JP2012219045A - Patch and patch preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a patch achieving a patch preparation having remarkably excellent cohesive power, showing no stringing when peeled off from the skin, and having excellent stability.SOLUTION: The patch includes a support and an adhesive layer arranged on at least one-side surface of the support. The adhesive layer includes an acryl-based copolymer formed by copolymerizing a monomer mixture containing (a) a (meth)acrylic alkyl ester, (b) a diketone group-containing monomer, and the acryl-based copolymer is cross-linked by a diamine-based compound.

Description

  The present invention relates to a patch having a support and an adhesive layer on at least one surface of the support, and a patch preparation containing a drug in the adhesive layer of such a patch.

  Patches and patch preparations that are applied to the skin for the purpose of protecting the skin, transdermal administration of drugs, etc. show sufficient adhesion when applied to the skin, and contaminate the skin surface after use ( For example, it is required to be able to be removed without causing adhesive residue or stickiness. Moreover, it is desirable that the patch and the patch preparation are hypoallergenic to the skin.

  Patent Document 1 describes a patch using an adhesive containing a copolymer containing 2-acetoacetoxyethyl methacrylate as a constituent component. However, a patch using such an adhesive may cause stringing when peeled from the skin depending on conditions.

International Publication No. 2006/064747 Pamphlet

  The present invention has been made in order to solve the above-described conventional problems, and its object is to have a remarkably excellent cohesive force, no stringing when peeling from the skin, and excellent An object of the present invention is to provide a patch capable of realizing a patch preparation having drug release properties.

The patch of the present invention comprises a support and a pressure-sensitive adhesive layer provided on at least one surface of the support, and the pressure-sensitive adhesive layer comprises (a) (meth) acrylic acid alkyl ester and (b) diketone. An acrylic copolymer obtained by copolymerizing a monomer mixture containing a group-containing monomer is included, and the acrylic copolymer is crosslinked with a diamine compound.
In a preferred embodiment, the pressure-sensitive adhesive layer contains an acrylic copolymer obtained by copolymerizing a monomer mixture containing 0.1 to 2% by weight of the diketone group-containing monomer (b).
In preferable embodiment, the addition amount of the said diamine type compound is 0.01 weight part-0.50 weight part with respect to 100 weight part of said acrylic copolymers.
In preferable embodiment, the said diamine type compound contains ethylenediamine.
In a preferred embodiment, the monomer mixture includes (c) an aggregating monomer.
In a preferred embodiment, the cohesion-imparting monomer is a hydroxyl group-containing monomer.
In a preferred embodiment, the pressure-sensitive adhesive layer contains an acrylic copolymer obtained by copolymerizing a monomer mixture containing 5 to 30% by weight of the cohesion-imparting monomer (c).
In a preferred embodiment, the pressure-sensitive adhesive layer further contains a plasticizer compatible with the acrylic copolymer, and the weight ratio of the acrylic copolymer to the plasticizer is 1: 0.1 to 0.1. 1: 5.
According to another aspect of the present invention, a patch preparation is provided. In the patch preparation, the adhesive layer contains a drug in the patch.

  According to the present invention, by combining an acrylic copolymer obtained by copolymerizing a monomer mixture containing a (meth) acrylic acid alkyl ester and a diketone group-containing monomer and a diamine compound as a crosslinking agent thereof, The cohesive force can be remarkably improved while maintaining the adhesiveness. As a result, it is possible to provide a patch that exhibits sufficient adhesiveness when applied to the skin and can be peeled off from the skin without causing stringing after use. Furthermore, since the acrylic copolymer does not substantially contain an acidic group, when the drug is contained in the adhesive layer, the acrylic copolymer and the drug do not cause an undesired reaction. Therefore, when a patch preparation is used, a patch preparation having excellent drug release properties (particularly when a basic drug is used) can be obtained.

  The patch of the present invention comprises a support and an adhesive layer provided on at least one surface of the support. The said adhesive layer contains the acryl-type copolymer formed by copolymerizing the monomer mixture containing (a) (meth) acrylic-acid alkylester and (b) diketone group containing monomer. The acrylic copolymer is crosslinked with a diamine compound. Hereinafter, each component and material will be described in detail.

A. Acrylic copolymer A-1. (Meth) acrylic acid alkyl ester The above (meth) acrylic acid alkyl ester (monomer (a)) is typically represented by the following formula (I).

In the formula, R ₁ represents a hydrogen atom or a methyl group, and R ₂ represents an alkyl group. As the alkyl group, an alkyl group having 4 to 18 carbon atoms is preferable. When the alkyl group has 4 to 18 carbon atoms, it becomes easy to obtain a pressure-sensitive adhesive having a sufficiently low glass transition temperature. As a result, it becomes easy to obtain a patch having good adhesiveness (tack).

  Examples of the (meth) acrylic acid alkyl ester include n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, (meth) acrylic acid alkyl ester having a linear alkyl group such as n-tridecyl, a branched alkyl group such as isobutyl, isopentyl, isohexyl, isooctyl and 2-ethylhexyl, a cyclic alkyl group such as cyclopentyl, cyclohexyl and cycloheptyl These may be used alone or in combination of two or more.

Among the esters, (meth) acrylic acid alkyl esters in which the alkyl group represented by R ₂ has 4 to 12 carbon atoms are more preferable in the formula (I). This is because such a (meth) acrylic acid alkyl ester can satisfactorily lower the glass transition temperature and, as a result, can give good adhesiveness to the resulting pressure-sensitive adhesive layer at room temperature. Specifically, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, cyclohexyl acrylate, cyclohexyl methacrylate, and the like are preferable, and 2-ethylhexyl acrylate is most preferable. This is because a polymer having a sufficiently low glass transition temperature (-70 ° C.) can be obtained when polymerized, and is easily available.

  The monomer (a) is preferably selected so that the glass transition temperature of the homopolymer formed thereby is preferably -80 ° C to -40 ° C, particularly preferably -70 ° C to -50 ° C.

  The content of the monomer (a) in the monomer mixture is preferably 50% by weight or more with respect to the total amount of the monomer mixture. When the content of the monomer (a) is 50% by weight or more, the adhesiveness (tack) when used as a pressure-sensitive adhesive is good. The content of the monomer (a) is more preferably 60% by weight or more, and particularly preferably 70% by weight or more. When the content of the monomer (a) is 60% by weight or more, a better tack can be obtained. On the other hand, the content of the monomer (a) is preferably 94.9% by weight or less, more preferably 90% by weight or less, based on the total amount of the monomer mixture. When the content of the monomer (a) in the monomer mixture is too large, the physical properties of the copolymer obtained are close to those of the homopolymer of the monomer (a), and it is difficult to obtain appropriate physical properties as an adhesive. There is.

A-2. Diketone Group-Containing Monomer Representative examples of the diketone group-containing monomer (monomer (b)) include acetoacetyl group-containing vinyl monomers, acetoacetyl group-containing (meth) acrylic monomers, and diacetone acrylamide. Specific examples of the acetoacetyl group-containing vinyl monomer include vinyl acetoacetate, allyl acetoacetate, allyl acetoacetate, and (2-acetoacetoxypropyl) allyl ether. Specific examples of the acetoacetyl group-containing (meth) acrylic monomer include acetoacetoxyethyl methacrylate, acetoacetoxyethyl acrylate, acetoacetoxypropyl methacrylate, acetoacetoxypropyl acrylate, acetoacetoxybutyl methacrylate, and acetoacetoxybutyl acrylate. These may be used alone or in combination of two or more.

  The content of the monomer (b) in the monomer mixture is preferably 0.1% by weight or more with respect to the total weight of the monomer mixture. On the other hand, the content of the monomer (b) is preferably less than 10% by weight, more preferably 2% by weight or less, and further preferably 1% by weight or less. When the content of the monomer (b) is less than 0.1% by weight, the cohesive force of the obtained pressure-sensitive adhesive layer may be insufficient. When the content of the monomer (b) is 10% by weight or more, the adhesiveness of the obtained pressure-sensitive adhesive layer may be insufficient.

  The total content of the monomer (a) and the monomer (b) in the monomer mixture is preferably 68% by weight or more, more preferably 75% by weight or more, further preferably 80% by weight or more, based on the total weight of the monomer mixture. It is. When a pressure-sensitive adhesive obtained from a copolymer having such a composition is used, it is possible to obtain a patch having good cohesive force and adhesive force when adhered to the skin surface.

A-3. Other monomer The monomer mixture may contain any appropriate other monomer in addition to the monomer (a) and the monomer (b). The monomer mixture preferably contains an aggregating monomer (monomer (c)). The monomer (c) can contribute to improving the cohesive force of the pressure-sensitive adhesive, for example, by the interaction between the molecules. The monomer (c) is preferably a hydroxyl group-containing monomer. The hydroxyl group-containing monomer is presumed to form a three-dimensional network structure in the pressure-sensitive adhesive layer by self-crosslinking the resulting acrylic copolymer due to the interaction between the hydroxyl group and the diketone group of the monomer (b). Therefore, the cohesive force of the pressure-sensitive adhesive can be further improved by copolymerizing the hydroxyl group-containing monomer and the monomer (b). As a result, stringing when peeling and removing the patch from the skin after use can be prevented very well.

  The monomer (c) is typically N-hydroxyalkyl (meth) acrylamide represented by the following formula (II).

In the formula, R ₃ represents a hydrogen atom or a methyl group, and R ₄ represents a hydroxyalkyl group.

  In the formula (II), the hydroxyalkyl group is preferably a hydroxyalkyl group having 2 to 4 carbon atoms. The alkyl group in the hydroxyalkyl group may be linear or branched. Examples of the N-hydroxyalkyl (meth) acrylamide represented by the formula (II) include N- (2-hydroxyethyl) acrylamide, N- (2-hydroxyethyl) methacrylamide, and N- (2-hydroxypropyl). Acrylamide, N- (2-hydroxypropyl) methacrylamide, N- (1-hydroxypropyl) acrylamide, N- (1-hydroxypropyl) methacrylamide, N- (3-hydroxypropyl) acrylamide, N- (3-hydroxy Propyl) methacrylamide, N- (2-hydroxybutyl) acrylamide, N- (2-hydroxybutyl) methacrylamide, N- (3-hydroxybutyl) acrylamide, N- (3-hydroxybutyl) methacrylamide, N- ( 4-hydroxybutyl) ac Ruamido, N-(4-hydroxybutyl) methacrylamide, and the like. These may be used alone or in combination of two or more. Among these, N- (2-hydroxyethyl) acrylamide and N- (2-hydroxyethyl) methacrylamide are preferable. Particularly preferred is N- (2-hydroxyethyl) acrylamide (HEAA). This is because a pressure-sensitive adhesive layer having a good balance between hydrophilicity and hydrophobicity and excellent adhesion can be formed. For example, the monomer (c) is preferably 50% by weight or more, more preferably 70% by weight or more, and still more preferably substantially all of HEAA. That is, 99.9% by weight or more of the monomer (c) is HEAA.

  Another typical example of the monomer (c) is hydroxyalkyl (meth) acrylate. Specific examples include 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 6-hydroxyhexyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, propylene glycol mono (meth) acrylate, 1 , 6-hexanediol mono (meth) acrylate and glycerin mono (meth) acrylate. These may be used alone or in combination of two or more. Further, N-hydroxyalkyl (meth) acrylamide and hydroxyalkyl (meth) acrylate may be used in combination.

  The content of the monomer (c) in the monomer mixture is preferably 5% by weight to 30% by weight and more preferably 7.5% by weight to 12% by weight with respect to the total weight of the monomer mixture. When the content of the monomer (c) is in such a range, a patch exhibiting better cohesive strength and adhesive strength can be obtained. When content of a monomer (c) is less than 5 weight%, the adhesiveness of the adhesive layer obtained may become inadequate. When the content of the monomer (c) exceeds 30% by weight, there are cases where the monomer mixture cannot be copolymerized due to problems such as the generation of aggregates.

  The monomer mixture may contain a vinyl monomer copolymerizable with the monomers (a) to (c). By adding an appropriate vinyl monomer, the adhesive strength and cohesive strength of the patch and patch preparation can be adjusted, and the solubility and release of the drug can be adjusted.

  When a vinyl monomer is used, the content in the monomer mixture is preferably 10% by weight or less, more preferably 5% by weight or less, based on the total amount of the monomer mixture. When the content of the vinyl monomer exceeds 10% by weight, the tack and adhesive strength of the obtained patch and patch preparation may be reduced.

  Examples of vinyl monomers include vinyl ethers such as methyl vinyl ether and ethyl vinyl ether; and nitrogen-containing complex such as N-vinyl-2-pyrrolidone, 1-vinylcaprolactam, 2-vinyl-2-piperidone and 1-vinylimidazole. A vinyl monomer having a ring can be used. These may be used alone or in combination of two or more. Among the vinyl monomers, it is preferable to use a vinyl monomer having a heterocyclic ring containing a nitrogen atom.

  In the present invention, the monomer mixture preferably contains substantially no carboxyl group-containing monomer. As the carboxyl group-containing monomer, typically, an ethylenically unsaturated monomer (typically a vinyl monomer) having at least one carboxyl group (may be in the form of an anhydride) in one molecule. ). Specific examples of the carboxyl group-containing monomer include ethylenically unsaturated monocarboxylic acids such as (meth) acrylic acid and crotonic acid; ethylenically unsaturated dicarboxylic acids such as maleic acid, itaconic acid and citraconic acid; maleic anhydride and anhydrous Examples thereof include anhydrides of ethylenically unsaturated dicarboxylic acids such as itaconic acid. In this specification, “the monomer mixture does not substantially contain a monomer having a carboxyl group” means not only the case where the monomer mixture does not contain any monomer having a carboxyl group, but the content thereof is the total amount of the monomer mixture. The case of 0.1% by weight or less is included.

  Furthermore, in the present invention, the monomer mixture not only substantially does not contain a carboxyl group-containing monomer, but also substantially includes monomers having acidic groups other than carboxyl groups (sulfo groups, phosphate groups, etc.). It is preferable not to contain. That is, the monomer mixture preferably contains no carboxyl group-containing monomer and other monomer having an acidic group, or contains these monomers in an amount of 0.1% by weight or less based on the total amount of the monomer mixture. According to the pressure-sensitive adhesive layer containing a copolymer obtained by copolymerizing such a monomer mixture, when a medical active ingredient such as a drug is contained, modification by reaction with a carboxyl group or the like of the active ingredient, It is possible to prevent movement inhibition and the like in the pressure-sensitive adhesive layer.

A-4. Crosslinking agent As described above, the acrylic copolymer is crosslinked with a diamine compound. By crosslinking with a diamine compound, crosslinking inhibition is suppressed even when a drug (for example, a basic drug) is contained in the pressure-sensitive adhesive, and the cohesive force of the pressure-sensitive adhesive can be significantly improved. As a result, stringing when the patch is peeled and removed from the skin after use can be remarkably prevented.

  The diamine compound is a compound having two amine groups in one molecule. Specific examples of the diamine compound include hexamethylenediamine, ethylenediamine, metaxylylenediamine, 1,2-cyclohexanediamine, nitroparaphenylenediamine, paranitroorthophenylenediamine, paraphenylenediamine, N-phenylparaphenylenediamine, meta Examples include phenylenediamine, toluene-2,5-diamine, and toluene-3,4-diamine. These may be used alone or in combination of two or more. Among these, Preferably, ethylenediamine is mentioned. This is because ethylenediamine has a precedent used as a pharmaceutical and can be particularly excellent in terms of safety. In addition, ethylenediamine has a low boiling point (117 ° C.), and unreacted substances that are not used for crosslinking of the acrylic copolymer can volatilize during drying (heating) described later. As a result, in the obtained pressure-sensitive adhesive layer, the remaining amount of unreacted substances is extremely low, skin irritation is well suppressed, and storage stability can be excellent. Furthermore, when ethylenediamine is used, the heat aging step (for example, exceeding 50 ° C., typically, 60 ° C. to 80 ° C., 24 hours to 48 hours) can be omitted. Can be formed.

  The addition amount of the diamine compound is preferably 0.005 to 0.50 parts by weight, more preferably 0.01 to 0.50 parts by weight, and more preferably 100 parts by weight of the acrylic copolymer. Preferably they are 0.01 weight part-0.40 weight part, Especially preferably, they are 0.01 weight part-0.30 weight part, Most preferably, they are 0.01 weight part-0.20 weight part. When the addition amount is in such a range, a patch exhibiting better cohesion and adhesion can be obtained. Specifically, when the addition amount of the diamine compound is less than 0.005 parts by weight, the cohesive force of the obtained pressure-sensitive adhesive layer may be insufficient. When the addition amount of the diamine compound exceeds 0.50 parts by weight, the crosslinking reaction proceeds excessively and gels, which may make it difficult to form the pressure-sensitive adhesive layer. Moreover, even if formation of an adhesive layer is possible, the adhesiveness of the obtained adhesive layer may become inadequate.

A-5. Polymerization method of acrylic copolymer The polymerization method for obtaining the acrylic copolymer from the monomer mixture is not particularly limited, and any appropriate polymerization method can be adopted. For example, a polymerization method performed using a thermal polymerization initiator (thermal polymerization method such as solution polymerization method, emulsion polymerization method, bulk polymerization method); irradiation with active energy rays (also referred to as high energy rays) such as light and radiation The polymerization method to be performed can be employed.

  Among the above polymerization methods, the solution polymerization method can be preferably employed. This is because it is excellent in workability and quality stability. The mode of the solution polymerization is not particularly limited, and any appropriate mode can be adopted. Specifically, any appropriate monomer supply method, polymerization conditions (polymerization temperature, polymerization time, polymerization pressure, etc.) and materials used (polymerization initiator, surfactant, etc.) can be employed. As the monomer supply method, any of a batch charging method, a continuous supply (dropping) method, a divided supply (dropping) method, and the like that supply the entire amount of the monomer mixture to the reaction vessel at a time can be employed. As a preferred embodiment, an embodiment (batch polymerization) in which a solution in which the total amount of the monomer mixture and the initiator are dissolved in a solvent is supplied into the reaction vessel and the monomer mixture is polymerized in one batch is exemplified. Such batch polymerization is preferable because the polymerization operation and process management are easy. In another preferred embodiment, an initiator (typically, a solution in which the initiator is dissolved in a solvent) is prepared in the reaction vessel, and polymerization is performed while dropping a solution in which the monomer mixture is dissolved in the solvent into the reaction vessel. An embodiment (drop polymerization or continuous polymerization) is exemplified. A portion of the monomer mixture (some components and / or a portion) may be placed in a reaction vessel, typically with a solvent, and the remaining monomer mixture may be dropped into the reaction vessel.

  Examples of thermal polymerization initiators include 2,2′-azobisisobutyronitrile, 2,2′-azobis-2-methylbutyronitrile, 2,2′-azobis (2-methylpropionic acid) dimethyl, 4'-azobis-4-cyanovaleric acid, azobisisovaleronitrile, 2,2'-azobis (2-amidinopropane) dihydrochloride, 2,2'-azobis [2- (5-methyl-2-imidazoline- 2-yl) propane] dihydrochloride, 2,2′-azobis (2-methylpropionamidine) disulfate, 2,2′-azobis (N, N′-dimethylisobutylamidine) dihydrochloride, 2,2 ′ -Azo compounds (azo initiators) such as azobis [N- (2-carboxyethyl) -2-methylpropionamidine] hydrate; potassium persulfate And persulfates such as ammonium persulfate; peroxides such as dibenzoyl peroxide, tert-butyl permaleate, t-butyl hydroperoxide, and hydrogen peroxide (peroxide-based initiators); phenyl-substituted ethane, etc. Substituted ethane type initiators; redox type initiators such as a mixture of persulfate and sodium bisulfite, a mixture of peroxide and sodium ascorbate, and the like. When the monomer mixture is polymerized by the thermal polymerization method, the polymerization temperature is preferably about 20 ° C to about 100 ° C, more preferably about 40 ° C to about 80 ° C.

  A polymerization method performed by irradiation with light (typically ultraviolet rays) is typically performed using a photopolymerization initiator. The photopolymerization initiator is not particularly limited, and examples thereof include a ketal photopolymerization initiator, an acetophenone photopolymerization initiator, a benzoin ether photopolymerization initiator, an acylphosphine oxide photopolymerization initiator, and an α-ketol photopolymerization initiator. Initiator, aromatic sulfonyl chloride photopolymerization initiator, photoactive oxime photopolymerization initiator, benzoin photopolymerization initiator, benzyl photopolymerization initiator, benzophenone photopolymerization initiator, thioxanthone photopolymerization initiator, etc. Can be used. Such a photoinitiator may be used independently and may be used in combination of 2 or more type.

  Examples of the ketal photopolymerization initiator include 2,2-dimethoxy-1,2-diphenylethane-1-one [for example, trade name “Irgacure 651” (manufactured by Ciba Japan)]. Examples of the acetophenone photopolymerization initiator include 1-hydroxycyclohexyl phenyl ketone [for example, trade name “Irgacure 184” (manufactured by Ciba Japan)], 2,2-diethoxyacetophenone, 2,2-dimethoxy-2-phenyl. Examples include acetophenone, 4-phenoxydichloroacetophenone, and 4- (t-butyl) dichloroacetophenone. Examples of the benzoin ether photopolymerization initiator include benzoin methyl ether, benzoin ethyl ether, benzoin propyl ether, benzoin isopropyl ether, and benzoin isobutyl ether. As the acylphosphine oxide photopolymerization initiator, for example, trade name “Lucirin TPO” (manufactured by BASF) or the like can be used. Examples of the α-ketol photopolymerization initiator include 2-methyl-2-hydroxypropiophenone and 1- [4- (2-hydroxyethyl) phenyl] -2-methylpropan-1-one. Examples of aromatic sulfonyl chloride photopolymerization initiators include 2-naphthalenesulfonyl chloride. Examples of the photoactive oxime photopolymerization initiator include 1-phenyl-1,1-propanedione-2- (o-ethoxycarbonyl) -oxime. An example of the benzoin photopolymerization initiator is benzoin. Examples of the benzyl photopolymerization initiator include benzyl. Examples of the benzophenone photopolymerization initiator include benzophenone, benzoylbenzoic acid, 3,3′-dimethyl-4-methoxybenzophenone, polyvinyl benzophenone, α-hydroxycyclohexyl phenyl ketone, and the like. Examples of the thioxanthone photopolymerization initiator include thioxanthone, 2-chlorothioxanthone, 2-methylthioxanthone, 2,4-dimethylthioxanthone, isopropylthioxanthone, 2,4-diisopropylthioxanthone, dodecylthioxanthone, and the like.

  The amount of the polymerization initiator used is not particularly limited. For example, the amount of the polymerization initiator used is preferably about 0.01 parts by weight to about 2 parts by weight, more preferably about 0.01 parts by weight to about 1 part by weight with respect to 100 parts by weight of the total amount of the monomer mixture. is there.

B. Pressure-sensitive adhesive layer The pressure-sensitive adhesive layer contains the acrylic copolymer described in the above section A. The thickness of the pressure-sensitive adhesive layer is preferably 10 μm to 400 μm, more preferably 20 μm to 200 μm, and more preferably 30 μm to 100 μm. The pressure-sensitive adhesive layer may be formed continuously, or may be formed in a predetermined pattern (for example, a regular pattern such as a dot shape or a stripe shape, or a random pattern) according to the purpose.

  The pressure-sensitive adhesive layer may preferably further contain a plasticizer having compatibility with the acrylic copolymer. The plasticizer can impart a soft feeling by plasticizing the pressure-sensitive adhesive layer. As a result, when the pressure-sensitive adhesive containing the acrylic copolymer is used as a pressure-sensitive adhesive layer, the adhesive or adhesive preparation such as a pressure-sensitive adhesive tape or a transdermal preparation is peeled off from the skin. Pain and skin irritation can be reduced. Therefore, any plasticizer can be used without particular limitation as long as it has a plasticizing action. In addition, when a drug is contained in the pressure-sensitive adhesive layer, it is preferable to use one having an absorption promoting action in order to improve transdermal absorbability.

  Examples of the plasticizer include vegetable oils such as olive oil, castor oil, and palm oil; animal oils such as lanolin; dimethyldecyl sulfoxide, methyl octyl sulfoxide, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, dimethyllaurylamide, methyl Organic solvents such as pyrrolidone and dodecylpyrrolidone; liquid surfactants such as polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester and polyoxyethylene fatty acid ester; plasticizers such as diisopropyl adipate, phthalate ester and diethyl sebacate; squalane , Hydrocarbons such as liquid paraffin; ethyl oleate, isopropyl palmitate, octyl palmitate, isopropyl myristate, isotridecyl myristate, ethyl laurate Fatty acid alkyl esters, preferably esters of fatty acids having 8 to 18 carbon atoms (more preferably 12 to 16) and monohydric alcohols having 1 to 18 carbon atoms; glycerol fatty acid esters, propylene glycol fatty acid esters, and the like Examples thereof include fatty acid esters of monohydric alcohols; ethoxylated stearyl alcohols; pyrrolidone carboxylic acid fatty acid esters and the like. These may be used alone or in combination of two or more.

  The plasticizer is in a weight ratio with respect to the acrylic copolymer, preferably 1: 0.1 to 1: 5, more preferably 1: 0.1 to 1: 2, and still more preferably 1: 0.1 to 1. : It may be contained in the pressure-sensitive adhesive layer in a ratio of 0.7. According to the present invention, such a high plasticizer content can be achieved as long as the adhesiveness is not impaired. In addition, when the amount of the plasticizer is within such a range, an adhesive layer having a small skin irritation can be obtained.

  The pressure-sensitive adhesive layer may further contain any other component as long as the effects of the present invention are not impaired. Examples of such optional components include antioxidants such as ascorbic acid, tocopherol acetate, natural vitamin E, dibutylhydroxytoluene and butylhydroxyanisole, and amine-ketones such as 2,6-tert-butyl-4-methylphenol. Type anti-aging agent, aromatic secondary amine type anti-aging agent such as N, N′-di-2-naphthyl-p-phenylenediamine, 2,2,4-trimethyl-1,2-dihydroquinoline polymer, etc. Monophenolic antioxidants, bisphenolic antioxidants such as 2,2′-methylenebis (4-ethyl-6-tert-butylphenol), polyphenolic antioxidants such as 2,5-tert-butylhydroquinone, kaolin , Fillers such as hydrous silicon dioxide, zinc oxide, starch acrylate 1000, propylene glycol Softeners such as cole, polybutene, macrogol 1500, benzoic acid, sodium benzoate, chlorhexidine hydrochloride, sorbic acid, methyl paraoxybenzoate, butyl paraoxybenzoate, and the like, yellow iron oxide, yellow iron sesquioxide, sesquioxide Iron, black iron oxide, carbon black, carmine, β-carotene, copper chlorophyll, edible blue No. 1, edible yellow No. 4, edible red No. 2, colorants such as licorice extract, fennel oil, d-camphor, dl-camphor , Refreshing agents such as peppermint oil, d-borneol, l-menthol, and perfumes such as spearmint oil, clove oil, vanillin, bergamot oil, lavender oil and the like. The kind and amount of other components to be contained can be appropriately set depending on the purpose.

  The gel fraction of the pressure-sensitive adhesive layer is preferably 30% by weight or more, more preferably 40% by weight or more, and still more preferably 50% by weight or more. On the other hand, the gel fraction is preferably 85% by weight or less, more preferably 80% by weight or less. If the gel fraction is in such a range, sufficient cohesive force is imparted to the pressure-sensitive adhesive layer, and adhesive residue, stringing, strong skin irritation, etc. may occur due to cohesive failure when the patch is peeled off. Absent. The gel fraction of the pressure-sensitive adhesive layer can achieve the preferable gel fraction by adjusting the contents of the acrylic copolymer and the plasticizer, for example.

“Gel fraction” means the ratio of the weight of insoluble matter obtained when the pressure-sensitive adhesive layer is immersed in an organic solvent such as ethyl acetate to the total weight of the components involved in crosslinking of the pressure-sensitive adhesive layer. The gel fraction can be determined using the following formula based on the weight of insoluble matter obtained by immersing the pressure-sensitive adhesive layer in an organic solvent such as ethyl acetate at room temperature (23 ° C.) for a predetermined period.
Gel fraction (% by weight) = (W ₂ × 100) / (W ₁ × A / B)
A: Weight of polymer and cross-linking agent B: Total weight of pressure-sensitive adhesive layer components W ₁ : Weight of pressure-sensitive adhesive layer used as sample W ₂ : Insoluble matter after dipping the pressure-sensitive adhesive layer used as a sample in an organic solvent weight

  The pressure-sensitive adhesive layer may be subjected to physical crosslinking treatment by irradiation with radiation such as ultraviolet irradiation or electron beam irradiation.

C. Support The support is not particularly limited. As the support, the components contained in the pressure-sensitive adhesive layer (for example, active ingredients such as drugs, additives) are lost from the back through the support and do not cause a decrease in content, that is, the pressure-sensitive adhesive What is comprised with the material which does not permeate | transmit an agent layer containing component is preferable.

  Examples of the support that can be used in the patch and patch preparation of the present invention include polyester resins such as polyethylene terephthalate; polyamide resins such as nylon; Saran (registered trademark), polyethylene, polypropylene, Surlyn (registered trademark), and the like. Olefin resins; vinyl resins such as ethylene-vinyl acetate copolymer, polyvinyl chloride, and polyvinylidene chloride; acrylic resins such as ethylene-ethyl acrylate copolymer; fluorocarbon resins such as polytetrafluoroethylene; A single film such as a metal foil, and a laminate film thereof can be used. The thickness of the support is preferably 10 μm to 500 μm, more preferably 10 μm to 200 μm.

The support is preferably a laminate sheet of a non-porous sheet made of the above material and a porous sheet. If it is such a structure, the adhesiveness (throwing property) between a support body and an adhesive layer can be improved. In this case, it is preferable to form an adhesive layer on the porous sheet side. The porous sheet is not particularly limited as long as it improves the anchoring property between the support and the pressure-sensitive adhesive layer. Examples thereof include paper, woven fabric, non-woven fabric, and a mechanically perforated sheet. In particular, paper, woven fabric, and non-woven fabric are preferable. The thickness of the porous sheet is preferably 10 μm to 500 μm. If it is such thickness, anchoring property will improve and it will be excellent in the softness | flexibility of an adhesive layer. In the case of using a woven fabric or nonwoven fabric as the porous sheet, the basis weight of the porous sheet is preferably ^{5g / m 2 ~30g / m 2} , more preferably ^{8g / m 2 ~20g / m 2} . This is because the throwing ability is improved. When the support is the above laminate sheet, the thickness of the non-porous sheet is preferably 1 μm to 25 μm.

Of the support, particularly suitable support, a polyester film 1.5μm~6μm thickness (preferably polyethylene terephthalate film), a basis weight ^8g / ^{m 2 ~20g} / m 2 of polyester (preferably, polyethylene It is a laminated film with a non-woven fabric made of terephthalate.

D. Patch and Patch Formulation The patch of the present invention has an adhesive layer formed on the at least one surface of the support described in the above section C with the adhesive described in the above sections A and B. The patch of the present invention can be provided as a medical or sanitary patch in the form of a sheet, film, pad, etc., and skin lesions such as gauze substitutes in adhesive bandages and non-woven fabric substitutes in wound dressings It can be used for applications such as site and wound site protection.

  The patch preparation of the present invention comprises the adhesive layer of the above-mentioned patch of the present invention containing a drug in the adhesive layer. The patch preparation of the present invention is provided as a transdermal absorption preparation, and is provided as a matrix-type patch preparation, a reservoir-type patch preparation, or the like, and particularly preferably provided as a matrix-type patch preparation.

  The drug contained in the adhesive layer in the patch preparation of the present invention is typically a drug that can be administered transdermally. The kind of the drug contained in the adhesive layer can be appropriately selected according to the purpose. Specific examples of drugs include corticosteroids, non-steroidal anti-inflammatory agents, anti-rheumatic agents, sleeping agents, antipsychotics, antidepressants, mood stabilizers, psychostimulants, anxiolytics, antiepileptics, Migraine treatment agent, Parkinson's disease treatment agent, cerebral circulation / metabolism improving agent, antidementia agent, autonomic agent, muscle relaxant, antihypertensive agent, diuretic agent, hypoglycemic agent, hyperlipidemia agent, gout treatment Agent, general anesthetic agent, local anesthetic agent, antibacterial agent, antifungal agent, antiviral agent, antiparasitic agent, vitamin agent, angina treatment agent, vasodilator, antiarrhythmic agent, antihistamine agent, mediator release inhibitor, Types of drugs that can be transdermally administered, such as leukotriene antagonists, female hormones, thyroid hormones, antithyroids, antiemetics, antitussives, bronchodilators, antitussives, expectorants, smoking cessation aids, etc. Can be mentioned. Among them, in the adhesive preparation of the present invention, a drug whose release property is extremely reduced in the pressure-sensitive adhesive layer containing a carboxyl group is preferably used because of the characteristics of the copolymer contained in the pressure-sensitive adhesive layer. It can be included.

  From the viewpoint of obtaining a patch preparation having high skin permeability, it is advantageous to use a basic drug as the drug in the present invention. A basic drug means a drug having a basic group in the molecule. In the adhesive preparation of the present invention containing an acrylic copolymer substantially free of carboxyl groups in the pressure-sensitive adhesive layer, the basic drug in the pressure-sensitive adhesive layer produced by the reaction of the basic group of the basic drug and the carboxyl group. It becomes possible to suppress movement inhibition and the like. As a result, excellent drug release can be achieved. From this viewpoint, the basic drug is preferably a basic drug having a basic nitrogen atom, more preferably a drug having a primary to tertiary amino group, and a drug having a primary to secondary amine group. Is more preferable. Needless to say, not only basic drugs but also acidic drugs and neutral drugs (such as ISDN or isosorbide nitrate) can be used as drugs.

  The content of the drug in the patch preparation of the present invention can be appropriately set according to the type of drug, the purpose of administration, the patient's age, sex, symptoms and the like. The drug is typically contained in the pressure-sensitive adhesive layer in an amount of about 0.1 wt% to 40 wt%, preferably about 0.5 wt% to 30 wt%. Since it differs depending on the selected drug, it cannot be generally stated, but in general, when the content is less than 0.1% by weight, a therapeutically effective amount of drug cannot be expected to be released, whereas 40% by weight. In many cases, the therapeutic effect is not improved even if the percentage exceeds 50%, which is also economically disadvantageous.

  The method for producing the patch and patch preparation of the present invention is not particularly limited, and a method commonly used in the art can be used. Hereinafter, the matrix-type patch preparation which is one embodiment of the patch preparation of the present invention will be specifically described. First, the acrylic copolymer, diamine compound (crosslinking agent), plasticizer, drug and the like are dissolved or dispersed in a solvent to prepare a coating solution. This coating solution is applied to at least one surface of the support and dried to form an adhesive layer. Furthermore, a release liner described below can be pressure-bonded and laminated. It can also be produced by applying a coating liquid on a release liner, drying to form a pressure-sensitive adhesive layer on the surface of the release liner, and then pressing and bonding the support onto the pressure-sensitive adhesive layer. .

  Examples of the release liner include glassine paper, polyethylene, polypropylene, polyester, polyethylene terephthalate, polystyrene, aluminum film, foamed polyethylene film, foamed polypropylene film, etc., or laminates of those selected from these, and those processed with silicone. , Embossed and the like. The thickness of the release liner is preferably 10 μm to 200 μm, more preferably 25 μm to 100 μm.

  The release liner is preferably a polyester (particularly polyethylene terephthalate) resin release liner from the viewpoint of barrier properties and cost. In this case, the thickness is preferably about 25 μm to 100 μm from the viewpoint of handleability.

  The coating liquid can be applied using, for example, a conventional coater such as a gravure roll coater, reverse roll coater, kiss roll coater, dip roll coater, bar coater, knife coater, or spray coater. The drying is preferably performed under heating from the viewpoint of promoting the crosslinking reaction and improving production efficiency. The drying temperature can vary depending on, for example, the type of support. The drying temperature is, for example, about 40 ° C. to about 150 ° C.

  Moreover, after manufacturing a patch or a patch preparation by the above-mentioned method, you may age, for the purpose of improving the anchoring property of an adhesive layer and a support body, for example. The aging temperature is typically room temperature or higher, preferably 25 ° C. to 80 ° C., more preferably 30 ° C. to 50 ° C. In the present invention, for example, heat aging for completing the crosslinking reaction is not particularly required.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples. Unless otherwise specified, “parts” and “%” in the examples are based on weight.

<Example 1>
In a separable flask equipped with a reflux condenser, a nitrogen gas inlet tube, a thermometer, a dropping funnel and a stirrer, 89 parts of 2-ethylhexyl acrylate (hereinafter referred to as 2-EHA), N-hydroxyethylacrylamide (hereinafter referred to as HEAA) And 10 parts of 2-acetoacetoxyethyl methacrylate (hereinafter referred to as AAEM), 0.2 part of 2,2′-azobisisobutyronitrile (AIBN) and 150 parts of ethyl acetate as a polymerization initiator. The mixture was stirred at room temperature for 1 hour while performing nitrogen gas bubbling (50 mL / min). Thereafter, the contents were heated, the temperature of the contents was controlled to be kept at 60 ° C., and reacted in a nitrogen gas stream for 6 hours, and further reacted at 76 ° C. for 18 hours. A solution of an acrylic copolymer (2-EHA / HEAA / AAEM = 89/10/1) was obtained by solution polymerization in the above manner.

60 parts (solid content) of the acrylic copolymer obtained above, 40 parts of isopropyl myristate (hereinafter referred to as IPM) and 0.15% ethylenediamine (hereinafter referred to as the solid content of the acrylic copolymer) , EDA) was added, and the viscosity was adjusted by adding ethyl acetate to prepare a coating solution. This coating solution was applied to the release surface of a 75 μm thick polyethylene terephthalate (PET) film release liner with an applicator so that the thickness after drying was 60 μm, and dried at 100 ° C. for 3 minutes to obtain an adhesive. A layer was formed. As the support, a laminate of a PET film having a thickness of 2 μm and a PET nonwoven fabric having a basis weight of 12 g / m ² was used. After the non-woven fabric surface of the support was pressure bonded to the adhesive layer, it was sealed with an aluminum wrapping material and aged at 40 ° C. for 24 hours to obtain a patch.

<Example 2>
A patch was obtained in the same manner as in Example 1 except that the amount of EDA added was 0.30%.

<Example 3>
A patch was obtained in the same manner as in Example 1 except that the addition amount of EDA was 0.005% and the addition amount of IPM was 30 parts.

<Example 4>
A patch was obtained in the same manner as in Example 3 except that the amount of EDA added was 0.01%.

<Example 5>
A patch was obtained in the same manner as in Example 3 except that the amount of EDA added was 0.03%.

<Example 6>
A patch was obtained in the same manner as in Example 3 except that the amount of EDA added was 0.05%.

<Example 7>
A patch was obtained in the same manner as in Example 6 except that the coating liquid was applied so that the thickness after drying was 160 μm when forming the pressure-sensitive adhesive layer.

<Example 8>
A patch was obtained in the same manner as in Example 7 except that the amount added to IPM was 60 parts.

<Example 9>
A patch was obtained in the same manner as in Example 6 except that an acrylic copolymer having the following formulation was used.
2-EHA: 89.5 parts, HEAA: 10 parts, AAEM: 0.5 parts

<Example 10>
A patch was obtained in the same manner as in Example 9 except that hexamethylenediamine (HMDA) was used instead of EDA.

<Example 11>
A patch was obtained in the same manner as in Example 9 except that the coating liquid was applied so that the thickness after drying was 160 μm when the pressure-sensitive adhesive layer was formed.

<Comparative Example 1>
Instead of EDA, 0.30% (solid content) of metal chelate compound (aluminum ethyl acetoacetate diisopropylate, trade name: ALCH, manufactured by Kawaken Fine Chemical Co., Ltd.) and aging at 60 ° C. for 48 hours A patch was obtained in the same manner as in Example 1 except that.

<Comparative example 2>
A patch was obtained in the same manner as in Comparative Example 1 except that the amount of the metal chelate compound added was 0.50%.

<Comparative Example 3>
A patch was obtained in the same manner as in Comparative Example 1 except that the amount of the metal chelate compound added was 0.75%.

<Comparative example 4>
A patch was obtained in the same manner as in Example 1 except that EDA was not added.

<Comparative Example 5>
A patch was obtained in the same manner as in Comparative Example 4 except that an acrylic copolymer having the following formulation was used.
2-EHA: 85 parts, HEAA: 10 parts, AAEM: 5 parts

<Comparative Example 6>
A patch was obtained in the same manner as in Example 1 except that an acrylic copolymer having the following formulation was used.
2-EHA: 70 parts, VP (N-vinyl-2-pyrrolidone): 20 parts, HEAA: 10 parts

<Comparative Example 7>
A patch was obtained in the same manner as in Example 2 except that an acrylic copolymer having the following formulation was used.
2-EHA: 70 parts, VP (N-vinyl-2-pyrrolidone): 20 parts, HEAA: 10 parts

<Evaluation>
The following evaluations were performed on the patches obtained in the above Examples and Comparative Examples. The evaluation results are summarized in Table 1. In the table, the amount of IPM added is shown as a ratio relative to 1 part by weight of the copolymer.
(1) Gel fraction The weight (W ₁ ) [g] of the pressure-sensitive adhesive layer of a sample obtained by cutting each patch into 10 cm ² was measured. Next, the sample was immersed in 100 mL of ethyl acetate for 24 hours to extract the solvent-soluble component. Then, after drying removed the sample, measuring the weight of the adhesive layer (W _{2) [g],} was calculated gel fraction by the following equation.
Gel fraction (% by weight) = (W ₂ × 100) / (W ₁ × A / B)
A: Weight of polymer B: Total weight of constituent components of pressure-sensitive adhesive layer W ₁ : Weight of pressure-sensitive adhesive layer used as sample W ₂ : Weight of insoluble matter after immersing sample of pressure-sensitive adhesive layer in organic solvent (2 ) Finger Tack (Thread Pulling) Test The release liner was peeled from the obtained patch and placed on a horizontal table so that the surface of the plaster (adhesive layer) was the upper surface. A finger was pressed against the plaster to evaluate tackiness and the degree of stringing. The evaluation criteria are as follows.
○: There is a cohesive force, a sufficient tack feeling is obtained, and no stringing is observed. Δ: There is a cohesive force and no stringing of the plaster is observed, but the tack feeling is slightly insufficient. There was no cohesive force and stringing of the plaster was observed. (3) Skin patch test The obtained patch was punched out to 10 cm ² to prepare a sample. This sample was affixed to the chest of an experimental collaborator and the adhesion for 24 hours was confirmed. The evaluation criteria are as follows.
○: Neither floating nor adhesive residue is observed △: No adhesive residue is observed, but floating occurs at the end ×: Adhesive residue is observed

As is apparent from Table 1, the patches of the examples of the present invention have a high gel fraction of the pressure-sensitive adhesive layer, are excellent in both stringiness (that is, adhesiveness) with finger tack, and have skin adhesiveness. Also excellent. In particular, when the amount of EDA added to the acrylic copolymer was 0.01% or more, extremely excellent cohesive force was obtained.
As is apparent from Examples 9 to 11, even when the copolymerization ratio of AAEM is lowered to 0.5% by weight, sufficient cohesive force is ensured and other physical properties are also good.
As is clear from Examples 7, 8, and 11, even when the thickness of the pressure-sensitive adhesive layer and the content of IPM are changed, sufficient cohesive force is ensured and other physical properties are also good.
Also in Example 10 using HMDA as the diamine compound, sufficient cohesive force is ensured and other physical properties are also good.

On the other hand, Comparative Examples 1 to 3 had a high gel fraction in the pressure-sensitive adhesive layer, excellent in stringiness (adhesiveness) with finger tack, and good initial physical properties. A decrease in cohesive force was clearly observed, and adhesive residue was observed at the time of peeling from the skin. This is considered to be one of the causes that the crosslinking (chelate) is broken by the influence of disturbance (for example, moisture).
In Comparative Example 4 in which no crosslinking agent was used, the gel fraction was low, and stringing was confirmed. As is clear from Comparative Example 5, when the copolymerization ratio of AAEA was increased, the gel fraction was increased, but excellent skin patchability was not obtained.
As is clear from Comparative Examples 6 and 7, the combination of the acrylic copolymer obtained without using the diketone group-containing monomer and EDA had an extremely low gel fraction and stringing was confirmed.

<Example 12>
A patch preparation was obtained in the same manner as in Example 6 except that 5 parts of a drug (pramipexole) was further added during the preparation of the coating solution.

<Example 13>
A patch preparation was obtained in the same manner as in Example 6 except that 5 parts of a drug (tulobuterol) was further added during the preparation of the coating solution.

<Example 14>
A patch preparation was obtained in the same manner as in Example 6 except that 5 parts of a drug (felbinac) was further added during the preparation of the coating solution.

<Evaluation>
For the patches (patch preparations) obtained in Examples 6 and 12 to 14, the gel fraction, logarithmic decay rate, adhesive force and finger tack were evaluated. The evaluation results are summarized in Table 2. In addition, the logarithmic decay rate and the evaluation method of adhesive force are as follows.
(4) Logarithmic decay rate The obtained patch (patch preparation) was used as a sample with a width of 10 mm. Using a rigid pendulum viscoelasticity measuring device (product name: RPT-3000W), it is composed of a brass round bar cylinder edge (product name: RBP-040) and a frame (product name: FRB-100) with a diameter of 4 mm. And measured with a rigid pendulum (inertia 6 × 10 ² g · cm ² , mass 13 g) (both manufactured by A & D Co., Ltd.). Specifically, after placing an edge on the sample, the pendulum was vibrated, and the logarithmic attenuation rate of the vibration was measured. The sample temperature was 23 ° C.
(5) Adhesive strength test The obtained patch (patch preparation) was punched into a rectangle of 50 mm length x 12 mm width. Peel off one end of the release liner of the punched patch about 5 mm, fold it back to 180 ° angle, cover all the part where the release liner was folded, and paste the auxiliary paper so that it protrudes from the end in the length direction of the patch It was. After peeling off the release liner, it was quickly pasted on a stainless steel plate to prepare a sample. Immediately thereafter, a rubber roller having a weight of 2 kg was passed over the sample twice at a speed of 300 mm / min. This sample was left for 30 minutes in an environment of 23 ± 2 ° C. and a relative humidity of 50 ± 10%. Next, a 180 ° tensile jig was attached to the tensile tester, one end of the auxiliary paper was firmly sandwiched between the clasps on the upper part of the jig, the sample was set on the jig, and continuously peeled off at a speed of 300 mm per minute. . The load at that time was measured and recorded. The load was read three times at equal intervals (reading positions: 20 mm, 40 mm and 60 mm) from the chart recording the measurement results, and averaged.

  A high gel fraction was also confirmed in Examples 12 and 13 in which a basic drug was blended, and it can be said that there is substantially no inhibition of crosslinking by the drug from comparison with Example 6 (placebo preparation). A high gel fraction was also confirmed in Example 14 in which an acidic drug having a carboxyl group in the molecule was blended, and from the comparison with Example 6 (placebo preparation), it can be said that there is substantially no inhibition of crosslinking by the drug. .

  The patch and patch preparation of the present invention can be suitably used for skin protection, transdermal administration of drugs and the like.

Claims (9)

A support and a pressure-sensitive adhesive layer provided on at least one surface of the support;
The pressure-sensitive adhesive layer includes an acrylic copolymer obtained by copolymerizing a monomer mixture containing (a) (meth) acrylic acid alkyl ester and (b) a diketone group-containing monomer,
The acrylic copolymer is crosslinked with a diamine compound,
Patch.   The patch according to claim 1, wherein the pressure-sensitive adhesive layer comprises an acrylic copolymer obtained by copolymerizing a monomer mixture containing 0.1 to 2% by weight of the diketone group-containing monomer (b). .   The patch according to claim 1 or 2, wherein the addition amount of the diamine compound is 0.01 to 0.50 parts by weight with respect to 100 parts by weight of the acrylic copolymer.   The patch according to any one of claims 1 to 3, wherein the diamine-based compound contains ethylenediamine.   The patch according to any one of claims 1 to 4, wherein the monomer mixture contains (c) an aggregating monomer.   The patch according to claim 5, wherein the cohesion-imparting monomer is a hydroxyl group-containing monomer.   The patch according to claim 5 or 6, wherein the pressure-sensitive adhesive layer comprises an acrylic copolymer obtained by copolymerizing a monomer mixture containing 5 to 30% by weight of the cohesion-imparting monomer (c). .   The pressure-sensitive adhesive layer further includes a plasticizer compatible with the acrylic copolymer, and a weight ratio of the acrylic copolymer to the plasticizer is 1: 0.1 to 1: 5. The patch according to any one of claims 1 to 7.   The patch preparation according to any one of claims 1 to 8, wherein the adhesive layer contains a drug.