JP7219177B2 - Non-aqueous patches - Google Patents

Description

TECHNICAL FIELD The present invention relates to a non-aqueous patch, and more particularly, to a non-aqueous patch that has re-adherability, water absorption resistance, and low skin irritation.

So far, proposals have been made to improve the compatibility of active ingredients, drug release, and durability of efficacy by incorporating a hydrophilic adhesive component into the adhesive layer of non-aqueous patches (also known as tapes). Also, proposals for controlling the adhesive force have been made.

For example, Patent Document 1 discloses a medical patch comprising a W/O type paste layer for the purpose of sustaining the pharmacological effect by stably releasing a medicinal ingredient and the like, and contains polyacrylic acid. Disclosed is that a hydrophilic phase and a lipophilic phase containing a methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion are mixed, coated on a liner and dried to form the W/O type paste layer. It is
Patent Document 2 describes a paste formed by coating and drying a paste composition containing an acrylic emulsion-type pressure-sensitive adhesive (Nikasol TS-620) and polyvinyl alcohol in order to achieve immediate effect and sustained effect. A rough skin treatment patch comprising a body layer is disclosed.
In Patent Documents 3 and 4, when applied, it is difficult to adhere to clothes, bedding, etc., the active ingredient is difficult to be wiped off by these, and furthermore, it is difficult to cause a decrease in cohesion (adhesive residue) due to moisture absorption of the plaster layer. The objective is to provide a therapeutic sheet for external use ⁽ sheet for external use). A therapeutic sheet for external use (sheet for external use) provided with an adhesive base (paste layer) that does not substantially contain water and a plaster layer containing a water-soluble polymer polysaccharide or the like is disclosed as follows. . In the examples, an external therapeutic sheet (external use sheet) having a plaster layer formed by coating and drying a plaster composition containing an acrylic emulsion type pressure-sensitive adhesive (Nikasol TS-620) and polyvinyl alcohol. is disclosed.
As another technique for blending a hydrophilic adhesive component in the adhesive layer of a non-aqueous patch, Patent Document 5 discloses a steroid agent and a methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (Nicazol TS-60) and polyvinyl alcohol are spread and dried to form a high-release antipruritic patch.

Patent No. 2849937 specification JP 2002-167335 A Patent No. 4268527 Patent No. 5259040 specification Patent No. 2501671 specification

In general, non-aqueous patches have high adhesive strength and are considered to have the advantage of being difficult to peel off from the application site. It has been pointed out that the adhesive strength when re-applied is reduced (poor re-adherability). Furthermore, if the adhesive layer absorbs water due to water entering between the patch and the application site (skin) from the outside, or sweating at the application site, the adhesive strength will decrease and the adhesive layer will easily peel off. It is said to have disadvantages such as high skin irritation during application and removal.
As mentioned above, there have been proposals to control the adhesive force by blending a hydrophilic adhesive component into a non-aqueous (also called hydrophobic or lipophilic) adhesive layer. and suppresses the decrease in adhesiveness during perspiration, suppresses adhesion between adhesive layers, improves re-adhesion to the skin, and further satisfies the suppression of skin irritation during application and removal. No non-aqueous patches have been proposed so far.

The present inventors have conducted intensive research to solve the above problems, and as a result, when 30 to 50% by mass of a monomer that becomes a polymer having a glass transition temperature (Tg) of 270 K or higher when homopolymerized, when homopolymerized containing an alkyl acrylate copolymer obtained by copolymerizing monomers that form a polymer having a Tg of 220 K or less so that the total amount of both monomers is 100% by mass, and a hydrophilic pressure-sensitive adhesive having a crosslinked structure, The non-aqueous adhesive patch, which does not substantially contain water, has reduced adhesiveness when absorbing water and perspiration, adhesion between adhesive layers, lack of re-adhesion to the skin, and skin irritation during application and removal. The inventors have found that these problems can be satisfied at the same time, and completed the present invention.

That is, the present invention provides a non-aqueous patch comprising a support, and a pressure-sensitive adhesive layer and a release liner provided on the support,
It relates to a non-aqueous patch, wherein the pressure-sensitive adhesive layer essentially contains the following components 1) to 5). 1) acrylic hydrophilic adhesive 2) acrylic acid alkyl ester copolymer which is a copolymer of a monomer mixture consisting of monomer A and monomer B,
The monomer A is a monomer that becomes a polymer having a glass transition temperature (Tg) of 270 K or higher when the monomer A is homopolymerized,
The monomer B is a monomer that becomes a polymer having a glass transition temperature (Tg) of 220 K or less when the monomer B is homopolymerized,
3) an organic solvent 4) a cross-linking agent 5) an organic acid, wherein the proportion of the monomer A is 30% by mass or more and 50% by mass or less relative to the total mass of the monomer mixture.

Further, according to the present invention, the following embodiments are provided.
1. 2) The non-aqueous adhesive patch, wherein the acrylic acid alkyl ester copolymer is blended in an amount of 0.1% by mass or more and 30% by mass or less based on the total mass of the adhesive layer.
2. The 2) acrylic acid alkyl ester-based copolymer and the 1) acrylic hydrophilic pressure-sensitive adhesive have a mass ratio of 2) acrylic acid alkyl ester-based copolymer: 1) acrylic hydrophilic pressure-sensitive adhesive = 2: The non-aqueous adhesive patch, which is formulated at a ratio of 1 to 1:1.
3. The monomer A is (meth)acrylic acid alkyl esters such as methyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, i-butyl methacrylate, and t-butyl methacrylate, vinyl acetate, acrylonitrile, and acrylamide. and at least one monomer selected from the group consisting of styrene,
The monomer B is at least one monomer selected from the group consisting of butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate, and lauryl methacrylate.
The non-aqueous adhesive patch.
4. the monomer A is at least one monomer selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl methacrylate and n-butyl methacrylate;
The non-aqueous patch, wherein the monomer B is at least one monomer selected from the group consisting of 2-ethylhexyl acrylate and butyl acrylate.
5. The non-aqueous patch, further comprising an active ingredient.

According to the present invention, a monomer mixture comprising a monomer A that becomes a polymer having a glass transition temperature (Tg) of 270 K or higher when homopolymerized and a monomer B that becomes a polymer having a Tg of 220 K or lower when homopolymerized. an acrylic acid alkyl ester-based copolymer in which the proportion of the monomer A is 30% by mass or more and 50% by mass or less relative to the total mass of the monomer mixture, and a hydrophilic polymer having a crosslinked structure By blending the combination with an adhesive into the adhesive layer of a non-aqueous patch that does not substantially contain water, it suppresses the decrease in adhesiveness when absorbing water and sweating, and suppresses the adhesion of the adhesive layers to each other. As a result, it is possible to provide a non-aqueous patch that has improved readhesion to the skin and less skin irritation during application and removal.

As described above, an alkyl acrylate copolymer such as methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name: Nikasol TS-620, Nippon Carbide Industry Co., Ltd.) and polyacrylic acid or polyvinyl Proposals have been made to incorporate a hydrophilic component such as alcohol into the pressure-sensitive adhesive layer of a non-aqueous patch.
However, in the proposals so far, the blending amount of the hydrophilic component is small compared to the blending amount of the alkyl acrylate copolymer (such as 1/30 or less of the alkyl acrylate copolymer). In addition, no detailed study has been made on the adhesiveness between adhesive layers, the reattachment to the skin, the water absorbency of the adhesive layer, and the skin irritation.
In order to solve the above problems, the present inventors focused on the types of monomers constituting alkyl acrylate copolymers, which have not been examined so far, and particularly on the blending ratio thereof, and evaluated the adhesive strength. Focusing on the glass transition temperature (Tg) of the homopolymer composed of the monomer, a monomer having a Tg of 270 K or higher when homopolymerized and a polymer having a Tg of 220 K or lower when homopolymerized are obtained. A combination with a monomer, and adoption of an acrylic acid alkyl ester copolymer in which the blending ratio of a monomer having a homopolymer Tg of 270K or more is 30% by mass or more and 50% by mass or less of all monomers. By combining the acrylic acid alkyl ester-based copolymer having this configuration with a hydrophilic pressure-sensitive adhesive having a crosslinked structure, the amount of the copolymer to be blended is much smaller than in the conventional proposals. However, it is possible to obtain sufficient adhesive strength as a patch, suppress adhesion between adhesive layers, improve re-adherability to the skin, and become a patch with low skin irritation. I found out.

In the non-aqueous patch of the present invention having the structure described above, a highly adhesive hydrophobic adhesive (the above-mentioned specific alkyl acrylate copolymer) is uniformly dispersed in a hydrophilic adhesive having a crosslinked structure. It is considered to have a structure that In the initial state, the sticking to the skin is realized by the adhesive force of the hydrophobic adhesive. In addition, due to the structure in which the hydrophobic adhesive is uniformly dispersed in the hydrophilic adhesive, when the adhesive layers (adhesive surfaces) contact each other or the adhesive layer and the application site (skin), the hydrophobic adhesive The contact of the agent is considered to be in a state of point contact, so to speak. Therefore, adhesion between adhesive surfaces is suppressed while maintaining adhesiveness, and even when applied to the skin, the contact of the highly adhesive hydrophobic adhesive is point contact, so the stratum corneum is peeled off when peeled off. can be reduced, and as a result, it can be expected that there is re-adhesion and mild irritation when peeled off. In addition, due to the above-mentioned structure, the pressure-sensitive adhesive layer can have appropriate air permeability, less stuffiness at the time of application, and during water absorption and perspiration, the hydrophilic pressure-sensitive adhesive having a crosslinked structure exhibits water absorption ability and exhibits adhesiveness. It is considered that the adhesiveness to the skin can be maintained. Furthermore, when the absorbed water evaporates, the adhesiveness to the skin can be maintained by the hydrophobic adhesive.
Non-aqueous adhesive patches (tape agents) in which a hydrophilic polymer or a water-absorbing resin is blended in the pressure-sensitive adhesive layer in order to improve water absorption have been proposed so far. However, in the proposals made so far, there have been problems such as stickiness due to elution of the hydrophilic component from the adhesive layer although the adhesive has water absorbency, and the desired adhesive strength cannot be obtained and the adhesive tends to be peeled off. In addition, the tape agent with improved skin irritation is
The problem is that the adhesive strength tends to be generally lower than that of ordinary tapes.
The non-aqueous patch of the present invention solves the conventional problems with the above-described structure, and simultaneously achieves high adhesive strength, suppression of adhesion between adhesive layers, improved re-adherability, and low skin irritation. It is what I did.
The configuration of the non-aqueous patch of the present invention is described below.

The non-aqueous patch of the present invention (hereinafter also simply referred to as "patch") comprises a support, and a pressure-sensitive adhesive layer and a release liner provided on the support.
The shape of the patch, particularly the preparation portion comprising a support and an adhesive layer provided on the support, is not particularly limited, and may be square (square, rectangle, etc.), quadrangle (trapezoid, rhombus, etc.), polygon. , circular, elliptical, semicircular, triangular, crescent, and combinations of these shapes.
The area of the patch (particularly, the drug product portion described above) can be determined as appropriate, and can be, for example, in the range of 2 to 300 cm ² in consideration of the amount of the active ingredient blended in the adhesive layer.

[Adhesive layer]
<Alkyl acrylate copolymer>
The non-aqueous adhesive patch of the present invention is characterized by containing an acrylic acid alkyl ester copolymer, which is an acrylic pressure-sensitive adhesive.
In the present specification, the "acrylic acid alkyl ester copolymer" is intended to include both alkyl esters of acrylic acid and methacrylic acid, and "acrylic pressure-sensitive adhesive" also includes an acrylic pressure-sensitive adhesive and a methacrylic It is intended to include both adhesives.
The acrylic acid alkyl ester copolymer (non-aqueous adhesive base) has an alkyl ester having 2 to 9 carbon atoms as a component that exhibits adhesive strength, and has a glass transition temperature (Tg) when homopolymerized. A monomer that forms a polymer at -55°C (218K) or less, a monomer that forms a polymer with a Tg of 8 to 165°C (281 to 438K) when homopolymerized as a component that improves cohesive strength, and, if necessary, a carboxyl It is a copolymer composed of a monomer having a functional group such as a group or a hydroxy group that serves as a cross-linking point (an example of the monomer is listed in Table 1).
The acrylic acid alkyl ester copolymer used in the present invention is composed of a monomer A that becomes a polymer having a glass transition temperature (Tg) of 270 K or higher when homopolymerized, and a monomer A having a glass transition temperature (Tg) of 220 K or lower when homopolymerized. It is a copolymer of a monomer mixture consisting of a monomer B that becomes a polymer. The upper limit of the glass transition temperature Tg of the homopolymer of the monomer A is about 500K, and the lower limit of the glass transition temperature Tg of the homopolymer of the monomer B is about 200K.

Homopolymers obtained by polymerizing only monomers that exhibit adhesive strength are said to have high adhesive strength but weak mechanical strength. Coalescence is used as an adhesive.
As shown in Table 1 above as a monomer that exhibits adhesive strength, in the present invention, as a monomer with higher adhesive strength, an acrylic polymer having a Tg of 220 K or less when the monomer is homopolymerized (homopolymer) Butyl acid, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate and the like are used. Among these, butyl acrylate and 2-ethylhexyl acrylate are preferred, and 2-ethylhexyl acrylate, which has a track record of use as a pharmaceutical additive and has high adhesive strength (low homopolymer Tg), can be preferably used. .
Monomers that improve cohesive strength (Tg of homopolymer is 270K or higher) include the monomers listed in Table 1. Among these, methyl acrylate, methyl methacrylate, ethyl methacrylate and n-butyl methacrylate are preferred. In the present invention, methyl acrylate is particularly preferred because it has high mechanical strength and does not significantly reduce adhesiveness (the Tg of the homopolymer is relatively low).

In addition, as mentioned in the prior art, as a commercially available alkyl acrylate copolymer used in patches, Nikasol (registered trademark) TS-620 (methyl acrylate/acrylic acid) manufactured by Nippon Carbide Co., Ltd. acid 2-ethylhexyl copolymer resin emulsion). Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion is listed in the Pharmaceutical Excipients Regulations.
The present inventors have found that Nikasol TS-620, which is used as an acrylic acid alkyl ester copolymer (methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion) in non-aqueous patches, provides desired adhesive strength. In view of the fact that the copolymer cannot be obtained, the inventors considered changing the copolymerization ratio of the above copolymer.
In the above copolymer, when the polymerization ratio of the monomer that makes the homopolymer Tg of 270 K or higher, that is, methyl acrylate, was varied, the Tg of the homopolymer was 270 K or higher, as shown in the results of Examples described later. It was confirmed for the first time that a system using a copolymer containing 30% by mass or more of a monomer (such as methyl acrylate) as the adhesive layer has excellent adhesive strength. In addition, if the amount of the monomer (such as methyl acrylate) that makes the Tg of the homopolymer 270K or higher exceeds 50% by mass, the emulsion aggregates and precipitates and becomes difficult to redisperse, so the upper limit is set to 50% by mass. The following was done.

In the adhesive layer of the non-aqueous patch of the present invention, the amount of the acrylic acid alkyl ester-based copolymer (in the case of an emulsion, the solid content conversion value) is based on the total weight of the adhesive layer of the non-aqueous patch. For example, it can be 0.1% by mass or more and 30% by mass or less, 1.0% by mass or more and 15% by mass or less, or 5.0% by mass or more and 10% by mass or less. When the acrylic acid alkyl ester copolymer is blended in the form of an emulsion, it can be, for example, 1.0% by mass or more and 50% by mass or less, depending on the solid content (copolymer) concentration.
In addition, the mixing ratio with the acrylic hydrophilic pressure-sensitive adhesive described later is, for example, the mass ratio of acrylic acid alkyl ester-based copolymer: acrylic hydrophilic pressure-sensitive adhesive = 10: 1 to 1: 10, the same = 5: 1 to 1:5, 3:1 to 1:2, 2:1 to 1:1, and the like.

<Active ingredient>
The adhesive layer in the non-aqueous patch of the present invention optionally contains an active ingredient. When the non-aqueous patch of the present invention does not contain an active ingredient, it can be used as a covering material for keloid-like skin and as a cushioning material for protecting calluses, spurs, and the like.
When the adhesive layer contains an active ingredient, it contains a physiologically active substance. 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 may be a water-soluble substance or a fat-soluble substance.
Examples of physiologically active substances include non-steroidal anti-inflammatory agents such as felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate (ethylene glycol salicylate), indomethacin, ketoprofen, ibuprofen, and esters thereof; diphenhydramine; , antihistamines such as chlorpheniramine; analgesics such as aspirin, acetaminophen, ibuprofen, loxoprofen sodium; local anesthetics such as lidocaine and dibucaine; muscle relaxants such as suxamethonium chloride; antifungal agents such as clotrimazole; Antihypertensive agents such as nitroglycerin and isosorbide dinitrate; vasodilators such as nitroglycerin and isosorbide dinitrate; vitamins and prostaglandins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin and riboflavin butyrate; extracts, nonylic acid vanillylamide, capsaicin, l-menthol, dl-camphor and the like. Physiologically active substances may be used singly or in combination of two or more.

The amount of the above-mentioned active ingredient can be appropriately determined according to its type. % by mass or less.

<Acrylic hydrophilic adhesive>
The adhesive layer of the non-aqueous patch of the present invention contains an acrylic hydrophilic adhesive. By adopting an acrylic hydrophilic pressure-sensitive adhesive as the hydrophilic pressure-sensitive adhesive, it has a high affinity with the acrylic acid alkyl ester copolymer (non-aqueous acrylic pressure-sensitive adhesive) and can be uniformly mixed. The hydrophilic pressure-sensitive adhesive can form a cross-linked structure when forming the pressure-sensitive adhesive layer with a cross-linking agent to be described later.
Water-soluble (meth)acrylic polymers are mentioned as said acryl-type hydrophilic adhesive. A 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). , to exhibit stickiness. Examples of water-soluble (meth)acrylic polymers include homopolymers such as polyacrylic acid and neutralized polyacrylic acid; and copolymers such as sodium acrylate-N-vinylacetamide copolymer.
The neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. Neutralized polyacrylic acid means polyacrylic acid salt, and for example, sodium salt, potassium salt, calcium salt, ammonium salt and the like can be used.

The amount of acrylic hydrophilic adhesive to be blended is, for example, 0.1% by mass or more and 10% by mass or less, or 1% by mass or more and 8% by mass or less, based on the total mass of the adhesive layer of the non-aqueous adhesive patch. can.

<Organic solvent>
The organic solvent blended in the adhesive layer of the non-aqueous patch of the present invention can help dissolve active ingredients such as drugs, and can play a role in preventing precipitation of active ingredients from the adhesive layer. Examples of such organic solvents (solubilizing agents) include crotamiton; N-methyl-2-pyrrolidone; macrogol 400 (polyethylene glycol), polyalkylene glycols such as polybutylene glycol; diethyl adipate, diisopropyl adipate, and diethyl sebacate. , diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, oleyl oleate and other fatty acid esters; sorbitan esters such as polyoxyalkylene fatty acid esters; polyhydric alcohols such as 1,3-butanediol; dimethylformamide; is mentioned. These can be used singly or in combination of two or more.

The blending amount of the organic solvent can be, for example, 0.1% by mass or more and 20% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the non-aqueous patch.

<Crosslinking agent>
Examples of the cross-linking agent blended in the pressure-sensitive adhesive layer of the non-aqueous patch of the present invention include polyvalent metal salts, particularly polyvalent metal compounds containing aluminum. Examples include hydroxides such as aluminum hydroxide and magnesium alumina hydroxide; aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxyaluminum aminoacetal), dihydroxyaluminum aminoacetate, synthetic aluminum silicate, dry hydroxide Normal salts of inorganic or organic acids such as aluminum gel, kaolin, aluminum stearate, or basic salts thereof; resalts such as aluminum alum; aluminates such as sodium aluminate; inorganic aluminum complex salts and organic aluminum chelate compounds polyvalent metal compounds such as synthetic hydrotalcite, magnesium aluminosilicate, and magnesium aluminometasilicate, which can be used alone or in combination of two or more.

The amount of the cross-linking agent to be blended may be appropriately selected in consideration of the degree of cross-linking, which may contribute to the adhesive residue on the skin and adhesiveness of the adhesive. Based on the total weight of the adhesive layer of the non-aqueous patch, for example, 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 A range of 2.0% by mass or less can be mentioned.

<Organic acid>
Examples of the organic acid to be incorporated in the adhesive layer of the non-aqueous patch of the present invention include citric acid, lactic acid, tartaric acid, gluconic acid, glycolic acid, malic acid, fumaric acid, methasulfonic acid, maleic acid, and acetic acid. , these can be used alone or in combination of two or more.
The blending amount of the organic acid can be in the range of, for example, 0.01% by mass or more and 5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the non-aqueous patch.

<Other optional ingredients>
The pressure-sensitive adhesive layer of the non-aqueous patch of the present invention may contain, as other optional components, a water-soluble polymer compound, a surfactant, a wetting agent, a stabilizer, an antioxidant, an inorganic powder, a coloring agent, a fragrance, and an antiseptic. Ingredients, such as agents, that can generally be incorporated in the adhesive layer of conventional non-aqueous patches (tapes) and water-containing adhesives (plasts) can be incorporated. These arbitrary components can be used individually or in combination of 2 or more types.

<Water-soluble polymer compound>
Examples of water-soluble polymer compounds include gelatin, agar, polyvinyl alcohol, polyvinylpyrrolidone, propylene carbonate, carboxymethylcellulose, carmellose sodium, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, sodium alginate, and maleic anhydride. polymer, carrageenan. These can be used singly or in combination of two or more.
The blending amount of the water-soluble polymer compound is usually, based on the total weight of the adhesive layer of the non-aqueous patch, for example, 1.0% by mass or more and 30% by mass or less, 3.0% by mass or more and 20% by mass or less, Alternatively, it can be in the range of 5.0% by mass or more and 20% by mass or less.

<Surfactant>
Examples of surfactants include polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol diolate, and polypropylene glycol dioleate. sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan monosesquiolate, and Sorbitan fatty acid esters such as these ethylene oxide adducts; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan trioleate and polyoxyethylene sorbitan triisostearate; polyoxyethylene dodecyl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, Polyoxyalkylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethylhexyl ether, polyoxyethylene iso Polyoxyethylene alkyl ethers such as decyl ether; Polyoxyethylene alkylphenol ethers such as polyoxyethylene styrenated phenyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene distyrenated phenyl ether, polyoxyethylene tribenzylphenyl ether; Glycerin fatty acid esters such as glycerin stearate and glycerin monooleate; and nonionic surfactants such as polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil and lecithin. These can be used individually by 1 type or in combination of 2 or more types as appropriate.
The blending amount of these surfactants is in the range of, for example, 0.001% by mass to 10% by mass, and 0.01% by mass to 5% by mass, based on the total mass of the adhesive layer of the non-aqueous patch. be able to.

<Wetting agent>
A humectant (also referred to as a humectant) can be blended in the adhesive layer of the non-aqueous patch of the present invention. Wetting agents include, for example, concentrated glycerin, D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,4-butanediol, maltitol, and xylitol. hydric alcohols. These can be used singly or in combination of two or more.
The amount of the wetting agent is usually, based on the total weight of the pressure-sensitive adhesive layer of the non-aqueous patch, for example, 1.0% by mass or more and 80% by mass or less, 5.0% by mass or more and 80% by mass or less, or 10% by mass. % or more and 80 mass % or less.

<Stabilizer>
The adhesive layer of the non-aqueous adhesive patch of the present invention may contain a stabilizer to improve the storage stability of the active ingredient against light (especially ultraviolet rays), heat or oxygen.
Stabilizers include, for example, sodium edetate (ethylenediaminetetraacetic acid disodium salt); antioxidants such as dibutylhydroxytoluene (BHT); ultraviolet absorbers such as benzoylmethane derivatives;
The amount of the stabilizer to be blended can generally be in the range of, for example, 0.01% by mass or more and 1% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the non-aqueous patch.

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

[Support]
The support used for the non-aqueous patch of the present invention includes flexible supports such as films, nonwoven fabrics, Japanese paper, cotton fabrics, knitted fabrics, woven fabrics, and laminated composites of nonwoven fabrics and films. These supports are preferably made of a flexible material that can adhere to the skin and follow the movement of the skin, and a material that can suppress the occurrence of rashes on the skin after being applied for a long period of time. Materials for these supports include, for example, polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon/polyethylene terephthalate composite, polyacrylonitrile, polyvinyl alcohol, Acrylic polyurethane, ester polyurethane, ether polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene rubber, ethylene-vinyl acetate Examples include those containing copolymers, cellophane, etc. as essential components.

In addition, the support such as cloth can be colored with a coloring agent to give a tone such as a skin color, thereby reducing the difference from the skin color at the time of application. In addition, from the point of view that the color tone of the skin under application can be easily seen through, it is possible to adopt the form of a highly transparent plastic film.

The thickness of the support is usually about 5 μm to 1 mm. When the support is cloth, its thickness is preferably 50 μm to 1 mm, more preferably 100 to 800 μm, still more preferably 200 to 700 μm. When the support is a plastic film, its thickness is
It is preferably 10 to 300 μm, more preferably 12 to 200 μm, still more preferably 15 to 150 μm. When the thickness of the support is as thin as about 5 μm to 30 μm, if a peelable carrier film layer is provided on the side opposite to the pressure-sensitive adhesive layer formed on the support, handling as an adhesive patch is improved. It is preferable because it improves. However, if the thickness of the backing is less than 5 μm, the strength and handleability of the patch are reduced, making it difficult to attach to the skin, tearing due to contact with other members, etc., and contact with water such as bathing. It may detach from the skin in a short time upon contact. On the other hand, if the thickness of the backing is too large (more than 1 mm), the patch becomes difficult to follow the movement of the skin, and the edges of the patch tend to peel off. There is a risk of peeling off or increased discomfort during application.
When the support is a film, one side or both sides of the support may be subjected to a treatment such as sandblasting or corona treatment for the purpose of improving the anchoring property of the pressure-sensitive adhesive to the support.
In addition, in order to facilitate removal from the packaging material, unevenness may be provided on one or both sides of the support by a method other than sandblasting.

[Release liner]
The release liner (also referred to as a release layer or release paper) used in the non-aqueous patch of the present invention is preferably made of a material that does not readily absorb or adsorb drugs, etc. in the adhesive layer, and is commonly used in the technical field of 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; fine paper, glassine paper, parchment paper, kraft Paper such as paper and synthetic paper; release processed paper obtained by coating the above plastic film, paper, synthetic paper, synthetic fiber, etc. with a release agent having release performance such as silicone resin or fluororesin; aluminum foil; Colorless or colored sheets, such as laminated laminated papers and laminated release papers in which the laminated papers are coated with a release agent, may be mentioned. It should be noted that the release liner can be provided with unevenness so that it can be easily removed from the packaging material.
The thickness of these release liners is not particularly limited, but usually ranges from 10 μm to 1 mm, for example from 20 μm to 500 μm, preferably from 40 μm to 200 μm.
The shape of the release liner can be square, rectangular, circular, etc., and can optionally have rounded corners. The size can be the same as or slightly larger than the size of the support in the patch. The release liner may be composed of one sheet or a plurality of divided sheets, and the cut line may be composed of a straight line, a wavy line, or a perforated line, and the release liners may partially overlap each other.

[Method for producing non-aqueous patch]
The non-aqueous patch of the present invention can be produced using a conventionally known method. For example, it can be produced through the following steps i) or ii).
i) A step of applying a water-containing pressure-sensitive adhesive layer-forming composition onto a support to form a water-containing pressure-sensitive adhesive layer, and a step of drying the water-containing pressure-sensitive adhesive layer to form a pressure-sensitive adhesive layer that does not substantially contain water. and a step of laminating the pressure-sensitive adhesive layer formed on the support and the release liner.
ii) A step of applying a water-containing pressure-sensitive adhesive layer-forming composition onto a release liner to form a water-containing pressure-sensitive adhesive layer, and a step of drying the water-containing pressure-sensitive adhesive layer to form a pressure-sensitive adhesive layer that does not substantially contain water. and a step of bonding the pressure-sensitive adhesive layer formed on the release liner and the support.
Although the thickness of the pressure-sensitive adhesive layer is not particularly limited, it is usually 10 μm to 200 μm, for example, about 20 μm to 100 μm.

The water-containing pressure-sensitive adhesive layer-forming composition includes various components contained in the pressure-sensitive adhesive layer described above: active ingredient, acrylic hydrophilic pressure-sensitive adhesive, acrylic acid alkyl ester copolymer, organic solvent, cross-linking agent, organic acid, It contains other optional components and, as described below, a solvent used when mixing various components, for example, when mixing an acrylic hydrophilic pressure-sensitive adhesive.
In the preparation of the water-containing pressure-sensitive adhesive layer-forming composition, water is preferably used as a solvent for blending the acrylic hydrophilic pressure-sensitive adhesive. The amount of water used is not particularly limited, but for example, 10% by mass or more and 90% by mass or less, 15% by mass or more and 70% by mass or less, 20% by mass or more and 50% by mass, based on the total mass of the water-containing pressure-sensitive adhesive layer-forming composition. It can be in the range of not more than 20% by mass and not more than 40% by mass.

In addition, the non-aqueous pressure-sensitive adhesive layer of the present invention does not substantially contain water. In the Japanese Pharmacopoeia, a tape is defined as a patch using a base containing almost no water, and the present invention also follows this rule.

The non-aqueous patch of the present invention is also a patch with low skin irritation.
Here, the skin irritation during application of the patch can be evaluated, for example, by the individual average value (mean PII) of the primary skin irritation index (PII) according to the Draize method. The patch of the invention can be, for example, 1.40 or less.
The primary skin irritation index (PII) (Primary Irritation Index) according to the Draize method is an evaluation method using lesions of rabbits. Specifically, the specimen (test substance) was applied to the back of the rabbit, and after a predetermined period of time, the specimen was removed. It is a value shown as the total value of two evaluation values (the average value if the evaluation time is multiple), considering the individual differences evaluated, and the individual average value (average P.4). I.I.) is calculated and evaluated.
In the present invention, after a sample (non-aqueous patch) was applied for 24 hours, after the sample was removed, the pasted site was observed after a predetermined period of time had elapsed, and the stimulus response was scored. 30 minutes and 24 hours after removal. based on scoring of stimulus response in mean P.O. I. I. is calculated to evaluate skin irritation.

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

<Preparation of adhesive patch>
Patches of Examples and Comparative Examples were produced according to the following procedure.

Example 1:
1.5 parts by mass of polyvinyl alcohol was dissolved in 20 parts by mass of purified water (aqueous phase).
Next, 1.25 parts by mass of ethylene glycol salicylate and 1 part by mass of L-menthol were dissolved by adding 1 part by mass of Macrogol (registered trademark) 400 (manufactured by Sanyo Chemical Industries, Ltd.) (oil phase).
Furthermore, 4 parts by mass of partially neutralized polyacrylic acid, 4 parts by mass of carmellose sodium, and 0.25 parts by mass of dihydroxyaluminum aminoacetate were uniformly dispersed in 25 parts by mass of concentrated glycerin (glycerin phase).
In a stirrer, an aqueous phase, a methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate content in the copolymer: 31.1% by mass, a small amount of polyoxyethylene nonylphenyl ether (30EO) contained in the emulsion ) 7 parts by mass (the solid content conversion value of the copolymer is 4.13 parts by mass), 0.20 parts by mass of sodium edetate hydrate, and 30 parts by mass of D-sorbitol 70% aqueous solution are added in this order and dispersed uniformly. or dissolved. An oil phase and a glycerin phase were added in this order and kneaded uniformly. Further, 1 part by mass of lactic acid was added, and after correcting the mass with purified water so that the total mass was 100 parts by mass, the mixture was uniformly kneaded under degassing conditions to obtain a water-containing pressure-sensitive adhesive layer-forming composition of Example 1. rice field.
The obtained composition for forming a water-containing pressure-sensitive adhesive layer was spread on the silicone surface of a PET (75 μm) silicone-treated on one side of the liner with a spreader adjusted to a slit width of 0.5 mm, and a knitted support (
(made of polyester) and then aged at 50° C. for 1 week. After aging, the liner was peeled off and the surface on which the water-containing pressure-sensitive adhesive layer-forming composition was spread was used as the upper surface, and dried overnight at 50°C to remove moisture to form a pressure-sensitive adhesive layer. After removing moisture, the liner was laminated and punched into an arbitrary shape to obtain the formulation of Example 1.

Example 2:
Example 1, except that the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate content: 31.1% by mass) was changed to an emulsion containing 40.8% by mass of methyl acrylate. The formulation of Example 2 was obtained in the same manner as above.

Example 3:
Example 1, except that the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate content: 31.1% by mass) was changed to an emulsion containing 46.7% by mass of methyl acrylate. The formulation of Example 3 was obtained in the same manner as above.

Example 4:
Methyl acrylate/2-ethylhexyl acrylate copolymer emulsion was added to 10 parts by mass of methyl methacrylate/2-ethylhexyl acrylate copolymer emulsion (the amount of methyl methacrylate in the copolymer was 30.0% by mass). A formulation of Example 4 was obtained in the same manner as in Example 1, except that the solid content conversion value was changed to 4.34 parts by mass).

Example 5:
Methyl acrylate/2-ethylhexyl acrylate copolymer emulsion was added to 10 parts by mass of ethyl methacrylate/2-ethylhexyl acrylate copolymer emulsion (ethyl methacrylate content in copolymer: 30.0% by mass). A formulation of Example 5 was obtained in the same manner as in Example 1, except that the solid content conversion value was changed to 4.14 parts by mass).

Example 6:
Methyl acrylate/2-ethylhexyl acrylate copolymer emulsion, n-butyl methacrylate/2-ethylhexyl acrylate copolymer emulsion (n-butyl methacrylate content in copolymer: 30.0% by mass) 10 parts by mass ( A formulation of Example 6 was obtained in the same manner as in Example 1, except that the solid content conversion value of the copolymer was changed to 4.34 parts by mass).

Example 7:
Methyl acrylate/2-ethylhexyl acrylate copolymer emulsion was added to 10 parts by mass of methyl acrylate/n-butyl acrylate copolymer emulsion (methyl acrylate content in copolymer: 30.0% by mass). A formulation of Example 7 was obtained in the same manner as in Example 1, except that the solid content conversion value was changed to 4.54 parts by mass).

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

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

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

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

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

Comparative Example 1:
Example 1, except that the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate content: 31.1% by mass) was changed to an emulsion containing 14.7% by mass of methyl acrylate. A formulation of Comparative Example 1 was obtained in the same manner as above.

Comparative Example 2:
The blending amount of the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount: 14.7% by mass) was changed to 10 parts by mass (the solid content conversion value of the copolymer was 5.90 parts by mass). A preparation of Comparative Example 2 was obtained in the same manner as in Comparative Example 1 except for the above.

Comparative Example 3:
The blending amount of the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount: 14.7% by mass) was changed to 15 parts by mass (the solid content conversion value of the copolymer was 8.85 parts by mass). A preparation of Comparative Example 3 was obtained in the same manner as in Comparative Example 1 except for the above.

Comparative Example 4:
The blending amount of the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount: 14.7% by mass) was changed to 20 parts by mass (the solid content conversion value of the copolymer was 11.80 parts by mass). A preparation of Comparative Example 4 was obtained in the same manner as in Comparative Example 1 except for the above.

Comparative Example 5:
The blending amount of the methyl acrylate/2-ethylhexyl acrylate copolymer emulsion (methyl acrylate blending amount: 14.7% by mass) was changed to 25 parts by mass (the solid content conversion value of the copolymer was 14.75 parts by mass). A preparation of Comparative Example 5 was obtained in the same manner as in Comparative Example 1 except for the above.

Reference Example 1, Reference Example 2:
A commercially available tape (Fatus (registered trademark) 5.0, Hisamitsu Pharmaceutical Co., Ltd., lot number: SC08T) was used as the preparation of Reference Example 1, and a commercially available poultice (Vanterin Kowa New Mini Pad, Kowa Co., Ltd., lot number: NA640) was used, and various tests described later were performed.

Tables 3 and 4 show the formulations of the pressure-sensitive adhesive layers of the formulations produced in Examples 1 to 12 and Comparative Examples 1 to 5. The values of each component shown in Tables 3 and 4 are based on the total mass of the pressure-sensitive adhesive layer. Moisture (in addition to the purified water used for the aqueous phase, methyl acrylate/2-ethylhexyl acrylate copolymer emulsion, methyl methacrylate/2-ethylhexyl acrylate copolymer emulsion, ethyl methacrylate/2-ethylhexyl acrylate copolymer emulsion , n-butyl methacrylate/2-ethylhexyl acrylate copolymer emulsion, methyl acrylate/n-butyl acrylate copolymer emulsion, D-sorbitol aqueous solution) mass) is 100% by mass.

Test Example 1 (Removability between plaster and reattachment)
The formulations of Examples 1 to 12, Comparative Examples 1 to 5, and Reference Examples 1 and 2 were evaluated for exfoliation and reattachment.
1) Peelability Between Plasters The liner of each preparation was peeled off, and the adhesive layers were adhered firmly to each other and allowed to stand. After 30 seconds had passed, the portion bonded together by hand was peeled off and evaluated according to the following criteria (N=3).
◯: Easily peeled △: Peeled but deformed ×: Not peeled 2) Reattachment The liner of each preparation was peeled off and applied to the forearm. After 30 seconds had passed, the patch was peeled off, applied again to another part of the forearm, and evaluated according to the following criteria (N=3).
○: reattachment Δ: weak reattachment ×: no reattachment The obtained results are shown in Tables 3 and 4.

Test Example 2 (adhesion test)
For each formulation of Examples 1 to 12, Comparative Examples 1 to 5, and Reference Examples 1 and 2, the inclined ball tack adhesive strength was measured according to Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3 .2 Performed according to the Inclined Ball Tack Test Method.
The results obtained are shown in Tables 3 and 4.

Test Example 3 (primary skin irritation index test, transepidermal water loss)
A primary skin irritation index (P.I.I.) test based on the Draize method was performed by the following method. For details of the Draize method, see Draize JH, Woodard, G. and Calvery, HO (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).

Each preparation of Examples 1 to 3, Comparative Examples 1 to 5, and Reference Examples 1 and 2 was punched out to 15 mm diameter, and after peeling off the release liner, white rabbits (17 weeks old) were clipped and shaved. 20 years old, male, JW) (N=3), and a moisture-permeable catheleep (transparent adhesive film, Nichiban Co., Ltd.) was applied over the preparation so as to cover the entire applied preparation.
After 24 hours of application, the catheter and the preparation were peeled off, the application site of the preparation was wiped with purified water, and the state of the skin at the application site was observed 30 minutes after removal and 24 hours later. The stimulus response was scored according to the criteria of .
Also, based on the scoring values after 30 minutes and 24 hours after peeling the formulation, the average scoring values after 30 minutes or 24 hours, and the individual average skin irritation index (PII) of each individual The degree of skin irritation was evaluated from the average skin primary irritation index (average PII). The results obtained are shown in Tables 3 and 4.

Furthermore, for the formulations of Example 3, Comparative Example 1, Reference Example 1 and Reference Example 2, the amount of transepidermal water loss (TEWL: transepidermal water loss) after 30 minutes and 24 hours after peeling off the formulation was measured using a VapoMeter (Delphin・Technology Co., Ltd.).
Transepidermal water loss (TEWL) is a value that measures how much water transpires from the body (skin). This means that the barrier function of the skin is maintained by Therefore, if the TEWL value is small, it means that there is little exfoliation of keratin, and it can be used as an indicator of skin irritation during exfoliation. The results obtained are shown in Tables 3 and 4.

As shown in Table 3, among the monomers constituting the acrylic acid alkyl ester-based copolymer, the blending amount of monomer A whose homopolymer Tg of the monomer is 270 K or more, that is, methyl acrylate/acrylic acid 2- Compounding amount of methyl acrylate in ethylhexyl copolymer resin, Compounding amount of methyl methacrylate in methyl methacrylate/2-ethylhexyl acrylate copolymer resin, Blending amount of ethyl methacrylate in ethyl methacrylate/2-ethylhexyl acrylate copolymer resin The amount of n-butyl methacrylate in the n-butyl methacrylate/2-ethylhexyl acrylate copolymer resin, and the amount of methyl acrylate in the methyl acrylate/n-butyl acrylate copolymer resin is 30% by mass or more. The formulations of Examples 1 to 12 using the resin emulsion exhibited an adhesive force equal to or greater than that of the commercially available tape agents (Reference Examples 1 and 2) shown in Table 4.
Further, as shown in the results of Examples 1 to 3, the skin irritation (average PII) was a result of mild irritation, and the transepidermal moisture obtained in Example 3 The transpiration value was also lower than that of the formulation of Reference Example described later.
Furthermore, the preparations of Examples 1 to 12 were able to be easily peeled off even when the adhesive layers were adhered to each other, and reattachment was also observed.

On the other hand, the formulation (Comparative Example 1) in which the blending amount of the above-mentioned monomer A, that is, the blending amount of methyl acrylate in the methyl acrylate/2-ethylhexyl acrylate copolymer resin is less than 30% by mass (Comparative Example 1) has poor ball tack adhesive strength. The results were lower than those of Examples 1-12. As described above, if the amount of methyl acrylate exceeds 50% by mass, the emulsion aggregates and precipitates, making redispersion difficult, and the upper limit of the amount was 50% by mass.
In addition, regarding the methyl acrylate/2-ethylhexyl acrylate copolymer resin having a methyl acrylate content of 14.7% by mass adopted in Comparative Example 1, the content of the copolymer resin was changed to that of the water-containing pressure-sensitive adhesive layer-forming composition. Even in the formulations (Comparative Examples 1 to 5) increased in the range of 7% to 25% by mass (6.42 to 19.68% by mass as solid content in the formulation after water removal) during the production of , the ball tack adhesive strength was lower than that of the formulations of Examples 1 to 12, and the ball tack adhesive strength of the formulation of Comparative Example 5, which had the highest compounding amount, was only 13.
The formulations of Comparative Examples 1 to 3 were evaluated for peelability and reattachment between the plaster in the same manner as the formulations of Examples. Both peelability and reattachment properties were evaluated below those of the preparations of Examples.

The preparation of Reference Example 1, which is a commercially available preparation, was evaluated as having no re-adherability because the pressure-sensitive adhesive layers were not peeled off when adhered to each other.
In the preparation of Reference Example 2, after the adhesive layers were adhered to each other, the adhesive layers peeled off, but resulted in deformation.
Furthermore, the formulation of Reference Example 1 had a large transepidermal water loss value, suggesting a large exfoliation of keratin.

As a blank, the TEWL of the back skin of clipped and shaved white rabbits to which no patch was applied was measured at N=3, and the average value was 5.4 (g/m ² ·h). there were. The difference between this blank TEWL and the TEWL of Example 3 (after 24 hours: 6.3 g/m ² ·h) was slight, and from this result also, the patch of Example caused less keratin exfoliation and skin irritation. was confirmed to be low.

From the above results, among the monomers constituting the acrylic acid alkyl ester-based copolymer, the amount of monomer A (such as methyl acrylate) whose homopolymer Tg is 270K or higher is 30 to 50% by mass. By adopting a certain acrylic acid alkyl ester copolymer (methyl acrylate/2-ethylhexyl acrylate copolymer resin, etc.), it is easy to peel off the paste, has re-adhesion, and has adhesiveness that is superior to that of commercially available tapes. It was confirmed that it is possible to provide a patch that is as strong as , and has low skin irritation not only when it is applied but also when it is peeled off.

Claims (5)

A non-aqueous patch comprising a support, and a pressure-sensitive adhesive layer and a release liner provided on the support,
A non-aqueous patch, wherein the pressure-sensitive adhesive layer essentially contains the following components 1) to 5).
1) acrylic hydrophilic adhesive 2) acrylic acid alkyl ester copolymer which is a copolymer of a monomer mixture consisting of monomer A and monomer B,
The monomer A is a monomer that becomes a polymer having a glass transition temperature (Tg) of 270 K or higher when the monomer A is homopolymerized, and includes methyl acrylate, methyl methacrylate, ethyl methacrylate, n-butyl methacrylate, at least one monomer selected from the group consisting of i-butyl methacrylate, t-butyl methacrylate, vinyl acetate, acrylonitrile, acrylamide and styrene;
The monomer B is a monomer that becomes a polymer having a glass transition temperature (Tg) of 220 K or less when the monomer B is homopolymerized, and is composed of butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate and isononyl acrylate. is at least one monomer selected from the group consisting of
3) an organic solvent 4) a cross-linking agent 5) an organic acid, wherein the proportion of the monomer A is 30% by mass or more and 50% by mass or less with respect to the total mass of the monomer mixture. 2) The acrylic acid alkyl ester copolymer is blended in an amount of 0.1% by mass or more and 30% by mass or less based on the total mass of the pressure-sensitive adhesive layer.
The non-aqueous patch according to claim 1. The 2) acrylic acid alkyl ester-based copolymer and the 1) acrylic hydrophilic pressure-sensitive adhesive have a mass ratio of 2) acrylic acid alkyl ester-based copolymer: 1) acrylic hydrophilic pressure-sensitive adhesive = 1: It is blended at a ratio of 2 to 3: 1,
The non-aqueous patch according to claim 1 or 2. the monomer A is at least one monomer selected from the group consisting of methyl acrylate, methyl methacrylate, ethyl methacrylate and n-butyl methacrylate;
The monomer B is at least one monomer selected from the group consisting of 2-ethylhexyl acrylate and butyl acrylate.
The non-aqueous patch according to any one of claims 1 to 3 . 5. The non-aqueous patch according to any one of claims 1 to 4 , further comprising an active ingredient.