JP2017105837A - Medical patches - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide medical patches in which an adhesive layer which contains an agent and solubilizing agent in large amount, is flexible without deformation and paste residues, and is excellent in agent release from the adhesive layer is formed.MEANS FOR SOLVING THE PROBLEM: A medical patch comprises an agent having a secondary or tertiary amine structure in molecules; a liquid adjuvant for agents; and a resin composition which contains (Meth)acrylic ester monomer as a monomer major component and in which a copolymerization acrylic resin having a functional group capable of forming a cross-linkage by reacting with a crosslinker having an isocyanate group is crosslinked by the crosslinker having a blocked isocyanate group, the solubility to the phosphate buffer (pH 6.4) of the agent is 0.5% by weight or more.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a medical patch having uses such as skin protection and administration of a drug through a skin surface in vivo.

  In recent years, various patch preparations such as patches and tape-shaped preparations have been developed that have uses such as protecting the skin, and administration of drugs into the living body through the skin surface. A patch containing a pharmacologically active ingredient) in an adhesive layer is disclosed (for example, see Patent Documents 1 and 2).

  Copolymerized acrylic resin or the like is used for the adhesive layer, but it contains a large amount of chemicals and solubilizing agents and does not lose its shape or substantially remain glue (hereinafter, "substantially no glue remains" In order to obtain an adhesive layer (expressed as “not remaining”), the adhesive layer is preferably crosslinked (see, for example, Patent Documents 3 and 4).

  However, it is difficult to control the cross-linking reaction when the copolymerized acrylic resin is cross-linked, and there is a problem that curing proceeds excessively in the manufacturing process of the patch. This tendency is particularly noticeable when the copolymerized acrylic resin has an amine structure or when a compound having an amine structure is used as a drug or additive.

  In this regard, it contains a large amount of liquid auxiliaries for drugs such as drugs and solubilizing agents, and does not cause adhesive residue on the skin. As a medical patch to be used, the inventors of the present application have a drug having a secondary or tertiary amine structure in the molecule, a liquid auxiliary agent for drug, and a monomer of (meth) acrylic acid ester as a monomer main component, A copolymer acrylic resin having a functional group capable of forming a crosslink by reacting with a crosslinker having an isocyanate group comprises a resin composition obtained by crosslinking with a blocked crosslinker having the isocyanate group. A medical patch was proposed. (See Patent Document 5)

  However, there is still a problem that the drug contained in the adhesive layer is hardly released to the skin surface.

JP 2000-7559 A JP-A-5-65460 JP 2010-024224 A JP 2005-170833 A International Publication No. WO 2011/118683

  An object of the present invention is to provide a medical patch that contains a large amount of a drug and a solubilizing agent, forms a flexible adhesive layer that does not lose its shape or remain unglue, and is excellent in drug release from the adhesive layer. That is.

The gist of the present invention is that
A drug having a secondary or tertiary amine structure in the molecule;
Liquid auxiliaries for drugs,
A copolymer acrylic resin having a functional group capable of forming a cross-link by reacting with a cross-linking agent having an isocyanate group comprising a monomer of (meth) acrylic acid ester as a main component is blocked with the blocked isocyanate group. A resin composition that is crosslinked by a crosslinking agent having
It is a medical patch in which the solubility of the drug in a phosphate buffer (pH 6.4) is 0.5% by weight or more.

  The agent may be selected from risperidone, haloperidol, paliperidone, olanzapine, lonacene, ondansetron.

  The copolymerized acrylic resin may contain a monomer having a tertiary amine structure in the molecule as a monomer component.

  The copolymerized acrylic resin may contain an aliphatic alcohol (C4-10) acrylate and dimethylaminoalkyl (meth) acrylate or dimethylaminoalkyl (meth) acrylamide as monomer components.

  The copolymerized acrylic resin is 40 to 80 parts by weight of an acrylate ester of an aliphatic alcohol (C4-10), 1 to 20 parts by weight of dimethylaminoalkyl (meth) acrylate or dimethylaminoalkyl (meth) acrylamide, and hydroxy. It may be formed by copolymerizing 0.5 to 20 parts by weight of alkyl acrylate or hydroxyalkyl acrylamide.

  The copolymerized acrylic resin may further contain 10 to 40 parts by weight of methoxyalkyl acrylate or ethoxyalkyl acrylate as a monomer component.

  The copolymerized acrylic resin comprises a copolymer of two or more acrylic monomers including an acrylic monomer having a tertiary amino group and an acrylic monomer having no carboxylic acid group and having an OH group, a nonionic acrylic resin, Can be mixed.

  The gist of the present invention resides in a composite medical patch in which a nonionic acrylic resin layer is laminated on an adhesive layer made of the medical patch.

  Further, the gist of the present invention is that it is a patch preparation comprising an adhesive layer composed of the medical patch and a support for supporting the adhesive layer.

  The patch preparation may be formed by laminating a nonionic acrylic resin layer on the upper surface of the adhesive layer.

  According to the present invention, a flexible adhesive layer that contains a large amount of a liquid auxiliary agent for drugs such as a drug and a solubilizing agent, does not cause adhesive residue on the skin, does not stick out during storage, and does not lose its shape. Further, a medical patch that is formed and has excellent drug release properties from the adhesive layer, and a patch preparation having this adhesive layer are provided.

The schematic diagram which shows the structure of the medical patch of this invention. The schematic diagram which shows the structure of the medical patch of the other aspect of this invention. The graph which shows the release | release property measurement of a chemical | medical agent. The graph which shows the skin permeability measurement result of a chemical | medical agent. The graph which shows the release | release property measurement of a chemical | medical agent.

The medical patch of the present invention is
A physiologically active drug having a secondary or tertiary amine structure in the molecule and having a solubility in a phosphate buffer (pH 6.4) of 0.5% by weight or more;
Liquid auxiliaries for drugs,
A copolymer acrylic resin having a functional group capable of forming a cross-link by reacting with a cross-linking agent having an isocyanate group comprising a monomer of (meth) acrylic acid ester as a main component is blocked with the blocked isocyanate group. And a resin composition that is crosslinked with a crosslinking agent.

  As shown in FIG. 1, a medical patch of the present invention supported on a support 4 as an adhesive layer 2 is used as a patch preparation 6a attached to the skin. Examples of the support include films made of polyolefin, polyester, polyurethane and the like, foam films, nonwoven fabrics, knitted fabrics, woven fabrics, and laminates of films and fabrics.

  In this specification, the tertiary amine structure means a general chemical structure having a structure in which three carbon atoms are directly bonded to a nitrogen atom, and the secondary amine structure means two carbon atoms in a nitrogen atom. It means a general chemical structure having a structure formed by direct bonding.

  The adhesive layer is a blocked isocyanate prepared by mixing the copolymerized acrylic resin, a drug having a secondary or tertiary amine structure in the molecule, and a liquid auxiliary agent for the drug, if necessary, in a solvent. It can be obtained by adding a crosslinking agent having a group and crosslinking.

  As the functional group capable of forming a crosslink by reacting with a crosslinker having an isocyanate group, one having active hydrogen is preferable, and examples thereof include a hydroxyl group and an amino group.

The patch preparation using the medical patch of the present invention is:
A copolymer acrylic resin having a functional group capable of forming a crosslink by reacting with a crosslinking agent having an isocyanate group, the main component of which is a (meth) acrylic acid ester monomer, and secondary or tertiary in the molecule A mixed liquid containing a drug having an amine structure, a liquid auxiliary agent for drugs, and a crosslinking agent having the isocyanate group blocked with a blocking agent is applied to a releasable sheet substrate (release sheet) to form a coating film. Obtaining step,
Heating the coating film applied to the release sheet at a temperature at which the blocking agent is desorbed;
It can be produced by a method for producing a patch preparation comprising a step of laminating a support on the heated coating film.

  The coating film laminated on the release sheet is usually heated at 80 ° C. to 130 ° C. in this heating step, but it is 80 to 100 ° C. in order to prevent the decomposition of the drug or to prevent the additive from being diffused. It is preferable to heat in this range, and by this heating, the copolymerized acrylic resin reacts with the crosslinking agent to crosslink.

  The step of laminating the support on the heated coating film is performed, for example, by laminating the support on the surface of the coating film opposite to the side facing the release sheet.

  The coating film laminated on the support may be reheated as necessary in order to complete the crosslinking.

  Examples of the release sheet on which the mixed solution is applied include resin films and paper made of polyester, fluororesin, polyvinylidene chloride, polypropylene, etc., and a release treatment is performed on the surface facing the adhesive layer. preferable.

  A laminate obtained by laminating a coating film on a support is cut into small pieces of a predetermined size and used as a patch preparation with a release sheet laminated as necessary.

  The patch preparation is generally provided on the market with a cover peelable sheet made of a release paper or release film attached to the surface of the adhesive layer. As the peelable sheet for the cover, the release sheet may be used as it is, but the peelable sheet may be replaced with the peelable sheet for the cover in the process of commercialization. The cover peelable sheet is peeled off when the patch preparation is used.

  Alternatively, the patch preparation using the medical patch of the present invention has a (meth) acrylic acid ester monomer as a main monomer component and has a functional group capable of forming a crosslink by reacting with an isocyanate group-containing crosslinker. A mixed liquid containing a copolymerized acrylic resin, a drug having a secondary or tertiary amine structure in the molecule, a liquid auxiliary agent for the drug, and a crosslinking agent having an isocyanate group blocked with a blocking agent. After coating, the coated coating film can be produced by heating at a temperature at which the blocking agent is released to crosslink the copolymer acrylic resin. Next, it is common that a peelable sheet for a cover made of a release paper or a release film is attached to the surface of the adhesive layer and then provided to the market.

  The copolymerized acrylic resin used in the present invention, after becoming a polymer, is an alkyl (meta) that does not have a functional group capable of forming a crosslink by reacting with a normal crosslinker under normal reaction conditions, for example, at 120 ° C. or lower. ) A vinyl monomer having a functional group capable of forming a crosslink by reacting with a monomer of (meth) acrylic ester such as acrylate and a crosslinker having an isocyanate group after becoming a polymer, such as a vinyl monomer having a hydroxyl group It is obtained by copolymerizing a monomer having an amino group to contain a large amount of a drug and a solubilizing agent and to exhibit adhesiveness, and to form a flexible adhesive layer that does not lose its shape or remain adhesive. It is preferable for obtaining a medical patch to be formed.

  This copolymerized acrylic resin tends to lose its shape due to the presence of this liquid substance, and glue sticking out and adhesive residue on the skin occur, but cross-linking stabilizes the shape and yields a flexible adhesive layer with no loss of shape or adhesive residue. It is done. However, when this copolymerized acrylic resin is cross-linked using a conventionally known cross-linking agent such as a compound having an epoxy group or a normal isocyanate cross-linking agent, the cross-linking reaction proceeds rapidly, and the cross-linking agent is added to the resin liquid. During the mixing, the reaction started and the resin was cured, so that a uniform solution could not be applied. In particular, as in the present invention, when a chemical having a secondary or tertiary amine structure is present in the molecule in the crosslinking reaction system, the crosslinking reaction proceeds very rapidly. The tendency of the reaction to start and the resin to harden during the period is remarkable.

  In the case of conventional general pressure-sensitive adhesives, copolymers of acrylic acid ester and acrylic acid are the main ones. Depending on the case, vinyl acetate may be copolymerized as another comonomer. In the case of an agent, amine-based drugs, particularly those having tertiary and quaternary amine structures, form salts with carboxylic acid groups such as acrylic acid and stabilize, and thus release from the patch does not proceed. As a result, when applied to the skin, there are problems such as poor release to the skin side, sometimes the amount of effective drug does not transfer to the skin, and the use efficiency of the drug is greatly deteriorated.

  In the present invention, this curing reaction is achieved by using blocked isocyanate as a cross-linking agent, despite the presence of a chemical or acrylic copolymer having a secondary or tertiary amine structure in the cross-linking reaction system. Was able to suppress the runaway. That is, the resin solution to which the blocked isocyanate is added is applied to a release sheet or a support, and is heated and dried to reach a predetermined temperature, for example, 90 ° C., thereby releasing the blocking agent and gradually causing the crosslinking reaction. In this way, a medical patch containing a large amount of a drug and a solubilizing agent and forming a flexible adhesive layer that does not lose its shape or remain glued can be obtained. Since the cleavage temperature is determined by the blocking agent, it is necessary to form a drying / crosslinking reaction at a temperature suitable for each. Since the cleavage reaction and the crosslinking reaction do not always proceed promptly, the crosslinking reaction is not completed in only a few minutes of drying, and it is important to perform a heat treatment after drying.

  In addition, the copolymerized acrylic resin used in the present invention includes a monomer having a tertiary amine structure such as dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, or dimethylaminopropylacrylamide. In the case of the copolymer used and / or when a tertiary amine compound is added to the drug, the above curing reaction is particularly likely to occur when a general crosslinking agent is used, but the isocyanate blocked with a blocking agent is used. When is used as a crosslinking agent, this runaway can be effectively suppressed.

  Furthermore, in this invention, it is preferable that this copolymerization acrylic resin contains the monomer which has a tertiary amine structure in a molecule | numerator as a monomer component. The reason for this is that when the drug is a compound having a secondary or tertiary amine structure, the drug in the adhesive layer is smoothly released from the patch. This is because the tertiary amine group is present in the copolymerized acrylic resin, which is a constituent element of the adhesive layer, so that the tertiary amine group and the drug are ionically repelled, and the drug is released from the adhesive layer. This is thought to be easy.

  In order to further enhance this effect, it is preferable to add an acid as a monomer component. In particular, in the case of an organic acid, it is easy to add and dissolve in an adhesive solution containing a drug, and the pH is also in the range of 2.8 to 6.8. It should be mild and mild, and should be acceptable when applied to the skin. Furthermore, monovalent organic acids are preferred for promoting release. Examples of the organic acid include acetic acid, propionic acid, α-hydroxy acid, that is, lactic acid, glycolic acid, salicylic acid, hydroxybutyric acid, and the like.

  Examples of the monomer having a tertiary amine structure include (meth) acrylate having a dialkylamino group and (meth) acrylamide having a dialkylamino group. Examples of the acrylate having a dialkylamino group include dialkylaminoalkyl (meth) acrylate. Examples of acrylamide having a dialkylamino group include dialkylaminoalkyl (meth) acrylamide.

  Examples of the acrylate having a dialkylamino group include dimethylaminoethyl (meth) acrylate, dimethylaminopropyl (meth) acrylate, diethylaminoethyl (meth) acrylate, ethylmethylaminoethyl (meth) acrylate, and the like.

  Examples of acrylamide having a dialkylamino group include dimethylaminoethyl (meth) acrylamide, diethylaminoethyl (meth) acrylamide, dimethylaminopropyl (meth) acrylamide, and diethylaminopropyl (meth) acrylamide.

  When the drug is a compound having a secondary or tertiary amine structure and the precursor monomer of the copolymerized acrylic resin contains a monomer such as acrylic acid, the drug is a carboxyl of the molecular skeleton of the copolymerized acrylic resin. Since it is taken into the acid group to form an ion pair, the release of the drug from the adhesive layer is inhibited.

  Accordingly, by cross-linking the pressure-sensitive adhesive layer comprising a polymer having a tertiary amine structure and having a size that does not dissolve out of the pressure-sensitive adhesive layer with a blocked cross-linking agent, a large amount of a drug or a solubilizing agent is contained. It can be expected that a medical adhesive patch that forms a flexible adhesive layer that does not lose shape or remain adhesive and that the drug is smoothly released from the adhesive layer. For this purpose, it is effective to use blocked isocyanate as a crosslinking agent.

  However, in the medical patch having such a structure, even if a medicine composed of a compound having a secondary or tertiary amine structure is released well into an aqueous methanol solution, the skin environment (pH ), The release of the drug from the adhesive layer to the inside of the skin is performed very smoothly, that is, the amount of the drug released from the adhesive layer to the inside of the skin is not always large.

  In view of this point, the inventors of the present invention can reduce the amount of drug released from the adhesive layer into the skin by using a drug having a solubility in a phosphate buffer (pH 6.4) of 0.5% by weight or more. The inventors found that the amount of the material was extremely large and reached the present invention.

  Examples of the drug having a tertiary amine structure used in the present invention and having a solubility in a phosphate buffer (pH 6.4) of 0.5% by weight or more include risperidone, haloperidol, paliperidone, olanzapine, lonacene, on Examples include dansetron, domperidone, granisetron hydrochloride, indisetron hydrochloride, tropisetron hydrochloride, ramosetron hydrochloride, methylphenidate hydrochloride, ropinirole hydrochloride, and talipexol hydrochloride. Table 1 shows the solubility of various drugs in phosphate buffer (pH 6.4). This solubility is obtained by dissolving the drug in a 1.1-fold mol of lactic acid-added aqueous solution (concentration: 0.1% by weight) and then dropping it into a phosphate buffer solution (pH 6.4). It calculated from the dripping amount at the time of being recognized that it started.

  In addition, a blocking agent is used for preparation of the blocked isocyanate used for this invention. The blocking agent refers to a low molecular weight compound that is temporarily reacted with an isocyanate group in the isocyanate in order to prevent the isocyanate from reacting at room temperature. Generally, the blocking agent is released from the isocyanate group under heating.

  Specific examples of isocyanates that can be used to prepare the blocked isocyanate include trimethylene diisocyanate, tetramethylene diisocyanate, pentamethylene diisocyanate, hexamethylene diisocyanate, 1,2-propylene diisocyanate, 1,2-butylene diisocyanate, Aliphatic compounds such as 2,3-butylene diisocyanate, 1,3-butylene diisocyanate, ethylidene diisocyanate, butylidene diisocyanate, aliphatic cyclic compounds such as 1,3-cyclopentane diisocyanate, m-phenylene diisocyanate, p-phenylene diisocyanate Aromatic compounds such as tolylene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate, 4,4'-toluidine diiso Aneto, 1,4 aliphatic such as xylene diisocyanate - aromatics, dianisidine diisocyanate, nucleus-substituted aromatic compounds such as chloro diphenyl diisocyanate.

  Examples of the blocking agent include phenol blocking agents such as phenol and cresol, lactam blocking agents such as ε-caprolactam, acetanilide, ε-caprolactam and γ-butyrolactam, dimethyl malonate, dibutyl malonate, methyl acetoacetate, aceto Active methylene blocking agents such as ethyl acetate, alcohol blocking agents such as methanol, ethanol, propanol, butanol, amyl alcohol, ethylene glycol monomethyl ether, formaldoxime, acetoaldoxime, acetoxime, methyl ethyl ketoxime, methyl isobutyl ketoxime, Oxime-based blocking agents such as diethyl ketoxime, cyclohexanone oxime, diacetyl monooxime, benzophenone oxime, butyl mercaptan, etc. Lucaptan block agent, acid amide block agent such as acetic acid amide, pyrazole block agent such as 3,5-dimethylpyrazole, imide block agent such as succinimide and maleic imide, urea block agent, M-phenyl Examples thereof include carbamic acid blocking agents such as phenyl carbamate, amine blocking agents such as diphenylamine and aniline, and imine blocking agents such as ethyleneimine and polyethyleneimine.

  Since the medical patch of the present invention contains a drug, it is not suitable for heating at a very high temperature. Therefore, a blocking agent that breaks the block in the range of 80 to 120 ° C. and participates in a crosslinking reaction is suitable. A blocking agent using dibutyl malonate is particularly suitable.

  After the polymer used in the present invention, it reacts with a normal crosslinking agent to form a (meth) acrylic acid ester monomer having no functional group capable of forming a crosslink, such as an alkyl (meth) acrylate or an alkoxyalkyl ( Examples include meth) acrylates and acrylates having a dialkylamino group.

  As this alkyl (meth) acrylate, a medical patch in which an ester of an aliphatic alcohol having 4 to 10 carbon atoms and acrylic acid contains a large amount of a drug or a solubilizing agent to form a flexible adhesive layer. It is preferable in obtaining. For example, methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, isobutyl (meth) acrylate, pentyl (meth) acrylate, hexyl (meth) acrylate, heptyl (meth) acrylate, isooctyl (meth) acrylate, 2 -Ethylhexyl acrylate, nonyl (meth) acrylate, decyl (meth) acrylate, isodecyl (meth) acrylate, lauryl acrylate, and the like. These monomers may be used independently and may use 2 or more types together.

  The proportion of the monomer having a Tg (glass transition temperature) such as an alkyl (meth) acrylate of 0 ° C. or less with respect to the entire copolymerized acrylic resin is 40 to 90% by weight. It is preferable for obtaining a medical patch that forms a flexible adhesive layer because it is contained and exhibits adhesiveness.

  As the alkoxyalkyl acrylate, those having an alkoxyalkyl group having 2 to 8 carbon atoms in the ester group portion are preferable, and examples include methoxymethyl acrylate, ethoxymethyl acrylate, methoxyethyl acrylate, ethoxyethyl acrylate, butoxyethyl acrylate, and propoxyethyl acrylate. Is done. Of these, methoxyalkyl acrylate or ethoxyalkyl acrylate is preferable for obtaining a medical patch that contains a large amount of a drug and a solubilizing agent and forms a flexible adhesive layer that does not lose its shape or remain glue.

  The proportion of monomers such as alkoxyalkyl acrylates that have a functional group capable of forming a cross-link by reacting with a normal cross-linking agent after becoming a polymer and having a Tg of room temperature (25 ° C.) or less is And 0 to 40% by weight in the polymer to obtain a medical patch containing a large amount of a drug and a solubilizing agent and improving water vapor permeability and forming a flexible adhesive layer that does not lose its shape or remain unglue. In addition, it is preferable.

  Examples of the vinyl monomer having a functional group capable of forming a crosslink by reacting with a crosslinking agent having an isocyanate group after becoming a polymer used in the present invention include a hydroxyl group-containing vinyl monomer and an amide group-containing vinyl monomer. . Among them, a hydroxyl group-containing vinyl monomer and an amine-containing vinyl monomer are preferable for obtaining a medical patch that contains a large amount of a drug and a solubilizing agent and forms a flexible adhesive layer that does not lose its shape or remain glue.

  Examples of the vinyl monomer containing an amide group include dimethylaminoethyl (meth) acrylamide and dimethylaminopropyl (meth) acrylamide.

  As the hydroxyl group-containing vinyl monomer, hydroxyalkyl acrylate is preferable for containing a chemical solution to obtain a flexible crosslinked polymer. As hydroxyalkyl acrylate, hydroxyethyl acrylate; methyl 2- (hydroxymethyl) acrylate, ethyl 2- (hydroxymethyl) acrylate, n-butyl 2- (hydroxymethyl) acrylate, tert-butyl 2- (hydroxymethyl) acrylate, 2-ethylhexyl alkyl 2- (hydroxymethyl) acrylates such as 2- (hydroxymethyl) acrylate and cyclohexyl 2- (hydroxymethyl) acrylate; methyl 2- (1-hydroxyethyl) acrylate, ethyl 2- (1-hydroxyethyl) ) Acrylate, n-butyl 2- (1-hydroxyethyl) acrylate, methyl 2- (1-hydroxybutyl) acrylate, ethyl 2- (1-hydroxybutyl) acrylate N-butyl 2- (1-hydroxybutyl) acrylate, methyl 2- (1-hydroxybenzyl) acrylate, ethyl 2- (1-hydroxybenzyl) acrylate, n-butyl 2- (1-hydroxybenzyl) acrylate, etc. Alkyl 2- (1-hydroxy-1-alkylmethyl) acrylate, 2-hydroxypropyl acrylate, 3-hydroxypropyl methacrylates, 4-hydroxybutyl methacrylate, diethylene glycol monomethacrylate, 2,3-dihydroxypropyl methacrylate, 2-methacryloxy Examples include ethyl glycoside. Moreover, it can also select from the acrylamide monomer which has these hydroxyacryl groups.

  The vinyl monomer having such a functional group contributes to the formation of a crosslink by blocked isocyanate.

  These vinyl monomers having a functional group can be used alone or in combination of two or more.

  The copolymerization ratio of the vinyl monomer having such a functional group in the copolymerized acrylic resin is 0.5 to 30% by weight based on the entire copolymer, and contains a large amount of a drug and a solubilizing agent. Therefore, it is preferable for obtaining a medical patch that forms a flexible adhesive layer that does not lose its shape or remain adhesive.

  Of these, the content of the monomer having a hydroxy group is preferably 0.5 to 20% by weight. If it is 0.1% by weight or less, the crosslinking density is low, and in a system containing many liquid components, the cohesive force is insufficient and adhesive residue is generated.

  As a monomer for the copolymerized acrylic resin, a hydrophobic monomer such as 2-ethylhexyl acrylate and a hydrophilic monomer such as hydroxyalkyl acrylate are used to make the hydrophilicity of the adhesive layer balanced. However, if the monomer having a hydroxyl group is excessive, the cohesiveness is high, and after polymerization, there is a possibility of dehydration and gelation. Therefore, as the copolymerized acrylic resin used in the composition of the present invention, 40 to 90 parts by weight of an acrylate ester of a group alcohol (C4-10), 0.5 to 20 parts by weight of dimethylaminoalkyl (meth) acrylate or dimethylaminoalkyl (meth) acrylamide (the alkyl chain is C1-4), Hydroxyalkyl acrylate (alkyl chain is C1-4) or hydroxyalkyl acrylamide (alkyl The chain is obtained by copolymerizing C1-4) with 0.5 to 20 parts by weight, and forms a proper cross-link and contains a large amount of solubilizing agents such as fatty acid esters, α-hydroxy acids and polyhydric alcohols. It is more preferable to obtain a medical patch that retains the medicine contained in the composition and forms a flexible adhesive layer that does not lose its shape or remain glue.

In addition, as a copolymer acrylic resin used in the composition of the present invention,
40 to 80 parts by weight of an acrylic ester of a fatty alcohol (C4-10),
1 to 20 parts by weight of dimethylaminoalkyl (meth) acrylate or dimethylaminoalkyl (meth) acrylamide,
1 to 20 parts by weight of hydroxyalkyl acrylate or hydroxyalkyl acrylamide,
In order to obtain a medical patch that forms a flexible adhesive layer that retains a drug containing a large amount of a solubilizing agent and that does not lose its shape or remain glue, preferable.

  Furthermore, as the copolymerized acrylic resin used in the composition of the present invention, the copolymerized acrylic resin may further contain 10 to 40 parts by weight of methoxyalkyl acrylate or ethoxyalkyl acrylate as a monomer component. It is most preferable to obtain a medical patch that retains a drug containing a large amount of a solubilizing agent and forms a flexible adhesive layer that does not lose its shape or remain unglue.

Moreover, as copolymerization acrylic resin used for the composition of this invention, the component ratio of the monomer main component of this copolymerization acrylic resin is alkyl (meth) acrylate ... 55-70 weight part alkoxy alkyl acrylate ... 20 to 30 parts by weight hydroxyalkyl acrylamide ·· 3 to 10 parts by weight dialkylaminoalkyl methacrylate ················································ Therefore, it is preferable to form a flexible adhesive layer that does not lose its shape or remain as a paste and to obtain a medical patch excellent in drug release. In particular, when hydroxyethyl acrylamide is added, even if a large amount of liquid additive is added in an amount of about 5 to 50% by weight as in the present invention, the cohesiveness is higher than when hydroxyethyl acrylate is used instead of hydroxyethyl acrylamide. It has also been found to increase, adhere to the skin and increase skin adhesion.

  In addition to the above-described components, the copolymerized acrylic resin can further contain a monomer component that can be contained as another monomer. Examples of such components include vinyl esters such as vinyl acetate, unsaturated nitriles such as acrylonitrile, vinyl aromatic compounds such as styrene, and the like.

  In another embodiment of the present invention, a copolymer of two or more acrylic monomers having no tertiary amino group and no carboxylic acid group that can be an adhesive having an OH group (copolymer A) 3 consisting of a copolymer (copolymer B) of a monomer having a tertiary amino group having a molecular weight of 3000 to 100,000, preferably 3000 to 30,000, and one or more (meth) acrylic acid esters. A polymer having a secondary amino group is added, a chemical having a secondary or tertiary amine is added, and the blocked agent is released from the isocyanate group under heating using the blocked isocyanate as a crosslinking agent. To form a composition for forming the medical patch of the present invention. .

  When the molecular weight (weight average molecular weight) of the copolymer B is 3000 to 30000, the ratio of the copolymer B to the copolymer A is 1 to 40% by weight. It is preferable for obtaining a medical patch that is held and forms a flexible adhesive layer that does not lose its shape or remain glue.

  In addition, the presence of a monomer having a tertiary amine in the adhesive or resin that is a polymer provides high drug release, and the monomer having a tertiary amine contains an additive. It is preferable that 4 to 100 mmol is contained per 100 g of the pressure-sensitive adhesive composition.

  The excellent characteristics of the adhesive layer can be obtained by crosslinking with a blocked crosslinking agent. When the molecular weight (weight average molecular weight) of the copolymer B is 3000 to 30000, 0.2 to 8 parts by weight of the blocked crosslinking agent is used with respect to 100 parts by weight of the copolymer (A + B). Is preferred. More preferably, 1.4 to 10 parts by weight are used.

  When the molecular weight (weight average molecular weight) of the copolymer B is 30,000 to 800,000, the ratio of the copolymer B to the copolymer A is 0.5 to 30% by weight, which contains a large amount of solubilizer. It is preferable for obtaining a medical patch that retains the drug and forms a flexible adhesive layer that does not lose its shape or remain glue. When the molecular weight (weight average molecular weight) of the copolymer B is 30,000 to 800,000, the blocked crosslinking agent is preferably used in an amount of 0.2 to 8 parts by weight with respect to 100 parts by weight of the copolymer (A + B). . More preferably, 0.5 to 8 parts by weight are used.

  Examples of the acrylic monomer having no tertiary amino group and having no carboxylic acid group, which are components of the copolymer A, include, for example, an acrylic ester having an alkyl chain having 10 or less carbon atoms, methoxyethyl acrylate, ethoxyethyl acrylate, Examples thereof include alkoxyalkyl (meth) acrylates having an alkoxy group having 4 or less carbon atoms in the alkyl chain, such as butoxyethyl acrylate.

  Furthermore, at least one of the monomers that are the components of the copolymer A is a monomer having a hydroxy group. Examples of this monomer include hydroxyalkyl (meth) acrylamides such as hydroxyethylacrylamide, and hydroxyalkyl (meth) acrylates such as hydroxyethyl acrylate, hydroxybutyl acrylate, hydroxyethyl methacrylate, and hydroxybutyl methacrylate.

  Examples of the monomer having a tertiary amino group, which is a component of the copolymer B, include acrylates having a dialkylamino group such as dialkylaminoalkyl (meth) acrylate. Examples thereof include dimethylaminoethyl (meth) acrylate and dimethylaminopropyl (meth) acrylate.

  Examples of the copolymer B include a (meth) acrylic acid ester having 4 to 10 carbon atoms or a (meth) acrylic acid ester having an alkoxy group having 4 to 10 carbon atoms and a dialkylaminoalkyl (meth) acrylate. A polymer is mentioned. Specific examples thereof include butyl methacrylate, dimethylaminoethyl acrylate methacrylate and methyl methacrylate copolymer, 2-ethylhexyl acrylate and methoxyethyl acrylate, dimethylaminoethyl acrylate and hydroxyethyl acrylamide copolymer. , Etc.

  The liquid auxiliaries for drugs used in the present invention can contain auxiliaries and additives such as solubilizers, absorption promoters, penetrants and stabilizers as components. It is preferable that about 10 to 50% by weight of the liquid auxiliary agent for medicine is contained in the composition of the present invention.

  Examples of solubilizers include polyhydric alcohols such as polyethylene glycol, propylene glycol, butylene glycol, and glycerin, isopropyl fatty acid esters such as isopropyl myristate and isopropyl palmitate, and diol compounds. Any sugar-fatty acid ester such as glycol / propylene glycol fatty acid ester or sorbitan fatty acid ester, fatty acid, higher alcohol, DMSO or the like can be used as long as it aids dissolution of a drug used in a pharmaceutically acceptable compound. The diol compound is preferably at least one of butanediol and propanediol. For example, 1-30% by weight of a solubilizer is added to the adhesive layer.

  Absorption accelerators include diethyl sebacate, crotamiton, α-hydroxy acid lactic acid, salicylic acid, glycolic acid, etc., or ethyl pyruvate, ethyl glycolate, triethyl citrate, ethyl resorcinate, ethyl retinoate, ethyl salicylate, malonic acid Examples include ethyl, ethyl acetate, and the like. Examples of the surfactant include polysorbate, lauric acid diethanolamide, lauroyl sarcosine, polyoxyethylene alkyl ether, and polyoxyethylene alkylamine.

  Examples of penetrants include organic acids. Examples of the stabilizer include antioxidants such as vitamin C as an antioxidant and derivatives thereof, butylhydroxytoluene, tocopherol, and tocopherol acetate, and pharmaceutically acceptable ones are used.

  If necessary, the solubilizing agent may be added with acid or alkali to adjust the stability and release of the drug.

  Note that the amount of drug released from the adhesive layer into the skin is extremely increased by using the medical patch of the present invention. However, depending on the purpose, the medical patch adjusts the amount of drug released to a predetermined level. Sometimes it is better. That is, it may be necessary to impart sustained release properties. The medical patch of the present invention can control the release amount of the medicine to a predetermined degree by interposing a nonionic acrylic resin layer such as copolymer B between the adhesive layer and the skin. . This control is achieved by providing a layer (protective layer 8) made of nonionic acrylic resin on the surface of the adhesive layer 2 as shown in FIG.

  Since the medical patch of the present invention has an extremely large amount of drug released from the adhesive layer 2 into the skin from the beginning, a protective layer 8 made of a nonionic acrylic resin is provided on the upper surface of the adhesive layer 2 to provide a composite medical patch 6b. Nonetheless, by adjusting the thickness d, the drug release amount can be selected and controlled from a wide range of values. Usually, the composite medical patch 6b is used as a patch preparation 6b with the lower surface of the adhesive layer 2 supported by the support 4. When the protective layer 8 is directly applied to the skin, the protective layer 8 itself needs to have sufficient adhesiveness, and the example illustrated has sufficient adhesiveness. If necessary for controlling the permeability of the drug, a solubilizing agent can be added, or the drug can be added at a saturation level. It is preferable to add a drug to the permeation control membrane at a saturation level because no time delay occurs with respect to permeation into the skin.

  The thickness d of the nonionic acrylic resin layer is preferably adjusted in the range of 1 to 20 μm.

  Also, the amount of drug released can be controlled by changing the content ratio of nonionic acrylic resin mixed in the adhesive layer using a mixture of two or more types of copolymers as the resin constituting the adhesive layer. Can do. When the mixing ratio of the nonionic acrylic resin mixed in the adhesive layer increases, the drug release rate becomes slow. The copolymer mixed in the adhesive layer together with the nonionic acrylic resin includes an acrylic monomer having a tertiary amino group and an acrylic monomer having no carboxylic acid group and having an OH group, such as the copolymer A described above. A copolymer of two or more kinds of acrylic monomers may be mentioned.

  Furthermore, since the nonionic acrylic resin suitably used in the present invention has a molecular weight of about 200,000 to 800,000, when mixed with an acrylic resin having a relatively low molecular weight such as the above-mentioned copolymer A, the nonionic acrylic resin Compared to the case where no resin is used, the amount of the necessary crosslinking agent can be reduced and a more stable pressure-sensitive adhesive can be obtained.

  The nonionic acrylic resin preferably has a glass transition temperature (Tg) of 10 ° C. or lower. Copolymer of alkyl (meth) acrylate, alkoxyalkyl acrylate and hydroxyalkyl acrylamide, Copolymer of alkyl (meth) acrylate and vinyl hydroxyalkyl acrylamide, alkyl (meth) acrylate, N-vinylpyrrolidone and hydroxyalkyl acrylate And a copolymer of alkyl (meth) acrylate and hydroxyalkyl acrylamide. Specific examples include copolymers comprising 60 to 80 parts of 2-ethylhexyl acrylate, 20 to 30 parts of methoxyethyl acrylate, and 5 to 10 parts of hydroxyethyl acrylamide.

  The support (4) used in the medical patch of the present invention is preferably flexible and stretchable in that it follows the curved shape of the human body and the movement of the human body when it is applied. However, a film made of a material that swells with an auxiliary agent contained in a medical patch, such as a urethane film, dissolves the auxiliary agent and the drug, and cannot keep the drug only in the adhesive layer. Thereby, since the chemical | medical agent density | concentration of an adhesion layer falls, it brings about the fall of the discharge | release speed | rate and release rate of a chemical | medical agent. Further, the auxiliary component dissolves in the support film, causing deformation such as swelling and wrinkles, and it is difficult to maintain the shape not only during use but also during storage.

  From this point, as the material for the film, a polyester resin, a polyamide resin, a polyolefin resin, a vinyl acetate (EVA) resin, or the like is preferable. Moreover, it is preferable to use a film having a thickness of 5 to 40 μm and a tensile elastic modulus of 10,000 MPa or less as the support. As the support, it is more preferable to use a laminated sheet in which a cloth is laminated, because both the strength and flexibility of the support are compatible. As the support, it is more preferable to use a laminated sheet obtained by laminating a cloth on a film having a thickness of 5 to 30 μm because both the strength, flexibility and handleability of the support are compatible. As a film used for a laminated sheet laminated with a cloth, a film having a tensile elastic modulus of 0.5 to 200 MPa and a thickness of 5 to 30 μm is preferable. Examples of such a film material include polyolefin elastomers, polyester elastomers, and acrylic elastomers.

  As the fabric for laminating, a knitted fabric or a non-woven fabric is preferable. Examples of the nonwoven fabric material include polyester fibers, polyolefin fibers, polyamide fibers, and polyvinyl alcohol fibers. The nonwoven fabric for lamination is most preferably a stretch nonwoven fabric. The stretchable nonwoven fabric is a nonwoven fabric in which the structural fibers are entangled three-dimensionally, for example, by hydroentanglement or the like, or a nonwoven fabric composed of elastic fibers having a tensile modulus of 500 MPa or less.

Test method

Adhesive A small piece of test piece tape cut to 20x70mm is wrapped around a finger after removing the release sheet, and when the state of application is checked at 24 hours, 80% or more does not peel off and adheres firmly. The time was ○, and the time below was ×.

Adhesive residue After the tape test, the tape is peeled to the extent that there is almost no discomfort and the stickiness is almost unnoticeable. When it was completed, it was marked as ◎, and when it was worrisome, it was marked as x.

A sample having a thickness of 60 μm was prepared, punched out into a 15 mmφ disk, and the sample surface (adhesive surface) was brought into contact with a phosphate buffer (pH 6.4, 20 ml), while shaking at 32 ° C., The amount of drug that began to dissolve was measured by liquid chromatography. Measurement was performed using samples sampled at appropriate time intervals from the start, and the ratio between the initial content of the drug and the cumulative release amount was calculated as the cumulative release rate ((cumulative release amount of drug from the phosphate buffer / The initial content in the drug sample) × 100 (%)). The initial content of the drug was determined by punching out a 15 mmφ sample from the vicinity of the sample piece used for the release test, and immersing it in methanol and extracting it. The initial drug content was measured by liquid chromatography under the same conditions as the release test.

Skin Permeability Hairless rat skin is peeled off, a sample punched out at 22 mmφ is pasted on the punched 25 mmφ skin surface, set in Franz cell (effective release area: 20 mmφ), and the receiving solution is phosphate buffered saline The drug that filled (PBS) and dissolved into the receiving PBS solution from the tape through the skin at 32 ° C. was measured by liquid chromatography to determine the cumulative amount of skin permeation (release amount).

Reference example 1
As acrylic monomers, 68 parts by weight of 2-ethylhexyl acrylate, 20 parts by weight of methoxyethyl acrylate, 7 parts by weight of hydroxyethyl acrylamide and 5 parts by weight of dimethylaminoethyl methacrylate were added in ethyl acetate under nitrogen gas at around 60-65 ° C. An adhesive polymer (A) having a tertiary amine was obtained by polymerization at a controlled temperature. Separately, a mixed solution is prepared by adding risperidone (6 parts by weight) to a mixed solution of IPM (isopropyl myristate) (15 parts by weight), butanediol (10 parts by weight), and a lactic acid solution (5 parts by weight). Then, a small amount of ethanol (external number) was added as necessary and mixed uniformly, and then the polymer (A) (5 parts by weight) was dissolved in this mixed solution. Furthermore, blocked isocyanate (1.5 parts by weight) and antioxidant (0.05 parts by weight) were added, mixed uniformly, degassed and cast, then dried at 98 ° C., and a thickness of 60 μm A layer sheet was obtained. This adhesive layer sheet was bonded to a polyester support to obtain a tape-type plaster.
(Note that, in the above Reference Example 1, various parts when obtaining an adhesive layer sheet using the polymer (A) and parts by weight described to represent the blending ratio of various monomers when obtaining the polymer (A). (It is irrelevant to the parts by weight described to express the compounding ratio of the compound. This also applies to the following examples and reference examples. )

  As a result of measuring the release property, the cumulative release rate after 6 hours from the start of measurement was 88%.

Reference example 2
Instead of the polymer (A) used in Reference Example 1, as an acrylic monomer, 68 parts by weight of 2-ethylhexyl acrylate, 25 parts by weight of methoxyethyl acrylate, and 7 parts by weight of hydroxyethyl acrylamide were added in ethyl acetate under nitrogen gas. Thus, an adhesive polymer (B) obtained by polymerization at a temperature of around 60-65 ° C. was used. Further, a tape-type plaster was obtained in the same manner as in Reference Example 1 except that the ratio of blocked isocyanate was (0.8 parts by weight).

As a result of measuring the release properties, the cumulative release rate after 6 hours from the start of the measurement was 40%.

Example 1
Instead of the polymer (A) used in Reference Example 1, an equivalent amount of the polymer (A) and the polymer (B) was used. Further, a tape-type plaster was obtained in the same manner as in Reference Example 1 except that the ratio of blocked isocyanate was (1.2 parts by weight).

  As a result of measuring the release property, the cumulative release rate 6 hours after the start of the measurement was 88.6%.

Example 2
Instead of the polymer (A) used in Reference Example 1, a polymer (A) and polymer (B) combined at 1: 4 (weight ratio) was used. Further, a tape-type plaster was obtained in the same manner as in Reference Example 1 except that the ratio of blocked isocyanate was (1.0 part by weight).

  As a result of measuring the release property, the cumulative release rate 6 hours after the start of the measurement was 58.3%.

Example 3
Instead of the polymer (A) used in Reference Example 1, a polymer containing a tertiary amine (dimethylaminoethyl methacrylate, methyl methacrylate and butyl methacrylate copolymer (trade name: Eudragid) and polymer (B) A tape-type plaster was obtained in the same manner as in Reference Example 1 except that the ratio of blocked isocyanate was changed to (0.1 part by weight). .

As a result of measuring the release properties, the cumulative release rate after 6 hours from the start of the measurement was 93%.

Reference example 3
A tape-type plaster was obtained in the same manner as in Reference Example 1 except that ondansetron was used as the drug.

Table 2 shows the test results of adhesiveness and adhesive residue of the tape-type plaster obtained in each of Examples 1 to 3 and Reference Examples 1 to 3 .

Comparative Example 1
Instead of polymer used in Reference Example 1 (A), 2-ethylhexyl acrylate 93 parts, except for using the pressure-sensitive adhesive obtained by polymerizing in the same manner as in Reference Example 1 7 parts acrylic acid Reference Example 1 A tape-type plaster was obtained in the same manner.

As a result of measuring the release properties, the cumulative release rate after 6 hours from the start of the measurement was 15%.

Comparative Example 2
Instead of polymer used in Reference Example 1 (A), 65 parts of 2-ethylhexyl acrylate, in addition to the 35 parts of vinyl acetate using the pressure-sensitive adhesive obtained by polymerizing in the same manner as in Reference Example 1 in ethyl acetate A tape-type plaster was obtained in the same manner as in Reference Example 1. This tape-type paste did not become a sticky paste. Since there was no cross-linking point, the cross-linking reaction did not occur with the pressure-sensitive adhesive polymer that was the reaction partner of the isocyanate that appeared after deblocking, and no cohesive force could be produced because many additives were added.

Comparative Example 3
Instead of the blocked isocyanate used in Reference Example 1, an attempt was made to obtain a tape-type plaster in the same manner as in Reference Example 1, except that TDI-based isocyanate (Coronate L, manufactured by Nippon Polyurethane) was used as a crosslinking agent. At the stage of adding the cross-linking agent, the reaction started shortly after the start of stirring, gelled, solidified and could not be applied thinly.

Comparative Example 4
A tape-type plaster was obtained in the same manner as in Reference Example 1 except that terbinafine was used as a drug instead of risperidone used in Reference Example 1. Although the release was measured, no drug release into the phosphate buffer (pH 6.4) was detected even after 48 hours from the start of the measurement.

FIG. 3 shows the measurement results of the drug release properties from the sample to the phosphate buffer for each of Examples 1 to 3 , Reference Example 1 and Reference Example 2, and Comparative Example 4. In the examples or reference examples using risperidone as a drug, the drug solution is released into the phosphate buffer over time, whereas in Comparative Example 4 using terbinafine as the drug, Even with time, the drug solution was hardly released into the phosphate buffer.

Moreover, when the adhesion layer does not contain a nonionic acrylic resin (resin B) ( Reference Example 1) and when the acrylic resin constituting the adhesion layer contains a nonionic acrylic resin (resin B) (Example 1) In addition , when compared with Example 2 and Reference Example 2 ), the latter has a smaller degree of drug release than the former, and the degree of drug release increases as the content of nonionic acrylic resin (resin B) increases. I found it smaller.

Measurement Results of Skin Permeability FIG. 4 shows the measurement results of skin permeability of risperidone from samples for each of Reference Example 1, Example 2 and Example 3 . For all of Reference Example 1 and Examples 2 and 3 , the results showed that the skin permeability of risperidone was good.

Example 4
After laminating a protective film having a thickness of 10 μm made of the polymer (B) obtained in Reference Example 2 on one side of the pressure-sensitive adhesive layer sheet obtained in Reference Example 3 , a polyester support is placed on the side of the pressure-sensitive adhesive layer sheet. The tape type plaster body with a protective film was obtained by bonding. The release property of the tape-type plaster with a protective film was measured. The measurement was performed such that the protective film side was in contact with the phosphate buffer.

FIG. 5 shows the measurement results of the release properties of the tape-type paste with protective film obtained in Example 4 together with the measurement results of the tape-type paste obtained in Reference Example 3 . It was found that the release of the chemical solution can be adjusted by providing a protective film.

Reference example 4
An adhesive layer sheet was obtained in the same manner as in Reference Example 1 . However, the thickness of the adhesive layer sheet obtained by casting was 50 μm. A laminate comprising a polyester elastomer (1.7 dtex) and a nonwoven fabric (20 g / m ² basis weight) laminated to a film (thickness 30 μm) made of a polyolefin elastomer (tensile elastic modulus 2 MPa) is used as a support. The film side of this support was put together and thermocompression bonded. Even after storage at 50 ° C. for one month, no elongation or wrinkle due to swelling of the support was observed. Further, it was flexible when applied to the skin, and could be easily handled and applied without a hard carrier layer on the surface.

Comparative Example 5
An adhesive layer sheet was obtained in the same manner as in Reference Example 4 . When a 30 μm-thick urethane film was bonded to this as a support and stored in the same manner, the components of the adhesive layer transferred to the film on the third day, and the urethane film swelled and wrinkled.

  The present invention can be widely applied to medical patches. There are many compounds with secondary and tertiary amines in pharmaceuticals, and in the aging society, in addition to swallowing drugs and injections, the present invention is applied as a third route of administration from the skin to the skin. It is easy to administer, and unlike oral and injection, it can be used for a long time and can maintain blood concentration stably for a long time. It will be applied.

The nonionic acrylic resin preferably has a glass transition temperature (Tg) of 10 ° C. or lower. Copolymer of alkyl (meth) acrylate, alkoxyalkyl acrylate and hydroxyalkyl acrylamide, Copolymer of alkyl (meth) acrylate, vinyl acetate and hydroxyalkyl acrylamide, alkyl (meth) acrylate, N-vinylpyrrolidone and hydroxyalkyl Examples thereof include a copolymer of acrylate and a copolymer of alkyl (meth) acrylate and hydroxyalkyl acrylamide. Specific examples include copolymers comprising 60 to 80 parts of 2-ethylhexyl acrylate, 20 to 30 parts of methoxyethyl acrylate, and 5 to 10 parts of hydroxyethyl acrylamide.

Claims (8)

A drug having a tertiary amine structure in the molecule,
Liquid auxiliaries for drugs,
A copolymer acrylic resin having a (meth) acrylic acid ester monomer as a main component and having a functional group capable of forming a crosslink by reacting with an isocyanate group crosslinker has a tertiary amine structure in the molecule. A resin composition comprising a monomer having a monomer component and crosslinked with a blocked crosslinking agent having the isocyanate group;
A medical patch comprising
The solubility of the drug in a phosphate buffer (pH 6.4) is 0.5% by weight or more,
The copolymerized acrylic resin is a mixture of an acrylic monomer having a tertiary amino group and a copolymer of two or more acrylic monomers including an acrylic monomer having no carboxylic acid group and having an OH group, and a nonionic acrylic resin. A medical patch characterized by being made . In the copolymerized acrylic resin, the weight ratio of the copolymer of the two or more acrylic monomers and the nonionic acrylic resin (weight of the copolymer of the two or more acrylic monomers: weight of the nonionic acrylic resin) ) Is from 1: 1 to 1: 4. The medical patch according to claim 1. The nonionic acrylic resin is a copolymer of an alkyl (meth) acrylate, an alkoxyalkyl acrylate and a hydroxyalkyl acrylamide, a copolymer of an alkyl (meth) acrylate and a vinyl hydroxyalkyl acrylamide, an alkyl (meth) acrylate, 2. A copolymer selected from the group consisting of a copolymer of N-vinylpyrrolidone and hydroxyalkyl acrylate, and a copolymer of alkyl (meth) acrylate and hydroxyalkyl acrylamide. The medical patch according to claim 2. The medical patch according to any one of claims 1 to 3, wherein the nonionic acrylic resin is a copolymer composed of 2-ethylhexyl acrylate, methoxyethyl acrylate, and hydroxyethyl acrylamide. 5. The drug according to claim 1, wherein the drug is any one drug selected from the group consisting of risperidone, haloperidol, paliperidone, olanzapine, lonacene, and ondansetron. Medical patch. A drug having a secondary or tertiary amine structure in the molecule,
Liquid auxiliaries for drugs,
And a copolymer acrylic resin having a functional group capable of forming a crosslink by reacting with a crosslinking agent having an isocyanate group, the main component of which is a (meth) acrylic acid ester monomer, is a tertiary amine in the molecule. A resin composition comprising a monomer having a structure as a monomer component and crosslinked by the blocked crosslinking agent having an isocyanate group
Comprising
A medical patch in which the solubility of the drug in a phosphate buffer (pH 6.4) is 0.5% by weight or more,
In order, a layer of nonionic acrylic resin,
An adhesive layer comprising the medical patch ;
With
A composite medical patch, wherein the nonionic acrylic resin layer faces the skin when applied to the skin. The composite medical patch according to claim 6 , wherein the drug is any one drug selected from the group consisting of risperidone, haloperidol, paliperidone, olanzapine, lonacene, and ondansetron. A drug having a secondary or tertiary amine structure in the molecule,
Liquid auxiliaries for drugs,
And a copolymer acrylic resin having a functional group capable of forming a crosslink by reacting with a crosslinking agent having an isocyanate group, the main component of which is a (meth) acrylic acid ester monomer, is a tertiary amine in the molecule. A resin composition comprising a monomer having a structure as a monomer component and crosslinked by the blocked crosslinking agent having an isocyanate group
Comprising
A medical patch in which the solubility of the drug in a phosphate buffer (pH 6.4) is 0.5% by weight or more,
In order, a layer of nonionic acrylic resin,
An adhesive layer comprising the medical patch ;
A support that supports the adhesive layer ;
Patch preparation according to claim Rukoto equipped with.

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