JP2016013993A - Patch and patch preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a patch and a patch preparation having excellent flexibility and water resistance, and capable of preventing the effusion of oily additive even when using it.SOLUTION: A patch and a patch preparation according to the present invention comprise a support that comprises a support film comprising urethane resin and a barrier layer comprising an ethylene-vinyl alcohol copolymer, and an adhesive layer comprising adhesive. The adhesive layer is disposed at the barrier layer side of the support.

Description

  The present invention relates to a patch and a patch preparation. More specifically, the present invention relates to a patch and a patch preparation comprising a support film comprising a urethane-based resin and a barrier layer comprising an ethylene-vinyl alcohol copolymer, and a pressure-sensitive adhesive layer comprising an adhesive. About.

  As one of pharmaceutical dosage forms, a percutaneous absorption preparation is known in which a drug is administered into the body from the outer skin or mucous membrane. Among the transdermal absorption preparations, the so-called patch-type transdermal absorption preparation, which contains a transdermal drug in an adhesive, allows the drug to be easily transdermally administered to the living body, and the dosage is strictly controlled. In recent years, drug development has been actively conducted. A general patch-type transdermal absorption preparation is one in which an adhesive layer containing a drug for percutaneous absorption is formed on one side of a support such as a plastic film or non-woven fabric, and is applied to the outer skin or mucous membrane. It is intended to prevent or treat various diseases by administering a drug for transdermal absorption into the body. Since a transdermally absorbable preparation is used by being attached to the skin or the like, flexibility is required to follow its movement. Moreover, in order to maintain the state which affixed, the characteristic that it is strong also to peeling by moisture, such as sweat, is requested | required.

  In a patch type transdermal absorption preparation, additives such as a transdermal absorption enhancer for promoting the percutaneous absorption of the drug and a drug dissolution aid for improving the solubility of the drug in the adhesive layer are incorporated. To be considered. In addition, in order to reduce skin irritation during application to the skin surface or at the time of peeling, an oily gel-like pressure-sensitive adhesive composition containing a relatively large amount of oily component has been developed. Transdermal absorption enhancers, drug dissolution aids, and oil components for reducing skin irritation are oil-based additives that dissolve in the pressure-sensitive adhesive layer even when liquid or solid at room temperature. Oily additives may be adsorbed to the support during storage of the transdermally absorbable preparation or may exude from the back of the support, and the effect of using the oily additive may not be fully demonstrated in the transdermally absorbed preparation after storage. is there. Moreover, when using an oil-based additive, since the pressure-sensitive adhesive is designed so as to exhibit a desired pressure-sensitive adhesive property in a state where the oil-based additive is blended, the pressure-sensitive adhesive property of the pressure-sensitive adhesive may change.

  In general, as a support for a patch having excellent flexibility, a material mainly composed of polyurethane is used. However, since the support mainly composed of polyurethane tends to adsorb the oil-based additive depending on the type of the oil-based additive, the oil-based additive contained in the pressure-sensitive adhesive layer may ooze out to the back surface of the support. A polyester-based support represented by polyethylene terephthalate having excellent barrier properties is expected to suppress the adsorption of oil-based additives. However, a polyester-based support generally has high rigidity, so that it becomes inflexible when the thickness is increased. As a result, the skin followability when the transdermal absorption preparation is applied to the skin surface is poor, and the uncomfortable feeling during application may increase. As a means for preventing the adsorption of the oil-based additive, Patent Document 1 discloses that a barrier layer containing polyvinyl alcohol and montmorillonite is laminated on one surface of polyurethane. The patch of Patent Document 1 discloses that it is possible to prevent the adsorption of oily components while maintaining the flexibility of the support. However, polyvinyl alcohol is a high water-soluble polymer, and when water is applied during application of the preparation, the support film is peeled off from the pressure-sensitive adhesive layer, and there is a problem in practical use.

International Publication No. 2012/014586 Pamphlet

  The present invention has been made in order to solve the above-described conventional problems. The object of the present invention is to have excellent flexibility and water resistance, and to prevent the exudation even when an oily additive is used. It is to provide a patch and a patch preparation that can be prevented.

  As a result of intensive studies, the present inventors have surprisingly achieved excellent flexibility and water resistance by disposing a barrier layer containing an ethylene-vinyl alcohol copolymer on one side of the support. Even if an oil-based additive is used, the support hardly absorbs the oil-based additive contained in the adhesive layer during storage of the patch, and the oil added to the adhesive layer during patch preparation The inventors have found that the content of the additive can be maintained even during storage, and have completed the present invention.

The patch of the present invention is a patch comprising a support comprising a support film containing a urethane-based resin and a barrier layer containing an ethylene-vinyl alcohol copolymer, and an adhesive layer containing an adhesive, The pressure-sensitive adhesive layer is disposed on the barrier layer side of the support.
In one embodiment, the saponification degree of the ethylene-vinyl alcohol copolymer is 99% to 100%.
In one embodiment, the molar ratio of the ethylene unit of the said ethylene-vinyl alcohol copolymer is 20 mol%-60 mol%.
In one embodiment, the adhesive is an acrylic adhesive.
In one embodiment, the pressure-sensitive adhesive layer further contains an oily additive.
According to another aspect of the present invention, a patch preparation is provided. In the patch preparation of the present invention, the adhesive layer further contains a drug in the patch.
In one embodiment, the drug has an octanol / water partition coefficient of -1 to 5.

  The patch of the present invention has a barrier layer in which the support contains an ethylene-vinyl alcohol copolymer. Therefore, even when an oily additive (for example, fatty acid alkyl ester or fatty acid glyceryl ester) is added to the pressure-sensitive adhesive layer, the oily additive does not adsorb and migrate to the support during storage of the patch. The content of the oily additive in the pressure-sensitive adhesive layer can be maintained. Therefore, even when the patch of the present invention is stored, the adhesive properties of the pressure-sensitive adhesive layer can be maintained. When the pressure-sensitive adhesive layer is a patch preparation further containing a drug, the desired transdermal absorbability can be obtained. It can be demonstrated. Furthermore, since the patch of the present invention is excellent in flexibility and water resistance, a patch having an excellent feeling of use can be provided.

1 is a schematic cross-sectional view of a patch according to a preferred embodiment of the present invention.

  FIG. 1 is a schematic cross-sectional view of a patch according to one embodiment of the present invention. The patch 100 includes a support 10 and an adhesive layer 20. The support 10 has a support film 11 containing a urethane resin and a barrier layer 12 containing an ethylene-vinyl alcohol copolymer. The pressure-sensitive adhesive layer 20 is disposed on the barrier layer 12 side of the support 10. The pressure-sensitive adhesive layer 20 includes a pressure-sensitive adhesive. In one embodiment, the patch 100 is used as a patch preparation in which the adhesive layer 20 further contains a drug. The patch 100 may contain any appropriate other layer other than these layers. Examples of the other layers include a nonwoven fabric layer, a film layer, a porous polymer layer, and an anchor coat layer between the support film 11 and the barrier layer 12.

<A. Support>
The support 10 includes a support film 11 and a barrier layer 12. The support 10 is a member that holds the pressure-sensitive adhesive layer 20 formed on one surface thereof.

A-1. Support Film The support film 11 contains a urethane resin. Any appropriate urethane-based resin can be used as the urethane-based resin. For example, polyether urethane resin, polyester urethane resin, polycarbonate urethane resin and the like can be mentioned. The support film 11 may contain a material other than the urethane-based resin as long as the effects of the present invention are not impaired. A commercially available urethane resin film may be used as the support film containing the urethane resin.

  The thickness of the support film 11 is preferably 10 μm to 200 μm, more preferably 15 μm to 100 μm. If thickness is in said range, the self-supporting property of a support film can be maintained favorable and the favorable sticking feeling at the time of skin sticking can be provided. Moreover, if thickness is in said range, a patch can be manufactured efficiently.

A-2. Barrier layer The barrier layer 12 contains an ethylene-vinyl alcohol copolymer. The ethylene-vinyl alcohol copolymer preferably has a saponification degree of 99% to 100%, more preferably a saponification degree of 99.9% to 100%, More preferably, the degree of conversion is substantially 100%. When the degree of saponification is within the above range, even when the pressure-sensitive adhesive layer contains an oily additive, adsorption and migration of the oily additive can be suppressed.

  The molar ratio of ethylene units in the ethylene-vinyl alcohol copolymer is preferably 20 mol% to 60 mol%, more preferably 25 mol% to 50 mol%. When the molar ratio of the ethylene units is less than 20 mol%, the water solubility of the barrier layer becomes high, and there is a possibility that the barrier layer is dissolved by the adhesion of water and the support and the pressure-sensitive adhesive layer are separated. When the molar ratio of ethylene units exceeds 60 mol%, the hydrophobicity of the barrier layer is increased, and when an oily additive is used, the oily additive may be easily adsorbed or absorbed on the support. The ethylene-vinyl alcohol copolymer used in the present invention may contain structural units other than ethylene and vinyl alcohol as long as the effects of the present invention are obtained.

  The thickness of the barrier layer is preferably 10 nm to 2000 nm, more preferably 100 nm to 1000 nm. When the thickness is less than 10 nm, the barrier performance is lowered, and when the oil-based additive is used, the oil-based additive may ooze out from the back surface (the surface on the side where the pressure-sensitive adhesive layer is not formed) of the support. On the other hand, if the thickness exceeds 2000 nm, the rigidity of the support is increased, and there is a possibility that an uncomfortable feeling may occur during the pasting.

  For the barrier layer, for example, a barrier coating agent obtained by dissolving an ethylene-vinyl alcohol copolymer in a mixed solvent of water and a lower alcohol is applied and dried by any appropriate method such as a gravure coating method or a slot die coating method. Can be formed.

  When forming a barrier layer, you may form a barrier layer after forming an anchor coat layer in a support film as needed. Moreover, you may form a barrier layer, after giving a dry surface treatment to a support film. Examples of the dry surface treatment include corona discharge treatment, plasma treatment, ultraviolet irradiation treatment, and sputter etching treatment.

<B. Adhesive layer>
In the patch of the present invention, the pressure-sensitive adhesive layer 20 is disposed in contact with the barrier layer 12 of the support 10. With such a configuration, even when the pressure-sensitive adhesive layer contains an oil-based additive, adsorption / absorption of the oil-based additive to the support can be prevented. Therefore, even when the patch of the present invention is stored, the content of the oily additive in the pressure-sensitive adhesive layer can be maintained, and desired pressure-sensitive adhesive properties can be maintained.

  The pressure-sensitive adhesive forming the pressure-sensitive adhesive layer is not particularly limited as long as it has adhesiveness. For example, an acrylic pressure-sensitive adhesive obtained by copolymerizing (meth) acrylic acid alkyl ester as a main component monomer, styrene- Rubber adhesives made of isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, polyisoprene, polybutadiene, polyisobutylene, neoprene, silicone rubber, silicone based on dimethylsiloxane, diphenylsiloxane Adhesives, vinyl ether adhesives made of polyvinyl methyl ether, polyvinyl ethyl ether, polyvinyl isobutyl ether, etc., vinyl ester adhesives made of vinyl acetate, ethylene-vinyl acetate, dimethyl phthalate, dimethyl isophthalate, etc. And the carboxylic acid component such as diethyl phthalate, polyester-based adhesives and the like obtained from a polyhydric alcohol component such as ethylene glycol. These pressure-sensitive adhesives may be used alone or in combination of two or more.

  In one embodiment, the pressure-sensitive adhesive layer (substantially pressure-sensitive adhesive) includes an acrylic polymer as a pressure-sensitive adhesive polymer. Preferably, the acrylic polymer has adhesiveness at normal temperature (for example, 25 ° C.). Such an acrylic polymer is preferably an acrylic polymer obtained by copolymerizing a (meth) acrylic acid alkyl ester and a functional monomer, and more preferably a (meth) acrylic acid alkyl ester. It is an acrylic polymer obtained by copolymerizing a functional monomer as a main component. Here, the main component means a monomer contained in an amount of 50% by weight or more based on the total weight of all monomers of the copolymer.

  Any appropriate (meth) acrylic acid alkyl ester can be used as the (meth) acrylic acid alkyl ester (hereinafter also referred to as a main component monomer) in the acrylic polymer. Typical examples include linear or branched alkyl groups in which the alkyl group has 4 to 13 carbon atoms (eg, butyl, pentyl, hexyl, heptyl, octyl, 2-ethylhexyl, nonyl, decyl, undecyl, dodecyl). , Tridecyl) (meth) acrylic acid alkyl ester. The (meth) acrylic acid alkyl ester may be used alone or in combination of two or more.

  In the present specification, the “functional monomer” means a monomer having at least one unsaturated double bond involved in the copolymerization reaction in the molecule and having a functional group in the side chain. Specific examples of functional monomers include (meth) acrylic acid, itaconic acid, maleic acid, maleic anhydride and other carboxyl group-containing monomers; (meth) acrylic acid hydroxyethyl ester, (meth) acrylic acid hydroxy Hydroxyl group-containing monomers such as propyl ester; Sulfoxyl group-containing monomers such as styrene sulfonic acid, allyl sulfonic acid, sulfopropyl (meth) acrylate, (meth) acryloyloxynaphthalene sulfonic acid, acrylamidomethylpropane sulfonic acid; Amino group-containing monomers such as (meth) acrylic acid aminoethyl ester, (meth) acrylic acid dimethylaminoethyl ester, (meth) acrylic acid tert-butylaminoethyl ester; (meth) acrylamide, dimethyl (meth) acrylamide, N -Methylo Amide group-containing monomers such as ru (meth) acrylamide, N-methylolpropane (meth) acrylamide, N-vinylacetamide; (meth) acrylic acid methoxyethyl ester, (meth) acrylic acid ethoxyethyl ester, (meth) acrylic Alkoxyl group-containing single groups such as acid methoxyethylene glycol ester, (meth) acrylic acid methoxydiethylene glycol ester, (meth) acrylic acid methoxypolyethylene glycol ester, (meth) acrylic acid methoxypolyprene glycol ester, (meth) acrylic acid tetrahydrofuryl ester A monomer is mentioned. A functional monomer may be used independently and may use 2 or more types together. Among these, from the viewpoint of pressure-sensitive adhesiveness and cohesiveness of the pressure-sensitive adhesive layer, a carboxyl group-containing monomer is preferable, and (meth) acrylic acid is more preferable.

  As the acrylic polymer, an acrylic polymer obtained by copolymerizing a main component monomer, a functional monomer, and another monomer may be used. Examples of the other monomers include (meth) acrylonitrile, vinyl acetate, vinyl propionate, N-vinyl-2-pyrrolidone, methyl vinyl pyrrolidone, vinyl pyridine, vinyl piperidone, vinyl pyrimidine, vinyl piperazine, vinyl pyrrole and vinyl. Examples include imidazole, vinyl caprolactam, and vinyl oxazole. Another monomer may be used independently and may use 2 or more types together.

  Particularly preferred acrylic polymers in the present invention include, for example, a copolymer of 2-ethylhexyl acrylate / acrylic acid, a copolymer of 2-ethylhexyl acrylate / acrylic acid / N-vinyl-2-pyrrolidone. Examples thereof include a polymer and a copolymer of 2-ethylhexyl acrylate / acrylic acid 2-hydroxyethyl ester / vinyl acetate. Preferred are a copolymer of 2-ethylhexyl acrylate / acrylic acid and a copolymer of 2-ethylhexyl acrylate / acrylic acid / N-vinyl-2-pyrrolidone.

  The copolymerization ratio in the acrylic polymer (monomer usage ratio) is, for example, 50% by weight of (meth) acrylic acid alkyl ester (main monomer) based on the total weight of the monomers used. ˜99.9% by weight, functional monomers from 0.1% by weight to 10% by weight, and other monomers from 0% by weight to 49.9% by weight. By adopting such a copolymerization ratio, an acrylic polymer having good adhesion to human skin and easy to repeat adhesion and peeling can be obtained.

  The acrylic polymer can be obtained by any appropriate polymerization method. For example, a polymerization initiator (for example, benzoyl peroxide, 2,2′-azobisisobutyronitrile, etc.) is added to the above-mentioned monomer, and the reaction is performed at 50 ° C. to 50 ° C. in a solvent (for example, ethyl acetate). It can be obtained by reacting at 70 ° C. for 5 to 48 hours.

  The amount of the pressure-sensitive adhesive (for example, the acrylic polymer) in the pressure-sensitive adhesive layer is preferably 30% by weight to 90% by weight, more preferably 40% by weight to 90% by weight, based on the total weight of the pressure-sensitive adhesive layer. It is. When the amount of the pressure-sensitive adhesive is less than 30% by weight, the internal cohesive force of the pressure-sensitive adhesive layer may be reduced. If the amount of the pressure-sensitive adhesive exceeds 90% by weight, the tackiness of the pressure-sensitive adhesive layer may be reduced, or the amount of the organic liquid component described later may be insufficient.

  In order to increase the cohesive force of the pressure-sensitive adhesive layer and increase the amount of oily additive to be described later, the pressure-sensitive adhesive layer may be subjected to a crosslinking treatment. Specifically, physical crosslinking by radiation irradiation such as ultraviolet irradiation or electron beam irradiation, chemical crosslinking by a crosslinking agent, and the like can be mentioned. Moreover, when preparing the polymer which forms an adhesive layer by polymerization reaction, you may use the polymer bridge | crosslinked by copolymerizing a polyfunctional monomer.

  The crosslinking agent is not particularly limited as long as the crosslinking agent is not inhibited by the drug. Specific examples of the crosslinking agent include peroxides (eg, benzoyl peroxide (BPO)), metal oxides (eg, magnesium aluminate metasilicate), polyfunctional isocyanate compounds, organometallic compounds (eg, zirconium). And zinc alaninate, zinc acetate, zinc glycine ammonium, titanium compounds, etc.), metal alcoholate compounds (eg, tetraethyl titanate, tetraisopropyl titanate, aluminum isopropylate, aluminum sec-butyrate, etc.), and metal chelate compounds (eg, dipropoxybis) (Acetylacetonate) titanium, tetraoctylene glycol titanium, aluminum isopropylate, ethyl acetoacetate aluminum diisopropylate, aluminum tris Tate), aluminum tris (acetylacetonate)) and the like. A crosslinking agent may be used independently and may be used in combination of 2 or more type.

  The amount of the crosslinking agent used is preferably 0.01% by weight to 10% by weight, more preferably 0.05% by weight to 5% by weight, based on the total weight of the pressure-sensitive adhesive layer. If the amount of the cross-linking agent is less than 0.01% by weight, there are too few cross-linking points and sufficient cohesive force cannot be imparted to the pressure-sensitive adhesive layer. is there. When the amount of the cross-linking agent exceeds 10% by weight, the cohesive force is large but sufficient skin adhesive force may not be obtained. In addition, there is a risk that skin irritation may occur due to residual unreacted crosslinking agent.

  The chemical cross-linking treatment can be carried out, for example, by passing through a step of storing at a temperature equal to or higher than the cross-linking reaction temperature after adding the cross-linking agent to the pressure-sensitive adhesive layer, that is, an aging step. The heating temperature and the heating time are appropriately selected according to the type of the crosslinking agent. The heating temperature is preferably 60 ° C to 90 ° C, more preferably 60 ° C to 80 ° C. The heating time is preferably 12 hours to 96 hours, more preferably 24 hours to 72 hours. The cross-linked pressure-sensitive adhesive layer containing an organic liquid component is preferable because it has a gel-like shape, has appropriate skin adhesiveness, and has cohesiveness that hardly causes adhesive residue at the time of peeling.

  The pressure-sensitive adhesive layer 20 preferably further contains an oily additive. The oil-based additive can be used, for example, for the purpose of plasticizing the pressure-sensitive adhesive layer to reduce skin irritation, the purpose of imparting flexibility to the pressure-sensitive adhesive layer, the purpose of imparting ultraviolet absorbing ability or antioxidant ability, and the like. . Further, in a patch preparation in which the pressure-sensitive adhesive layer contains a drug, it can be used for the purpose of improving the transdermal absorbability and stability of the drug contained, and for the purpose of improving the solubility of the drug in the pressure-sensitive adhesive layer. . The oily additive is preferably a compound that is liquid at normal temperature (usually 25 ° C.) from the viewpoint of uniform dispersibility and compatibility with the pressure-sensitive adhesive layer. In the present invention, the oily additive includes not only an additive having the above function but also an oily additive itself having a pharmacological action.

  Examples of oil-based additives include glycols such as ethylene glycol, diethylene glycol, propylene glycol, triethylene glycol, polyethylene glycol, polypropylene glycol, and dipropylene glycol, oils such as olive oil, castor oil, squalane, and lanolin, and liquid paraffin Hydrocarbons, various surfactants, long-chain aliphatic alcohols such as ethoxylated stearyl alcohol, ethyl laurate, isopropyl myristate, isotridecyl myristate, octyl palmitate, isopropyl palmitate, ethyl oleate, diisopropyl adipate, etc. Fatty acid alkyl ester, oleic acid monoglyceride, caprylic acid monoglyceride, lauric acid monoglyceride, glycerin diester, glycerin tries Fatty acid glyceryl esters such as oleic acid, fatty acids such as oleic acid, levulinic acid and caprylic acid, glyceryl tricaprylate, medium chain fatty acid triglycerides such as tri (caprylic / capric) glyceryl, N-methylpyrrolidone, 1,3-butanediol Etc. Oily additives may be used alone or in combination of two or more oily additives.

  Of oil-based additives, those composed of fatty acids having too many carbon atoms (for example, fatty acids having 18 or more carbon atoms) or fatty acids having too few carbon atoms (for example, fatty acids having 3 or less carbon atoms) are adhesive. The compatibility with the agent layer may be deteriorated or it may be easily volatilized in the heating process when the patch is produced. In addition, when the oily additive has a double bond, the storage stability may be adversely affected by oxidative decomposition or the like.

  The content of the oily additive is preferably 0.1% by weight to 60% by weight, more preferably 1% by weight to 50% by weight in the pressure-sensitive adhesive layer. When the content of the oily additive is less than 0.1% by weight, the effect of containing the oily additive may not be sufficiently exhibited. When the content of the oily additive exceeds 60% by weight, the oily additive cannot be stably retained in the pressure-sensitive adhesive layer, and the oily additive is not retained from the pressure-sensitive adhesive layer during storage of the patch or during application to the skin surface. In some cases, the oil may exude and cannot exhibit a stable effect, and even if the pressure-sensitive adhesive layer is subjected to a crosslinking treatment, the oil-based additive may not be retained in the pressure-sensitive adhesive layer.

  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.

  From the viewpoint of skin adhesiveness, the thickness of the pressure-sensitive adhesive layer is preferably 10 μm to 200 μm, more preferably 15 μm to 150 μm.

  Practically, in order to protect the adhesive surface of the adhesive layer before use, it can be covered with a release liner. The release liner is not particularly limited. Specific examples of the release liner include glassine paper, polyethylene, polypropylene, polyester, polyethylene terephthalate, polystyrene, aluminum film, foamed polyethylene film, foamed polypropylene film, etc., or a laminate of those selected from these, and further processed with silicone. And those that have been embossed. A polyester (particularly, polyethylene terephthalate) resin release liner is preferred in terms of barrier properties, cost, and ease of material selection. In order to make the release liner more easily peelable from the pressure-sensitive adhesive layer, a surface peeling treatment may be applied to the pressure-sensitive adhesive layer side surface of the release liner.

  In view of ease of processing and processing accuracy, the release liner preferably has a uniform thickness. The thickness of the release liner is preferably 25 μm to 200 μm, more preferably 50 μm to 150 μm, from the viewpoints of ease of manufacture of the patch, cost of the release liner, portability of the patch, operability, and the like.

  The patch of the present invention can be produced by any appropriate method. For example, the following method is mentioned. First, a support is prepared. Specifically, a barrier layer is formed by applying a barrier coating agent in which an ethylene-vinyl alcohol copolymer is dissolved in a mixed solvent of water and lower alcohol to a polyurethane film to obtain a support. Next, a release liner is prepared, an adhesive layer is laminated on one side of the release liner, and a support is laminated on the adhesive layer to obtain a laminated sheet. Alternatively, an adhesive layer is laminated on the barrier layer of the support, and a release liner is laminated on the adhesive layer to obtain a laminated sheet. The method for laminating the support and the pressure-sensitive adhesive layer is not particularly limited. Specific examples include application, adhesion, fusion, and welding. Preferably, a method of preparing a pressure-sensitive adhesive containing a pressure-sensitive polymer and an organic solvent, applying the pressure-sensitive adhesive on a release liner or a support, and drying and removing the organic solvent is employed. The obtained laminated sheet is cut into a predetermined shape to obtain a patch. The patch may be hermetically packaged with a packaging material to ensure storage stability until use. As a patch packaging container, a resin film, a metal foil, a bag made of a laminated film thereof, or the like is usually used.

<C. Patch preparation>
In the patch preparation of the present invention, in the above patch, the adhesive layer further contains a drug. As described above, the adhesive preparation of the present invention can suppress adsorption / absorption of the oily additive during storage to the support even when the oily additive is used. Therefore, even when the patch preparation is stored, the adhesive properties of the adhesive layer can be maintained, and the content of the oily additive in the adhesive layer can be maintained, and the desired transdermal Absorbency can be demonstrated.

  The drug is not particularly limited as long as it can be used for transdermal absorption. For example, corticosteroids, analgesic / anti-inflammatory agents, hypnotic sedatives, product stabilizers, antihypertensive agents, antihypertensive diuretics, antibiotics Substance, anesthetic, antibacterial agent, antifungal agent, vitamin agent, coronary vasodilator, antihistamine, antitussive, sex hormone, antidepressant, cerebral circulation improving agent, antiemetic, antitumor agent, antiepileptic agent, anti-Alzheimer agent, One kind or two or more kinds of drugs such as an anti-parkinsonian agent, an antithrombotic agent and a biomedicine can be used together.

  The drug in the patch preparation of the present invention preferably has a drug octanol / water partition coefficient (log P) of -1 to 5, more preferably 0 to 4. If the octanol / water partition coefficient of the drug is within the above range, it can be effectively blocked by the barrier layer. The octanol / water partition coefficient (log P) is an index that represents hydrophilicity or hydrophobicity. , Shake FIask Method ”, the value measured for each drug, and the logarithmic base of logPow is 10. In this specification, logPow was calculated using logP calculation software Cache (registered trademark, manufactured by Fujitsu). In the measurement (calculation) of logPow, the structural formula of the compound is input to the calculation software to calculate logPow.

  The drug can be present in the adhesive layer in an amount sufficient to produce a desired result in the treatment of a disease, condition or disorder, eg, a desired therapeutic result (ie, an effective amount). By effective amount of drug is meant, for example, an amount of drug that is non-toxic but sufficient to produce a selected effect over a specified period of time. Such an amount can be readily determined by one skilled in the art.

  The amount of the drug in the pressure-sensitive adhesive layer is not particularly limited as long as it satisfies the effect of the drug for transdermal absorption and does not impair the pressure-sensitive adhesive properties of the pressure-sensitive adhesive layer. Specifically, the amount of the drug is preferably 0.1% to 60% by weight, more preferably 0.5% to 40% by weight, based on the total weight of the pressure-sensitive adhesive layer. When the amount of the drug is less than 0.1% by weight, the therapeutic effect may not be sufficient. If the amount of the drug is more than 60% by weight, the content of the pressure-sensitive adhesive constituting the pressure-sensitive adhesive layer and other additives may be low, and sufficient skin adhesiveness may not be obtained. There may be disadvantages.

  The patch preparation of the present invention can be produced by any appropriate method. For example, in the above method for producing a patch, when preparing a composition for forming an adhesive layer, a drug may be added to form an adhesive layer.

  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.

<Preparation of adhesive layer forming composition 1>
50 parts by weight of pressure-sensitive adhesive (acrylic acid 2-ethylhexyl ester (EHA) / N-vinyl-2-pyrrolidone (NVP) / acrylic acid (AA) copolymer = 72/25/3 (weight ratio)) 50 parts by weight of an additive (isopropyl myristate (IPM), standard pharmaceutical additive) was added to prepare an adhesive layer forming composition 1.

<Preparation of adhesive layer forming composition 2>
49 parts by weight of adhesive (copolymer of 2-ethylhexyl acrylate (EHA) / N-vinyl-2-pyrrolidone (NVP) / acrylic acid (AA) = 72/25/3 (weight ratio)) 50 parts by weight of an additive (isopropyl myristate (IPM), pharmaceutical additive standard product) and 1 part by weight of indomethacin (octanol / water partition coefficient: 3.8) were added to prepare an adhesive layer forming composition 2 did.

[Example 1]
A barrier film having a thickness of 300 nm is applied to one side of a support film (polyether urethane film (thickness: 30 μm)) with an ethylene-vinyl alcohol copolymer (EVOH) (degree of saponification 99.9%, ethylene ratio 44 mol%). Next, the pressure-sensitive adhesive layer forming composition 1 was applied on the barrier layer to form a pressure-sensitive adhesive layer having a thickness of 75 μm, thereby obtaining a patch.

[Example 2]
A patch was obtained in the same manner as in Example 1 except that the thickness of the barrier layer was 600 nm.

[Example 3]
A patch preparation was obtained in the same manner as in Example 1 except that the pressure-sensitive adhesive forming composition 2 was used.

[Example 4]
A patch preparation was obtained in the same manner as in Example 2 except that the pressure-sensitive adhesive forming composition 2 was used.

(Comparative Example 1)
A patch was obtained in the same manner as in Example 1 except that polyvinyl alcohol resin (PVA) (saponification degree: 80%) was used as the barrier layer forming material.

(Comparative Example 2)
A patch was obtained in the same manner as in Example 2 except that PVA (saponification degree: 80%) was used as the barrier layer forming material.

(Comparative Example 3)
10 parts by weight of montmorillonite (powder) was added to 90 parts by weight of PVA (degree of saponification 80%) to prepare a barrier layer forming composition. A patch was obtained in the same manner as in Example 1 except that the obtained barrier layer-forming composition was used.

(Comparative Example 4)
A patch was obtained in the same manner as in Example 2 except that the barrier layer forming composition prepared in Comparative Example 3 was used.

(Comparative Example 5)
A pressure-sensitive adhesive layer-forming composition 1 was applied to one side of a support film (polyether-based urethane film (thickness: 30 μm) to form a pressure-sensitive adhesive layer having a thickness of 75 μm to obtain a patch.

(Comparative Example 6)
A patch was obtained in the same manner as in Comparative Example 5 except that a polyethylene terephthalate film (thickness: 12 μm) was used as the support film.

  The following evaluations were performed using the patches or patch preparations obtained in Examples 1 to 4 and Comparative Examples 1 to 6. The evaluation results are shown in Table 1.

<IPM exudation amount>
The wrapping paper was brought into close contact with the back surface (supporting film side) of the obtained patch or patch preparation, and held at 25 ° C. under a pressure (0.5 kPa) for 3 days. Thereafter, the patch or patch preparation and the medicine wrapper were separated, the medicine wrapper was punched out to 2 cm ² , and IPM was extracted from the medicine wrapper with hexane. The amount of IPM exuded from the back of the support was quantified with a FID detector using gas chromatography from the obtained extract.

<Tension at 20% elongation>
A sample having a size of 30 mm × 5 mm was obtained from the obtained patch or patch preparation so that the direction of application of the adhesive was the longitudinal direction. The obtained sample was uniaxially stretched at a speed of 300 mm / min in the longitudinal direction using a tensile tester (manufactured by Shimadzu Corporation), and the tension when the stretch ratio reached 20% was measured.

<Peeling off during bathing>
The obtained patch or patch preparation was molded into a sample having a size of 10 cm ² , and each sample was pasted on the chest three by three. After bathing in 40 ° C. hot water for about 10 minutes, the number of peeled sheets was evaluated.

  In Examples 1 to 4, there was no exudation of IPM from the back surface of the support, and peeling during bathing did not occur. Furthermore, the tension at the time of 20% elongation was similar to that of the polyurethane film alone. In Comparative Examples 1 to 4 in which the barrier layer was PVA, the IPM exudation amount and the tension at 20% elongation were similar to those in the Examples, but they were peeled off during bathing, and there was a problem in water resistance. Further, in Comparative Example 5 using a polyurethane film having no barrier layer, a large amount of IPM exudes, although the tension at the time of 20% elongation and the peeling result at the time of bathing were excellent. In Comparative Example 6 using a PET film having no barrier layer, although IPM did not exude, the tension at 20% elongation was large, and it was difficult to use.

  As described above, the patches and patch preparations according to the examples of the present invention can prevent the oily additive from exuding. Furthermore, the patches and patch preparations according to the examples of the present invention are excellent in flexibility and water resistance. Therefore, it is possible to provide a patch and a patch preparation that achieve an excellent patch feeling.

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

DESCRIPTION OF SYMBOLS 10 Support body 11 Support film 12 Barrier layer 20 Adhesive layer 100 Patch

Claims (7)

A patch comprising a support film comprising a urethane-based resin and a barrier layer comprising an ethylene-vinyl alcohol copolymer, and a pressure-sensitive adhesive layer comprising a pressure-sensitive adhesive,
A patch, wherein the pressure-sensitive adhesive layer is disposed on the barrier layer side of the support.   The patch according to claim 1, wherein the saponification degree of the ethylene-vinyl alcohol copolymer is 99% to 100%.   The patch according to claim 1 or 2, wherein a molar ratio of ethylene units of the ethylene-vinyl alcohol copolymer is 20 mol% to 60 mol%.   The patch according to any one of claims 1 to 3, wherein the pressure-sensitive adhesive is an acrylic pressure-sensitive adhesive.   The patch according to any one of claims 1 to 4, wherein the pressure-sensitive adhesive layer further contains an oily additive.   The patch preparation according to any one of claims 1 to 5, wherein the adhesive layer further contains a drug. The patch preparation according to claim 6, wherein the drug has an octanol / water partition coefficient of -1 to 5.

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