TW202228657A - Medicinal hydrous adhesive patch - Google Patents

Abstract

To provide a hydrous adhesive patch that exhibits favorable adhesive strength even after moisture in an adhesive layer has evaporated. A medicinal hydrous adhesive patch obtained by including, at a ratio of 20-70 mass% in an adhesive layer, an emulsion of an acrylic acid alkyl ester copolymer, which is a copolymer of a monomer mixture comprising a monomer A and a monomer B, wherein the monomer A becomes a polymer having a glass transition temperature (Tg) of 270-290 K when the monomer A is homopolymerized, and the monomer B becomes a polymer having a glass transition temperature (Tg) of 210 K or less when the monomer B is homopolymerized.

Description

Aqueous adhesives for pharmaceuticals

The present invention relates to an aqueous adhesive for pharmaceuticals, and more specifically, to an aqueous adhesive of high practical quality that maintains high adhesive force even after the water in the adhesive layer is volatilized, can be produced well, and is practical Adjuvant.

Commonly known as "dressing", the adhesive base containing water (referred to as water-based adhesive in this specification) is a woven cloth, woven cloth, non-woven cloth and other supports containing drugs, etc. One of the stickers for the paste layer (adhesive layer) of the active ingredient. The compress uses an adhesive base containing water in the ointment layer, so although the skin irritation is low, the adhesive force is weak, especially as the water in the ointment layer is volatilized, the adhesive force decreases over time, and it is easy to peel off from the skin. question. In order to solve such a problem, it is known to formulate an emulsion (also called latex) base in which a well-known alkyl acrylate copolymer is dispersed as a component constituting a non-aqueous (also called hydrophobic, lipophilic) adhesive The technology of the paste layer (adhesive layer) of the water-based adhesive.

For example, Patent Document 1 discloses a sticker for the purpose of providing a water-based adhesive agent which has excellent adhesive force and re-adhesion force even if it is attached for a long time, and realizes hardening and suppression of flexibility due to loss of moisture. Adhesives containing 5.0 mass % or more and 10 mass % or less of methyl acrylate-2-ethylhexyl acrylate copolymer, 0.01 mass % or more and 10.0 mass % or less with respect to the entire composition for aqueous external adhesive preparations. Water dispersible surfactant. Furthermore, Patent Document 2 aims to provide a dressing having sufficient adhesion even when the water content of the dressing decreases over time, and discloses a dressing comprising a polyacrylic acid neutralized product, the Methyl acrylate-2-ethylhexyl acrylate copolymer and polyacrylic acid of 2.5 to 10 times the mass of the neutralized product (5 to 25 mass % on a paste basis). Patent Document 3 discloses a poly(methyl acrylate/2-ethylhexyl acrylate) and polyethylene as a surfactant for the purpose of providing a dressing capable of peeling off a release liner with a smaller force. Formulations of mono-fatty acid esters of diols, etc. [Prior Art Literature] [Patent Literature]

[Patent Document 1] Japanese Patent No. 5650684 [Patent Document 2] Japanese Patent No. 5921779 [Patent Document 3] Japanese Patent No. 6469136

[Problems to be Solved by Invention]

As described above, it is known that an alkyl acrylate copolymer such as a methyl acrylate-2-ethylhexyl acrylate copolymer is blended in an adhesive layer in order to improve the adhesion sustainability of the aqueous adhesive. However, in the previously disclosed water-based adhesive preparation, in particular, the adhesive force after the water in the adhesive layer is volatilized is not sufficiently satisfactory compared with the adhesive preparation. In addition, conventionally, hydrophilic acrylic adhesives (partially neutralized polyacrylic acid products (manufactured by Showa Denko Co., Ltd., Vicomate (registered trademark) NP-800, etc.), etc.) or increased Thickeners (sodium carboxymethyl cellulose, etc.) are usually high-hydrophilic polymer compounds, so if they are directly put into water, caking may occur. In addition, a crosslinking agent (dihydroxyaluminumaminoacetate (manufactured by Kyowa Chemical Industry Co., Ltd., Glycinal, etc.), etc.) may not lose its function after being dissolved in water, and the dissolution must be suppressed. For this reason, a method of dispersing the ingredients in a wetting agent containing almost no water and throwing it into an adhesive layer-forming composition is generally practiced in the manufacture of poultices. However, when the above-mentioned emulsion is prepared at a ratio of more than 20% by mass, a non-water wetting agent (concentrated glycerin) plays the role of dispersing the above-mentioned hydrophilic acrylic adhesive, thickener and crosslinking agent in the adhesive layer. etc.) becomes relatively small. Therefore, these components cannot be sufficiently dispersed in the adhesive layer, and as a result, there is a problem that agglomeration occurs in the adhesive. In addition, if more than 20% of alkyl acrylate copolymers such as methyl acrylate-2-ethylhexyl acrylate copolymers are prepared, the amount of other components to be prepared will be reduced, and the cross-linking reaction will not be easily carried out or the shape retention will be lost. . [Technical means to solve problems]

The inventors of the present invention have conducted intensive studies in order to solve the above-mentioned problems, and as a result, they have found that, as a result of preparing the adhesive layer of the water-containing adhesive for pharmaceutical products at a ratio of more than 20 mass % and less than 70 mass %, which is far more than the previous amount Alkyl acrylate-based copolymers are homopolymerized with monomers that become polymers with a glass transition temperature (Tg) of 270 or more and 290 K or less and monomers that become polymers with Tg of 210 K or less during homopolymerization. The emulsion of the copolymer formed by copolymerization can inhibit the formation of agglomeration when the adhesive layer is formed, without impairing the crosslinking property or the shape retention property, and the adhesive force does not decrease even after the water in the adhesive layer is volatilized, on the contrary The invention is significantly improved and has manufacturability and practicability, thereby completing the present invention.

That is, the present invention is as follows: [1] An aqueous adhesive for pharmaceuticals, It comprises a support, an adhesive layer and a release liner arranged on the support, wherein The above adhesive layer contain: 1) Active ingredients, 2) acrylic hydrophilic adhesive, 3) Alkyl acrylate copolymer emulsion (solid content 57-61% by mass), 4) Cross-linking agent, 5) Thickener, 6) Wetting agents containing almost no water (with a moisture content of 17% or less), and 7) water, The above-mentioned alkyl acrylate copolymer is a copolymer comprising a monomer mixture of monomer A and monomer B, The above-mentioned monomer A is a monomer which becomes a polymer having a glass transition temperature (Tg) of 270 or more and 290 K or less when the monomer A is homopolymerized, The above-mentioned monomer B is a monomer that makes a polymer having a glass transition temperature (Tg) of 210 K or less when the monomer B is homopolymerized, and The alkyl acrylate copolymer emulsion is contained in a ratio of more than 20 mass % and less than 70 mass % with respect to the total mass of the adhesive layer.

Furthermore, according to the present invention, the following embodiments are further provided. [2] The water-based adhesive preparation for pharmaceuticals according to [1], characterized by having one or more of the following items a) to c); a) The mass ratio of the above-mentioned alkyl acrylate copolymer emulsion to the above-mentioned acrylic hydrophilic adhesive is 5 or more and 30 or less. b) The pH value of the above-mentioned adhesive layer is 4.5-5.5. c) The mass ratio of the powdery components (the above-mentioned acrylic hydrophilic adhesive, cross-linking agent and thickener) to the above-mentioned almost water-free wetting agent is 0.01 or more and 0.35 or less. [3] The water-based adhesive preparation for pharmaceuticals as described in [1] or [2], wherein the above-mentioned almost water-free wetting agent is selected from concentrated glycerin, glycerin, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid A group consisting of paraffin, 1,3-propanediol and 1,4-butanediol. [4] The aqueous adhesive for pharmaceuticals according to any one of [1] to [3], wherein The above-mentioned adhesive layer further contains: 8) Cooling agent, 9) organic solvent, 10) pH regulator, 11) Chelating agents. [Effect of invention]

ADVANTAGE OF THE INVENTION According to the present invention, there can be provided a water-based adhesive for pharmaceuticals, wherein an alkyl acrylate-based copolymer of more than 20% by mass and less than 70% by mass is blended in the adhesive layer of the water-containing adhesive for pharmaceuticals The emulsion, the alkyl acrylate copolymer contains monomer A which becomes a polymer with a glass transition temperature (Tg) of 270 K or more and 290 K or less when homopolymerized, and a Tg of 210 K or less when homopolymerized. The copolymer of the monomer mixture of the monomer B of the polymer, and, in a preferred aspect, a) the mass ratio of the above-mentioned alkyl acrylate copolymer emulsion to the above-mentioned acrylic hydrophilic adhesive is set to 5 or more 30 or less, or b) the pH value of the above-mentioned adhesive layer is set to 4.5 to 5.5, or c) the powdery components (the above-mentioned acrylic hydrophilic adhesive, cross-linking agent and thickener) are mixed with the above-mentioned almost water-free material. The mass ratio of the wetting agent is set to 0.01 or more and 0.35 or less, thereby suppressing the generation of caking when forming the adhesive layer, and maintaining the adhesive force even after the water in the adhesive layer is volatilized, and has adhesion during production Good manufacturability such as no agglomeration in the material for forming the adhesive layer, good releasability between the adhesive layer and the liner or good releasability between the adhesive layers, and the adhesive layer has a certain degree of cross-linking (no Practicality such as deformation of the shape of the adhesive layer due to sweat, etc., such as significant swelling of the adhesive layer.

As mentioned above, in order to improve the sustainability of the adhesive force of the water-based adhesive, there is a methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (trade name NiKasol TS-620, Japan Calcium Carbide Industry Co., Ltd.) Wait for the idea of formulating the alkyl acrylate copolymer emulsion in the adhesive layer or the idea of increasing the formula. However, even in the case where the compounding amount of the copolymer is increased, the adhesive force after water volatilization in the adhesive layer (after water volatilization) is not sufficient compared with the adhesive patch. The inventors of the present invention have found that the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (hereinafter, also referred to as the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex) is prepared by mixing the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex in an amount exceeding 20 mass % and less than 70 mass % in excess of the previously proposed compounding amount when the above-mentioned problem was carried out. (referred to as copolymer emulsion) is formulated in the adhesive layer to provide an aqueous adhesive for pharmaceuticals, which can maintain the adhesive force even after the water in the adhesive layer is volatilized, and produce caking during production. There is no problem in terms of manufacturability such as difficulty in supporting the support, and it has the following practicability: the releasability between the adhesive layers or the adhesive layer and the release liner is good, and the adhesive layer does not swell significantly due to sweat or the like. Deformation degree of cross-linking, etc. The constitution of the aqueous adhesive preparation for pharmaceuticals of the present invention will be described below.

The aqueous adhesive agent for pharmaceuticals of the present invention (hereinafter also simply referred to as "the patch") includes a support, an adhesive layer and a release liner provided on the support. The shape of the above-mentioned patch especially the preparation part comprising the support and the adhesive layer arranged on the support is not particularly limited, and can be selected from square (square, rectangle, etc.), quadrilateral (trapezoid, rhombus, etc.), polygon, Various shapes can be selected according to the attachment site, such as circle, ellipse, semicircle, triangle, crescent, and a combination of these. Furthermore, the area of the patch (especially the above-mentioned formulation part) can be appropriately determined, for example, in consideration of the amount of the active ingredient prepared in the adhesive layer, and can be set to, for example, a range of 2 to 300 cm ² .

[Adhesive layer] The water-based adhesive for pharmaceuticals of the present invention is characterized in that, in the water-containing adhesive layer, in addition to the hydrophilic acrylic adhesive described later, an acrylic acid alkane, which normally constitutes a non-aqueous acrylic adhesive, is also prepared. Latex of base ester copolymer. In general, polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, and N-vinylacetamide-sodium acrylate are widely used as the adhesive used in the adhesive layer (paste layer) of the aqueous adhesive. Hydrophilic acrylic adhesives such as copolymer resins. From the viewpoint of having high affinity with the above-mentioned hydrophilic acrylic adhesive and being able to knead uniformly, as the non-aqueous adhesive prepared in the aqueous adhesive layer of the aqueous adhesive, it is preferable to prepare an acrylic and an acrylic adhesive. Methacrylic emulsion type adhesive. Furthermore, in this specification, "acrylic acid alkyl ester copolymer" is intended to include both acrylic acid and methacrylic acid alkyl esters, and "acrylic adhesive" is also intended to include acrylic adhesive and methacrylic acid Both adhesives.

<Alkyl acrylate copolymer> The acrylic acid alkyl ester-based copolymer (non-aqueous adhesive base) constituting the non-aqueous acrylic adhesive is a copolymer containing the following monomers: The carbon number of the alkyl ester as a component that exhibits adhesive force is 2 to 9 , and when homopolymerized, it becomes a monomer of a polymer whose glass transition temperature (Tg) is below -55 °C (218 K); as a component to improve cohesion, when homopolymerized, it becomes a Tg of 8 ~ 165 ° C (281 ~ 438 K) monomer of the polymer; further depending on the need, a monomer having a functional group such as a carboxyl group or a hydroxyl group that becomes a cross-linking point (an example of the monomer is listed in Table 1). The alkyl acrylate copolymer used in the present invention contains monomer A (hard segment) that becomes a polymer having a glass transition temperature (Tg) of 270 K or more and 290 K or less when homopolymerized, and when homopolymerized It is a copolymer of monomer mixture of monomer B (soft segment) of a polymer whose glass transition temperature (Tg) is 210 K or less. The lower limit of the glass transition temperature Tg of the above-mentioned homopolymer of monomer B is about 200 K.

[Table 1] Table 1 monomer The number of carbon atoms in the alkyl ester moiety Homopolymer Tg Tg(K) Tg(℃) Adhesion performance Tg: -55℃ or less Butyl acrylate 4 218.1 -55 2-ethylhexyl acrylate 8 203.1 -70 Octyl acrylate 8 208.1 -65 isononyl acrylate 9 213.1 -60 Cohesion improvement Tg: 8～165℃ Methyl acrylate 1 281.1 8 methyl methacrylate 1 378.1 105 Ethyl methacrylate 2 338.1 65 n-butyl methacrylate 4 293.1 20 Isobutyl methacrylate 4 321.1 48 tert-butyl methacrylate 4 380.1 107 vinyl acetate - 305.1 32 Acrylonitrile - 370.1 97 acrylamide - 438.1 165 Styrene - 353.1 80 Contains functional group (crosslinking point) acrylic acid 0 379.1 106 2-Hydroxyethyl acrylate 2 213.1 -60 Methacrylate 0 501.1 228 2-hydroxyethyl methacrylate 2 328.1 55 Glycidyl methacrylate 3 323.1 50 Hydroxypropyl methacrylate 3 299.1 26

Furthermore, a homopolymer obtained by polymerizing only a monomer that exhibits adhesive force has high adhesive force but weak mechanical strength. Generally, it is a copolymer that increases the mechanical strength by copolymerizing with a monomer that enhances the cohesion force. material is used as an adhesive. As exemplified by the monomers exhibiting adhesive force shown in the above Table 1, in the present invention, as a monomer with higher adhesive force, the Tg of the monomer when homopolymerized (homopolymer) is 210. 2-ethylhexyl acrylate, octyl acrylate, etc. below K. Among these, 2-ethylhexyl acrylate, which has a proven track record as a pharmaceutical additive and has a high adhesive force (low Tg of a homopolymer), can be preferably used. In addition, as a monomer for improving the cohesion force (the Tg of the homopolymer is 270 K or more and 290 K or less), among the monomers exemplified in Table 1, methyl acrylate can be exemplified. Methyl acrylate has high mechanical strength and is not suitable for use. It is preferable in that the tackiness is significantly reduced (the Tg of the homopolymer is relatively low).

Furthermore, as exemplified in the prior art, as an emulsion of a commercially available alkyl acrylate copolymer used in the adhesive, there is NiKasol (registered trademark) TS-620 (methyl acrylate) manufactured by Nippon Calcium Carbide Co., Ltd. ester-2-ethylhexyl acrylate copolymer resin latex). Methyl acrylate-2-ethylhexyl acrylate copolymer resin latex is included in the specifications of pharmaceutical additives. NiKasol TS-620 was evaporated to dryness on a water bath according to the specifications for pharmaceutical additives (2018), and then dried at 105°C for 3 hours. The amount of evaporation residue was 57-61%. Furthermore, in the above-mentioned copolymer, by setting the ratio of the monomer A whose Tg of the homopolymer is 270 K or more and 290 K or less to 40 mass % or more and 50 mass % or less, the vapour volatilization of the adhesive layer can be expected. Adhesion increases over time.

In the adhesive layer of the aqueous adhesive for pharmaceuticals of the present invention, the amount of the alkyl acrylate copolymer emulsion to be formulated is based on the total mass of the adhesive layer of the aqueous adhesive for pharmaceuticals. The lower limit value can be set to be more than 20 mass %, 30 mass % or more, or more than 30 mass %, and the upper limit value can be set to less than 70 mass %, 60 mass % or less, less than 60 mass %, 50 mass % or less, less than 50% by mass. Regarding the mixing ratio with the acrylic hydrophilic adhesive described later, for example, the mass ratio of the alkyl acrylate copolymer emulsion and the acrylic hydrophilic adhesive can be set to 5 or more and 30 or less, 5 or more and 25 or less, 10 or more. Above 30, below 10, above 25, etc.

＜Active ingredients＞ The pressure-sensitive adhesive layer in the aqueous adhesive preparation for pharmaceuticals of the present invention contains an active ingredient. The above-mentioned active ingredients can be exemplified by physiologically active substances. The physiologically active substances are not particularly limited as long as they have transdermal absorbability and exhibit pharmacological activity when administered into the body, and may be water-soluble substances, or may be Fat-soluble substances. Examples of physiologically active substances include felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, ethylene glycol salicylate (ethylene glycol salicylate), and indomethacin. Caprylic, ketoprofen, ibuprofen and other non-steroidal anti-inflammatory agents or their esters; diphenhydramine, clofeniramine and other antihistamines; aspirin, acetaminophen, ibuprofen, lofenac Analgesics such as soprofen sodium; local anesthetics such as lidocaine and dibucaine; muscle relaxants such as succinylcholine chloride; antifungal agents such as clotrimazole; blood pressure lowering agents such as clonidine; nitroglycerin, nitric acid Vasodilators such as isosorbide; vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, ottothiamine, riboflavin butyrate and other vitamins, prostaglandins; scopolamine, fentanyl, Capsicum extract, vanillamide pelargonate, capsaicin, l-menthol, dl-camphor, etc. A physiologically active substance may be used individually by 1 type, and may be used in combination of 2 or more types.

The above-mentioned active ingredient can be appropriately formulated in an appropriate amount depending on the type. For example, based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, it can be 0.1 mass % or more and 30 mass % or less, or 0.5 mass % or more. 15 mass % or less.

<Acrylic Hydrophilic Adhesive> The adhesive layer of the water-containing adhesive agent for pharmaceuticals of the present invention contains an acrylic hydrophilic adhesive. As said acrylic hydrophilic adhesive, a water-soluble (meth)acrylic-type polymer is mentioned. The water-soluble (meth)acrylic polymer is a polymer obtained by polymerizing a (meth)acryloyl group-containing monomer containing a water-soluble functional group (hydrophilic group), and is obtained by mixing with water When it is formulated into the adhesive layer, it will exert adhesiveness. Examples of the water-soluble (meth)acrylic polymer include homopolymers such as polyacrylic acid and neutralized polyacrylic acid; and copolymers such as N-vinylacetamide-sodium acrylate copolymer resin. The above-mentioned neutralized polyacrylic acid may be a complete neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. The neutralized polyacrylic acid means polyacrylate, and for example, sodium salt, potassium salt, calcium salt, ammonium salt, etc. can be used.

The blending amount of the acrylic hydrophilic adhesive is based on the total mass of the adhesive layer of the aqueous adhesive for pharmaceuticals, and can be, for example, 0.1% by mass to 10% by mass, and 1% by mass to 8% by mass.

＜Crosslinking agent＞ The adhesive layer of the water-based adhesive agent for pharmaceuticals of the present invention further contains a crosslinking agent. Examples of the crosslinking agent include polyvalent metal salts, and among them, polyvalent metal compounds containing aluminum are exemplified. As an example, hydroxides such as aluminum hydroxide and aluminum magnesium hydroxide; aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxyaluminumamine acetal), dihydroxyaluminumamine group Normal salts of inorganic or organic acids such as acetate, synthetic aluminum silicate, dry aluminum hydroxide gel, kaolin, aluminum stearate, or their basic salts; double salts such as aluminum alum; aluminates such as sodium aluminate ; Inorganic aluminum zirconium salts and organic aluminum chelate compounds; Synthesized aluminum magnesium carbonate, magnesium aluminosilicate, magnesium aluminosilicate and other polyvalent metal compounds; These can be used alone, or two or more can be added together used in combination.

The compounding amount of the cross-linking agent may be appropriately selected in consideration of the degree of cross-linking which may be a factor of the residual of the adhesive on the skin or the adhesion to the skin. For example, on the basis of the total mass of the adhesive layer of the water-containing adhesive agent for pharmaceutical products, the compounding amount may be, for example, 0.01 mass % or more and 6.0 mass % or less, 0.01 mass % or more and 4.0 mass % or less, or 0.01 mass %. More than the range of 2.0 mass % or less.

＜Thickener＞ The adhesive layer of the water-containing adhesive agent for pharmaceuticals of the present invention contains a thickener, and the function of the thickener to improve the shape retention property or the adhesiveness of the adhesive can be expected. Examples of the thickener include celluloses such as ethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose, and methyl cellulose, Sodium alginate, carrageenan, Sanxian gum, sodium hyaluronate and other polysaccharides, gelatin, urea, etc. Among them, sodium carboxymethyl cellulose with thixotropy and improved ductility is preferred. These may be used individually by 1 type, and may be used in combination of 2 or more types suitably. The compounding amount of the thickener is usually based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, and can be, for example, 0.1 mass % or more and 10 mass % or less, 0.5 mass % or more and 20 mass % or less, or 16.0 mass %. % or more and 10 mass % or less.

＜Wetting agent＞ The adhesive layer of the water-containing adhesive agent for pharmaceuticals of the present invention contains a wetting agent (also referred to as a moisturizing agent). This wetting agent can be expected to have the function of inhibiting the evaporation of water over time, and it can also be expected to inhibit the direct use of water-soluble polymers such as hydrophilic acrylic adhesives, thickeners such as sodium carboxymethyl cellulose, and cross-linking agents. The function of creating agglomeration or increasing viscosity due to cross-linking when it is formulated in water. For the latter reason to avoid direct formulation with water, it is desirable to use a humectant that contains little water. That is, when forming the adhesive layer, the above-mentioned hydrophilic acrylic adhesive, thickener, cross-linking agent, etc. are prepared in an anhydrous wetting agent or a wetting agent with a very small amount (for example, 17% by mass or less) even if it contains water. After the pre-formulation is prepared, it can be mixed with other components constituting the adhesive layer, so as to inhibit the generation of agglomeration or increase the viscosity. As such a wetting agent, polyalcohols, such as concentrated glycerin, glycerin, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1, 3- propylene glycol, and 1, 4- butanediol, are mentioned, for example. These may be used individually by 1 type, and may be used in combination of 2 or more types suitably. Furthermore, for the former reason of suppressing evaporation of water over time, a wetting agent containing water can be preferably formulated. For example, D-sorbitol liquid, which is usually used as a 70% aqueous solution, is not easy to be used for inhibiting caking or thickening (preparation of the above-mentioned preformulation) because it contains water, but it can be formulated together with other ingredients when it is subsequently mixed. The blending amount of the wetting agent (the total amount of the wetting agent containing almost no water and the wetting agent containing water) is usually based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, and can be, for example, 1.0% by mass or more. 70 mass % or less, 5.0 mass % or more and 60 mass % or less, or 10 mass % or more and 60 mass % or less. Furthermore, by setting the mass ratio of the total amount <A> of the above-mentioned hydrophilic acrylic adhesive, thickener and crosslinking agent to the amount <B> of the almost water-free wetting agent (such as concentrated glycerin) When <A>/<B>=0.01 to 0.35, it is preferable to mix them so that they can be uniformly kneaded without caking.

＜Water＞ As described above, the water-containing patch for pharmaceuticals of the present invention is one that contains water (water) in the adhesive layer. In this specification, the "water" contained in the adhesive layer includes not only what is separately added in the form of water when forming the adhesive layer, but also includes water contained in the form of latex or aqueous solution. The amount of water to be prepared is not particularly limited, and based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, it can be, for example, 10 mass % or more and 90 mass % or less, 15 mass % or more and 70 mass % or less, The range of 20 mass % or more and 50 mass % or less. Furthermore, the amount of water to be prepared is the value during the preparation of the patch or before the patch is attached, and is not limited to the case where the water is volatilized from the adhesive layer with the passage of time.

＜Cooling agent＞ In the aqueous adhesive for pharmaceuticals of the present invention, especially when a non-steroidal anti-inflammatory and analgesic such as loxoprofen sodium is used as an active ingredient to be formulated into the adhesive layer, a cooling agent can be preferably formulated. Examples of the cooling agent include l-menthol, dl-camphor, cinnamon oil, geraniol, peppermint oil, citron oil, d-borneol, eucalyptus oil, and the like, which may be used alone or may also be used. It is used in combination of 2 or more types. In addition, although l-menthol and dl-camphor are also included in the above-mentioned <active ingredient>, they can be formulated as <refreshing agent> in an amount that does not contribute to the degree of expressing the effect as an active ingredient. In the case of preparing a cooling agent, the amount of the preparation can be appropriately selected as long as it is considered within the range of the amount used as a pharmaceutical additive, does not exhibit a medicinal effect, and exhibits a cooling sensation when attached. For example, the compounding amount of l-menthol as a cooling agent is based on the total mass of the adhesive layer of the water-based adhesive agent for pharmaceutical products, for example, 0.01 mass % or more and 4.0 mass % or less, and 0.01 mass % or more and 3.0 mass %. % or less.

＜Organic solvent＞ The adhesive layer of the water-containing adhesive agent for pharmaceuticals of the present invention may further be prepared with an organic solvent. The organic solvent prepared in the adhesive layer can assist in dissolving active ingredients such as drugs, and can also prevent the active ingredients from being separated from the adhesive layer. As such an organic solvent (solubilizer), polyalkylene glycols such as crotamiton; N-methyl-2-pyrrolidone; Macrogol 400 (polyethylene glycol) and polytetramethylene glycol may, for example, be mentioned. ; Diethyl adipate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, oleate and other fats acid esters; sorbitan esters such as polyoxyalkylene fatty acid esters; polyols such as 1,3-butanediol; dimethylformamide; dimethylsulfoxide, etc. These may be used individually by 1 type, and may be used in combination of 2 or more types.

The compounding amount of the organic solvent is based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, and can be, for example, 0.1 mass % or more and 20 mass % or less, 0.5 mass % or more and 10 mass % or less, or 1.0 mass % or more. The range of 5 mass % or less.

＜pH adjuster＞ A pH adjuster can be further formulated into the adhesive layer of the aqueous adhesive agent for pharmaceuticals of the present invention. As a pH adjuster, either an organic acid or an inorganic acid may be used, and these may be used together. Examples of the organic acid include citric acid, lactic acid, tartaric acid, gluconic acid, glycolic acid, malic acid, fumaric acid, metasulfonic acid, maleic acid, and acetic acid, and these can be used alone. , and two or more of them may be used in combination. Hydroxy acids such as lactic acid among the organic acids also have the effect of improving the solubility of the poorly soluble aluminum compound (crosslinking agent). Moreover, as this inorganic acid, hydrochloric acid, boric acid, phosphoric acid, sulfuric acid, etc. are mentioned, for example, These can be used individually or in combination of 2 or more types. The compounding quantity of an organic acid can be made into the range of 0.01 mass % or more and 5 mass % or less on the basis of the total mass of the adhesive layer of the water-containing adhesive agent for pharmaceuticals. The compounding quantity of an inorganic acid can be made into the range of 0.1 mass % or more and 1.2 mass % or less based on the total mass of the adhesive layer of the water-containing adhesive agent for pharmaceuticals.

＜Chelating agent＞ A chelating agent can be formulated in the adhesive layer of the water-based adhesive for pharmaceuticals of the present invention to control the dissolution rate of the poorly soluble aluminum compound (crosslinking agent). As a chelating agent, sodium ethylenediaminetetraacetate (disodium salt of ethylenediaminetetraacetic acid) is mentioned, for example. The compounding quantity of a chelating agent is normally based on the total mass of the adhesive layer of the water-containing adhesive agent for pharmaceuticals, and can be set to the range of 0.01 mass % or more and 1 mass % or less, for example.

<Other optional ingredients> In the adhesive layer of the water-based adhesive agent for pharmaceuticals of the present invention, water-soluble polymer compounds, surfactants, stabilizers (antioxidants, ultraviolet absorbers, etc.), Inorganic powders, colorants, fragrances, preservatives and other ingredients that can be generally formulated in the adhesive layer of the previous aqueous adhesives (dressings) or non-aqueous adhesives (patches). These optional components may be used alone or in combination of two or more.

＜Water-soluble polymer compound＞ As a water-soluble polymer compound, a polyvinyl alcohol, a polyvinyl pyrrolidone, a carboxyvinyl polymer, a sucrose fatty acid ester etc. are mentioned, for example. These may be used individually by 1 type, and may be used in combination of 2 or more types suitably. The compounding amount of the water-soluble polymer compound is usually based on the total mass of the adhesive layer of the water-based adhesive for pharmaceutical products, and can be, for example, 1.0 mass % or more and 30 mass % or less, 3.0 mass % or more and 20 mass % or less, or The range of 5.0 mass % or more and 20 mass % or less.

＜Surfactant＞ As surfactant, for example, polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol di Polyoxyethylene fatty acid esters such as oleate and polypropylene glycol dioleate; sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate , Sorbitan Monostearate, Sorbitan Distearate, Sorbitan Tristearate, Sorbitan Monooleate, Sorbitan Trioleate, Sorbitan Monosemirate Oleate, and sorbitan fatty acid esters such as ethylene oxide adducts; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitol Anhydride monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan triisohard Polyoxyethylene sorbitan fatty acid esters such as fatty acid esters; polyoxyethylene lauryl ether (polyoxyethylene lauryl ether), polyoxyethylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyethylene lauryl ether Alkyl tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene- 2-ethylhexyl ether, polyoxyethylene isodecyl ether and other polyoxyethylene alkyl ethers; polyoxyethylene styrenated phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene distyrenated phenyl ether ether, polyoxyethylene tribenzyl phenyl ether and other polyoxyethylene alkyl phenol ethers; glycerol fatty acid esters such as glycerol monostearate and glycerol monooleate; polyethylene glycol, polyoxyethylene hydrogenated castor oil, Nonionic surfactants such as polyoxyethylene castor oil and lecithin. These may be used individually by 1 type, and may be used in combination of 2 or more types suitably. The blending amount of these surfactants is based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, and can be, for example, in the range of 0.001% by mass to 10% by mass, and 0.01% by mass to 5% by mass. .

＜Stabilizer＞ In the adhesive layer of the water-based adhesive for pharmaceuticals of the present invention, a stabilizer for light (especially ultraviolet rays), heat or oxygen can be adjusted to improve the storage stability of the above-mentioned active ingredients. Examples of the stabilizer include antioxidants such as dibutylhydroxytoluene (BHT); ultraviolet absorbers such as benzalkonium methane derivatives, and the like. The blending amount of the stabilizer is usually based on the total mass of the adhesive layer of the water-based adhesive for pharmaceuticals, and can be, for example, in the range of 0.01 mass % or more and 1 mass % or less.

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

[support body] Examples of the support used in the aqueous adhesive for pharmaceutical products of the present invention include films, non-woven fabrics, Japanese paper, cotton fabrics, woven fabrics, woven fabrics, laminated composites of non-woven fabrics and films, and the like having flexibility. support body. These supports are preferably made of soft materials that can adhere closely to the skin, can follow the movement of the skin, and can suppress the occurrence of rashes and the like on the skin after being adhered for a long time. As the material of these supports, for example, polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon can be exemplified. , cotton, rayon acetate, rayon, rayon/polyethylene terephthalate compound, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, Ether-based polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butylene Diene rubber, ethylene-vinyl acetate copolymer, and celofen are essential components.

Moreover, the support body, such as a cloth, is colored in a color tone such as skin color with a coloring agent, so that the difference from the skin color at the time of sticking can be reduced. In addition, in terms of easily revealing the color tone of the attached skin, the form of a plastic film excellent in transparency can be adopted.

The thickness of the support is usually about 5 μm to 1 mm. When the support is cloth, the thickness is preferably 50 μm to 1 mm, more preferably 100 to 800 μm, and still more preferably 200 to 700 μm. When the support is a plastic film, its thickness is preferably 10-300 μm, more preferably 12-200 μm, and still more preferably 15-150 μm. When the thickness of the support is extremely thin around 5 μm to 30 μm, if a peelable carrier film layer is provided on the surface opposite to the adhesive layer formed on the support, the workability as an adhesive increase, so it is better. However, if the thickness of the support is less than 5 μm, the strength and workability of the adhesive agent are reduced, and it becomes difficult to stick to the skin, and there is a possibility of cracking due to contact with other members, etc., or shortness due to contact with water such as bathing. The condition of peeling from the skin over time. In addition, if the thickness of the support is too large (over 1 mm), the adhesive agent is not easy to follow the movement of the skin, and the starting point of peeling is easily formed at the edge of the adhesive agent. The risk of increased discomfort. Furthermore, when the support is a film, in order to improve the grip between the adhesive and the support, one or both sides of the support may be treated by sandblasting, corona treatment, or the like. Moreover, in order to make it easy to take out from the packaging material, it is also possible to provide unevenness on one side or both sides of the support by a method other than sandblasting.

[release liner] As the release liner (also referred to as release layer and release paper) used in the water-based adhesive for pharmaceuticals of the present invention, it is preferably a material that is difficult to absorb and absorb, such as the drug in the adhesive layer, and can be used for the adhesive layer. Those commonly used in the technical field of additives. For example, polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (unstretched, stretched, etc.), polyethylene, Polyurethane, polyvinyl chloride, polystyrene and other plastic films; high-grade paper, cellophane, parchment, kraft paper and other paper or synthetic paper; the above plastic film, paper or synthetic paper, coating silicone on synthetic fibers, etc. Released paper with release agent with release properties such as resin or fluororesin; aluminum foil; laminated paper with various such films and sheets laminated, and laminated release paper coated with release agent on the laminated paper and other colorless or colored sheets. In addition, the release liner may be provided with unevenness for easy removal from the packaging material. The thickness of these release liners is not particularly limited, and is usually in the range of 10 μm to 1 mm, for example, 20 μm to 500 μm, preferably 40 μm to 200 μm. The shape of the release liner can be set to square, rectangular, circular, etc., and can be set to a shape with rounded corners as needed. The size can be set to the same shape or slightly larger than the size of the support in the above-mentioned patch. The release liner may be one piece or divided to include a plurality of pieces, and the gap may include a straight line, a wavy line, or a stitched line, and may be in a state where a part of the release liners overlaps each other.

[Manufacturing method of aqueous adhesive for pharmaceuticals] The aqueous adhesive preparation for pharmaceuticals of the present invention can be produced by a conventionally known method. For example, as an example, it can be manufactured through the following i) or ii) steps. i) A step of coating an adhesive layer forming composition on a support to form an adhesive layer, and a step of attaching the adhesive layer formed on the support to a release liner. ii) The step of coating the adhesive layer forming composition on the release liner to form the adhesive layer, and the step of bonding the adhesive layer formed on the release liner to the support. Furthermore, the thickness of the above-mentioned adhesive layer is not particularly limited, and can usually be set to about 10 μm to 1000 μm, for example, about 20 μm to 800 μm.

The above-mentioned adhesive layer forming composition refers to the various components contained in the above-mentioned adhesive layer: active ingredient, acrylic hydrophilic adhesive, alkyl acrylate copolymer, crosslinking agent, thickener, wetting agent and water , may contain cooling agents, organic solvents, pH adjusters and chelating agents, and may contain other components in semi-solid form. Furthermore, by setting the pH value of the adhesive layer-forming composition to 4.5 to 5.5, since good crosslinkability and shape retention can be expected, it is preferable.

Furthermore, the water-based adhesive preparation for pharmaceuticals of the present invention is characterized by maintaining the adhesive force when containing moisture (immediately after attaching) and when containing no moisture (after the moisture is volatilized after attaching), and can be satisfactorily maintained. Manufactured, practical adhesive with higher quality. [Example]

The following examples are given to illustrate the present invention in further detail, but the present invention is not limited to these examples.

＜Preparation of adhesive agent＞ The patches of Examples and Comparative Examples were produced in the following procedure.

Example 1: After heating 1 part by mass of polyvinyl alcohol and 10 parts by mass of purified water to 70° C. to dissolve 1 part by mass of polyvinyl alcohol in 10 parts by mass of purified water, it was cooled to room temperature (pre-formulation 1). Next, 1.5 parts by mass of Macrogol (registered trademark) 400 and 1 part by mass of lactic acid were added to 1.13 parts by mass (in terms of hydrate) of loxoprofen sodium and 1 part by mass of l-menthol, and dissolved at 40° C. After that, it was cooled to room temperature (pre-formulation 2). Further, 4 parts by mass of the partially neutralized polyacrylic acid, 3 parts by mass of sodium carboxymethyl cellulose, and 0.25 parts by mass of dihydroxyaluminumaminoacetate were uniformly dispersed in 20 parts by mass of concentrated glycerin (preformulation 3). 1, 40 parts by mass of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (containing 46.7% methyl acrylate (hard segment), 60% solid content, latex containing a trace amount of polyoxy Ethylene nonyl phenyl ether (30EO)) and 0.2 parts by mass of sodium EDTA hydrate were put into the mixer, and were uniformly dispersed or dissolved under degassing conditions. Here, the preformulation 2 was put in and kneaded uniformly under deaeration conditions. Further, preformulation 3 was put in, and after mass correction was performed with purified water so that the total amount would be 100 parts by mass, it was kneaded uniformly under degassing conditions to obtain the adhesive layer-forming composition (paste) of Example 1. . The obtained adhesive layer-forming composition was stretched on the silicone surface of the liner (one-side silicone-treated PET (75 μm)) using a stretching machine adjusted to a slit width of 0.5 mm, and the woven support was After lamination (made of polyester), it was punched out into an arbitrary shape, sealed in an aluminum bag, and aged at 40° C. for 1 week to obtain the preparation of Example 1.

Example 2: The preparation of Example 2 was obtained in the same manner as in Example 1, except that the compounding amount of the partially neutralized polyacrylic acid was changed to 3.5 parts by mass.

Example 3: The preparation of Example 3 was obtained in the same manner as in Example 1 except that the compounding amount of the partially neutralized polyacrylic acid was changed to 3.0 parts by mass.

Example 4: The preparation of Example 4 was obtained in the same manner as in Example 1 except that the compounding amount of the partially neutralized polyacrylic acid was changed to 2.5 parts by mass.

Example 5: The preparation of Example 5 was obtained in the same manner as in Example 1 except that the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass.

Example 6: The same procedure as in Example 1 was carried out, except that the compounding amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex was changed to 30 parts by mass, and the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass. The preparation of Example 6 was obtained in the same way.

Example 7: The same procedure as in Example 1 was carried out, except that the compounding amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex was changed to 50 parts by mass, and the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass. The preparation of Example 7 was obtained in the same way.

Example 8: Except changing the blending amount of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to 60 parts by mass, changing the blending amount of the partially neutralized polyacrylic acid to 2.0 mass parts, and changing the blending amount of concentrated glycerin to 15 parts by mass Except for parts by mass, the preparation of Example 8 was obtained in the same manner as in Example 1.

Comparative Example 1: The same procedure as in Example 1 was carried out, except that the compounding amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex was changed to 10 parts by mass, and the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass. The preparation of Comparative Example 1 was obtained in the same way.

Comparative Example 2: The same procedure as in Example 1 was carried out, except that the compounding amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex was changed to 20 parts by mass, and the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass. The preparation of Comparative Example 2 was obtained in the same way.

Comparative Example 3: Except changing the blending amount of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to 70 parts by mass, changing the blending amount of the partially neutralized polyacrylic acid to 2.0 mass parts, and changing the blending amount of concentrated glycerin to Except for 15 parts by mass, an adhesive layer-forming composition was obtained in the same manner as in Example 1, but a large amount of agglomeration occurred in the obtained adhesive layer-forming composition, and subsequent spreading on the liner could not be performed, Preparation not available.

Comparative Example 4: Except changing the blending amount of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to 80 parts by mass, changing the blending amount of the partially neutralized polyacrylic acid to 2.0 mass parts, and changing the blending amount of concentrated glycerin to Except for 8.1 parts by mass, the adhesive layer-forming composition was obtained in the same manner as in Example 1, but a large amount of agglomeration occurred in the obtained adhesive layer-forming composition, and subsequent spreading on the liner could not be performed, Preparation not available.

Example 9: Except changing the grade of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to contain 23.8% methyl acrylate (hard segment), and changing the blending amount of the partially neutralized polyacrylic acid to 2.0 parts by mass, The formulation of Example 9 was obtained in the same manner as in Example 1.

Example 10: Except changing the grade of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to contain 31.1% methyl acrylate (hard segment), and changing the blending amount of the partially neutralized polyacrylic acid to 2.0 parts by mass, The formulation of Example 10 was obtained in the same manner as in Example 1.

Example 11: Except changing the grade of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to 40.8% methyl acrylate (hard segment), and changing the blending amount of the partially neutralized polyacrylic acid to 2.0 parts by mass, The formulation of Example 11 was obtained in the same manner as in Example 1.

Comparative Example 5: In addition to changing methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to n-butyl methacrylate-2-ethylhexyl acrylate copolymer resin latex (containing 43.3% of n-butyl methacrylate (hard segment) )), except that the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass, the preparation of Comparative Example 5 was obtained in the same manner as in Example 1.

Comparative Example 6: Except changing the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to methyl methacrylate-2-ethylhexyl acrylate copolymer resin latex (containing 43.4% methyl methacrylate (hard segment)) , except that the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass, the preparation of Comparative Example 6 was obtained in the same manner as in Example 1.

Comparative Example 7: In addition to changing the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to methyl acrylate-n-butyl acrylate copolymer resin latex (containing 45.4% of methyl acrylate (hard segment)), partially neutralize the polyacrylic acid The preparation of Comparative Example 7 was obtained in the same manner as in Example 1 except that the compounding amount of the compound was changed to 2.0 parts by mass.

Comparative Example 8: Except for changing methyl acrylate-2-ethylhexyl acrylate copolymer resin latex to ethyl methacrylate-2-ethylhexyl acrylate copolymer resin latex (containing 41.4% of ethyl methacrylate (hard segment)) , the preparation of Comparative Example 8 was obtained in the same manner as in Example 1, except that the compounding amount of the partially neutralized polyacrylic acid was changed to 2.0 parts by mass.

Example 12: The preparation of Example 12 was obtained in the same manner as in Example 1, except that the compounding amount of concentrated glycerin was changed to 25.0 parts by mass, and 10 parts by mass of 1N hydrochloric acid was newly added.

Example 13: A preparation of Example 13 was obtained in the same manner as in Example 1 except that the compounding amount of concentrated glycerin was changed to 25.0 parts by mass.

Example 14: The preparation of Example 14 was obtained in the same manner as in Example 1, except that the compounding amount of concentrated glycerin was changed to 25.0 parts by mass, and 10 parts by mass of 1N sodium hydroxide was newly added.

Test Example 1 (Appearance of adhesive layer (adhesive layer forming composition (paste))) For the formulations of Examples 1 to 14, and Comparative Examples 1 to 8, when containing moisture (after curing) and without moisture (after curing, the adhesive layer was exposed with a release liner at a temperature of 50 °C. After storing at °C for 16 hours and drying), the color of the adhesive layer (the composition for forming an adhesive layer) was visually evaluated.

Test Example 2 (liner peelability of adhesive layer (adhesive layer-forming composition (paste))) The formulations of Examples 1 to 14 and Comparative Examples 1 to 8 were cut into 4 cm×4 cm, and the liner was released from the formulation, and the liner releasability was evaluated by the following evaluation criteria. It is practical in the range of peelability of + to +++. <Evaluation Criteria> -: cannot be stripped +: Heavier peeling ++: Stripping is medium +++: lighter peel

Test Example 3 (Paste-to-paste peelability of adhesive layer (adhesive layer-forming composition (paste)) The formulations of Examples 1 to 14 and Comparative Examples 1 to 8 were cut to 4 cm × 4 cm, and the liner was peeled off from the formulation, and the paste surfaces were attached to each other for 30 seconds, and evaluated by the following Criteria The peelability between pastes at the time of peeling was evaluated. It is practical in the range of peelability of + to +++. <Evaluation Criteria> -: cannot be stripped +: Heavier peeling ++: Stripping is medium +++: lighter peel

Test Example 4 (Swelling degree and cross-linked state of adhesive layer (adhesive layer-forming composition (paste)) For the formulations of Examples 1 to 14, and Comparative Examples 1 to 8, when containing moisture (after curing) and without moisture (after curing, the adhesive layer was exposed with a release liner at a temperature of 50 °C. After storing at °C for 16 hours and drying), after cutting into 1 cm×4 cm, the liner was peeled off from the formulation, and the mass thereof was measured (initial formulation mass). Next, the support (woven support, polyester product) used in the production of the preparation was cut into 1 cm×4 cm, and the mass (initial support mass) was measured. The preparations and supports of the above examples and comparative examples were immersed in 20 mL of purified water at room temperature for 24 hours. After immersion, after taking out the formulation and wiping off the moisture on the surface, its mass was measured (formulation mass after immersion). In the same manner, the mass of the support taken out after dipping (mass of the support after dipping) was determined. The degree of swelling was calculated using the following formula from the measured values of the formulation and the support. Swelling degree = (preparation mass after dipping - support mass after dipping)/(initial preparation mass - initial support mass) In addition, the degree of crosslinking at the time of moisture content (after aging) was evaluated according to the following evaluation criteria. Furthermore, the degree of crosslinking is preferably ++ or more, and if it is + or -, the shape retention of the paste is insufficient, and there is a possibility that a large amount of the paste remains on the skin when peeled off after sticking. <Evaluation Criteria> -: Not cross-linked (the paste dissolves in purified water and cannot be recovered) +: Slightly cross-linked (swelling degree of 50 or more) ++: Moderate degree of crosslinking (swelling degree is 10 or more and less than 50) +++: Severely cross-linked (swelling degree less than 10)

Test Example 5 (pH value of adhesive layer (adhesive layer forming composition (paste))) The formulations of Examples 1 to 14 and Comparative Examples 1 to 8 were cut into 4 cm×4 cm, and then the liner was peeled off and immersed in 20 mL of purified water. After shaking for 30 minutes, the pH value was measured using a pH meter.

Test Example 6 (Adhesion Test of Adhesive Layer (Adhesive Layer Forming Composition (Paste)) For the formulations of Examples 1 to 14, and Comparative Examples 1 to 8, when containing moisture (after curing) and without moisture (after curing, the adhesive layer was exposed with a release liner at a temperature of 50 °C. After storing at ℃ for 16 hours and drying), the adhesion test using the probe adhesion was carried out in accordance with the Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3.4 Probe Adhesion Test Method. In addition, this evaluation reflects the adhesive force of the adhesive layer, and the value is preferably 1.13 N/5 mmϕ or more, which is equal to or higher than the commercially available patch when no moisture is contained.

<Reference example> About each formulation of the following Reference Example 1 to Reference Example 3 (commercial product), after opening the package of the product, the test was carried out according to Test Examples 4 and 6. In addition, the formulations of Reference Example 1 to Reference Example 3 are as follows. Reference Example 1: Patch (Loxonin S tape, Daiichi Sankyo Healthcare (stock), batch number CO58S) Reference example 2: poultice (Loxonin S pap, Daiichi Sankyo Healthcare (stock), lot number JO297) Reference Example 3: Potion (Vantelin kowa pat EX, Xinghe (stock), batch number FA9W)

The results regarding the effect of the blending ratio of the alkyl acrylate copolymer emulsion and the acrylic hydrophilic adhesive are shown in Table 2 together with the reference example, and the results regarding the effect of the blending amount of the alkyl acrylate copolymer emulsion are shown in Table 2. shown in Table 3. In addition, the results regarding the influence of the type of monomers in the alkyl acrylate copolymer emulsion are shown in Table 4, and the results regarding the influence of the pH value change of the adhesive layer due to the addition of hydrochloric acid and sodium hydroxide are shown in Table 4. table 5.

[Table 2][Table 2] Formulation, specification and measurement results Example 1 Example 2 Example 3 Example 4 Example 5 Reference Example 1 Reference example 2 Reference Example 3 formula Loxoprofen Sodium Hydrate 1.13 1.13 1.13 1.13 1.13 l-Menthol 1.00 1.00 1.00 1.00 1.00 polyvinyl alcohol 1.00 1.00 1.00 1.00 1.00 Methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (i) 40.00 40.00 40.00 40.00 40.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 0.20 Macrogol 400 1.50 1.50 1.50 1.50 1.50 Lactic acid 1.00 1.00 1.00 1.00 1.00 Concentrated glycerin (humectant: <A>) 20.00 20.00 20.00 20.00 20.00 Partially neutralized polyacrylic acid (ii) (powder component <B>) 4.00 3.50 3.00 2.50 2.00 Sodium carboxymethyl cellulose (powder ingredient <B>) 3.00 3.00 3.00 3.00 3.00 Dihydroxyaluminumaminoacetate (powder ingredient <B>) 0.25 0.25 0.25 0.25 0.25 purified water Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Specification Copolymer emulsion (i) formulation amount (%) 40 40 40 40 40 Copolymer emulsion (i)/polyacrylic acid partially neutralized product (ii) formulation ratio 10 11.4 13.3 16 20 Powder ingredient <B>/wetting agent <A> mixing ratio 0.36 0.34 0.31 0.29 0.26 Emulsion monomer Hard segment (monomer A) ^{※ 3} MA MA MA MA MA Soft segment (monomer B) ^{* 3} 2EHA 2EHA 2EHA 2EHA 2EHA Hard segment deployment amount (%) 46.7 46.7 46.7 46.7 46.7 The measurement results Exterior when hydrated cloudy cloudy cloudy translucent translucent without moisture transparent transparent transparent transparent transparent liner release when hydrated ++ ++ +++ +++ +++ Peelability between pastes when hydrated +++ +++ +++ +++ ++ Degree of swelling when hydrated 19.4 15.1 13.2 9.9 8.9 ND ^{※ 1} 35.30 without moisture 37.7 29.6 26.6 19.7 19.2 2.30 degree of cross-linking when hydrated ++ ++ ++ +++ +++ ++ pH when hydrated 4.91 4.78 4.77 4.76 4.93 Probe Viscosity (N/5 mmϕ) when hydrated 0.93 0.67 0.82 0.64 0.71 1.13 ^{※ 2} 0.57 0.51 without moisture 2.03 2.65 2.56 2.90 2.68 0.57 0.45 ※1 The paste cannot be recovered and cannot be measured. ※2 Since it is a patch, the measurement was performed without drying. ※3 MA: Methyl acrylate, 2EHA: 2-ethylhexyl acrylate

[Table 3][Table 3] Formulation, specification and measurement results Example 6 Example 5 (represented again) Example 7 Example 8 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 formula Loxoprofen Sodium Hydrate 1.13 1.13 1.13 1.13 1.13 1.13 1.13 1.13 l-Menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 polyvinyl alcohol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (i) 30.00 40.00 50.00 60.00 10.00 20.00 70.00 80.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Macrogol 400 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Concentrated glycerin (humectant: <A>) 20.00 20.00 20.00 15.00 20.00 20.00 15.00 8.10 Partially neutralized polyacrylic acid (ii) (powder component <B>) 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 Sodium carboxymethyl cellulose (powder ingredient <B>) 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 Dihydroxyaluminumaminoacetate (powder ingredient <B>) 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 purified water Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Specification Copolymer emulsion (i) formulation amount (%) 30 40 50 60 10 20 70 80 Copolymer emulsion (i)/polyacrylic acid partially neutralized product (ii) formulation ratio 15 20 25 30 5 10 35 40 Powder ingredient <B>/wetting agent <A> mixing ratio 0.26 0.26 0.26 0.35 0.26 0.26 0.35 0.64 Emulsion monomer Hard segment (monomer A) ^{※ 1} MA MA MA MA MA MA MA MA Soft segment (monomer B) ^{※ 1} 2EHA 2EHA 2EHA 2EHA 2EHA 2EHA 2EHA 2EHA Hard segment deployment amount (%) 46.7 46.7 46.7 46.7 46.7 46.7 46.7 46.7 The measurement results Exterior when hydrated translucent translucent cloudy cloudy transparent transparent Not easy to manufacture Not easy to manufacture without moisture transparent transparent transparent transparent transparent transparent liner release when hydrated + +++ ++ ++ + + Peelability between pastes when hydrated +++ ++ ++ + +++ +++ Degree of swelling when hydrated 8.7 8.9 11.0 10.5 8.7 8.3 without moisture 17.0 19.2 19.8 18.2 16.1 15.8 degree of cross-linking when hydrated +++ +++ ++ ++ +++ +++ pH when hydrated 4.67 4.93 4.67 4.72 4.81 4.67 Probe Viscosity (N/5 mmϕ) when hydrated 0.24 0.71 0.69 1.03 0.22 0.16 without moisture 1.55 2.68 2.95 3.57 1.07 1.12 *1 MA: methyl acrylate, 2EHA: 2-ethylhexyl acrylate

[Table 4][Table 4] Formulation, specification and measurement results Example 9 Example 10 Example 11 Example 5 (represented again) Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 formula Loxoprofen Sodium Hydrate 1.13 1.13 1.13 1.13 1.13 1.13 1.13 1.13 l-Menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 polyvinyl alcohol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (i) 40.00 40.00 40.00 40.00 40.00 40.00 40.00 40.00 Sodium EDTA hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Macrogol 400 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Concentrated glycerin (humectant: <A>) 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 Partially neutralized polyacrylic acid (ii) (powder component <B>) 2.00 2.00 2.00 2.00 2.00 2.00 2.00 2.00 Sodium carboxymethyl cellulose (powder ingredient <B>) 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 Dihydroxyaluminumaminoacetate (powder ingredient <B>) 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 purified water Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Total 100 g Specification Copolymer emulsion (i) formulation amount (%) 40 40 40 40 40 40 40 40 Copolymer emulsion (i)/polyacrylic acid partially neutralized product (ii) formulation ratio 20 20 20 20 20 20 20 20 Powder ingredient <B>/wetting agent <A> mixing ratio 0.26 0.26 0.26 0.26 0.26 0.26 0.26 0.26 Emulsion monomer Hard segment (monomer A) ^{※ 1} MA nBMA MMA MA EMA Soft segment (monomer B) ^{※ 1} 2EHA nBA 2EHA Hard segment deployment amount (%) 23.8 31.1 40.8 46.7 43.3 43.4 45.4 41.4 The measurement results Exterior when hydrated cloudy cloudy cloudy translucent cloudy cloudy cloudy cloudy without moisture transparent transparent transparent transparent transparent transparent transparent transparent liner release when hydrated + ++ ++ +++ +++ ++ + ++ Peelability between pastes when hydrated +++ +++ +++ ++ +++ +++ +++ +++ Degree of swelling when hydrated 8.6 10.1 10.5 8.9 7.6 11.4 7.6 12.2 without moisture 18.5 20.5 21.4 19.2 15.7 23.2 15.7 24.6 degree of cross-linking when hydrated +++ ++ ++ +++ +++ ++ +++ ++ pH when hydrated 4.62 4.82 4.94 4.93 4.77 4.64 4.65 4.67 Probe Viscosity (N/5 mmϕ) when hydrated 0.41 0.34 0.35 0.71 0.32 0.27 0.35 0.27 without moisture 1.19 1.19 2.02 2.68 0.53 0.73 0.66 0.67 *1 MA: methyl acrylate, nBMA: n-butyl methacrylate, MMA: methyl methacrylate, EMA: ethyl methacrylate 2EHA: 2-ethylhexyl acrylate, nBA: n-butyl acrylate

[Table 5][Table 5] Formulation, specification and measurement results Example 12 Example 13 Example 14 formula Loxoprofen Sodium Hydrate 1.13 1.13 1.13 l-Menthol 1.00 1.00 1.00 polyvinyl alcohol 1.00 1.00 1.00 Methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (i) 40.00 40.00 40.00 Sodium EDTA hydrate 0.20 0.20 0.20 Macrogol 400 1.50 1.50 1.50 Lactic acid 1.00 1.00 1.00 Concentrated glycerin (humectant: <A>) 25.00 25.00 25.00 Partially neutralized polyacrylic acid (ii) (powder component <B>) 4.00 4.00 4.00 Sodium carboxymethyl cellulose (powder ingredient <B>) 3.00 3.00 3.00 Dihydroxyaluminumaminoacetate (powder ingredient <B>) 0.25 0.25 0.25 1N hydrochloric acid 10.00 0.00 0.00 1N sodium hydroxide 0.00 0.00 10.00 purified water Total 100 g Total 100 g Total 100 g Specification Copolymer emulsion (i) formulation amount (%) 40 40 40 Copolymer emulsion (i)/polyacrylic acid partially neutralized product (ii) formulation ratio 10 10 10 Powder ingredient <B>/wetting agent <A> mixing ratio 0.29 0.29 0.29 Emulsion monomer Hard segment (monomer A) ^{※ 1} MA Soft segment (monomer B) ^{※ 1} 2EHA Hard segment deployment amount (%) 46.7 46.7 46.7 The measurement results Exterior when hydrated cloudy cloudy cloudy without moisture transparent transparent transparent liner release when hydrated ++ + + Peelability between pastes when hydrated +++ +++ ++ Degree of swelling when hydrated 19.3 25.7 8.3 without moisture 28.3 45.4 12.2 degree of cross-linking when hydrated ++ ++ +++ pH when hydrated 4.87 5.18 5.27 Probe Viscosity (N/5 mmϕ) when hydrated 0.83 0.65 0.49 without moisture 2.69 2.64 3.17 *1 MA: methyl acrylate, 2EHA: 2-ethylhexyl acrylate

In Examples 1 to 5 shown in Table 2, the mixing ratio (mass ratio) of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex/polyacrylic acid partially neutralized product was changed in the range of 10-20 By. These formulations have no problem in terms of manufacturability, and the liner peelability, the peelability between pastes, and the degree of crosslinking are all within the range that has no problem in terms of practicality. In addition, the adhesive force when no water was contained was superior to that of the commercially available patch shown in Reference Example 1. Examples 5 to 8 and Comparative Examples 1 to 4 shown in Table 3 are those in which the blending amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex was changed in the range of 10 to 80% . When the compounding amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex is 70% or more (Comparative Examples 3 and 4), a large amount of agglomeration occurs in the adhesive layer-forming composition obtained in the formulation, and the It was not uniform and the preparation could not be obtained. If the compounding amount of methyl acrylate-2-ethylhexyl acrylate copolymer resin latex is 20% or less (Comparative Example 1 and Comparative Example 2), there is no problem in production, and the preparation can be obtained, but the problem when it does not contain moisture The adhesive force of the needle is lower than that of the commercial patch, and it is not considered to have sufficient adhesive force. If the blending amount of the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex is in the range of more than 20% by mass and less than 70% by mass, there is no problem in terms of manufacturability, and the liner peelability and the inter-paste peelability , and the degree of crosslinking are all within the range that has no problem in terms of practicability. In addition, the adhesive force when water is not contained is superior to that of the commercially available patch. Example 5, Example 9 to Example 11, and Comparative Example 5 to Comparative Example 8 shown in Table 4 are the results showing the effect of the kinds of monomers constituting the alkyl acrylate copolymer emulsion. When the content of methyl acrylate in the methyl acrylate-2-ethylhexyl acrylate copolymer resin latex (copolymer) was changed in the range of 23.8 to 46.7%, there was no problem in the manufacturability, liner peelability, paste Both the interbody releasability and the degree of crosslinking are within a range that does not pose a problem in terms of practicality. In addition, the adhesive force when water is not contained is superior to that of the commercially available patch. In the case of changing the monomer of the alkyl acrylate copolymer, that is, if the monomer A (hard segment) is changed to n-butyl methacrylate (Comparative Example 5: the Tg of the homopolymer is 293.1 K), methyl methacrylate Methyl methacrylate (Comparative Example 6: Tg of the homopolymer is 378.1 K) and ethyl methacrylate (Comparative Example 8: The Tg of the homopolymer is 338.1 K), the probe sticks without moisture The force is 0.53 to 0.73 N/5 mmϕ, which is lower than that of commercial patches. Similarly, if the monomer B (soft segment) is changed to n-butyl acrylate (Comparative Example 7: the Tg of the homopolymer is 218.1 K), the adhesive force of the probe without moisture is 0.66 N/ 5 mmϕ, lower than commercially available patches. Examples 12 to 14 shown in Table 5 were evaluated for the effect of changing the pH of the adhesive layer (adhesive layer-forming composition (paste)) by adding hydrochloric acid and sodium hydroxide . In the range of pH value of 5.27 or less, there is no problem in terms of manufacturability, and the liner peelability, the peelability between pastes, and the degree of crosslinking are all in the range in which there is no problem in terms of practicality. In addition, the adhesive force when water is not contained is superior to that of the commercially available patch. From the above results, the water-based adhesive for pharmaceuticals in which the latex of the alkyl acrylate-based copolymer is contained at a ratio of more than 20% by mass and less than 70% by mass in the adhesive layer has no problem in terms of manufacturability, and The liner releasability, the inter-paste releasability, and the degree of crosslinking are all within the range that does not cause problems in terms of practicality. In addition, the adhesive force when water is not contained is superior to that of the commercially available patch.

Claims (4)

An aqueous adhesive for pharmaceuticals, It comprises a support, an adhesive layer and a release liner arranged on the support, and The above adhesive layer contains: 1) Active ingredients, 2) acrylic hydrophilic adhesive, 3) Alkyl acrylate copolymer emulsion (solid content 57-61% by mass), 4) Cross-linking agent, 5) Thickener, 6) Wetting agents containing almost no water (with a moisture content of 17% or less), and 7) water, and The above-mentioned alkyl acrylate copolymer is a copolymer comprising a monomer mixture of monomer A and monomer B, The above-mentioned monomer A is a monomer which becomes a polymer having a glass transition temperature (Tg) of 270 or more and 290 K or less when the monomer A is homopolymerized, The above-mentioned monomer B is a monomer that makes a polymer having a glass transition temperature (Tg) of 210 K or less when the monomer B is homopolymerized, and The alkyl acrylate copolymer emulsion is contained in a ratio of more than 20 mass % and less than 70 mass % with respect to the total mass of the adhesive layer. As claimed in claim 1, the water-based adhesive preparation for pharmaceuticals has one or more of the following items a) to c): a) The mass ratio of the above-mentioned alkyl acrylate copolymer emulsion to the above-mentioned acrylic hydrophilic adhesive is more than 5 and less than 30; b) The pH value of the above-mentioned adhesive layer is 4.5 to 5.5; c) The mass ratio of the powdery components (the above-mentioned acrylic hydrophilic adhesive, cross-linking agent and thickener) to the above-mentioned almost water-free wetting agent is 0.01 or more and 0.35 or less. As claimed in claim 1 or claim 2, the water-based adhesive for pharmaceuticals, wherein the above-mentioned almost water-free wetting agent is selected from concentrated glycerin, glycerin, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, A group consisting of 1,3-propanediol and 1,4-butanediol. As claimed in any one of claims 1 to 3, the water-based adhesive for pharmaceutical products, wherein The above-mentioned adhesive layer further contains: 8) Cooling agent, 9) organic solvent, 10) pH regulator, 11) Chelating agents.