KR20070089692A - Indometacin-containing adhesive patch - Google Patents

Abstract

An indometacin-containing adhesive patch which comprises a moisture-permeable polyethylene film and, superposed thereon through an adhesive, a (non)woven fabric and an indometacin-containing plaster, characterized in that the indometacin-containing plaster comprises 0.1-10 mass% indometacin, 0.01-10 mass% arginine or salt thereof, 0.1-20 mass% partially neutralized polyacrylics acid, and 10-70 mass% water. The indometacin-containing adhesive path is highly convenient and has satisfactory long-term stability of indometacin content.

Description

Indomethacin-containing patch {INDOMETACIN-CONTAINING ADHESIVE PATCH}

The present invention relates to an indomethacin-containing patch having good content stability over time with increased convenience.

Indomethacin-containing patch is commercially available for the purpose of improving hay salt, muscle pain, etc., but the moisture in the solid is volatilized over time, the adhesive strength is reduced, and the absorbency of indomethacin is from the beginning of the patch. Since it fell after several hours, it was necessary to affix it to a affected part several times a day, and the convenience was bad. Therefore, the patch which improved the convenience of a patch once a day by lasting absorbency for a long time, ie, the patch which improved the compliance was calculated | required.

As a method of sustaining the absorbency of a drug for a long time in a water-containing patch, a method of weakening the crosslinkability of a solid to increase adhesiveness, a method of combining a moisture-permeable film with a nonwoven fabric, and the like are known. However, if the crosslinkability of the solid is weakened, solid residues may occur on the skin, resulting in a deterioration of the usability, and a problem of softening and dissolving of the solid at the time of sweating. Moreover, as a method of combining a moisture permeable film with a nonwoven fabric, although a polyurethane type or PET type moisture permeable film is used as a moisture permeable film, wrinkles generate | occur | produce by absorbing a hydrophilic domain over time, and a moisture permeability also Is not preferred because is changed. In addition, the PET-based moisture-permeable film is not preferred because the film lacks flexibility, and thus the usability is poor and control of the moisture-permeability is difficult. On the other hand, since the polyethylene moisture vapor permeable film has a small change in moisture permeability over time, continuous drug release can be expected. In addition, it is flexible and soft to the touch, and therefore has a high product value.

In addition, although an indomethacin-containing external patch containing a basic amino acid is known (Patent Document 1), the basic amino acid is formulated as an elution aid and a transdermal absorption accelerator, and no description is given about stabilization of indomethacin in the formulation. It is not.

Patent Document 1: Japanese Patent Application Laid-Open No. 57-81409

Patent Document 2: Japanese Patent Application Laid-Open No. 9-12450

Patent Document 3: Japanese Patent Application Laid-Open No. 10-158165

Disclosure of the Invention

Problems to be Solved by the Invention

Then, the present inventors made various examinations in order to discover the indomethacin containing patch which improved convenience. As a result, it has been found that a decrease in the indomethacin content occurs when a polyethylene moisture-permeable film having a good sustained drug release property, flexibility, and feel in a conventional indomethacin-containing patch. And it was estimated that the cause was alkaline earth metal salt (calcium carbonate etc.) in the polyethylene moisture permeable film mix | blended for the purpose of control of moisture permeability. The lowering of the indomethacin content is not preferable because the absorption amount of indomethacin may be lowered and sufficient efficacy may not be obtained. It is therefore an object of the present invention to provide convenience and improve indomethacin-containing patch over time.

Moreover, regarding the stabilization of indomethacin, the patch (patent document 2) which improved the stability of indomethacin by mix | blending crotamitone and the dihydric alcohol which has C4-C6, for example, sodium edetate, dibutyl The patch (patent document 3) etc. which improved the stability of indomethacin are known by mix | blending hydroxytoluene and tartaric acid, and adjusting the pH of solid to 4-6. However, crotamiton and dihydric alcohols having 4 to 6 carbon atoms cause irritation and odor, and dibutylhydroxytoluene is carcinogenic, which is not preferable in terms of safety. Although there is a method of improving the stability of indomethacin by blending a buffer or a stabilizer, a sufficient effect is not obtained even by combining glycine or the like which is generally used as a buffer.

Means to solve the problem

Therefore, the present inventors further investigated, in a specific amount of polyacrylic acid partial neutralization in indomethacin-containing solids of a nonwoven or woven fabric laminated with a polyethylene moisture-permeable film and a patch and an indomethacin-containing solid. And water, and further containing arginine or a salt thereof, finds that an indomethacin-containing patch having a good content stability over time is obtained, in which a sufficient effect is obtained with a patch once a day, thereby increasing convenience. The present invention has been completed.

That is, the present invention is a patch composed of a nonwoven fabric or a woven fabric laminated with a polyethylene moisture-permeable film and a patch, and an indomethacin-containing solid, wherein the indomethacin-containing solid is 0.1-10% by mass of indomethacin, arginine or a salt thereof. 0.01-10 mass%, 0.1-20 mass% of polyacrylic-acid partial neutralizations, and 10-70 mass% of water are provided, The indomethacin containing patch is provided.

Effects of the Invention

The indomethacin-containing patch of the present invention can be absorbed for a long time, and once applied once a day, is an agent having improved convenience that is effective for improving hay salt, myalgia, and the like, and is an agent having improved compliance. In addition, it is excellent in quality due to good adhesion to skin over time, stability of indomethacin content, and water absorption. Moreover, when affixing, the surface of a formulation is soft and the usability is good, it is hard to peel off, there is no solid residue, and there is no irritation.

To practice the invention  Best form for

The polyethylene moisture-permeable film used by this invention can be manufactured by a conventional method. For example, after manufacturing the polyethylene film which mix | blended the alkaline-earth metal salt with melt film, and extending | stretching this, the polyethylene moisture permeable film with a pore can be obtained. Examples of the alkaline earth metal salt to be used include calcium carbonate, barium sulfate, calcium nitrite, magnesium sulfate, calcium phosphate, basic magnesium carbonate and barium carbonate, and calcium carbonate is preferable in terms of productivity. Although the thickness of a polyethylene moisture permeable film is not restrict | limited especially, When it is too thin, it may become difficult to control water vapor transmission rate, and when too thick, uncomfortable feeling may arise when affixing, and it may impair a feeling, 5-100 Μm, particularly 10 to 50 µm, is preferred. In addition, when a moisture permeability is insufficient, a polyethylene moisture permeable film can further impart moisture permeability by performing a perforation treatment.

As the adhesive for laminating the polyethylene moisture-permeable film and the nonwoven fabric or the woven fabric used in the present invention, for example, polyvinyl acetate type, polyvinyl alcohol type, polyvinyl acetal type, polyvinyl chloride type, acrylic type, polyamide type, cellulose Thermoplastic resins and urea-based, melamine-based, phenol-based, epoxy-based, polyester-based, polyurethane-based, and polyaromatic-based thermosetting resins, and in particular, polyurethane-based adhesives in terms of adhesion between nonwoven fabric and polyethylene moisture-permeable film. desirable.

The material of the nonwoven fabric or woven fabric used in the present invention includes cotton, polyester, rayon, nylon, polyolefin, polyethylene, vinylon, acetate, polypropylene, polyurethane, and the like, and polyester, rayon and polyolefin are particularly preferable. Do. Moreover, as a manufacturing method of a nonwoven fabric, the needle punch method, the span lace method, the span bond method, the stitch bond method, the melt blown method, etc. are mentioned, Especially the needle punch method and the span lace method are preferable. The apparent weight of the nonwoven fabric or woven fabric is not particularly limited, but if the amount is too small, the amount of water evaporation increases and the solid is cured, and if it is too large, there is a possibility that the continuous effect is not obtained. Since the usability may worsen, 20-200 g / m <2>, especially 40-150 g / m <2> is preferable.

The moisture permeability of the nonwoven fabric or woven fabric (hereinafter sometimes referred to as a support) laminated through a polyethylene moisture-permeable film and an adhesive is not particularly limited, but 200-3000 (g) in terms of skin irritation, absorbency of drugs, and persistence of drug efficacy. / M 2 / 24h) is preferred, 200 to 2500 (g / m 2 / 24h) is more preferred, 200 to 2000 (g / m 2 / 24h) is more preferred, and 200 to 1000 (g / m 2 / 24h) is Particularly preferred. If the water vapor transmission rate is in the above range, as a result of moderately suppressing the amount of water evaporation from the solid, curing of the solid can be suppressed and the durability of the drug can be expected. In addition, breathability is maintained moderately and there is no irritation to the skin.

Although content of indomethacin is 0.1-10 mass% with respect to the indomethacin containing solid mass, 0.1-5 mass% is especially preferable especially 0.3-1.5 mass%. When content of indomethacin exceeds 10 mass%, the irritation to the skin of the drug itself may become a problem, and when it is less than 0.1 mass%, it will become difficult to obtain the anticipated effect.

As a salt of arginine, arginine hydrochloride etc. are mentioned, for example. As arginine or its salt, L-arginine and L-arginine hydrochloride are preferable, and L-arginine is especially preferable. Although content of arginine or its salt is 0.01-10 mass% with respect to the indomethacin containing solid mass, in terms of time-lapse stability of indomethacin, it is 0.01-5 mass%, More 0.01-1 mass%, Especially 0.01-0.5 mass% Is preferred.

Polyacrylic acid partial neutralization is what superposed | polymerized acrylic acid partially and contains it in order to improve the adhesiveness of a solid. As a neutralization road, 70 mol% or less is preferable, Furthermore, 60 mol% or less, especially 50 mol% or less are preferable. Moreover, it is preferable from a viewpoint of productivity that neutralization degree is 10 mol% or more. Although content of polyacrylic-acid partial neutralization is 0.1-20 mass% with respect to indomethacin containing solid mass, 0.5-10 mass% is especially preferable. When content of polyacrylic-acid partial neutralization exceeds 20 mass%, solid may aggregate and adhesive force may fall. Moreover, when content is less than 0.1 mass%, the problem that the shape retention of a solid falls or adhesiveness to skin worsens. As a commercial item of polyacrylic-acid partial neutralization, biscomate NP-600, biscomate NP-700, biscomate NP-800 (made by Showa Denko) etc. are mentioned, for example.

Although content of water is 10-70 mass% with respect to indomethacin containing solid mass, Preferably it is 10-60 mass%, Especially 20-50 mass% is preferable. When the content of water exceeds 70% by mass, the shape retention and adhesiveness of the solid may be remarkably lowered, and when the content is less than 10% by mass, the crosslinking reaction does not occur well, and when peeling after sticking It is not preferable because a solid residue of is generated.

When the indomethacin-containing solid of the present invention further contains a crosslinking agent, a mineral powder and a curing regulator, the cohesiveness of the solid is suitably adjusted, which is preferable.

As a crosslinking agent, magnesium aluminate, magnesium aluminum hydroxide, magnesium aluminate silicate, synthetic hydrotalcite, dihydroxy aluminum amino acetate, dry aluminum hydroxide gel, etc. are mentioned. Although content of a crosslinking agent is not restrict | limited especially, when too much crosslinking may become excessive and a problem may arise that a solid aggregates, On the other hand, when too small, crosslinking may become inadequate and a solid residue may generate | occur | produce metaphor. 0.001-1 mass% with respect to the god containing solid mass is especially preferable 0.001-0.3 mass%.

Examples of the mineral powders include kaolin, bentonite, montmorillonite, zinc oxide, titanium oxide, silicic anhydride, and the like. The content of the mineral powder is not particularly limited. However, if the content is excessively large, it is difficult to prepare the formulation, and a uniform formulation may not be obtained. On the other hand, if the content is too small, the solid may agglomerate and the adhesion may be lowered. 0.5-15 mass% with respect to solid mass is especially preferable 1-10 mass%.

Examples of the curing regulator include citric acid, malic acid, tartaric acid, disodium edate, gluconic acid and lactic acid. The content of the curing regulator is not particularly limited. However, when the amount is too large, crosslinking may be excessive and agglomeration of solids may occur, resulting in a decrease in adhesive strength. On the other hand, when the amount is too small, crosslinking may be insufficient to cause solid residue. 0.001-3 mass% with respect to a metasine containing solid mass is especially preferable at 0.01-2 mass%.

In indomethacin containing solid, the additive added to these components and used for a normal solid can be mix | blended suitably according to the objective. As an additive, an adhesion promoter, a solvent, an oil component, an absorption promoter, a stabilizer, surfactant, etc. are mentioned. These additives can be used individually or in combination of 2 or more types.

Examples of the adhesion enhancer include ester gums, xanthan gums, carmellose sodium, alicyclic saturated hydrocarbon resins, and polybutene rosin. Although content in particular of an adhesion promoter is not restrict | limited, 0.1-50 mass%, 0.5-40 mass%, and especially 1-30 mass% are preferable with respect to an indomethacin containing solid mass from an adhesive enhancement effect.

As a solvent, (concentration) glycerin, D-sorbitol liquid, propylene glycol, dipropylene glycol, ethylene glycol, macrogol, diethylene glycol, 1,3-butylene glycol, dipropylene glycol polyethylene glycol, 2-ethyl-1 Polyhydric alcohols such as, 3-hexanediol and polypropylene glycol 2000; Monohydric alcohols such as ethanol, isopropanol, benzyl alcohol, stearyl alcohol and oleyl alcohol; Esters such as heavy chain fatty acid triglycerides having 6 to 12 carbon atoms such as adipic acid diisopropyl, myristic acid isopropyl, triacetin, diisopropyl sebacate, diethyl sebaxate and triisooctanoic acid; Ketones, such as a crotamiton, etc. are mentioned. These solvents can be used individually or in combination of 2 or more types. Although content in particular of a solvent is not restrict | limited, 10-60 mass% with respect to indomethacin containing solid mass is especially preferable 20-50 mass%.

Examples of the oil component include olive oil, camellia oil, castor oil, safflower oil, sunflower oil, sanda oil, soybean oil, cottonseed oil, sesame oil, palm oil, palm oil, clove oil and the like.

Examples of the absorption accelerator include L-menthol, oleic acid, isopropyl myristate, and the like.

As a stabilizer, Phenolic substances, such as methyl paraoxybenzoate and propyl paraoxybenzoic acid; Neutral substances such as chlorobutanol and phenylethyl alcohol; Reverse soaps such as benzalkonium chloride and benzetonium chloride; Antioxidants such as vitamin E, butylhydroxyanisole, tocopherol acetate, propyl gallate and 2-mercaptobenzimidazole; Reducing agents, such as ascorbic acid, sodium hydrogen sulfite, sodium thiosulfate, and chelating agents, such as sodium edetate, are mentioned. Although content in particular of a stabilizer is not restrict | limited, 0-0.5 mass% with respect to indomethacin containing solid mass is especially preferable 0.001-0.1 mass%.

As surfactant, Anionic surfactant, such as calcium stearate, magnesium stearate, sodium lauryl sulfate, Cationic surfactant, such as cetylpyridium chloride; And nonionic surfactants such as glyceryl monostearate, sucrose fatty acid ester, polyoxyethylene hardened castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, and polyoxyethylene alkyl ether. Although content in particular of surfactant is not restrict | limited, It is 0-3 mass% with respect to indomethacin containing solid mass, Especially 0.01-1 mass% is preferable.

Moreover, although the adhesive force of an indomethacin containing solid is not restrict | limited, It is preferable that the tack adhesive force of a water-containing drug containing solid is N0.4 or more, and especially N0.5 or more from a viewpoint of preventing peeling off in a sticking. .

The indomethacin-containing patch of the present invention may cover the surface with a liner. Examples of the liner include plastic liners such as polyethylene and polypropylene, the above liners and paper sheets coated on the surface of a cellulose liner and a silicone releasing agent. Liner is preferred.

As a manufacturing method of the patch of this invention, a conventional formulation method can be used, For example, it contains indomethacin between the nonwoven fabric or woven fabric surface of a support body which laminated | stacked the moisture permeable film on the nonwoven fabric via the adhesive agent, and a liner. A patch is produced by extending the solid.

Although an Example demonstrates this invention concretely below, this invention is not limited to these Examples.

<Water vapor transmission test>

It measured by the calcium chloride method based on JISL1099-1993 "the moisture permeability test method of a fiber product" (A-1 method, 40 degreeC, 90% RH).

About 33 g of a moisture absorbent (calcium chloride) is uniformly put into the moisture permeation cup heated previously at about 40 degreeC. The test piece was put on a moisture-permeable cup, the packing and the ring were mounted in order, and fixed with a thumbscrew, and the mounting side was sealed with vinyl adhesive tape to make a test body.

The test body was put into the constant temperature / humidity apparatus of temperature 40 +/- 2 degreeC, and humidity 90 +/- 5% RH. After 1 hour, the test body is taken out and the mass (a ₁ ) is measured up to ₁ mg. After the measurement, the test body was put into the constant temperature and humidity device again, and after 1 hour, the test body was taken out and the mass (a ₁ ) was measured immediately to ₁ mg. The water vapor transmission rate was calculated by the following equation.

Water vapor permeability (g / ㎡ / 24h) = (a ₂ -a ₁ ) / (S × 24 × 10000)

S: moisture permeation area (cm 2)

Example 1

0.8 mass part of polyvinyl alcohol was added to 30 mass parts of purified water, and it heated to 60 degreeC, melt | dissolved, and cooled to room temperature. After dissolving 1.3 parts by mass of tartaric acid, 0.1 parts by mass of sodium edetate and 0.1 parts by mass of L-arginine (produced by Kyowa Fermentation Industry), 25 parts by mass of D-sorbitol solution (70%) and 3 parts by mass of kaolin are uniformly suspended. The water phase was prepared. Separately, 0.5 parts by mass of indomethacin and 0.5 parts by mass of L-menthol were dissolved in 2 parts by mass of Macrogol 400 at 40 ° C, cooled to room temperature, and then 20 parts by mass of concentrated glycerin was dissolved, followed by 3.5 parts of sodium carmellose. 6 parts by mass of polyacrylic acid partial neutralized and 0.1 parts by mass of dihydroxyaluminum acetate were uniformly dispersed to prepare an oil phase.

After adding the said water phase to the produced said oil phase and making the mass 100 mass parts with purified water, it mixed for 15 minutes with the mixer (made by Dalton: 40 rpm of revolutions, rotating: 80 rpm), and obtained the indomethacin containing solid. The tack-sensitive adhesive force of the patch aged at 25 ° C. for 2 weeks was N0.13.

Nonwoven fabric surface and polypropylene liner of a support on which a polyethylene nonwoven fabric (apparent weight: 100 g / m 2) was laminated on a polyethylene moisture-permeable film (thickness: 20 μm) formed with pores of calcium carbonate via a polyurethane-based adhesive. In the meantime, the water-containing drug-containing solid was inverted so that the thickness of the solid was 1 mm using a rolling machine (manufactured by Ikeda Machinery Industries), and the formulation was prepared by cutting into a size of 10 × 14 cm. Moreover, the water vapor transmission rate of the support body was 310 (g / m <2> / 24h).

Comparative Examples 1 to 4

Borax Arginine (Comparative Example 1: Kozakai Pharmaceutical Co., Ltd.), Benzoic acid (Comparative Example 2: Wako Pure Chemical Co., Ltd.), Glycine (Comparative Example 3: Kyowa Fermentation Industry Co., Ltd.) or L-isoleucine (Comparative Example 4: Kyowa Fermentation Co., Ltd.) Instead of manufacturing), a patch was prepared in the same manner as in Example 1.

Comparative Example 5

0.8 mass part of polyvinyl alcohol was added to 14.5 mass parts of purified water, and it heated to 60 degreeC, melt | dissolved, and cooled to room temperature. After dissolving 0.1 mass part of sodium edetate and 0.1 mass part of L-arginine (made by Kyowa fermentation industry), 25 mass parts of D-sorbitol liquids (70 mass%), 20 mass parts of concentrated glycerin, and macrogol 400 2 mass Part was added in order, and 3 mass parts of kaolin was suspended uniformly. Next, after adding 0.5 mass part of indomethacin, 0.5 mass part of L-menthols, and 3.5 mass parts of sodium carmellose, it mixed sufficiently. Next, 4 mass parts of 10 mass% dialdehyde starch aqueous solution, and 25 mass parts of 40 mass% gelatin aqueous solution were added and mixed.

After making the mass 100 mass parts with purified water, it mixed for 15 minutes with the propeller mixer (HEIDON make: 500 rpm), and obtained the water-containing drug-containing solid. Between the nonwoven surface of the same support body (moisture permeability 310 (g / m <2> / 24h)) of Example 1 and the liner made from polypropylene, the thickness of a solid is 1 mm using a water-containing drug-containing solid-state machine (made by Ikeda Machinery Industries). The preparation was prepared by cutting to 10 × 14 cm in size to invert to.

Test Example 1

The patch obtained in Example 1 and Comparative Examples 1-5 was put one by one in an aluminum bag, and it sealed, and aged at 25 degreeC for 2 weeks. At the start of aging, the indomethacin content after storage at 60 ° C. for one week was measured, and the residual ratio of indomethacin when the content at the start was 100% was calculated. The prescription and the results are shown in Table 1.

Ingredient (g) Example Comparative example One One 2 3 4 5 Indomethacin 0.5 0.5 0.5 0.5 0.5 0.5 L-arginine 0.1 - - - - 0.1 borax - 0.1 - - - - Benzoic acid - - 0.1 - - - Glycine - - - 0.1 - - L-isoleucine - - - - 0.1 - L-menthol 0.5 0.5 0.5 0.5 0.5 0.5 Polyvinyl Alcohol ^{* 1} 0.8 0.8 0.8 0.8 0.8 0.8 Dihydroxy Aluminum Amino Acetate 0.1 0.1 0.1 0.1 0.1 - Dark glycerin 20 20 20 20 20 20 Sodium Edetate 0.1 0.1 0.1 0.1 0.1 0.1 Tartaric acid 1.3 1.3 1.3 1.3 1.3 - D-sorbitol solution (70%) 25 25 25 25 25 25 kaoline 3 3 3 3 3 3 Macrogol 400 2 2 2 2 2 2 Carmellose Sodium 3.5 3.5 3.5 3.5 3.5 3.5 Polyacrylic acid partial neutralization ^{* 2} 6 6 6 6 6 - Dialdehyde Starch - - - - - 0.4 Gelatin ^{* 3} - - - - - 10 Purified water Full 100 Full 100 Full 100 Full 100 Full 100 Full 100 Indomethacin residual rate% ^{* 4} 99.4 93.5 95.3 96.1 95.4 96.7

* 1: PVA217S (manufactured by Kuraray)

* 2: Biscomate NP-700 (neutralization degree 50 mol%, Showa Denko)

* 3 Gelatin E1 (made by Nippi)

* 4: 60 ℃, after 1 week

Indomethacin-containing patch (Example 1) of the present invention was excellent in stability of indomethacin content over time. On the other hand, indomethacin-containing patch containing borax (Comparative Example 1), benzoic acid (Comparative Example 2), glycine (Comparative Example 3) or isoleucine (Comparative Example 4) instead of arginine, contains indomethacin of the present invention. Compared to the patch, the content stability over time was poor. Moreover, indomethacin containing patch (comparative example 5) which mix | blended gelatin instead of polyacrylic acid partial neutralization was inferior in content stability over time compared with the indomethacin containing patch of this invention.

Example 2

0.8 mass part of polyvinyl alcohol was added to 30 mass parts of purified water, and it heated to 60 degreeC, melt | dissolved, and cooled to room temperature. After dissolving 1.3 mass parts of tartaric acid, 0.1 mass part of sodium edetate, and 0.5 mass part of L-arginine here, 25 mass parts of D-sorbitol liquid (70%) and 3 mass parts of kaolin were suspended uniformly, and the water phase was prepared. Separately, 0.5 parts by mass of indomethacin and 0.5 parts by mass of L-menthol were dissolved in 2 parts by mass of Macrogol 400 at 40 ° C, and then cooled to room temperature. After dissolving 20 mass parts of concentrated glycerin here, 3.5 mass parts of carmellose sodium, 6 mass parts of polyacrylic-acid partial neutralization, and 0.1 mass part of dihydroxy aluminum acetate were uniformly dispersed, and the oil phase was prepared.

Indomethacin-containing patch was prepared in the same manner as in Example 1.

Example 3

1 mass part of gelatin was melt | dissolved at 60 degreeC in 27 mass parts of purified water. After dissolving 1.25 parts by mass of lactic acid and 0.1 parts by mass of L-arginine (produced by Kyowa Fermentation Industry), 22 parts by mass of D-sorbitol solution (70%) and 3 parts by mass of kaolin were added and dispersed uniformly to prepare an aqueous phase. . Separately, 2.5 mass parts of hard-flowing paraffin was melt | dissolved in 120 mass parts of ester gum at 120 degreeC, and the adhesive phase was prepared. In addition, 1 mass part of indomethacin and 1 mass part of L-menthol were melt | dissolved at 40 degreeC, and it cooled to room temperature. 22 mass parts of concentrated glycerin, 3 mass parts of sodium carmellose, 3.5 mass parts of polyacrylic-acid partial neutralization, and 0.2 mass part of dry aluminum hydroxide gel were added, it was made to disperse | distribute uniformly, and the oil phase was prepared.

The aqueous phase was warmed to 120 ° C., and then the pressure-sensitive adhesive phase was added to uniformly disperse. After cooling to room temperature, an oil phase was added, and an indomethacin-containing solid was prepared by further adjusting the total mass to 100 parts by mass with purified water.

In the same manner as in Example 1, the indomethacin-containing patch was prepared by leading to a thickness of 0.2 mm.

The stability of the indomethacin content over time of the indomethacin-containing patch prepared in Examples 2 and 3 was all good. Moreover, when affixed, the surface was smooth and the usability was good, it did not come off easily, there was no solid residue, and there was no irritation.

Claims (5)

A patch consisting of a nonwoven fabric or a woven fabric laminated through a polyethylene moisture-permeable film and an adhesive, and an indomethacin-containing solid, wherein the indomethacin-containing solid is 0.1-10% by mass of indomethacin, arginine or a salt thereof 0.01-. 10 mass%, 0.1-20 mass% of polyacrylic-acid partial neutralizations, and 10-70 mass% of water contain indomethacin containing patch. The method of claim 1, Indomethacin containing patch whose water vapor transmission rate of the nonwoven fabric or woven fabric laminated | stacked through the polyethylene moisture permeable film and an adhesive agent is 200-3000 (g / m <2> / 24h). The method according to claim 1 or 2, Furthermore, indomethacin containing patch containing 0.001-1 mass% of crosslinking agents in indomethacin containing solid. The method according to any one of claims 1 to 3, Furthermore, indomethacin containing patch containing 0.5-15 mass% of mineral powder in indomethacin containing solid. The method according to any one of claims 1 to 4, The indomethacin-containing patch further containing 0.001-3 mass% of hardening regulators in indomethacin containing solid.