KR20220158748A - patch - Google Patents

Abstract

[Problem] To provide a water-based patch with improved stability of salicylic acid glycol, adhesive strength and crosslinking degree of the preparation.
[Solution] A water-containing adhesive comprising a support, an adhesive layer provided on the support, and a release liner applied on the adhesive layer, wherein the adhesive layer comprises a) salicylic acid glycol, b) (meth)acrylic acid alkyl ester copolymer, c ) partially neutralized polyacrylic acid, d) a water-soluble high molecular compound containing carmellose sodium, e) a wetting agent containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water; A water-containing patch in which the blending amount of glycerin in is greater than 15 times and not more than 18 times, on a mass basis, with respect to the blending amount of salicylic acid glycol.

Description

patch

The present invention relates to a water-containing patch, and more particularly, to a water-containing patch that has good adhesive strength despite being a water-based patch, and also has good stability of the salicylic acid glycol to be blended and has an appropriate degree of crosslinking.

A patch using an adhesive base containing water, which is generally referred to as a "patch" (referred to as a water-containing patch in this specification), is a solid layer containing active ingredients such as drugs (adhesive layer) on a support such as non-woven fabric. Since the gel patch uses an adhesive base containing water in the solid layer, skin irritation is low, but the adhesive force is weak. In particular, as moisture in the solid layer evaporates, the adhesive force decreases over time, making it difficult to peel off from the skin. Easy was the problem.

In order to solve this problem, an emulsion (also called emulsion) base in which an acrylic acid alkyl ester copolymer, known as a component constituting a non-aqueous (also referred to as hydrophobic, lipophilic) adhesive, is dispersed is used as a solid A technique of blending into a layer (pressure-sensitive adhesive layer) is known.

For example, in Patent Document 1, a patch prepared by mixing 1% of a methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name: Nikazole TS-620, Nippon Carbide Kogyo Co., Ltd.) in a patch base (solid) ( Comparative product) is disclosed.

In Patent Document 2, the expression of adhesive strength and re-adhesiveness at the time of long-term sticking, suppression of deterioration of hardening and softness accompanying water loss, and suppression of breakage of the support at the time of peeling are obtained. Aiming at providing a hydrous adhesive, 0.01% by mass or more and 10.0% by mass or less of a water-dispersible surfactant and 5.0% by mass or more and 10% by mass or less of methyl acrylate/2-ethylhexyl acrylate copolymer with respect to the entire composition for a water-based external patch. A water-containing patch for external use is disclosed.

In Patent Literature 3, the problem is to provide a gel patch having sufficient adhesive strength even when the water content of the gel patch decreases over time, and a partially neutralized product of polyacrylic acid and 2.5 to 10 times the mass of the neutralized product (on a solid basis) 5 to 25% by mass) of methyl acrylate/2-ethylhexyl acrylate copolymer and polyacrylic acid are disclosed.

Patent Literature 4 discloses a gel patch containing poly(methyl acrylate/2-ethylhexyl acrylate) and a surfactant such as polyethylene glycol fatty acid ester for the purpose of providing a gel patch capable of peeling off a release liner with less force. has been

Patent Document 5 discloses that a heat-cooling sheet was obtained using an adhesive composition containing 1.5% by weight of an acrylic resin emulsion (trade name: Nikazole TS-620) and 6.2% by weight of sodium polyacrylate.

Japanese Unexamined Patent Publication No. 9-208462 Japanese Patent Publication No. 5650684 Specification Japanese Patent Publication No. 5921779 Specification International Publication No. 2016/104227 Japanese Unexamined Patent Publication No. 2002-104957

As described above, it is known to incorporate an alkyl acrylate ester copolymer such as a methyl acrylate-2-ethylhexyl acrylate copolymer into the pressure-sensitive adhesive layer in order to improve the adhesive durability of the hydrous adhesive. However, salicylic acid glycol has problems with its drug stability in an aqueous solvent, that is, it has not yet been able to say that it can be said to be sufficiently satisfactory for the stability and adhesiveness of the drug in a hydrous patch containing salicylic acid glycol.

As a result of intensive research to solve the above problems, the inventors of the present invention have found that, in order to achieve both the stability of salicylic acid glycol in a water-based patch and the improvement in the adhesiveness of the formulation and the appropriate degree of crosslinking, the pH of the adhesive (solid) was adjusted. Adjustment, particularly when adjusting pH, by indispensably blending hydrochloric acid, found that the above subject can be solved, and completed the present invention.

That is, the present invention is a water-containing adhesive comprising a support, an adhesive layer provided on the support, and a release liner applied on the adhesive layer,

The pressure-sensitive adhesive layer is made by essentially containing the following components a) to h),

a) salicylic acid glycol;

b) (meth)acrylic acid alkyl ester copolymer;

c) partially neutralized polyacrylic acid;

d) a water-soluble high molecular compound containing carmellose sodium;

e) humectants comprising glycerin;

f) a crosslinking agent;

g) hydrochloric acid, and

h) water;

In addition,

The blending amount of glycerin in the pressure-sensitive adhesive layer is more than 15 times and 18 times or less, on a mass basis, with respect to the blending amount of salicylic acid glycol,

It relates to a hydrous patch.

And according to this invention, the following embodiment is further provided.

1) The above water-based patch, wherein the pH value of the pressure-sensitive adhesive layer is 4.00 to 4.85.

2) When the pressure-sensitive adhesive layer makes the total mass of the pressure-sensitive adhesive layer 100% by mass

a) 0.1 to 30% by mass of salicylic acid glycol;

b) 0.1 to 5% by mass of (meth)acrylic acid alkyl ester copolymer;

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

d) 2.0 to 30% by mass of a water-soluble high molecular compound containing carmellose sodium;

e) 30 to 70% by mass of a humectant containing glycerin;

f) 0.01 to 6.0% by mass of a crosslinking agent;

g) 0.1 to 1.5% by mass of hydrochloric acid;

h) 10 to 90% by mass of water;

The above water-based patch, which is blended in a ratio of

3) The water-based patch, wherein the swelling degree of the pressure-sensitive adhesive layer calculated as the ratio of the weight of the pressure-sensitive adhesive layer after 24 hours of immersion to the weight of the pressure-sensitive adhesive layer before immersion in purified water is less than 50.

4) Storage conditions: The above-mentioned hydrous patch, in which the decrease (%) of the residual rate (%) of salicylic acid glycol before and after storage at 60 ° C. for 2 weeks is less than 5%.

Moreover, the following is mentioned as an example of a suitable aspect of this invention.

(i) In the pressure-sensitive adhesive layer, the total compounding amount of partially neutralized polyacrylic acid and carmellose sodium is within 7% by mass based on the total mass of the pressure-sensitive adhesive layer, and the compounding amount of partially neutralized polyacrylic acid is the same It is 3.5 mass % or more, and the said water-based patch whose compounding quantity of carmellose sodium is 2.0 mass % or more.

(ii) The alkyl (meth)acrylate is a copolymer of a monomer mixture composed of monomers A and B, wherein the monomer A is a polymer having a glass transition temperature (Tg) of 270 K or higher when homopolymerizing the monomer A. The above-mentioned water-based patch, wherein 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.

(iii) The above water-based patch, wherein the partially neutralized polyacrylic acid has a neutralization degree of 30% to 65%, and the viscosity of a 0.2% by mass aqueous solution thereof is 450 to 650 mPa·s.

(iv) The above-mentioned hydrous patch, wherein the carmellose sodium has a viscosity of 1,000 to 3,000 mPa·s in a 1% by mass aqueous solution and an ester substitution degree of 0.60 to 0.95.

(v) The water-containing patch in which the crosslinking agent is a sparingly soluble aluminum compound.

(vi) The above-mentioned water-containing patch, wherein the pressure-sensitive adhesive layer is formed of a pressure-sensitive adhesive layer forming composition containing the components a) to h) and having a viscosity of 90 to 250 Pa·s.

(vii) the pressure-sensitive adhesive layer, further

i) sodium edetate hydrate as chelating agent

The hydrous patch comprising a.

According to the present invention, in the hydrous patch containing salicylic acid glycol in the pressure-sensitive adhesive layer, by blending hydrochloric acid into the pressure-sensitive adhesive layer, the active ingredient, salicylic acid glycol, is stable over time, the adhesive strength of the preparation is high, and the degree of crosslinking is also improved. A good water-containing patch can be provided.

Further, according to the present invention, even after the moisture in the pressure-sensitive adhesive layer has evaporated, the adhesive force can be maintained, and the skin irritation is low and the solid-to-solid adhesion is low, so that it can be applied to the skin.

As described above, the inventors of the present invention, in a water-containing patch, particularly a water-containing patch in which a non-aqueous adhesive base is blended with a solid layer (adhesive layer) of the water-based adhesive, hydrochloric acid, which is an inorganic acid, is added to the pressure-sensitive adhesive layer By blending, the pH of the pressure-sensitive adhesive (solid) is adjusted, and specifically, it was found that the stability of the drug: salicylic acid glycol in the presence of water can be improved by tilting the pH value of the pressure-sensitive adhesive layer from the neutral side to the acidic side. . Particularly surprisingly, it was found that, in addition to drug stability, the blending of hydrochloric acid can improve both the degree of crosslinking and adhesive strength, which is difficult to say sufficient when employing other acids.

Hereinafter, the structure of the hydrous patch of the present invention will be described.

The water-containing patch (hereinafter, simply referred to as "patch") of the present invention consists of a support, an adhesive layer provided on the support, and a release liner applied to the adhesive layer.

The shape of the formulation part composed of the patch, particularly the support, and the pressure-sensitive adhesive layer provided on the support is not particularly limited, and may be square (square, rectangle, etc.), rectangle (trapezoid, lozenge, etc.), polygonal shape, circular shape, oval shape, semicircular shape, Various shapes can be selected according to the pasting location, such as a triangle, a crescent shape, and a shape in which these are combined.

In addition, the area of the patch (particularly the formulation part described above) can be appropriately determined, and can be, for example, in the range of 2 to 300 cm ² in consideration of the amount of the active ingredient to be incorporated into the pressure-sensitive adhesive layer.

[Adhesive layer]

The pressure-sensitive adhesive layer in the hydrous adhesive of the present invention is a) salicylic acid glycol, b) (meth)acrylic acid alkyl ester copolymer, c) polyacrylic acid partially neutralized, d) water-soluble polymer containing carmellose sodium, e ) a wetting agent including glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water.

The water-containing adhesive of the present invention, in addition to the hydrophilic acrylic pressure-sensitive adhesive described later, that is, c) partially neutralized polyacrylic acid, for the water-containing pressure-sensitive adhesive layer, generally constitutes a non-aqueous acrylic pressure-sensitive adhesive b) (meta ) Characterized in that an acrylic acid alkyl ester-based copolymer is also blended.

In general, as the pressure-sensitive adhesive used for the pressure-sensitive adhesive layer (solid layer) of the hydrous adhesive, there are widely used hydrophilic acrylic pressure-sensitive adhesives such as polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, and N-vinyl acetamide sodium acrylate copolymer resin. It is being used. From the viewpoint of being highly compatible with the above-described hydrophilic acrylic adhesive and capable of being uniformly combined, as the non-aqueous adhesive to be blended into the hydrous adhesive layer of the hydrophobic adhesive, acrylic and methacrylic emulsions A type of pressure-sensitive adhesive is preferably blended.

In the present specification, "(meth)acrylic acid alkyl ester copolymer" is intended to include both acrylic acid and methacrylic acid alkyl esters, and "acrylic pressure-sensitive adhesive" is also a combination of an acrylic pressure-sensitive adhesive and a methacrylic pressure-sensitive adhesive. It is made with the intention of including both sides.

<a) salicylic acid glycol>

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

In addition, if necessary, in addition to salicylic acid glycol, non-steroidal anti-inflammatory agents such as felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, ibuprofen, or esters thereof; antihistamines such as diphenhydramine and chlorpheniramine; analgesics such as aspirin, acetaminophen, ibuprofen, and sodium loxoprofen; local anesthetics such as lidocaine and dibucaine; muscle relaxants such as mastermethonium chloride; antifungal agents such as clotrimazole; antihypertensives such as clonidine; vasodilators such as nitroglycerin and isosorbide nitrate; vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin, and riboflavin butyrate; prostaglandins; Scopolamine, fentanyl, red pepper extract, nonylic acid vanillylamide, capsaicin, dl-camphor, etc. may be used in combination.

The compounding amount of the glycolic acid salicylic acid and the total compounding amount of the glycolic acid salicylic acid and the other active ingredient in the case of containing other active ingredients can be appropriately determined depending on the type of the other active ingredient, but for example, the adhesive layer of the hydrous patch It can be 0.1 mass % or more and 30 mass % or less, or 0.5 mass % or more and 15 mass % or less based on the total mass of.

<b) (meth)acrylic acid alkyl ester copolymer>

The (meth)acrylic acid alkyl ester-based copolymer (non-aqueous adhesive base material) constituting the non-aqueous acrylic adhesive is a component that exhibits adhesive strength, and the (meth)alkyl ester has 2 to 9 carbon atoms, and when homopolymerized, A monomer that becomes a polymer with a glass transition temperature (Tg) of -55 ° C (218 K) or less, and a monomer that becomes a polymer with a Tg of 8 to 165 ° C (281 to 438 K) when homopolymerized as a component that improves cohesion, Furthermore, it is a copolymer composed of a monomer having a functional group such as a carboxyl group or a hydroxyl group, such as a crosslinking point, if necessary (an example of the monomer is listed in Table 1).

monomer Number of carbon atoms in the alkyl ester moiety Tg of homopolymer Tg (K) Tg (℃) Adhesion expression
Tg: -55℃ or lower 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 improve cohesion
Tg: 8~165℃ methyl acrylate One 281.1 8 methyl methacrylate One 378.1 105 Ethyl methacrylate 2 338.1 65 n-butyl methacrylate 4 293.1 20 i-butyl methacrylate 4 321.1 48 t-butyl methacrylate 4 380.1 107 vinyl acetate - 305.1 32 Acrylonitrile - 370.1 97 acrylamide - 438.1 165 Styrene - 353.1 80 containing functional groups
(bridging point) acrylic acid 0 379.1 106 2-hydroxyethyl acrylate 2 213.1 -60 methacrylic acid 0 501.1 228 2-hydroxyethyl methacrylic acid 2 328.1 55 glycidyl methacrylate 3 323.1 50 Hydroxypropyl Methacrylic Acid 3 299.1 26

In addition, a homopolymer obtained by polymerizing only monomers exhibiting adhesive force is considered to have high adhesive force but low mechanical strength. In general, a copolymer having improved mechanical strength by copolymerization with a monomer that enhances cohesive force is used as an adhesive.

As mentioned as the monomers exhibiting the adhesive strength shown in Table 1 above, in the present invention, butyl acrylate and 2-ethyl acrylate having a Tg of 220K or less when the monomer is homopolymerized (homopolymer) as monomers having higher adhesive strength Hexyl, octyl acrylate, isononyl acrylate and the like are used. Among these, 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.

In addition, the monomers listed in Table 1 can be cited as monomers that improve cohesion (the Tg of the homopolymer is 270K or more), and among them, in the present invention, the mechanical strength is high and the adhesiveness is not significantly reduced (the Tg of the homopolymer is relatively low) methyl acrylate is preferred.

In addition, as mentioned in the prior art, as a commercially available acrylic acid alkyl ester copolymer used in patches, Nippon Carbide Co., Ltd. product, Nikazole (registered trademark) TS-620 (methyl acrylate/2-ethyl acrylate) hexyl copolymer resin emulsion). The methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion is a modified product of the pharmaceutical additives standard.

In the pressure-sensitive adhesive layer of the water-based adhesive of the present invention, the amount of the (meth)acrylic acid alkyl ester-based copolymer (in the case of an emulsion, the amount in terms of solid content) is based on the total mass of the pressure-sensitive adhesive layer of the water-based adhesive. For example, it can be 0.1 mass % or more and 5 mass % or less, 0.5 mass % or more and 4.5 mass % or less, and 1.0 mass % or more and 4.5 mass % or less.

In addition, the blending ratio with the acrylic hydrophilic adhesive described later is, for example, in mass ratio, acrylic acid alkyl ester copolymer: acrylic hydrophilic adhesive = 1.5: 1 to 1: 10, same = 1.5: 1 to 1: 5, same = 1.5:1 to 1:1, etc.

<c) Partially Neutralized Polyacrylic Acid>

The pressure-sensitive adhesive layer of the hydrous adhesive of the present invention contains partially neutralized polyacrylic acid as an acrylic hydrophilic pressure-sensitive adhesive.

Further, if necessary, an acrylic hydrophilic pressure-sensitive adhesive other than partially neutralized polyacrylic acid may be incorporated into the pressure-sensitive adhesive layer. In general, water-soluble (meth)acrylic polymers are exemplified as the acrylic hydrophilic adhesive. The water-soluble (meth)acrylic polymer is a polymer obtained by polymerizing a (meth)acryloyl group-containing monomer having a water-soluble functional group (hydrophilic group), and exhibits adhesiveness by blending with water in the pressure-sensitive adhesive layer. Water-soluble (meth)acrylic polymers include, for example, homopolymers such as partially neutralized products of polyacrylic acid and polyacrylic acid; and copolymers such as N-vinylacetamide/sodium acrylate copolymer resin.

The partially neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. That is, in the present specification, "partially neutralized polyacrylic acid" includes both neutralized products in which some of the acid groups of polyacrylic acid are neutralized as well as neutralized products in which all of the acid groups of polyacrylic acid are neutralized. Partially neutralized polyacrylic acid means a polyacrylic acid salt, and for example, sodium salt, potassium salt, calcium salt, ammonium salt and the like can be used. For example, Biscomate NP-800 (made by Showa Denko) is mentioned.

In a preferred embodiment, the partially neutralized polyacrylic acid used in the present invention is a partially neutralized product having a neutralization degree of 30% to 65%. It is also preferable to use a partially neutralized polyacrylic acid having a viscosity of 450 to 650 mPa·s at 20°C when the partially neutralized polyacrylic acid is used as an aqueous solution having a concentration of 0.2% by mass.

By using partially neutralized polyacrylic acid, in particular, by using partially neutralized polyacrylic acid having such a degree of neutralization and viscosity, more adhesion to the skin can be expressed when moistened, and crosslinking with a crosslinking agent is more promoted, Dissolution at the time of water retention can be prevented.

The compounding amount of the partially neutralized polyacrylic acid and the total compounding amount of the partially neutralized polyacrylic acid and the other acrylic hydrophilic adhesive in the case of containing other acrylic hydrophilic adhesives are based on the total mass of the adhesive layer of the hydrous adhesive, for example It can be 0.1 mass % or more and 10 mass % or less, and 1 mass % or more and 8 mass % or less.

For example, the compounding amount of the partially neutralized polyacrylic acid can be 3.5% by mass or more and 4.5% by mass or less based on the total mass of the pressure-sensitive adhesive layer.

<d) Water-soluble high molecular compound>

As said water-soluble high molecular compound, carmellose sodium (sodium carboxymethylcellulose) is contained as essential in the adhesive layer in the patch of this invention.

By using carmellose sodium, the shape-retaining properties of the preparation can be maintained more, and the pain at the time of peeling can be further reduced with thixotropic properties.

In a preferred embodiment, the carmellose sodium used in the present invention can have a viscosity of 1,000 to 3,000 mPa·s at 20°C in a 1% by mass aqueous solution. In addition, carmellose sodium preferably has an ester substitution degree of 0.60 to 0.95.

It may also contain water-soluble high molecular compounds other than carmellose sodium, such as gelatin, agar, polyvinyl alcohol (including partially saponified products), polyvinylpyrrolidone, propylene carbonate, carboxymethylcellulose, hydroxyl and propyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, sodium alginate, maleic anhydride copolymer, and carrageenan. These can be used together with carmellose sodium by appropriately combining 1 type or 2 or more types.

The amount of the water-soluble polymer compound is usually, for example, 1.0% by mass or more and 30% by mass or less, 2.0% by mass or more and 30% by mass or less, 2.5% by mass or more 20 It can be set as the range of mass % or less, or 3.0 mass % or more and 10 mass % or less.

Further, for example, the compounding amount of carmellose sodium can be 2.0% by mass or more and 3.5% by mass or less based on the total mass of the pressure-sensitive adhesive layer.

<e) Wetting agent containing glycerin>

A humectant (also referred to as a humectant) is incorporated into the pressure-sensitive adhesive layer of the water-based patch of the present invention to suppress evaporation of moisture over time.

As the wetting agent, glycerin is necessarily blended into the adhesive layer in the patch of the present invention.

In addition, wetting agents other than glycerin may be blended, and examples thereof include D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, liquid paraffin, 1,3-propanediol, 1,4-butanediol, maltitol, Polyhydric alcohols, such as xylitol, are mentioned. These can be used together with glycerin by appropriately combining 1 type or 2 or more types.

The amount of the wetting agent is usually, based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive, for example, 30% by mass or more and 70% by mass or less, 40% by mass or more and 60% by mass or less, 40% by mass or more and 50% by mass It can be set as the following or the range of 45 mass % or more and 55 mass % or less.

Further, in the present invention, the blending amount of glycerin in the pressure-sensitive adhesive layer is more than 15 times and 18 times or less, on a mass basis, with respect to the blending amount of a) salicylic acid glycol, for example, 15.5 times or more and 18.0 times or less, and 16.0 times or less. 17.9 times or more, 16.5 times or more and 17.9 times or less, 16.7 times or more and 17.9 times or less, 17.0 times or more and 17.9 times or less, 17.5 times or more and 17.9 times or less, or 15.5 times or more and 17 times or less. . When the blending amount of glycerin is small, there is a possibility that the moisture content of the adhesive may be easily evaporated due to insufficient moisturizing properties, and when the blending amount of glycerin is large, there is a possibility that the stability of the drug may decrease. On the other hand, there is a concern that a safety problem may occur if the amount of the drug (salicylic acid glycol) is excessively increased to improve stability.

<f) Crosslinking agent>

Examples of the crosslinking agent blended in the pressure-sensitive adhesive layer of the water-containing patch of the present invention include polyvalent metal salts, and among them, polyvalent metal compounds containing aluminum. As an example, hydroxides, such as aluminum hydroxide, alumina hydroxide, and magnesium; of inorganic or organic acids such as aluminum chloride, aluminum sulfate, potassium aluminum sulfate, aluminum glycinate (dihydroxyaluminumaminoacetal), dihydroxyaluminumaminoacetate, synthetic aluminum silicate, dry aluminum hydroxide gel, kaolin, and aluminum stearate. salts or basic salts thereof; double salts such as aluminum alum; aluminates such as sodium aluminate; inorganic aluminum complex salts and organic aluminum chelate compounds; and polyvalent metal compounds such as synthetic hydrotalcite, magnesium aluminate silicate, and magnesium metasilicate aluminate, which may be used alone or in combination of two or more.

Among them, it is preferable to use dihydroxyaluminumaminoacetate, which is a poorly soluble aluminum compound, synthetic aluminum silicate, and dried aluminum hydroxide gel.

The compounding amount of the crosslinking agent may be appropriately selected in consideration of the degree of crosslinking that may cause the residual of the pressure-sensitive adhesive on the skin and adhesiveness. Based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive, for example, 0.01% by mass or more and 6.0% by mass or less, 0.01% by mass or more and 4.0% by mass or less, or 0.01% by mass or more and 2.0% by mass or less. have.

<g) hydrochloric acid>

Hydrochloric acid is incorporated into the pressure-sensitive adhesive layer of the hydrous patch of the present invention.

The compounding amount of hydrochloric acid can be, for example, in the range of 0.1% by mass or more and 1.5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the hydrous patch.

In addition, if hydrochloric acid is not blended and only other acids such as acids included in <organic acids> described later or inorganic acids other than hydrochloric acid are blended, it becomes difficult to obtain both appropriate crosslinking properties and good adhesive strength. For example, when tartaric acid is used, good adhesive strength cannot be obtained, and when phosphoric acid is used, the stability of salicylic acid glycol and the expression of appropriate crosslinking properties may be inferior to those when hydrochloric acid is used. There is, and in order to obtain the same effect from the viewpoint of stability as the case of using hydrochloric acid, a larger amount of compounding may be required. Phosphoric acid is preferably not added, but it may be added as long as the effects of the present invention, particularly the degree of crosslinking, are not affected.

<h) water>

As described above, the hydrous adhesive of the present invention contains water (moisture) in the pressure-sensitive adhesive layer. In this specification, "water" contained in the pressure-sensitive adhesive layer includes not only water separately added as water when forming the pressure-sensitive adhesive layer, but also water contained in the form of an emulsion or aqueous solution. The blending amount of water is not particularly limited, but based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive, 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 It can be set within the following ranges. In addition, this water content is a value at the time of preparing the patch or before sticking the patch, and is not applied when water evaporates from the pressure-sensitive adhesive layer with the progress of sticking.

<i) Chelating agent>

A chelating agent may be incorporated into the pressure-sensitive adhesive layer of the water-containing patch of the present invention to control the viscosity of the solid at the time of production. Examples of the chelating agent include sodium edetate (disodium ethylenediaminetetraacetic acid disodium salt).

The blending amount of the chelating agent is usually, for example, 0.01% by mass or more and 1% by mass or less, or 0.1% by mass or more and 0.3% by mass or less, based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive.

<Organic Solvent>

In the pressure-sensitive adhesive layer of the water-based patch of the present invention, as a component that can play a role in assisting the dissolution of active ingredients such as drugs (i.e., functioning as a dissolution aid) and preventing the active ingredient from precipitating from the pressure-sensitive adhesive layer, An organic solvent may be blended.

As such an organic solvent (solubility aid), crotamiton; N-methyl-2-pyrrolidone; polyalkylene glycols such as Macrogol 400 (polyethylene glycol) and polybutylene glycol; polyvinyl alcohol; fatty acid esters such as diethyl adipate, diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl myristate, isopropyl palmitate, and oleyl oleate; polyoxyalkylene fatty acid esters and the like; sorbitan esters; polyhydric alcohols such as 1,3-butanediol; dimethylformamide; Dimethyl sulfoxide etc. are mentioned. These can be used individually by 1 type or in combination of 2 or more types.

In the case of using an organic solvent, the blending amount 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 hydrous adhesive.

<organic acid>

An organic acid may be blended into the pressure-sensitive adhesive layer of the hydrous patch of the present invention. Organic acids that can be blended include, for example, tartaric acid, citric acid, lactic acid, gluconic acid, glycolic acid, malic acid, fumaric acid, metasulfonic acid, maleic acid, acetic acid, and the like, and these can be used alone or in combination of two or more.

In the case of using an organic acid, the blending amount can be, for example, in the range of 0.1% by mass or more and 5% by mass or less based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive. By using the organic acid in this range, the problem of insufficient crosslinking, dissolution of the adhesive, or stickiness can be suppressed, and on the other hand, the problem that the crosslinking reaction proceeds excessively and the solid becomes hard and cannot be produced can be suppressed. can be expected

<Surfactant>

A surfactant may be incorporated into the pressure-sensitive adhesive layer of the hydrous patch of the present invention. Examples of such a surfactant include polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol diolate, and polypropylene glycol dioleate. ethylene fatty acid esters; Sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan sorbitan fatty acid esters such as bitantrioleate, sorbitan monosesquioleate, and ethylene oxide adducts thereof; Polyoxyethylene Sorbitan Monolaurate, Polyoxyethylene Sorbitan Monopalmitate, Polyoxyethylene Sorbitan Monostearate, Polyoxyethylene Sorbitan Tristearate, Polyoxyethylene Sorbitan Monooleate, Polyoxyethylene Sorbitan polyoxyethylene sorbitan fatty acid esters such as trioleate and polyoxyethylene sorbitan triisostearate; Polyoxyethylene dodecyl ether (polyoxyethylene lauryl ether), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyalkyleneridedecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene alkyl ethers such as polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethylhexyl ether, and polyoxyethylene isodecyl ether; polyoxyethylene alkyl phenol ethers such as polyoxyethylene styrenated phenyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene distyrenated phenyl ether, and polyoxyethylene tribenzyl phenyl ether; glycerin fatty acid esters such as glycerin monostearate 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 suitably.

When using these surfactants, the blending amount is, for example, 0.001% by mass or more and 10% by mass or less, 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 hydrous adhesive. can

<Other optional components>

In the pressure-sensitive adhesive layer of the hydrous patch of the present invention, as other optional components, antioxidants such as dibutylhydroxytoluene (BHT), calcium carbonate, magnesium carbonate, silicate, zinc oxide, titanium oxide, magnesium sulfate, Inorganic powders such as calcium sulfate, UV absorbers such as benzoylmethane derivatives, colorants, fragrances, preservatives, etc., generally used in adhesive layers in conventional water-based adhesives (papes) or non-aqueous adhesives (tape products) Components that can be formulated into can be formulated. When these optional components are used, each alone or in combination of two or more, usually, based on the total mass of the pressure-sensitive adhesive layer of the hydrous adhesive, for example, in the range of 0.01% by mass or more and 1% by mass or less. can be used

[support]

Examples of the support used for the water-containing patch of the present invention include a support having flexibility such as a film, nonwoven fabric, Japanese paper, cotton fabric, knitted fabric, woven fabric, and a laminate composite of a nonwoven fabric and a film. These supports are preferably made of a material that is flexible enough to adhere to the skin and follow the movements of the skin, and a material that can suppress occurrence of dermatitis or the like after long-term application. Examples of materials for these supports include polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon/polyethylene terephthalate composite, and polyacrylic. Ronitrile, polyvinyl alcohol, acrylic polyurethane, ester polyurethane, ether polyurethane, styrene-isoprene-styrene copolymer, styrene-butadiene-styrene copolymer, styrene-ethylene-propylene-styrene copolymer, styrene-butadiene Examples include rubber, ethylene-vinyl acetate copolymer, cellophane, and the like as essential components.

In addition, by coloring a support such as fabric with a colorant such as a skin color, the difference from the color of the skin can be reduced at the time of application. In addition, in terms of being easy to see the color tone of the skin under application, a form of a plastic film having excellent transparency can be employed.

The thickness of the support is usually about 5 µm to 1 mm. When the support is a cloth stream, 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 to 300 μm, more preferably 12 to 200 μm, still more preferably 15 to 150 μm. When the thickness of the support is very thin, about 5 μm to 30 μm, it is preferable to provide a peelable carrier film layer on the surface opposite to the pressure-sensitive adhesive layer formed on the support because handling as a patch improves. However, when the thickness of the support is smaller than 5 μm, the strength and handling of the patch are reduced, making it difficult to attach to the skin, causing tearing due to contact with other members, or contact with water such as bathing in a short time. It may exfoliate from the skin. In addition, if the thickness of the support is too large (exceeding 1 mm), it becomes difficult for the patch to follow the movement of the skin, and it is easy to form a trigger for peeling off in the periphery of the patch. There is a possibility that the discomfort in the stomach may increase.

Further, when the support is a film, processing such as sandblasting or corona treatment may be performed on one side or both sides of the support for the purpose of improving the anchoring properties of the pressure-sensitive adhesive and the support.

Further, in order to facilitate removal from the wrapping material, unevenness may be provided on one side or both sides of the support body by a method other than sandblasting.

[Releasable liner]

As the release liner (also referred to as a release layer or release paper) used in the water-based patch of the present invention, a material that is difficult to absorb and adsorb drugs or the like in the adhesive layer is preferable, and those commonly used in the technical field of adhesives are used. can be used

For example, plastic films such as polyester (polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, etc.), polypropylene (non-stretching, stretching, etc.), polyethylene, polyurethane, polyvinyl chloride, polystyrene; paper and synthetic paper such as fine paper, glassine paper, parchment paper, and kraft paper; release processed paper coated with a release agent having release performance such as silicone resin or fluororesin on the plastic film, paper, synthetic paper, or synthetic fiber; aluminum foil; Colorless or colored sheets, such as laminated paper obtained by laminating various types of these films/sheets, and laminated peelable paper obtained by coating the laminated paper with a release agent, are exemplified. In addition, it is also possible to provide the release liner with irregularities so that it can be easily taken out from the wrapping material.

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

Moreover, it is preferable that the peeling force at the time of peeling the adhesive layer from a peeling liner is a peeling force within a specific range. This is because if the peeling force of the pressure-sensitive adhesive layer from the release liner is too weak, the adhesive layer (ie, the patch) may come off from the release liner and peel off when the patch is caught on the wrapper when taking out the patch in the wrapper. Moreover, it is because there exists a possibility that the handling property at the time of use may worsen, when the peeling force of the adhesive layer (patch) from a peeling liner is too strong. The peeling force of the pressure-sensitive adhesive layer from the peeling liner depends on the type of peeling liner used, but can be, for example, 0.01 N/15 mm to 0.5 N/15 mm.

[Method for producing hydrous patch]

The water-based patch of the present invention can be produced using a conventionally known method. For example, as an example, it can be manufactured through the process of the following (i) or (ii).

(i) The process of coating the pressure-sensitive adhesive layer forming composition on the support to form the pressure-sensitive adhesive layer, and the process of bonding the pressure-sensitive adhesive layer formed on the support and the release liner.

(ii) The process of coating the pressure-sensitive adhesive layer forming composition on the release liner to form the pressure-sensitive adhesive layer, and the process of bonding the pressure-sensitive adhesive layer formed on the release liner and the support.

In addition, the thickness of the pressure-sensitive adhesive layer is not particularly limited, but is usually 10 μm to 1000 μm, for example, about 20 μm to 800 μm.

The composition for forming the pressure-sensitive adhesive layer includes various components included in the pressure-sensitive adhesive layer: salicylic acid glycol (others, active ingredient), (meth)acrylic acid alkylester-based copolymer, partially neutralized polyacrylic acid (others, acrylic-based hydrophilic pressure-sensitive adhesive), carmelo Contains a water-soluble high molecular compound containing aus sodium, a wetting agent containing glycerin, a crosslinking agent, hydrochloric acid, and water, and further contains a chelating agent, an organic solvent, an organic acid, a surfactant, and other optional components as desired. It is a semi-goose-shaped composition that can be made.

The pressure-sensitive adhesive layer forming composition preferably has a viscosity of 90 to 250 Pa·s, 100 to 250 Pa·s, more preferably 130 to 250 Pa·s at 20°C to 30°C from the viewpoint of operability during production. do. If the viscosity is less than 90 Pa·s, solids may ooze out when a knitted or woven fabric is used as a support. When the viscosity exceeds 250 Pa·s, it becomes difficult to spread.

[pH value of pressure-sensitive adhesive layer in water-containing patch]

In the water-based patch of the present invention, the pH value of the pressure-sensitive adhesive layer is preferably acidic (less than 6.0), 3.5 or more and less than 6.0, such as 4.00 to 4.85, preferably 4.40 to 4.80, more preferably may be 4.50 to 4.80. By controlling the pH value of the pressure-sensitive adhesive layer in an appropriate range, the stability of salicylic acid glycol can be improved, and furthermore, the coatability (flexibility) of the pressure-sensitive adhesive is improved. .

In addition, the pH value of the pressure-sensitive adhesive layer can be measured at a temperature of 20 to 25 ° C., for example, according to the pH measurement method of the Japanese Pharmacopoeia General Test Methods.

In addition, there are cases in which the pH value of a liquid obtained by diluting an adhesive (solid) with water is treated as the pH value of the adhesive layer (for example, International Publication No. 2016/104226). As a specific procedure, the release liner is peeled off from the prepared patch, the adhesive is scratched from the exposed adhesive layer using spatel or the like, purified water is added to the collected adhesive, and diluted 20 times, for example, to form a uniform solution. do. The obtained solution is kept warm at room temperature (25.0±0.2° C.), and the glass composite electrode of a calibrated pH meter is inserted into the solution to measure the pH value.

<Swelling degree>

When the pressure-sensitive adhesive layer (pressure-sensitive adhesive layer forming composition) of the present invention is immersed in purified water for 24 hours, the pressure-sensitive adhesive layer swelling degree calculated as the ratio of the weight of the pressure-sensitive adhesive layer after immersion for 24 hours to the weight of the pressure-sensitive adhesive layer before immersion It is preferable that is less than 50.

The procedure for measuring and calculating the degree of swelling is, for example, as follows: the water-based adhesive and the support are cut into predetermined sizes, and the water-based adhesive is weighed separately with the liner peeled off. (Initial water-based adhesive (liner release) weight, initial support weight). After that, they were immersed in purified water for 24 hours, and the weight after 24 hours of immersion was measured (the weight of the hydrous adhesive (liner peeling) after the purified water, the weight of the support after the purified water), and the swelling degree according to the following formula can be calculated

Degree of swelling of the pressure-sensitive adhesive layer = (water-containing adhesive (liner peeling) weight after purified water-settling - support weight after purified water-settling) / (initial water-containing adhesive (liner peeling) weight - initial support weight)

By setting the degree of swelling of the pressure-sensitive adhesive layer to less than 50, the shape-retaining property of the pressure-sensitive adhesive layer is maintained, and a water-containing patch in which the possibility of the pressure-sensitive adhesive layer remaining on the skin after peeling is suppressed can be provided.

Example

The present invention will be described in more detail by way of examples below, but the present invention is not limited to these examples.

<Production of patch>

Patches (formulations) of Examples, Comparative Examples, and Production Examples were prepared in the following procedure.

Example 1:

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

Next, 1 part by mass of Macrogol 400 was added to 1.25 parts by mass of ethylene glycol salicylate and 1 part by mass of L-menthol, and dissolved (oil phase).

In addition, 4 parts by mass of partially neutralized polyacrylic acid (degree of neutralization: 35%, viscosity: when used as an aqueous solution with a concentration of 0.2% by mass, its viscosity at 20 ° C. is 547 mPa s), sodium carmellose (degree of ester substitution: 0.82, viscosity: 1,840 mPa·s) 3 parts by mass and 0.25 parts by mass of dihydroxyaluminumaminoacetate were uniformly dispersed in 22 parts by mass of concentrated glycerin (glycerin phase).

In a stirrer, aqueous phase, 7 parts by mass of methyl acrylate/2-ethylhexyl acrylate copolymer emulsion, 0.20 parts by mass of sodium edetate hydrate, 30 parts by mass of D-sorbitol 70% aqueous solution, and 0.9 parts by mass of hydrochloric acid diluted with purified water (remaining amount) in this order added and uniformly dispersed or dissolved. Here, the oil phase and the glycerin phase were added in that order and kneaded uniformly. Further, 1 part by mass of lactic acid was added and uniformly kneaded under deaeration conditions to obtain the pressure-sensitive adhesive layer forming composition of Example 1. Furthermore, Test Example 4 (viscosity of the pressure-sensitive adhesive) described later was conducted using the obtained pressure-sensitive adhesive layer forming composition.

The obtained pressure-sensitive adhesive layer-forming composition was spread on the silicone side of a liner (PET (75 μm) treated with single-sided silicone) with a rolling machine, and a knit support (made of polyester) was laminated thereafter, and then aged at 40° C. for one week. After aging, it was punched into an arbitrary shape to obtain the formulation of Example 1.

Examples 2 to 9, Comparative Examples 1 to 9, Preparation Examples 1 to 20:

Examples 2 to 9 and Comparative Examples 1 to 9 in the same manner as in Example 1, except that the type and blending amount of each component was changed as described in Tables 2, 3, and 4 to 6. , Preparations of Production Example 1 to Production Example 20 were obtained. In addition, when mixing|blending phosphoric acid and tartaric acid, it manufactured by throwing in at the same timing as hydrochloric acid. In addition, glycerin monostearate, polysorbate 80, polyoxyethylene hydrogenated castor oil 10, lauromacrogol, polyoxyethylene oleyl ether, diisopropyl adipate, diethyl sebacate, isopropyl myristate, When blending isopropyl mitate, it was prepared by introducing each at the same timing as Macrogol 400.

Test Example 1 (measurement of pH of pressure-sensitive adhesive layer)

The pH of each formulation in Examples and Comparative Examples was measured at 25.0±0.2° C. according to the pH measurement method of General Test Methods of the Japanese Pharmacopoeia. The obtained results are shown in Table 2 and Table 3.

Test Example 2: Evaluation of the stability of salicylic acid glycol (SG)

To evaluate the stability of glycol salicylate, the content of glycol salicylate contained in the pressure-sensitive adhesive layer was measured by high performance liquid chromatography (HPLC) immediately after preparation of the preparation (initial) and after storage at 60 ° C. for 2 weeks (2W).

In detail, each formulation of Examples and Comparative Examples was cut into 40 mm × 40 mm (16 cm ² ), the release liner was peeled off, gauze (medical gauze, type I, 50 mm × 50 mm) was attached to the pressure-sensitive adhesive layer, and this was used as a test formulation. made with

Using 27 mL of methanol as an extraction solvent, a test agent was added to this, and extraction operation was performed by shaking. The extract was filtered through a membrane filter having a pore diameter of 0.45 µm to obtain a sample solution.

The sample solution was analyzed under the following HPLC conditions.

The stability of glycol salicylate (residual % in the pressure-sensitive adhesive layer) was evaluated by comparing the relative amount of the decomposition product with respect to the sum of the peak area of glycol salicylate (holding time: about 11 minutes) and the area of other peaks. . Further, from the initial value (residual % of salicylic acid glycol in the pressure-sensitive adhesive layer before storage), the reduction width of salicylic acid glycol after storage at 60 ° C. for 2 weeks (2W) (vs. initial value decrease (%)) was calculated. The obtained results are shown in Table 2 and Table 3.

Measurement wavelength: 240nm

Column: Mightysil RP-18 (150 mm × 4.6 mm, 5 μm)

Column temperature: 30°C

Flow: 0.5mL/min

Mobile phase A: water/methanol = 50/50

Analysis time: 30 minutes

Injection volume: 10 μL

In addition, regarding the stability evaluation of glycol salicylate, the storage condition of 40 ° C. for 6 months and the storage condition of 60 ° C. 2 W can be regarded as the same degree, and the stability of salicylate glycol (vs. initial value decrease (%)) is 60 ° C. Less than 5.0%, which does not show a clear change in quality, is desirable in the value after storage for 2W (vs. initial value decrease (%)).

Test Example 3: Adhesion Test Ball Tack

The release liner of each formulation (immediately after preparation) of Examples and Comparative Examples was peeled off to expose the adhesive layer, and the ball tack adhesiveness of the adhesive layer was measured according to Japanese Pharmacopoeia General Test Method 6.12 Adhesion Test Method 3.2. It was conducted according to the inclined ball tack test method. The average value (ball No.) of n = 3 was taken as the value of the ball tack test. The obtained results are shown in Table 2 and Table 3.

In addition, the evaluation of this ball tack reflects the adhesive strength of the pressure-sensitive adhesive layer, and the value is preferably 15 or more.

Test Example 4: Viscosity of pressure-sensitive adhesive

The viscosity of the pressure-sensitive adhesive layer forming compositions of Examples and Comparative Examples prepared in the procedure of <Preparation of Patch> was measured with a handy rotational viscometer before liner coating (measurement temperature: 20°C to 30°C). The obtained results are shown in Table 2 and Table 3.

Test Example 5: Pressure-sensitive adhesive layer crosslinking degree

Each formulation and support of Examples and Comparative Examples was cut to 12 × 100 mm, and each formulation was weighed (initial formulation weight, initial support weight) in a state where the liner was peeled off, and in a glass bottle containing purified water (room temperature). ), respectively, for 24 hours. After standing still, the formulation and the support were taken out of purified water and weighed (the weight of the formulation after water purification and the weight of the support after water purification), and the degree of swelling of the solid (adhesive layer) was calculated from the following formula.

Swelling degree of the solid = (preparation weight after purification - support weight after purification) / (initial formulation weight - initial support weight)

Based on the calculated degree of swelling, the degree of crosslinking was evaluated according to the following evaluation criteria. The obtained results are shown in Table 2 and Table 3. In addition, the degree of crosslinking is preferably + or more, and if it is ± or -, the shape retention of the solid becomes insufficient, and there is a risk that a large amount of solid remains on the skin during peeling after application.

<Evaluation of degree of crosslinking>

++: degree of swelling less than 10

+: degree of swelling 10 or more and less than 50

±: swelling degree of 50 or more

-: Most of the solid is dispersed in purified water and cannot be extracted

Test Example 6: Manufacturability

Manufacturability was evaluated according to the following evaluation criteria for difficulty in spreading the pressure-sensitive adhesive layer forming compositions of Examples and Comparative Examples prepared in the procedure of <Production of Patch> on the silicone surface of the liner with a spreading machine. The obtained results are shown in Table 2 and Table 3.

<Manufacturability evaluation>

++: easily spreadable

+: can spread

±: May be spreadable, but not stable

-: cannot be transferred

Ingredients (mixing amount: parts by mass) Example One 2 3 4 5 6 7 8 9 Ethylene glycol salicylic acid 1.25 1.25 1.25 1.25 1.40 2.00 2.00 1.25 1.25 L-Menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (60% solid content) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 carmellose sodium 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 2.00 concentrated glycerin 22.00 22.00 22.00 22.00 25.00 32.50 31.00 22.00 22.00 D-sorbitol solution 30.00 30.00 30.00 30.00 30.00 21.60 23.10 30.00 30.00 Edetate Sodium Hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.40 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 Hydrochloric acid 0.90 0.45 0.35 0.70 0.40 0.40 0.40 1.35 0.45 lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Macrogol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Purified water ^※ 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total Pressure-sensitive adhesive layer pH value 4.42 4.70 4.78 4.55 4.68 4.63 4.64 4.11 4.70 Salicylic acid glycol stability evaluation
(remaining %) Early 99.09 99.09 99.16 99.22 98.95 98.82 99.11 99.13 NT After 60℃ 2W 96.31 95.16 94.34 95.97 94.39 94.49 94.30 97.46 NT vs. initial value decrease (%) 2.8 3.9 4.8 3.3 4.6 4.3 4.8 1.7 NT Adhesion: ball tack (ball No.) 27.0 24.3 23.3 26.0 20.0 19.7 20.0 26.7 NT Viscosity of the pressure-sensitive adhesive layer (Pa s) 250 150 150 180 150 130 160 250 95 Degree of crosslinking of adhesive layer + + + + + + + ++ + Ratio of Glycerin/Glycol Salicylic Acid 17.6 17.6 17.6 17.6 17.9 16.3 15.5 17.6 17.6 manufacturability + ++ ++ ++ ++ ++ ++ + ++

※Adjust the amount of purified water so that the total of all ingredients is 100 parts by mass.

NT: no test

Ingredients (mixing amount: parts by mass) comparative example One 2 3 4 5 6 7 8 9 Ethylene glycol salicylic acid 1.25 1.40 1.40 1.40 1.40 1.40 2.00 2.00 2.00 L-Menthol 1.00 0.70 0.70 0.70 0.70 0.70 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (60% solid content) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 carmellose sodium 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 concentrated glycerin 22.00 25.00 25.00 25.00 25.00 25.00 32.50 32.50 32.50 D-sorbitol solution 30.00 30.00 30.00 30.00 30.00 30.00 21.60 21.60 21.60 Edetate Sodium Hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 Hydrochloric acid 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 phosphoric acid 0.00 0.25 0.50 0.75 1.00 2.00 0.00 0.00 0.00 tartaric acid 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.25 0.50 lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Macrogol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Purified water ^※ 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total Pressure-sensitive adhesive layer pH value 4.90 4.94 4.75 4.58 4.38 3.71 5.10 4.89 4.68 Salicylic acid glycol stability evaluation
(remaining %) Early 97.15 97.60 98.40 97.80 97.90 97.70 99.21 99.28 99.28 After 60℃ 2W 91.27 91.80 93.10 93.80 94.50 96.00 93.28 94.55 95.55 vs. initial value decrease (%) 5.9 5.8 5.3 4.0 3.4 1.7 5.9 4.7 3.7 Adhesion: ball tack (ball No.) NT NT NT NT NT NT 15.0 10.0 13.0 Viscosity of the pressure-sensitive adhesive layer (Pa s) 150 150 150 180 230 110 130 130 140 Degree of crosslinking of adhesive layer + ± - - - - + + + Ratio of Glycerin/Glycol Salicylic Acid 17.6 17.9 17.9 17.9 17.9 17.9 16.3 16.3 16.3 manufacturability ++ ++ ++ ++ + ++ ++ ++ ++

※Adjust the amount of purified water so that the total of all ingredients is 100 parts by mass.

NT: no test

Ingredients (mixing amount: parts by mass) Manufacturing Examples One 2 3 4 Ethylene glycol salicylic acid 1.25 1.25 1.25 1.25 L-Menthol 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (60% solid content) 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 carmellose sodium 3.00 3.00 3.00 3.00 Glycerin Monostearate 1.00 1.00 1.00 1.00 concentrated glycerin 20.00 20.00 20.00 20.00 D-sorbitol solution 25.00 25.00 25.00 25.00 Edetate Sodium Hydrate 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 Hydrochloric acid 0.90 0.90 0.90 0.90 lactic acid 1.00 1.00 1.00 1.00 Macrogol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 Diisopropyl adipic acid 1.00 diethyl sebacate 1.00 isopropyl myristic acid 1.00 Isopropyl Palmitate 1.00 Purified water ^※ 100 copies in total 100 copies in total 100 copies in total 100 copies in total

※Adjust the amount of purified water so that the total of all ingredients is 100 parts by mass.

Ingredients (mixing amount: parts by mass) Manufacturing Examples 5 6 7 8 9 10 11 12 Ethylene glycol salicylic acid 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 L-Menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (60% solid content) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 carmellose sodium 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 Polysorbate 80 (polyoxyethylene (20) sorbitan monooleate) 1.00 1.00 1.00 1.00 Polyoxyethylene Hydrogenated Castor Oil 1.00 1.00 1.00 1.00 concentrated glycerin 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 D-sorbitol solution 25.00 25.00 25.00 25.00 25.00 25.00 25.00 25.00 Edetate Sodium Hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 Hydrochloric acid 0.90 0.90 0.90 0.90 0.90 0.90 0.90 0.90 lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Macrogol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Diisopropyl adipic acid 1.00 1.00 diethyl sebacate 1.00 1.00 isopropyl myristic acid 1.00 1.00 Isopropyl Palmitate 1.00 1.00 Purified water ^※ 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total

※Adjust the amount of purified water so that the total of all ingredients is 100 parts by mass.

Ingredients (mixing amount: parts by mass) Manufacturing Examples 13 14 15 16 17 18 19 20 Ethylene glycol salicylic acid 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 L-Menthol 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Polyvinyl alcohol (partially saponified) 1.50 1.50 1.50 1.50 1.50 1.50 1.50 1.50 Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (60% solid content) 7.00 7.00 7.00 7.00 7.00 7.00 7.00 7.00 Partially neutralized polyacrylic acid 4.00 4.00 4.00 4.00 4.00 4.00 4.00 4.00 carmellose sodium 3.00 3.00 3.00 3.00 3.00 3.00 3.00 3.00 Lauromacrogol (polyoxyethylene lauryl ether) 1.00 1.00 1.00 1.00 Polyoxyethylene oleyl ether 1.00 1.00 1.00 1.00 concentrated glycerin 20.00 20.00 20.00 20.00 20.00 20.00 20.00 20.00 D-sorbitol solution 25.00 25.00 25.00 25.00 25.00 25.00 25.00 25.00 Edetate Sodium Hydrate 0.20 0.20 0.20 0.20 0.20 0.20 0.20 0.20 Dihydroxyaluminumaminoacetate 0.25 0.25 0.25 0.25 0.25 0.25 0.25 0.25 Hydrochloric acid 0.90 0.90 0.90 0.90 0.90 0.90 0.90 0.90 lactic acid 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Macrogol 400 (polyethylene glycol) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Diisopropyl adipic acid 1.00 1.00 diethyl sebacate 1.00 1.00 isopropyl myristic acid 1.00 1.00 isopropyl palmitate 1.00 1.00 Purified water ^※ 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total 100 copies in total

※Adjust the amount of purified water so that the total of all ingredients is 100 parts by mass.

As shown in Table 2, in the formulations (water-based patches) of Examples, by blending a predetermined amount of hydrochloric acid, in the evaluation of the stability of salicylic acid glycol as an active ingredient, the range of decrease in the initial value after storage at 60 ° C. for 2 weeks was 5 %, the vortex value is 15 or more, and the swelling degree, which is an indicator of the degree of crosslinking of the pressure-sensitive adhesive layer (solid), is less than 50 (evaluation of + or higher), and the stability of the active ingredient, the adhesive strength of the formulation, and the degree of crosslinking are also good functions. It became a concubine.

On the other hand, as shown in Table 3, in Comparative Examples 1 and 7 containing no hydrochloric acid, the range of reduction of salicylic acid glycol to the initial value exceeded 5%, resulting in formulations with poor stability of the active ingredient. In addition, when phosphoric acid was added instead of hydrochloric acid (Comparative Examples 2 to 6), the stability of salicylic acid glycol increased by increasing the blending amount, but the crosslinking degree was rather deteriorated, and when tartaric acid was blended instead of hydrochloric acid ( In Comparative Examples 8 and 9), the vortex value was less than 15, and the desired adhesive force could not be obtained.

From the results of the above examples, according to the present invention, in the hydrous patch containing salicylic acid glycol in the pressure-sensitive adhesive layer, by blending hydrochloric acid into the pressure-sensitive adhesive layer, salicylic acid glycol, which is an active ingredient, is stable over time even in a small amount. In addition, it was confirmed that a water-containing patch having an appropriate degree of crosslinking and good adhesive strength and also excellent in manufacturability could be provided.

Claims (5)

A water-containing adhesive comprising a support, an adhesive layer provided on the support, and a release liner applied on the adhesive layer,
The pressure-sensitive adhesive layer is made by essentially containing the following components a) to h),
a) salicylic acid glycol;
b) (meth)acrylic acid alkyl ester copolymer;
c) partially neutralized polyacrylic acid;
d) a water-soluble high molecular compound containing carmellose sodium;
e) humectants comprising glycerin;
f) a crosslinking agent;
g) hydrochloric acid, and
h) water;
In addition,
The blending amount of glycerin in the pressure-sensitive adhesive layer is more than 15 times and 18 times or less, on a mass basis, with respect to the blending amount of salicylic acid glycol
Functional patch. According to claim 1,
pH value of the pressure-sensitive adhesive layer is 4.00 ~ 4.85
Functional patch. According to claim 1 or 2,
When the pressure-sensitive adhesive layer makes the total mass of the pressure-sensitive adhesive layer 100% by mass
a) 0.1 to 30% by mass of salicylic acid glycol;
b) 0.1 to 5% by mass of (meth)acrylic acid alkyl ester copolymer;
c) 3.5 to 4.5% by mass of partially neutralized polyacrylic acid;
d) 2.0 to 30% by mass of a water-soluble high molecular compound containing carmellose sodium;
e) 30 to 70% by mass of a humectant containing glycerin;
f) 0.01 to 6.0% by mass of a crosslinking agent;
g) 0.1 to 1.5% by mass of hydrochloric acid;
h) 10 to 90% by mass of water;
made by mixing in the ratio of
Functional patch. According to any one of claims 1 to 3,
A water-containing patch having a degree of swelling of the pressure-sensitive adhesive layer calculated as a ratio of the weight of the pressure-sensitive adhesive layer after 24 hours of immersion to the weight of the pressure-sensitive adhesive layer before immersion in purified water. According to any one of claims 1 to 4,
Storage conditions: A water-based patch in which the residual rate (%) of salicylic acid glycol before and after storage at 60 ° C. for 2 weeks is less than 5%.