting pressure-sensitive adhesive layer-forming composition was used to perform Test Example 4 (adhesive viscosity), which will be described later. The obtained pressure-sensitive adhesive layer-forming composition was spread on the silicone surface of a liner (one-side silicone-treated PET (75 μm)) using a spreader, and a knit support (made of polyester) was laminated, followed by aging for 1 week at 40° C. After aging, the mixture was punched into a desired shape to obtain the formulation of Example 1.

[0051] Examples 2 to 9, Comparative Examples 1 to 9, and Production Examples 1 to 20: Except for changing the types and blending amounts of the respective components as described in Tables 2, 3, 4 to 6, preparations of Examples 2 to 9, Comparative Examples 1 to 9, and Production Examples 1 to 20 were obtained in the same manner as in Example 1. When phosphoric acid and tartaric acid were blended, they were produced by adding them at the same timing as hydrochloric acid. Also, when glycerin monostearate, polysorbate 80, polyoxyethylene hydrogenated castor oil 10, lauromacrogol, polyoxyethylene oleyl ether, diisopropyl adipate, workman dicyclohexyl sebacate, isopropyl myristate, and isopropyl palmitate were blended, they were produced by adding them at the same timing as macrogol 400, respectively.

[0052] Test Example 1 (Measurement of pH of Adhesive Layer) The pH of each preparation of the examples and comparative examples was measured at 25.0 ± 0.2 °C in accordance with the pH measurement method of the General Test Methods of the Japanese Pharmacopoeia. The results obtained are shown in Tables 2 and 3.

[0053] Test Example 2: Stability Evaluation of Glycol Salicylate (SG) For the stability evaluation of glycol salicylate, the content of glycol salicylate contained in the adhesive layer was measured by high performance liquid chromatography (HPLC) immediately after the production of the preparation (initial) and after storage at 60 °C for 2 weeks (2W). Specifically, each preparation of the examples and comparative examples was cut into 40 mm × 40 mm (16 cm 2 ), the release liner was peeled off, and gauze (medical gauze, type I, 50 mm × 50 mm) was attached to the adhesive layer, and this was used as the test preparation. Using 27 mL of methanol as the extraction solvent, the test preparation was added thereto, and the extraction operation was performed by shaking. The extract was filtered through a membrane filter with a pore size of 0.45 μm to obtain a sample solution. The sample solution was analyzed under the following HPLC conditions. The stability of glycol salicylate (% remaining in the adhesive layer) was evaluated by comparing the relative amount of decomposition products from the peak area of glycol salicylate (retention time: approximately 11 minutes) and the sum of the areas of the other peaks. Furthermore, the reduction in glycol salicylate (% reduction from the initial value) after 2 weeks (2W) of storage at 60°C was calculated from the initial value (% remaining glycol salicylate in the adhesive layer before storage). The results are shown in Tables 2 and 3. Measurement wavelength: 240nm Column: Mightysil RP-18 (150 mm x 4.6 mm, 5 μm) Column temperature: 30℃ Flow rate: 0.5mL / min Mobile phase A: water / methanol = 50 / 50 Analysis time: 30 minutes Injection volume: 10μL Regarding the stability evaluation of glycol salicylate, storage conditions of 40°C for 6 months and 60°C for 2W can be considered to be equivalent, and it is desirable that the stability of glycol salicylate (decrease in percentage from the initial value) after storage at 60°C for 2W be less than 5.0%, which does not result in a clear change in quality.

[0054] Test Example 3: Adhesion Test Ball Tack The release liner was peeled off from each formulation (immediately after production) in the Examples and Comparative Examples to expose the adhesive layer, and the ball tack adhesive strength of the adhesive layer was measured in accordance with the Japanese Pharmacopoeia General Test Method 6.12 Adhesion Strength Test Method 3.2 Inclined Ball Tack Test Method. The average value (ball number) of n=3 was taken as the ball tack test value. The results are shown in Tables 2 and 3. The ball tack evaluation reflects the adhesive strength of the adhesive layer, and the value is preferably 15 or more.

[0055] Test Example 4: Viscosity of adhesive The viscosity of the pressure-sensitive adhesive layer-forming compositions of the Examples and Comparative Examples produced according to the procedure in <Preparation of Patches> was measured using a handy rotational viscometer (measurement temperature: 20° C. to 30° C.) before liner coating. The results are shown in Tables 2 and 3.

[0056] Test Example 5: Degree of crosslinking of adhesive layer Each formulation and support in the Examples and Comparative Examples were cut to a size of 12 x 100 mm, and the weights of the formulations were measured with the liner removed (initial formulation weight, initial support weight), and each was left to stand in a glass bottle containing purified water (room temperature) for 24 hours. After standing, the formulation and support were removed from the purified water and weighed (formulation weight after standing in purified water, support weight after standing in purified water), and the swelling degree of the plaster (adhesive layer) was calculated using the following formula. Swelling degree of plaster = (weight of preparation after standing in purified water - weight of support after standing in purified water) / (initial weight of preparation - initial weight of support) The degree of crosslinking was evaluated based on the calculated degree of swelling according to the following criteria. The results are shown in Tables 2 and 3. Note that a degree of crosslinking of + or higher is preferable; if it is ± or -, the shape retention of the paste may be insufficient, and a large amount of the paste may remain on the skin when removed after application. <Crosslinking degree evaluation> ++: Swelling degree less than 10 +: Swelling degree 10 or more and less than 50 ± : Swelling degree 50 or more - Most of the paste is dispersed in the purified water and cannot be extracted.

[0057] Test Example 6: Manufacturability The adhesive layer-forming compositions of the Examples and Comparative Examples produced according to the procedure in <Preparation of Patches> were evaluated for ease of spreading onto the silicone surface of the liner using a spreading machine, and manufacturability was evaluated according to the following evaluation criteria. The results are shown in Tables 2 and 3. <Manufacturability evaluation> ++: Easily spreadable + : Can be extended ±: Spreadable but not stable - : Cannot be extended

[0058] [Table 2]

[0059] [Table 3]

[0060]

Table 4

[0061]

Table 5

[0062]

Table 6

[0063] As shown in Table 2, in the preparation (aqueous patch) of the example, by blending a predetermined amount of hydrochloric acid, in the stability evaluation of glycol salicylate as the active ingredient, the reduction width with respect to the initial value after storage at 60 °C for 2 weeks was less than 5%, the ball tack value was also 15 or more, and the swelling degree, which is an index of the crosslinking degree of the pressure-sensitive adhesive layer (paste), was less than 50 (+ or more evaluation). Thus, it became an aqueous patch with good stability of the active ingredient, adhesiveness of the preparation, and crosslinking degree. On the other hand, as shown in Table 3, in Comparative Examples 1 and 7 that do not contain hydrochloric acid, the reduction width of glycol salicylate with respect to the initial value exceeded 5%, resulting in a preparation with poor stability of the active ingredient. Also, when phosphoric acid was added instead of hydrochloric acid (Comparative Examples 2 to 6), although the stability of glycol salicylate increased by increasing its blending amount, the crosslinking degree rather deteriorated. Furthermore, when tartaric acid was blended instead of hydrochloric acid (Comparative Examples 8 to 9), the ball tack value was less than 15, and the desired adhesiveness could not be obtained.

[0064] From the results of the above examples, according to the present invention, in an aqueous patch containing glycol salicylate in the pressure-sensitive adhesive layer, by blending hydrochloric acid in the pressure-sensitive adhesive layer, even with a small blending amount, glycol salicylate as the active ingredient is stable over time, and has an appropriate crosslinking degree and good adhesiveness. Furthermore, it was confirmed that an aqueous patch excellent in productivity can be provided.

Claims

1. An aqueous adhesive patch comprising a support, an adhesive layer provided on the support, and a release liner adhered on the adhesive layer, wherein the adhesive layer essentially contains the following components a) to h) and lactic acid, a) glycol salicylate, b) an alkyl (meth)acrylate copolymer, c) a partially neutralized polyacrylic acid, d) a water-soluble polymer compound containing sodium carboxymethylcellulose, e) a humectant containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water, and the blending amount of glycerin in the adhesive layer is more than 15 times and not more than 18 times, based on mass, relative to the blending amount of glycol salicylate, and the pH value of the adhesive layer is 4.00 to 4.85, an aqueous adhesive patch.

2. when the total mass of the adhesive layer is taken as 100% by mass, a) glycol salicylate is 0.1 to 30% by mass, b) an alkyl (meth)acrylate copolymer is 0.1 to 5% by mass, c) a partially neutralized polyacrylic acid is 3.5 to 4.5% by mass, d) a water-soluble polymer compound containing sodium carboxymethylcellulose is 2.0 to 30% by mass, e) a humectant containing glycerin is 30 to 70% by mass, f) a crosslinking agent is 0.01 to 6.0% by mass, g) hydrochloric acid is 0.1 to 1.5% by mass, h) water is 10 to 90% by mass, and lactic acid is 0.1% by mass or more and 5% by mass or less are blended in the following proportions, the aqueous adhesive patch according to Claim 1.

3. The aqueous adhesive patch according to Claim 1 or Claim 2, wherein the degree of swelling of the adhesive layer, calculated as the ratio of the weight of the adhesive layer after immersion and standing for 24 hours to the weight of the adhesive layer before immersion and standing in purified water, is less than 50.

4. Storage conditions: The decrease percentage (%) of the residual rate (%) of glycol salicylate before and after storage at 60°C for 2 weeks is less than 5%, the aqueous adhesive patch according to any one of Claims 1 to 3.

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