CN115315262A

CN115315262A - Patch preparation

Info

Publication number: CN115315262A
Application number: CN202180015558.5A
Authority: CN
Inventors: 村田笃; 金箱真; 萩原勲
Original assignee: Nichiban Co Ltd
Current assignee: Nichiban Co Ltd
Priority date: 2020-03-27
Filing date: 2021-03-25
Publication date: 2022-11-08
Also published as: TW202202147A; JPWO2021193874A1; KR20220158748A; WO2021193874A1

Abstract

The invention provides an aqueous patch which is improved in the stability of ethylene glycol salicylate, the adhesion of the preparation and the degree of crosslinking. The aqueous adhesive comprises a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, wherein the adhesive layer contains a) ethylene glycol salicylate, b) (meth) acrylic acid alkyl ester copolymer, c) partially neutralized polyacrylic acid, d) a water-soluble polymer compound containing sodium carboxymethylcellulose, e) a glycerin-containing wetting agent, f) a crosslinking agent, g) hydrochloric acid, and h) water, and the amount of glycerin blended in the adhesive layer is more than 15 times and 18 times or less on a mass basis relative to the amount of ethylene glycol salicylate blended.

Description

Patch preparation

Technical Field

The present invention relates to an aqueous patch, and more particularly to an aqueous patch which has good adhesion even though it is aqueous, and in which ethylene glycol salicylate is incorporated with good stability and has a moderate degree of crosslinking.

Background

A patch using a water-containing adhesive base (referred to as a water-containing patch in the present specification) generally called a "gel patch" is one of patches having a patch layer (adhesive layer) containing an active ingredient such as a drug on a support such as a nonwoven fabric. The gel paste has a problem that, since a hydrous adhesive base is used for the paste layer, although the skin irritation is low, the adhesive force is weak, and particularly, as the moisture in the paste layer is volatilized and dissipated, the adhesive force is reduced with time and is easily peeled from the skin.

In order to solve such a problem, the following techniques are known: an emulsion (also referred to as emulsion) base in which an alkyl acrylate copolymer known as one component constituting a nonaqueous (also referred to as hydrophobic or lipophilic) adhesive is dispersed is compounded in a paste layer (adhesive layer) of an aqueous adhesive patch.

For example, patent document 1 discloses a patch (comparative product) prepared by blending a gel paste base (paste) with 1% methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name: nikasol TS-620, manufactured by Nippon carbide industries, ltd.).

Patent document 2 discloses a water-containing external patch which is intended to provide a water-containing patch that exhibits adhesion and re-adhesion when stuck for a long period of time, suppresses curing accompanying water loss and reduction in softness, and suppresses breakage of a support during peeling, and which contains a water-dispersible surfactant in an amount of 0.01 to 10.0 mass% and a methyl acrylate/2-ethylhexyl acrylate copolymer in an amount of 5.0 to 10 mass% relative to the entire composition for a water-containing external patch.

Patent document 3 discloses a gel paste, and an object thereof is to provide a gel paste having sufficient adhesion even when the water content of the gel paste decreases with the lapse of time, and containing a partially neutralized product of polyacrylic acid, a 2.5 to 10 times by mass (5 to 25% by mass based on the paste) of a methyl acrylate/2-ethylhexyl acrylate copolymer and polyacrylic acid of the neutralized product.

Patent document 4 discloses a gel paste, the object of which is to provide a gel paste capable of releasing a release liner with a smaller force, the gel paste containing a surfactant such as poly (methyl acrylate/2-ethylhexyl acrylate) and polyethylene glycol fatty acid ester.

Patent document 5 discloses a cold-hot sheet obtained by using an adhesive composition containing 1.5 wt% of an acrylic resin emulsion (trade name: nikasol TS-620) and 6.2 wt% of sodium polyacrylate.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 9-208462

Patent document 2: japanese patent No. 5650684

Patent document 3: japanese patent No. 5921779 Specification

Patent document 4: PCT International publication No. 2016/104227

Patent document 5: japanese patent laid-open publication No. 2002-104957

Disclosure of Invention

Problems to be solved by the invention

As described above, it is known that an alkyl acrylate copolymer such as a methyl acrylate/2-ethylhexyl acrylate copolymer is incorporated in the adhesive layer in order to improve the adhesive durability of the aqueous patch. However, glycol salicylate has a problem in terms of drug stability in an aqueous solvent, that is, stability and adhesion to a drug in an aqueous patch containing glycol salicylate have not been sufficiently satisfactory.

Technical scheme for solving problems

The present inventors have intensively studied to solve the above problems, and as a result, they have found that the above problems can be solved by adjusting the pH of an adhesive agent (paste), particularly by adding hydrochloric acid when adjusting the pH, in order to achieve both stability of ethylene glycol salicylate in a water-containing adhesive patch, improvement of the adhesiveness of a preparation, and an appropriate degree of crosslinking, and have completed the present invention.

That is, the present invention relates to an aqueous adhesive patch comprising a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, wherein the adhesive layer contains the following components a) to h):

a) Glycol salicylate, glycol ester,

b) An alkyl (meth) acrylate copolymer,

c) Partially neutralized polyacrylic acid,

d) A water-soluble high molecular compound containing sodium carboxymethylcellulose,

e) A humectant containing glycerin,

f) A cross-linking agent,

g) Hydrochloric acid, and

h) The amount of water is controlled by the amount of water,

and the amount of glycerin blended in the adhesive layer is more than 15 times and not more than 18 times on a mass basis with respect to the amount of ethylene glycol salicylate blended.

Further, according to the present invention, there is provided the following embodiments:

1) The aqueous patch is characterized in that the adhesive layer has a pH value of 4.00-4.85.

2) The aqueous patch is prepared from the following components in a ratio of, when the total mass of the adhesive layer is 100 mass%:

a) 0.1 to 30 mass% of glycol salicylate,

b) 0.1 to 5 mass% of an alkyl (meth) acrylate copolymer,

c) 3.5 to 4.5 mass% of partially neutralized polyacrylic acid,

d) 2.0 to 30 mass% of a water-soluble polymer compound containing sodium carboxymethylcellulose,

e) 30 to 70 mass% of a glycerin-containing wetting agent,

f) 0.01 to 6.0 mass% of a crosslinking agent,

g) 0.1 to 1.5 mass% of hydrochloric acid,

h) 10 to 90 mass% of water.

3) The aqueous patch is characterized in that the swelling degree of the adhesive layer calculated by the ratio of the weight of the adhesive layer after being immersed and left standing in purified water for 24 hours to the weight of the adhesive layer before being immersed and left standing is less than 50.

4) The water-containing patch is preserved under the following conditions: the reduction of the residual ratio (%) of ethylene glycol salicylate after storage at 60 ℃ for 2 weeks was less than 5%.

In addition, the following can be mentioned as examples of preferred embodiments of the present invention.

(i) The aqueous patch is characterized in that the total amount of the partially neutralized polyacrylic acid and the sodium carboxymethylcellulose in the adhesive layer is 7% by mass or less based on the total mass of the adhesive layer, the amount of the partially neutralized polyacrylic acid is 3.5% by mass or more of the adhesive layer, and the amount of the sodium carboxymethylcellulose is 2.0% by mass or more.

(ii) The alkyl (meth) acrylate is a copolymer of a monomer mixture containing a monomer A that becomes a polymer having a glass transition temperature (Tg) of 270K or higher when homopolymerizing the monomer A, and a monomer B that becomes a polymer having a glass transition temperature (Tg) of 220K or lower when homopolymerizing the monomer B.

(iii) The aqueous patch has a degree of neutralization of 30-65% by a partially neutralized polyacrylic acid, and has a viscosity of 450-650 mPas in a 0.2 mass% aqueous solution.

(iv) The aqueous patch is characterized in that a 1 mass% aqueous solution of sodium carboxymethylcellulose has a viscosity of 1,000-3,000mPa · s and a degree of ester substitution of 0.60-0.95.

(v) The aqueous patch is characterized in that the crosslinking agent is an aluminum compound which is hardly soluble.

(vi) The aqueous patch is characterized in that the adhesive layer is formed from an adhesive layer-forming composition containing the components a) to h) and having a viscosity of 90 to 250Pa · s.

(vii) The aqueous patch, wherein the adhesive layer further contains i) sodium ethylenediaminetetraacetate hydrate as a chelating agent.

Effects of the invention

According to the present invention, an aqueous adhesive agent can be provided, which is an aqueous adhesive agent containing ethylene glycol salicylate in an adhesive agent layer, wherein the ethylene glycol salicylate as an active ingredient is stable with time, the adhesive force of the agent is high, and the crosslinking degree is good by adding hydrochloric acid to the adhesive agent layer.

Further, according to the present invention, it is possible to provide an aqueous adhesive patch which can maintain adhesion even after moisture in an adhesive layer is volatilized, has low skin irritation, has low adhesion between pastes, and can be attached to the skin again.

Detailed Description

As described above, the present inventors have found that in an aqueous adhesive patch, particularly an aqueous adhesive patch in which a non-aqueous adhesive base is incorporated in a plaster layer (adhesive layer) of an aqueous adhesive patch, the pH of the adhesive (plaster) is adjusted by incorporating an inorganic acid, i.e., hydrochloric acid, in the adhesive layer, and specifically, the stability of a drug in the presence of water, i.e., ethylene glycol salicylate, can be improved by inclining the pH of the adhesive layer from the neutral side to the acidic side. In particular, it has been found that, surprisingly, the incorporation of hydrochloric acid, in addition to the stability of the drug, improves the degree of crosslinking and the adhesion, which is difficult to satisfy with other acids.

The configuration of the aqueous adhesive patch of the present invention will be described below.

The aqueous adhesive patch of the present invention (hereinafter, also simply referred to as "patch") includes a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer.

The shape of the patch, particularly the shape of the preparation portion including the support and the adhesive layer provided on the support, is not particularly limited, and various shapes such as a square (square, rectangle, etc.), a quadrangle (trapezoid, rhombus, etc.), a polygon, a circle, an ellipse, a semicircle, a triangle, a crescent, and a combination thereof can be selected depending on the adhesion site.

The area of the patch (particularly, the preparation part) can be appropriately determined, and can be set to, for example, 2 to 300cm in consideration of the amount of the active ingredient incorporated in the adhesive layer and the like ² The range of (1).

[ adhesive layer ]

The adhesive layer in the aqueous adhesive patch of the present invention is required to contain a) ethylene glycol salicylate, b) a copolymer of (meth) acrylic acid alkyl ester, c) a partially neutralized polyacrylic acid, d) a water-soluble polymer containing sodium carboxymethylcellulose, e) a humectant containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water.

The aqueous adhesive patch of the present invention is characterized in that the aqueous adhesive layer contains a hydrophilic acrylic adhesive, i.e., c) a partially neutralized polyacrylic acid, which will be described later, and b) an alkyl (meth) acrylate copolymer, which normally constitutes a non-aqueous acrylic adhesive.

Generally, as an adhesive used in an adhesive layer (paste layer) of an aqueous adhesive patch, a hydrophilic acrylic adhesive such as polyacrylic acid, a partially neutralized polyacrylic acid, sodium polyacrylate, and an N-vinylacetamide/sodium acrylate copolymer resin is widely used. From the viewpoint of high affinity with the hydrophilic acrylic adhesive and uniform kneading, an acrylic or methacrylic emulsion adhesive is preferably added as the nonaqueous adhesive to be added to the aqueous adhesive layer of the aqueous patch.

In the present specification, the term "alkyl (meth) acrylate copolymer" is intended to include both alkyl esters of acrylic acid and methacrylic acid, and the term "acrylic adhesive" also includes both acrylic adhesives and methacrylic adhesives.

< a) glycol Salicylate >

The adhesive layer in the aqueous patch of the present invention contains ethylene glycol salicylate (also referred to as ethylene glycol salicylate) as an active ingredient.

Further, the following components may be used in combination, if necessary, in addition to ethylene glycol salicylate: nonsteroidal anti-inflammatory agents such as felbinac, flurbiprofen, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, ibuprofen, and esters thereof; antihistamines such as diphenhydramine and chlorphenamine; analgesic agents 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; cola, blood pressure lowering drugs; vasodilators such as nitroglycerin and isosorbide dinitrate; vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octylthiamine, and riboflavin butyrate, and prostaglandins; scopolamine, fentanyl, capsicum extract, vanillylnonanamide, capsaicin, dl-camphor, etc.

When the amount of the ethylene glycol salicylate to be blended and the other active ingredients to be contained are contained, the total blending amount of the ethylene glycol salicylate and the other active ingredients may be appropriately determined depending on the kind of the other active ingredients, and for example, may be set to 0.1% by mass or more and 30% by mass or less, or 0.5% by mass or more and 15% by mass or less, based on the total mass of the adhesive layer of the aqueous patch.

< b) alkyl (meth) acrylate copolymer >

The alkyl (meth) acrylate copolymer (nonaqueous adhesive base) constituting the nonaqueous acrylic adhesive is a copolymer composed of the following monomers: as a component for exhibiting adhesion, a monomer having 2 to 9 carbon atoms in a (methyl) alkyl ester, which becomes a polymer having a glass transition temperature (Tg) of-55 ℃ (218K) or less upon homopolymerization; a monomer which becomes a polymer having a Tg of 8 to 165 ℃ (281 to 438K) at the time of homopolymerization as a component for improving cohesive force; and, if necessary, a monomer having a functional group such as a crosslinking point such as a carboxyl group or a hydroxyl group (an example of the monomer is shown in table 1).

[ Table 1]

In addition, a homopolymer obtained by polymerizing only a monomer exhibiting adhesion has high adhesion but low mechanical strength, and a copolymer having improved mechanical strength by copolymerization with a monomer improving cohesion is generally used as an adhesive.

Examples of the monomers showing adhesion shown in table 1 above include, but are not limited to, the monomers having higher adhesion: butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate, and the like having a Tg of 220K or less when homopolymerizing the monomer (homopolymer). Among them, 2-ethylhexyl acrylate, which has been used as a pharmaceutical additive and has high adhesion (low Tg of homopolymer), can be preferably used.

Further, as the monomer for increasing the cohesive force (the Tg of the homopolymer is 270K or more), the monomers listed in table 1 are exemplified, and among them, methyl acrylate having high mechanical strength and not significantly reducing the adhesiveness (the Tg of the homopolymer is relatively low) is preferable in the present invention.

Further, as exemplified in the prior art, examples of commercially available alkyl acrylate copolymers used for the patch include Nikasol (registered trademark) TS-620 (methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion) manufactured by Nippon carbide industries, ltd. The methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion is a standard recorded product of medicinal additives.

In the adhesive layer of the aqueous adhesive patch of the present invention, the amount of the alkyl (meth) acrylate copolymer to be blended (the amount converted to solid content in the case of emulsion) may be, for example, 0.1 mass% or more and 5 mass% or less, 0.5 mass% or more and 4.5 mass% or less, or 1.0 mass% or more and 4.5 mass% or less, based on the total mass of the adhesive layer of the aqueous adhesive patch.

The blending ratio of the acrylic hydrophilic adhesive to be described later may be set, for example, in mass ratios of alkyl acrylate copolymer to acrylic hydrophilic adhesive = 1.5: 1 to 1: 10, alkyl acrylate copolymer to acrylic hydrophilic adhesive = 1.5: 1 to 1: 5, alkyl acrylate copolymer to acrylic hydrophilic adhesive = 1.5: 1 to 1: 1, and the like.

< c) partial neutralization of polyacrylic acid >

The adhesive layer of the aqueous patch of the present invention contains a partially neutralized product of polyacrylic acid as an acrylic hydrophilic adhesive.

Further, if necessary, an acrylic hydrophilic adhesive other than partially neutralized polyacrylic acid may be blended in the adhesive layer. In general, examples of the acrylic hydrophilic adhesive include water-soluble (meth) acrylic polymers. The water-soluble (meth) acrylic polymer is a polymer obtained by polymerizing a (meth) acryloyl group-containing monomer having a water-soluble functional group (hydrophilic group), and exhibits adhesiveness when incorporated into an adhesive layer together with water. The water-soluble (meth) acrylic polymer may be, for example, a partially neutralized product of the above polyacrylic acid, a homopolymer such as polyacrylic acid, or a copolymer such as an N-vinylacetamide/sodium acrylate copolymer resin.

The polyacrylic acid partial neutralizer may be a polyacrylic acid complete neutralizer, a polyacrylic acid partial neutralizer, or a mixture thereof. That is, in the present specification, the "partially neutralized product of polyacrylic acid" includes not only a neutralized product in which a part of acid groups of polyacrylic acid is neutralized, but also a neutralized product in which all acid groups of polyacrylic acid are neutralized. The partially neutralized polyacrylic acid refers to polyacrylate, and for example, sodium salt, potassium salt, calcium salt, ammonium salt, and the like can be used. For example, VISCOMATE NP-800 (available from Showa Denko K.K.) can be mentioned.

In a preferred embodiment, the partially neutralized polyacrylic acid used in the present invention is a partially neutralized polyacrylic acid having a degree of neutralization of 30% to 65%. When the partially neutralized polyacrylic acid is prepared as an aqueous solution having a concentration of 0.2 mass%, it is preferable to use a partially neutralized polyacrylic acid having a viscosity of 450 to 650 mPas at 20 ℃.

By using the polyacrylic acid partial neutralizer, particularly by using the polyacrylic acid partial neutralizer having such a neutralization degree and viscosity, adhesion to the skin can be further exhibited when water is contained, and crosslinking with the crosslinking agent can be further promoted, and dissolution in water can be prevented.

The amount of the partially neutralized polyacrylic acid and the total amount of the partially neutralized polyacrylic acid and the other acrylic hydrophilic adhesive when the adhesive contains the other acrylic hydrophilic adhesive may be, for example, 0.1 to 10 mass%, 1 to 8 mass%, based on the total mass of the adhesive layer of the aqueous adhesive patch.

For example, the amount of the partially neutralized polyacrylic acid may be 3.5 mass% or more and 4.5 mass% or less based on the total mass of the adhesive layer.

< d) Water-soluble Polymer Compound >

The adhesive layer of the patch of the present invention must contain sodium carboxymethylcellulose (sodium carboxymethylcellulose) as the water-soluble polymer compound.

By using sodium carboxymethylcellulose, the shape retention of the preparation can be further maintained, and the preparation has thixotropy, and can further reduce pain in peeling.

In a preferred embodiment, the viscosity of the 1 mass% aqueous solution of the sodium carboxymethylcellulose used in the present invention at 20 ℃ may be 1,000 to 3,000mpa · s. The sodium carboxymethylcellulose preferably has an ester substitution degree of 0.60 to 0.95.

In addition, a water-soluble polymer compound other than sodium carboxymethylcellulose may be contained, and examples thereof include gelatin, agar, polyvinyl alcohol (including partially saponified products), polyvinylpyrrolidone, propylene carbonate, carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium alginate, maleic anhydride copolymer, and carrageenan. These may be used in combination with sodium carboxymethylcellulose in 1 kind or in appropriate combination of 2 or more kinds.

The amount of the water-soluble polymer compound to be blended is usually set in a range of, for example, 1.0 mass% to 30 mass%, 2.0 mass% to 30 mass%, 2.5 mass% to 20 mass%, or 3.0 mass% to 10 mass% based on the total mass of the adhesive agent layer of the water-containing adhesive patch.

For example, the amount of sodium carboxymethylcellulose added may be 2.0 mass% or more and 3.5 mass% or less based on the total mass of the adhesive layer.

< e) humectant containing glycerin >

In order to suppress evaporation of water with time, a humectant (also referred to as a humectant) is incorporated in the adhesive layer of the aqueous patch of the present invention.

As the humectant, glycerin must be added to the adhesive layer of the patch of the present invention.

In addition, can also contain glycerin other wetting agent, as its examples can be cited, D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propylene glycol, 1,4-butylene glycol, maltitol, xylitol and other polyols. These may be used in combination with glycerin in an appropriate combination of 1 or 2 or more.

The amount of the humectant to be blended is usually set in a range of, for example, 30 to 70 mass%, 40 to 60 mass%, 40 to 50 mass%, or 45 to 55 mass%, based on the total mass of the adhesive layer of the water-containing adhesive patch.

In the present invention, the amount of glycerin to be blended in the adhesive agent layer is more than 15 times and 18 times or less, for example, 15.5 times or more and 18.0 times or less, 16.0 times or more and 17.9 times or less, 16.5 times or more and 17.9 times or less, 16.7 times or more and 17.9 times or less, 17.0 times or more and 17.9 times or less, 17.5 times or more and 17.9 times or less, or 15.5 times or more and 17 times or less, on a mass basis, relative to the amount of the ethylene salicylate a) described above. When the amount of glycerin is small, the moisture retention becomes insufficient, and the moisture of the adhesive is easily volatilized and dissipated; in addition, when the amount of glycerin to be blended is large, the stability of the drug may be lowered. 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 a problem may occur in safety.

< f) crosslinking agent >

The crosslinking agent to be incorporated into the adhesive layer of the aqueous adhesive patch of the present invention includes polyvalent metal salts, and among them, polyvalent metal compounds containing aluminum. Examples thereof include hydroxides such as aluminum hydroxide and aluminum magnesium hydroxide; normal salts of inorganic or organic acids such as aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxyaluminum aminoacetal), dihydroxyaluminum aminoacetate, synthetic aluminum silicate, dried aluminum hydroxide gel, kaolin, aluminum stearate, or basic salts thereof; double salts such as aluminum alum; aluminates such as sodium aluminate; inorganic aluminum complex salt and organic aluminum chelate; synthetic hydrotalcite, magnesium aluminum silicate, magnesium aluminum metasilicate, and other polyvalent metal compounds, and these may be used alone or in combination of 2 or more.

Among them, aluminum dihydroxyglycinate, synthetic aluminum silicate and dried aluminum hydroxide gel, which are hardly soluble aluminum compounds, are preferably used.

The amount of the crosslinking agent to be blended may be appropriately selected in consideration of the degree of crosslinking that can cause the adhesive agent to remain on the skin or to be sticky. Examples of the range include 0.01 to 6.0 mass%, 0.01 to 4.0 mass%, or 0.01 to 2.0 mass% based on the total mass of the adhesive layer of the aqueous adhesive patch.

< g) hydrochloric acid >

The aqueous patch of the present invention is characterized in that hydrochloric acid is added to the adhesive layer.

The amount of the hydrochloric acid to be added may be, for example, in the range of 0.1 to 1.5% by mass based on the total mass of the adhesive layer of the aqueous patch.

Further, if hydrochloric acid is not added but only other acids such as acids listed in < organic acid > described later and inorganic acids other than hydrochloric acid are added, it is difficult to obtain both appropriate crosslinkability and good adhesion. For example, when tartaric acid is used, good adhesion cannot be obtained, and when phosphoric acid is used, the result is inferior to that in the case of using hydrochloric acid from the viewpoint of stability of ethylene glycol salicylate and expression of appropriate crosslinking property, and from the viewpoint of stability, a larger amount of blending is sometimes required in order to obtain the same effect as that in the case of using hydrochloric acid. Phosphoric acid is preferably not added, but may be added within a range not affecting the effect of the present invention, particularly the degree of crosslinking.

< h) Water >

As described above, the aqueous patch of the present invention contains water (moisture) in the adhesive layer. In the present specification, "water" contained in the adhesive layer includes not only water that is separately added as water form at the time of forming the adhesive layer, but also water contained in the form of emulsion, aqueous solution, or the like. The amount of water to be added is not particularly limited, and may be set, for example, in the range of 10 mass% to 90 mass%, 15 mass% to 70 mass%, 20 mass% to 50 mass%, based on the total mass of the adhesive layer of the aqueous adhesive patch. The amount of water to be added is a value at the time of preparation of the adhesive patch or before the adhesive patch is attached, and is not limited to this when water is volatilized from the adhesive layer along with the attaching process.

< i) chelating agent >

The adhesive layer of the aqueous patch of the present invention may contain a chelating agent for controlling the viscosity of the paste during production. An example of a chelating agent is sodium edetate (disodium edetate).

The amount of the chelating agent to be added is usually set in the range of, for example, 0.01 to 1 mass%, 0.1 to 0.3 mass%, based on the total mass of the adhesive layer of the water-containing adhesive patch.

< organic solvent >

In the adhesive layer of the aqueous adhesive patch of the present invention, an organic solvent may be blended as an ingredient capable of assisting dissolution of an active ingredient such as a drug (i.e., functioning as a dissolution assistant) and preventing precipitation of the active ingredient from the adhesive layer.

Examples of such an organic solvent (dissolution aid) include: crotamiton; n-methyl-2-pyrrolidone; polyalkylene glycols such as polyethylene glycol 400 (polyethylene glycol) and polytetramethylene glycol; polyvinyl alcohol; fatty acid esters such as diethyl adipate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, and oleyl oleate; polyoxyalkylene fatty acid esters and the like; sorbitan esters; 1,3-butanediol and other polyols; dimethylformamide; dimethyl sulfoxide, and the like. These may be used singly or in combination of two or more.

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

< organic acid >

The adhesive layer of the aqueous patch of the present invention may contain an organic acid. Examples of the organic acid which can be blended include tartaric acid, citric acid, lactic acid, gluconic acid, glycolic acid, malic acid, fumaric acid, meta-sulfonic acid, maleic acid, acetic acid, and the like, and these can be used alone or in combination of 2 or more.

When an organic acid is used, the amount of the organic acid to be added may be, for example, 0.1 mass% or more and 5 mass% or less based on the total mass of the adhesive layer of the aqueous patch. It is expected that the use of the organic acid in such a blending amount range can suppress the problems of insufficient crosslinking property, dissolution of the adhesive and stickiness, and on the other hand, can suppress the problems of excessive crosslinking reaction and hardening of the paste, which makes the production impossible.

< surfactant >

A surfactant may be incorporated into the adhesive layer of the aqueous patch of the present invention. Examples of such surfactants include polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol dioleate, and polypropylene glycol dioleate; sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan monooleate, and ethylene oxide adducts thereof; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, and polyoxyethylene sorbitan triisostearate; polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyalkylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethylhexyl ether, and polyoxyethylene isodecyl ether; polyoxyethylene alkylphenol ethers such as polyoxyethylene styrenated phenyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene distyrenated phenyl ether, and polyoxyethylene tribenzylphenyl ether; glycerin fatty acid esters such as glycerin monostearate and glycerin monooleate; nonionic surfactants such as polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, and lecithin. These substances may be used alone in 1 kind, or in appropriate combination of 2 or more kinds.

When these surfactants are used, the amount to be blended may be, for example, in the range of 0.001 mass% or more and 10 mass% or less, or 0.01 mass% or more and 5 mass% or less, based on the total mass of the adhesive layer of the aqueous adhesive patch.

< other optional ingredients >

The adhesive layer of the aqueous patch of the present invention may further contain, as other optional components, the following components which are generally incorporated in the adhesive layer of a conventional aqueous patch (gel paste) or non-aqueous patch (adhesive tape): antioxidants such as dibutylhydroxytoluene (BHT), inorganic powders such as calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, and calcium sulfate, ultraviolet absorbers such as benzoylmethane derivatives, colorants, perfumes, and preservatives. When these optional components are used, they may be used each alone or in combination of two or more, for example, in a range of 0.01 mass% or more and 1 mass% or less, based on the total mass of the adhesive layer of the aqueous patch.

[ support ]

Examples of the support used in the aqueous adhesive patch of the present invention include a support having flexibility such as a film, a nonwoven fabric, japanese paper, a cotton fabric, a knitted fabric, a woven fabric, and a laminated composite of a nonwoven fabric and a film. These supports are preferably made of a flexible material that can adhere to the skin and follow the movement of the skin, and that can suppress the occurrence of skin spots and the like after being attached for a long time. Examples of the material of the support include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, rayon acetate, rayon, a rayon/polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, acrylic urethane, ester urethane, ether urethane, a styrene-isoprene-styrene copolymer, a styrene-butadiene-styrene copolymer, a styrene-ethylene-propylene-styrene copolymer, a styrene-butadiene rubber, an ethylene-vinyl acetate copolymer, cellophane, and the like.

Further, by coloring a support such as a cloth with a coloring agent into a color tone such as a skin color, a difference between the color tone and the skin color at the time of sticking can be reduced. In addition, a plastic film having excellent transparency can be used from the viewpoint of easily transmitting the color tone of the skin to be stuck.

The thickness of the support is usually about 5 μm to 1 mm. When the support is a cloth, the thickness thereof is preferably 50 to 1mm, more preferably 100 to 800 μm, and still more preferably 200 to 700 μm. When the support is a plastic film, the thickness thereof is preferably 10 to 300. Mu.m, more preferably 12 to 200. Mu.m, and still more preferably 15 to 150. Mu.m. In the case where the support is extremely thin, having a thickness of about 5 μm to 30 μm, it is preferable to provide a releasable carrier film layer on the opposite surface of the adhesive layer formed on the support, because the workability as an adhesive patch is improved. However, if the thickness of the support is less than 5 μm, the strength and handling properties of the patch are reduced, and the patch is difficult to adhere to the skin, and may be broken by contact with other members or the like, or may be peeled off from the skin in a short time by contact with water in a bath or the like. Further, if the thickness of the support is too large (more than 1 mm), the adhesive patch is difficult to follow the movement of the skin, and a peeling starting point is easily formed at the edge portion of the adhesive patch, and therefore, there is a possibility that the adhesive patch is peeled from the skin in a short time or a feeling of discomfort is increased during the application.

When the support is a thin film, one or both surfaces of the support may be subjected to a treatment such as sandblasting or corona treatment in order to improve the anchoring properties between the adhesive and the support.

In addition, the support may be provided with irregularities on one or both surfaces thereof by a method other than sandblasting, in order to facilitate removal from the packaging material.

[ Release liner ]

Release liner as the release liner (also referred to as a release layer or release paper) used in the aqueous adhesive patch of the present invention, a material that is difficult to absorb or adsorb a drug or the like in the adhesive layer is preferable, and a material that is commonly used in the technical field of adhesive patches can be used.

For example, plastic films such as polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unstretched, stretched, etc.), polyethylene, polyurethane, polyvinyl chloride, polystyrene, etc.; high-quality paper, such as cellophane, parchment, kraft paper, etc. or synthetic paper; release paper obtained by coating the plastic film, paper, synthetic fiber, or the like with a release agent having a release property such as silicone resin or fluororesin; aluminum foil; a laminated paper obtained by laminating these films and sheets in various ways, and a colorless or colored sheet such as a laminated release paper coated with a release agent on the laminated paper. Further, the release liner may be provided with irregularities for easy removal from the packaging material.

The thickness of these release liners is not particularly limited, but is usually 10 μm to 1mm, for example, 20 μm to 500 μm, preferably 40 μm to 200 μm.

Further, the release force when the adhesive layer is released from the release liner is preferably a release force in a specific range. This is because, if the release force of the adhesive layer from the release liner is too weak, the adhesive layer (i.e., patch) may fall off from the release liner if the patch gets stuck on the packaging material when the patch in the package is taken out. Further, if the release force of the adhesive layer (adhesive patch) from the release liner is too strong, the handling property during use may be deteriorated. The release force of the adhesive layer from the release liner varies depending on the type of release liner used, and may be set to, for example, 0.01N/15mm to 0.5N/15mm.

[ method for producing aqueous adhesive preparation ]

The hydrous adhesive patch of the present invention can be produced by a conventionally known method. For example, the production can be performed through the following steps (i) and (ii).

(i) The method for producing the pressure-sensitive adhesive sheet includes a step of applying a pressure-sensitive adhesive layer-forming composition to a support to form a pressure-sensitive adhesive layer, and a step of bonding the pressure-sensitive adhesive layer formed on the support to a release liner.

(ii) The method for producing the pressure-sensitive adhesive layer includes a step of applying a pressure-sensitive adhesive layer-forming composition to a release liner to form a pressure-sensitive adhesive layer, and a step of bonding the pressure-sensitive adhesive layer formed on the release liner to a support.

The thickness of the adhesive layer is not particularly limited, but may be usually set to 10 μm to 1000 μm, for example, about 20 μm to 800 μm.

The adhesive layer-forming composition is a semisolid composition containing the following components contained in the adhesive layer: the adhesive composition may contain, as necessary, ethylene glycol salicylate (other active ingredient), alkyl (meth) acrylate copolymer, partially neutralized polyacrylic acid (other acrylic hydrophilic adhesive), water-soluble high molecular compound containing sodium carboxymethylcellulose, humectant containing glycerin, crosslinking agent, hydrochloric acid, water, and further a chelating agent, an organic solvent, an organic acid, a surfactant, and other optional ingredients.

From the viewpoint of workability at the time of production, the adhesive layer-forming composition preferably has a viscosity of 90 to 250Pa · s, 100 to 250Pa · s, and more preferably 130 to 250Pa · s at 20 to 30 ℃. If the viscosity is less than 90 pas, the paste may penetrate when the woven or knitted fabric is used as a support. If the viscosity is more than 250 pas, the elongation becomes difficult.

[ pH value of adhesive layer containing aqueous adhesive ]

In the aqueous patch of the present invention, the pH of the adhesive layer is preferably on the acidic side (less than 6.0), and may be 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 of the adhesive layer within a preferred range, the stability of ethylene glycol salicylate can be improved, and the applicability (spreadability) of the adhesive can be improved, whereby an aqueous adhesive patch having excellent productivity of the patch can be produced.

The pH of the adhesive layer can be measured at a temperature of 20 to 25 ℃ by a pH measurement method according to general test methods in japanese pharmacopoeia, for example.

Further, the pH of a liquid obtained by diluting the adhesive (paste) with water may be treated as the pH 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 patch, the adhesive is scraped off from the exposed adhesive layer using a spatula or the like, and purified water is added to the collected adhesive, for example, diluted 20 times to prepare a uniform solution. The resulting solution was incubated at room temperature (25.0. + -. 0.2 ℃ C.), a glass composite electrode of a calibrated pH meter was inserted into the solution, and the pH value was measured.

< degree of swelling >

The adhesive layer (adhesive layer-forming composition) of the present invention preferably has a swelling degree of the adhesive layer of less than 50, which is calculated as the ratio of the weight of the adhesive layer after being left standing for 24 hours after being soaked in purified water and left standing, to the weight of the adhesive layer before being left standing after being soaked.

The measurement and calculation steps of the swelling degree are, for example, as follows: the hydrous adhesive patch and the support were cut into predetermined sizes, and the weights (initial hydrous adhesive patch (liner-peeled) weight and initial support weight) of the hydrous adhesive patch and the support were measured in a state where the liner was peeled. Then, these were immersed in purified water and left to stand for 24 hours, and the weights (weight of the aqueous adhesive patch (release liner) after the immersion and left to stand, and weight of the support after the standing of the purified water) after the immersion and left to stand for 24 hours were measured, respectively, whereby the swelling degree was calculated from the following equation.

Degree of swelling of adhesive layer = (weight of aqueous patch after standing with purified water (liner release) — weight of support after standing with purified water)/(weight of initial aqueous patch after standing with purified water (liner release) — weight of initial support)

By setting the swelling degree of the adhesive layer to less than 50, an aqueous patch can be provided which maintains the shape retention of the adhesive layer and suppresses the possibility of the adhesive layer remaining on the skin after peeling.

Examples

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

< production of adhesive >

The patches (preparations) of examples, comparative examples, and production examples were produced by the following procedures.

Example 1:

1.5 parts by mass of polyvinyl alcohol was dissolved in purified water (aqueous phase).

Subsequently, 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).

Further, 4 parts by mass of a partially neutralized polyacrylic acid (viscosity at 20 ℃ C. Is 547 mPas in the case of an aqueous solution having a neutralization degree of 35% and a viscosity of 0.2% by mass), 3 parts by mass of sodium carboxymethylcellulose (ester substitution degree: 0.82, viscosity: 1% by mass of an aqueous solution having a viscosity of 1,840 mPas at 20 ℃ C.), and 0.25 part by mass of aluminum dihydroxyglycinate were uniformly dispersed in 22 parts by mass of concentrated glycerin (glycerin phase).

A water phase, 7 parts by mass of methyl acrylate/2-ethylhexyl acrylate copolymer emulsion, 0.20 part by mass of sodium ethylenediaminetetraacetate hydrate, 30 parts by mass of a 70% aqueous solution of D-sorbitol, and 0.9 part by mass of hydrochloric acid diluted with purified water (balance) were sequentially added to a stirrer to be uniformly dispersed or dissolved. Wherein, the oil phase and the glycerol phase are added in sequence and mixed evenly. Further, 1 part by mass of lactic acid was added and kneaded uniformly under degassing conditions to obtain an adhesive layer-forming composition of example 1. Further, using the obtained adhesive layer-forming composition, test example 4 (viscosity of adhesive) described later was performed.

The obtained adhesive layer-forming composition was spread on the silicon surface of a spacer (PET (75 μm) with silicon treated on one side) by a spreader, and after laminating a knitted fabric support (made of polyester), it was cured at 40 ℃ for 1 week. After aging, the mixture was punched out into an arbitrary shape to obtain the preparation of example 1.

Examples 2 to 9, comparative examples 1 to 9, production examples 1 to 20:

preparations of examples 2 to 9, comparative examples 1 to 9, and production examples 1 to 20 were obtained in the same manner as in example 1 except that the kinds and blending amounts of the respective components were changed as described in tables 2, 3, and 4 to 6. When phosphoric acid and tartaric acid are added, they are added at the same time as hydrochloric acid. In addition, when glyceryl monostearate, polysorbate 80, polyoxyethylene hydrogenated castor oil 10, lauryl polyethylene glycol, polyoxyethylene oleyl ether, diisopropyl adipate, diethyl sebacate, isopropyl myristate, and isopropyl palmitate were added, the above components were added at the same time points as those of polyethylene glycol 400.

Test example 1 (measurement of pH of adhesive layer)

The pH of each preparation of examples and comparative examples was measured at 25.0. + -. 0.2 ℃ according to the pH measurement method of the general test method of Japanese pharmacopoeia. The obtained results are shown in tables 2 and 3.

Test example 2: evaluation of stability of ethylene glycol Salicylate (SG)

The stability of ethylene glycol salicylate was evaluated by measuring the content of ethylene glycol salicylate contained in the adhesive layer by a High Performance Liquid Chromatography (HPLC) method immediately after the preparation (initial) and after storage at 60 ℃ for 2 weeks (2W).

In detail, each of the preparations of examples and comparative examples was cut into 40mm × 40mm (16 cm) ² ) A release liner was peeled off, and gauze (medical gauze, type I,50 mm. Times.50 mm) was attached to the adhesive layer to prepare a test preparation.

27mL of methanol was used as an extraction solvent, and the test preparation was added thereto, and extraction was performed by shaking. The extract was filtered through a membrane filter having a pore size of 0.45 μm to prepare a sample solution.

The sample solutions were analyzed under the following HPLC conditions.

The stability of ethylene salicylate (% residue in the adhesive layer) was evaluated by comparing the relative amounts of the decomposition products by the sum of the peak area of ethylene salicylate (retention time about 11 minutes) and the peak areas other than that. Further, the reduction width of ethylene glycol salicylate (reduction width (%) from the initial value) after storage at 60 ℃ for 2 weeks (2W) was calculated from the initial value (residual% of ethylene glycol salicylate in the adhesive layer before storage). The obtained results are shown in tables 2 and 3.

Measuring wavelength: 240nm;

and (3) chromatographic column: mightysil RP-18 (150 mm. Times.4.6 mm, 5 μm);

column temperature: 30 ℃;

flow rate: 0.5mL/min;

mobile phase A: water/methanol =50/50;

analysis time: 30 minutes;

injection amount: 10 μ L.

In addition, the stability evaluation of ethylene glycol salicylate was carried out in such a manner that the storage condition at 40 ℃ for 6 months and the storage condition at 60 ℃ for 2 weeks were approximately equal to each other, and the stability of ethylene glycol salicylate (the reduction width (%) from the initial value) was preferably less than 5.0% at which no significant quality change was observed in the value after storage at 60 ℃ for 2 weeks (the reduction width (%) from the initial value).

Test example 3: adhesion test and initial adhesion by rolling ball method

The release liners of the respective formulations of examples and comparative examples (immediately after production) were peeled off to expose the adhesive layer, and the initial adhesive force of the adhesive layer by the rolling method was performed according to japanese pharmacopoeia general test method 6.12 adhesion test method 3.2. The average value (ball number) of n =3 was used as the value of the initial tack test by the rolling ball method. The obtained results are shown in tables 2 and 3.

In addition, the evaluation of initial tack by the rolling ball method reflects the adhesion of the adhesive layer, and the value thereof is preferably 15 or more.

Test example 4: viscosity of the adhesive

The adhesive layer-forming compositions of examples and comparative examples, which were produced in the order of < production of adhesive patch >, were measured for viscosity (measurement temperature 20 ℃ to 30 ℃) with a hand-held rotational viscometer before application of the release liner. The obtained results are shown in tables 2 and 3.

Test example 5: degree of crosslinking of adhesive layer

The preparations and supports of examples and comparative examples were cut into 12X 100mm pieces, and the weights (initial preparation weight, initial support weight) of the preparations were measured in a state where the release liner was peeled off, and the pieces were left to stand in a glass bottle filled with purified water (room temperature) for 24 hours. After standing, the preparation and the support were taken out from the purified water, and the weights (the weight of the preparation after the purified water was left standing and the weight of the support after the purified water was left standing) were measured to calculate the swelling degree of the paste (adhesive layer) from the following formula.

Swelling degree of paste = (weight of preparation after purified water is left to stand-weight of support after purified water is left to stand)/(weight of initial preparation-weight of 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. The degree of crosslinking is preferably + or more, and if it is. + -. Or-, the shape retention of the paste becomes insufficient, and a large amount of the paste may remain on the skin when peeled off after application.

< evaluation of degree of crosslinking >

++: the swelling degree is less than 10;

+: the swelling degree is more than 10 and less than 50;

+ -: the swelling degree is more than 50;

-: the paste was substantially dispersed in purified water and could not be removed.

Test example 6: manufacturability of

The ease of spreading the adhesive layer-forming compositions of examples and comparative examples, which were produced in the order of < production of adhesive patch >, on the silicon surface of the backing was evaluated according to the following evaluation criteria. The obtained results are shown in tables 2 and 3.

< evaluation of the production Property >

++: easy to extend;

+: can be extended;

+ -: can be extended but not stabilized;

-: it cannot be extended.

[ Table 2]

The amount of purified water is adjusted to make all the components added account for 100 mass parts

NT: the test was not carried out

[ Table 3]

NT: the test was not carried out

[ Table 4]

[ Table 5]

[ Table 6]

Adjusting the amount of purified water by adding 100 parts by mass of all the components

As shown in table 2, the preparations (aqueous adhesive patches) of the examples were prepared by adding a predetermined amount of hydrochloric acid, and in the evaluation of the stability of ethylene glycol salicylate as an active ingredient, the reduction width from the initial value after storage at 60 ℃ for 2 weeks was less than 5%, the initial rolling ball tack value was 15 or more, and the swelling degree as an index of the degree of crosslinking of the adhesive layer (paste) was less than 50 (+ or more), and thus the stability of the active ingredient, the adhesive force of the preparations, and the degree of crosslinking were all good.

On the other hand, as shown in table 3, in comparative example 1 and comparative example 7 which did not contain hydrochloric acid, the reduction width of ethylene salicylate from the initial value was more than 5%, and the preparation was poor in the stability of the active ingredient. In addition, in the case of adding phosphoric acid instead of hydrochloric acid (comparative examples 2 to 6), by increasing the amount of blending thereof, the stability of ethylene glycol salicylate was increased, but the degree of crosslinking was rather deteriorated; further, when tartaric acid was added in place of hydrochloric acid (comparative examples 8 to 9), the initial tack value by the rolling ball method 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, the following aqueous adhesive patch can be provided: in the aqueous patch containing glycol salicylate in the adhesive layer, the glycol salicylate as an effective component is stable with time even if the amount of the hydrochloric acid added is small, and the aqueous patch has a moderate degree of crosslinking, good adhesion and excellent manufacturability.

Claims

1. An aqueous adhesive patch comprising a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, wherein the adhesive layer contains the following components a) to h):

a) Glycol salicylate, glycol ester,

b) An alkyl (meth) acrylate copolymer,

c) Partially neutralized polyacrylic acid,

e) A humectant containing glycerin,

f) A cross-linking agent,

g) Hydrochloric acid, and

h) The amount of water is controlled by the amount of water,

and the amount of glycerin blended in the adhesive layer is more than 15 times and not more than 18 times the amount of ethylene glycol salicylate blended on a mass basis.

2. The aqueous patch according to claim 1, wherein the adhesive layer has a pH of 4.00 to 4.85.

3. The aqueous patch according to claim 1 or claim 2, wherein the adhesive layer is formulated in the following ratio when the total mass of the adhesive layer is 100% by mass:

a) 0.1 to 30 mass% of glycol salicylate,

b) 0.1 to 5 mass% of an alkyl (meth) acrylate copolymer,

c) 3.5 to 4.5 mass% of partially neutralized polyacrylic acid,

e) 30 to 70 mass% of a glycerin-containing wetting agent,

f) 0.01 to 6.0 mass% of a crosslinking agent,

g) 0.1 to 1.5 mass% of hydrochloric acid,

h) 10 to 90 mass% of water.

4. The aqueous patch according to any one of claims 1 to 3, wherein the degree of swelling of the adhesive layer calculated as the ratio of the weight of the adhesive layer after being immersed and left standing in the purified water for 24 hours to the weight of the adhesive layer before being immersed and left standing is less than 50.

5. The aqueous patch according to any one of claims 1 to 4, wherein the storage conditions are: the residual ratio (%) of ethylene glycol salicylate decreased by less than 5% after storage at 60 ℃ for 2 weeks.