JP5185509B2 - Patch - Google Patents

Description

  The present invention relates to a patch.

A patch to be applied to human skin or the like is generally widely known as a preparation in which an adhesive is applied to a sheet-like support surface.
Conventionally, a nonwoven fabric, a knitted fabric, a resin film, or a laminated sheet thereof is used for the support. Usually, a nonwoven fabric or a knitted fabric is used, but a resin film may be used to obtain a thin patch.
As the resin film, polyethylene (PE), polyethylene terephthalate (PET) or the like is generally used, but these resin films refer to anchoring properties with an adhesive (adhesiveness between a support and an adhesive). )) Is bad, and therefore, the adhesive remaining on the skin when the patch is peeled off from the skin is a problem.

  As a means for improving anchoring property in this patch, a method of providing an anchor layer such as a primer layer, a nonwoven fabric, a knitted fabric between the resin film and the adhesive layer (for example, see Patent Documents 1 to 3), A method of roughening the surface of a resin film by performing a sandblast treatment (see Patent Document 4) is disclosed.

On the other hand, in the case of a patch, transparency (inconspicuousness of the patch when the patch is applied to the skin) and feeling of sticking (stretchability / flexibility of the patch when the patch is applied to the skin) It is also required to have the following characteristics.
As means for improving these properties, a support for patches and the like, which is excellent in stretch flexibility and drug penetration-preventing property made of a 20-200 μm thick film made of a polyolefin-based thermoplastic elastomer, and the like have been proposed. (See Patent Document 5).
JP 2003-95929 A JP 2003-169823 A JP 2000-119129 A JP 2004-10552 A Japanese Patent Laid-Open No. 10-101551

However, the methods described in Patent Documents 1 to 4 do not have sufficient transparency and feeling of patch.
In the method described in Patent Document 5, the anchoring property between the film made of polyolefin-based thermoplastic elastomer and the pressure-sensitive adhesive layer is not sufficient.

Moreover, even if the laminated sheet (patch) described in Patent Documents 1 to 3, for example, is produced using the patch support described in Patent Document 5, the anchoring property may be poor.
Further, when the method described in Patent Document 4 is used for the patch support, it is not yet sufficient in terms of anchoring properties, and the transparency of the patch is also inferior.

  This invention is made | formed in view of the said situation, and makes it a subject to provide the patch which is excellent in transparency and sticking feeling, and was excellent in anchoring property.

As a result of intensive studies, the present inventors have completed the present invention in order to solve the above problems.
That is, the present invention provides a patch having a non-aqueous pressure-sensitive adhesive layer containing a pressure-sensitive adhesive base on the support surface, wherein the support is made of a polyolefin-based elastomer film, and the non-aqueous pressure-sensitive adhesive layer has the following general formula ( A patch comprising the fatty acid ester represented by 1).
^{R 2 OOC-R 1 - (} COOR 3) n ··· (1).
[Wherein, R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, R ² is a hydrocarbon group having 1 to 20 carbon atoms, and R ³ is a hydrocarbon group having 1 to 10 carbon atoms or a hydrogen atom. Yes, n is an integer of 0 or 1. ]

Moreover, in this invention, it is preferable that the said polyolefin-type elastomer is a copolymer of ethylene and C3-C12 alpha olefin.
In the present invention, it is preferable that a surface treatment selected from a corona discharge treatment, a plasma treatment and a surface unevenness treatment is applied to the surface of the support on the non-aqueous adhesive layer side.
Moreover, in this invention, the said adhesive base is a polymer which has a monomer unit chosen from 50-100 mass% (meth) acrylic-acid alkylester with respect to all the monomer units which comprise this adhesive base. It is preferable.

  ADVANTAGE OF THE INVENTION According to this invention, the transparency and the feeling of sticking can be provided, and the patch excellent in anchoring property can be provided.

The patch of the present invention has a non-aqueous pressure-sensitive adhesive layer containing an adhesive base on the support surface.
Hereinafter, the non-aqueous pressure-sensitive adhesive layer and the support will be described in detail.

<Non-aqueous adhesive layer>
In the present invention, the non-aqueous pressure-sensitive adhesive layer contains a pressure-sensitive adhesive base, and further contains a fatty acid ester represented by the general formula (1).
Moreover, the non-aqueous pressure-sensitive adhesive layer may contain other components such as medicinal components in addition to the pressure-sensitive adhesive base and the fatty acid ester.
The non-aqueous pressure-sensitive adhesive layer is a coating layer formed by applying a non-aqueous pressure-sensitive adhesive layer coating solution described later on a support surface or a silicon surface-treated release film and drying it. In this specification, what constitutes the coating layer is expressed as “non-aqueous adhesive composition” and “plaster”.
The non-aqueous pressure-sensitive adhesive composition may contain moisture from the raw material, the manufacturing process, or the environment, but the smaller the moisture content, the better. Specifically, the water content is preferably 5% by mass or less, more preferably 2% by mass or less, in the non-aqueous pressure-sensitive adhesive composition. By setting the water content to 5% by mass or less, the cohesive force of the non-aqueous pressure-sensitive adhesive composition is increased, and the peelability of the patch from the skin is improved. For example, a non-aqueous pressure-sensitive adhesive composition containing about 0.5% by mass of water is a non-aqueous pressure-sensitive adhesive composition with good effects of the present invention.

(Adhesive base)
It does not specifically limit as an adhesive base, A various thing can be used. Of these, acrylic adhesives and rubber adhesives are preferred because the anchoring property when used as a patch is favorable, and acrylic adhesives are particularly preferable because the anchoring property is better. Is preferred.

As the acrylic pressure-sensitive adhesive, for example, a polymer having a monomer unit selected from (meth) acrylic acid alkyl ester, a monomer unit selected from a monomer containing a carboxy group) or the like is preferably used.
Here, the “monomer unit” means a structural unit (monomer unit) constituting the polymer.
“(Meth) acrylic acid” refers to one or both of methacrylic acid and acrylic acid.

In the (meth) acrylic acid alkyl ester that provides a monomer unit, the alkyl group preferably has 1 to 30 carbon atoms, more preferably 4 to 20 carbon atoms from the viewpoint of ensuring high tackiness. It may be a chain or a branched chain.
Examples of the alkyl group include linear alkyl groups such as butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, and branched alkyl groups such as 2-ethylhexyl. .
Specifically, as the (meth) acrylic acid alkyl ester, ethyl acrylate, n-butyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, methyl methacrylate, and dodecyl methacrylate are particularly preferable.
Specific examples of the monomer containing a carboxy group that provides a monomer unit include (meth) acrylic acid, itaconic acid, maleic acid, and maleic anhydride. Of these, acrylic acid and methacrylic acid are particularly preferable.
In the acrylic pressure-sensitive adhesive, the monomers providing the monomer units may be used alone or in combination of two or more.
Especially, it is preferable that this acrylic adhesive is a polymer which has a monomer unit chosen from the (meth) acrylic-acid alkylester from the point of adhesiveness and cohesiveness.

The proportion of the monomer units in the acrylic pressure-sensitive adhesive is preferably from 0.1 to 100% by mass, more preferably from 1 to 100% by mass, based on all monomer units constituting the acrylic pressure-sensitive adhesive. By being more than the lower limit of this range, adhesiveness with a support body increases and the anchoring property of a patch improves.
In particular, when a monomer unit selected from (meth) acrylic acid alkyl esters is used, the proportion of the monomer unit is preferably 30 to 100% by mass, and 50 to 100% by mass with respect to all monomer units constituting the acrylic pressure-sensitive adhesive. % Is more preferable. If it is this range, said effect will become easy to be acquired.

As the acrylic pressure-sensitive adhesive, in addition to the monomer that provides the monomer unit, a comonomer that can be copolymerized with the monomer that provides the monomer unit can be used as necessary.
Such comonomers include hydroxyl-containing monomers such as vinyl alcohol, 2-hydroxy (meth) acrylate, hydroxypropyl (meth) acrylate, and (meth) acrylic acid hydroxyethyl ester; styrene sulfonic acid, allyl sulfonic acid, sulfopropyl Sulfon group-containing monomers such as acrylates; Amino group-containing monomers such as dimethylaminoethyl acrylate and vinylpyrrolidone; Amides such as (meth) acrylamide, dimethyl (meth) acrylamide, and N-butyl (meth) acrylamide Group-containing acrylic monomer; alkylamino group-containing acrylic monomer such as (meth) acrylic acid aminoethyl ester, (meth) acrylic acid dimethylaminoethyl ester, (meth) acrylic acid diethylaminoethyl ester; A) Monomers containing alkoxy groups (or ether bonds in the side chain) such as methoxyethyl acrylate and ethoxyethyl methacrylate; glycosyloxyethyl (meth) acrylate, galactosyloxy (meth) acrylate Sugar chain-containing monomers such as ethyl; vinyl monomers such as N- (meth) acryloylamino acids; acrylic monomers such as urethane esters, urea esters and isocyanate esters of acrylic acid; Acrylonitrile, vinyl acetate, vinyl propionate, vinyl chloride, vinylpyridine, vinylpyrazine, vinylpiperazine, vinylpiperidone, vinylpyrimidine, vinylpyrrole, vinylimidazole, vinylcaprolactam, vinyloxazole, vinylthiazole, vinylmorpholine , Styrene, alpha-methyl styrene, bis (N, N-dimethylaminoethyl) vinyl monomers, such as maleate, and the like.
These comonomers may be used individually by 1 type, and may use 2 or more types together.

The acrylic pressure-sensitive adhesive can be synthesized using, for example, a polymerization initiator.
Examples of the polymerization initiator include persulfates such as ammonium persulfate and sodium persulfate; aqueous radical polymerization initiators such as aqueous hydrogen peroxide, lauroyl peroxide and t-butyl hydroperoxide, or a mixture thereof.
The amount of the polymerization initiator used is preferably 0.01 to 5% by mass and more preferably 0.1 to 2% by mass with respect to the total mass of the monomers used for the synthesis.
Also, a redox system can be formed by combining a polymerization initiator and a reducing agent.
Examples of the reducing agent include alkali metal salts such as sulfites, hydrogen sulfites, pyrosulfites, and formaldehyde sulfonates; and carboxylic acids such as ammonium salts, L-ascorbic acid, and tartaric acid.
The amount of the reducing agent used is preferably 0.01 to 5% by mass and more preferably 0.1 to 2% by mass with respect to the total mass of the monomers used for the synthesis.

Specifically, the acrylic pressure-sensitive adhesive can be preferably produced by emulsion polymerization.
As the surfactant used in the emulsion polymerization, an anionic surfactant, a cationic surfactant, a nonionic surfactant, an amphoteric surfactant or a mixture thereof can be used.
Examples of the anionic surfactant include alkyl or alkyl allyl sulfates such as sodium lauryl sulfate and sodium dodecylbenzene sulfonate, alkyl or alkyl allyl sulfonates; dialkyl sulfosuccinates; polyoxyethylene (3) sodium lauryl ether sulfates ( And polyoxyethylene alkyl ether sulfates such as polyoxyethylene (4) sodium lauryl ether sulfate (the average added mole number of ethylene oxide is 4) and the like. Examples of the salt include alkali metal salts and ammonium salts.
Nonionic surfactants include: polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether; polyoxyethylene alkyl phenyl ethers such as polyoxyethylene nonylphenyl ether and polyoxyethylene octylphenyl ether; monolaurin And polyoxyethylene fatty acid esters such as polyethylene glycol acid and polyethylene glycol monooleate.
Examples of amphoteric surfactants include betaines and amino acid derivatives.
Moreover, Surfactin sodium which is a peptide-type surfactant can also be mentioned.
These surfactants may be used alone or in combination of two or more.
The amount of the surfactant used is preferably 0.1 to 10% by mass and more preferably 0.5 to 5% by mass with respect to the total mass of the monomers used for the synthesis. When the amount used is 0.1% by mass or more, the emulsion polymerization reaction proceeds more stably and the formation of aggregates is suppressed. On the other hand, when the content is 10% by mass or less, drying property and water resistance are improved.

  In addition, the emulsion polymerization may be performed by chain transfer of a chelating agent such as sodium ethylenediaminetetraacetate, a dispersing agent such as polycarboxylate, an inorganic salt such as phosphate and carbonate, a thiol compound, and a halogen compound as necessary. It can also be carried out in the presence of an agent. By carrying out in the presence of the chain transfer agent, the molecular weight of the resulting acrylic pressure-sensitive adhesive can be controlled within a certain range.

  More specifically, as acrylic adhesives, for example, acrylic acid / acrylic acid octyl ester copolymers, acrylic acid esters / acetic acid, which are listed as adhesives in the Pharmaceutical Additives Encyclopedia 2000 (edited by Japan Pharmaceutical Additives Association) Vinyl copolymer, 2-ethylhexyl acrylate / vinyl pyrrolidone copolymer, 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer, methyl acrylate / 2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin Adhesives such as acrylic polymers contained in the alkanolamine liquid, DURO-TAK acrylic adhesive series (trade name, manufactured by National Starch and Chemical), Eudragit series (trade name, Higuchi Shokai) and the like can be suitably used.

In this invention, an acrylic adhesive may be used individually by 1 type, and may use 2 or more types together.
It is preferable that the compounding quantity of an acrylic adhesive is 30-95 mass% in a non-aqueous adhesive composition, More preferably, it is 50-90 mass%, Most preferably, it is 55-85 mass%. By being in this range, the adhesiveness when the patch is applied to the skin is improved, and peeling and turning are further reduced.

In the present invention, it is preferable to subject the polymer used as the acrylic pressure-sensitive adhesive to a crosslinking treatment. By performing the crosslinking treatment, the outflow of the liquid component contained in the non-aqueous pressure-sensitive adhesive layer is better suppressed, and good adhesiveness is obtained.
As such crosslinking treatment, for example, physical crosslinking treatment by radiation irradiation such as ultraviolet irradiation or electron beam irradiation, chemical using a crosslinking agent such as polyisocyanate compound, organic peroxide, polyvalent metal compound, polyfunctional compound, etc. Crosslinking treatment and the like can be mentioned. Of these, chemical crosslinking treatment is preferred. The crosslinking agent used in the chemical crosslinking treatment is preferably a polyvalent metal compound or a trifunctional isocyanate compound, particularly a polyvalent metal compound, from the viewpoint of the temporal stability of the nonaqueous pressure-sensitive adhesive composition and the manufacturability of the patch. preferable.

Examples of the polyvalent metal compound include magnesium compounds, calcium compounds, zinc compounds, cadmium compounds, aluminum compounds, titanium compounds, tin compounds, iron compounds, chromium compounds, manganese compounds, cobalt compounds, nickel compounds, and the like. Of these, aluminum compounds, calcium compounds, and magnesium compounds are preferable from the viewpoint of safety to the skin.
Any of these aluminum compounds, calcium compounds and magnesium compounds can be suitably used.
Specifically, alums such as potassium alum, ammonium alum, iron alum, aluminum hydroxide, aluminum sulfate, aluminum ammonium sulfate, potassium aluminum sulfate, aluminum chloride, aluminum lactate, dihydroxyaluminum aminoacetate, aluminum acetate, aluminum oxide, Synthetic aluminum silicate, aluminum metasilicate; calcium hydroxide, calcium carbonate, calcium sulfate, calcium nitrate, calcium chloride, calcium acetate, calcium oxide, calcium phosphate; magnesium hydroxide, magnesium carbonate, magnesium sulfate, magnesium acetate, magnesium silicate, Magnesium oxide, alumina hydroxide / magnesium, magnesium aluminate metasilicate, aluminate silicate Magnesium, synthetic hydrotalcite and the like. Of these, water-soluble compounds are preferable from the viewpoint of manufacturability of the patch, and alums, chlorides, and sulfates are particularly preferable.
These polyvalent metal compounds may be used alone or in combination of two or more.
The compounding amount of the polyvalent metal compound is preferably 0.01 to 2% by mass, more preferably 0.05 to 1% by mass, and still more preferably 0.001% by mass with respect to the solid content of the acrylic pressure-sensitive adhesive. It is 1-1 mass%.

In the acrylic pressure-sensitive adhesive, it is preferable to use a chelating agent that forms a chelate with the polyvalent metal compound. The chelating agent is a compound having the ability to form a chelate with the polyvalent metal ion of the polyvalent metal compound. By using this chelating agent, the increase in the viscosity of the non-aqueous pressure-sensitive adhesive layer coating liquid is suppressed, and the coating property is improved.
Examples of the chelating agent include ethylenediamine, N-methylethylenediamine, N, N′-dimethylethylenediamine, N, N, N ′, N′-tetramethylethylenediamine, trimethylenediamine, cis-1,2-diaminocyclohexane, 2- Nitroso-1-naphthol-8-hydroxynazoline, citric acid, malic acid, tartaric acid, edetic acid, diethylenetriaminepentaacetic acid, or monovalent metal salts thereof (for example, alkali metal salts such as sodium salt and potassium salt), Amine salts, ammonium salts and the like are preferably used. Of these, citric acid, edetic acid, diethylenetriaminepentaacetic acid, or monovalent metal salts thereof are more preferably used.
These chelating agents may be used alone or in combination of two or more.
It is preferable that the compounding quantity of a chelating agent is 0.01-5 mass% with respect to solid content of an acrylic adhesive, More preferably, it is 0.1-2 mass%.

The rubber-based adhesive is an adhesive composed of a rubber-based polymer and a tackifying resin.
Examples of the rubber polymer include rubber styrene-isoprene-styrene block copolymer (hereinafter abbreviated as “SIS”), isoprene rubber, polyisobutylene (hereinafter abbreviated as “PIB”), and styrene-butadiene. -Styrene block copolymer (hereinafter abbreviated as "SBS"), styrene-butadiene rubber (hereinafter abbreviated as "SBR"), polysiloxane and the like. Among them, SIS and PIB are preferable, SIS Is particularly preferred.
These rubber polymers may be used alone or in combination of two or more.
The compounding amount of the rubber-based polymer is preferably 10 to 90% by mass, more preferably 30 to 90% by mass in the rubber-based adhesive from the viewpoint of the formability and permeability of the non-aqueous adhesive layer. Yes, more preferably 30 to 70% by mass.

Examples of tackifying resins include rosin derivatives (eg, rosin, glycerin ester of rosin, hydrogenated rosin, glycerin ester of hydrogenated rosin, pentaerythrester ester of rosin), alicyclic saturated hydrocarbon resins (eg, trade names) : Alcon P100, manufactured by Arakawa Chemical Industries), aliphatic hydrocarbon resin (for example, trade name: Quinton B170, manufactured by Nippon Zeon), terpene resin (for example, Clearon P-125, manufactured by Yasuhara Chemical), maleic resin, etc. It is done. Of these, hydrogenated rosin glycerin ester, alicyclic saturated hydrocarbon resin, aliphatic hydrocarbon resin, and terpene resin are preferable.
These tackifier resins may be used alone or in combination of two or more.
The compounding amount of the tackifying resin is preferably 5 to 70% by mass, more preferably 5 to 60% in the rubber adhesive from the viewpoint of adhesive strength as a patch and irritation to the skin at the time of peeling. It is 10 mass%, More preferably, it is 10-50 mass%.

In this invention, a rubber-type adhesive may be used individually by 1 type, and may use 2 or more types together.
It is preferable that the compounding quantity of a rubber-type adhesive is 40-95 mass% in a non-aqueous adhesive composition, More preferably, it is 50-90 mass%, Most preferably, it is 55-85 mass%. By being in this range, the adhesiveness when the patch is applied to the skin is improved, and peeling and turning are further reduced.

In the present invention, it is preferable to further add a plasticizer. By blending a plasticizer, the wettability of the non-aqueous pressure-sensitive adhesive layer to the skin is improved and the adhesion is increased, and at the same time, pain when the patch is peeled off is reduced.
Plasticizers include petroleum oils (eg, paraffinic process oil, naphthenic process oil, aromatic process oil, etc.), squalane, squalene, vegetable oils (eg, olive oil, camellia oil, castor oil, tall oil, peanut Oil), silicone oil, dibasic acid ester (eg, dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (eg, polybutene, liquid isoprene rubber, etc.); polyethylene glycol, ethylene glycol, propylene glycol, 1,3-butylene glycol Dihydric alcohols such as diethylene glycol, dipropylene glycol and 1,3-hexylene glycol; trihydric alcohols such as glycerin and trimethylolpropane; erythritol, pentaerythritol, jig Tetrahydric alcohols such as serine; Pentavalent alcohols such as xylitol; Hexavalent alcohols such as sorbitol and dipentaerythritol; Sugars such as glucose, mannose, sucrose, sorbitan, trehalose, and alkylglycosides; Polymerization such as polypropylene glycol and polyglycerin And polyhydric alcohols such as N-methyl-2-pyrrolidone.
These plasticizers may be used alone or in combination of two or more.
It is preferable that the compounding quantity of a plasticizer is 5-50 mass% in a non-aqueous adhesive composition, More preferably, it is 10-40 mass%, More preferably, it is 15-30 mass%. When it is within this range, the effect of including a plasticizer can be sufficiently obtained.

(Fatty acid ester)
The fatty acid ester used in the present invention is a compound represented by the following general formula (1).
^{R 2 OOC-R 1 - (} COOR 3) n ··· (1).
[Wherein, R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, R ² is a hydrocarbon group having 1 to 20 carbon atoms, and R ³ is a hydrocarbon group having 1 to 10 carbon atoms or a hydrogen atom. Yes, n is an integer of 0 or 1. ]

  By using the fatty acid ester, the adhesiveness between the support and the non-aqueous pressure-sensitive adhesive layer is increased, and the anchoring property of the patch is improved. The reason why such an effect is obtained is not clear, but the compatibility between the fatty acid ester contained in the non-aqueous pressure-sensitive adhesive layer and the polyolefin-based elastomer (described later) constituting the support is good. It is presumed that the water-based adhesive layer is compatible with each other in the vicinity of the surface in the production process.

R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, preferably 4 to 20 carbon atoms, may be linear or branched, saturated or unsaturated. Also good. Moreover, when n is 0, it is preferable that carbon number is 10-36, and when n is 1, it is preferable that carbon number is 3-20.
R ² has 1 to 20 carbon atoms, preferably a hydrocarbon group having 1 to 18 carbon atoms, may be linear or branched, and may be saturated or unsaturated. Also good. Moreover, when n is 0, it is preferable that carbon number is 1-18. When n is 1, it is preferable that carbon number is 1-10, More preferably, it is 1-6, More preferably, it is 1-3.
R ³ represents a hydrogen atom or a hydrocarbon group having 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, and the hydrocarbon group may be linear or branched and saturated. It may be unsaturated. R ² and R ³ may be the same as or different from each other.
n is an integer of 0 or 1. Formula (1) is a monoester when n is 0, and is a diester when n is 1.

Specific examples of fatty acid esters include diethyl sebacate, diisopropyl sebacate, diethyl adipate, diisopropyl adipate, oleyl oleate, decyl oleate, isopropyl myristate, isopropyl palmitate, ethyl linoleate, and isopropyl linoleate. It is done. Of these, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, oleyl oleate, decyl oleate, and isopropyl myristate are preferred.
These fatty acid esters may be used alone or in combination of two or more.
1-50 mass% is preferable in a non-aqueous adhesive composition, as for the compounding quantity of fatty acid ester, 3-40 mass% is more preferable, 5-30 mass% is further more preferable, and 10-30 mass% is especially preferable. If it is this range, the anchoring property of the patch will be improved. In addition, the transdermal absorbability of the drug is improved.

(Medicinal ingredients)
The kind of medicinal component that can be used in the present invention is not particularly limited, and among them, a poorly water-soluble drug, generally a drug that is generally difficult to be percutaneously absorbed as an external preparation can be used.
The “poorly water-soluble drug” refers to a drug having a solubility in water at 20 ° C. of 0 to 30 mg / mL, preferably 0 to 10 mg / mL.
Specifically, for example, non-steroidal anti-inflammatory agents such as indomethacin, ferbinac, ketoprofen, flurbiprofen, diclofenac, salicylic acid derivatives or ester derivatives thereof; antihistamines such as diphenhydramine; central nervous system drugs such as isoprenaline hydrochloride; estradiol Hormonal agents such as testosterone; analgesics such as aspirin, acetaminophen, ibuprofen; antiarrhythmic agents such as disopyramide phosphate; coronary vasodilators such as trazoline hydrochloride; local anesthetics such as lidocaine; muscles such as squismethonium chloride Antifungal agents such as relaxants, clotrimazole, antineoplastic agents such as fluorouracil, dysuria such as tamsulosin hydrochloride, antiepileptic agents such as diazepam, antiparkinsonian agents such as bromocriptine mesylate; furosemide Antihypertensive agents such as clonidine; vasodilators such as nitroglycerin and isosorbide nitrate; smoking cessation aids such as nicotine; bronchodilators such as tulobuterol; hypnotic sedatives such as phenobarbital and triazolam; tranquilizers such as fluphenazine and theoritadine Vitamins such as vitamin A, vitamin E, vitamin K, octothiacin, riboflavin butyrate, prostaglandins, scopolamine, fentanyl, l-menthol, red pepper extract, nonylic acid vanillylamide and the like.
Among the above-mentioned medicinal ingredients, since the effect of the present invention is particularly remarkably obtained, a poorly water-soluble drug is preferable, and nonsteroidal anti-inflammatory agents such as indomethacin, ferbinac, ketoprofen, flurbiprofen, diclofenac, salicylic acid derivatives; Hormonal agents such as estradiol and testosterone; antihypertensive agents such as furosemide and clonidine; vasodilators such as nitroglycerin and isosorbide nitrate; smoking cessation aids such as nicotine; bronchodilators such as tulobtail; scopolamine, fentanyl and red pepper extract are more preferred .
One of these medicinal components may be used alone, or two or more thereof may be used in combination.
The compounding quantity of a medicinal ingredient can be made into the effective quantity in each medicinal ingredient in a non-aqueous adhesive composition.
As a compounding quantity of a medicinal component, it is preferable that it is about 0.01-65 mass% in a non-aqueous adhesive composition, for example.

(Optional component)
In the present invention, the non-aqueous pressure-sensitive adhesive layer includes, for example, a cooling agent, a warming agent, a coloring matter, a fragrance, a pH adjuster (preferably potassium hydroxide) within the range not inhibiting the effects of the present invention, in addition to the above components. , Diisopropanolamine, etc.) can be included.

<Support>
In the patch of the present invention, a support made of a polyolefin elastomer film is used. By using the support, the adhesiveness with the non-aqueous pressure-sensitive adhesive layer containing the fatty acid ester is increased, and the anchoring property of the patch is improved. Further, the stretchability / flexibility of the patch is increased, and the feeling of sticking (stretchability / flexibility of the patch) is improved.

In the polyolefin elastomer film, preferred examples of the polyolefin elastomer include a copolymer of ethylene and α-olefin.
The copolymer of ethylene and α-olefin is particularly preferably a copolymer of ethylene and an α-olefin having 3 to 12 carbon atoms from the viewpoint of stretchability and flexibility. Specific examples of the α-olefin having 3 to 12 carbon atoms include propylene, butene-1, pentene-1, hexene-1,4-methyl-1-pentene, octene-1, and decene-1.

  The polyolefin-based elastomer film can be usually produced by the same production method as the resin film used for the support of the patch, but it is particularly preferred to produce it using a metallocene catalyst which is a single site catalyst. By producing using a metallocene catalyst, a polyolefin-based elastomer film having a uniform polymer structure with a narrow weight average molecular weight distribution is obtained, and the developability when it is formed into a scroll shape is improved.

Density of the polyolefin-based elastomer film of is preferably 0.860~0.920g / cm ^3, more preferably 0.880~0.900g / cm ^3. By being in this range, it becomes easy to obtain good stretchability and flexibility.
Here, “density” means specific gravity (relative density).
Further, the “density” refers to a value measured by the test method of ASTM D-792.

  Moreover, the thickness of a polyolefin-type elastomer film is not specifically limited, It is preferable that it is 5-300 micrometers, More preferably, it is 7-200 micrometers, More preferably, it is 10-100 micrometers. If it is this range, both moderate moisture permeability and elasticity will be obtained, and a favorable sticking feeling etc. will be obtained when it is set as a patch.

Moreover, it is preferable that the water vapor transmission rate of a polyolefin-type elastomer film is 2000 g / m < ² > / 24hr or less, More preferably, it is 50-1000 g / m < ² > / 24hr, More preferably, it is 100-700g / m < ² > / 24hr. is there. If it is below the upper limit of the range, good skin adhesiveness and feeling of use can be obtained without reducing the transdermal absorbability of the drug. On the other hand, especially if ^50g / m 2 / 24hr or more, hardly stuffy during which the patch is applied to the skin.
Here, “moisture permeability” refers to a value measured according to the condition B of the JIS general test method “moisture-proof packaging material moisture permeability test method (cup method)” (JIS Z 0208-1976).

  Moreover, it is preferable that melting | fusing point of a polyolefin-type elastomer film is 40-120 degreeC, More preferably, it is 50-110 degreeC, More preferably, it is 60-100 degreeC. By being this range, the anchoring property of the patch is improved. The reason for this is that when the non-aqueous pressure-sensitive adhesive layer coating liquid is applied to the support surface during the manufacture of the patch, the drying temperature at the time of drying should be controlled to the same level as the melting point in the range. Therefore, it is presumed that the adhesiveness with the non-aqueous pressure-sensitive adhesive layer is increased by melting the vicinity of the surface of the polyolefin-based elastomer film (support) on the non-aqueous pressure-sensitive adhesive layer side by the drying treatment.

Furthermore, the surface of the polyolefin-based elastomer film (support) on the non-aqueous pressure-sensitive adhesive layer side is a surface such as corona discharge treatment, plasma treatment, surface unevenness treatment, ozone irradiation, chromic acid treatment, hot air treatment, etc. Processing may be performed. Of these, from the viewpoint of improving the anchoring property and operability of the patch, the surface on the non-aqueous pressure-sensitive adhesive layer side is subjected to a surface treatment selected from corona discharge treatment, plasma treatment and surface unevenness treatment. Preferably it is.
The corona discharge treatment can be performed, for example, by bringing the film into contact with a corona atmosphere generated using a known corona discharge treatment device. The corona discharge density can be appropriately set depending on the resin used, conditions, and the like.
The plasma treatment can be performed, for example, by spraying a gas such as argon or helium excited by a known plasma jet onto the surface of the support on the non-aqueous adhesive layer side. Known methods, conditions, and the like can be employed as the plasma processing method, processing conditions, and the like.
The surface unevenness treatment can be performed by, for example, a known sandblasting method.
In addition, the ozone treatment can be performed, for example, by spraying ozone generated by a known ozone generator onto the non-aqueous adhesive layer side surface of the support. Known methods, conditions, and the like can be employed as the ozone treatment method, treatment conditions, and the like.

The patch of the present invention can be preferably produced, for example, by the following production method.
(1) Preparation of coating solution for non-aqueous pressure-sensitive adhesive layer.
Various components constituting the non-aqueous pressure-sensitive adhesive composition such as the above-mentioned pressure-sensitive adhesive base, fatty acid ester, and medicinal component, and a solvent are mixed, and a non-aqueous pressure-sensitive adhesive layer coating liquid (hereinafter referred to as “coating liquid”). May be prepared).
As the solvent, water; organic solvents such as methanol, ethanol, acetone, ethyl acetate, and toluene are used, and among them, it is easy to prepare a coating liquid having a good viscosity. Ethyl acetate is preferably used.
The solid content (% by mass) of the coating solution is preferably 30 to 80% by mass and more preferably 40 to 60% by mass because a coating solution having a good viscosity is easily obtained. Solid content (mass%) of this coating liquid can be adjusted with the usage-amount of a solvent.

In the preparation of the non-aqueous pressure-sensitive adhesive layer coating solution, when water is used as a solvent, for example, after preparing a small product by dissolving a polyvalent metal compound (preferably a water-soluble polyvalent metal compound) and a chelating agent in water. The pH of the accessory is preferably adjusted to the alkali side (preferably pH 8 or more, more preferably pH 9 to 12) with a pH adjuster (preferably sodium hydroxide, potassium hydroxide, ammonia water or the like). By adjusting to the alkali side, it becomes easy to prepare a coating liquid having a good viscosity.
After that, the accessory (alkaline aqueous solution) and other raw materials (adhesive base, fatty acid ester, medicinal component, etc.) are mixed and stirred well until uniform to prepare a non-aqueous adhesive layer coating solution. To do.
In the case of using ethyl acetate other than water as the solvent, for example, all the raw materials to be used and ethyl acetate are mixed and sufficiently stirred until uniform to prepare a non-aqueous pressure-sensitive adhesive layer coating solution.

(2) Coating.
Next, the obtained non-aqueous pressure-sensitive adhesive layer coating solution is applied to the support surface.
The coating method is not particularly limited and is usually selected, for example, a forward rotation roll coater, a reverse roll coater, a gravure coater, a doctor knife coater, a blade coater, a rod coater, an air doctor coater, a curtain coater, and a fountain coater. A kiss coater, dip coating, screen coating, spin coating, cast coating, spray coating, extrusion coating, vacuum coating or the like can be used.
The coating amount of the coating liquid is preferably 1 to 500 g / m ² as the solid content after drying, more preferably 5 to 250 g / m ² , and still more preferably 5 to 200 g / m ² . is there. By being more than the lower limit of the range, the adhesiveness of the patch is improved. On the other hand, by being below the upper limit value, a non-aqueous pressure-sensitive adhesive layer can be formed by a single coating process.
In addition, you may apply this coating liquid beforehand to the peeling film surface provided on a non-aqueous adhesive layer.

(3) Drying.
After coating the non-aqueous pressure-sensitive adhesive layer coating liquid on the support surface, drying is performed to distill off the solvent.
The drying method uses, for example, hot air high-speed air cap, hot air tunnel type, hot air air floating, air through, N ₂ gas displacement drying system, infrared, microwave, (electromagnetic) induction heating, ultraviolet curing, lamp, reflector, etc. A method is mentioned. Among these, a method using a hot air high-speed air cap, a hot air tunnel type, or a hot air air floating is preferable.
The drying condition is preferably set to a temperature at which the adhesive base is crosslinked or a temperature at which the solvents are volatilized. The drying temperature is preferably 40 to 150 ° C, more preferably 60 to 130 ° C, and further preferably 70 to 120 ° C. By setting it as this range, the anchoring property at the time of using as a patch as mentioned above improves especially. In addition, when drying temperature exceeds 150 degreeC, since stability, such as a medicinal ingredient, a plasticizer, and a fatty acid ester, may worsen, it is unpreferable.

(4) Finish.
After forming a non-aqueous pressure-sensitive adhesive layer on the support surface by drying, for example, a release film is laminated on the surface of the non-aqueous pressure-sensitive adhesive layer opposite to the support, and the whole is cut into an appropriate size. Can produce a patch.
When a non-aqueous pressure-sensitive adhesive layer is formed on the release film surface, for example, a support is laminated on the surface of the non-aqueous pressure-sensitive adhesive layer opposite to the release film surface, and the whole is cut into an appropriate size. Thus, a patch can be produced.
As the release film, a vinyl chloride film, a polyethylene film, a polypropylene film, a polyester film, a medicinal rule polyethylene terephthalate separator, and a release paper (release paper) are preferably used. By performing a silicon surface treatment on the surface of the release film in contact with the non-aqueous pressure-sensitive adhesive layer, the peelability of the release film from the non-aqueous pressure-sensitive adhesive layer can be improved.

  In the patch of the present invention, a peelable support film for lamination is laminated on the surface of the support opposite to the non-aqueous pressure-sensitive adhesive layer so that the sticking operation is easy when using the patch. The layer configuration of the patch is preferably (release film / non-aqueous adhesive layer / support / supporting film for pasting). Thereby, a patch can be easily stuck in the procedure which peels a peeling film from a patch, sticks the non-aqueous adhesive layer side to skin, and peels off the support film for sticking.

ADVANTAGE OF THE INVENTION According to this invention, the transparency and the feeling of sticking are favorable, and the patch which was excellent in anchoring property can be provided.
In the patch of the present invention, the transparency can be expressed using transparency (L value) as an index.
As a measurement method, using a color difference meter (manufactured by Nippon Denshoku Industries Co., Ltd., product name: SE2000), measurement is performed by a transmission method at 25 ° C., and (L *, a *, b *) values are obtained, Transparency is evaluated by using L * therein as an index of transparency (L value).
Note that a standard white plate having characteristic values of (X, Y, Z = 94.59, 92.57, 111.43) is used as a measurement standard.
The transparency (L value) in the patch of the present invention is preferably 20 or more as the L value, more preferably 30 or more, and particularly preferably 40 or more. The higher the L value, the higher the transparency and the better, but it is substantially 90 or less.

Moreover, according to the present invention, a patch is provided in which almost no adhesive remains on the skin when the patch is peeled from the skin.
In addition, according to the present invention, it is possible to provide a patch that is not noticeable when applied to the skin.
Further, according to the present invention, it is possible to provide a patch that is difficult to peel off from the skin after being applied to the skin.
In addition, the patch of the present invention can be particularly preferably used as a pharmaceutical preparation that is expected to have immediate effects and sustainability such as anti-inflammatory analgesia and antipruritics.

  Hereinafter, the present invention will be described in more detail using examples, but the present invention is not limited to these examples. Further, “parts” and “%” in the examples are solid contents excluding water unless otherwise specified, and indicate mass parts and mass%, respectively.

<Manufacture of patches>
A patch having a non-aqueous pressure-sensitive adhesive layer having each composition on the support was produced by the following production method. It shows in Table 1 about the composition of the component which comprises a non-aqueous adhesive layer, and a support body.

(Manufacturing method of patch)
1) An adhesive base and a fatty acid ester in which a medicinal component was dissolved or a mixture of a fatty acid ester in which a medicinal component was dissolved and a plasticizer were mixed.
2) Separately, a polyvalent metal compound and a chelating agent (or only a polyvalent metal compound) are mixed and dissolved in 20 parts by mass of water (with respect to 1 part by mass of the polyvalent metal compound), and the pH is adjusted with a pH adjuster as necessary. Was adjusted to 10. In addition, the quantity of the mix | blended pH adjuster was balanced on the basis of the compounding quantity of an acrylic adhesive.
3) The mixed solution prepared in 1) was mixed with the solution prepared in 2) and stirred sufficiently until the whole became uniform to prepare a non-aqueous pressure-sensitive adhesive layer coating solution. Thereafter, the non-aqueous pressure-sensitive adhesive layer coating solution is applied by a comma coater onto the support subjected to each surface treatment so that the amount of the paste after drying is 1.4 g / (10 cm × 14 cm). Worked and dried. Drying was performed at 90 ° C. for 5 minutes by hot air air floating.
4) The support having a non-aqueous pressure-sensitive adhesive layer after drying was cut into an appropriate size to obtain a patch of each example.
The details of the adhesive base and the support used in the preparation of the patch are shown below.

[Adhesive base]
Acrylic adhesive 1: Methacrylic acid / n-butyl acrylate copolymer (manufactured by Dow Corning Toray, trade name “MG-0581”).
Acrylic pressure-sensitive adhesive 2: 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate = 10/80/10 (mass ratio). Lauroyl peroxide was used as a polymerization initiator.
Rubber adhesive 1: SIS (trade name “Clayton D-1107”, manufactured by Kraton Polymer Japan) / alicyclic hydrocarbon (trade name “Arcon P-100”, manufactured by Arakawa Chemical) = 60/40 (mass ratio) .
Rubber adhesive 2: SIS (trade name “Clayton D-1107”, manufactured by Clayton Polymer Japan) / SIS (trade name “Clayton D-1117P”, same as above) / rosin ester (trade name “Pine Crystal KE-311”, Arakawa Chemical Co., Ltd.) = 35/25/40 (mass ratio).
Rubber adhesive 3: SIS (trade name “Clayton D-1107”, manufactured by Kraton Polymer Japan) / alicyclic hydrocarbon (trade name “Arcon P-100”, manufactured by Arakawa Chemical Co., Ltd.) = 45/55 (mass ratio) ).

[Support]
Polyethylene (PE) elastomer film: an ethylene-octene copolymer having a polymer structure having a long-chain branched chain (octene) of the same length as the main chain polyethylene, manufactured by Dow Chemical Co., Ltd., trade name: “engage 8552” "
Polyethylene (PE) film: manufactured by Tamapoli, trade name: “LDPE grade, V1”.
Polyurethane (PU) film: polyurethane film ester, Nisshinbo, trade name: "Mobi Ron film" thickness of 30 [mu] m, moisture permeability 1000g ^/ m 2 ^/ 24hr, the adhesive surface of the non-aqueous adhesive layer: polyurethane nonwoven fabric ( 30 μm thick) laminated.

<Evaluation method>
Using the patch of each example, the anchoring property described below was evaluated.
Further, the skin permeation amount of the drug was evaluated by the skin permeation test for the patches of Example 1 and Comparative Example 3. The results are also shown in Table 1.

(Evaluation of anchorage)
The amount of the entire plaster when the patch of each example was applied to the skin (sex: male, age 20-30, age 10) for 3 hours and the patch was peeled off (total amount of non-aqueous adhesive composition) The ratio (mass%) of the amount of plaster remaining on the skin with respect to was determined as an index of anchoring properties between the support and the non-aqueous pressure-sensitive adhesive layer. If the ratio (% by mass) was 5% by mass or less, it was judged that “the anchoring property was good”.

(Skin penetration test)
A Franz diffusion cell (applicable area: 4), in which the skin collected from the back of a Hos: HR-1 female hairless mouse (7 weeks old) was circulated through a phosphate buffer (pH 7.4 isotonic buffer) at 37 ° C. 91 cm ² ).
The patches of Example 1 and Comparative Example 3 were laminated on the worn skin, and samples in the cell were collected every unit time.
The collected sample was subjected to high performance liquid chromatography analysis, and the amount of each drug that permeated through the skin after 4 hours (the amount of drug permeated through the skin, μg / cm ² ) was determined.
A large amount of the drug permeated through the skin “after 4 hours” means that the drug has excellent percutaneous absorbability.

  From the results in Table 1, it was confirmed that the patches of Examples 1 to 9 according to the present invention were superior in anchoring properties as compared with Comparative Examples 1 to 3.

Further, in the skin permeation test, the skin permeation amount of the drug 4 hours after Example 1 was 4.5 μg / cm ² , and Comparative Example 3 was 1.7 μg / cm ² .
Therefore, it was confirmed that Example 1 according to the present invention had a large amount of drug permeation after 4 hours and good percutaneous absorption of the drug compared to Comparative Example 3.

Furthermore, with respect to the patches of Examples 1 to 9 according to the present invention, transparency measurement using a color difference meter (trade name “SE2000”, manufactured by Nippon Denshoku Industries Co., Ltd.) and 10 volunteers (male, age 20) (30 years old) was evaluated for the feeling of sticking (stretchability / flexibility) when the patch of each case was applied to the elbow.
As a result, all the patches were excellent in transparency (L value 40 or more), and the patches themselves were not conspicuous when applied to the skin, and it was confirmed that the appearance at the time of application was good.
Further, sensory evaluation by 10 volunteers confirmed that the feeling of sticking (stretchability / flexibility) was good.
From the above, it was confirmed that the patches of Examples 1 to 9 according to the present invention had good transparency and sticking feeling and were excellent in anchoring properties.

Claims (4)

In the patch having a non-aqueous adhesive layer containing an adhesive base on the support surface,
The support comprises a polyolefin elastomer film,
The polyolefin elastomer in the polyolefin elastomer film is a copolymer of ethylene and an α-olefin having 3 to 12 carbon atoms,
The patch, wherein the non-aqueous pressure-sensitive adhesive layer contains a fatty acid ester represented by the following general formula (1).
R ² OOC-R ^1- (COOR ³ ) _n (1)
[Wherein, R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, R ² is a hydrocarbon group having 1 to 20 carbon atoms, and R ³ is a hydrocarbon group having 1 to 10 carbon atoms or a hydrogen atom. Yes, n is an integer of 0 or 1. ] The non-aqueous pressure-sensitive adhesive layer is formed by applying a coating solution for a non-aqueous pressure-sensitive adhesive layer containing the fatty acid ester and a pressure-sensitive adhesive base to the support, followed by drying.
The patch of claim 1, wherein the polyolefin elastomer film has a melting point of 40 to 120 ° C. The patch according to claim 1 or 2 , wherein a surface treatment selected from corona discharge treatment, plasma treatment and surface unevenness treatment is applied to the surface of the support on the non-aqueous pressure-sensitive adhesive layer side. The adhesive base, relative to the total monomer units constituting the PSA base, any of claim 1 to 3 is a polymer having a monomer unit selected from 50 to 100 wt% (meth) acrylic acid alkyl ester The patch according to crab.