TW202011993A - Hydrated adhesive skin patch - Google Patents

Abstract

There is provided a hydrated adhesive skin patch that keeps viscosity even after moisture in an adhesive layer evaporates. A hydrated adhesive skin patch to be combined with an acrylic acid alkyl ester copolymer in an adhesive layer, the acrylic acid alkyl ester copolymer being the copolymer of a monomer mixture comprising monomer A and monomer B. The monomer A is a polymer where a glassy-transition temperature (Tg) is 270K or more when the monomer A is homopolymerized while the monomer B is a polymer where a glassy-transition temperature (Tg) is 220K or less when the monomer B is homopolymerized. The ratio of the monomer A is 30 mass% or more and 50 mass% or less relative to the whole mass of the monomer mixture.

Description

Aqueous patch

The present invention relates to an aqueous patch. In detail, it relates to an aqueous patch that maintains a high adhesive force even after the water in the adhesive layer is scattered and has low skin irritation.

Adhesives that use water-based adhesive bases (referred to as aqueous-based adhesives in this specification), also known as "dressings", are provided on a support such as a nonwoven fabric with a paste layer (adhesive) containing active ingredients such as drugs Layer) is a kind of adhesive. The adhesive layer contains a water-based adhesive base, so although the skin irritation is low, the adhesion is weak, especially the adhesion will be reduced with the sway of the water in the paste layer over time, it is easier to self The problem of skin peeling. In order to solve this problem, there is known a technique in which an emulsion of an alkyl acrylate copolymer known as one of the components constituting a non-aqueous (also called hydrophobic and lipophilic) adhesive is dispersed ( (Also called emulsion) The base is formulated into the paste layer (adhesive layer) of the water-based adhesive.

For example, Patent Document 1 discloses a patch (comparative product), which is a 1% methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion (trade name NiKasol TS-620, Japan calcium carbide industry (share )) It is formulated into the base of the dressing (paste). Patent Document 2 discloses an aqueous external-use adhesive, which provides an adhesive and re-adhesive force capable of exhibiting long-term adhesion, suppressing hardening and loss of flexibility accompanying loss of moisture, and suppressing peeling The water-based adhesive agent of the fracture of the support is for the purpose of containing the water-dispersible surfactant at a ratio of 0.01% by mass or more and 10.0% by mass or less with respect to the entire composition of the aqueous system-use external adhesive agent. The composition for an aqueous external-use patch composition contains a methyl acrylate-2-ethylhexyl acrylate copolymer in a ratio of 5.0% by mass or more and 10% by mass or less. Patent Document 3 discloses a dressing that aims to provide a dressing that has sufficient adhesion even when the water content of the dressing decreases with time, and contains a polyacrylic acid neutralizer and the neutralizer 2.5 to 10 times the mass (5 to 25% by mass based on the paste) of methyl acrylate-2-ethylhexyl acrylate copolymer and polyacrylic acid. Patent Document 4 discloses a dressing which contains poly(methyl acrylate/2-ethylhexyl acrylate) and polyethylene for the purpose of providing a dressing capable of peeling off the release liner with less force. Surfactants such as glycol fatty acid esters. Patent Document 5 discloses the idea 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 Technical 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 the invention]

As described above, it is known that in order to improve the adhesion durability of the water-based adhesive, an alkyl acrylate copolymer such as methyl acrylate-2-ethylhexyl acrylate copolymer is blended with the adhesive layer. However, in the case where the amount of the copolymer described above is small, such as the patch disclosed in Patent Document 1, the initial viscosity and the persistent adhesion are not good due to the small amount of the formulation As a result, the desired effect of improving the adhesive force cannot be obtained, and even when the amount of formulation is increased, especially the adhesive force after the water in the adhesive layer has been evaporated is not enough compared with the patch. [Technical means to solve the problem]

The inventors conducted intensive research in order to solve the above-mentioned problems, and as a result, it was found that by blending the following copolymers as alkyl acrylate-based copolymers into the adhesive layer of the above-mentioned water-based adhesive agent, even the adhesive After the water in the layer is swayed, the adhesion will not decrease but will increase, and the skin irritation is also low, thus completing the present invention. The copolymer is formulated in the following manner: the glass transition temperature (Tg) when it is homopolymerized ) Is 30-50% by mass of the monomer of the polymer of 270 K or more, and the monomer of the polymer with a Tg of 220 K or less at the time of homopolymerization is adjusted so that the total amount of the two monomers becomes 100% by mass.

That is, the present invention relates to a water-based adhesive which contains a support, an adhesive layer provided on the support, and a release liner, The adhesive layer system contains the following components 1) to 6) as essential components. 1) Acrylic hydrophilic adhesive; 2) Alkyl acrylate copolymer, which is a copolymer containing a monomer mixture of monomer A and monomer B, When the above monomer A homopolymerizes the monomer A, it will become a polymer having a glass transition temperature (Tg) of 270 K or more, The above monomer B becomes a polymer having a glass transition temperature (Tg) of 220 K or less when the monomer B is homopolymerized, and Relative to the total mass of the monomer mixture, the ratio of the monomer A is 30% by mass or more and 50% by mass or less; 3) Organic solvents; 4) Crosslinking agent; 5) Organic acids; 6) Water.

Furthermore, according to the present invention, the following embodiments are further provided. 1. An above-mentioned aqueous patch, wherein The monomer A is selected from (meth)acrylic acid such as methyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, and third butyl methacrylate. At least one monomer in the group consisting of alkyl esters, vinyl acetate, acrylonitrile, acrylamide and styrene, The monomer B is at least one monomer selected from the group consisting of butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, and isononyl acrylate. 2. The above-mentioned aqueous patch, wherein the above-mentioned monomer A is at least one monomer selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl methacrylate, and n-butyl methacrylate. , The above monomer B is at least one monomer selected from the group consisting of 2-ethylhexyl acrylate and butyl acrylate. 3. The above-mentioned aqueous patch, which further contains an active ingredient. [Effect of invention]

According to the present invention, it is possible to provide an aqueous-based patch by blending the following alkyl acrylate-based copolymer into the adhesive layer of the aqueous-based patch, even after the moisture in the adhesive layer has been evaporated Maintains adhesion, low skin irritation, no adhesion between pastes, and can be attached to the skin again. The alkyl acrylate copolymer contains a glass transition temperature (Tg) of 270 when it becomes homopolymerized. A copolymer of a monomer mixture of a polymer of K or more and a monomer mixture of monomer B of a polymer having a Tg of 220 K or less when homopolymerized, and relative to the total mass of the monomer mixture, the above monomers The ratio of A is 30% by mass or more and 50% by mass or less.

As mentioned above, in order to improve the continuity of the adhesive force of the water-based adhesive, it is proposed to copolymerize the acrylic resin with methyl acrylate and 2-ethylhexyl acrylate (trade name NiKasol TS-620, Japan Carbide Industry Co., Ltd.) It is the solution to adjust the alkyl acrylate copolymer to the adhesive layer, or to increase the preparation amount. However, in the previous proposal, even when the amount of the copolymer is increased, especially after the water in the adhesive layer is swayed (after the water is swayed), the adhesion is not sufficient compared with the patch. . The present inventors have focused on the above-mentioned problems, focusing on the types of monomers constituting the alkyl acrylate copolymer that have not been studied before, especially the blending ratio thereof, and adhesion to water content and after drying (after water is scattered) Evaluation. Then, looking at the glass transition temperature (Tg) of the homopolymer containing the monomer, it was found that by using the following alkyl acrylate copolymer, even when the amount of the copolymer is small, Not only is the adhesive with excellent adhesion when water is included, but also the adhesive with good adhesion when dried, and it becomes an adhesive with low skin irritation. The alkyl acrylate copolymer system will become Tg when homopolymerized. Combination of monomers for polymers above 270 K and monomers for polymers with a Tg of 220 K or less when homopolymerized, and the blending ratio of monomers with a homopolymer Tg of 270 K or more is set to all monomers 30% by mass or more and 50% by mass or less. Hereinafter, the structure of the water-based adhesive agent of the present invention will be described.

The water-based adhesive of the present invention (hereinafter, also simply referred to as "adhesive") includes a support, an adhesive layer provided on the support, and a release liner. The shape of the above-mentioned adhesive, especially the preparation part including the support and the adhesive layer provided on the support is not particularly limited, and squares (squares, rectangles, etc.) and quadrilaterals (trapezoids, diamonds) can be selected according to the attachment site Etc.), polygons, circles, ellipses, semi-circles, triangles, crescents, and combinations of these shapes. In addition, the area of the adhesive agent (particularly the above-mentioned preparation part) can be appropriately determined, for example, considering the amount of the active ingredient formulated in the adhesive layer, etc., for example, it can be set in the range of 2 to 300 cm ² .

[Adhesive layer] The water-based adhesive of the present invention is characterized in that, for the water-based adhesive layer, in addition to the following hydrophilic acrylic adhesive, the alkyl acrylate generally constituting a non-aqueous acrylic adhesive is also formulated. Department of copolymers. As an adhesive commonly used for the adhesive layer (paste layer) of aqueous adhesives, polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, N-vinylacetamide-sodium acrylate copolymer resin, etc. are widely used Hydrophilic acrylic adhesive. From the viewpoint of having a high affinity with the above-mentioned hydrophilic acrylic adhesives and being able to uniformly knead them, it is preferable to use acrylic acid as the non-aqueous adhesive to be formulated into the aqueous adhesive layer of the aqueous adhesive. And methacrylic acid emulsion adhesive. In addition, the "alkyl acrylate copolymer" in this specification is intended to include both acrylic acid and methacrylic acid alkyl esters, and the "acrylic adhesive" is also intended to include acrylic adhesives and Based on acrylic adhesives.

<alkyl acrylate copolymer> The alkyl acrylate copolymer (non-aqueous adhesive base) constituting the non-aqueous acrylic adhesive is a copolymer containing the following monomers (one example of monomers is listed in Table 1): as a component that exhibits adhesion Monomer whose alkyl ester has 2 to 9 carbon atoms and will become a polymer with a glass transition temperature (Tg) of -55°C (218 K) or less during homopolymerization; a monomer that acts as a component to increase cohesion It will become a polymer with a Tg of 8 to 165°C (281 to 438 K) during homopolymerization; and, if necessary, a monomer having a functional group such as a crosslinking point such as a carboxyl group or a hydroxyl group. The alkyl acrylate copolymer used in the present invention is a copolymer of a monomer mixture including a monomer A which will become a polymer having a glass transition temperature (Tg) of 270 K or more during homopolymerization. The monomer B that will become a polymer with a glass transition temperature (Tg) of 220 K or less during homopolymerization. The upper limit of the glass transition temperature Tg of the homopolymer of the above monomer A is about 500 K, and the lower limit of the glass transition temperature Tg of the above homopolymer of the monomer B is about 200 K.

[Table 1]

Furthermore, homopolymers obtained by polymerizing only monomers exhibiting adhesion have higher adhesion but weaker mechanical strength, and generally use copolymerization with monomers that increase cohesion to improve mechanical strength The copolymer as an adhesive. As exemplified as the monomer exhibiting adhesive force shown in Table 1 above, in the present invention, as the monomer with higher adhesive force, the Tg when the monomer is homopolymerized (homopolymer) is 220 Butyl acrylate below K, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate, etc. Among them, butyl acrylate and 2-ethylhexyl acrylate are preferred. Among them, those which are actually used as additives for medical products can be preferably used, and the adhesion is high (the Tg of the homopolymer is low) 2-ethylhexyl acrylate. In addition, as the monomer for improving cohesion (the homopolymer Tg is 270 K or more), the monomers listed in Table 1 can be cited, and among them, methyl acrylate and methyl methacrylate are preferred , Ethyl methacrylate and n-butyl methacrylate, in the present invention, particularly preferred is methyl acrylate which has high mechanical strength and does not significantly reduce the adhesion (the homopolymer Tg is relatively low).

In addition, as listed in the prior art, commercially available alkyl acrylate-based copolymers used as adhesives include NiKasol (registered trademark) TS-620 (methyl acrylate- (2-ethylhexyl acrylate copolymer resin emulsion). Methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion is a catalogue of pharmaceutical additives. The present inventors have considered that NiKasol TS-620 (methyl acrylate-2-ethylhexyl acrylate copolymer resin emulsion) used in the previous aqueous patch has not obtained the required adhesion, especially in With regard to the reduction of the adhesive strength after the water from the adhesive layer was scattered, the change of the copolymerization ratio of the above copolymer was studied. In addition, in the above copolymers, various changes were made to the polymerization ratio of the monomer whose Tg of the homopolymer became 270 K or more, that is, methyl acrylate. As a result, as shown in the results of the following examples, the following were first confirmed: A system using a homopolymer whose Tg becomes a monomer (methyl acrylate, etc.) with a Tg of 270 K or more and a copolymer with a blending amount of 30% by mass or more can maintain the adhesion even when the moisture of the adhesive layer evaporates. In addition, if the Tg of the homopolymer becomes 270 K or more of the monomer (methyl acrylate, etc.), the blending amount exceeds 50% by mass, the emulsion aggregates and precipitates, and it becomes difficult to redisperse, so the upper limit value is set to 50 Mass% or less.

In the adhesive layer of the aqueous adhesive of the present invention, the formulation amount of the alkyl acrylate copolymer (in the case of an emulsion is the amount of solid content conversion) is the total amount of the adhesive layer of the aqueous adhesive The mass is based on, for example, 0.1 mass% or more and 30 mass% or less, 1.0 mass% or more and 15 mass% or less, 5.0 mass% or more and 10 mass% or less. In addition, the formulation ratio with the following acrylic hydrophilic adhesive can be set as an alkyl acrylate copolymer in terms of mass ratio, for example: acrylic hydrophilic adhesive = 10:1 to 1:10, alkyl acrylate Base ester copolymer: Acrylic hydrophilic adhesive = 5:1 to 1:5, alkyl acrylate copolymer: Acrylic hydrophilic adhesive = 3:1 to 1:2, alkyl acrylate copolymer: Acrylic hydrophilic adhesion = 2:1:1 to 1:1, etc.

<active ingredient> The adhesive layer in the aqueous patch of the present invention optionally contains an active ingredient. As an application of the aqueous patch of the present invention when no active ingredient is contained, it can be used as a protective material for swollen crab foot skin, a buffer material for protecting calluses, blisters, etc. When the adhesive layer contains active ingredients, it contains physiologically active substances. The physiologically active substance is not particularly limited as long as it has transdermal absorbability and exhibits pharmacological activity when administered into the body, and it may be a water-soluble substance or a fat-soluble substance. Examples of the physiologically active substance include biphenylacetic acid, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate (glycol salicylate), indomethacin, Non-steroidal anti-inflammatory agents such as ketoprofen and ibuprofen or their esters; antihistamines such as diphenhydramine and chlorfeniramine; aspirin, acetaminophen, ibuprofen, loxolol Analgesics such as fen sodium; local anesthetics such as lidocaine and dibucaine; muscle relaxants such as succinylcholine chloride; antifungal agents such as clotrimazole; antihypertensive agents such as clonidine; nitroglycerin, isosorbide dinitrate Vasodilators such as esters; vitamins A, vitamin E (tocopherol), vitamin E acetate, vitamin K, otothiamin, riboflavin and other vitamins, prostaglandins; scopolamine, fentanyl, chili Extract, undecanoic acid nonanoic acid, capsaicin, l-menthol, dl-camphor etc. The physiologically active substance may be used alone or in combination of two or more.

The above-mentioned effective ingredient can be appropriately determined according to the type of formulation, for example, based on the total mass of the adhesive layer of the water-based adhesive, it can be set to 0.1 mass% or more and 30 mass% or less, or 0.5 mass% or more and 15 mass% the following.

<Acrylic hydrophilic adhesive> The adhesive layer of the aqueous adhesive of the present invention contains an acrylic hydrophilic adhesive. Examples of the acrylic hydrophilic adhesive include water-soluble (meth)acrylic polymers. The water-soluble (meth)acrylic polymer is obtained by polymerizing a (meth)acryloyl group-containing monomer having a water-soluble functional group (hydrophilic group), and is formulated together with water to Adhesive layer to achieve adhesion. Examples of the water-soluble (meth)acrylic polymer include homopolymers such as polyacrylic acid and polyacrylic acid neutrals; and copolymers such as N-vinylacetamide-sodium acrylate copolymer resin. The polyacrylic acid neutralized product may be a polyacrylic acid completely neutralized product, a polyacrylic acid partially neutralized product, or a mixture thereof. The term "polyacrylic acid neutralized product" refers to polyacrylate. For example, sodium salt, potassium salt, calcium salt, ammonium salt and the like can be used.

The blending amount of the acrylic hydrophilic adhesive is based on the total mass of the adhesive layer of the water-based adhesive, and it can be, for example, 0.1 mass% or more and 10 mass% or less, and 1 mass% or more and 8 mass% or less.

<Organic solvent> The organic solvent formulated to the adhesive layer of the aqueous adhesive of the present invention may have the following effects, that is, to dissolve the effective ingredients such as drugs, and to prevent the effective ingredients from being chromatized from the adhesive. Examples of such organic solvents (dissolution aids) include: crotamiton; N-methyl-2-pyrrolidone; polyalkylene glycols such as polyethylene glycol 400 (polyethylene glycol) and polybutylene glycol Diol; diethyl adipate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, oleic oil and fat Etc. fatty acid esters; sorbitan esters such as polyoxyalkylene fatty acid esters; polyhydric alcohols such as 1,3-butanediol; dimethylformamide; dimethyl sulfoxide, etc. These can be used alone or in combination of two or more.

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

<Crosslinking agent> Examples of the crosslinking agent formulated in the adhesive layer of the aqueous adhesive of the present invention include polyvalent metal salts, and among them, polyvalent metal compounds containing aluminum. As an example, hydroxides such as aluminum hydroxide and aluminum magnesium hydroxide; aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxy aluminum amino acetal), dihydroxy aluminum amino acetate, Synthetic positive salts of inorganic or organic acids such as aluminum silicate, dried aluminum hydroxide gel, kaolin, aluminum stearate or their alkaline salts; composite salts such as aluminum alum; aluminates such as sodium aluminate; inorganic Aluminum complex salts and organic aluminum chelate compounds; synthetic polyvalent metal compounds such as aluminum magnesium carbonate, aluminum magnesium silicate, aluminum magnesium silicate, etc., which can be used alone or in combination of two or more.

The formulation amount of the cross-linking agent may be appropriately selected considering the residual of the adhesive on the skin or the degree of cross-linking which may be one of the reasons for the conformability. Based on the total mass of the adhesive layer of the water-based adhesive, for example, a range of 0.01% by mass or more and 6.0% by mass or less, 0.01% by mass or more and 4.0% by mass or less, or 0.01% by mass or more and 2.0% by mass or less can be cited.

<Organic acid> Examples of the organic acid formulated in the adhesive layer of the aqueous adhesive of the present invention include citric acid, lactic acid, tartaric acid, gluconic acid, glycolic acid, malic acid, fumaric acid, methanesulfonic acid, maleic acid, Acetic acid and the like can be used alone or in combination of two or more. Regarding the amount of organic acid to be formulated, based on the total mass of the adhesive layer of the water-based adhesive, for example, it can be set in the range of 0.01% by mass or more and 5% by mass or less.

<Water> As described above, the water-based adhesive of the present invention contains water (moisture) in the adhesive layer. In this specification, the "water" contained in the adhesive layer includes not only those added separately 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 mixed is not particularly limited, and can be set to 10% by mass or more, 90% by mass or less, 15% by mass or more, 70% by mass or less, or 20% by mass based on the total mass of the adhesive layer of the water-based adhesive. 50% by mass or less. In addition, the water blending amount 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 this when the water evaporates from the adhesive layer as the adhesive agent passes.

<Other arbitrary ingredients> Water-soluble polymer compounds, surfactants, wetting agents, stabilizers, antioxidants, inorganic powders, colorants, fragrances, preservatives, etc. can also be formulated in the adhesive layer of the aqueous adhesive of the present invention. The ingredients formulated in the adhesive layer in the previous aqueous-based patch (dressing) or non-aqueous-based patch (patch) are used as any other ingredients. These arbitrary components can be used individually or in combination of 2 or more types.

<Water-soluble polymer compound> Examples of the water-soluble polymer compound include gelatin, agar, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxy Propyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium alginate, maleic anhydride copolymer, carrageenan. These can be used alone or in combination of two or more. The formulation amount of the water-soluble polymer compound is usually based on the total mass of the adhesive layer of the water-based adhesive, for example, it can be set to 1.0% by mass or more and 30% by mass or less, 3.0% by mass or more and 20% by mass or less, or 5.0% by mass or more and 20% by mass or less.

<surfactant> Examples of the surfactant include polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, and polyethylene glycol dioleate. Polyoxyethylene fatty acid esters such as acid esters and polypropylene glycol dioleate; sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, Sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan sesqui oil Acid esters, and other ethylene oxide adducts and other sorbitan fatty acid esters; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan Monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan triisostearate Polyoxyethylene sorbitan fatty acid esters such as esters; polyoxyethylene lauryl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyalkylene Tridecyl ether, polyoxyethylene tetradecyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene- 2-ethylhexyl ether, polyoxyethylene isodecyl ether and other polyoxyethylene alkyl ethers; polyoxyethylene styrenated phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene distyrenated phenyl ether, polyoxyethylene Polyoxyethylene alkyl phenol ethers such as oxyethylene tribenzyl phenyl ether; glycerol fatty acid esters such as glyceryl monostearate and glyceryl monooleate; polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor Nonionic surfactants such as sesame oil and lecithin. These can be used alone or in combination of two or more. The formulation amount of these surfactants is based on the total mass of the adhesive layer of the water-based adhesive, and can be set, for example, in the range of 0.001 mass% or more and 10 mass% or less, and 0.01 mass% or more and 5 mass% or less.

<wetting agent> In order to suppress the evaporation of water over time, a wetting agent (also known as a humectant) can be formulated into the adhesive layer of the aqueous adhesive of the present invention. Examples of the wetting agent include concentrated glycerin, D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,4-butanediol, and maltitol , Xylitol and other polyols. These can be used alone or in combination of two or more. The formulation amount of the wetting agent is usually based on the total mass of the adhesive layer of the water-based adhesive, for example, it can be set to 1.0% by mass or more, 70% by mass or less, 5.0% by mass or more, 60% by mass or less, or 10% by mass Above 60% by mass range.

<Stabilizer> In order to improve the storage stability of the above active ingredients, etc. against light (especially ultraviolet rays), heat or oxygen, a stabilizer may be formulated in the adhesive layer of the aqueous adhesive of the present invention. Examples of stabilizers include sodium edetate and sodium edetate (ethylenediaminetetraacetic acid 2 sodium salt); antioxidants such as dibutylhydroxytoluene (BHT); and ultraviolet adsorbents such as benzoylmethane derivatives. . The formulation amount of the stabilizer is usually based on the total mass of the adhesive layer of the water-based adhesive, and it can be set, for example, in the range of 0.01% by mass or more and 1% by mass or less.

<Inorganic powder> As inorganic powder, calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, calcium sulfate, etc. can be formulated.

[Support] Examples of the support used in the aqueous patch of the present invention include flexible supports such as films, nonwoven fabrics, Japanese paper, cotton cloth, woven fabrics, woven fabrics, and laminated composites of nonwoven fabrics and films. The support is preferably a soft material that can be in close contact with the skin and can follow the degree of skin activity, and can suppress the occurrence of skin rashes and the like after long-term attachment. Examples of the material of these supports include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, Cotton, acetic acid rayon, rayon, rayon/polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, ether Polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene Vinyl rubber, ethylene-vinyl acetate copolymer, seruphen, etc. are essential ingredients.

In addition, cloths and other supports can be colored into skin tones and the like by using coloring agents, which can reduce the difference in color from the skin when they are attached. In addition, from the viewpoint that the color tone of the skin is easily revealed in the attached state, a form of a plastic film with excellent transparency can be adopted.

The thickness of the support is usually about 5 μm to 1 mm. When the support is cloth, 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, the thickness is preferably 10 to 300 μm, more preferably 12 to 200 μm, and still more preferably 15 to 150 μm. In the case where the thickness of the support is extremely thin, about 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 operability as an adhesive is improved , So it is better. However, if the thickness of the support is less than 5 μm, the strength or operability of the patch may be reduced and it may become difficult to stick to the skin, or may be damaged due to contact with other members, or may be in contact with water due to bathing, etc. And peel off from the skin in a short time. In addition, if the thickness of the support is too large (more than 1 mm), the patch becomes difficult to follow the movement of the skin, and the edge of the patch is easy to form a starting point for peeling, so there is a short time to peel from the skin, or the patch is in progress Increased discomfort. In addition, when the support is a film, the adhesive and the support can be improved for the purpose of sandblasting, corona treatment, etc. on one or both sides of the support. In addition, for easy removal from the packaging material, irregularities may be provided on one side or both sides of the support by a method other than sandblasting.

[Release liner] As the release liner (also called release layer and release paper) used in the water-based adhesive of the present invention, it is preferably a material that is not easily absorbed and absorbs drugs in the adhesive layer, and can be used for the adhesive Material commonly used in the technical field. For example, polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unextended, extended, etc.), polyethylene, polyamine Carbamate, PVC, polystyrene and other plastic films; Dowling paper, cellophane, parchment, kraft paper and other paper or synthetic paper; apply polysiloxane resin to the above plastic film, paper or synthetic paper, synthetic fiber, etc. Peeling paper made of peeling agent with fluororesin or other peeling properties; aluminum foil; laminated paper made by laminating these films and sheets in various layers; and applying peeling agent to the laminated paper Colorless or colored sheets such as laminated peeling paper. Furthermore, the peeling material can also be provided with concavities and convexities to facilitate removal from the packaging material. The thickness of the release liner is not particularly limited, and it is usually 10 μm to 1 mm, for example, 20 μm to 500 μm, preferably 40 μm to 200 μm. The shape of the peeling material can be set as square, rectangle, circle, etc., and can be made into a shape with rounded corners as required. The size can be set to the same shape as the size of the support in the above-mentioned attachment material, or slightly larger. The peeling material may be formed by one piece or a plurality of divided pieces, and the cutout may be formed by a straight line, a wavy line, or a suture shape, or a state where part of the peeling materials overlap each other.

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

The above-mentioned adhesive layer-forming composition contains various components contained in the above-mentioned adhesive layer: active ingredient, acrylic hydrophilic adhesive, alkyl acrylate copolymer, organic solvent, crosslinking agent, organic acid and water In addition, it may contain a semi-solid composition of other optional components.

In addition, the water-based adhesive agent of the present invention is characterized in that the adhesive force is maintained when it is hydrated and when it is dried (after water is scattered), and it is also an adhesive agent that has low skin irritation. Here, the skin irritation can be evaluated by, for example, the individual average value (average P.I.I.) of the skin primary irritation index (P.I.I.) based on the Chui test method, and the patch of the present invention can be set to, for example, 1.40 or less. The so-called Primary Irritation Index (P.I.I.) (Primary Irritation Index) based on the Choi's test method is an evaluation method using a rabbit's lesion. Specifically, the specimen (substance to be tested) is attached to the back of the rabbit, and the specimen is removed after a certain time, and then the reaction to the attachment site after a certain time (observing the state of erythema and the size of puffiness) The evaluation is carried out in 5 stages from 0 to 4, and the value is expressed in the form of the total value of the 2 evaluation values (the average value when the judgment time is plural), taking into account the individual differences evaluated, The individual average value (average PII) was calculated and evaluated. In the present invention, after the specimen (aqueous patch) is attached for 24 hours, the specimen is removed, and then, after a certain period of time, the attachment site is observed, and a stimulus response score is performed based on 30 minutes after removal After scoring the irritation response after 24 hours, the average PII was calculated, and the skin irritation was evaluated. [Example]

Hereinafter, the present invention will be described in further detail with examples, but the present invention is not limited to these examples.

＜Production of adhesive patch＞ The adhesives of Examples and Comparative Examples were produced in the following order.

Example 1: 1.5 parts by mass of polyvinyl alcohol was dissolved in 20 parts by mass of purified water (aqueous phase). Next, add 1.25 parts by mass of ethylene glycol salicylate, 1 part by mass of L-menthol, and 1 part by mass of polyethylene glycol (registered trademark) 400 (manufactured by Sanyo Chemical Industry Co., Ltd.), and dissolve it (oil phase). Furthermore, 4 parts by mass of polyacrylic acid partial neutralized product, 4 parts by mass of sodium carboxymethylcellulose, and 0.25 parts by mass of dihydroxy aluminum aminoacetate were uniformly dispersed in 25 parts by mass of concentrated glycerin (glycerin phase). Aqueous phase, methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (the amount of methyl acrylate in the copolymer is 31.1% by mass, and the emulsion contains a small amount of polyoxyethylene nonylphenyl ether (30EO )) 7 parts by mass, 0.20 parts by mass of sodium edetate hydrate, and 30 parts by mass of a 70% aqueous solution of D-sorbitol, which are uniformly dispersed or dissolved. Put oil phase and glycerin phase in this order, and mix evenly. Furthermore, after adding 1 part by mass of lactic acid and performing mass correction using purified water so that the total mass becomes 100 parts by mass, the mixture was uniformly kneaded under degassing conditions to obtain the adhesive layer forming composition of Example 1. Using a spreader with slit width adjusted to 0.5 mm, the obtained adhesive layer forming composition was placed on the liner (PET (Polyethylene Terephthalate, polyethylene terephthalate) treated on one side with polysiloxane) (75 μm)) The polysilicon surface is stretched, and the knitted fabric support (made of polyester) is laminated and then cured at 50°C for 1 week. After aging, it was punched into an arbitrary shape to obtain the preparation of Example 1.

Example 2: It was the same as Example 1 except that the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 40.8% by mass. The formulation of Example 2 was obtained in a manner.

Example 3: It was the same as Example 1 except that the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass. The formulation of Example 3 was obtained in a manner.

Example 4: Changed methyl acrylate-2-ethylhexyl acrylate copolymer emulsion to methyl methacrylate-2-ethylhexyl acrylate copolymer emulsion (the amount of methyl methacrylate in the copolymer is 30.0% by mass) 10 parts by mass (The conversion value of the solid content of the copolymer is 4.34 parts by mass), except that the preparation of Example 4 is obtained in the same manner as in Example 1.

Example 5: Changed methyl acrylate-2-ethylhexyl acrylate copolymer emulsion to ethyl methacrylate-2-ethylhexyl acrylate copolymer emulsion (the amount of ethyl methacrylate in the copolymer is 30.0% by mass) 10 parts by mass (The conversion value of the solid content of the copolymer is 4.14 parts by mass), except that the preparation of Example 5 is obtained in the same manner as in Example 1.

Example 6: Changed methyl acrylate-2-ethylhexyl acrylate copolymer emulsion to n-butyl methacrylate-2-ethylhexyl acrylate copolymer emulsion (the amount of n-butyl methacrylate in the copolymer is 30.0% by mass) 10 The formulation of Example 6 was obtained in the same manner as in Example 1 except for parts by mass (the conversion value of the solid content of the copolymer was 4.34 parts by mass).

Example 7: Changed methyl acrylate-2-ethylhexyl acrylate copolymer emulsion to methyl acrylate-n-butyl acrylate copolymer emulsion (the amount of methyl acrylate in the copolymer is 30.0% by mass) 10 parts by mass (solid content of the copolymer) The conversion value was 4.54 parts by mass), except that the preparation of Example 7 was obtained in the same manner as Example 1.

Example 8: The methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass, and the blending amount was changed to 5 parts by mass ( The conversion value of the solid content of the copolymer was 2.95 parts by mass), except that the preparation of Example 8 was obtained in the same manner as Example 1.

Example 9: The methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass, and the blending amount was changed to 10 parts by mass ( The conversion value of the solid content of the copolymer was 5.9 parts by mass), except that the preparation of Example 9 was obtained in the same manner as in Example 1.

Example 10: The methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass, and the blending amount was changed to 12 parts by mass ( The conversion value of the solid content of the copolymer was 7.08 parts by mass), except that the preparation of Example 10 was obtained in the same manner as in Example 1.

Example 11: The methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass, and the blending amount was changed to 15 parts by mass ( The conversion value of the solid content of the copolymer was 8.85 parts by mass), except that the preparation of Example 11 was obtained in the same manner as in Example 1.

Example 12: The methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 46.7% by mass, and the blending amount was changed to 20 parts by mass ( The conversion value of the solid content of the copolymer was 11.8 parts by mass), except that the preparation of Example 12 was obtained in the same manner as in Example 1.

Comparative example 1: It was the same as Example 1 except that the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 14.7% by mass. To obtain the preparation of Comparative Example 1.

Comparative example 2: It was the same as Example 1 except that the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount 31.1% by mass) was changed to an emulsion of methyl acrylate blending amount of 27.0% by mass. To obtain the preparation of Comparative Example 2.

Comparative Example 3: The formulation amount of the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate formulation amount 14.7% by mass) was changed to 10 parts by mass (10% by mass), except that it was the same as in Comparative Example 1. The preparation of Comparative Example 3 was obtained.

Comparative Example 4: The formulation amount of the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate formulation amount 14.7% by mass) was changed to 15 parts by mass (15% by mass), except that it was the same as in Comparative Example 1. The preparation of Comparative Example 4 was obtained.

Comparative Example 5: The formulation amount of the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate formulation amount 14.7% by mass) was changed to 20 parts by mass (20% by mass), except that it was the same as in Comparative Example 1. The preparation of Comparative Example 5 was obtained.

Comparative Example 6: The formulation amount of the methyl acrylate-2-ethylhexyl acrylate copolymer emulsion (methyl acrylate formulation amount 14.7% by mass) was changed to 25 parts by mass (25% by mass), except that it was the same as Comparative Example 1. The preparation of Comparative Example 6 was obtained.

In addition, regarding the blending amount of the copolymer emulsion in the above Examples 1 to 3, Comparative Example 1 and Comparative Example 2, the conversion value of the solid content of the copolymer is 4.13 based on the mass of all components constituting the adhesive layer Mass%, Example 4 and Example 6 are 4.34 mass% on the same basis, Example 5 and Example 7 are 4.14 mass% on the same basis, Example 8 is 2.95 mass% on the same basis, and Example 9 is the same basis Was 5.90 mass%, Example 10 was 7.08 mass% on the same basis, Example 11 was 8.85 mass% on the same basis, Example 12 was 11.80 mass% on the same basis, and Comparative Example 3 was 5.90 mass% on the same basis. Example 4 is 8.85 mass% on the same basis, Comparative Example 5 is 11.80 mass% on the same basis, and Comparative Example 6 is 14.75 mass% on the same basis.

Reference Example 1, Reference Example 2: Using a commercially available patch (FEITAS (registered trademark) 5.0, Jiuguang Pharmaceutical Co., Ltd., batch number: SC08T) as the formulation of Reference Example 1, a commercially available patch (Vantelin kowa new mini pad, Xinghe Co., Ltd., batch number) : NA640) As the preparation of Reference Example 2, it was used for various tests described below.

Test Example 1 (Adhesion Test) Regarding the preparations of Examples 1 to 12, Comparative Examples 1 to 6, and Reference Examples 1 and 2, for the initial (hereinafter referred to as "aqueous"), the preparations of Examples and Comparative Examples were just manufactured After that, the formulation of the reference example is just after opening the package of the product), and when it is dried at 50°C overnight (hereinafter referred to as "dried"), all formulations are in a state where the liner is peeled off (the adhesive layer is exposed State) maintained at 50°C for one night) of the tilting ball adhesive force, measured according to the Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3.2 Inclined Ball Adhesive Test Method. The obtained results are shown in Table 2 and Table 3.

Test Example 2 (Removability and re-adhesion test between pastes) The formulations of Examples 1 to 12, Comparative Examples 1 to 6, and Reference Examples 1 and 2 were evaluated for releasability and reattachability between pastes. The obtained results are combined and shown in Table 2 and Table 3. 1) Peelability between pastes Peel off the liner of each preparation cut to a size of 5 cm×5 cm, fold the preparations in half so that the adhesive layers are firmly attached to each other, and stand still for 30 seconds. Thereafter, the bonded portion was peeled off and evaluated according to the following criteria (N=3). ○: easily peeled off △: Deformed although peeling off ×: Not peeled 2) Reattachment The liner of each preparation (10 cm×7 cm) was peeled off and attached to the inside of the person's upper arm. After 30 seconds, it was peeled off and attached to the other parts of the forearm again, and evaluated according to the following criteria (N=3). ○: Reattachability △: Reattachment is weak ×: No re-adhesion

[Table 2]

[table 3]

<Test results> As shown in Table 2, regarding the preparations of Examples 1 to 9, among the monomers constituting the alkyl acrylate copolymer, the homopolymer of the monomer has a Tg of 270 K or more. The blending amount, that is, the blending amount of methyl acrylate in the methyl acrylate-2-ethylhexyl acrylate copolymer resin, the methyl methacrylate in the methyl methacrylate-2-ethylhexyl acrylate copolymer resin Blending amount, blending amount of ethyl methacrylate in ethyl methacrylate-2-ethylhexyl acrylate copolymer resin, methacrylic acid in n-butyl methacrylate-2-ethylhexyl acrylate copolymer resin The compounding amount of n-butyl ester and the compounding amount of methyl acrylate in the methyl acrylate-n-butyl acrylate copolymer resin is 30% by mass or more, although the result is the ball adhesiveness immediately after manufacturing (when water is contained) The force is slightly lower than the commercially available patch (Reference Example 1) and the commercially available dressing (Reference Example 2) (refer to Table 3), but the dry ball (drying at 50 ℃ overnight) shows the adhesive strength of the rolling ball It has almost the same adhesive strength as the commercially available patch. In addition, as shown in the results of Example 3 and Example 8 to Example 12, with the increase in the blending amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin (methyl acrylate blending amount: 46.7% by mass), The adhesive strength increases at any point immediately after manufacturing (when water is included) and when it is dried, especially in Examples 10 to 12, even when it is water, it exhibits the same market as shown in Reference Examples 1 and 2 above. Compared with the same level of adhesion. Moreover, in any of the embodiments, even if the adhesive layers are attached to each other, they can be easily peeled off, and re-adhesion is also found. Even if the amount of the alkyl acrylate copolymer is increased, these properties are maintained.

On the other hand, as a result, the preparation amount of the monomer A, that is, the preparation amount of the methyl acrylate of the methyl acrylate-2-ethylhexyl acrylate copolymer resin was less than 30% by mass (Comparative Examples 1 and 2) The adhesive strength of the roller ball during drying is lower than that of Examples 1-12. In addition, as described above, if the blending amount of methyl acrylate exceeds 50% by mass, the emulsion will agglomerate and precipitate, making it difficult to redisperse, and the upper limit of the blending amount is 50% by mass. In addition, regarding the methyl acrylate-2-ethylhexyl acrylate copolymer resin with the compounding amount of methyl acrylate used in Comparative Example 1 being 14.7% by mass, the following result was obtained, that is, the compounding amount of the copolymer resin was 7 Formulations (Comparative Example 1, Comparative Example 3 to Comparative Example 6) that increase in the range of mass% to 25% by mass (4.13% by mass to 14.75% by mass in terms of solid content) are sticky when they are hydrated and when dried The adhesive strength is lower than the preparations of Examples 1 to 3. In addition, the preparations of Comparative Examples 1 to 4 were evaluated as having peelability between pastes, and the re-adhesion was the same as the preparations of Examples, but the preparations of Comparative Examples 5 and 6 were evaluated as having peelability between pastes, The reattachability was not as good as the formulations of the examples, and it was found that these properties tended to deteriorate due to the increased amount of alkyl acrylate copolymers.

In addition, the preparation of Reference Example 1, which is a commercially available preparation, was evaluated so that the adhesive layers did not peel off when they were attached to each other, and did not have reattachability. In addition, in the preparation of Reference Example 2, the result was that after the adhesive layers were adhered to each other, they were peeled but deformed, and after being attached again, the adhesion became weak.

Based on the above results, it was confirmed that by using the monomer constituting the alkyl acrylate copolymer, the amount of the monomer A (methyl acrylate, etc.) whose homopolymer has a Tg of 270 K or more is 30-50% by mass of alkyl acrylate copolymer (methyl acrylate-2-ethylhexyl acrylate copolymer resin, etc.), which is not only excellent in adhesion when water is contained, but also excellent in adhesion even when dried Also, it was confirmed that it was easy to peel between the pastes and had re-adhesion.

Test Example 3 (Skin Irritation Index Test) The skin primary irritation index (P.I.I.) test based on the Choi test method is performed by the following method. Furthermore, the details of the Choi test method are shown in Draize JH, Woodard, G. and Calvery, H.0. (1944): Methods for the study of irritation and Toxicity of substances applied topically to the skin and mocous membranes, J . Pharmacol Exp. Ther., 82:377-390).

，將剝離襯墊剝離後，貼附於經剪毛及剃毛處理之白色兔子(17週齡，雄，JW)(N＝3)之背部，以覆蓋所貼附之製劑整體之方式自該製劑之上方貼附具有透濕性之CATHEREEP(透明黏著膜，米其邦(股))。 貼附24小時後，將CATHEREEP及製劑剝離，利用純化水擦拭該製劑之貼附部位，觀察剝離30分鐘後及經過24小時之時之貼附部位之皮膚狀態，依據表4所示之崔氏試驗之基準而實施刺激反應之評分。 又，基於製劑剝離30分鐘後及24小時後之評分值，根據30分鐘後或24小時後之評分平均值、及各個體之皮膚一次刺激性指數(P.I.I)，獲得作為個體平均值之平均皮膚一次刺激性指數(平均P.I.I.)。 再者，使用DNBC(2,4-dinitrochloro-benzene，二硝基氯苯)作為陽性對照，使用市售之敷劑(Nobinobi Salonsip(註冊商標)FH溫感，久光製藥(股))作為參考例3之製劑，使用市售之敷劑(Halix(註冊商標)55EX溫感，LION(股))作為參考例4之製劑，以相同方式實施皮膚一次刺激性指數試驗，獲得30分鐘後或24小時後之評分平均值、各個體之皮膚一次刺激性指數(P.I.I)及皮膚一次刺激性指數(平均P.I.I.)。 將所獲得之結果示於表5。Punch the preparations of Example 3 and Comparative Example 1 to 15 mm

After peeling off the release liner, attach it to the back of a white rabbit (17 weeks old, male, JW) (N=3) treated with shearing and shaving, and cover the whole of the attached preparation from the preparation Attach the CATHEREEP (transparent adhesive film, Miqibang (share)) with moisture permeability on the top. After 24 hours of application, remove the CATHEREEP and the preparation, wipe the application site of the preparation with purified water, and observe the skin condition of the application site after 30 minutes of peeling and 24 hours, according to Choi's shown in Table 4 The stimulus response was scored based on the test. Also, based on the score values after 30 minutes and 24 hours after the preparation was peeled off, the average skin as an individual average value was obtained based on the average score after 30 minutes or 24 hours and the skin primary irritation index (PII) of each individual One-time irritation index (average PII). In addition, DNBC (2,4-dinitrochloro-benzene) was used as a positive control, and a commercially available compress (Nobinobi Salonsip (registered trademark) FH Wengan, Jiuguang Pharmaceutical Co., Ltd.) was used as a reference example. For the preparation of 3, using a commercially available compress (Halix (registered trademark) 55EX Wengan, LION (share)) as the preparation of Reference Example 4, a skin irritation index test was carried out in the same manner, after 30 minutes or 24 hours The average of the subsequent scores, the primary skin irritation index (PII) and the primary skin irritation index (average PII) of each body. Table 5 shows the obtained results.

[Table 4] Table 4 Evaluation criteria for one skin irritation test (Cui's test criteria)

*1 平均＝各個體中之紅斑及浮腫之評價之合計分數之平均值(3隻) *2 一次刺激性指數(P.I.I.)＝製劑剝離後30分鐘及24小時之各個評分之合計/2 *3 平均一次刺激性指數(平均P.I.I.)＝各個體之P.I.I.之合計/3(隻) *4 SE：標準誤差[Table 5] Table 5 Results of a skin irritation test for rabbits

*1 Average = the average value of the total score of the evaluation of erythema and edema in each body (3 animals) *2 Primary Irritation Index (PII) = the total score of each score 30 minutes and 24 hours after the peeling of the preparation/2 *3 Average primary irritation index (average PII) = total PII of each individual/3 (only) *4 SE: standard error

As shown in Table 5, as a result, the average primary irritation index (average P.I.I.) in the preparations of Example 3, Comparative Example 1, Reference Example 3, and Reference Example 4 became 0.7 to 1.0, which was mild stimulation. On the other hand, the average primary irritation index (average P.I.I.) in the positive control became 2.8, which was a moderate irritation.

Based on the results of the above examples, it was confirmed that according to the present invention, among the monomers constituting the alkyl acrylate copolymer, the homopolymer of the monomer has a Tg of 270 K or more of monomer A (methyl acrylate Etc.) The alkyl acrylate copolymer (methyl acrylate-2-ethylhexyl acrylate copolymer resin, etc.) with a content of 30 to 50% by mass is formulated into the adhesive layer of the water-based adhesive to provide a means to maintain water content. Adhesive with high adhesiveness when dry and dry, and low skin irritation.

Claims (4)

An aqueous adhesive, which contains a support, an adhesive layer provided on the support, and a release liner, and The above adhesive layer system contains the following components 1) to 6) as essential components: 1) Acrylic hydrophilic adhesive; 2) Alkyl acrylate copolymer, which is a copolymer containing a monomer mixture of monomer A and monomer B, When the above monomer A homopolymerizes the monomer A, it will become a polymer having a glass transition temperature (Tg) of 270 K or more, The above monomer B becomes a polymer having a glass transition temperature (Tg) of 220 K or less when the monomer B is homopolymerized, and Relative to the total mass of the monomer mixture, the ratio of the monomer A is 30% by mass or more and 50% by mass or less; 3) Organic solvents; 4) Crosslinking agent; 5) Organic acids; and 6) Water. If the water-based patch of claim 1, wherein The above monomer A is selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, isobutyl methacrylate, third butyl methacrylate, vinyl acetate, propylene At least one monomer in the group consisting of nitrile, acrylamide and styrene, The monomer B is at least one monomer selected from the group consisting of butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, and isononyl acrylate. If the water-based patch of claim 2, wherein The above monomer A is at least one monomer selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl methacrylate and n-butyl methacrylate, The above monomer B is at least one monomer selected from the group consisting of 2-ethylhexyl acrylate and butyl acrylate. The aqueous patch according to any one of claims 1 to 3, which further contains an active ingredient.