JPWO2007126067A1 - Non-aqueous adhesive composition, patch and method for producing the patch - Google Patents

Abstract

The present invention relates to a nonaqueous pressure-sensitive adhesive composition comprising a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion, and a polyvalent metal compound (B). And a patch comprising the non-aqueous pressure-sensitive adhesive composition laminated on a support. The present invention also provides a mixed solution in which a polyvalent metal compound (B) and a chelating agent (C) that forms a chelate with the polyvalent metal compound (B) are previously dissolved in a water-containing solvent and the pH is adjusted to 7 or more. Then, the mixed solution is mixed with a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion to prepare an aqueous dispersion. The present invention also relates to a method for producing a patch, which is coated on a liner or a support and dried to provide a non-aqueous pressure-sensitive adhesive layer.

Description

The present invention relates to a non-aqueous adhesive composition, a patch using the non-aqueous adhesive composition, and a method for producing the patch.
This application claims priority based on Japanese Patent Application No. 2006-126716 for which it applied on April 28, 2006, and uses the content here.

Conventionally, as a preparation for percutaneously absorbing a drug, for example, a patch in which a plaster (adhesive composition) is laminated on a support has been used.
As the patch, a so-called hydrous patch using a polymer such as polyacrylic acid swollen with water, a rubber-based adhesive such as styrene-isoprene-styrene block copolymer (SIS) or polyisobutene, or There are so-called non-aqueous patches using an acrylic adhesive.

In the case of a water-containing patch, there is a problem that water is evaporated and the paste becomes hard during sticking to the skin, or the adhesiveness of the paste is impaired.
On the other hand, non-aqueous patches do not change over time, which is a problem with hydrous patches, and high adhesive strength can be obtained even if the plaster layer (adhesive layer) is thin. It is more effective than the system patch.
However, the non-aqueous patch has a problem that, when peeled from the skin, the adhesive strength of the plaster is too strong and the stratum corneum of the skin peels off.

In order to solve the above problems in non-aqueous patches, for example, an acrylic copolymer, a plasticizer in liquid or paste form at room temperature having a molecular weight of 800 or more and a hydrophobic parameter of −20 to 45, and crosslinking A skin pressure-sensitive adhesive composition (see Patent Document 1) having good adhesiveness to human skin, comprising an agent (isocyanate-based crosslinking agent) has been proposed.
In addition, an acrylic copolymer obtained by copolymerizing a monomer mixture containing (meth) acrylic acid alkyl ester and a functional monomer as essential components in the pressure-sensitive adhesive layer, and a carbon number of 12 to 16 A fatty acid ester comprising a higher fatty acid and a lower monohydric alcohol having 1 to 4 carbon atoms, a monoglyceride comprising a higher fatty acid having 8 to 10 carbon atoms and glycerin, and a transdermally absorbable drug, and an adhesive A percutaneous absorption preparation (see Patent Document 2) having a low skin irritation, in which a layer is crosslinked with an isocyanate-based crosslinking agent or the like, has been proposed.
Moreover, it is a percutaneous absorption preparation which provided the plaster layer containing buprenorphine hydrochloride and / or buprenorphine and an absorption enhancer in one side of the support, and the absorption enhancer has 6 to 8 carbon atoms. A transdermal absorption preparation (see Patent Document 3) excellent in skin permeability of a drug, comprising a combination of a fatty acid monoglyceride and isopropyl myristate and having a plaster layer crosslinked with a crosslinking agent has been proposed.
JP 2005-89438 A JP-A-8-143451 JP-A-7-304672

However, the techniques described in Patent Documents 1 and 2 have production problems such as high energy costs because it takes several tens of minutes to 2.5 days for drying and heat aging in the manufacturing process of the patch. .
For example, in the example described in Patent Document 1 (when an isocyanate-based crosslinking agent is used), the drying condition for forming the pressure-sensitive adhesive layer on the release sheet (release film) is 80 ° C. for 20 minutes (implementation). See Example 1, paragraph [0040]).
Moreover, in the Example (when an isocyanate type crosslinking agent is described) described in Patent Document 2, the heat aging condition after bonding the pressure-sensitive adhesive layer to the support (laminated film) is 70 ° C. for 60 hours ( Examples and Comparative Examples, see paragraph [0038]).

In addition, a cross-linking agent other than an isocyanate-based cross-linking agent, for example, an organic metal salt such as an example described in Patent Document 3 (see Example 10, paragraph [0048]) or a metal alcoholate is also used. It takes several days in the manufacturing process of the adhesive, or the viscosity increases during the application of the adhesive layer coating liquid to the support surface, and it cannot be applied uniformly, and the coating time is limited. There is an inferior problem.
Furthermore, the obtained patch does not necessarily satisfy the adhesiveness to the skin and the suppression of pain at the time of peeling at the same time.

  The present invention has been made in view of the above circumstances, and is a non-aqueous pressure-sensitive adhesive that provides a patch having excellent manufacturability, good adhesiveness to the skin, and reduced pain during peeling. It is an object to provide a composition, a patch, and a method for producing the patch.

As a result of intensive studies, the present inventors have completed the present invention in order to solve the above problems.
That is, the first embodiment of the present invention comprises a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion, and a polyvalent metal compound (B). It is a non-aqueous pressure-sensitive adhesive composition.
In the present invention, the polyvalent metal compound (B) is preferably a water-soluble polyvalent metal compound.
Moreover, in this invention, it is preferable to contain further the chelating agent (C) which forms a chelate with the said polyvalent metal compound (B).
Moreover, in this invention, the said water-insoluble polymer compound (A) is chosen from the monomer unit chosen from the (meth) acrylic-acid alkylester containing a C4-C12 alkyl group, and the monomer containing a carboxy group. It is preferable that the polymer has a monomer unit.
Moreover, in this invention, it is preferable to contain a plasticizer (D) further.
In the present invention, it is preferable to further contain a drug (E).

Moreover, the 2nd embodiment of this invention is a patch by which the said non-aqueous adhesive composition is laminated | stacked on a support body.
In the third embodiment of the present invention, the polyvalent metal compound (B) and the chelating agent (C) that forms a chelate with the polyvalent metal compound (B) are previously dissolved in a water-containing solvent, and the pH is adjusted to 7 After preparing the mixed solution prepared as described above, the aqueous solution is prepared by mixing the mixed solution and the water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion. The method for producing a patch is characterized in that the aqueous dispersion is applied to a liner or a support and dried to provide a non-aqueous pressure-sensitive adhesive layer.

  According to the present invention, a non-aqueous pressure-sensitive adhesive composition, a patch, and a patch that provide a patch having excellent manufacturability, good adhesiveness to the skin, and reduced pain at the time of peeling. A manufacturing method can be provided.

≪Nonaqueous adhesive composition≫
The non-aqueous pressure-sensitive adhesive composition of the present invention contains a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion, and a polyvalent metal compound (B).
The non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a chelating agent (C) that forms a chelate with the polyvalent metal compound (B).
The non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a plasticizer (D).
Moreover, the non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a drug (E).

The non-aqueous pressure-sensitive adhesive composition of the present invention constitutes a non-aqueous pressure-sensitive adhesive layer of a patch (non-aqueous patch) comprising, for example, a support layer, a non-aqueous pressure-sensitive adhesive layer, and a liner layer.
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.

<Water-insoluble polymer compound (A)>
The water-insoluble polymer compound (A) (hereinafter sometimes referred to as component (A)) used in the present invention has a functional group that forms a crosslinking point with a polyvalent metal ion.
In the present specification and claims, the “water-insoluble polymer compound” refers to a polymer compound having a solubility in water at 20 ° C. of less than 1 mg / mL.
In addition, the “functional group that forms a cross-linking point with a polyvalent metal ion” means a group having a characteristic of forming a ring structure (chelate ring) by coordination with a polyvalent metal ion sandwiched between them. In the above, a carboxyl group, an amino group, a sulfone group, and a hydroxyl group are preferable, and among them, a carboxyl group is particularly preferable.
By containing the component (A), the adhesiveness to the skin is improved when a patch is prepared.

As the water-insoluble polymer compound (A), an acrylic polymer is preferable because of its good adhesiveness to the skin when used as a patch.
Among the acrylic polymers, a polymer having a monomer unit selected from (meth) acrylic acid alkyl ester, a monomer unit selected from a monomer containing a carboxy group, and the like is preferably used.
In the present specification and claims, “monomer unit” means a structural unit (monomer unit) constituting a 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, and particularly preferably has good adhesive strength. Are 4 to 12, and may be linear or branched.
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.
Among these, the acrylic polymer contains a monomer unit selected from (meth) acrylic acid alkyl esters containing an alkyl group having 4 to 12 carbon atoms and a carboxy group from the viewpoints of adhesiveness, crosslinkability, and aggregation. A polymer having a monomer unit selected from monomers is preferred.

The proportion of the monomer units in the acrylic polymer (the total of the (meth) acrylic acid alkyl ester and the monomer containing the carboxyl group) is 10 to 100% by mass with respect to all monomer units constituting the acrylic polymer. Preferably, 40-100 mass% is more preferable. By being above the lower limit of the range, the tackiness, crosslinkability, cohesiveness, and water resistance are improved.
In particular, when a polymer having a monomer unit selected from a (meth) acrylic acid alkyl ester containing an alkyl group having 4 to 12 carbon atoms and a monomer unit selected from a monomer containing a carboxy group is used, the polymer is constituted. The proportion of the former is preferably from 30 to 99 mass%, more preferably from 50 to 97 mass%, based on all monomer units. The ratio of the latter is preferably 1 to 70% by mass, and more preferably 3 to 50% by mass. By being in this range, the above effects can be obtained more easily.

As the acrylic polymer, 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 proportion of monomer units provided by the comonomer is preferably 50% by mass or less based on the total monomer units constituting the acrylic polymer.

The acrylic polymer 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 parts by mass and more preferably 0.1 to 2 parts by mass with respect to 100 parts by mass of the total mass of 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 parts by mass, and more preferably 0.1 to 2 parts by mass with respect to 100 parts by mass of the total mass of the monomers used for the synthesis.

Specifically, the acrylic polymer 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 parts by mass, more preferably 0.5 to 5 parts by mass with respect to 100 parts by mass of the total mass of monomers used for the synthesis. When the amount used is 0.1 parts 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 parts by mass or less, the 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, if 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 polymer can be controlled within a certain range.

  More specifically, examples of the acrylic polymer include acrylic acid / octyl acrylate copolymer, acrylic ester / acetic acid, which are listed as adhesives in, for example, Pharmaceutical Additives Dictionary 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, methacrylic acid・ N-butyl acrylate copolymer, adhesives such as acrylic polymers contained in acrylic resin 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, a water-insoluble high molecular compound (A) may be used individually by 1 type, and may use 2 or more types together.
The blending amount of the water-insoluble polymer compound (A) is preferably 30 to 95% by mass, more preferably 50 to 90% by mass, and particularly preferably 55 to 85% in the non-aqueous pressure-sensitive adhesive composition. % By mass. By being more than the lower limit of the range, the adhesiveness when the patch is applied to the skin is improved, and the peeling and turning of the patch from the skin are further reduced. On the other hand, by being below the upper limit, pain when the patch is peeled from the skin is reduced.

<Polyvalent metal compound (B)>
In the present invention, a polyvalent metal compound (B) (hereinafter sometimes referred to as component (B)) is used. By containing the component (B), it is possible to adjust the adhesiveness of the patch to the skin by crosslinking reaction with the component (A). The effect of suppressing pain at the time of peeling is obtained. In addition, when a non-aqueous pressure-sensitive adhesive layer coating solution is prepared, the viscosity change of the non-aqueous pressure-sensitive adhesive layer coating solution is suppressed, and the coating property to the liner or the support becomes good, and the patch productivity is improved. The effect of improvement is obtained.

Examples of the polyvalent metal compound (B) used in the present invention include magnesium compounds, calcium compounds, zinc compounds, aluminum compounds, titanium compounds, tin compounds, iron compounds, manganese compounds, cobalt compounds, nickel compounds and the like. Of these, aluminum compounds, magnesium compounds, and calcium compounds are preferred from the viewpoint of safety to the skin.
Any of these aluminum compounds, calcium compounds and magnesium compounds can be suitably used.
Specifically, aluminum hydroxide, aluminum sulfate, ammonium aluminum sulfate, aluminum potassium sulfate, aluminum chloride, aluminum lactate, dihydroxyaluminum aminoacetate, aluminum acetate, synthetic aluminum silicate, aluminum metasilicate; calcium sulfate, calcium nitrate, chloride Calcium, calcium acetate, calcium oxide; magnesium hydroxide, magnesium carbonate, magnesium sulfate, magnesium acetate, magnesium oxide, alumina hydroxide / magnesium, magnesium aluminate metasilicate, magnesium aluminate silicate, synthetic hydrotalcite, their metals Water-soluble compounds such as double salts containing atoms, and poorly water-soluble compounds are exemplified. Of these, water-soluble polyvalent metal compounds are preferred from the viewpoint of adhesiveness to the skin of the patch and manufacturability, and include aluminum sulfate, aluminum ammonium sulfate, potassium aluminum sulfate, aluminum chloride, aluminum lactate, aluminum acetate, nitric acid. Calcium, calcium chloride, calcium acetate, magnesium sulfate and magnesium acetate are preferred, and potassium aluminum sulfate, ammonium ammonium sulfate, aluminum lactate and aluminum chloride are particularly preferred.
In the present specification and claims, “water-soluble polyvalent metal compound” refers to a polyvalent metal compound having a solubility in water at 20 ° C. of 1 mg / mL or more, preferably 10 mg / mL or more. .
These polyvalent metal compounds (B) may be used alone or in combination of two or more.
The blending amount of the polyvalent metal compound (B) is preferably 0.01 to 2 parts by mass, more preferably 0.05 to 1 part by mass with respect to 100 parts by mass of the solid content of the acrylic polymer. More preferably, it is 0.1 to 1 part by mass. By being more than the lower limit of this range, the crosslinkability with the said (A) component increases, and the pain at the time of peeling a patch from skin is suppressed more.
On the other hand, by being below the upper limit, the crosslinking with the component (A) is appropriately controlled, and the adhesiveness to the skin when used as a patch is further improved.

<Chelating agent (C)>
The non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a chelating agent (C) that forms a chelate with the polyvalent metal compound (B) (hereinafter also referred to as component (C)). .
The component (C) is a compound having the ability to form a chelate with the polyvalent metal ion of the polyvalent metal compound (B). By containing the component (C), the crosslinkability between the component (A) and the component (B) is controlled. As a result, in the manufacture of patches, the viscosity change of the non-aqueous pressure-sensitive adhesive layer coating solution containing the non-aqueous pressure-sensitive adhesive composition, particularly the increase in viscosity is suppressed, and the coating property to the liner or the support is good. Thus, the manufacturability of the patch is improved and a patch having a uniform and good pressure-sensitive adhesive layer is obtained.
Examples of the chelating agent include ethylenediamine, N-methylethylenediamine, N, N′-dimethylethylenediamine, N, N, N ′, N′-tetramethylethylenediamine, trimethylenediamine, cis-1,2-diaminocyclohexane, 1, 2,3-triaminopropane, diethylenetriamine, triethylenetetramine, pyridine-2,6-dicarboxylic acid, nicotinic acid hydrazide, histamine, iminodiacetic acid, hydroxyethylacetic acid, nitrilotriacetic acid, N, N′-ethylenediaminediacetic acid, N ′ -Hydroxyethyl-N, N, N'-triacetic acid, ethylenediamine-N, N'-diacetic acid-N, N'-dipropionic acid, ethylenediaminetetrapropionic acid, 1,2-propylenediaminetetraacetic acid, trimethylenediamine Tetraacetic acid, trans- Chlohexane-1,2-diaminetetraacetic acid, ethyl etherdiaminetetraacetic acid, diethylenetriaminepentaacetic acid, glycol etherdiaminetetraacetic acid, glycine, sarcosine, alanine, leucine, serine, cysteine, glutamic acid, tryptophan, adenine, acetylacetone, 2-nitroso -1-naphthol-8-hydroxynazoline, citric acid, malic acid, tartaric acid, disodium edetate, diethylenetriaminepentaacetic acid, or monovalent metal salts thereof (alkali metal salts such as sodium salts and potassium salts), amines Preferred examples include salts and ammonium salts. Of these, citric acid, disodium edetate, diethylenetriaminepentaacetic acid, and monovalent metal salts of these compounds are more preferable.
These chelating agents (C) may be used individually by 1 type, and may use 2 or more types together.
It is preferable that the compounding quantity of a chelating agent (C) is 0.01-5 mass parts with respect to 100 mass parts of solid content of an acrylic adhesive, More preferably, it is 0.1-2 mass parts. By being more than the lower limit of the range, an increase in the viscosity of the non-aqueous pressure-sensitive adhesive layer coating solution containing the non-aqueous pressure-sensitive adhesive composition is suppressed, and the productivity of the patch is improved. Moreover, when it is used as a patch, the adhesion to the skin is improved. On the other hand, by being below the upper limit, the pain when the patch is peeled from the skin is further suppressed.

  In the non-aqueous pressure-sensitive adhesive composition of the present invention, the mixing ratio of the polyvalent metal compound (B) and the chelating agent (C) is preferably 1/10 to 5/1 in terms of mass ratio. More preferably, it is 5 to 3/1. In the mass ratio, when the ratio of the component (B) is at least the lower limit, the crosslinkability with the component (A) is increased, and the pain when the patch is peeled from the skin is further suppressed. On the other hand, when the ratio of the component (B) is not more than the upper limit value, the crosslinking with the component (A) is appropriately controlled, and the adhesiveness to the skin when used as a patch is further improved.

<Plasticizer (D)>
The non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a plasticizer (D) (hereinafter sometimes referred to as component (D)). By containing the component (D), the wettability of the non-aqueous pressure-sensitive adhesive layer in the patch to the skin is improved and the adhesion is increased, and at the same time, pain when the patch is peeled from the skin is reduced.
Examples of the component (D) include dihydric alcohols (for example, ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, dipropylene glycol, 1,3-hexylene glycol), and trihydric alcohols (for example, glycerin). , Trimethylolpropane, etc.), tetrahydric alcohol (eg, erythritol, pentaerythritol, diglycerin, etc.), pentavalent alcohol (eg, xylitol, etc.), hexavalent alcohol (eg, sorbitol, dipentaerythritol, etc.), etc. Alcohol; sugars such as glucose, mannose, sucrose, sorbitan, trehalose, alkylglycoside; polymers of polyhydric alcohols such as polyethylene glycol, polypropylene glycol, polyglycerin; fats Ester, or derivatives thereof, higher alcohols or their derivatives having 8 to 20 carbon atoms such as octyldodecanol; olive oil, and the like fats and oils such as castor oil. Of these, polyhydric alcohols, fatty acid esters, and fats and oils are preferable, and fatty acid esters are particularly preferable because the effects of containing the component (D) are improved and the transdermal absorbability of the drug is good.

As the fatty acid ester, a compound represented by the following general formula (1) is particularly preferable.
^{R 2 OOC-R 1 -R 3} ··· (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; R ³ is a hydrogen atom or a group represented by “—COOR ⁴ ”. It is. R ⁴ is a hydrocarbon group having 1 to 10 carbon atoms. ]

In the formula (1), R ¹ is a hydrocarbon group having 3 to 36 carbon atoms, preferably 4 to 20 carbon atoms, which may be linear or branched and saturated. Or unsaturated.
In addition, when R ³ is a hydrogen atom, the number of carbon atoms of R ¹ is preferably 10 to 36, and when R ³ is a group represented by “—COOR ⁴ ”, the number of carbon atoms of R ¹ is 3 It is preferably ~ 20.
R ² represents a hydrocarbon group having 1 to 20 carbon atoms, preferably 1 to 18 carbon atoms, and may be linear or branched, and may be saturated or unsaturated. . Further, when ^{R 3} is a hydrogen atom, the number of carbon atoms in ^{R 2} is preferably 1 to 18. When R ³ is a group represented by “—COOR ⁴ ”, the carbon number of R ² is preferably 1 to 10, more preferably 1 to 6, and further preferably 1 to 3.
R ⁴ is a hydrocarbon group having 1 to 10 carbon atoms, preferably a hydrocarbon group having 1 to 8 carbon atoms, and the hydrocarbon group may be linear or branched, It may be saturated or unsaturated. R ² and R ⁴ may be the same as or different from each other.
Formula (1) is a monoester when R ³ is a hydrogen atom, and is a diester when R ³ is a group represented by “—COOR ⁴ ”.

  Specific examples of fatty acid esters include isopropyl myristate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, ethyl oleate, isopropyl palmitate, octyl palmitate, oleyl oleate, isotridecyl myristate, ethyl laurate, etc. It is done. Of these, isopropyl myristate, diethyl sebacate, diisopropyl sebacate, diisopropyl adipate, isopropyl palmitate, octyl palmitate, and oleyl oleate are preferred.

These plasticizers (D) may be used individually by 1 type, and may use 2 or more types together.
5-80 mass parts is preferable with respect to 100 mass parts of solid content of an acrylic polymer, as for the compounding quantity of a plasticizer (D), 10-80 mass parts is more preferable, 15-75 mass parts is more preferable. By being more than the lower limit of the range, the pain when the patch is peeled from the skin is further reduced. In addition, the percutaneous absorption of the drug (E) is increased, and the productivity is improved. On the other hand, by being below the upper limit value, the adhesiveness to the skin when it is used as a patch is further improved, and the patch is difficult to peel off from the skin.

<Drug (E)>
The non-aqueous pressure-sensitive adhesive composition of the present invention preferably further contains a drug (E) (hereinafter sometimes referred to as “component (E)”). By containing the component (E), a patch (pharmaceutical preparation) having a medicinal effect of each drug can be provided.
The kind of the drug (E) that can be used in the present invention is not particularly limited, and among them, it is possible to use even a poorly water-soluble drug, generally a drug that is hardly percutaneously absorbed as an external preparation.
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.
Specific examples of the component (E) include non-steroidal anti-inflammatory agents such as indomethacin, ferbinac, ketoprofen, flurbiprofen, diclofenac, and salicylic acid derivatives, or ester derivatives thereof; antihistamines such as diphenhydramine; Neuroactive agents; Hormonal agents such as estradiol and testosterone; analgesics such as aspirin, acetaminophen and ibuprofen; antiarrhythmic agents such as disopyramide phosphate; coronary vasodilators such as trazoline hydrochloride; local anesthetics such as lidocaine; Anti-Parkinson's disease such as muscle relaxants such as kissamethonium chloride, antifungal agents such as clotrimazole, antineoplastic agents such as fluorouracil, dysuria such as tamsulosin hydrochloride, antiepileptics such as diazepam, and bromocriptine mesylate Antihypertensive agents such as furosemide and 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; fluphenazine and theoritadine Tranquilizers; vitamins such as vitamin A, vitamin E, vitamin K, octothiacin, riboflavin butyrate; prostaglandins, scopolamine, fentanyl, red pepper extract, nonylic acid vanillylamide, etc. Since the effects of the invention can be obtained particularly remarkably, a poorly water-soluble drug is preferable, and non-steroidal anti-inflammatory agents such as indomethacin, felbinac, ketoprofen, flurbiprofen, diclofenac, salicylic acid derivatives; Hormonal agents such as testosterone; antihypertensive agents such as furosemide and clonidine; vasodilators such as nitroglycerin and isosorbide nitrate; smoking cessation aids such as nicotine; bronchodilators such as tulobuterol; Is more preferable.
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 non-aqueous pressure-sensitive adhesive composition of the present invention, in addition to the above-mentioned components, it contains optional components such as a cooling agent, a warming agent, a dye, a fragrance, and a pH adjuster, as long as the effects of the present invention are not impaired. Can be made.

Examples of the pH adjuster that can be used in the present invention include alkali compounds. Specifically, sodium citrate, potassium acetate, sodium acetate, diethanolamine, sodium bicarbonate, sodium carbonate, potassium bicarbonate, potassium carbonate, triethanolamine, diisopropanolamine, triisopropanolamine, monoethanolamine, aqueous ammonia, Potassium hydroxide, calcium hydroxide, sodium hydroxide, magnesium hydroxide, sodium hydrogen phosphate, trisodium phosphate, dipotassium phosphate, etc. can be preferably used, among which sodium citrate, sodium acetate, diethanolamine, carbonic acid Sodium hydrogen, diisopropanolamine, triethanolamine, triisopropanolamine, monoethanolamine, aqueous ammonia, potassium hydroxide, calcium hydroxide, sodium hydroxide , Sodium hydrogen phosphate, trisodium phosphate are more preferred, and sodium hydroxide, potassium hydroxide, aqueous ammonia, sodium bicarbonate, diisopropanolamine are more preferable.
These pH adjusters may be used alone or in combination of two or more.
The blending amount of the pH adjuster can be blended in an appropriate amount, for example, to adjust to the pH described in the method for producing the patch of the present invention described later.

  The method for preparing the non-aqueous pressure-sensitive adhesive composition of the present invention is not particularly limited. Preferably, the non-aqueous pressure-sensitive adhesive composition is preferably applied to the liner or the support described in the method for producing the patch of the present invention described later. The same method as that for forming the aqueous pressure-sensitive adhesive layer is used.

≪Patch≫
The patch of the present invention is obtained by laminating the non-aqueous pressure-sensitive adhesive composition of the present invention on a support.

<Support>
Examples of the support used in the patch of the present invention include polyethylene, polyurethane / vinyl chloride copolymer, polyurethane, polyethylene elastomer (for example, a copolymer of ethylene and α-olefin), and polyester elastomer (for example, terephthalic acid). A film made of a resin selected from a copolymer of dimethyl and 1,4-butylene glycol or the like, or a film in which the film and a porous sheet are integrated is preferably used. Among these, a polyurethane film, a polyethylene elastomer film, a polyester elastomer film, or a film in which these films and a porous sheet are integrated is more preferably used.
Nonwoven fabric, woven fabric, knitted fabric and the like are preferably used as the porous sheet here. Further, polyester, rayon, nylon, polypropylene, polyethylene, polyurethane or the like is used as the material for these fibers.
When using a nonwoven fabric, the nonwoven fabric manufactured by the needle punch method, the spunlace method, the spun bond method, the stitch bond method, the melt blown method etc. is mentioned.
The film made of the resin and the porous sheet can be integrated by heat fusion, bonding with an adhesive, or the like, or a method of integrally forming the molten resin while extruding the porous sheet.
Although there is no restriction | limiting in particular in the thickness of the film which consists of resin, It is preferable that it is 5-500 micrometers, More preferably, it is 7-300 micrometers, More preferably, it is 10-200 micrometers. If it is this range, both moderate moisture permeability and elasticity will be obtained, and when it is set as a patch, favorable usability (easiness of sticking etc.) will be obtained.
Moisture permeability of the support is preferably not more than 8000g ^/ m 2 ^/ 24hr, more preferably 100~4000g ^/ m 2 ^/ 24hr, more preferably from 100~3000g ^/ m 2 ^/ 24hr. 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 100g ^/ m 2 ^/ 24hr or more, skin irritation when the patch used is reduced.
The moisture permeability of the support can be adjusted by the thickness of the film, the hydrophilicity, the porosity, the basis weight of the porous sheet, and the like.
In addition, the moisture permeability of the said support body shows the value measured by the condition B of JIS general test method "moisture-proof packaging material moisture permeability test method (cup method)" (JIS Z 0208-1976).

  Furthermore, the surface of the support on which the non-aqueous pressure-sensitive adhesive composition is laminated (non-water-based pressure-sensitive adhesive layer) may be subjected to corona discharge treatment, plasma treatment, surface unevenness treatment, ozone irradiation, chromic acid as necessary. Surface treatment such as treatment, hot air treatment, anchor coating with polyurethane resin, etc. may be applied. Of these, surface treatment selected from corona discharge treatment, plasma treatment, and surface unevenness treatment is applied from the viewpoint of improving the operability of the patch (adhesion between the support and the non-aqueous adhesive layer) and operability. It is preferable that

The patch of the present invention is prepared, for example, by preparing a nonaqueous adhesive layer coating solution containing the nonaqueous adhesive composition of the present invention, and applying the nonaqueous adhesive layer coating solution onto the support. It can manufacture by the method of apply | coating and laminating | stacking. Alternatively, the non-aqueous pressure-sensitive adhesive layer coating solution is coated on a liner and laminated, and then the support is laminated on the surface opposite to the liner-side surface of the coating layer. You can also Preferably, it can be produced by a method similar to the method for producing the patch of the present invention described later.
As the liner, a vinyl chloride film, a polyethylene film, a polypropylene film, a polyester film, a medicinal rule polyethylene terephthalate separator, a release paper (release paper), or the like is preferably used. The surface of these liners in contact with the non-aqueous pressure-sensitive adhesive layer can be treated with a silicon surface to improve the releasability of the liner from the non-aqueous pressure-sensitive adhesive layer.

  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 structure of the patch is preferably (liner / non-aqueous pressure-sensitive adhesive layer / support / supporting film for sticking). Thereby, a patch can be easily stuck in the procedure which peels a liner from a patch, sticks the non-aqueous adhesive layer side to skin, and peels off the support film for sticking.

The adhesive patch of the present invention adjusts the adhesive strength so that the ball tack value (measured at an inclination angle of 30 ° according to JIS Z 0237 test) is preferably 4 to 25, more preferably 4 to 15. It is preferable to do. If it is more than the lower limit of this range, adhesiveness to the use site of the patch will be sufficiently obtained. On the other hand, if the amount is not more than the upper limit value, the patch can be peeled off with less skin pain.
The adhesive strength in the patch can be adjusted by selecting the water-insoluble polymer compound (A), the polyvalent metal compound (B), the plasticizer (D), controlling the blending amount, and the like.

In addition, the patch of the present invention preferably has a transparency measured by the method described below of 20 or more as an L * value, more preferably 30 or more, and particularly preferably 40 or more. The higher the L * value, the better the transparency, but it is practically 90 or less.
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 * as an index.
A standard white plate having characteristic values (X, Y, Z = 94.59, 92.57, 111.43) is used as a measurement standard.

≪Method for producing patch≫
In the method for producing the patch of the present invention, the polyvalent metal compound (B) and the chelating agent (C) that forms a chelate with the polyvalent metal compound (B) are previously dissolved in a water-containing solvent, and the pH is adjusted to 7 or more. After preparing the adjusted mixed solution, the aqueous solution is prepared by mixing the mixed solution and the water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with the polyvalent metal ion, In this production method, an aqueous dispersion is applied to a liner or a support and dried to provide a non-aqueous pressure-sensitive adhesive layer.

The method for producing the patch of the present invention can be performed, for example, as follows.
The polyvalent metal compound (B) and the chelating agent (C) are preliminarily dissolved in a water-containing solvent, and the pH is adjusted to 7 or higher, preferably 8 or higher, more preferably 8 to 12, more preferably using a pH adjuster or the like. Prepare a mixed solution (S) adjusted to 9-12 (pH: value at 20 ° C.). By setting the pH to 7 or more, the crosslinking rate between the water-insoluble polymer compound (A) and the polyvalent metal compound (B) is controlled, and the viscosity of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution) is controlled. There is little change, coating unevenness hardly occurs, and uniform coating is easy to perform. In addition, after the preparation of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution), a decrease in the adhesive strength with time of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution) is suppressed. On the other hand, by setting the pH to 12 or less, an increase in viscosity of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating liquid) is suppressed.
The water-containing solvent means a solvent which may be 40% by mass or more, preferably 60% by mass or more, and 100% by mass with respect to the whole solvent, and particularly preferably a solvent composed only of water.
As a solvent other than water, ethanol, acetone or the like may be contained.
The content of the component (B) in the mixed solution (S) is preferably 1 to 15% by mass and more preferably 2 to 8% by mass in the mixed solution (S).
The content of the component (C) in the mixed solution (S) is preferably 1 to 15% by mass and more preferably 2 to 10% by mass in the mixed solution (S).
In addition, as (B) component, (C) component, and a pH adjuster, the thing similar to what was illustrated in said << non-aqueous adhesive composition >> can be used.

Separately from the mixed solution (S), the water-insoluble polymer compound (A) and, if necessary, predetermined amounts of the plasticizer (D), the drug (E), and the optional component are mixed.
Subsequently, these mixtures are mixed with a solvent to prepare a mixed solution (T) having a solid content of preferably 30 to 80% by mass, more preferably 40 to 60% by mass. By setting the solid content in this range, a mixed solution (T) having an appropriate viscosity can be obtained and handled easily, and the operability is improved.
Examples of the solvent include water; organic solvents such as methanol, ethanol, and acetone. Among them, water and ethanol are preferable, and water is most preferable.
In addition, the water-insoluble polymer compound (A) is preferably used in the form of a solution or an emulsion from the viewpoint of operability. In that case, the content of the component (A) in the solution or emulsion is preferably 30 to 80% by mass, and more preferably 40 to 60% by mass. As the solvent used for the solution or emulsion, water, methanol, ethanol, acetone or the like is preferably used.
In addition, as (A) component, (D) component, (E) component, and arbitrary components, the thing similar to what was demonstrated in the said << non-aqueous adhesive composition >> can be used.

Next, the mixed solution (S) and the mixed solution (T) are mixed to prepare an aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution).
The mixing ratio of the mixed solution (S) and the mixed solution (T) is adjusted so that each component has a desired blending amount in the non-aqueous pressure-sensitive adhesive composition constituting the non-aqueous pressure-sensitive adhesive layer.
After stirring sufficiently until the entire aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating liquid) is uniform, the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating liquid) is applied to the liner or support. Work.
The viscosity at 20 ° C. of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution) is preferably about 300 to 30000 mPa · s, more preferably about 1000 to 10000 mPa · s.
In addition, a viscosity here shows the value measured by the viscosity measuring method by a single cylindrical rotational viscometer according to JISZ8803.
In the present invention, there is little change in the viscosity of the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution), and it is particularly difficult for the viscosity to increase, and a coating film having a uniform thickness is easily applied to the liner or the support. Can be crafted.
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 10 to 200 g / m ² . is there. By setting it to be equal to or higher than the lower limit of the range, the adhesiveness of the patch is improved. In addition, percutaneous absorption of the drug is enhanced. On the other hand, by setting it to the upper limit value or less, it is possible to form a non-aqueous pressure-sensitive adhesive layer by a single coating process.
As the liner and the support, those similar to those exemplified in the above << Patch >> can be used.

Then, after applying an aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution) to the liner or support surface, drying is performed to distill off the solvent. By drying, a non-aqueous pressure-sensitive adhesive layer can be provided on the liner or the support surface.
Examples of the drying method include hot air high-speed air cap, hot air tunnel type, hot air air floating, air through, N2 gas replacement drying system, infrared, microwave, (electromagnetic) induction heating, ultraviolet curing, lamp, and reflector. Can be mentioned. Among them, it is preferable to use a hot air high-speed air cap, a hot air tunnel type, or a hot air air floating method.
The drying conditions are preferably set to a temperature at which the water-insoluble polymer compound (A) 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 the drying temperature to 40 ° C. or higher, the solvents can be easily volatilized. On the other hand, by setting the drying temperature to 150 ° C. or lower, the stability to heat of the plasticizer (D), the drug (E) and the like is improved.
The drying time (crosslinking time) is preferably 15 seconds to 15 minutes, and more preferably 30 seconds to 10 minutes. In the present invention, since the polyvalent metal compound (B) and the water-insoluble polymer compound (A) are crosslinked, the drying time is longer than when a conventional crosslinking agent (for example, an isocyanate-based crosslinking agent) is used. (Crosslinking time) can be shortened.

When a non-aqueous pressure-sensitive adhesive layer is provided on the support surface, after drying, a liner is further laminated on the surface opposite to the support of the non-aqueous pressure-sensitive adhesive layer, and the whole is cut into an appropriate size. A patch of a desired size can be obtained.
When a non-aqueous pressure-sensitive adhesive layer is provided on the liner surface, after drying, a support is further laminated on the surface opposite to the liner surface of the non-aqueous pressure-sensitive adhesive layer, and the whole is cut into an appropriate size. By doing so, a patch of a desired size can be obtained.

According to the present invention, a non-aqueous pressure-sensitive adhesive composition, a patch, and a patch that provide a patch having excellent manufacturability, good adhesiveness to the skin, and reduced pain at the time of peeling. A manufacturing method can be provided.
According to the present invention, there is provided a non-aqueous pressure-sensitive adhesive composition capable of preparing a coating solution for a non-aqueous pressure-sensitive adhesive layer having a small change in viscosity when applied to a liner or a support, a short drying time, and excellent coating suitability. Obtainable.
According to the present invention, it is possible to obtain a patch that does not peel off and does not hurt when peeled off.
The patch of the present invention can be used as an adhesive tape or sheet 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 with reference to 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. Regarding the composition of the non-aqueous pressure-sensitive adhesive composition constituting the non-aqueous pressure-sensitive adhesive layer, the support and the like, Example 1 is shown below, and other examples are shown in Table 1, respectively.

(Manufacturing method of patch)
1) 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 to 10 with a pH adjuster as necessary. To prepare a mixed solution (S).
2) Separately, a mixed solution (T) was prepared by mixing a mixture of a water-insoluble polymer compound and a plasticizer in which a drug was dissolved. (Solid content: Depending on the polymer, it is about 50 to 65%.)
3) The mixed solution (S) is mixed with the mixed solution (S), and the mixture is sufficiently stirred until the whole becomes uniform, and an aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution, nonvolatile content 50% by mass) is obtained. Prepared. Thereafter, the aqueous dispersion (non-aqueous pressure-sensitive adhesive layer coating solution) is polyurethane film (support, sheet-like) so that the amount of the paste (non-aqueous pressure-sensitive adhesive composition) after drying becomes a predetermined amount. ) Were coated with a comma coater and dried. Drying was performed at 90 ° C. for 5 minutes by hot air air floating.
4) After drying, the silicone film of the PET film was covered with the surface of the non-aqueous pressure-sensitive adhesive layer, and the whole was cut into an appropriate size to obtain a patch of each example.
In addition, the compounding quantity of a water-insoluble high molecular compound (acrylic adhesive) shows the value which subtracted this suitable quantity, when a pH adjuster is mix | blended an appropriate quantity.

(Example 1)
Non-aqueous pressure-sensitive adhesive composition: acrylic pressure-sensitive adhesive 4 (water-insoluble polymer compound) 80.00 mass%, potassium aluminum sulfate (polyvalent metal compound) 0.50 mass%, diisopropyl sebacate (plasticizer) 15. 00% by mass, felbinac (drug) 0.50% by mass, l-menthol (drug) 4.00% by mass, potassium hydroxide (pH adjuster) appropriate amount.
Nonvolatile content (mass%) of coating solution for non-aqueous pressure-sensitive adhesive layer: 50 mass%.
Coating method: Comma coater coating.
Support: Same as the following polyurethane film.
Liner: PET silicone coat.
Amount of plaster (g / cm ² ): 100 (g / cm ² ).

  Details of the water-insoluble polymer compound and the support used for the preparation of the patch are shown below.

[Water-insoluble polymer compound]
Acrylic pressure-sensitive adhesive 1: 2-ethylhexyl acrylate / N-vinyl-2-pyrrolidone / acrylic acid = 75/22/3 (mass ratio). As a polymerization initiator, ammonium persulfate (0.3 parts by mass with respect to 100 parts by mass of the total mass of the monomer) was used.
Acrylic pressure-sensitive adhesive 2: 2-ethylhexyl acrylate / methyl methacrylate / acrylic acid = 90/7/3 (mass ratio). As a polymerization initiator, ammonium persulfate (0.3 parts by mass with respect to 100 parts by mass of the total mass of the monomer) was used.
Acrylic adhesive 3: Acrylic acid / octyl acrylate = 7/93 (mass ratio). As a polymerization initiator, ammonium persulfate (0.3 parts by mass with respect to 100 parts by mass of the total mass of the monomer) was used.
Acrylic adhesive 4: methacrylic acid / n-butyl acrylate copolymer (manufactured by Dow Corning Toray, trade name: MG-0581).

[Support]
Polyurethane Film: polyurethane film ester, Nisshinbo, trade name: "Mobilon (R) 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>
The coating property, adhesiveness, and painlessness at the time of peeling described below were evaluated. The results are also shown in Table 1. The coatability is an evaluation index for manufacturability of the patch.

(1) Coating property The non-aqueous pressure-sensitive adhesive layer coating solution prepared in the method for producing a patch is continuously applied to the support surface by a comma coater so that the thickness of the coating film is 200 μm. Coated.
At that time, the viscosity of the non-aqueous pressure-sensitive adhesive layer coating liquid and the change in the thickness of the coating film were observed by visual observation one hour after the start of coating, and the coating properties were determined based on the following criteria. Based on the evaluation.
(Double-circle): Compared with immediately after the start of coating, there was no change in viscosity, or even if there was a change in viscosity, it was a state in which a coating film having a uniform thickness could be applied.
○: Although the viscosity increased compared to immediately after the start of coating, it was possible to apply a coating film having a uniform thickness.
Δ: Viscosity increased compared to immediately after the start of coating, and it was impossible to apply a coating film having a uniform thickness 1 hour after the start of coating.
X: Viscosity was too high immediately after the start of coating, or coating was impossible due to generation of aggregates and the like.

(2) Adhesiveness Each patch (sheet form) of each example was cut into a size of 7 cm × 10 cm and pasted on elbows of 5 panelists.
Three hours after application, the state of peeling of the patch from the elbow was evaluated by sensory evaluation (visual observation) based on the following criteria.
4 points: The entire surface of the patch was in close contact with the skin.
3 points: An area of less than about 20% of the patch was peeled off.
2 points: About 20% or more and less than 50% of the patch was peeled off.
1 point: About 50% or more of the patch was peeled off.

(3) No pain at the time of peeling In the above (2) evaluation of adhesiveness, the patch was peeled from the elbow 3 hours after sticking, and the skin irritation at that time was evaluated based on the following criteria.
4 points: There was no pain at all.
3 points: Although there was some pain, it was a level not to worry about.
2 points: I felt a lot of pain.
1 point: I felt very painful.
From the skin irritation evaluation results, the average score of 5 panelists was calculated, and the absence of pain was evaluated based on the following criteria.
A: 3.5 points or more.
○: 2.5 points or more and less than 3.5 points.
Δ: 1.5 points or more and less than 2.5 points.
X: Less than 1.5 points.

  The patch of Example 1 according to the present invention containing a water-insoluble polymer compound and a polyvalent metal compound is good in all evaluation items, excellent in manufacturability, and has good adhesiveness to the skin. It was confirmed that the pain at the time of peeling was suppressed.

From the results of Table 1, the patches of Examples 2 to 13 according to the present invention, which contain a water-insoluble polymer compound, a polyvalent metal compound, and a chelating agent, all have good evaluation items. It was confirmed that it was excellent in manufacturability, had good adhesiveness to the skin, and pain at the time of peeling was suppressed.
On the other hand, Comparative Example 1, which does not contain the polyvalent metal compound (B) and is different from the present invention, was poor in pain during peeling.

  According to the present invention, a non-aqueous pressure-sensitive adhesive composition, a patch, and a patch that provide a patch having excellent manufacturability, good adhesiveness to the skin, and reduced pain at the time of peeling. A manufacturing method can be provided.

Claims (8)

  A non-aqueous pressure-sensitive adhesive composition comprising a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion, and a polyvalent metal compound (B).   The non-aqueous pressure-sensitive adhesive composition according to claim 1, wherein the polyvalent metal compound (B) is a water-soluble polyvalent metal compound.   The non-aqueous pressure-sensitive adhesive composition according to claim 1 or 2, further comprising a chelating agent (C) that forms a chelate with the polyvalent metal compound (B).   The water-insoluble polymer compound (A) has a monomer unit selected from (meth) acrylic acid alkyl ester containing an alkyl group having 4 to 12 carbon atoms and a monomer unit selected from a monomer containing a carboxy group. The non-aqueous pressure-sensitive adhesive composition according to any one of claims 1 to 3, which is a coalescence.   The non-aqueous pressure-sensitive adhesive composition according to any one of claims 1 to 4, further comprising a plasticizer (D).   The non-aqueous pressure-sensitive adhesive composition according to any one of claims 1 to 5, further comprising a drug (E).   A patch obtained by laminating the nonaqueous pressure-sensitive adhesive composition according to any one of claims 1 to 6 on a support.   After preparing a mixed solution in which the polyvalent metal compound (B) and the chelating agent (C) that forms a chelate with the polyvalent metal compound (B) are preliminarily dissolved in a water-containing solvent and the pH is adjusted to 7 or more, A mixed solution and a water-insoluble polymer compound (A) having a functional group that forms a crosslinking point with a polyvalent metal ion are mixed to prepare an aqueous dispersion, and the aqueous dispersion is used as a liner or a support. A method for producing a patch, which is coated and dried to provide a non-aqueous pressure-sensitive adhesive layer.