JP2024048993A - Patches - Google Patents

Abstract

[Problem] To provide a hydrous patch that satisfies both the adhesive strength over time of the patch after production as well as the handleability (manufacturability) during patch production. [Solution] A hydrous patch comprising a support, an adhesive layer provided on the support, and a release liner attached to the adhesive layer, the adhesive layer essentially containing the following components a) to h): a) an active ingredient, b) a (meth)acrylic acid alkyl ester copolymer, c) a partially neutralized polyacrylic acid, d) a water-soluble polymeric compound containing carmellose sodium, e) a wetting agent containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water, and the blending amount of water in the adhesive layer is 40% by mass or more and 70% by mass or less. [Selected Figure] None

Description

The present invention relates to a water-containing patch that has good adhesive strength over time.

Patches using a water-containing adhesive base, commonly referred to as "cataplasms" (referred to as water-containing patches in this specification), are a type of patch that has a paste layer (adhesive layer) containing an active ingredient such as a drug on a support such as a nonwoven fabric. Catplasms use an adhesive base containing water in the paste layer, so although they cause little skin irritation, they have weak adhesive strength, and the adhesive strength decreases over time as the moisture in the paste layer evaporates, making them prone to peeling off from the skin.
To solve these problems, a known technology involves blending an emulsion base (also called emulsion) in which an acrylic acid alkyl ester copolymer, known as one of the components that make up non-aqueous (also called hydrophobic or lipophilic) adhesives, is dispersed, into the paste layer (adhesive layer) of an aqueous adhesive patch.

For example, Patent Document 1 discloses a patch (comparison product) in which 1% of a methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion (trade name: Nikasol TS-620, Nippon Carbide Industries Co., Ltd.) is blended in a cataplasm base (plaster).
Patent Document 2 discloses an aqueous-based external patch which contains, relative to the entire composition for an aqueous-based external patch, 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 a methyl acrylate-2-ethylhexyl acrylate copolymer, for the purpose of providing an aqueous-based external patch which exhibits adhesive strength and re-adhesive strength when applied for a long period of time, inhibits hardening and loss of flexibility due to moisture loss, and inhibits rupture of the support when removed.
Patent Document 3 discloses a cataplasm containing a partially neutralized polyacrylic acid, a methyl acrylate-2-ethylhexyl acrylate copolymer in an amount 2.5 to 10 times the neutralized product by mass (5 to 25% by mass based on the plaster), and polyacrylic acid, with the objective of providing a cataplasm that has sufficient adhesive strength even when the water content of the cataplasm decreases over time.
Patent Document 4 discloses a cataplasm containing poly(methyl acrylate/2-ethylhexyl acrylate) and a surfactant such as a polyethylene glycol fatty acid ester, with the aim of providing a cataplasm from which a release liner can be peeled off with less force.
Patent Document 5 discloses that a cooling/heating sheet was obtained using a pressure-sensitive adhesive composition containing 1.5% by weight of an acrylic resin emulsion (trade name: Nikasol TS-620) and 6.2% by weight of sodium polyacrylate.

Japanese Patent Application Laid-Open No. 9-208462 Patent No. 5650684 Patent No. 5921779 International Publication No. 2016/104227 JP 2002-104957 A

As described above, it is known that in order to increase the adhesive durability of aqueous patches, an acrylic acid alkyl ester copolymer such as a methyl acrylate-2-ethylhexyl acrylate copolymer is blended in the adhesive layer.
On the other hand, from the viewpoint of suppressing the increase in viscosity of the adhesive layer-forming composition (coating liquid) during the production of the aqueous patch and improving the stability of the adhesive layer, it is also important to control the crosslinking degree of the adhesive. That is, if the crosslinking rate of the adhesive is fast, the viscosity increase during production makes coating (spreading) difficult and causes coating defects, which may lead to a decrease in manufacturability, while if the crosslinking rate is slow, it may lead to problems such as the adhesive remaining on the skin and the quality of the adhesive layer after production being unstable.
Thus, there is a demand for a water-containing patch that is fully satisfactory in terms of both adhesive strength over time after production, as well as ease of handling (manufacturability) during patch production.

As a result of intensive research conducted by the inventors to solve the above problems, they found that the above problems could be solved by reviewing and adjusting the amount of water in the formulation in order to improve the stability of adhesiveness over time in a water-containing patch while also improving the manufacturability (operability during manufacturing) of the patch, and thus completed the present invention.

That is, the present invention provides a water-containing patch comprising a support, a pressure-sensitive adhesive layer provided on the support, and a release liner attached on the pressure-sensitive adhesive layer,
The pressure-sensitive adhesive layer essentially contains the following components a) to h):
a) an active ingredient,
b) (meth)acrylic acid alkyl ester copolymer;
c) partially neutralized polyacrylic acid;
d) a water-soluble polymer compound containing sodium carmellose;
e) a humectant comprising glycerin;
f) a crosslinking agent;
g) hydrochloric acid, and h) water;
and,
The amount of water in the pressure-sensitive adhesive layer is 40% by mass or more and 70% by mass or less.
This relates to a water-containing patch.

Furthermore, the present invention further provides the following embodiments.
1) The above aqueous patch, wherein the active ingredient of the above adhesive layer is glycol salicylate.
2) The pressure-sensitive adhesive layer has a content of a) 0.1 to 30% by mass of an active ingredient, when the total mass of the pressure-sensitive adhesive layer is taken as 100% by mass.
b) 0.1 to 5% by mass of a (meth)acrylic acid alkyl ester copolymer
c) 0.1 to 10% by mass of partially neutralized polyacrylic acid
d) 1 to 30% by mass of a water-soluble polymer compound containing sodium carmellose
e) 30 to 70% by weight of a humectant containing glycerin
f) 0.01 to 6.0% by mass of a crosslinking agent
g) 0.1 to 1.5 mass% hydrochloric acid
The aqueous patch is prepared in the ratio of
3) Storage condition: the aforementioned aqueous patch having a ball tack remaining rate of 70% or more before and after storage at 60° C. for 2 weeks.

According to the present invention, by setting the moisture content of the adhesive layer in a water-containing patch within a specified range, it is possible to provide a water-containing patch that achieves stability of adhesive strength over time and is also easy to manufacture.

As described above, the present inventors have discovered that in an aqueous patch, particularly an aqueous patch in which a non-aqueous adhesive base is incorporated into the paste layer (adhesive layer) of an aqueous patch, by adjusting the moisture content in the paste layer (adhesive layer), it is possible to provide stability in adhesive strength over time and also to provide excellent spreadability of the adhesive layer-forming composition when forming the paste layer (adhesive layer).
The constitution of the aqueous patch of the present invention will be described below.

The aqueous patch of the present invention (hereinafter also simply referred to as "patch") comprises a backing, an adhesive layer provided on the backing, and a release liner attached to the adhesive layer.
The shape of the above-mentioned patch, particularly the preparation portion consisting of the backing and the adhesive layer provided on the backing, is not particularly limited, and various shapes can be selected according to the application site, such as a rectangle (square, rectangle, etc.), quadrilateral (trapezoid, rhombus, etc.), polygon, circle, ellipse, semicircle, triangle, crescent, and combinations of these.
The area of the patch (particularly the above-mentioned preparation portion) can be appropriately determined, and can be, for example, in the range of 2 to 300 ^cm2 , taking into consideration the amount of active ingredient to be blended in the adhesive layer.

[Adhesive layer]
The adhesive layer in the aqueous patch of the present invention essentially contains a) an active ingredient, b) a (meth)acrylic acid alkyl ester copolymer, c) a partially neutralized polyacrylic acid, d) a water-soluble polymer containing sodium carmellose, e) a wetting agent containing glycerin, f) a crosslinking agent, g) hydrochloric acid, and h) water.
The aqueous adhesive layer of the aqueous adhesive preparation of the present invention contains, in addition to the hydrophilic acrylic adhesive described below, i.e., c) a partially neutralized polyacrylic acid, b) an alkyl (meth)acrylate copolymer which generally constitutes a non-aqueous acrylic adhesive.
Generally, hydrophilic acrylic adhesives such as polyacrylic acid, partially neutralized polyacrylic acid, sodium polyacrylate, N-vinylacetamide-sodium acrylate copolymer resin, etc. are widely used as adhesives for the adhesive layer (paste layer) of aqueous patches. From the viewpoint of high affinity with the above-mentioned hydrophilic acrylic adhesives and ability to be kneaded uniformly, acrylic and methacrylic emulsion-type adhesives are preferably used as non-aqueous adhesives to be blended in the aqueous adhesive layer of aqueous patches.
In this specification, the term "(meth)acrylic acid alkyl ester copolymer" is intended to include both alkyl esters of acrylic acid and methacrylic acid, and the term "acrylic pressure-sensitive adhesive" is intended to include both acrylic pressure-sensitive adhesives and methacrylic pressure-sensitive adhesives.

<a) Active ingredient>
The adhesive layer in the aqueous patch of the present invention contains an active ingredient (such as a drug).
Examples of the active ingredients include nonsteroidal anti-inflammatory agents such as glycol salicylate (also called ethylene glycol salicylate), felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, indomethacin, ketoprofen, and ibuprofen, or esters thereof; antihistamines such as diphenhydramine and chlorpheniramine; analgesics such as aspirin, acetaminophen, ibuprofen, and loxoprofen sodium; Examples of such agents include local anesthetics such as sucrose and dibucaine, muscle relaxants such as suxamethonium chloride, antifungal agents such as clotrimazole, antihypertensives such as clonidine, vasodilators such as nitroglycerin and isosorbide dinitrate, vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin, riboflavin butyrate, prostaglandins, scopolamine, fentanyl, capsicum extract, vanillylamide nonylate, capsaicin, dl-camphor, etc. These agents may be used alone or in combination of two or more.

The amount of the active ingredients can be appropriately determined depending on the type and combination of the active ingredients, but can be, for example, 0.1% by mass to 30% by mass, or 0.5% by mass to 15% by mass, based on the total mass of the adhesive layer of the aqueous patch.

<b) (Meth)acrylic acid alkyl ester copolymer>
The (meth)acrylic acid alkyl ester copolymer (non-aqueous adhesive base) constituting the non-aqueous acrylic adhesive is a copolymer composed of a monomer having 2 to 9 carbon atoms in the (meth)alkyl ester as a component that exerts adhesive strength, which monomer becomes a polymer having a glass transition temperature (Tg) of −55° C. (218 K) or lower when homopolymerized, a monomer that becomes a polymer having a Tg of 8 to 165° C. (281 to 438 K) as a component that improves cohesive strength, and, if necessary, a monomer having a functional group that can serve as a crosslinking point, such as a carboxyl group or a hydroxyl group (an example of the monomer is shown in Table 1).

In addition, homopolymers made by polymerizing only monomers that exhibit adhesive strength are said to have high adhesive strength but weak mechanical strength, so copolymers whose mechanical strength has been improved by copolymerization with monomers that improve cohesive strength are generally used as adhesives.
As listed as monomers exhibiting adhesive strength in Table 1 above, in the present invention, as monomers with higher adhesive strength, butyl acrylate, 2-ethylhexyl acrylate, octyl acrylate, isononyl acrylate, etc., which have a Tg of 220 K or less when the monomer is homopolymerized (homopolymer), are used. Of 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.
Furthermore, examples of monomers that improve the cohesive strength (Tg of the homopolymer is 270 K or more) include the monomers listed in Table 1. Among these, in the present invention, methyl acrylate is preferred because it has high mechanical strength and does not significantly reduce adhesiveness (Tg of the homopolymer is relatively low).

As mentioned in the prior art, a commercially available acrylic acid alkyl ester copolymer used in patches is Nikazol (registered trademark) TS-620 (methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion) manufactured by Nippon Carbide Corporation. Methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion is listed in the pharmaceutical additives standard.

In the pressure-sensitive adhesive layer of the aqueous patch of the present invention, the amount of the (meth)acrylic acid alkyl ester copolymer (in the case of an emulsion, the amount converted into solid content) can be, for example, from 0.1 mass % to 5 mass %, from 0.5 mass % to 4.5 mass %, or from 1.0 mass % to 4.5 mass %, based on the total mass of the pressure-sensitive adhesive layer of the aqueous patch.
The blending ratio with an acrylic hydrophilic pressure-sensitive adhesive described later can be, for example, by mass ratio, acrylic acid alkyl ester copolymer:acrylic hydrophilic pressure-sensitive adhesive=1.5:1 to 1:10, 1.5:1 to 1:5, or 1.5:1 to 1:1.

<c) Partially Neutralized Polyacrylic Acid>
The adhesive layer of the aqueous patch of the present invention contains a partially neutralized polyacrylic acid as an acrylic hydrophilic adhesive.
If necessary, the adhesive layer may contain an acrylic hydrophilic adhesive other than the partially neutralized polyacrylic acid. In general, the above-mentioned acrylic hydrophilic adhesive includes a water-soluble (meth)acrylic polymer. 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 when blended with water in the adhesive layer. Examples of the water-soluble (meth)acrylic polymer include the partially neutralized polyacrylic acid described above, homopolymers of polyacrylic acid, etc., 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 of these. In other words, in this specification, "partially neutralized polyacrylic acid" includes not only neutralized polyacrylic acid in which some of the acid groups are neutralized, but also neutralized polyacrylic acid in which all of the acid groups are neutralized. Partially neutralized polyacrylic acid means a polyacrylic acid salt, and for example, a sodium salt, a potassium salt, a calcium salt, an ammonium salt, etc. can be used. Examples include Viscomate NP-600, NP-700, and NP-800 (manufactured by Showa Denko KK).

In a preferred embodiment, the partially neutralized polyacrylic acid used in the present invention has a degree of neutralization of 35% to 70%. 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 made into an aqueous solution with a concentration of 0.2% by mass.
By using a partially neutralized polyacrylic acid, particularly one having such a degree of neutralization and viscosity, the adhesiveness to the skin can be enhanced when the polyacrylic acid contains water, and crosslinking with the crosslinking agent can be promoted, thereby preventing dissolution when the polyacrylic acid contains water.

The blending amount of the partially neutralized polyacrylic acid, and the combined blending amount of the partially neutralized polyacrylic acid and other acrylic hydrophilic adhesives when other acrylic hydrophilic adhesives are contained, can be, for example, from 0.1% by mass to 10% by mass, or from 1% by mass to 8% by mass, based on the total mass of the adhesive layer of the aqueous patch.
For example, the amount of the partially neutralized polyacrylic acid blended 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 polymer compound>
As the water-soluble polymer compound, the adhesive layer in the patch of the present invention contains carmellose sodium (sodium carboxymethylcellulose) as an essential component.
The use of carmellose sodium enables the preparation to better maintain its shape, and also provides thixotropy, thereby further reducing pain during peeling.
In a preferred embodiment, the carmellose sodium used in the present invention can have a viscosity of 50 to 2,000 mPa·s in a 1% by weight aqueous solution at 20° C. The carmellose sodium preferably has a degree of ester substitution of 0.60 to 0.85.

Water-soluble polymeric compounds other than carmellose sodium may also be contained, examples of which include gelatin, agar, polyvinyl alcohol (including partially saponified products), polyvinylpyrrolidone, propylene carbonate, carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, sodium alginate, maleic anhydride copolymer, and carrageenan. These may be used alone or in appropriate combinations of two or more with carmellose sodium.

The amount of the water-soluble polymer compound blended can usually be in the range of, 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 and 20% by mass or less, or 3.0% by mass or more and 10% by mass or less, based on the total mass of the adhesive layer of the aqueous patch.
For example, the amount of carmellose sodium can be from 2.0% by mass to 4.0% by mass, based on the total mass of the adhesive layer.

<e) Glycerin-containing humectant>
The adhesive layer of the aqueous patch of the present invention contains a wetting agent (also called a moisturizing agent) in order to inhibit evaporation of water over time.
As the above-mentioned wetting agent, glycerin is blended as an essential component in the adhesive layer of the patch of the present invention.
Furthermore, a humectant other than glycerin may be blended, examples of which include polyhydric alcohols such as D-sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, polypropylene glycol, 1,3-propanediol, 1,4-butanediol, maltitol, xylitol, etc. These may be used alone or in appropriate combination with glycerin.

The amount of the humectant may typically be in the range of, for example, 30% by mass to 70% by mass, 30% by mass to 60% by mass, 30% by mass to 50% by mass, or 30% by mass to 40% by mass, based on the total mass of the adhesive layer of the aqueous patch.

<f) Crosslinking Agent>
The crosslinking agent to be incorporated in the adhesive layer of the aqueous patch of the present invention includes polyvalent metal salts, and among them, polyvalent metal compounds containing aluminum. Examples include hydroxides such as aluminum hydroxide and magnesium alumina hydroxide; aluminum chloride, aluminum sulfate, aluminum potassium sulfate, aluminum glycinate (dihydroxyaluminum aminoacetate), synthetic aluminum silicate, dried aluminum hydroxide gel, kaolin,
Examples of the aluminum stearate and other normal salts of inorganic or organic acids or their basic salts; 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 aluminosilicate, and magnesium aluminometasilicate. These can be used alone or in combination of two or more.
Among these, it is preferable to use dihydroxyaluminum aminoacetate, which is a poorly soluble aluminum compound, synthetic aluminum silicate, and dried aluminum hydroxide gel.

The amount of crosslinking agent to be used may be appropriately selected taking into consideration the degree of crosslinking, which may be a factor in the adhesive remaining on the skin or its adhesiveness. Based on the total mass of the adhesive layer of the aqueous patch, the amount may be in the range of, for example, 0.01% by mass to 6.0% by mass, 0.01% by mass to 4.0% by mass, or 0.01% by mass to 2.0% by mass.

<g) Hydrochloric Acid>
The pressure-sensitive adhesive layer of the aqueous patch of the present invention contains hydrochloric acid, and the blending amount of hydrochloric acid can be in the range of, for example, from 0.1 mass % to 1.5 mass %, from 0.1 mass % to 1.0 mass %, or from 0.1 mass % to 0.5 mass %, based on the total mass of the pressure-sensitive adhesive layer of the aqueous patch.

<h) Water>
As described above, the aqueous patch of the present invention contains water (moisture) in the adhesive layer. In this specification, the "water" contained in the adhesive layer includes not only water added separately when the adhesive layer is formed, but also water contained in the form of an emulsion, an aqueous solution, etc.
In the present invention, the content of water is essentially 40% by mass or more based on the total mass of the adhesive layer of the aqueous patch. For example, the content of water can be in the range of 40% by mass or more and 70% by mass or less, 40% by mass or more and 60% by mass or less, or 40% by mass or more and 50% by mass or less. Note that this water content is the value at the time of preparation of the patch or before application of the patch, and does not apply when water volatilizes from the adhesive layer as the patch is applied.
By making the amount of water 40 mass% or more, the adhesive strength of the adhesive layer can be stabilized over time, and the adhesive layer-forming composition has excellent spreadability when forming the adhesive layer, making it possible to realize a formulation with excellent manufacturability.

<i) Chelating Agent>
A chelating agent may be blended into the adhesive layer of the aqueous patch of the present invention in order to control the viscosity of the paste during production. Examples of the chelating agent include sodium edetate (disodium ethylenediaminetetraacetic acid).
The amount of the chelating agent can usually be in the range of, for example, from 0.01% by mass to 1% by mass, or from 0.1% by mass to 0.3% by mass, based on the total mass of the pressure-sensitive adhesive layer of the aqueous patch.

<Organic solvent>
The adhesive layer of the aqueous patch of the present invention may contain an organic solvent as a component that assists in the dissolution of active ingredients such as drugs (i.e., functions as a dissolution aid) and can prevent the active ingredients from precipitating from the adhesive layer.
Examples of such organic solvents (solubilizing agents) include 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, sorbitan esters, polyhydric alcohols such as 1,3-butanediol, dimethylformamide, and dimethyl sulfoxide. These may be used alone or in combination of two or more.

When an organic solvent is used, the amount of the organic solvent may be, for example, 0.1% by mass or more and 20% by mass or less based on the total mass of the adhesive layer of the aqueous patch.

<Organic Acid>
The adhesive layer of the aqueous patch of the present invention may contain an organic acid, such as tartaric acid, citric acid, lactic acid, gluconic acid, glycolic acid, malic acid, fumaric acid, methanesulfonic acid, maleic acid, acetic acid, etc., which may be used alone or in combination of two or more.
When an organic acid is used, its blending amount can be, for example, in the range of 0.1% by mass to 5% by mass based on the total mass of the adhesive layer of the aqueous patch. By using an organic acid in this blending amount range, it is expected that problems such as adhesive dissolution or stickiness due to insufficient crosslinking can be suppressed, while problems such as the crosslinking reaction proceeding too far, causing the paste to harden and making it impossible to manufacture can be suppressed.

<Surfactant>
A surfactant may be blended in the adhesive layer of the aqueous patch of the present invention. Examples of such surfactants include polyoxyethylene fatty acid esters such as polyoxyethylene monolaurate, polyoxyethylene monostearate, polyoxyethylene monooleate, polyethylene glycol distearate, polyethylene glycol dioleate, and polypropylene glycol dioleate; sorbitan fatty acid esters such as sorbitan monocaprylate, sorbitan monolaurate, sorbitan monomyristate, sorbitan monopalmitate, sorbitan monostearate, sorbitan distearate, sorbitan tristearate, sorbitan monooleate, sorbitan trioleate, sorbitan monosesquioleate, and ethylene oxide adducts thereof; polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan tristearate, polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan trioleate, and polyoxyethylene sorbitan triisostearate; fatty acid esters; polyoxyethylene dodecyl ether (polyoxyethylene lauryl ether, lauromacrogol), polyoxyalkylene lauryl ether, polyoxyethylene tridecyl ether, polyoxyalkylene tridecyl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene oleyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether, polyoxyethylene-2-ethylhexyl ether, polyoxyethylene isodecyl ether and other polyoxyethylene alkyl ethers; polyoxyethylene styrenated phenyl ether, polyoxyethylene nonyl phenyl ether, polyoxyethylene distyrenated phenyl ether, polyoxyethylene tribenzyl phenyl ether and other polyoxyethylene alkyl phenol ethers; glycerin monostearate, glycerin monooleate and other glycerin fatty acid esters; polyethylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, lecithin and other nonionic surfactants. These may be used alone or in appropriate combination of two or more.
When these surfactants are used, the amount of the surfactant can be in the range of, for example, 0.001% by mass or more and 10% by mass or less, or 0.01% by mass or more and 5% by mass or less, based on the total mass of the adhesive layer of the aqueous patch.

<Other optional ingredients>
The adhesive layer of the aqueous patch of the present invention may further contain, as optional components, components that can generally be contained in the adhesive layer of a conventional aqueous patch (poultice) or non-aqueous patch (tape), such as antioxidants such as dibutylhydroxytoluene (BHT), inorganic powders such as calcium carbonate, magnesium carbonate, silicates, zinc oxide, titanium oxide, magnesium sulfate, calcium sulfate, ultraviolet absorbers such as benzoylmethane derivatives, colorants, fragrances, preservatives, etc. When these optional components are used, they may be used alone or in combination of two or more, usually in an amount of, for example, 0.01% by mass or more and 1% by mass or less based on the total mass of the adhesive layer of the aqueous patch.

[Support]
Examples of the support used in the aqueous patch of the present invention include flexible supports such as films, nonwoven fabrics, Japanese paper, cotton fabrics, knitted fabrics, woven fabrics, and laminated composites of nonwoven fabrics and films. These supports are preferably made of a material that can adhere to the skin and is flexible enough to follow the movement of the skin, and that can suppress the occurrence of skin rashes and the like after long-term application. Examples of the material of these supports include those containing, as essential components, polyethylene, polypropylene, polyethylene terephthalate, polybutylene terephthalate, polyethylene naphthalate, polystyrene, nylon, cotton, acetate rayon, rayon, rayon/polyethylene terephthalate composites, polyacrylonitrile, polyvinyl alcohol, acrylic polyurethanes, ester polyurethanes, ether polyurethanes, styrene-isoprene-styrene copolymers, styrene-butadiene-styrene copolymers, styrene-ethylene-propylene-styrene copolymers, styrene-butadiene rubber, ethylene-vinyl acetate copolymers, cellophane, etc.

In addition, by coloring the support material such as fabric with a coloring agent to a color tone such as flesh color, the difference in color from the skin when applied can be reduced. In addition, a plastic film with excellent transparency can be used so that the color tone of the skin underneath can be easily seen through.

The thickness of the support is usually about 5 μm to 1 mm. When the support is a cloth, its thickness is preferably 50 μm to 1 mm, more preferably 100 to 800 μm, and even 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, and even more preferably 15 to 150 μm. When the thickness of the support is very thin, such as about 5 μm to 30 μm, it is preferable to provide a peelable carrier film layer on the surface opposite to the adhesive layer formed on the support, since this improves the handleability as a patch. However, when the thickness of the support is smaller than 5 μm, the strength and handleability of the patch are reduced, making it difficult to apply to the skin, and it may be torn by contact with other members, etc. Furthermore, if the thickness of the support is too large (greater than 1 mm), the patch will have difficulty following the movement of the skin and will be more likely to form an opening at the edge of the patch that causes it to peel off, which may result in the patch peeling off from the skin in a short period of time or increased discomfort while in application.
When the support is a film, one or both sides of the support may be subjected to a treatment such as sandblasting or corona treatment in order to improve the anchoring property between the pressure-sensitive adhesive and the support.
In order to facilitate removal from the packaging material, one or both sides of the support may be provided with projections and recesses by a method other than sandblasting.

[Release liner]
The release liner (also called release layer or release paper) used in the aqueous patch of the present invention is preferably made of a material that is unlikely to absorb or adsorb drugs, etc. in the adhesive layer, and any material commonly used in the technical field of patches can be used.
For example, polyester (polyethylene terephthalate, polybutylene terephthalate,
Examples of the material include plastic films such as polyethylene naphthalate, polypropylene (unstretched, stretched, etc.), polyethylene, polyurethane, polyvinyl chloride, polystyrene, etc.; paper or synthetic paper such as fine paper, glassine paper, parchment paper, craft paper, etc.; release-processed paper obtained by coating the above-mentioned plastic films, paper or synthetic paper, synthetic fibers, etc. with a release agent having release properties such as silicone resin or fluororesin; aluminum foil; laminated paper obtained by laminating these films/sheets in various layers, and laminated release-processed paper obtained by coating the laminated paper with a release agent, etc., and other colorless or colored sheets. The release liner can also be provided with irregularities to make it easier to remove from the packaging 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, and preferably 40 μm to 200 μm.
The peeling force when peeling the adhesive layer from the release liner is preferably within a specific range. This is because if the peeling force of the adhesive layer from the release liner is too weak, the adhesive layer (i.e., the patch) may slip off the release liner and peel off if the patch gets caught on the packaging material when the patch is removed from the packaging material. Also, if the peeling force of the adhesive layer (patch) from the release liner is too strong, the handling during use may be poor. The peeling force of the adhesive layer from the release liner may be, for example, 0.01 N/15 mm to 0.5 N/15 mm, depending on the type of release liner used.

[Method of manufacturing aqueous patch]
The aqueous patch of the present invention can be produced by a conventional method, for example, through the following steps (i) or (ii):
(i) A step of applying a pressure-sensitive adhesive layer-forming composition onto a support to form a pressure-sensitive adhesive layer, and a step of laminating the pressure-sensitive adhesive layer formed on the support to a release liner.
(ii) a step of applying a pressure-sensitive adhesive layer-forming composition onto a release liner to form a pressure-sensitive adhesive layer, and a step of laminating the pressure-sensitive adhesive layer formed on the release liner to a support.
The thickness of the pressure-sensitive adhesive layer is not particularly limited, but may usually be about 10 μm to 1000 μm, for example about 20 μm to 800 μm.

The pressure-sensitive adhesive layer-forming composition is a semi-solid composition which contains the various components contained in the pressure-sensitive adhesive layer described above: an active ingredient, a (meth)acrylic acid alkyl ester copolymer, a partially neutralized polyacrylic acid (and other acrylic hydrophilic pressure-sensitive adhesives), a water-soluble polymer compound containing sodium carmellose, a wetting agent containing glycerin, a crosslinking agent, hydrochloric acid, and water, and may further contain a chelating agent, an organic solvent, an organic acid, a surfactant, and other optional components, as desired.
From the viewpoint of operability during production, the pressure-sensitive adhesive layer-forming composition preferably has a viscosity of 90 to 250 Pa·s, 100 to 250 Pa·s, and more preferably 130 to 250 Pa·s at 20° C. to 30° C. If the viscosity is less than 90 Pa·s, there is a risk of the paste striking through when a knitted or woven fabric is used as a support. If the viscosity exceeds 250 Pa·s, the composition becomes difficult to spread.

<Ball tack remaining rate>
In the aqueous patch of the present invention, it is preferable that the ball tack adhesive strength of the adhesive layer remains at 70% or more even after storage for 2 weeks at 60° C. In other words, it is preferable that the ball tack value indicated by the ball tack No. after storage for 2 weeks at 60° C. is 70% or more (residual rate 70%) of the value before storage.
As described above, by having a ball tack remaining rate of 70% or more after a specified period of time and temperature has elapsed, it is possible to provide a water-containing patch having an adhesive layer with excellent stability over time with respect to adhesiveness.

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

<Preparation of patch>
The patches (preparations) of the Examples, Comparative Examples, and Production Examples were produced according to the following procedures.

Example 1:
1.3 parts by mass of polyvinyl alcohol was dissolved in purified water (aqueous phase).
Next, 2.00 parts by mass of ethylene glycol salicylate and 1.00 parts by mass of L-menthol were added to 1.00 part by mass of macrogol 400, 0.50 part by mass of lauromacrogol, and 1.30 parts by mass of diisopropyl adipate and dissolved (oil phase).
Furthermore, 4 parts by mass of partially neutralized polyacrylic acid, 3.00 parts by mass of sodium carmellose, and 0.25 parts by mass of dihydroxyaluminum aminoacetate were uniformly dispersed in 32.50 parts by mass of concentrated glycerin (glycerin phase).
Into a stirrer, the aqueous phase, 7 parts by mass of methyl acrylate/2-ethylhexyl acrylate copolymer emulsion, 0.20 parts by mass of sodium edetate hydrate, 10.00 parts by mass of a 70% aqueous solution of D-sorbitol, and 0.40 parts by mass of hydrochloric acid diluted with purified water were added in this order and uniformly dispersed or dissolved. The oil phase and glycerin phase were added in this order and uniformly kneaded. Furthermore, 1.00 parts by mass of lactic acid was added, and the mixture was uniformly kneaded under degassing conditions to obtain a pressure-sensitive adhesive layer-forming composition of Example 1.
The obtained pressure-sensitive adhesive layer-forming composition was spread on the silicone surface of a liner (one-sided silicone-treated PET (thickness 75 μm)) using a spreader, and a knit support (polyester knitted fabric, thickness 650 μm, basis weight 100 g/ ^m2 ) was laminated thereon, followed by aging for 1 week at 40° C. After aging, the product was punched out into a random shape to obtain the formulation of Example 1.

Examples 2 to 4 and Comparative Examples 1 to 5:
Preparations of Examples 2 to 4 and Comparative Examples 1 to 5 were obtained in the same manner as in Example 1, except that the types and amounts of each component were changed as shown in Tables 2 and 3.
When sorbitan monooleate, glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil 10, and polyoxyethylene oleyl ether were blended, they were added at the same time as Macrogol 400 to produce the composition.

Test Example 1: Manufacturability The manufacturability was evaluated according to the following evaluation criteria with respect to the difficulty of spreading the adhesive layer-forming compositions of the Examples and Comparative Examples produced in the procedure of <Preparation of Patch> onto the silicone surface of the liner with a spreading machine. The results obtained are shown in Tables 2 and 3.
<Manufacturability evaluation>
++: Easily spreadable +: Spreadable ±: Spreadable but not stable -: Cannot be spreadable

Test Example 2: Adhesive Strength Test Ball Tack The release liner of each preparation (immediately after production: initial stage) of the Examples and Comparative Examples was peeled off to expose the adhesive layer, and the ball tack adhesive strength of the adhesive layer was measured according to the Japanese Pharmacopoeia General Test Method 6.12 Adhesive Strength Test Method 3.2. Inclined Ball Tack Test Method. The average value (ball No.) of n=3 was taken as the ball tack test value.
After each of the preparations of the Examples and Comparative Examples was stored at 60° C. for 2 weeks, the release liner was peeled off to expose the adhesive layer, and the ball tack adhesive strength was measured in the same manner as above.
The results are shown in Tables 2 and 3. Also shown are the numerical ratios [residual rate, %] of the ball numbers after aging (2 weeks at 60° C.) to the initial ball numbers.
The ball tack evaluation reflects the adhesive strength of the adhesive layer, and the value is preferably 10 or more immediately after production (initial state), and if the value after aging is 70% or more of the initial value, the adhesive can be evaluated as having excellent stability over time.

As shown in Table 2, the preparations of Examples 1 to 4, in which the amount of water in the adhesive layer was 40 mass% or more, maintained a ball tack value of more than 85% of the initial ball tack value even after aging (2 weeks at 60°C), making them hydrous patches with excellent stability of adhesive strength over time.
Furthermore, during production of the patch, the adhesive layer-forming composition could be easily spread onto the liner, resulting in a water-containing patch with excellent manufacturability.

On the other hand, as shown in Table 3, the formulations of Comparative Example 1 to Comparative Example 5, in which the amount of water in the adhesive layer was less than 40% by mass, showed a large decrease in ball tack value after aging (2 weeks at 60°C) to less than 50% compared to the initial ball tack value, confirming that the adhesive strength had poor stability over time.

The results of the above examples confirm that, according to the present invention, by adjusting the water content of the adhesive layer to 40% by mass or more and 70% by mass or less, it is possible to provide a water-containing patch that is easy to manufacture and has stable adhesive strength over time.

Claims (4)

A water-containing patch comprising a support, an adhesive layer provided on the support, and a release liner attached on the adhesive layer,
The pressure-sensitive adhesive layer essentially contains the following components a) to h):
a) an active ingredient,
b) (meth)acrylic acid alkyl ester copolymer;
c) partially neutralized polyacrylic acid;
d) a water-soluble polymer compound containing sodium carmellose;
e) a humectant comprising glycerin;
f) a crosslinking agent;
g) hydrochloric acid, and h) water;
and,
The amount of water in the pressure-sensitive adhesive layer is 40% by mass or more and 70% by mass or less.
A hydrous patch. The aqueous patch according to claim 1, wherein the active ingredient of the adhesive layer is glycol salicylate. The pressure-sensitive adhesive layer contains: a) 0.1 to 30% by mass of an active ingredient, when the total mass of the pressure-sensitive adhesive layer is taken as 100% by mass;
b) 0.1 to 5% by mass of a (meth)acrylic acid alkyl ester copolymer
c) 0.1 to 10% by mass of partially neutralized polyacrylic acid
d) 1 to 30% by mass of a water-soluble polymer compound containing sodium carmellose
e) 30 to 70% by weight of a humectant containing glycerin
f) 0.01 to 6.0% by mass of a crosslinking agent
g) 0.1 to 1.5 mass% hydrochloric acid
The mixture is mixed in a ratio of
The aqueous patch according to claim 1 or 2. Storage conditions: The hydrous patch according to claim 1 or 2, in which the ball tack remaining rate is 70% or more before and after storage at 60°C for 2 weeks.