TW202202147A - Transdermal patch - Google Patents

Abstract

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. 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

patch

The present invention relates to an aqueous adhesive, in detail, to an aqueous adhesive, which has good adhesive force and good stability of the prepared ethylene glycol salicylate, and further has a moderate Aqueous adhesive with cross-linking degree.

The adhesive agent using water-containing adhesive base (in this specification, referred to as the water-based adhesive agent), which is generally also called "packaging agent", is a paste layer containing active ingredients such as drugs on a support such as a non-woven fabric ( Adhesive layer) one of the adhesives. Since the plaster 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 water in the ointment layer. , easily peels off the skin. In order to solve such a problem, there is known a technique of dispersing an emulsion (also known as an alkyl acrylate copolymer) known as a component constituting a non-aqueous (also called hydrophobic, lipophilic) adhesive. A base called an emulsion) is formulated into the paste layer (adhesive layer) of the aqueous adhesive.

For example, Patent Document 1 discloses a patch (comparative product) in which a methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (trade name Nikasol) is prepared in a dressing base (paste). TS-620, Japan calcium carbide industry (shares)) 1%. Patent Document 2 discloses a water-based external adhesive agent that can exhibit adhesive force and re-adhesion force during long-term sticking, suppress hardening and decrease in softness due to loss of moisture, and suppress peeling. For the purpose of the water-based adhesive agent for breaking the support, the water-dispersible surfactant is contained in a ratio of 0.01% by mass to 10.0% by mass relative to the entire composition for an aqueous-based external adhesive agent, and the amount relative to The entire composition for an aqueous external patch contains a methyl acrylate-2-ethylhexyl acrylate copolymer in a ratio of 5.0 mass % or more and 10 mass % or less. Patent Document 3 discloses a dressing, which aims to provide a dressing that has sufficient adhesion even when the water content of the dressing decreases over time, and contains a partially neutralized polyacrylic acid, Methyl acrylate-2-ethylhexyl acrylate copolymer and polyacrylic acid of 2.5 to 10 times the mass of the neutralized product (5 to 25 mass % based on the paste). Patent Document 4 discloses a dressing containing poly(methyl acrylate/2-ethylhexyl acrylate), polyethylene Surfactants such as glycol fatty acid esters. Patent Document 5 discloses a viewpoint of obtaining a hot and cold sheet 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. [Prior Art Literature] [Patent Literature]

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

[Problems to be Solved by Invention]

As described above, it is known that an alkyl acrylate copolymer such as a methyl acrylate-2-ethylhexyl acrylate copolymer is formulated into an adhesive layer in order to improve the adhesive durability of the aqueous adhesive. However, in aqueous solvent, the drug stability of ethylene glycol salicylate has problems, that is, the stability and adhesion of the drug in the aqueous adhesive prepared with ethylene glycol salicylate are still difficult to say. fully satisfactory. [Technical means to solve problems]

The inventors of the present invention have made diligent studies to solve the above-mentioned problems, and as a result, they have found that, in order to take into account the stability of ethylene glycol salicylate in the water-based adhesive preparation, the improvement of the adhesiveness of the preparation, and the moderate degree of cross-linking, the The above-mentioned problems can be solved by adjusting the pH of the adhesive (paste), especially by adding hydrochloric acid as an essential component when adjusting the pH, and the present invention has been completed.

That is, the present invention relates to an aqueous adhesive 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 system 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 macromolecular compounds comprising sodium carboxymethyl cellulose, e) humectants containing glycerin, f) cross-linking agent, g) hydrochloric acid, and h) water, and The blending amount of glycerin in the above-mentioned adhesive layer is more than 15 times and 18 times or less with respect to the blending amount of ethylene glycol salicylate on a mass basis.

Furthermore, according to the present invention, the following embodiments are further provided. 1) The above-mentioned water-based adhesive agent, wherein the pH value of the above-mentioned adhesive layer is 4.00 to 4.85. 2) The water-based patch as above, wherein The above-mentioned adhesive layer is based on the total mass of the adhesive layer as 100% by mass. a) Ethylene 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 mass%, d) 2.0 to 30% by mass of a water-soluble polymer compound containing sodium carboxymethylcellulose, e) 30-70% by mass of humectant containing glycerin, f) Cross-linking agent 0.01～6.0% by mass, g) Hydrochloric acid 0.1～1.5% by mass, h) Water 10～90% by mass, The ratio is adjusted. 3) The above-mentioned aqueous adhesive, wherein the adhesive layer is calculated as the ratio of the weight of the adhesive layer after immersion in purified water for 24 hours to the weight of the adhesive layer before immersion in purified water The degree of swelling is less than 50. 4) In the above-mentioned water-based adhesive preparation, the storage conditions are as follows: the residual ratio (%) of ethylene glycol salicylate before and after storage at 60°C for 2 weeks does not decrease by 5%. In addition, the following are mentioned as an example of preferable aspect of this invention. (i) The above-mentioned water-based adhesive agent, wherein in the above-mentioned adhesive agent layer, the total compounding amount of the partially neutralized polyacrylic acid and sodium carboxymethylcellulose is 7% by mass based on the total mass of the adhesive agent layer and the amount of polyacrylic acid partially neutralized is 3.5% by mass or more based on the total mass of the adhesive layer, and the amount of sodium carboxymethyl cellulose is based on the total mass of the adhesive layer. above. (ii) The above-mentioned water-based adhesive agent, wherein the above-mentioned alkyl (meth)acrylate is a copolymer comprising a monomer mixture of monomer A and monomer B, and the above-mentioned monomer A is to make the monomer A Monomers of polymers whose glass transition temperature (Tg) during homopolymerization is 270 K or higher, and the monomer B is a monomer for polymers whose glass transition temperature (Tg) is 220 K or lower during homopolymerization of the monomer B . (iii) The above-mentioned aqueous adhesive, wherein the partially neutralized polyacrylic acid has a degree of neutralization of 30% to 65%, and the viscosity of its 0.2 mass % aqueous solution is 450 to 650 mPa·s. (iv) The above-mentioned aqueous adhesive preparation, wherein the viscosity of the 1 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 above-mentioned water-based adhesive agent, wherein the above-mentioned crosslinking agent is a poorly soluble aluminum compound. (vi) The above-mentioned water-based adhesive agent, wherein the above-mentioned adhesive layer contains the above-mentioned components a) to h), and is formed from an adhesive layer-forming composition having a viscosity of 90 to 250 Pa·s. (vii) The above-mentioned water-based adhesive agent, wherein the above-mentioned adhesive layer further contains Sodium EDTA hydrate as i) chelating agent. [Effect of invention]

According to the present invention, in the aqueous adhesive containing ethylene glycol salicylate in the adhesive layer, by mixing hydrochloric acid into the adhesive layer, an ethylene glycol salicylate can be provided as an active ingredient The ester is stable over time, and the adhesive force of the preparation is also high, and the cross-linking degree is also a good water-based adhesive. In addition, according to the present invention, it is possible to provide an aqueous system that can maintain the adhesive force even after the water in the adhesive layer is volatilized, has low skin irritation, and low adhesion between pastes, and can be re-adhered to the skin sticker.

As described above, the inventors of the present invention have found that in an aqueous adhesive, especially in an aqueous adhesive prepared with a non-aqueous adhesive base in the paste layer (adhesive layer) of the aqueous adhesive , by adjusting the pH of the adhesive (paste) by adding hydrochloric acid as an inorganic acid to the adhesive layer, specifically, by shifting the pH of the adhesive layer from the neutral side to the acidic side, the drug can be improved : Stability of ethylene glycol salicylate in the presence of water. Surprisingly, it was found that by formulating hydrochloric acid, in addition to the drug stability, the degree of cross-linking and adhesion, which are hardly sufficient when other acids are used, can also be improved. Hereinafter, the structure of the water-containing adhesive agent of this invention is demonstrated.

The aqueous adhesive agent of the present invention (hereinafter, also simply 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 shape of the above-mentioned patch, especially the preparation part comprising the support and the adhesive layer arranged on the support is not particularly limited, and square (square, rectangle, etc.), quadrilateral (trapezoid, rhombus, etc.) can be selected according to the attachment site. etc.), polygons, circles, ellipses, semicircles, triangles, crescents, and combinations of these shapes. In addition, the area of the patch (especially the above-mentioned preparation part) can be appropriately determined, for example, the amount of the active 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 water-based adhesive of the present invention contains a) ethylene glycol salicylate, b) (meth)alkyl acrylate copolymer, c) partially neutralized polyacrylic acid, d) containing carboxylate A water-soluble polymer of sodium methylcellulose, e) a wetting agent containing glycerin, f) a cross-linking agent, g) hydrochloric acid, and h) water as essential components. The water-based adhesive of the present invention is characterized in that, for the water-containing adhesive layer, in addition to the following hydrophilic acrylic adhesive, i.e., c) a partially neutralized polyacrylic acid, a non-aqueous-based adhesive is also formulated. b) (meth)acrylic acid alkyl ester copolymer of the acrylic adhesive. As the adhesive generally used for the adhesive layer (paste layer) of the water-based adhesive, polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, N-vinylacetamide-sodium acrylate copolymer resin, etc. are widely used Hydrophilic acrylic adhesive. From the viewpoint of having high affinity with the above-mentioned hydrophilic acrylic adhesive and enabling uniform kneading, as the non-aqueous adhesive to be formulated into the aqueous adhesive layer of the aqueous adhesive, acrylic is preferably formulated. and methacrylic emulsion type adhesive. In addition, in this specification, "(meth)acrylic acid alkyl ester type copolymer" means containing both acrylic acid and methacrylic acid alkyl ester, and "acrylic adhesive" also means containing acrylic acid type adhesive. Both adhesives and methacrylic adhesives.

<a) Ethylene glycol salicylate> In the adhesive layer of the water-containing adhesive agent of the present invention, ethylene glycol salicylate (also referred to as ethylene glycol salicylate) is contained as an active ingredient. Also, if necessary, in addition to ethylene glycol salicylate, felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, ibuprofen may be used in combination Non-steroidal anti-inflammatory agents such as fennel or their esters; antihistamines such as diphenhydramine and chlorofenilamine; analgesics such as aspirin, acetaminophen, ibuprofen, and loxoprofen sodium; Local anesthetics such as lidocaine and dibucaine; muscle relaxants such as succinylcholine chloride; antifungal agents such as clotrimazole; blood pressure-lowering agents such as clonidine; vasodilators such as nitroglycerin and isosorbide dinitrate; Vitamin A, vitamin E (tocopherol), vitamin E acetate, vitamin K, octyamine, riboflavin butyrate and other vitamins, prostaglandins; scopolamine, fentanyl, capsicum extract, vanillamide pelargonate, Capsaicin, dl-camphor, etc.

The dosage of the above-mentioned ethylene glycol salicylate and the total dosage of ethylene glycol salicylate and other active ingredients in the case of containing other active ingredients can be appropriately determined according to the types of other active ingredients, for example It can be 0.1 mass % or more and 30 mass % or less, or 0.5 mass % or more and 15 mass % or less based on the total mass of the adhesive bond layer of a water-containing adhesive agent.

<b) (meth)acrylic acid alkyl ester type copolymer> The alkyl (meth)acrylate copolymer (non-aqueous adhesive base) constituting the non-aqueous acrylic adhesive is a copolymer containing the following monomers (an example of the monomer is listed in Table 1): The monomer of strength, the number of carbon atoms of (methyl) alkyl ester is 2 to 9, and the glass transition temperature (Tg) during homopolymerization will be a polymer below -55°C (218 K); as a cohesive force improvement The monomer of the component will become a polymer with a Tg of 8-165°C (281-438 K) during homopolymerization; and a monomer having a functional group such as a carboxyl group or a hydroxyl group as a cross-linking point as needed.

[Table 1] [Table 1] monomer The number of carbon atoms in the alkyl ester moiety Homopolymer Tg Tg(K) Tg(℃) Adhesion performance Tg: -55℃ or less 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 Cohesion 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, a homopolymer obtained by polymerizing only a monomer that exhibits adhesive force has high adhesive force but weak mechanical strength. Generally, a copolymer whose mechanical strength is increased by copolymerizing with a monomer that increases the cohesion force is used. as an adhesive. As exemplified as the monomers exhibiting adhesive force shown in Table 1 above, in the present invention, as a monomer having higher adhesive force, the Tg when the monomer is homopolymerized (homopolymer) is 220 K The following are butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate and the like. Among these, 2-ethylhexyl acrylate, which is actually used as a pharmaceutical additive and has high adhesive force (low Tg of the homopolymer) can be preferably used. In addition, as the monomer for improving the cohesion force (the Tg of the homopolymer is 270 K or more), the monomers listed in Table 1 can be mentioned. Among them, in the present invention, it is preferable to have high mechanical strength and not cause the Methyl acrylate with significantly reduced tack (relatively low homopolymer Tg).

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

In the adhesive layer of the water-based adhesive of the present invention, the compounding amount of the alkyl (meth)acrylate-based copolymer (in the case of an emulsion, the amount in terms of solid content) is based on the adhesiveness of the water-based adhesive. Based on the total mass of the agent layer, for example, it can be 0.1 mass % or more and 5 mass % or less, 0.5 mass % or more and 4.5 mass % or less, and 1.0 mass % or more and 4.5 mass % or less. Moreover, regarding the mixing ratio with the following acrylic hydrophilic adhesive, for example, in mass ratio, it can be set as an alkyl acrylate copolymer: acrylic hydrophilic adhesive=1.5:1 to 1:10, alkyl acrylate Base ester copolymer: acrylic hydrophilic adhesive = 1.5:1 to 1:5, alkyl acrylate copolymer: acrylic hydrophilic adhesive = 1.5:1 to 1:1, etc.

<c) Partially neutralized polyacrylic acid> In the adhesive layer of the aqueous adhesive of the present invention, the partially neutralized polyacrylic acid is contained as an acrylic hydrophilic adhesive. In addition, an acrylic hydrophilic adhesive other than the partially neutralized polyacrylic acid can also be prepared in the adhesive layer as required. Generally, water-soluble (meth)acrylic-type polymers are mentioned as said acrylic-type hydrophilic adhesive agent. The water-soluble (meth)acrylic polymer is a polymer obtained by polymerizing a (meth)acryloyl group-containing monomer containing a water-soluble functional group (hydrophilic group), and is prepared by mixing with water to the adhesive layer to exert adhesion. 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 fully neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. That is, in this specification, the "partially neutralized product of polyacrylic acid" includes both a neutralized product of partially neutralized polyacrylic acid groups and a neutralized product of completely neutralized polyacrylic acid groups. The partially neutralized product of polyacrylic acid means polyacrylate, and for example, sodium salt, potassium salt, calcium salt, ammonium salt, etc. can be used. For example, Vicomate NP-800 (manufactured by Showa Denko Co., Ltd.) can be mentioned.

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%. In addition, 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 used as 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 having such a degree of neutralization and viscosity, it is possible to further exhibit adhesion to the skin when hydrated, and further promote the interaction with the skin. The cross-linking of the cross-linking agent prevents dissolution when water is contained.

The above-mentioned compounding amount of the partially neutralized polyacrylic acid and the total compounding amount of the partially neutralized polyacrylic acid and other acrylic hydrophilic adhesives in the case of including other acrylic hydrophilic adhesives are based on the adhesiveness of the aqueous adhesive. Based on the total mass of the agent layer, for example, it can be 0.1 mass % or more and 10 mass % or less, and 1 mass % or more and 8 mass % or less. For example, the compounding quantity of the said polyacrylic acid partial neutralization product can be 3.5 mass % or more and 4.5 mass % or less based on the total mass of an adhesive bond layer.

<d) Water-soluble polymer compound> As the water-soluble polymer compound, the adhesive layer of the adhesive agent 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, the above-mentioned sodium carboxymethyl cellulose used in the present invention may have a viscosity of 1,000 to 3,000 mPa·s in a 1 mass % aqueous solution at 20°C. Moreover, as for sodium carboxymethylcellulose, it is preferable that the ester substitution degree is 0.60-0.95.

In addition, water-soluble polymer compounds other than sodium carboxymethylcellulose may be contained, and examples thereof include gelatin, agar, polyvinyl alcohol (partially saponified), 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 alone or in combination with sodium carboxymethyl cellulose in an appropriate combination of two or more.

The compounding amount of the above-mentioned water-soluble polymer compound is usually based on the total mass of the adhesive layer of the water-based adhesive, for example, 1.0 mass % or more and 30 mass % or less, 2.0 mass % or more and 30 mass % or less, 2.5 mass % or more and 20 mass % or less, or 3.0 mass % or more and 10 mass % or less. Moreover, for example, the compounding quantity of sodium carboxymethylcellulose can be 2.0 mass % or more and 3.5 mass % or less based on the total mass of an adhesive layer.

<e) Wetting agent containing glycerin> In order to suppress the evaporation of moisture over time, a humectant (also referred to as a moisturizing agent) is formulated into the adhesive layer of the water-based adhesive agent of the present invention. As the above-mentioned wetting agent, glycerin is formulated as an essential component in the adhesive layer of the adhesive agent of the present invention. In addition, wetting agents other than glycerin may be formulated, and examples thereof include D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propylene glycol, 1,3-propylene glycol, 4-Butanediol, maltitol, xylitol and other polyols. These can be used singly or in combination with glycerin in an appropriate combination of two or more.

The blending amount of the above-mentioned wetting agent is generally based on the total mass of the adhesive layer of the water-based adhesive, and can be, for example, 30 mass % or more and 70 mass % or less, 40 mass % or more, 60 mass % or less, or 40 mass %. More than 50 mass % or less, or 45 mass % or more and 55 mass % or less. Furthermore, in the present invention, the amount of glycerin in the adhesive layer is more than 15 times and 18 times or less with respect to the amount of a) ethylene glycol salicylate described above on a mass basis. For example, it can be set as The amount of glycerin in the adhesive layer is 15.5 times or more and not more than 18.0 times the amount of ethylene glycol salicylate in the above-mentioned a) ethylene glycol salicylate. In the above-mentioned a) the preparation 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 preparation amount of glycerin in the adhesive layer relative to the above a) salicylate ethylene glycol The compounding amount of the ester is 16.5 times or more and 17.9 times or less based on the mass basis; the compounding amount of the glycerin in the adhesive layer can be set as the compounding amount of the above a) ethylene glycol salicylate based on the mass basis. 16.7 times or more and 17.9 times or less; can be set as 17.0 times or more and 17.9 times or less on a mass basis with respect to the preparation amount of glycerin in the adhesive layer relative to the above-mentioned a) ethylene glycol salicylate preparation amount; The amount of glycerin in the adhesive layer is 17.5 times or more and not more than 17.9 times the amount of ethylene glycol salicylate in the above-mentioned a) ethylene glycol ester; or it can be set as the amount of glycerin in the adhesive layer. It is 15.5 times or more and 17 times or less on a mass basis with respect to the compounding quantity of the said a) ethylene glycol salicylate. When the amount of glycerin formulated is small, the moisturizing property may be insufficient, and the moisture of the adhesive may be easily volatile, and when the amount of glycerin formulated is increased, the stability of the drug may be reduced. 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 may be a problem.

<f) Cross-linking agent> Examples of the crosslinking agent to be formulated into the adhesive layer of the water-based adhesive of the present invention include polyvalent metal salts, and among them, aluminum-containing polyvalent metal compounds. Examples include hydroxides such as aluminum hydroxide and aluminum magnesium hydroxide; aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxyaluminumaminoacetal), and dihydroxyaluminumaminoacetic acid. Salts, normal salts of inorganic or organic acids such as synthetic aluminum silicate, dry aluminum hydroxide gel, kaolin, aluminum stearate, or their basic salts; complex salts such as bauxite; aluminates such as sodium aluminate; Inorganic aluminum zirconium salts and organic aluminum chelate compounds; synthetic aluminum magnesium carbonate, aluminum magnesium silicate, aluminum magnesium silicate and other polyvalent metal compounds, which can be used alone or in combination of two or more. Among them, it is preferable to use dihydroxyaluminumaminoacetate which is a poorly soluble aluminum compound, synthetic aluminum silicate, and dry aluminum hydroxide gel.

The compounding amount of the crosslinking agent may be appropriately selected in consideration of the residual of the adhesive on the skin or the degree of crosslinking which may be one of the reasons for the adhesion. Based on the total mass of the adhesive layer of the water-containing adhesive agent, for example, a range of 0.01 mass % or more and 6.0 mass % or less, 0.01 mass % or more and 4.0 mass % or less, or 0.01 mass % or more and 2.0 mass % or less can be mentioned.

<g) Hydrochloric acid> The adhesive layer of the water-based adhesive agent of the present invention is characterized in that hydrochloric acid is prepared therein. The compounding quantity of hydrochloric acid can be made into the range of 0.1 mass % or more and 1.5 mass % or less, for example based on the total mass of the adhesive layer of the water-containing adhesive agent. Furthermore, if hydrochloric acid is not prepared, but only other acids such as those listed in the following <Organic acids> or inorganic acids other than hydrochloric acid are prepared, it is difficult to obtain both moderate crosslinkability and good adhesion. . For example, in the case of using tartaric acid, good adhesion cannot be obtained, and in the case of using phosphoric acid, in terms of the stability of ethylene glycol salicylate or the expression of moderate crosslinking properties, it is different from the use of hydrochloric acid. Compared with the case of the present invention, the result may be inferior, and in order to obtain the same effect as when using hydrochloric acid from the viewpoint of stability, there is a case where a larger amount of compounding is required. Phosphoric acid is preferably not added, but 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 (water) in the adhesive layer. In this specification, the so-called "water" contained in the adhesive layer includes not only what is separately added as water when forming the adhesive layer, but also water contained in the form of an emulsion or an aqueous solution. The amount of water to be prepared is not particularly limited, and based on the total mass of the adhesive layer of the water-containing adhesive agent, it can be, for example, 10% by mass or more and 90% by mass or less, 15% by mass or more, 70% by mass or less, or 20% by mass. More than 50 mass % or less. In addition, the amount of water to be prepared is the value at the time of preparation of the adhesive agent or before the application of the adhesive agent, and it is not limited to the case where the water is volatilized from the adhesive agent layer along with the pasting process.

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

＜Organic solvent＞ The organic solvent can also be formulated into the adhesive layer of the water-based adhesive of the present invention as a component that can play the following functions: assisting the dissolution of active ingredients such as drugs (that is, as a solubilizer), and, Prevent active ingredients from separating out from the adhesive layer. Examples of such organic solvents (solubilizers) include: crotamiton; N-methyl-2-pyrrolidone; polyalkylene glycols such as polyethylene glycol 400 (polyethylene glycol) and 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; polyols such as 1,3-butanediol; dimethylformamide; These can be used individually by 1 type or in combination of 2 or more types.

In the case of using an organic solvent, the compounding amount can be, for example, 0.1 mass % or more and 20 mass % or less based on the total mass of the adhesive layer of the water-containing adhesive agent.

＜Organic acid＞ The organic acid can also be formulated into the adhesive layer of the aqueous adhesive of the present invention. As organic acids that can be formulated, 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. more than one type of use. In the case of using an organic acid, the compounding amount can be set in the range of, for example, 0.1 mass % or more and 5 mass % or less based on the total mass of the adhesive layer of the water-containing adhesive agent. By using the organic acid within such a compounding amount range, it can be expected that the problem of stickiness due to insufficient cross-linkability due to the dissolution of the adhesive can be suppressed. manufacturing problem.

＜Surfactant＞ A surfactant can also be formulated into the adhesive layer of the aqueous adhesive 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 monopalmitic acid Esters, Sorbitan Monostearate, Sorbitan Distearate, Sorbitan Tristearate, Sorbitan Monooleate, Sorbitan Trioleate, Sorbitan Mono Hemioleate, and sorbitan fatty acid esters such as ethylene oxide adducts; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan Alcohol Anhydride Monostearate, Polyoxyethylene Sorbitan Tristearate, Polyoxyethylene Sorbitan Monooleate, Polyoxyethylene Sorbitan Trioleate, Polyoxyethylene Sorbitan Triiso Polyoxyethylene sorbitan fatty acid esters such as stearate; polyoxyethylene lauryl ether (polyoxyethylene lauryl ether), polyoxyethylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyethylene lauryl ether Alkylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethyl ether Polyoxyethylene alkyl ethers such as hexyl hexyl ether and polyoxyethylene isodecyl ether; polyoxyethylene styrenated phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene distyrenated phenyl ether, polyoxyethylene tribenzyl Polyoxyethylene alkylphenol ethers such as phenyl ether; glycerol fatty acid esters such as glycerol monostearate and glycerol monooleate; polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, lecithin and other non-ionic surfactants. These can be used individually by 1 type or in suitable combination of 2 or more types. In the case of using these surfactants, the compounding amount is based on the total mass of the adhesive layer of the water-based adhesive, for example, 0.001 mass % or more and 10 mass % or less, and 0.01 mass % or more and 5 mass %. the following range.

<Other optional ingredients> Antioxidants such as dibutylhydroxytoluene (BHT), calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, Inorganic powders such as calcium sulfate, ultraviolet absorbers such as benzalkonium methane derivatives, colorants, fragrances, preservatives, etc., can generally be formulated into the previous aqueous adhesives (dressings) or non-aqueous adhesives (patches). ) in the adhesive layer as other optional components. When these optional components are used, they can be used alone or in combination of two or more, for example, within the range of 0.01 mass % or more and 1 mass % or less based on the total mass of the adhesive layer of the water-based adhesive. use.

[support body] 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, woven fabrics, woven fabrics, and laminated composites of non-woven fabrics and films. Such a support is preferably a material that is soft enough to be in close contact with the skin and can follow the movement of the skin, and can suppress the occurrence of skin rashes and the like after being adhered for a long time. Examples of the material of these supports include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, Cotton, rayon acetate, rayon, rayon/polyethylene terephthalate complex, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, ether Polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene An olefin rubber, an ethylene-vinyl acetate copolymer, a celofen, etc. as an essential component.

In addition, the support such as cloth can be colored with a colorant in a color tone such as skin color, thereby reducing the difference between the color of the skin and the skin at the time of sticking. Moreover, from the viewpoint of easily permeating the skin tone in the attached state, the form of a plastic film excellent in transparency can be adopted.

The thickness of the support is usually about 5 μm to 1 mm. When the support is cloth, the 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 as thin as 5 μm to 30 μm, if a peelable carrier film layer is provided on the opposite side of the adhesive layer formed on the support, the workability as an adhesive increase, so it is better. However, if the thickness of the support is less than 5 μm, the strength or workability of the adhesive agent may decrease, making it difficult to stick to the skin, and may be damaged by contact with other members, or may be damaged by contact with water due to bathing or the like. And peel off from the skin in a short time. Also, if the thickness of the support is too large (more than 1 mm), it becomes difficult for the patch to follow the movement of the skin, and the edge of the patch tends to form the starting point of peeling, so it peels off from the skin in a short time, or during the attachment. The risk of increased discomfort. Furthermore, when the support is a film, for the purpose of improving the adhesion between the adhesive and the support, sandblasting, corona treatment and other treatments can also be performed on one or both sides of the support. Moreover, in order to make it easy to take out from the packaging material, the unevenness|corrugation may be provided in the single surface or both surfaces of a support body by the method other than sandblasting.

[release liner] The release liner (also referred to as release layer, release paper) used in the water-based adhesive of the present invention is preferably a material that does not easily absorb and absorb the drugs in the adhesive layer, and can be used for the adhesive layer. used in the technical field. For example, polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unstretched, stretched, etc.), polyethylene, polyamine Plastic films such as carbamate, polyvinyl chloride, and polystyrene; Dowling paper, cellophane, parchment, kraft paper, and other papers or synthetic papers; coating the above plastic films, papers, synthetic papers, and synthetic fibers with silicone resin or Released paper made of a release agent with release properties such as fluororesin; aluminum foil; laminated paper formed by laminating these films and sheets in various ways, and lamination paper coated with release agent Colorless or colored sheets such as laminated release paper. Furthermore, the release liner can also be provided with concavities and convexities for easy removal 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. Furthermore, the peeling force when peeling the adhesive layer from the release liner is desirably 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 layer in the packaging material is taken out and the adhesive is caught by the packaging material, there will be an adhesive layer (that is, the adhesive agent) is deviated from the release liner and peeled off. In addition, the reason for this is that when the peeling force of the adhesive layer (sticker) from the release liner is too strong, the workability at the time of use may be deteriorated. The peeling force of the adhesive layer from the release liner also varies according to the type of the release liner used, for example, it can be set to 0.01 N/15 mm to 0.5 N/15 mm.

[Manufacturing method of water-containing adhesive agent] The water-based adhesive preparation of the present invention can be produced by a conventionally 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 the adhesive layer, and the step of laminating 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 the adhesive layer, and the step of bonding the adhesive layer formed on the release liner to the support. Furthermore, the thickness of the above-mentioned adhesive layer is not particularly limited, and is usually 10 μm to 1000 μm, for example, 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 active ingredients), alkyl (meth)acrylate-based copolymer, polyacrylic acid partially neutralized (other acrylic hydrophilic adhesives), water-soluble polymer compounds containing sodium carboxymethyl cellulose, wetting agents containing glycerin, cross-linking agents, hydrochloric acid, and water, and optionally chelating agents, Semi-solid composition of organic solvent, organic acid, surfactant, and other optional ingredients. From the viewpoint of workability at the time of production, the adhesive layer-forming composition preferably has 90 to 250 Pa·s, 100 to 250 Pa·s, and more preferably 130 to 250 Pa·s at 20°C to 30°C. Pa·s viscosity. If the viscosity is less than 90 Pa·s, there is a possibility that the paste may ooze out when a woven cloth or a woven cloth is used as a support. When the viscosity exceeds 250 Pa·s, it becomes difficult to spread.

[pH value of the adhesive layer in the aqueous adhesive] In the aqueous adhesive 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, for example, 4.00 to 4.85, preferably 4.40 to 4.80 , and more preferably 4.50 to 4.80. By controlling the pH value of the adhesive layer within an appropriate range, the stability of the ethylene glycol salicylate can be improved, and the adhesive can be used to improve the coatability (ductility) of the adhesive. A water-based adhesive with excellent properties. Furthermore, the pH value of the adhesive layer can be measured at a temperature of 20 to 25° C. in accordance with, for example, the pH measurement method of the Japanese Pharmacopoeia General Test Method.

Furthermore, there is a case 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 produced adhesive, the adhesive is scraped from the exposed adhesive layer with a spatula or the like, and purified water is added to the collected adhesive, for example, by diluting 20 times. Homogeneous solution. The obtained solution was kept at room temperature (25.0±0.2°C), and the glass composite electrode of the calibrated pH meter was inserted into the solution to measure the pH value.

＜Swelling degree＞ Regarding the adhesive layer (adhesive layer forming composition) of the present invention, when the adhesive layer (adhesive layer forming composition) is immersed in purified water for 24 hours, the weight of the adhesive layer after immersion and standing for 24 hours is relative to the adhesion before immersion and standing. The swelling degree of the adhesive layer calculated from the weight ratio of the adhesive layer is preferably less than 50. Furthermore, the procedure for measuring and calculating the degree of swelling is, for example, as follows: the water-based adhesive agent and the support are cut into specific sizes, and the water-based adhesive agent is measured in a state where the liner is peeled off, respectively. (initial water-based adhesive (liner peel) weight, initial support weight). After that, the equal parts were immersed in purified water and left to stand for 24 hours, and the weight after immersion and standing for 24 hours (the weight of the water-based adhesive (liner peeling) after the purified water was left to stand, and the support after the purified water stood still was measured. Body weight), the swelling degree can be calculated according to the following formula. Swelling degree of the adhesive layer = (weight of aqueous adhesive (liner peeling) after standing with purified water - weight of support body after standing with purified water)/(initial weight of aqueous adhesive (liner peeling) - Initial support body weight) By setting the degree of swelling of the adhesive layer to less than 50, it is possible to provide an aqueous adhesive that maintains the shape retention of the adhesive layer and suppresses the risk that the adhesive layer remains on the skin after peeling. [Example]

Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these Examples.

＜Preparation of adhesive agent＞ The adhesive preparations (formulations) of Examples, Comparative Examples, and Production Examples were produced in the following procedure.

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 the like was dissolved (oil phase). Furthermore, 4 parts by mass of the partially neutralized polyacrylic acid (when the degree of neutralization: 35% and the viscosity: an aqueous solution with a concentration of 0.2 mass %, the viscosity at 20° C. is 547 mPa·s), carboxymethyl 3 parts by mass of sodium cellulose (ester substitution degree: 0.82, viscosity: 1,840 mPa·s in 1 mass % aqueous solution at 20°C), 0.25 parts by mass of dihydroxyaluminumaminoacetate in 22 parts by mass of concentrated glycerin ground dispersion (glycerol phase). The water phase, 7 parts by mass of methyl acrylate-2-ethylhexyl acrylate copolymer emulsion, 0.20 parts by mass of sodium EDTA hydrate, 30 parts by mass of D-sorbitol 70% aqueous solution, 0.9 parts by mass of hydrochloric acid diluted with purified water (residual amount) was dispersed or dissolved uniformly. The oil phase and the glycerin phase were put into this in this order and kneaded uniformly. Further, 1 part by mass of lactic acid was added, and the mixture was uniformly kneaded under degassing conditions to obtain the adhesive layer-forming composition of Example 1. In addition, the following test example 4 (viscosity of an adhesive) was implemented using the obtained adhesive agent layer forming composition. The obtained adhesive layer-forming composition was stretched on the silicone side of the liner (one-side silicone-treated PET (polyethylene terephthalate) (75 μm)) using a stretching machine , after laminating a knitted fabric support (made of polyester), it was aged 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, Manufacturing Example 1 to Manufacturing Example 20: Except having changed the kind and compounding amount of each component as described in Table 2, Table 3, and Table 4 to Table 6, the same procedure as in Example 1 was carried out to obtain Examples 2 to 9, and Comparative Examples 1 to Comparative Examples. Example 9. Preparation of the preparations from Example 1 to Example 20. In addition, in the case of preparing phosphoric acid and tartaric acid, it is produced at the same timing as hydrochloric acid. In addition, in the preparation of glycerol monostearate, polysorbate 80, polyoxyethylene hydrogenated castor oil 10, polyvinyl alcohol, polyoxyethylene oleyl ether, diisopropyl adipate, diethyl sebacate, In the case of isopropyl myristate and isopropyl palmitate, it was produced by separately adding it at the same timing as polyethylene glycol 400.

Test Example 1 (pH Measurement of Adhesive Layer) The pH of each formulation of Examples and Comparative Examples was measured at 25.0±0.2°C according to the pH measurement method of the Japanese Pharmacopoeia General Test Method. The obtained results are shown in Tables 2 and 3.

Test Example 2: Stability evaluation of ethylene glycol salicylate (SG) Regarding the stability evaluation of ethylene glycol salicylate, immediately after preparation (initial stage), and stored at 60° C. for 2 weeks (2 After W), the content of ethylene glycol salicylate contained in the adhesive layer is measured by high performance liquid chromatography (HPLC). Specifically, each formulation of 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. mm), which was made into a 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. The extract was filtered through a membrane filter with a pore size of 0.45 μm to prepare a sample solution. The sample solutions were analyzed under the HPLC conditions described below. Based on the peak area of ethylene glycol salicylate (holding time of about 11 minutes) and the sum of the areas of other peaks, the relative amounts of the decomposition products were compared, and the stability (adhesion) of ethylene glycol salicylate was compared. The residual % in the agent layer) was evaluated. Also, based on the initial value (residual % of ethylene glycol salicylate in the adhesive layer before storage), the reduction range of ethylene glycol salicylate after storage at 60°C for 2 weeks (2 W) was calculated (Decrease (%) relative to the initial value). The obtained results are shown in Tables 2 and 3. Measurement wavelength: 240 nm Column: Mightysil RP-18 (150 mm×4.6 mm, 5 μm) Column temperature: 30°C 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 for 6 months at 40°C and the storage conditions for 2 W at 60°C can be considered to be the same level. Stability (decrease (%) relative to the initial value) is ideally less than 5.0 if there is no obvious quality change at the value (decrease (%) relative to the initial value) after being stored at 60°C for 2 W %.

Test Example 3: Adhesion Test Rolling Ball Adhesion The release liner of each formulation (immediately after production) of the examples and comparative examples was peeled off to expose the adhesive layer, and the rolling ball adhesive force of the adhesive layer was in accordance with the Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3.2. Inclination The rolling ball viscosity test method was implemented. The average value (rolling ball No.) of n=3 was set as the value of the rolling ball viscosity test. The obtained results are shown in Tables 2 and 3. Furthermore, the evaluation of the stickiness 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 compositions of the Examples and Comparative Examples manufactured in the procedure of <Preparation of the Adhesive Agent>, the viscosity was measured with a hand-held rotational viscometer (measurement temperature: 20°C to 30°C) before the liner coating. ). The obtained results are shown in Tables 2 and 3.

Test Example 5: Adhesive Layer Crosslinking Degree The formulations and supports of the examples and comparative examples were cut into 12×100 mm, and the weights (initial formulation weight, initial support weight) were measured for the formulations with the liner peeled off, respectively. placed in glass bottles (room temperature) for 24 hours. After standing, the preparation and the support were taken out from the purified water, and the weights were measured (the weight of the preparation after standing with purified water, the weight of the support after standing with purified water), and the swelling of the paste (adhesive layer) was calculated from the following formula Spend. The swelling degree of the paste = (the weight of the preparation after standing with purified water - the weight of the support after standing with purified water)/(the weight of the initial preparation - the weight of the initial support) Based on the calculated swelling degree, the degree of crosslinking was evaluated according to the following evaluation criteria. The obtained results are shown in Tables 2 and 3. Furthermore, the degree of crosslinking is preferably + or more, and when it is ± or -, the shape retention of the paste is insufficient, and there is a possibility that a large amount of the paste remains on the skin when peeling off after sticking. <Evaluation of degree of crosslinking> ++: Degree of swelling is less than 10 +: Swelling degree is 10 or more and less than 50 ±: Swelling degree 50 or more -: Almost all the paste is dispersed in purified water and cannot be taken out

Test Example 6: Manufacturability Regarding the difficulty of spreading the adhesive layer-forming compositions of Examples and Comparative Examples to be produced in the procedure of <Adhesive Formulation> on the silicone surface of the gasket with a spreading machine, the following evaluation criteria were used to evaluate the The manufacturability was evaluated. The obtained results are shown in Tables 2 and 3. <manufacturability evaluation> ++: can be easily extended + : can be extended ± : ductile but unstable - : cannot be extended

[Table 2] [Table 2] Compounding ingredients (compounding amount: parts by mass) Example 1 2 3 4 5 6 7 8 9 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 EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.40 Dihydroxyaluminumaminoacetate 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 in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in 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 (residual %) initial 99.09 99.09 99.16 99.22 98.95 98.82 99.11 99.13 NT 60℃ after 2 W 96.31 95.16 94.34 95.97 94.39 94.49 94.30 97.46 NT Decrease from the initial value (%) 2.8 3.9 4.8 3.3 4.6 4.3 4.8 1.7 NT Adhesion: Rolling Ball Stickiness (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 + + + + + + + ++ + Glycerin/Glycol Salicylate Ratio 17.6 17.6 17.6 17.6 17.9 16.3 15.5 17.6 17.6 manufacturability + ++ ++ ++ ++ ++ ++ + ++ ※ The amount of purified water NT was adjusted so that the total of all the ingredients was 100 parts by mass: the test was not carried out

[Table 3] [Table 3] Compounding ingredients (compounding amount: parts by mass) Comparative example 1 2 3 4 5 6 7 8 9 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 EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 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 in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in 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 (residual %) initial 97.15 97.60 98.40 97.80 97.90 97.70 99.21 99.28 99.28 60℃ after 2 W 91.27 91.80 93.10 93.80 94.50 96.00 93.28 94.55 95.55 Decrease relative to the initial value (%) 5.9 5.8 5.3 4.0 3.4 1.7 5.9 4.7 3.7 Adhesion: Rolling Ball Stickiness (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 + ± - - - - + + + Glycerin/Glycol Salicylate Ratio 17.6 17.9 17.9 17.9 17.9 17.9 16.3 16.3 16.3 manufacturability ++ ++ ++ ++ + ++ ++ ++ ++ ※ The amount of purified water NT was adjusted so that the total of all the ingredients was 100 parts by mass: the test was not carried out

[Table 4] [Table 4] Compounding ingredients (compounding amount: parts by mass) Manufacturing Example 1 2 3 4 Glycol Salicylate 1.25 1.25 1.25 1.25 L-Menthol 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 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 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 Sodium carboxymethyl cellulose 3.00 3.00 3.00 3.00 Glyceryl Monostearate 1.00 1.00 1.00 1.00 Concentrated glycerin 20.00 20.00 20.00 20.00 D-sorbitol liquid 25.00 25.00 25.00 25.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 hydrochloric acid 0.90 0.90 0.90 0.90 Lactic acid 1.00 1.00 1.00 1.00 Polyethylene Glycol 400 (Polyethylene Glycol) 1.00 1.00 1.00 1.00 Diisopropyl adipate 1.00 Diethyl Sebacate 1.00 Isopropyl myristate 1.00 Isopropyl Palmitate 1.00 Purified water ^※ 100 servings in total 100 servings in total 100 servings in total 100 servings in total ※ Adjust the amount of purified water so that the total of all the ingredients is 100 parts by mass

[Table 5] [Table 5] Compounding ingredients (compounding amount: parts by mass) Manufacturing Example 5 6 7 8 9 10 11 12 Glycol Salicylate 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 L-Menthol 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 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 Partially neutralized polyacrylic acid 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 Polysorbate 80 (polyoxyethylene (20) sorbitan monooleate) 1.00 1.00 1.00 1.00 Polyoxyethylene hydrogenated castor oil 1.00 1.00 1.00 1.00 Concentrated glycerin 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 D-sorbitol liquid 25.00 25.00 25.00 25.00 25.00 25.00 25.00 25.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 hydrochloric acid 0.90 0.90 0.90 0.90 0.90 0.90 0.90 0.90 Lactic acid 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 Diisopropyl adipate 1.00 1.00 Diethyl Sebacate 1.00 1.00 Isopropyl myristate 1.00 1.00 Isopropyl Palmitate 1.00 1.00 Purified water ^※ 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total ※ Adjust the amount of purified water so that the total of all the ingredients is 100 parts by mass

[Table 6] [Table 6] Compounding ingredients (compounding amount: parts by mass) Manufacturing Example 13 14 15 16 17 18 19 20 Glycol Salicylate 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 L-Menthol 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 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 Partially neutralized polyacrylic acid 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 Polyuryl alcohol (polyoxyethylene lauryl ether) 1.00 1.00 1.00 1.00 polyoxyethylene oleyl ether 1.00 1.00 1.00 1.00 Concentrated glycerin 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 D-sorbitol liquid 25.00 25.00 25.00 25.00 25.00 25.00 25.00 25.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 hydrochloric acid 0.90 0.90 0.90 0.90 0.90 0.90 0.90 0.90 Lactic acid 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 Diisopropyl adipate 1.00 1.00 Diethyl Sebacate 1.00 1.00 Isopropyl myristate 1.00 1.00 Isopropyl Palmitate 1.00 1.00 Purified water ^※ 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total 100 servings in total ※ Adjust the amount of purified water so that the total of all the ingredients is 100 parts by mass

As shown in Table 2, the preparations (water-based adhesive preparations) of Examples were stored at 60°C for 2 days in the stability evaluation of ethylene glycol salicylate as an active ingredient by preparing a specific amount of hydrochloric acid. After one week, the reduction rate relative to the initial value was less than 5%, the rolling ball viscosity value was also more than 15, and the degree of swelling, which is an indicator of the degree of crosslinking of the adhesive layer (paste), was also less than 50. (+Evaluation above), thereby becoming an aqueous adhesive with good stability of the active ingredient, adhesive force of the formulation, and degree of cross-linking. On the other hand, as shown in Table 3, in Comparative Examples 1 and 7 not containing hydrochloric acid, the reduction range of ethylene glycol salicylate from the initial value exceeded 5%, and the stability of the active ingredient was poor. In addition, when phosphoric acid was added in place of hydrochloric acid (Comparative Examples 2 to 6), the stability of ethylene glycol salicylate was increased by increasing the preparation amount, but the degree of cross-linking was deteriorated instead. When tartaric acid was used instead of hydrochloric acid (Comparative Examples 8 to 9), the rolling ball viscosity value was less than 15, and the desired adhesive force could not be obtained.

From the results of the above examples, it was confirmed that according to the present invention, in the water-based adhesive agent containing ethylene glycol salicylate in the adhesive agent layer, by adding hydrochloric acid to the adhesive agent layer, even if it is relatively A small amount of preparation can provide an aqueous adhesive that is stable over time as an active ingredient of ethylene glycol salicylate, has a moderate degree of crosslinking and good adhesion, and is also excellent in manufacturability.

Claims (5)

A water-based adhesive, which comprises a support, an adhesive layer disposed on the support, and a release liner attached to the adhesive layer, and The above-mentioned adhesive layer system 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 macromolecular compounds comprising sodium carboxymethyl cellulose, e) humectants containing glycerin, f) cross-linking agent, g) hydrochloric acid, and h) water, and The blending amount of glycerin in the above-mentioned adhesive layer is more than 15 times and 18 times or less with respect to the blending amount of ethylene glycol salicylate on a mass basis. As claimed in claim 1, the water-based adhesive, wherein The pH value of the above-mentioned adhesive layer is 4.00-4.85. As claimed in claim 1 or 2, the water-based adhesive, wherein The above-mentioned adhesive layer is based on the total mass of the adhesive layer as 100% by mass. a) Ethylene glycol salicylate 0.1-30 mass%, b) (meth)acrylic acid alkyl ester copolymer 0.1 to 5 mass %, c) Partially neutralized polyacrylic acid 3.5-4.5 mass%, d) 2.0 to 30% by mass of a water-soluble polymer compound containing sodium carboxymethylcellulose, e) 30-70 mass% of humectants containing glycerin, f) Cross-linking agent 0.01～6.0% by mass, g) Hydrochloric acid 0.1～1.5% by mass, h) Water 10～90% by mass, The ratio is adjusted. The aqueous adhesive according to any one of claims 1 to 3, wherein the weight of the adhesive layer after immersion in purified water for 24 hours is the weight of the adhesive layer before immersion in purified water The calculated swelling degree of the adhesive layer is less than 50. The water-based adhesive according to any one of Claims 1 to 4, the storage conditions are: the reduction rate (%) of the residual ratio (%) of ethylene glycol salicylate before and after storage at 60°C for 2 weeks less than 5%.