TW202135830A - Patch - Google Patents

Abstract

To provide a water-containing patch in which the stability of glycol salicylate, and the adhesive force and crosslinking degree of a preparation are improved. This water-containing patch comprises: a support body; an adhesive layer provided on the support body; and a release liner attached on the adhesive layer, wherein the adhesive layer contains (a) glycol salicylate, (b) (meth)acrylic acid alkyl ester copolymer, (c) a partially neutralized product of polyacrylic acid, (d) a water-soluble polymer compound containing carmellose sodium, (e) a humectant containing glycerin, (f) a crosslinker, (g) a hydrochloric acid, and (g) water, and the added amount of glycerin in the adhesive layer is 15 times to 18 times (exclusive of 15) greater, by mass, than the added amount of glycol salicylate.

Description

Patch

The present invention relates to a water-based patch. In detail, it relates to a water-based adhesive agent that has good adhesion, and the stability of the formulated glycol salicylate is good, and thus has a moderate Water-based patch with degree of cross-linking.

Adhesives that use water-containing adhesive bases (referred to as water-based adhesives in this specification), which are generally called "pockets", are provided on a support such as non-woven fabrics with a paste layer containing active ingredients such as drugs ( Adhesive layer) one of the adhesives. Because the paste layer uses a water-containing adhesive base, there are the following problems: Although the skin irritation is low, the adhesive force is weak, especially the adhesive force will decrease over time with the volatilization of the moisture in the paste layer , Easy to peel from the skin. In order to solve this problem, the following technology is known: an emulsion (also known as an acrylic acid alkyl ester copolymer) is dispersed as a component of a non-aqueous (also called hydrophobic and lipophilic) adhesive. Called emulsion) base is formulated to the paste layer (adhesive layer) of the water-based adhesive agent.

For example, Patent Document 1 discloses an adhesive agent (comparative product) which is formulated in a poultice base (paste) with a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (trade name Nikasol). TS-620, Japan's calcium carbide industry (shares)) 1%. Patent Document 2 discloses a water-based external adhesive agent, which provides an adhesive and re-adhesive force that can be exhibited during long-term sticking, suppressing hardening and reduction of softness accompanying moisture loss, and suppressing peeling. For the purpose of the ruptured water-based patch of the support, it contains a water-dispersible surfactant at a ratio of 0.01% by mass to 10.0% by mass with respect to the total water-based external patch composition, and with respect to The entire composition for a water-containing external patch contains a methyl acrylate-2-ethylhexyl acrylate copolymer at a ratio of 5.0% by mass to 10% by mass. Patent Document 3 discloses a cataplasm, which aims to provide a cataplasm that has sufficient adhesion even when the water content of the cataplasm decreases due to the passage of time, and contains a partially neutralized polyacrylic acid, 2.5-10 times the mass of the neutralized product (5-25% by mass based on the paste) of methyl acrylate-2-ethylhexyl acrylate copolymer and polyacrylic acid. Patent Document 4 discloses a cataplasm, which aims to provide a cataplasm capable of peeling off the release liner with less force, and contains poly(methyl acrylate/2-ethylhexyl acrylate) and polyethylene Surfactants such as glycol fatty acid esters. Patent Document 5 discloses a viewpoint of using an adhesive composition containing 1.5% by weight of acrylic resin emulsion (trade name Nikasol TS-620) and 6.2% by weight of sodium polyacrylate to obtain a hot and cold sheet. [Prior Technical Literature] [Patent Literature]

[Patent Document 1] Japanese Patent Laid-Open No. 9-208462 [Patent Document 2] Japanese Patent No. 5650684 Specification [Patent Document 3] Japanese Patent No. 5921779 Specification [Patent Document 4] International Publication No. 2016/104227 [Patent Document 5] Japanese Patent Laid-Open No. 2002-104957

[The problem to be solved by the invention]

As described above, it is known that in order to improve the adhesion persistence of an aqueous adhesive agent, an alkyl acrylate copolymer such as a methyl acrylate-2-ethylhexyl acrylate copolymer is blended into an adhesive layer. However, in aqueous solvents, there are problems with the drug stability of ethylene glycol salicylate, that is, the stability and adhesion of the drug in an aqueous patch prepared with ethylene glycol salicylate are still difficult to say. Fully satisfactory. [Technical means to solve the problem]

The inventors of the present invention have made diligent studies to solve the above-mentioned problems and found that in order to balance the stability of the ethylene glycol salicylate in the aqueous patch and the improvement of the adhesiveness of the formulation with a moderate degree of crosslinking, By adjusting the pH of the adhesive (paste), especially by preparing hydrochloric acid as an essential component when adjusting the pH, the above-mentioned problems can be solved, and the present invention has been completed.

That is, the present invention relates to an aqueous adhesive agent comprising a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, and The above-mentioned adhesive layer contains the following components a) to h) as essential components: a) Ethylene glycol salicylate, b) Alkyl (meth)acrylate copolymer, c) Partially neutralized polyacrylic acid, d) Water-soluble polymer compounds containing sodium carboxymethyl cellulose, e) Wetting agents containing glycerin, f) Crosslinking agent, g) Hydrochloric acid, and h) water, and The blending amount of glycerin in the adhesive layer is more than 15 times and 18 times or less on a mass basis with respect to the blending amount of ethylene glycol salicylate.

Furthermore, according to the present invention, the following implementation aspects are further provided. 1) The aqueous adhesive agent as described above, wherein the pH of the adhesive layer is 4.00-4.85. 2) The above-mentioned water-containing patch, wherein The above-mentioned adhesive layer is when the total mass of the adhesive layer is set to 100% by mass, with a) Glycol salicylate 0.1-30% by mass, b) Alkyl (meth)acrylate copolymer 0.1-5 mass%, c) Partially neutralized polyacrylic acid 3.5~4.5% by mass, d) 2.0-30% by mass of a water-soluble polymer compound containing sodium carboxymethyl cellulose, e) Wetting agent containing glycerol 30 to 70% by mass, f) Cross-linking agent 0.01~6.0% by mass, g) Hydrochloric acid 0.1~1.5% by mass, h) Water 10 to 90% by mass, The ratio is deployed. 3) The above-mentioned aqueous adhesive agent, which is calculated as the ratio of the weight of the adhesive layer after immersing and standing in purified water for 24 hours to the weight of the adhesive layer before being immersed and standing in purified water The swelling degree is less than 50. 4) The storage condition of the above-mentioned water-based patch is that the residual rate (%) of ethylene glycol salicylate before and after storage at 60°C for 2 weeks does not reach 5%. Furthermore, as an example of a preferable aspect of the present invention, the following can be cited. (i) The aqueous adhesive agent as described above, wherein in the adhesive layer, the total blending amount of the partially neutralized polyacrylic acid and sodium carboxymethyl cellulose is 7% by mass based on the total mass of the adhesive layer The blending amount of the partially neutralized polyacrylic acid is 3.5% by mass or more based on the total mass of the adhesive layer, and the blending amount of sodium carboxymethyl cellulose is 2.0% by mass based on the total mass of the adhesive layer above. (ii) The aqueous adhesive agent as described above, wherein the alkyl (meth)acrylate is a copolymer containing a monomer mixture of monomer A and monomer B, and the monomer A becomes the monomer A The monomer of the polymer whose glass transition temperature (Tg) is higher than 270 K during homopolymerization. The above monomer B is the monomer of the polymer whose glass transition temperature (Tg) is 220 K or less when the monomer B is homopolymerized. . (iii) The aqueous adhesive agent as described above, wherein the partially neutralized polyacrylic acid has a neutralization degree of 30% to 65%, and the viscosity of the 0.2% by mass aqueous solution is 450 to 650 mPa·s. (iv) The aqueous patch as described above, wherein the viscosity of the 1% by mass aqueous solution of sodium carboxymethyl cellulose is 1,000 to 3,000 mPa·s, and the degree of ester substitution is 0.60 to 0.95. (v) The aqueous patch as described above, wherein the crosslinking agent is a poorly soluble aluminum compound. (vi) The aqueous adhesive agent as described above, wherein the adhesive layer contains the above components a) to h) and is formed of an adhesive layer forming composition having a viscosity of 90 to 250 Pa·s. (vii) The aqueous adhesive agent as described above, wherein the adhesive layer further contains Sodium ethylenediaminetetraacetate hydrate is used as i) chelating agent. [Effects of Invention]

According to the present invention, in an aqueous patch containing ethylene glycol salicylate in the adhesive layer, by blending hydrochloric acid into the adhesive layer, it is possible to provide a ethylene glycol salicylate as an effective ingredient The ester is stable over time, and the adhesive force of the formulation is also high, and the degree of crosslinking is also good. Furthermore, according to the present invention, it is possible to provide a water-containing system that can maintain adhesion even after the moisture in the adhesive layer is evaporated, has low skin irritation, and has low adhesion between pastes, and can be attached to the skin again. Patches.

As described above, the inventors of the present invention found that in aqueous adhesives, especially in aqueous adhesives prepared with a non-aqueous adhesive base in the paste layer (adhesive layer) of the aqueous adhesive , Adjust the pH of the adhesive (paste) by blending hydrochloric acid as an inorganic acid into the adhesive layer. Specifically, by making the pH of the adhesive layer from the neutral side to the acidic side, the drug can be improved ：The stability of ethylene glycol salicylate in the presence of water. It is particularly surprising to find that, in addition to the stability of the drug, the degree of cross-linking and adhesion can be improved when other acids are used. Hereinafter, the structure of the water-containing patch of the present invention will be described.

The aqueous adhesive agent of the present invention (hereinafter, also referred to as "adhesive agent") includes a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer. The above-mentioned patch, especially the shape of the preparation part including the support and the adhesive layer provided on the support is not particularly limited, and square (square, rectangular, etc.), quadrilateral (trapezoid, rhombus, etc.) can be selected according to the application site. Etc.), polygons, circles, ellipses, semicircles, triangles, crescent shapes, and combinations of these shapes. Furthermore, the area of the patch (especially the above-mentioned preparation part) can be appropriately determined. For example, the amount of the effective ingredient to be blended into the adhesive layer can be considered. For example, it can be set in the range of ^{2 to 300 cm 2.}

[Adhesive layer] The adhesive layer of the aqueous adhesive agent of the present invention contains a) ethylene glycol salicylate, b) alkyl (meth)acrylate copolymer, c) partially neutralized polyacrylic acid, and d) contains carboxylic acid A water-soluble polymer of sodium methylcellulose, e) a humectant containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water as essential components. The water-based adhesive agent of the present invention is characterized in that for its water-based adhesive layer, in addition to the following hydrophilic acrylic adhesive, that is, c) partially neutralized polyacrylic acid, it is also formulated to generally constitute a non-aqueous adhesive layer. The acrylic adhesive b) (meth)acrylic acid alkyl ester copolymer. As an adhesive generally used for the adhesive layer (paste layer) of aqueous adhesives, polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, N-vinylacetamide-sodium acrylate copolymer resin, etc. are widely used Hydrophilic acrylic adhesive. From the viewpoint that it has high affinity with the above hydrophilic acrylic adhesives and can be uniformly kneaded, as a non-aqueous adhesive formulated to the aqueous adhesive layer of the aqueous adhesive, it is preferable to formulate acrylic It is an emulsion adhesive of methacrylic and methacrylic series. In addition, in this specification, the "(meth)acrylic acid alkyl ester copolymer" means both acrylic acid and methacrylic acid alkyl esters, and the "acrylic adhesive" also means acrylic acid Both adhesive and methacrylic adhesive.

＜a) Ethylene glycol salicylate＞ The adhesive layer of the aqueous adhesive agent of the present invention contains ethylene glycol salicylate (also called ethylene glycol salicylate) as an active ingredient. Moreover, if necessary, in addition to ethylene glycol salicylate, felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, and ibuprofen can also be used in combination. Non-steroidal anti-inflammatory agents such as phenhydramine or their esters; antihistamines such as diphenhydramine and clofenilamine; analgesics such as aspirin, acetaminophen, ibuprofen, and loxoprofen sodium; Local anesthetics such as lidocaine and dibucaine; muscle relaxants such as succinylcholine chloride; antifungals such as clotrimazole; antihypertensive agents such as clonidine; vasodilators such as nitroglycerin and isosorbide dinitrate; Vitamin A, vitamin E (tocopherol), vitamin E acetate, vitamin K, octthiamine, riboflavin butyrate and other vitamins, prostaglandins; scopolamine, fentanyl, pepper extract, nonanoic acid vanillamide, Capsaicin, dl-camphor, etc.

The blending amount of the above-mentioned ethylene glycol salicylate and the total blending amount of ethylene glycol salicylate and other active ingredients in the case of containing other effective ingredients can be appropriately determined according to the types of other effective ingredients, for example, Based on the total mass of the adhesive layer of the water-containing patch, it can be set to 0.1% by mass or more and 30% by mass or less, or 0.5% by mass and 15% by mass or less.

＜b)(Meth)acrylic acid alkyl ester copolymer＞ The (meth)acrylic acid alkyl ester copolymer (non-aqueous adhesive base) that constitutes the non-aqueous acrylic adhesive is a copolymer containing the following monomers (an example of the monomers listed in Table 1): as exhibiting adhesion A strong monomer, (methyl) alkyl ester has 2-9 carbon atoms, and will become a polymer with a glass transition temperature (Tg) below -55°C (218 K) during homopolymerization; it is used to enhance cohesion The monomer of the component will become a polymer with a Tg of 8 to 165°C (281 to 438 K) during homopolymerization; and, if necessary, a monomer having a carboxyl group or a hydroxyl group that becomes a functional group such as a cross-linking point.

[Table 1] [Table 1] monomer Number of carbon atoms in alkyl ester Tg of homopolymer Tg(K) Tg(℃) Adhesion performance Tg: below -55℃ Butyl acrylate 4 218.1 -55 2-ethylhexyl acrylate 8 203.1 -70 Octyl acrylate 8 208.1 -65 Isononyl acrylate 9 213.1 -60 Cohesive power increase Tg: 8～165℃ Methyl acrylate 1 281.1 8 Methyl methacrylate 1 378.1 105 Ethyl methacrylate 2 338.1 65 N-Butyl methacrylate 4 293.1 20 Isobutyl methacrylate 4 321.1 48 Tert-butyl methacrylate 4 380.1 107 Vinyl acetate - 305.1 32 Acrylonitrile - 370.1 97 Acrylamide - 438.1 165 Styrene - 353.1 80 Contains functional groups (crosslinking points) acrylic acid 0 379.1 106 2-hydroxyethyl acrylate 2 213.1 -60 Methacrylate 0 501.1 228 2-hydroxyethyl methacrylate 2 328.1 55 Glycidyl methacrylate 3 323.1 50 Hydroxypropyl methacrylate 3 299.1 26

Furthermore, homopolymers formed by polymerizing only monomers that exhibit adhesive strength have higher adhesive strength but weaker mechanical strength. Generally, copolymers whose mechanical strength is improved by copolymerizing with monomers that enhance cohesion are used. As an adhesive. As listed as the monomers exhibiting adhesive force shown in Table 1 above, in the present invention, as a monomer with higher adhesive force, when the monomer is used for homopolymerization (homopolymer), the Tg is 220 K The following are butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate and the like. Among these, 2-ethylhexyl acrylate, which has been actually used as an additive for pharmaceuticals, and has a higher adhesive force (lower Tg of a homopolymer) can be preferably used. In addition, as the monomer for enhancing the cohesive force (the Tg of the homopolymer is 270 K or more), the monomers listed in Table 1 can be cited. Among them, in the present invention, it is preferable that the mechanical strength is higher and does not cause Methyl acrylate with significantly reduced adhesion (the Tg of the homopolymer is relatively low).

Furthermore, as listed in the prior art, as a commercially available alkyl acrylate copolymer used in an adhesive agent, there is Nikasol (registered trademark) TS-620 (methyl acrylate- 2-ethylhexyl acrylate copolymer resin emulsion). Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is an accepted product in the specification of pharmaceutical additives.

In the adhesive layer of the aqueous adhesive agent of the present invention, the blending amount of the alkyl (meth)acrylate copolymer (in the case of an emulsion is the solid content conversion amount) is the adhesive of the aqueous adhesive agent The total mass of the agent layer is a reference, and it can be set to, for example, 0.1% by mass or more and 5% by mass or less, 0.5% by mass or more and 4.5% by mass or less, and 1.0% by mass or more and 4.5% by mass or less. In addition, regarding the blending ratio with the following acrylic hydrophilic adhesive, for example, in terms of mass ratio, it can be an alkyl acrylate copolymer: acrylic hydrophilic adhesive = 1.5:1 to 1:10, alkyl acrylate Base ester copolymer: acrylic acid hydrophilic adhesive = 1.5:1 to 1:5, acrylic acid alkyl ester copolymer: acrylic acid hydrophilic adhesive = 1.5:1 to 1:1, etc.

<c) Partially neutralized polyacrylic acid> The adhesive layer of the aqueous adhesive agent of the present invention contains a partially neutralized polyacrylic acid as an acrylic hydrophilic adhesive. In addition, an acrylic hydrophilic adhesive other than the partially neutralized polyacrylic acid can also be formulated into the adhesive layer as needed. Generally, as the above-mentioned acrylic hydrophilic adhesive, a water-soluble (meth)acrylic polymer can be cited. The water-soluble (meth)acrylic polymer is a polymer obtained by polymerizing a (meth)acrylic acid group-containing monomer containing a water-soluble functional group (hydrophilic group), and is formulated with water To the adhesive layer to exert adhesiveness. Examples of the water-soluble (meth)acrylic polymer include partially neutralized products of the above-mentioned polyacrylic acid, homopolymers such as polyacrylic acid, and copolymers such as N-vinylacetamide-sodium acrylate copolymer resin.

The above-mentioned partially neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, or a partially neutralized polyacrylic acid, or a mixture of these. That is, in this specification, the term "polyacrylic acid partially neutralized product" includes both a partially neutralized product of polyacrylic acid and a neutralized product of all polyacrylic acid groups. The partially neutralized polyacrylic acid means polyacrylate, and for example, sodium salt, potassium salt, calcium salt, ammonium salt, etc. can be used. For example, Viscomate NP-800 (manufactured by Showa Denko) can be cited.

In a preferred aspect, the partially neutralized polyacrylic acid used in the present invention is a partially neutralized product with a degree of neutralization of 30% to 65%. Moreover, it is preferable to use a partially neutralized polyacrylic acid with a viscosity of 450 to 650 mPa·s at 20° C. when the partially neutralized polyacrylic acid is made into an aqueous solution with a concentration of 0.2% by mass. By using a partially neutralized polyacrylic acid, especially by using a partially neutralized polyacrylic acid with such a degree of neutralization and viscosity, the adhesion to the skin can be further exhibited when water is contained, and the adhesion to the skin can be further promoted. The cross-linking of the cross-linking agent prevents dissolution in water.

The blending amount of the above-mentioned partially neutralized polyacrylic acid and the total blending amount of the partially neutralized polyacrylic acid and other acrylic hydrophilic adhesives in the case of containing other acrylic hydrophilic adhesives are based on the adhesion of aqueous adhesives The total mass of the agent layer is a reference, and it can be set to, for example, 0.1% by mass or more and 10% by mass or less, and 1% by mass or more and 8% by mass or less. For example, the blending amount of the above-mentioned partially neutralized polyacrylic acid can be set to 3.5% by mass or more and 4.5% by mass or less based on the total mass of the adhesive layer.

＜d) Water-soluble polymer compound＞ As the above-mentioned water-soluble polymer compound, the adhesive layer of the patch of the present invention contains carmellose sodium as an essential component. By using sodium carboxymethyl cellulose, the shape retention of the preparation can be further maintained, and it has thixotropy, which can further reduce the pain during peeling. In a preferred aspect, regarding the above-mentioned sodium carboxymethyl cellulose used in the present invention, the viscosity of its 1% by mass aqueous solution at 20° C. can be set to 1,000 to 3,000 mPa·s. In addition, the sodium carboxymethyl cellulose is preferably one having an ester substitution degree of 0.60 to 0.95.

In addition, it may also contain water-soluble polymer compounds other than sodium carboxymethyl cellulose. Examples thereof include gelatin, agar, polyvinyl alcohol (including partial saponification), polyvinylpyrrolidone, and propylene carbonate. Esters, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium alginate, maleic anhydride copolymer, carrageenan. These can be used together with sodium carboxymethyl cellulose, 1 type or in combination of 2 or more types suitably.

Regarding the blending amount of the above-mentioned water-soluble polymer compound, it is usually based on the total mass of the adhesive layer of the water-containing adhesive agent. For example, it can be set to 1.0 mass% to 30 mass%, 2.0 mass% to 30 mass%, The range is between 2.5% by mass and 20% by mass, or between 3.0% and 10% by mass. Moreover, for example, the compounding amount of sodium carboxymethyl cellulose can be set to 2.0% by mass or more and 3.5% by mass or less based on the total mass of the adhesive layer.

＜e) Humectant containing glycerin＞ In order to suppress the evaporation of water over time, a humectant (also referred to as a humectant) is blended into the adhesive layer of the water-based adhesive agent of the present invention. As the above-mentioned humectant, glycerin is blended as an essential component in the adhesive layer of the adhesive agent of the present invention. In addition, humectants other than glycerin can also be formulated. As examples, D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1, Polyols such as 4-butanediol, maltitol, and xylitol. These can be used in combination with glycerin 1 type or in appropriate combination of 2 or more types.

Regarding the blending amount of the above-mentioned wetting agent, it is usually based on the total mass of the adhesive layer of the water-based adhesive agent. For example, it can be 30 mass% or more, 70 mass% or less, 40 mass% or more, 60 mass% or less, or 40 mass%. Above 50% by mass or less, or 45% by mass to 55% by mass or less. Furthermore, in the present invention, the compounding amount of glycerin in the adhesive layer relative to the compounding amount of a) ethylene glycol salicylate is more than 15 times and 18 times or less on a mass basis. For example, it can be set as The compounding amount of glycerin in the adhesive layer is 15.5 times or more and 18.0 times or less on a mass basis with respect to the compounding amount of glycerol salicylate in the above-mentioned a); it can be set as the relative compounding amount of glycerin in the adhesive layer In the above a) the compounding amount of ethylene glycol salicylate is 16.0 times or more and 17.9 times or less on a mass basis; it can be set as the compounding amount of glycerin in the adhesive layer relative to the above a) ethylene glycol salicylate The blending amount of ester is 16.5 times or more and 17.9 times or less on a mass basis; it can be set as the blending amount of glycerin in the adhesive layer relative to the blending amount of a) ethylene glycol salicylate, calculated on a quality basis 16.7 times or more and 17.9 times or less; can be set as the blending amount of glycerin in the adhesive layer relative to the blending amount of a) ethylene glycol salicylate, on a mass basis, 17.0 times or more and 17.9 times or less; can be set The compounding amount of glycerin in the adhesive layer is 17.5 times or more and 17.9 times or less on a mass basis with respect to the compounding amount of ethylene glycol salicylate in the above-mentioned a); or it can be set as the compounding amount of glycerin in the adhesive layer The blending amount of the above a) ethylene glycol salicylate is 15.5 times or more and 17 times or less on a mass basis. If the blended amount of glycerin is small, the moisture retention may be insufficient and the moisture of the adhesive may easily evaporate. Also, if the blended amount of glycerin is increased, the stability of the drug may decrease. On the other hand, if the amount of the drug (ethylene glycol salicylate) is excessively increased in order to improve stability, there is a concern that safety problems may arise.

＜f) Crosslinking agent＞ As the crosslinking agent formulated into the adhesive layer of the aqueous adhesive agent of the present invention, polyvalent metal salts can be cited, and among them, aluminum-containing polyvalent metal compounds can be cited. Examples include: hydroxides such as aluminum hydroxide and magnesium aluminum hydroxide; aluminum chloride, aluminum sulfate, potassium aluminum sulfate, aluminum glycinate (dihydroxyaluminum amino acetal), and dihydroxyaluminum amino acetic acid Salt, synthetic aluminum silicate, dry aluminum hydroxide gel, kaolin, aluminum stearate and other inorganic or organic acid normal salts or their basic salts; bauxite and other composite salts; sodium aluminate and other aluminates; Inorganic aluminum complex salts and organic aluminum chelate compounds; synthetic polyvalent metal compounds such as hydrotalcite, aluminum magnesium silicate, aluminum magnesium silicate, etc., which can be used alone or in combination of two or more. Among them, it is preferable to use dihydroxyaluminumaminoacetate, synthetic aluminum silicate, and dry aluminum hydroxide gel, which are poorly soluble aluminum compounds.

Regarding the blending amount of the cross-linking agent, it is only necessary to consider the residue of the adhesive on the skin or the degree of cross-linking that can be one of the reasons for the fit, and appropriately select it. Based on the total mass of the adhesive layer of the water-containing patch, for example, a range of 0.01% by mass to 6.0% by mass, 0.01% by mass to 4.0% by mass, or 0.01% by mass to 2.0% by mass can be mentioned.

＜g) Hydrochloric acid＞ The adhesive layer of the aqueous adhesive agent of the present invention is characterized in that hydrochloric acid is formulated therein. Regarding the blending amount of hydrochloric acid, based on the total mass of the adhesive layer of the water-containing patch, it can be set to a range of 0.1% by mass to 1.5% by mass, for example. Furthermore, if hydrochloric acid is not prepared, but only the acids listed in the following "organic acid" or other acids such as inorganic acids other than hydrochloric acid are prepared, it is difficult to obtain both moderate crosslinking properties and good adhesion. . For example, in the case of using tartaric acid, good adhesion cannot be obtained. In the case of using phosphoric acid, in terms of the stability of ethylene glycol salicylate or the performance of moderate cross-linking, it is different from the use of hydrochloric acid. Compared with the situation, it may be a worse result. In order to obtain the same effect as when using hydrochloric acid from the viewpoint of stability, there are situations where a larger amount of compounding is required. Phosphoric acid is preferably not added, but it may be added within a range that does not affect the effects of the present invention, especially the degree of crosslinking.

＜h)Water＞ As described above, the water-containing adhesive agent of the present invention contains water (moisture) in the adhesive layer. In this specification, the so-called "water" contained in the adhesive layer includes not only what is added separately as water when forming the adhesive layer, but also water contained in the form of an emulsion or an aqueous solution. The mixing amount of water is not particularly limited. It is based on the total mass of the adhesive layer of the water-based adhesive agent. For example, it can be set to 10% by mass or more, 90% by mass or less, 15% by mass or more, 70% by mass or less, and 20% by mass. The range of above 50% by mass. Furthermore, the water content is the value at the time of preparation of the patch or before the patch is attached, and it is not limited to this when the water evaporates from the adhesive layer along with the pasting of the patch.

＜i) Chelating agent＞ In order to control the viscosity of the paste during manufacture, a chelating agent can also be blended into the adhesive layer of the aqueous adhesive agent of the present invention. As a chelating agent, sodium ethylenediaminetetraacetate (ethylenediaminetetraacetic acid disodium salt) can be mentioned, for example. Regarding the compounding amount of the chelating agent, it is usually based on the total mass of the adhesive layer of the water-based adhesive agent, and for example, it can be set in the range of 0.01% by mass to 1% by mass, and 0.1% by mass to 0.3% by mass.

＜Organic solvents＞ Organic solvents can also be formulated into the adhesive layer of the aqueous adhesive agent of the present invention as components that can perform the following functions: assisting the dissolution of active ingredients such as drugs (that is, the function as a solubilizer), and, Prevent the active ingredients from chromatographing out of the adhesive. Examples of such organic solvents (solubilizers) include: Crotamiton; N-methyl-2-pyrrolidone; polyethylene glycol 400 (polyethylene glycol) and polyalkylene glycols such as polybutylene glycol. Diol; Polyvinyl Alcohol; Diethyl Adipate, Diisopropyl Adipate, Diethyl Sebacate, Diisopropyl Sebacate, Isopropyl Myristate, Isopropyl Palmitate, Fatty acid esters such as oleic acid oleate; polyoxyalkylene fatty acid esters, etc.; sorbitan esters; 1,3-butanediol and other polyols; dimethylformamide; dimethyl sulfide, etc. These can be used individually by 1 type or in combination of 2 or more types.

When an organic solvent is used, the blending amount is based on the total mass of the adhesive layer of the water-containing adhesive agent, and can be set to, for example, 0.1% by mass or more and 20% by mass or less.

＜Organic acid＞ Organic acids can also be formulated into the adhesive layer of the aqueous adhesive agent of the present invention. As the organic acid that can be adjusted, for example, tartaric acid, citric acid, lactic acid, gluconic acid, glycolic acid, malic acid, fumaric acid, methanesulfonic acid, maleic acid, acetic acid, etc. can be used alone or in combination. 2 More than one kind of use. When an organic acid is used, the blending amount is based on the total mass of the adhesive layer of the water-containing adhesive agent, and can be set to a range of 0.1% by mass to 5% by mass, for example. By using an organic acid within such a compounding amount range, it can be expected to prevent insufficient crosslinkability and dissolution of the adhesive, resulting in stickiness. On the other hand, it can prevent the crosslinking reaction from proceeding excessively and the paste becomes hard. The problem of manufacturing.

＜Surface active agent＞ Surfactants can also be formulated into the adhesive layer of the aqueous adhesive agent of the present invention. Examples of such surfactants include: polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol Polyoxyethylene fatty acid esters such as dioleate and polypropylene glycol dioleate; sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate Ester, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan single Sorbitan fatty acid esters such as hemioleate and ethylene oxide adducts; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan Alkyd monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan triiso Polyoxyethylene sorbitan fatty acid esters such as stearates; polyoxyethylene lauryl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyethylene Tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethyl Polyoxyethylene alkyl ethers such as hexyl ether and polyoxyethylene isodecyl ether; polyoxyethylene styrenated phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene stilbene phenyl ether, polyoxyethylene tribenzyl Polyoxyethylene alkylphenol ethers such as phenylene ether; glycerol fatty acid esters such as glycerol monostearate and glycerol monooleate; polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, lecithin Other nonionic surfactants. These can be used individually by 1 type or in combination of 2 or more types suitably. In the case of using these surfactants, the blending amount is based on the total mass of the adhesive layer of the water-containing adhesive agent. For example, it can be set to 0.001% by mass to 10% by mass, and 0.01% by mass to 5% by mass. The following range.

＜Other optional ingredients＞ In the adhesive layer of the aqueous adhesive agent of the present invention, antioxidants such as dibutyl hydroxytoluene (BHT), calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, Inorganic powders such as calcium sulfate, ultraviolet absorbers such as benzyl methane derivatives, colorants, fragrances, preservatives, etc. are generally adjusted to the previous aqueous patch (dressing) or non-aqueous patch (patch) The components of the adhesive layer in) are used as other optional components. When using these optional ingredients, usually based on the total mass of the adhesive layer of the water-based adhesive agent, it can be used alone or in combination of two or more within the range of, for example, 0.01% by mass to 1% by mass. use.

[Support Body] Examples of the support used in the water-containing patch of the present invention include flexible supports such as films, non-woven fabrics, Japanese paper, cotton cloth, woven fabrics, woven fabrics, laminated composites of non-woven fabrics and films. The support is preferably a soft material that can be closely attached to the skin and can follow the activity of the skin, and can suppress the generation of skin rashes after a long time of attachment. As the material of these supports, for example, polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, Cotton, rayon acetate, rayon, rayon/polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, ether Based on polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene Ethylene rubber, ethylene-vinyl acetate copolymer, cellufin, etc. as essential components.

In addition, supports such as cloth can be colored with a coloring agent into a color tone such as skin color, so that the color difference between the skin and the color at the time of application can be reduced. In addition, from the viewpoint that the skin tone is easily revealed in the attached state, a form of a plastic film with excellent transparency can be adopted.

The thickness of the support is usually about 5 μm to 1 mm. When the support is 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 10-300 μm, more preferably 12-200 μm, and still more preferably 15-150 μm. When the thickness of the support is extremely thin about 5 μm-30 μm, if a peelable carrier film layer is provided on the side opposite to the adhesive layer formed on the support, it can be used as an adhesive agent. Improved, so better. However, if the thickness of the support is less than 5 μm, the strength or workability of the patch may decrease, and it may become difficult to stick to the skin. It may be damaged due to contact with other members, or it may be exposed to water due to bathing. And it peels off from the skin in a short time. In addition, if the thickness of the support is too large (more than 1 mm), the patch will not easily follow the movement of the skin, and the edge of the patch will easily form a starting point for peeling, so it will peel off the skin in a short time or be attached. The discomfort may increase. Furthermore, when the support is a film, for the purpose of improving the grip of the adhesive and the support, it is also possible to perform sandblasting, corona treatment, etc., on one or both sides of the support. Moreover, in order to be easily taken out from the packaging material, it is also possible to provide concavities and convexities on one or both sides of the support by a method other than sandblasting.

[Release Liner] The release liner (also called release layer, release paper) used as the water-containing adhesive agent of the present invention is preferably a material that is not easy to absorb and adsorb the drugs in the adhesive layer, and can be used for the adhesive agent. Those who are habitually used in the technical field. Examples include: polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unstretched, stretched, etc.), polyethylene, polyamine Base format, polyvinyl chloride, polystyrene and other plastic films; Daolin paper, cellophane, parchment, kraft paper and other paper or synthetic paper; the above-mentioned plastic film, paper or synthetic paper, synthetic fiber, etc. are coated with silicone resin or Peeling processed paper made of peeling agent with peeling properties such as fluororesin; aluminum foil; laminated processed paper made by laminating these films and sheets in various ways, and laminated processed paper coated with a peeling agent Laminate colorless or colored sheets such as peel-off processed paper. Furthermore, the release liner can also be provided with concavities and convexities for easy removal from the packaging material. The thickness of the release liners is not particularly limited, and is usually 10 μm to 1 mm, for example, 20 μm to 500 μm, preferably in the range of 40 μm to 200 μm. Furthermore, the peeling force when the adhesive layer is peeled from the release liner is preferably a peeling force within a specific range. The reason is that if the peeling force of the adhesive layer from the release liner is too weak, when the adhesive is jammed by the packaging material when the adhesive is taken out from the packaging material, there is an adhesive layer Agent) There is a risk of peeling off from the release liner. In addition, the reason is that if the peeling force of the adhesive layer (adhesive agent) from the release liner is too strong, the workability during use may deteriorate. The peeling force of the adhesive layer from the release liner also varies according to the type of release liner used, for example, it can be set to 0.01 N/15 mm～0.5 N/15 mm.

[Manufacturing method of water-based adhesive agent] The water-containing patch of the present invention can be manufactured using a previously known method. For example, as an example, it can be manufactured through the following steps (i) or (ii). (i) The step of coating the adhesive layer forming composition on the support to form an adhesive layer, and the step of bonding the adhesive layer formed on the support to the release liner. (ii) The step of coating the adhesive layer forming composition on the release liner to form an adhesive layer, and the step of bonding the adhesive layer formed on the release liner to the support. Furthermore, the thickness of the adhesive layer is not particularly limited, and is usually 10 μm to 1000 μm, for example, it can be set to about 20 μm to 800 μm.

The above-mentioned adhesive layer forming composition contains various components contained in the above-mentioned adhesive layer: ethylene glycol salicylate (other effective ingredients), alkyl (meth)acrylate copolymers, partially neutralized polyacrylic acid (Other acrylic hydrophilic adhesives), water-soluble polymer compounds containing sodium carboxymethyl cellulose, wetting agents containing glycerin, cross-linking agents, hydrochloric acid, and water, and may contain chelating agents as needed, Semi-solid composition of organic solvents, organic acids, surfactants, and other optional ingredients. From the viewpoint of operability at the time of manufacture, the adhesive layer forming composition preferably has 90 to 250 Pa·s, 100 to 250 Pa·s, and more preferably 130 to 250 at 20°C to 30°C The viscosity of Pa·s. If the viscosity is less than 90 Pa·s, the paste may ooze out when the woven cloth or woven cloth is used as the support. If the viscosity exceeds 250 Pa·s, it becomes difficult to stretch.

[The pH value of the adhesive layer in the water-based patch] In the aqueous patch of the present invention, the pH value of the adhesive layer is preferably on the acidic side (less than 6.0), and can be set to 3.5 or more and less than 6.0, such as 4.00-4.85, preferably 4.40-4.80 , More preferably, it is 4.50-4.80. By controlling the pH value of the adhesive layer within an appropriate range, the stability of ethylene glycol salicylate can be improved, and the adhesive can be made into the manufacture of adhesives such as improved coating properties (ductility) A water-based patch with excellent properties. Furthermore, the pH value of the adhesive layer can be measured at a temperature of 20-25°C in accordance with the pH measurement method of the Japanese Pharmacopoeia General Test Method, for example.

Furthermore, there are cases where the pH value of the liquid obtained by diluting the adhesive (paste) in water is 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 adhesive, the adhesive is scraped off from the exposed adhesive layer using a spatula, etc., and purified water is added to the collected adhesive, for example, diluted 20 times, etc. Homogeneous solution. The obtained solution is kept at room temperature (25.0±0.2°C), the glass composite electrode of the calibrated pH meter is inserted into the solution, and the pH value is measured.

＜Swelling degree＞ Regarding the adhesive layer (adhesive layer forming composition) of the present invention, when it is immersed and left in purified water for 24 hours, the weight of the adhesive layer after immersion and standing for 24 hours is relative to the weight of the adhesive layer before immersion and standing. The swelling degree of the adhesive layer calculated by the weight ratio of the agent layer is preferably less than 50. In addition, the procedure for measuring and calculating the degree of swelling is, for example, as follows: cut the water-based adhesive agent and the support into a specific size, and measure the water-based adhesive agent in a state where the liner is peeled off. The weight (the weight of the initial water-containing adhesive (liner peeling), the weight of the initial support). After that, immerse the equivalent in purified water and stand for 24 hours, and measure the weight after immersing and standing for 24 hours (the weight of the aqueous adhesive (liner peeling) after the purified water is left standing), and the support after the purified water is standing still. Body weight), according to the following formula, the degree of swelling can be calculated. The swelling degree of the adhesive layer = (weight of the water-containing adhesive (liner peeled) after purified water is allowed to stand-weight of the support after the purified water is allowed to stand)/(initial water-containing adhesive (liner peeled off) weight －Initial support weight) By making the swelling degree of the adhesive layer less than 50, it is possible to provide a water-containing patch that maintains the shape retention of the adhesive layer and prevents the adhesive layer from remaining on the skin after peeling. [Example]

Hereinafter, examples are given to explain the present invention in further detail, but the present invention is not limited to these examples.

＜Production of Adhesives＞ The patches (formulations) of Examples, Comparative Examples, and Reference Examples were manufactured in the following order.

Example 1: 1.5 parts by mass of polyvinyl alcohol was dissolved in purified water (aqueous phase). Next, 1 part by mass of polyethylene glycol 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 polyacrylic acid partially neutralized product (when the neutralization degree: 35%, viscosity: 0.2% by mass aqueous solution is prepared, the viscosity at 20°C is 547 mPa·s), carboxymethyl Sodium cellulose (degree of ester substitution: 0.82, viscosity: 1% by mass aqueous solution at 20°C with a viscosity of 1,840 mPa·s) 3 parts by mass, 0.25 parts by mass of dihydroxyaluminoacetate, uniform in 22 parts by mass of concentrated glycerin Ground dispersion (glycerin phase). The water phase, 7 parts by mass of methyl acrylate-2-ethylhexyl acrylate copolymer emulsion, 0.20 parts by mass of sodium edetate hydrate, 30 parts by mass of D-sorbitol 70% aqueous solution, 0.9 parts by mass of hydrochloric acid diluted with purified water (remaining amount), and disperse or dissolve them uniformly. The oil phase and the glycerin phase are sequentially poured into it, and kneaded uniformly. Furthermore, 1 part by mass of lactic acid was added and kneaded uniformly under degassing conditions to obtain the adhesive layer forming composition of Example 1. Furthermore, using the obtained adhesive layer forming composition, the following test example 4 (viscosity of adhesive) was implemented. Spread the obtained adhesive layer forming composition on the silicone surface of the gasket (PET (polyethylene terephthalate) (75 μm) treated with silicone on one side) using a spreading machine , After laminating a knitted fabric support (made of polyester), it was cured at 40°C for 1 week. After aging, it was punched into any shape to obtain the preparation of Example 1.

Example 2 to Example 9, Comparative Example 1 to Comparative Example 9: The preparations of Examples 2 to 9, and Comparative Examples 1 to 9 were obtained in the same manner as in Example 1, except that the types and blending amounts of each component were changed as described in Table 2 and Table 3. In addition, when phosphoric acid and tartaric acid are blended, they are added at the same time as hydrochloric acid to manufacture.

Test Example 1 (Measurement of pH of Adhesive Layer) The pH of each preparation is measured at 25.0±0.2℃ in accordance with the pH measurement method of the Japanese Pharmacopoeia General Test Method. The obtained results are shown in Table 2 and Table 3.

Test Example 2: Evaluation of Stability of Glycol Salicylate (SG) Regarding the evaluation of the stability of ethylene glycol salicylate, immediately after the formulation was manufactured (initial), and stored at 60°C for 2 weeks (2 After W), the content of ethylene glycol salicylate contained in the adhesive layer was measured by high performance liquid chromatography (HPLC). In detail, each preparation 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 to prepare Into the test preparation. As the extraction solvent, 27 mL of methanol was used, the test preparation was added thereto, and the extraction operation was performed by shaking. Use a membrane filter with a pore size of 0.45 μm to filter the extract to prepare a sample solution. The sample solution was analyzed under the following HPLC conditions. Based on the sum of the peak area of ethylene glycol salicylate (holding time about 11 minutes) and the areas of other peaks, the relative amount of decomposition products is compared to improve the stability (adhesion) of ethylene glycol salicylate. The remaining% in the agent layer) was evaluated. Also, based on the initial value (the remaining% of ethylene glycol salicylate in the adhesive layer before storage), it is calculated as the reduction of ethylene glycol salicylate after storage at 60°C for 2 weeks (2 W) (Relative to the initial value of reduction (%)). The obtained results are shown in Table 2 and Table 3. Measurement wavelength: 240 nm Column: Mightysil RP-18 (150 mm×4.6 mm, 5 μm) Column temperature: 30℃ Flow rate: 0.5 mL/min Mobile phase A: water/methanol=50/50 Analysis time: 30 minutes Injection volume: 10 μL In addition, regarding the stability evaluation of ethylene glycol salicylate, the storage conditions at 40℃ for 6 months and the storage conditions at 60℃ 2 W can be regarded as the same level. Stability (relative to the initial value of reduction (%)) is ideally stored at 60°C for 2 W (relative to the initial value of the reduction (%)), there will be no significant quality changes less than 5.0 %.

Test Example 3: Adhesion Test Rolling Ball Adhesion Peel off the release liner of each formulation (just after manufacture) to expose the adhesive layer, and the rolling ball adhesive force of the adhesive layer shall be in accordance with the Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3.2. Tilted Rolling Ball Viscosity Test Law enforcement. Let the average value of n=3 (rolling ball No.) be the value of the rolling ball viscosity test. The obtained results are shown in Table 2 and Table 3. Furthermore, the evaluation of the viscosity of the rolling ball reflects the adhesive force of the adhesive layer, and its value is preferably 15 or more.

Test Example 4: Viscosity of Adhesive For the adhesive layer forming composition manufactured in the procedure of <Preparation of Adhesive Agent>, the viscosity was measured with a handheld rotary viscometer (measurement temperature: 20°C to 30°C) before the liner was coated. The obtained results are shown in Table 2 and Table 3.

Test Example 5: Adhesive layer Crosslinking degree Cut the preparation and support into 12×100 mm. For the preparation, measure the weight (initial preparation weight, initial support weight) with the liner removed, and place them in a glass bottle filled with purified water (room temperature). ) Let stand for 24 hours respectively. After standing, the preparation and support are taken out of the purified water and the weight is measured (the weight of the preparation after the purified water is standing, the weight of the support after the purified water is standing), and the swelling of the paste (adhesive layer) is calculated from the following formula Spend. The swelling degree of the paste = (the weight of the preparation after the purified water is allowed to stand-the weight of the support after the purified water is allowed to stand)/(the weight of the initial preparation-the weight of the initial support) Based on the calculated degree of swelling, the degree of crosslinking was evaluated according to the following evaluation criteria. The obtained results are shown in Table 2 and Table 3. Furthermore, the degree of crosslinking is preferably + or more. When it is ± or -, the shape retention of the paste is insufficient, and a large amount of the paste may remain on the skin when it is peeled off after application. ＜Crosslinking degree evaluation＞ ++: The swelling degree is less than 10 +: The swelling degree is more than 10 and less than 50 ±: swelling degree above 50 －: The paste is almost dispersed in purified water and cannot be taken out

Test Example 6: Manufacturability Regarding the difficulty of spreading the adhesive layer-forming composition produced in the procedure of <Adhesive Preparation> on the silicone surface of the liner using a spreading machine, the manufacturability was evaluated according to the following evaluation criteria. The obtained results are shown in Table 2 and Table 3. ＜Manufacturability Evaluation＞ ++: Can be easily extended +: Can be extended ±: Can be stretched but not stable -: Cannot be extended

[Table 2] [Table 2] Blending ingredients (allocation amount: parts by mass) Example 1 2 3 4 5 6 7 8 9 Ethylene glycol salicylate 1.25 1.25 1.25 1.25 1.40 2.00 2.00 1.25 1.25 L-menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (solid content 60%) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 Sodium carboxymethyl cellulose 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 2.00 Concentrated glycerin 22.00 22.00 22.00 22.00 25.00 32.50 31.00 22.00 22.00 D-sorbitol liquid 30.00 30.00 30.00 30.00 30.00 21.60 23.10 30.00 30.00 Sodium ethylenediaminetetraacetate hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.40 Dihydroxyaluminum amino acetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 hydrochloric acid 0.90 0.45 0.35 0.70 0.40 0.40 0.40 1.35 0.45 Lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyethylene glycol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Purified water ^※ 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total Adhesive layer pH 4.42 4.70 4.78 4.55 4.68 4.63 4.64 4.11 4.70 Stability Evaluation of Ethylene Glycol Salicylate (Remaining %) initial 99.09 99.09 99.16 99.22 98.95 98.82 99.11 99.13 NT After 60℃2 W 96.31 95.16 94.34 95.97 94.39 94.49 94.30 97.46 NT Relative to the initial value reduction (%) 2.8 3.9 4.8 3.3 4.6 4.3 4.8 1.7 NT Adhesion: Rolling ball viscosity (rolling ball No.) 27.0 24.3 23.3 26.0 20.0 19.7 20.0 26.7 NT Adhesive layer viscosity (Pa･s) 250 150 150 180 150 130 160 250 95 Adhesive layer crosslinking degree + + + + + + + ++ + Ratio of glycerol/glycol salicylate 17.6 17.6 17.6 17.6 17.9 16.3 15.5 17.6 17.6 Manufacturability + ++ ++ ++ ++ ++ ++ + ++ ※ Adjust the amount of purified water so that the total of all the ingredients becomes 100 parts by mass. NT: The test has not been implemented

[Table 3] [Table 3] Blending ingredients (allocation amount: parts by mass) Comparative example 1 2 3 4 5 6 7 8 9 Ethylene glycol salicylate 1.25 1.40 1.40 1.40 1.40 1.40 2.00 2.00 2.00 L-menthol 1.00 0.70 0.70 0.70 0.70 0.70 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (solid content 60%) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 Sodium carboxymethyl cellulose 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 Concentrated glycerin 22.00 25.00 25.00 25.00 25.00 25.00 32.50 32.50 32.50 D-sorbitol liquid 30.00 30.00 30.00 30.00 30.00 30.00 21.60 21.60 21.60 Sodium ethylenediaminetetraacetate hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminum amino acetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 hydrochloric acid 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 Phosphoric acid 0.00 0.25 0.50 0.75 1.00 2.00 0.00 0.00 0.00 tartaric acid 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.25 0.50 Lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyethylene glycol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Purified water ^※ 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total 100 servings total Adhesive layer pH 4.90 4.94 4.75 4.58 4.38 3.71 5.10 4.89 4.68 Stability Evaluation of Ethylene Glycol Salicylate (Remaining %) initial 97.15 97.60 98.40 97.80 97.90 97.70 99.21 99.28 99.28 After 60℃2 W 91.27 91.80 93.10 93.80 94.50 96.00 93.28 94.55 95.55 Relative to the initial value of reduction (%) 5.9 5.8 5.3 4.0 3.4 1.7 5.9 4.7 3.7 Adhesion: Rolling ball viscosity (rolling ball No.) NT NT NT NT NT NT 15.0 10.0 13.0 Adhesive layer viscosity (Pa･s) 150 150 150 180 230 110 130 130 140 Adhesive layer crosslinking degree + ± - - - - + + + Ratio of glycerol/glycol salicylate 17.6 17.9 17.9 17.9 17.9 17.9 16.3 16.3 16.3 Manufacturability ++ ++ ++ ++ + ++ ++ ++ ++ ※ Adjust the amount of purified water so that the total of all the ingredients becomes 100 parts by mass. NT: The test has not been implemented

As shown in Table 2, the preparations (aqueous adhesives) of the examples were stored at 60°C by mixing a specific amount of hydrochloric acid in the evaluation of the stability of the effective ingredient of ethylene glycol salicylate 2 The reduction from the initial value after a week has become less than 5%, the rolling ball viscosity value has also become 15 or more, and the swelling degree, which is an indicator of the degree of crosslinking of the adhesive layer (paste), has also become less than 50. (+ the above evaluation), so as to become a water-based patch with good stability of active ingredients, adhesion of formulations, and degree of cross-linking. On the other hand, as shown in Table 3, in Comparative Examples 1 and 7 that do not contain hydrochloric acid, the reduction range of ethylene glycol salicylate from the initial value exceeds 5%, which is a formulation with poor stability of the active ingredient. In addition, when phosphoric acid was added instead of hydrochloric acid (Comparative Examples 2-6), by increasing its blending amount, the stability of ethylene glycol salicylate increased, but the degree of crosslinking deteriorated instead, and the blending When tartaric acid was substituted for hydrochloric acid (Comparative Examples 8-9), the rolling ball viscosity value was less than 15, and the required adhesive force could not be obtained.

According to the results of the above examples, it is confirmed that according to the present invention, in an aqueous adhesive agent containing ethylene glycol salicylate in an adhesive layer, by blending hydrochloric acid into the adhesive layer, even if it is relatively high With a small blending amount, it can provide ethylene glycol salicylate as an effective ingredient that is also stable over time, has a moderate degree of cross-linking and good adhesion, and has excellent manufacturability.

Claims (5)

An aqueous adhesive agent comprising a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, and The above-mentioned adhesive layer contains the following components a) to h) as essential components: a) Ethylene glycol salicylate, b) Alkyl (meth)acrylate copolymer, c) Partially neutralized polyacrylic acid, d) Water-soluble polymer compounds containing sodium carboxymethyl cellulose, e) Wetting agents containing glycerin, f) Crosslinking agent, g) Hydrochloric acid, and h) water, and The blending amount of glycerin in the adhesive layer is more than 15 times and 18 times or less on a mass basis with respect to the blending amount of ethylene glycol salicylate. Such as the water-containing patch of claim 1, where The pH of the adhesive layer is 4.00-4.85. Such as the water-containing patch of claim 1 or 2, where The above-mentioned adhesive layer is when the total mass of the adhesive layer is set to 100% by mass, with a) Glycol salicylate 0.1-30% by mass, b) (meth)acrylic acid alkyl ester copolymer 0.1-5 mass%, c) Partially neutralized polyacrylic acid 3.5~4.5% by mass, d) 2.0-30% by mass of a water-soluble polymer compound containing sodium carboxymethyl cellulose, e) Wetting agent containing glycerol 30 to 70% by mass, f) Cross-linking agent 0.01~6.0% by mass, g) Hydrochloric acid 0.1~1.5% by mass, h) Water 10 to 90% by mass, The ratio is deployed. The water-containing patch according to any one of claims 1 to 3, wherein the weight of the adhesive layer after being immersed and standing in purified water for 24 hours is relative to the weight of the adhesive layer before being immersed and standing in purified water The calculated swelling degree of the adhesive layer is less than 50. Such as the water-containing patch of any one of Claims 1 to 4, the storage conditions are: the residual rate (%) of the salicylic acid ethylene glycol ester before and after storage at 60°C for 2 weeks (%) Less than 5%.