JP7257410B2 - Hydrous patch - Google Patents

Description

TECHNICAL FIELD The present invention relates to a water-containing patch, and more particularly, to a water-containing patch that maintains high adhesive strength even after volatilization of water in the adhesive layer and has low skin irritation.

A patch using an adhesive base containing water, which is generally referred to as a "plast" (herein referred to as a water-containing patch), has a base layer (adhesive layer) containing an active ingredient such as a drug. It is a type of adhesive patch provided on a support such as non-woven fabric. Since cataplasms use an adhesive base containing water in the paste layer, they have low skin irritation but weak adhesive strength. The problem was that it was easy to peel off from the skin.
In order to solve these problems, an emulsion (also known as an emulsion) base in which an acrylic acid alkyl ester copolymer, which is known as one component constituting a non-aqueous (also known as hydrophobic or lipophilic) pressure-sensitive adhesive, is dispersed, A technique of blending in a base layer (adhesive layer) of a water-containing patch is known.

For example, in Patent Document 1, 1% of methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name Nikasol TS-620, Nippon Carbide Industry Co., Ltd.) is added to the poultice base (plaster). A patch (comparative product) is disclosed.
Patent document 2 provides a water-containing adhesive patch that exhibits adhesive strength and re-adhesive strength when applied for a long period of time, suppresses deterioration of hardening and flexibility due to moisture loss, and suppresses breakage of the backing during peeling. For this purpose, a water-dispersible surfactant of 0.01% by mass or more and 10.0% by mass or less and a methyl acrylate/2-ethylhexyl acrylate copolymer of the same amount are added to the entire aqueous patch composition for external use. A water-containing patch for external use containing 5.0% by mass or more and 10% by mass or less is disclosed.
In Patent Document 3, the object is to provide a poultice that has sufficient adhesion even when the water content of the poultice decreases with the passage of time. A poultice containing a methyl acrylate/2-ethylhexyl acrylate copolymer and polyacrylic acid in an amount up to 10 times the weight (5 to 25% by weight based on the plaster) is disclosed.
Patent Document 4 discloses a poultice containing poly(methyl acrylate/2-ethylhexyl acrylate) and a surfactant such as polyethylene glycol fatty acid ester for the purpose of providing a poultice that allows the release liner to be peeled off with a smaller force. A poultice is disclosed.
Patent Document 5 discloses that a cooling sheet is obtained using an adhesive composition containing 1.5% by weight of an acrylic resin emulsion (trade name: Nikasol TS-620) and 6.2% by weight of sodium polyacrylate. ing.

JP-A-9-208462 Patent No. 5650684 Patent No. 5921779 specification WO2016/104227 JP-A-2002-104957

As described above, it is known to incorporate an acrylic acid alkyl ester copolymer such as methyl acrylate/2-ethylhexyl acrylate copolymer into the adhesive layer in order to increase the adhesive durability of the water-containing adhesive patch. ing. However, when the blending amount of the copolymer is small, for example, in the adhesive patch disclosed in Patent Document 1, the result shows that both the initial tackiness and the persistent adhesiveness are lacking due to the low blending amount. Even if the desired effect of improving the adhesive strength is not obtained and the amount is increased, the adhesive strength, especially after the water in the adhesive layer has volatilized, can be said to be sufficiently satisfactory as compared with the tape agent. It was nothing.

As a result of intensive research to solve the above problems, the present inventors have found that the glass transition temperature (Tg ) is 30 to 50% by mass, and a monomer that becomes a polymer with a Tg of 220K or less when homopolymerized is blended so that the total amount of both monomers is 100% by mass. By blending, even after the moisture in the adhesive layer volatilizes, the adhesive strength does not decrease but rather improves, and the skin irritation is low, and the present invention was completed.

That is, the present invention provides a water-containing adhesive patch comprising a backing, and a pressure-sensitive adhesive layer and a release liner provided on the backing,
It relates to a water-containing patch, wherein the pressure-sensitive adhesive layer essentially contains the following components 1) to 6).
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,
acrylic acid alkyl ester copolymer, wherein the ratio 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 3) organic solvent 4) cross-linking agent 5) organic acid 6) water

Further, according to the present invention, the following embodiments are provided.
1. 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 and isononyl acrylate.
The water-containing adhesive patch.
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 water-containing patch, wherein the monomer B is at least one monomer selected from the group consisting of 2-ethylhexyl acrylate and butyl acrylate.
3. The water-containing adhesive 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. Adhesive for water-containing adhesive patch is an acrylic acid alkyl ester copolymer in which 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. By blending in layers, the adhesive strength can be maintained even after the moisture in the adhesive layer evaporates, and the water-containing system can be reapplied to the skin with low skin irritation and no adhesion between the adhesive layers. We can provide patches.

As described above, in order to increase the durability of the adhesive strength of water-containing patches, acrylic resins such as methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name: Nikasol TS-620, Nippon Carbide Industry Co., Ltd.) are used. Proposals have been made to incorporate an acid alkyl ester copolymer into the pressure-sensitive adhesive layer and to increase the amount of this compound. However, in the proposals so far, even when the blending amount of the copolymer is increased, the adhesive strength after the moisture in the adhesive layer evaporates (after water volatilization) is still insufficient compared to the tape agent. It was not something that could be said.
In view of the above problems, the present inventors have focused on the types of monomers that constitute acrylic acid alkyl ester copolymers, which have not been studied so far, and particularly on the blending ratio thereof. After) was evaluated for adhesive strength. Then, focusing on the glass transition temperature (Tg) of the homopolymer composed of the monomer, a monomer that becomes a polymer having a Tg of 270 K or more when homopolymerized and a polymer having a Tg of 220 K or less when homopolymerized By combining a monomer that becomes They have found that even when the blending amount of the copolymer is small, the patch is excellent in adhesive strength not only when wet but also when dry, and is low in skin irritation.
The configuration of the water-containing adhesive patch of the present invention will be described below.

The water-containing 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]
The water-containing adhesive patch of the present invention has a water-containing pressure-sensitive adhesive layer, in addition to a hydrophilic acrylic pressure-sensitive adhesive described later, an acrylate alkyl ester-based copolyester that generally constitutes a non-aqueous acrylic pressure-sensitive adhesive. It is characterized by blending a polymer as well.
Adhesives generally used for the adhesive layer (plaster layer) of water-containing patches include polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, N-vinylacetamide/sodium acrylate copolymer Hydrophilic acrylic adhesives such as resins are widely used. From the viewpoint of high affinity with the hydrophilic acrylic adhesive and uniform kneading, acrylic and methacrylic adhesives are used as non-aqueous adhesives to be blended in the water-containing adhesive layer of the water-containing patch. An emulsion-type adhesive is preferably blended.
In this specification, the term "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 acrylic pressure-sensitive adhesive and methacrylic acid. It is intended to include both system adhesives.

<Alkyl acrylate copolymer>
The acrylic acid alkyl ester copolymer (non-aqueous adhesive base) that constitutes the non-aqueous acrylic adhesive is an alkyl ester having 2 to 9 carbon atoms and homopolymerized as a component that exhibits adhesive strength. A monomer that becomes a polymer with a glass transition temperature (Tg) of −55° C. (218 K) or less when homopolymerized, and a polymer that has a Tg of 8 to 165° C. (281 to 438 K) when homopolymerized as a component that improves cohesive strength. It is a copolymer composed of a monomer having a functional group such as a carboxyl group or a hydroxy group, which serves as a cross-linking point, if necessary (one 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 (methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion), which has been used in water-based adhesive patches, does not provide the desired adhesive strength. In view of the fact that the adhesive strength is lowered after volatilization of water from the adhesive layer, a change in the copolymerization ratio of the copolymer was examined.
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 can maintain adhesive strength even when water evaporates from the adhesive layer. 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 pressure-sensitive adhesive layer of the water-containing patch of the present invention, the amount of the acrylic acid alkyl ester copolymer (in terms of solid content in the case of emulsion) is based on the total weight of the pressure-sensitive adhesive layer of the water-containing 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.
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 water-containing adhesive patch of the present invention optionally contains an active ingredient. The water-containing patch of the present invention when it does not contain an active ingredient can be used as a covering material for keloid-like skin or 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 depending on the type thereof. % by mass or less.

<Acrylic hydrophilic adhesive>
The pressure-sensitive adhesive layer of the water-containing patch of the present invention contains an acrylic hydrophilic pressure-sensitive adhesive.
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 N-vinylacetamide/sodium acrylate copolymer resin.
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 water-containing adhesive patch. can.

<Organic solvent>
The organic solvent blended in the adhesive layer of the water-containing adhesive patch of the present invention may play a role in assisting dissolution of active ingredients such as drugs and 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 water-containing patch.

<Crosslinking agent>
Examples of the cross-linking agent blended in the pressure-sensitive adhesive layer of the water-containing adhesive 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. For example, 0.01% to 6.0% by mass, 0.01% to 4.0% by mass, or 0.01% by mass or more based on the total mass of the adhesive layer of the water-containing patch. 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 water-containing adhesive 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 water-containing patch.

<Water>
As described above, the water-containing patch of the present invention contains water (moisture) in the pressure-sensitive adhesive layer. As used herein, "water" contained in the pressure-sensitive adhesive layer includes not only water separately added as water when the pressure-sensitive adhesive layer is formed, but also water contained in the form of an emulsion, an aqueous solution, or the like. The content of water 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 adhesive layer of the water-containing patch. % or less. Note that this water content is the value at the time of preparation of the patch or before application of the patch, and is not limited to the case where water volatilizes from the adhesive layer during the course of application.

<Other optional ingredients>
The pressure-sensitive adhesive layer of the water-containing adhesive patch of the present invention may contain, as other optional components, water-soluble polymer compounds, surfactants, wetting agents, stabilizers, antioxidants, inorganic powders, colorants, fragrances, and preservatives. Ingredients, such as agents, that can generally be blended in the adhesive layer of conventional hydrous patches (plasts) or non-aqueous patches (tapes) can be blended. 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 pressure-sensitive adhesive layer of the water-containing 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, or 0.01% by mass to 5% by mass, based on the total mass of the adhesive layer of the water-containing patch. be able to.

<Wetting agent>
A humectant (also referred to as a humectant) can be blended into the pressure-sensitive adhesive layer of the water-containing adhesive patch of the present invention in order to suppress evaporation of water over time. 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 water-containing patch, for example, 1.0% by mass or more and 70% by mass or less, 5.0% by mass or more and 60% by mass or less, or 10% by mass. % or more and 60 mass % or less.

<Stabilizer>
The pressure-sensitive adhesive layer of the water-containing 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 water-containing 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 water-containing 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 preferably 10-300 μm, more preferably 12-200 μm, still more preferably 15-150 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 water-containing adhesive 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 water-containing patch]
The water-containing 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 pressure-sensitive adhesive layer-forming composition onto a support to form a pressure-sensitive adhesive layer, and a step of laminating the pressure-sensitive adhesive layer formed on the support and a release liner.
ii) A step of applying a pressure-sensitive adhesive layer-forming composition onto a release liner to form a pressure-sensitive adhesive layer, and a step of laminating the pressure-sensitive adhesive layer formed on the release liner and a support.
Although the thickness of the pressure-sensitive adhesive layer is not particularly limited, it is usually 10 μm to 1000 μm, for example, about 20 μm to 800 μm.

The 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 and water. and may further contain other optional ingredients.

The water-containing adhesive patch of the present invention is characterized in that it maintains its adhesive strength both when it contains water and when it dries (after volatilization of water), and it also has low skin irritation.
Here, the skin irritation can be evaluated, for example, by the individual average value (average PII) of the primary skin irritation index (PII) according to the Draize method. .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 (water-containing patch) was applied for 24 hours, after the sample was removed and after a predetermined period of time had elapsed, the site of application was observed and the stimulus response was scored, and 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).
Further, 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 ), 0.20 parts by mass of sodium edetate hydrate, and 30 parts by mass of a 70% aqueous solution of D-sorbitol were added in this order, and dispersed or dissolved uniformly. An oil phase and a glycerin phase were added in this order and kneaded uniformly. Furthermore, 1 part by mass of lactic acid was added, and the mass was corrected with purified water so that the total mass was 100 parts by mass. .
The pressure-sensitive adhesive layer-forming composition thus obtained was spread on the silicone surface of a liner (PET (75 μm) with one side treated with silicone) using a spreader adjusted to have a slit width of 0.5 mm, and a knit support (made of polyester) was formed. After lamination, it was aged at 50° C. for 1 week. After aging, it was punched into an arbitrary shape to obtain the preparation 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:
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 27.0% by mass of methyl acrylate. A formulation of Comparative Example 2 was obtained in the same manner as above.

Comparative Example 3:
In the same manner as in Comparative Example 1, except that 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 (10% by mass), A formulation of Comparative Example 3 was obtained.

Comparative Example 4:
In the same manner as in Comparative Example 1, except that 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 (15% by mass), A formulation of Comparative Example 4 was obtained.

Comparative Example 5:
In the same manner as in Comparative Example 1, except that 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 (20% by mass), A formulation of Comparative Example 5 was obtained.

Comparative Example 6:
In the same manner as in Comparative Example 1, except that 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 (25% by mass), A formulation of Comparative Example 6 was obtained.

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

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.

Test Example 1 (adhesion test)
For each formulation of Examples 1 to 12, Comparative Examples 1 to 6, and Reference Examples 1 and 2, the initial stage (hereinafter referred to as "when containing water"; the formulations of Examples and Comparative Examples were immediately after production, Immediately after opening the package of the product in the reference example), and after drying overnight at 50 ° C. , held overnight at 50°C) was measured according to the General Test Methods of the Japanese Pharmacopoeia 6.12 Adhesive Force Test Method 3.2 Inclined Ball Tack Test Method.
The results obtained are shown in Tables 2 and 3.

Test Example 2 (Plaster peelability and reattachment test)
The formulations of Examples 1 to 12, Comparative Examples 1 to 6, and Reference Examples 1 and 2 were evaluated for exfoliation and reattachment.
The obtained results are also shown in Tables 2 and 3.
1) Peeling property between plaster The liner of each formulation cut into a size of 5 cm x 5 cm was peeled off, each formulation was folded in two, the adhesive layers were adhered firmly together, and left still for 30 seconds. After that, the bonded portion 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 formulation (10 cm × 7 cm) was peeled off and applied to the inside of a human upper arm. 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).
○: Re-adhesion △: Weak re-adhesion ×: No re-adhesion

<Test results>
As shown in Table 2, among the monomers constituting the acrylic acid alkyl ester-based copolymer, the blending amount of monomer A whose homopolymer Tg is 270 K or higher, 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 amount, n-butyl methacrylate/2-acrylic acid
Examples 1 to 1 using resin emulsions in which the blending amount of n-butyl methacrylate in the ethylhexyl copolymer resin and the blending amount of methyl acrylate in the methyl acrylate/n-butyl acrylate copolymer resin are 30% by mass or more. The formulation of Example 9 had a slightly lower ball tack adhesive strength immediately after production (when containing water) than the commercially available tape (Reference Example 1) and the commercially available poultice (Reference Example 2) (see Table 3). However, the ball tack adhesive strength when dried (dried overnight at 50° C.) showed almost the same adhesive strength as the commercially available tape agent. Further, as shown in the results of Examples 3 and 8 to 12, the blending amount of the methyl acrylate/2-ethylhexyl acrylate copolymer resin (methyl acrylate blending amount: 46.7% by mass) was increased. Accordingly, the adhesive strength increased both immediately after production (when containing water) and during drying. showed equal or higher adhesive strength. In any of the examples, even when the pressure-sensitive adhesive layers were adhered to each other, they could be easily peeled off, and re-adhesion was also observed. was preserved.

On the other hand, the amount of monomer A, that is, the amount of methyl acrylate in the methyl acrylate/2-ethylhexyl acrylate copolymer resin is less than 30% by mass (Comparative Examples 1 and 2), the ball when dry The result was that the tack adhesive strength was lower than that 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 from 7% by mass to 25% by mass. (4.13% by mass to 14.75% by mass as solid content) formulations (Comparative Example 1, Comparative Example 3 to Comparative Example 6) were used in Examples 1 to 6 both when wet and when dry. It resulted in lower ball tack adhesion than the formulation of Example 3.
The formulations of Comparative Examples 1 to 4 were evaluated for peelability and reattachment between the plaster in the same manner as the formulations of Examples, but the formulations of Comparative Examples 5 and 6 were evaluated as Both peelability and reattachability were evaluated as being inferior to those of the formulations of the examples, and there was a tendency that these performances rather deteriorated with an increase in the blending amount of the acrylic acid alkyl ester-based copolymer.

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.

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 becomes a formulation that has excellent adhesive strength not only when it is wet but also when it is dry. was confirmed, and it was confirmed that the preparation can be easily peeled off between the plaster and reattached.

Test Example 3 (primary skin irritation index test)
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).

The formulations of Example 3 and Comparative Example 1 were punched into 15 mm diameter pieces, and after peeling off the release liner, the cut and shaved white rabbits (17-week-old, male, JW) (N=3) were attached to the backs of the rabbits. A moisture-permeable catheleep (transparent adhesive film, Nichiban Co., Ltd.) was applied over the formulation so as to cover the entire formulation.
After 24 hours of application, the catheleep and the preparation were peeled off, the application site of the preparation was wiped with purified water, and the skin condition of 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 scored values 30 minutes and 24 hours after peeling off the formulation, the average scored after 30 minutes or 24 hours, and the individual average value from the primary skin irritation index (PI) of each individual A mean skin primary irritation index (mean P.I.I.) was obtained.
DNBC (2,4-dinitrochloro-benzene) was used as a positive control. Using a commercially available poultice (Halix (registered trademark) 55EX warming sensation, Lion Corporation), the primary skin irritation index test was performed in the same way, and the average score after 30 minutes or 24 hours, the score of each individual A primary skin irritation index (P.I.I.) and a primary skin irritation index (mean P.I.I.) were obtained.
Table 5 shows the results obtained.

As shown in Table 5, 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 was 0.7 to 1.0. It was a result that it was the stimulus of
On the other hand, the mean primary irritation index (mean P.I.I.) in the positive control was 2.8, indicating moderate irritation.

From the results of the above examples, according to the present invention, among the monomers constituting the alkyl acrylate copolymer, the content of monomer A (such as methyl acrylate) whose homopolymer Tg is 270 K or higher By blending an acrylic acid alkyl ester copolymer (methyl acrylate/2-ethylhexyl acrylate copolymer resin, etc.) with a content of 30 to 50% by mass in the adhesive layer of a water-containing patch, It was confirmed that a patch with low skin irritation can be provided while maintaining high adhesiveness.

Claims (3)

A water-containing adhesive patch comprising a backing, and a pressure-sensitive adhesive layer and a release liner provided on the backing,
A water-containing patch, wherein the pressure-sensitive adhesive layer essentially contains the following components 1) to 6) in the following proportions based on the total weight of the pressure-sensitive adhesive layer .
1) 0.1% by mass or more and 10% by mass or less of acrylic hydrophilic adhesive,
2) an acrylic acid alkyl ester-based copolymer that is a copolymer of a monomer mixture consisting of a monomer A and a 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
0.1% by mass or more and 30% by mass or less of an acrylic acid alkyl ester copolymer in which 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;
3) 0.1% by mass or more and 20% by mass or less of an organic solvent;
4) 0.01% by mass or more and 6.0% by mass or less of a cross-linking agent;
5) 0.01% by mass or more and 5% by mass or less of an organic acid;
6) 10% by mass or more and 90% by mass or less of water. 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 water-containing patch according to claim 1 . 3. The water-containing patch according to claim 1 , further comprising an active ingredient.