JPWO2010125691A1 - Patch - Google Patents

Abstract

Provided is a patch in which wrinkles of a support which is a polyurethane resin film are prevented and the anchoring property is good. A primer layer and a pressure-sensitive adhesive layer containing a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit are sequentially laminated on one side of a support which is an ester polyurethane resin film, and the primer layer is an ether. A patch comprising a polyurethane-based polyurethane resin film.

Description

  The present invention relates to a patch comprising a support, a primer layer and an adhesive layer.

  The polyurethane resin film has excellent stretchability and is suitable as a support for a patch (see, for example, Patent Documents 1 to 3: JP-A-6-345638, JP-A-2005-89438, and 2005-21896). However, when a pressure-sensitive adhesive layer containing an acrylic (co) polymer is used for this, a cooling agent such as l-menthol, which is a component in the pressure-sensitive adhesive layer, or a transdermal route such as N-methyl-2-pyrrolidone. The absorption promoter migrated, and there were problems such as generation of wrinkles due to swelling of the film and weak anchoring property between the pressure-sensitive adhesive layer and the film. That is, it was difficult to achieve both the wrinkle prevention of the film support and the anchoring property.

JP-A-6-345638 JP 2005-89438 A Japanese Patent Laid-Open No. 2005-218496

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a patch in which wrinkles of a support, which is a polyurethane resin film, are prevented and the anchoring property is good.

  As a result of intensive studies to achieve the above object, the present inventors have found that a pressure-sensitive adhesive layer includes a support that is an ester polyurethane resin film and a (co) polymer having (meth) acrylic acid alkyl ester as a structural unit. In the meantime, by providing a primer layer which is an ether-based polyurethane resin film, the wrinkle generation etc. of the film is improved, and it has been found that the anchoring property is good, and has led to the present invention. is there.

Therefore, the present invention
[1]. A primer layer and a pressure-sensitive adhesive layer containing a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit are sequentially laminated on one side of a support which is an ester polyurethane resin film, and the primer layer is an ether. A patch characterized by being a polyurethane-based polyurethane resin film,
[2]. The patch according to [1], wherein the (co) polymer having the (meth) acrylic acid alkyl ester as a structural unit is a crosslinked (co) polymer,
[3]. The adhesive patch according to [1] or [2], wherein the pressure-sensitive adhesive layer contains a cooling agent,
[4]. The refreshing agent is selected from 1-menthol, N-substituted-p-menthane-3-carboxamide, 3-substituted-p-menthane, 2- or 3-substituted-p-menthanediol and trialkyl substituted cyclohexanecarboxyamide The patch according to [3], which is one type or two or more types,
[5]. The adhesive patch according to [3] or [4], wherein the adhesive layer further contains a transdermal absorption enhancer,
[6]. The patch according to [5], wherein the transdermal absorption enhancer is one or more selected from pyrrolidones, fatty acids, polybasic acids, and dihydric alcohols.

  According to the present invention, there is provided a pressure-sensitive adhesive layer containing a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit, which is capable of preventing wrinkles of a support made of a polyurethane film and having good anchoring properties. A patch can be provided.

  In the patch of the present invention, a pressure-sensitive adhesive layer containing a primer layer and a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit is sequentially laminated on one side of a support which is an ester-based polyurethane resin film. Thus, the primer layer is an adhesive polyurethane resin film.

(1) Support The support of the present invention is composed of an ester polyurethane resin film. The ester-based polyurethane resin comprises a curing agent having an isocyanate group (polyisocyanate) and a polyester polyol having a hydroxyl group at the polymer terminal, and can be obtained by forming a urethane bond by a reaction between the hydroxyl group and the isocyanate group and curing it. it can. An ester polyurethane resin can be used individually by 1 type or in combination of 2 or more types.

  Examples of the isocyanate include tolylene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate, naphthalene diisocyanate, and the like, which can be used alone or in combination of two or more.

  The polyester polyol is obtained by reacting a polybasic acid and a hydroxyl compound (glycol or polyhydric alcohol), and is an adipate-based polyol such as ethylene glycol adipate, diethylene adipate glycol, butylene glycol adipate, trimethylolpropane / diethylene glycol adipate, Polycaprolactone polyol (PCL) obtained by ring-opening polymerization of ε-caprolactone, aromatic polyester polyol which is a polyester polyol containing terephthalic acid or isophthalic acid in dibasic acid, and linear polymer diol having hydroxyl groups at both ends Polycarbonate diol (PCD) etc. are mentioned, It can use individually by 1 type or in combination of 2 or more types.

  The ester-based polyurethane resin film of the present invention can be mixed with a resin other than the ester-based polyurethane as long as the effects of the present invention are not impaired, but the resin is preferably composed of an ester-based polyurethane resin. Further, as an optional additive, an ultraviolet absorber, an anti-aging agent, a filler, a pigment, a colorant, a plasticizer, a flame retardant, an antistatic agent, a lubricant and the like are blended within a range not impairing the effects of the present invention. Can do.

  The thickness of the support is preferably 5 to 40 μm, and more preferably 10 to 30 μm. If the thickness is less than 5 μm, the film may not be firm and may be difficult to stick to the skin. If the thickness exceeds 40 μm, the resulting sheet will be hard, and the required flexibility such as poor texture and conformity to the skin will not be achieved. May be sufficient.

  The 50% modulus of the support is not particularly limited, but is preferably 3.5 N / 25 mm or less, and more preferably 2.0 N / 25 mm or less. If it exceeds 3.5 N / 25 mm, there is a risk that it will not smoothly follow the expansion and contraction of the skin during application. The 50% modulus is obtained by taking a 25 × 60 mm sample in both the vertical (flow direction during spreading) and horizontal (perpendicular to the flow direction during spreading), and using a tensile tester, Measure the stress when stretched by 25 mm at a pulling speed of 200 mm / min.

The 50% elongation recovery rate of the support is not particularly limited, but is preferably 75% or more, and more preferably 85% or more in both the vertical and horizontal directions. If it is less than 75%, there is a possibility that the skin does not smoothly follow the expansion and contraction at the time of application. The 50% elongation recovery rate in the present invention is obtained by taking a 10 × 150 mm sample in both directions (vertical direction of flow) and horizontal direction (perpendicular to the flow direction of spreading). Used, stretched by 50 mm at a gripping interval of 100 mm and a pulling speed of 200 mm / min, and returned until the stress becomes zero at the same speed. The initial length A (100 mm) of the sample and the length B of the sample after the tensile test are read from the chart paper and calculated from the following formula.
50% elongation recovery rate (%) = {100− (BA)} × 100 / (A × 0.5)
(In the above formula, A represents the initial length (100 mm) of the sample, and B represents the length (mm) of the sample after the tensile test.)

Moisture permeability of the support is preferably ^{600~2600 (g / m 2 · 24hr} ) ^{is, 800~1900 (g / m 2 ·} 24hr) is more preferable. If the moisture permeability is less than 600 (g / m ² · 24 hr), there is a risk of peeling during application, and if the moisture permeability exceeds 2600 (g / m ² · 24 hr), the skin permeability of the drug may be reduced. . In the present invention, moisture permeability refers to a value measured according to condition B of JIS general test method “moisture-proof packaging material moisture permeability test method (cup method)” (JIS Z 0208-1976).

(2) Primer layer The primer layer of the present invention comprises an ether-based polyurethane resin film. The ether-based polyurethane resin film comprises a curing agent having an isocyanate group (polyisocyanate) and a polyether polyol having a hydroxyl group at the polymer terminal, and is obtained by forming a urethane bond by the reaction between the hydroxyl group and the isocyanate group and curing it. be able to.

  Examples of the isocyanate include tolylene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate, naphthalene diisocyanate, and the like, which can be used alone or in combination of two or more.

  Examples of the polyether polyol include polypropylene (ethylene) polyol (PPG), polytetramethylene ether glycol (PTMEG), and the like, which can be used alone or in combination of two or more.

  The ether-based polyurethane resin film can be mixed with a resin other than the ether-based polyurethane as long as the effects of the present invention are not impaired, but the resin is preferably composed of an ether-based polyurethane resin. Further, as an optional additive, an ultraviolet absorber, an anti-aging agent, a filler, a pigment, a colorant, a plasticizer, a flame retardant, an antistatic agent, a lubricant and the like are blended within a range not impairing the effects of the present invention. Can do.

  60-100 mass% is preferable in an ether polyurethane resin film, and, as for the compounding quantity of an ether polyurethane resin, 80-100 mass% is more preferable. As for the compounding quantity of an additive, 1-10 mass% is further more preferable in an ether type polyurethane resin film.

  Examples of the ether-based polyurethane resin film used in the primer layer of the present invention include “Sapilia” (all resins are made of ether-based polyurethane resin, manufactured by Sakata Inx Corporation).

  As a method of laminating a primer layer, which is an ether-based polyurethane resin film, on one side of the support, an ether-based polyurethane resin is dissolved in an appropriate solvent to prepare a primer layer coating solution, and this is applied to the support surface. The primer layer can be laminated by coating and drying. The said additive can be suitably mix | blended with the coating liquid for primer layers. The coating method is not particularly limited and is usually selected, for example, a forward rotation roll coater, a reverse roll coater, a gravure coater, a doctor knife coater, a blade coater, a rod coater, an air doctor coater, a curtain coater, a fountain. A coater, kiss coater, dip coating, screen coating, spin coating, cast coating, spray coating, extrusion coating, vacuum coating, etc. can be used.

  1-20 micrometers is preferable and, as for the thickness of a primer layer, 3-10 micrometers is more preferable. If the thickness of the primer layer is less than 1 μm, the anchoring force may be insufficient, and if it exceeds 20 μm, the primer layer may become hard and the flexibility required for the resulting sheet may be insufficient. .

  The thickness of the support on which the primer layer is laminated is preferably 6 to 40 μm, and more preferably 13 to 30 μm. If the thickness is less than 6 μm, the stiffness of the film becomes insufficient. If the thickness exceeds 40 μm, the obtained sheet is hard, the texture and the familiarity with the skin are deteriorated, and the required flexibility may be insufficient.

  The 50% modulus of the support on which the primer layer is laminated is not particularly limited, but is preferably 3.5 N / 25 mm or less, and more preferably 2.0 N / 25 mm or less. If it exceeds 3.5 N / 25 mm, it may not follow the expansion and contraction of the skin smoothly at the time of application. The 50% modulus is obtained by taking a 25 × 60 mm sample in both the vertical (flow direction during spreading) and horizontal (perpendicular to the flow direction during spreading), and using a tensile tester, Measure the stress when stretched by 25 mm at a pulling speed of 300 mm / min.

  The 50% elongation recovery rate of the support on which the primer layer is laminated is not particularly limited, but the 50% elongation recovery rate is preferably 75% or more, more preferably 85% or more in both the vertical and horizontal directions. If it is less than 75%, there is a possibility that the skin does not smoothly follow the expansion and contraction at the time of application.

Moisture permeability of the support that the primer layer is laminated is preferably ^{500~2500 (g / m 2 · 24hr} ) ^{is, 700~1800 (g / m 2 ·} 24hr) is more preferable. If the moisture permeability is less than 500 (g / m ² · 24 hr), there is a risk of peeling during application, and if the moisture permeability exceeds 2500 (g / m ² · 24 hr), the skin permeability of the drug may be reduced. .

(3) Adhesive layer The adhesive layer of this invention contains the (co) polymer which has a (meth) acrylic-acid alkylester as a structural unit. Hereinafter, what constitutes the pressure-sensitive adhesive layer is referred to as “pressure-sensitive adhesive composition (plaster)”. As the (meth) acrylic acid alkyl ester, specifically, a linear alkyl group having 4 to 13 carbon atoms such as butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, etc. And branched alkyl groups such as 2-ethylhexyl, and the like can be used singly or in appropriate combination of two or more. Among them, acrylic acid, methacrylic acid, ethyl acrylate, n-butyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl acrylate, 2-ethylhexyl methacrylate, methyl methacrylate, dodecyl methacrylate preferable. In the present invention, (meth) acrylic acid refers to acrylic acid and / or methacrylic acid.

  60-100 mass% is preferable and, as for the ratio of the (meth) acrylic-acid alkylester monomer with respect to the monomer whole quantity which comprises a (co) polymer, 85-100 mass% is more preferable.

  As the (co) polymer, a monomer copolymerizable with the above (meth) acrylic acid alkyl ester can be used. Such monomers include hydroxyl-containing monomers such as (meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride, vinyl alcohol, 2-hydroxy (meth) acrylate, hydroxypropyl (meth) acrylate, Sulfoxyl group-containing monomers such as styrene sulfonic acid, allyl sulfonic acid and sulfopropyl acrylate, amino group-containing monomers such as dimethylaminoethyl acrylate and vinyl pyrrolidone, (meth) acrylic acid hydroxyethyl ester, (meth) acrylic acid Hydroxyl group-containing monomers such as hydroxypropyl ester, (meth) acrylamide, dimethyl (meth) acrylamide, amide group-containing acrylic monomers such as N-butyl (meth) acrylamide, (meth) acrylic acid aminoethyl ester, (Meth) acrylic acid Alkyl aminoalkyl group-containing acrylic monomers such as methylaminoethyl ester, (meth) acrylic acid diethylaminoethyl ester, alkoxy groups (or sides) such as (meth) acrylic acid methoxyethyl ester, (meth) acrylic acid ethoxyethyl ester Ether-chain-containing monomer, sugar chain-containing monomers such as glycosyloxyethyl (meth) acrylate and galactosyloxyethyl (meth) acrylate, and vinyl monomers such as N- (meth) acryloylamino acid Acrylic monomers such as urethane esters of acrylic acid, urea esters, and isocyanate esters, and (meth) acrylonitrile, vinyl acetate, vinyl propionate, vinyl chloride, vinyl pyrrolidone, vinyl pyridine, vinyl pyrazine, vinyl piperazine, Bi Vinyl monomers such as lupiperidone, vinylpyrimidine, vinylpyrrole, vinylimidazole, vinylcaprolactam, vinyloxazole, vinylthiazole, vinylmorpholine, styrene, α-methylstyrene, and bis (N, N-dimethylaminoethyl) maleate Is mentioned. These can be used individually by 1 type or in combination of 2 or more types. Of these, (meth) acrylic acid is preferred. In the present invention, (meth) acrylamide refers to acrylamide and / or methacrylamide.

  The copolymer of the present invention includes a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit, a (co) polymer having a (meth) acrylic acid alkyl ester and (meth) acrylic acid as a structural unit. Is particularly preferred.

  Examples of the polymerization initiator used in the synthesis of the (co) polymer of the present invention include aqueous radical polymerization such as persulfates such as ammonium persulfate and sodium persulfate, lauroyl peroxide, hydrogen peroxide, and t-butyl hydroperoxide. An initiator or a mixture thereof can be used, and the amount used is usually 0.1 to 5% by mass of the polymerization initiator, preferably 0.1 to 2% by mass, based on the total amount of monomers. . A redox system can be formed in combination with a reducing agent together with a polymerization initiator. Examples of such reducing agents include alkali metal salts and ammonium salts such as sulfites, hydrogen sulfites, pyrosulfites, and formaldehyde sulfonates, and carboxylic acids such as L-ascorbic acid and tartaric acid. The amount used is preferably from 0.1 to 5 mass%, more preferably from 0.1 to 2 mass%, based on the total amount of monomers.

  The polymerization may be emulsion polymerization, and the surfactant used in the emulsion polymerization may be an anionic, cationic, nonionic, amphoteric surfactant or a mixture thereof. Examples of anionic surfactants include alkyl or alkyl allyl sulfates such as sodium lauryl sulfate and sodium dodecylbenzene sulfonate, alkyl or alkyl allyl sulfonates, dialkyl sulfosuccinates, polyoxyethylene (3) lauryl ether sulfates Examples thereof include alkali metal salts such as sodium and polyoxyethylene alkyl ether sulfates such as sodium polyoxyethylene (4) lauryl ether sulfate and ammonium salts.

  Nonionic surfactants include polyoxyethylene lauryl ether, polyoxyethylene alkyl ethers such as polyoxyethylene oleyl ether, polyoxyethylene alkyl phenyl ethers such as polyoxyethylene nonyl phenyl ether, polyoxyethylene octyl phenyl ether, and monolaurin. And polyoxyethylene fatty acid esters such as polyethylene glycol acid and polyethylene glycol monooleate.

  Examples of amphoteric surfactants include betaines and amino acid derivatives. An example of a peptide surfactant is surfactin sodium. 0.1-5 mass parts is preferable with respect to the monomer whole quantity, and, as for the usage-amount of these surfactant, 0.3-3 mass parts is more preferable. If the amount used is less than 0.1 parts by mass, the reaction may become unstable, and if it exceeds 5 parts by mass, the drying property and water resistance may be deteriorated.

  In addition, if necessary, emulsion polymerization may be carried out with a chain transfer agent such as a chelating agent such as ethylenediaminetetraacetic acid sodium, a dispersant such as polycarboxylate, an inorganic salt such as phosphate or carbonate, a thiol compound, or a halogen compound. You may go in the presence.

  Specific examples of the (co) polymer of the present invention include, for example, acrylic acid / acrylic acid octyl ester copolymers and acrylics listed in the Pharmaceutical Additives Encyclopedia 2000 (edited by Japan Pharmaceutical Additives Association) as an adhesive. Acid ester / vinyl acetate copolymer, 2-ethylhexyl acrylate / vinyl pyrrolidone copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer A polymer resin emulsion, DURO-TAK acrylic pressure-sensitive adhesive series (National Starch and Chemical Co., Ltd.), Eudragit series (Higuchi Shokai) and the like can be suitably used.

  The blending amount of the (co) polymer of the present invention is not particularly limited and can be appropriately selected. Usually, the solid content relative to the total amount of the pressure-sensitive adhesive composition (composition constituting the pressure-sensitive adhesive layer). 40 to 95% by mass, preferably 50 to 90% by mass, and more preferably 55 to 85% by mass. Within this range, there is little peeling or turning when applied to the skin.

  The (co) polymer of the present invention is further subjected to a crosslinking treatment by a crosslinking means, and the crosslinked (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit is aggregated as an adhesive layer. Imparting force, and preventing components such as 1-menthol and other refreshing agents and transdermal absorption promoters such as N-methyl-2-pyrrolidone in the adhesive layer to be described later from being transferred to the film, It is preferable to suppress the generation of wrinkles due to swelling of the film and the decrease in anchoring property between the pressure-sensitive adhesive layer and the film. Cross-linking treatment includes physical cross-linking by irradiation such as ultraviolet ray irradiation and electron beam irradiation, and chemical cross-linking treatment using cross-linking agents such as polyisocyanate compounds, organic peroxides, organometallic salts, metal alcoholates, and polyfunctional compounds. Etc. are used. Of these cross-linking means, when radiation irradiation or organic peroxide is used, a decomposition reaction may occur depending on the drug species. Also, highly reactive polyisocyanates, metal salts used in ordinary cross-linking reactions, and organic salts With a metal salt, a thickening phenomenon of the solution may occur after blending and the workability may be inferior. A method of previously copolymerizing a polyfunctional monomer such as diacrylate with an acrylate ester polymer is also conceivable, but in this case, the solution viscosity may increase. Accordingly, in the present invention, among these crosslinking agents, potassium aluminum sulfate, zinc sulfate and trifunctional isocyanate are preferable, and potassium aluminum sulfate and zinc sulfate are more preferable. These cross-linking agents do not cause a thickening phenomenon of the solution until coating and drying, are extremely excellent in workability, and increase the anchoring property of the pressure-sensitive adhesive and the film by coating uniformly. Moreover, it is preferable to use EDTA, EDTA2Na, etc. as a crosslinking regulator.

  The crosslinking agent used for the crosslinking means can be used singly or in appropriate combination of two or more, and the blending amount is not particularly limited and can be appropriately selected, and the total amount of the pressure-sensitive adhesive composition On the other hand, 0.1-5.0 mass% is preferable normally, and also 0.4-3.0 mass% is preferable. When the amount used is less than 0.1% by mass, components such as l-menthol and N-methyl-2-pyrrolidone tend to migrate to the film, and wrinkles due to swelling of the film may occur. If it exceeds 5.0% by mass, the adhesive strength of the adhesive may be reduced.

  A cooling agent and a drug can also be mix | blended with an adhesive composition as needed. The refreshing agent is not limited as long as it is a substance that imparts a refreshing sensation. Examples of such a refreshing agent include 1-menthol, N-substituted-p-menthane-3-carboxamide, 3- Examples thereof include substituted-p-menthane, 2- or 3-substituted-p-menthanediol, trialkyl-substituted cyclohexanecarboxyamide, and the like. These can be used alone or in combination of two or more. Among these, l-menthol is particularly preferable because it gives a strong refreshing feeling, and it is desirable to use l-menthol alone or in combination with other cooling agents. The blending amount is preferably 0.1 to 10.0% by mass, and more preferably 0.5 to 7.0% by mass with respect to the total amount of the pressure-sensitive adhesive composition. If the amount used is less than 0.1% by mass, a refreshing feeling may not be imparted. If it exceeds 10.0% by mass, wrinkles due to swelling of the film and anchorage between the pressure-sensitive adhesive layer and the film may be reduced.

  Drugs include warmth-imparting agents, non-steroidal anti-inflammatory agents, steroidal anti-inflammatory agents, antihistamines such as diphenhydramine, central nervous system drugs such as isoprenaline hydrochloride; hormonal agents such as estradiol and testosterone; aspirin, acetaminophen, Analgesics such as ibuprofen; antiarrhythmic agents such as disopyramide phosphate, coronary vasodilators such as trazoline hydrochloride, local anesthetics such as lidocaine, muscle relaxants such as squismethonium chloride, antifungal agents such as clotrimazole, fluorouracil Antineoplastic agents such as tamsulosin hydrochloride, urination disorder improving agents such as diazepam, antiparkinsonian agents such as bromocriptine mesylate; antihypertensive agents such as furosemide and clonidine; vasodilators such as nitroglycerin and isosorbide nitrate Agents; smoking cessation aids such as nicotine, Bronchodilators such as lobuterol; hypnotic sedatives such as phenobarbital and triazolam; tranquilizers such as fluphenazine and theoritadine; vitamins such as vitamin A, vitamin E, vitamin K, octothiacin and riboflavin butyrate; prostaglandins It is also possible to add scopolamine, fentanyl and the like.

  Capsicoside, capsaicin, capsaicinoid, capsaicin analogues such as capsaicin, capsicum extract, capsicum extract, capsicum extract 20, capsicum tincture, capsicum derived material such as capsicum powder, nicotinic acid benzyl, nicotinic acid β- Examples include butoxyethyl, N-acyl vanillamide, nonyl acid vanillamide, vanillyl alcohol alkyl ether, and the like.

  Non-steroidal anti-inflammatory agents include salicylic acid and its salts, salicylic acid derivatives such as aspirin, acetaminophen, aminopyrine, antipyrine, oxyphenbutazone, sulpyrine, ampenac sodium, indomethacin, diclofenac, diclofenac sodium, felbinac, ibuprofen , Sulindac, naproxen, ketoprofen, suprofen, etofenamate, salicylamide, triethanolamine salicylate, flufenamic acid and its salts and derivatives, meclofenamic acid and its salts and derivatives, colchicine, bufexamac, ibufenac, loxoprofen , Fenbufen, diflunisal, alclofenac, phenylbutazone, mefenamic acid and its salts and derivatives, pheno Rofen, bendazac, piroxicam, flurbiprofen, zaltoprofen, etodolac, and the like.

  Examples of steroidal anti-inflammatory agents include amsinoid, prednisolone valerate, prednisolone valerate, diflucortron valerate, betamethasone valerate, betamethasone acetate, dexamethasone acetate, dexamethasone hydrochloride, betamethasone dipropionate, dexamethasone, triamcinolone acetonide, rilcinonide. , Hydrocortisone, hydrocortisone acetate, flumethasone pivalate, fluocinonide, fluocinolone acetonide, fluotometholone, fludroxycortide, prednisolone, prednisolone acetate, clobetasol propionate, beclomethasone propionate, betamethasone, methylprednisolone acetate And hydrocortisone.

  The drug can be used singly or in appropriate combination of two or more, and the blending amount thereof is not particularly limited and can be appropriately selected, and is 0.1% relative to the total amount of the pressure-sensitive adhesive composition. -10.0 mass% is preferable and 0.1-7.0 mass% is more preferable.

  In addition, antioxidants, surfactants, alcohols, pigments, fragrances, preservatives and the like can be used alone or in combination of two or more.

A transdermal absorption enhancer can be blended in the pressure-sensitive adhesive composition. The percutaneous absorption enhancer may be any agent that improves the percutaneous absorbability of the active ingredient in the external preparation for skin. Examples of such a component include pyrrolidones, azone (1-dodecylazacycloheptane-2- ON), calcium thioglycolate, higher alcohols, enamines and derivatives thereof, fatty acids, dihydric alcohols, salicylic acids, polybasic acids, crotamiton, terpenes, benzyl alcohol, squalane and the like. In this case, these can be used alone or in combination of two or more.
Here, specific examples of pyrrolidones include 2-pyrrolidone, N-methyl-2-pyrrolidone, 5-methyl-2-pyrrolidone, 1,5-dimethyl-2-pyrrolidone, 1-ethyl-2-pyrrolidone, Examples include pyrrolidone such as 2-pyrrolidone-5-carboxylic acid and salts thereof, and derivatives and salts thereof. Specific examples of higher alcohols include oleyl alcohol, lauryl alcohol, myristyl alcohol, and 2-octyldodecanol. Saturated or unsaturated higher alcohols having 8 to 22 carbon atoms such as 2-hexyldodecanol and derivatives thereof having a transdermal absorption promoting action, and polybasic acids include, for example, diethyl adipate, adipine Polybasic acids having 2 or more carbon atoms, such as isopropyl acid and diisopropyl adipate, and their derivatives Specific examples of fatty acids having transdermal absorption promoting action include fatty acids having 8 to 22 carbon atoms such as sodium caprate, linoleic acid, oleic acid, sodium lauryl sulfate, sodium cetyl sulfate, and salts thereof. , Ethyl myristate, octyldodecyl myristate, isopropyl myristate, diisopropyl sebacate, diethyl sebacate, isopropyl palmitate, decyl oleate, oleyl oleate, ethyl laurate, ethyl butyrate, ethyl caprate, monoglyceride caprate A fatty acid derivative which is an ester of a fatty acid having 8 or more carbon atoms and a linear or branched alkyl group having 8 to 22 carbon atoms, which has a transdermal absorption promoting action, specifically as a dihydric alcohol, For example, polyethylene glycol, ethyl Specific examples of salicylic acids such as N-glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, 1,3-hexylene glycol, and the like include salicylic acid, sodium salicylate, methyl salicylate, ethyl salicylate, 5- Methyl salicylate, salicylic acid such as glycol salicylate, salts and derivatives thereof, and terpenes, specifically mint oil, eucalyptus, and other specific compounds include diethyl succinate, triacetin, tributyrin, etc. .
Among these, N-methyl-2-pyrrolidone, isopropyl myristate, diisopropyl adipate, decyl oleate, oleyl oleate, and dipropylene glycol are particularly preferable from the viewpoint of promoting percutaneous absorption of drugs.

  The percutaneous absorption enhancer can be used singly or in appropriate combination of two or more, and the total blending amount thereof is not particularly limited and can be appropriately selected, and relative to the total amount of the pressure-sensitive adhesive composition 0.5-30.0 mass% is preferable, and 5.0-25.0 mass% is more preferable. If this blending amount is less than 0.5% by mass, the transdermal absorbability of the drug may be lowered, and if it exceeds 30.0% by mass, it tends to shift to a film, causing wrinkles due to swelling of the film and an adhesive. There is a possibility that the anchoring property between the layer and the film is lowered. In particular, the blending amount of N-methyl-2-pyrrolidone is preferably 0.5 to 5.0% by mass.

  The pressure-sensitive adhesive layer of the present invention is a non-aqueous pressure-sensitive adhesive formed by applying a coating liquid for a pressure-sensitive adhesive layer, which will be described later, on a primer layer or a liner, which will be described later, and drying from the viewpoint of adhesive strength and cohesive strength. It is preferable to use an agent layer. The non-aqueous pressure-sensitive adhesive layer may contain moisture from the raw material, between manufacturing steps, or from the environment, but the smaller the moisture content, the better. Specifically, the water content is preferably 3.0% by mass or less, more preferably 1.0% by mass or less, and preferably no water in the non-aqueous pressure-sensitive adhesive layer.

(4) Patch The primer layer and the pressure-sensitive adhesive layer are sequentially laminated on one side of the support, and a patch including the support, the primer layer, and the pressure-sensitive adhesive layer is formed. Lamination of the pressure-sensitive adhesive layer to the primer layer laminated on the support is performed, for example, by (i) preparing a coating solution for the pressure-sensitive adhesive layer, and (ii) applying this pressure-sensitive adhesive solution to the liner and drying it. The adhesive layer is laminated on one side of the liner. (Iii) The pressure-sensitive adhesive layer provided on one side of the liner is laminated on the surface of the primer layer laminated on the support.

(I) Preparation of coating solution for pressure-sensitive adhesive layer After mixing a (co) polymer having a (meth) acrylic acid alkyl ester as a constituent unit and other optional components, the solid content is 30 to 80% by mass, preferably It adjusts with a solvent so that it may become 40-60 mass%, and the coating liquid for adhesive layers is obtained. As this solvent, water, methanol, ethanol, acetone, ethyl acetate, toluene, and other organic solvents can be used, but water, ethanol, and ethyl acetate are preferable.

(Ii) Coating / drying This pressure-sensitive adhesive solution is coated on a liner. When the solvent of the pressure-sensitive adhesive layer coating solution is water, for example, after dissolving the cross-linking agent and the chelating agent in water, preferably with sodium hydroxide, potassium hydroxide or ammonia water, the pH to the alkali side, Preferably, the pH is adjusted to 8 or more, more preferably pH 9-12. This is mixed with an acrylic (co) polymer and other optional components, and after sufficiently stirring until the whole becomes uniform, coating is performed. When the solvent is ethyl acetate, the above (co) polymer, preferably a cross-linking agent, and other components are mixed in ethyl acetate and stirred sufficiently until the whole becomes uniform, and then coating is performed. Do.

  Examples of the liner include a vinyl chloride film, a polyethylene film, a polypropylene film, a polyester film, a medicinal rule polyethylene terephthalate separator, a release paper (release paper), and the like.

  The coating method is not particularly limited, and a method conventionally selected on the surface of the primer layer laminated on the support, for example, a comma coater, a forward rotation roll coater, a reverse roll coater, a gravure coater, a doctor knife coater, a blade. Coating is performed by a coater, rod coater, air doctor coater, curtain coater, fountain coater, kiss coater, dip coating, screen coating, spin coater, cast coating, spray coating, extrusion coating, vacuum coating and the like.

As a coating amount (plaster amount) of an adhesive composition, 1-500 g / m < ² > is preferable, 5-250 g / m < ² > is more preferable, 10-200 g / m < ² > is still more preferable. For example, in the case of a 10 × 7 cm patch, 0.03 to 1.7 g is preferable, and 0.07 to 1.4 g / m ² is more preferable.

The drying process for distilling off the solvent is, for example, hot air high-speed air cap, hot air tunnel type, hot air air floating, air through, N ₂ gas displacement drying system, infrared, microwave, (electromagnetic) induction heating, ultraviolet curing, lamp In the present invention, a hot air high-speed air cap, a hot air tunnel type, and a hot air air floating are preferably used. Although the drying conditions in this invention should just be more than the temperature at which an adhesive is bridge | crosslinked or the temperature from which solvents volatilize, it is 40-150 degreeC normally, Preferably it is 60-130 degreeC, More preferably, it is 70-120 degreeC. When this temperature is too low, the volatilization of the solvent becomes insufficient, and when it exceeds 150 ° C., when a drug or plasticizer is blended, these may be affected.

(Iii) Lamination of the pressure-sensitive adhesive layer on the surface of the primer layer After drying to form a pressure-sensitive adhesive layer, the pressure-sensitive adhesive layer provided on one side of the liner is laminated and supported on the surface of the primer layer laminated on the support. A patch in which the body, the primer layer, the pressure-sensitive adhesive layer, and the liner are laminated in this order is obtained, and can be cut into an appropriate size and used.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition represents “mass%”, and “part” represents “part by mass”.

[Examples 1-11, 13-18, Comparative Examples 1-4]
(I) A copolymer emulsion and a percutaneous absorption enhancer in which a drug was dissolved were mixed to obtain a mixed solution 1. Separately, the crosslinking agent and the crosslinking regulator were mixed and dissolved in 20 parts of water (with respect to 1 part by mass of the crosslinking agent), and the pH was adjusted to 10 with a pH regulator as necessary to obtain a mixed solution 2. The liquid mixture 2 was mixed with the liquid mixture 1, and it stirred sufficiently until the whole became uniform, and the coating liquid for adhesive layers was prepared.
(Ii) A liner (polyester film (75 μm)) was applied to a liner (polyester film (75 μm)) with a comma coater so that the amount of plaster after drying was 1.0 g / 10 × 7 cm, and dried. Drying was performed in a 90 ° C. dryer for 15 minutes.
(Iii) The primer layer was laminated | stacked by apply | coating the coating liquid for primer layers used for primer layer formation shown to a table | surface to the single side | surface of the table | surface in a table | surface, and drying. A pressure-sensitive adhesive layer provided on one side of the liner was laminated on the surface of the primer layer laminated on the support, and cut into an appropriate size to obtain a patch. In the table, the pressure-sensitive adhesive composition after drying is shown.

[Example 12]
(I) A copolymer emulsion, a percutaneous absorption enhancer in which a drug was dissolved, and a crosslinking agent were mixed and sufficiently stirred until the whole became uniform to prepare an adhesive layer coating solution.
(Ii) A liner (polyester film (75 μm)) was applied to a liner (polyester film (75 μm)) with a comma coater so that the amount of plaster after drying was 1.0 g / 10 × 7 cm, and dried. Drying was performed in a 90 ° C. dryer for 15 minutes.
(Iii) The primer layer was laminated | stacked by apply | coating the coating liquid for primer layers used for primer layer formation shown to a table | surface to the single side | surface of the table | surface in a table | surface, and drying. The pressure-sensitive adhesive layer provided on one side of the liner was laminated on the surface of the primer layer laminated on the support, and cut into an appropriate size to obtain a patch of each example. In the table, the pressure-sensitive adhesive layer composition after drying is shown.

About 5 obtained patches, it evaluated by the following method and the average value was computed. The results are also shown in the table.
<Wrinkle evaluation of film>
5: No wrinkles 4: Slightly wrinkled 3: Pretty wrinkled 2: Slightly wrinkled 1: Very wrinkled

<Throwing property evaluation>
The amount of plaster remaining on the skin relative to the total amount of the paste (total amount of the adhesive composition) when the patch was applied to the skin (sex; male, age 20-40, age 10) for 3 hours and peeled off The ratio (%) was obtained. This was used as an index of anchoring property between the support and the adhesive.

What was used by Tables 1-5 is shown below.
[Copolymer]
Copolymer (1) : Methacrylic acid / acrylic acid n-butyl copolymer (trade name “RODERM” manufactured by Rohm and Haas)
Copolymer (2) : 2-ethylhexyl acrylate (10 parts), 2-ethylhexyl methacrylate (80 parts), dodecyl methacrylate (10 parts), lauroyl peroxide used as a polymerization initiator
Copolymer (3) : ethyl acrylate (3 parts), ethyl methacrylate (7 parts), 2-ethylhexyl methacrylate (90 parts), lauroyl peroxide used as a polymerization initiator [primer layer]
Primer layer coating solution
Ether polyurethane resin film :
"Sapiria" manufactured by Sakata Inx (ether urethane resin 13-20%, additive 4-8%, solvent (hydrocarbon, alcohol, acetate, etc.) 50-77%)
Vinyl chloride-ester polyurethane resin film :
"XGL-010" manufactured by Sakata Inx Corporation (Ester urethane resin 9-15%, additive 1-5%, solvent (hydrocarbon, alcohol, ketones, etc.) 54-89%)
Ester-based polyurethane resin film :
"Lamiol Mark III" manufactured by Sakata Inx (Ester polyurethane resin 10-15%, Additive 1-2%, Solvent (hydrocarbon, alcohol, ketone, etc.) 39-84%)
[Support]
Ester-based polyurethane resin film (1) :
Made by Seiren Co., Ltd., thickness 10μm, surface mat processing
Ester-based polyurethane resin film (2) :
Toray Industries, Inc., thickness 15μm, surface mat processing
Ester-based polyurethane resin film (3) :
Made by Sea Dam Co., Ltd., thickness 30μm, surface mat processing
Ether polyurethane resin film :
Toray Industries, Inc., thickness 15μm, surface mat processing

Claims (6)

  A primer layer and a pressure-sensitive adhesive layer containing a (co) polymer having a (meth) acrylic acid alkyl ester as a structural unit are sequentially laminated on one side of a support which is an ester polyurethane resin film, and the primer layer is an ether. A patch comprising a polyurethane-based polyurethane resin film.   The patch according to claim 1, wherein the (co) polymer having the (meth) acrylic acid alkyl ester as a structural unit is a crosslinked (co) polymer.   The patch according to claim 1 or 2, wherein the pressure-sensitive adhesive layer contains a cooling agent.   The refreshing agent is selected from 1-menthol, N-substituted-p-menthane-3-carboxamide, 3-substituted-p-menthane, 2- or 3-substituted-p-menthanediol and trialkyl substituted cyclohexanecarboxyamide The patch according to claim 3, wherein the patch is one or more.   The patch according to claim 3 or 4, wherein the pressure-sensitive adhesive layer further contains a transdermal absorption enhancer.   The patch according to claim 5, wherein the percutaneous absorption accelerator is one or more selected from pyrrolidones, fatty acids, polybasic acids and dihydric alcohols.