JP2023026537A - poultice - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cataplasm having excellent storage stability for ketoprofen.

SOLUTION: Provided is a cataplasm having a cataplasm layer on a support. The cataplasm layer contains ketoprofen or a pharmaceutically acceptable salt thereof, propylene glycol, l-menthol, water, and at least one of poly(methyl acrylate/2-ethylhexyl acrylate) and poly(methacrylate/n-butyl acrylate). The mass of propylene glycol in the cataplasm layer is 3 times or less the mass of ketoprofen, and the content of l-menthol is 0.1 to 0.5 mass% based on the total mass of the cataplasm layer.

SELECTED DRAWING: None

COPYRIGHT: (C)2023,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to a poultice and a method for producing the same.

A poultice is a type of patch that is manufactured by spreading a plaster layer containing a drug on a support such as cloth. It has the feature that there is little stimulation to. In addition, the adhesive strength of poultices often decreases with the passage of time after application, and the development of poultices that do not easily lose adhesive strength even after continuous application for a long period of time has been studied (Patent Document 1). ~4).

Patent Document 1 discloses that a decrease in adhesion can be suppressed by adding poly(methyl acrylate/2-ethylhexyl acrylate) to a poultice containing partially neutralized polyacrylic acid. In particular, Patent Document 2 discloses that when polyacrylic acid is further blended into the plaster layer, a poultice with excellent moldability and shape retention can be obtained. In addition, poultices contain the drug in the water-containing plaster layer, and therefore tend to have lower drug permeation through the skin than tapes (eg, Patent Document 3).

WO2006/090782 WO2015/025935 WO2015/129808 JP-A-10-95728

The present inventors, while studying the development of poultices containing ketoprofen as an active ingredient, found that a portion of ketoprofen is likely to be converted to its ester analogue by transesterification or the like during storage of the poultice. Found it. Accordingly, an object of the present invention is to provide a poultice in which ketoprofen has excellent storage stability.

[1] A poultice comprising an adhesive layer on a support, wherein the adhesive layer contains ketoprofen or a pharmaceutically acceptable salt thereof, propylene glycol, l-menthol, and water; A poultice in which the mass of propylene glycol in the body layer is not more than three times the mass of ketoprofen, and the content of l-menthol is 0.1 to 0.5% by mass based on the total mass of the plaster layer. .
[2] The poultice of [1], wherein the plaster layer further contains a fatty acid alkyl ester.
[3] A poultice comprising an adhesive layer containing ketoprofen or a pharmaceutically acceptable salt thereof on a support, wherein the adhesive layer contains propylene glycol in a mass not more than three times the mass of ketoprofen. In addition, a method for stabilizing ketoprofen.

According to the present invention, it is possible to provide a poultice in which ketoprofen has excellent storage stability. By improving the storage stability of ketoprofen, it is possible to extend the expiration date of poultices as pharmaceuticals, from the viewpoint of stable supply of pharmaceuticals, reduction of the economic burden on users, and reduction of environmental burden. can also be beneficial.

As used herein, "excellent storage stability of ketoprofen" means that the amount of ketoprofen ester produced is small. is 2.1% or less, preferably 1.9% or less based on the content of ketoprofen immediately after preparation of the poultice, it can be judged that the storage stability of ketoprofen is excellent. If the content of the ester analogue of ketoprofen is 2.1% or less, sufficient therapeutic effect of ketoprofen as a pharmaceutical can be exhibited even after two years have passed since its production.

Preferred embodiments of the present invention are described in detail below.

A poultice according to one embodiment of the present invention is a poultice comprising a base layer on a support, wherein the base layer comprises ketoprofen or a pharmaceutically acceptable salt thereof, propylene glycol, l-menthol, and water, the mass of propylene glycol in the paste layer is not more than three times the mass of ketoprofen, and the content of l-menthol is 0.1 to 0.5 based on the total mass of the paste layer. % by mass.

Any support can be used as long as it can support a water-containing paste, and those well known to those skilled in the art can be used. Examples of the support include woven fabrics (including knitted fabrics), nonwoven fabrics, resin films, foam sheets and paper. When a woven fabric, nonwoven fabric, or resin film is used as the support, examples of the material include polyolefins such as polyethylene, polypropylene, and polybutylene, polyesters such as polyethylene terephthalate, rayon, polyurethane, and cotton. A seed|species may be used individually and may be used in combination of 2 or more types. As the material for the support, polyester is more preferable.

The support is preferably a nonwoven fabric or a woven fabric, and particularly preferably a nonwoven fabric or a woven fabric having a predetermined elongation recovery rate (elongation elastic modulus). As used herein, "elongation recovery rate" is a value measured according to JIS L1096:2010, and means "elongation modulus at constant load" or "elongation modulus at constant elongation". For example, "50% elongation recovery rate" is the elongation elastic modulus when elongation is 50% (constant rate elongation), and "load at 50% elongation" is the elongation rate of 50%. It is the load (constant load) required for elongation to be It is preferable to use a non-woven fabric or woven fabric having a predetermined elongation recovery rate, because when applied to a movable part such as a joint, the backing expands and contracts according to the movement of the applied part.

When the support is a nonwoven fabric, for example, the 50% elongation recovery rate of the nonwoven fabric is 60 to 99%, preferably 65 to 95%, more preferably 70 to 90%. In addition, the load at 50% elongation of the nonwoven fabric is, for example, 1 to 5 N/2.5 cm in the longitudinal direction (major axis direction) and 0.1 to 3 N/2.5 cm in the lateral direction (minor axis direction). is preferred. A preferred weight of the support is, for example, 80 to 120 g/m ² , preferably 90 to 110 g/m ² . A suitable thickness of the support is, for example, 0.5 to 2 mm. In addition, the bending resistance of the support (the bending resistance is measured by JIS L1096:2010 A method (45° cantilever method)) is, for example, 20 to 40 mm in the longitudinal direction (long axis direction) and short axis direction) can be 10 to 35 mm, preferably longitudinal direction (major axis direction) 25 to 35 mm and lateral direction (minor axis direction) 15 to 30 mm. It is preferable that the nonwoven fabric has a thickness of 0.5 to 2 mm. Moreover, it is preferable that the nonwoven fabric has a basis weight of 80 to 150 g/m ² .

The knitted fabric used as the support also includes a knitted fabric processed into a cloth by assembling stitches by circular knitting, warp knitting, weft (horizontal) knitting, or the like. A knitted fabric made of one or a combination of two or more of materials such as polyester, nylon, polypropylene, and rayon is preferable, and a knitted fabric made of polyethylene terephthalate, which has little interaction with drugs, is more preferable.

In particular, when the support is a woven fabric, the 50% elongation recovery rate of the woven fabric is, for example, 60 to 99%, preferably 65 to 95%, more preferably 70 to 90%. preferable. The load at 50% elongation is, for example, 1 to 5 N/2.5 cm in the vertical direction (major axis direction) and preferably 0.1 to 3 N/2.5 cm in the lateral direction (minor axis direction). The bending resistance of the support can be, for example, 10 to 30 mm in the vertical direction (long axis direction) and 10 to 30 mm in the horizontal direction (short axis direction), preferably 15 to 25 mm in the vertical direction (long axis direction). It is 15 to 25 mm in the lateral direction (minor axis direction). Preferably, the thickness of the woven fabric is 0.5 to 2 mm.

In particular, when a polyethylene terephthalate woven fabric having a basis weight of 80 to 150 g/m ² is used, the water contained in the plaster is less likely to seep out through the mesh of the woven fabric during spreading, and the woven fabric and the plaster are more difficult to seep out. Better anchorage between

In addition, the polyethylene terephthalate woven fabric preferably has a longitudinal (major axis) modulus of 2 to 12 N/5 cm and a transverse (minor axis) modulus of 2 to 8 N/5 cm (the modulus measurement method is JIS L1018. : 1999). If the modulus is lower than 2 N/5 cm, the woven fabric may stretch when the plaster is spread, and the adhesive may permeate into the mesh, degrading the function as a poultice. Also, if the modulus is higher than 12 N/5 cm (longitudinal direction) or 8 N/5 cm (horizontal direction), the stretchability is inferior, and it may become difficult to follow the stretch of the skin when applied to the movable part.

The plaster layer contains ketoprofen or a pharmaceutically acceptable salt thereof, propylene glycol, and water.

Ketoprofen is a compound represented by the chemical formula (1), and has two optical isomers, R-form and S-form. In this embodiment, any one optical isomer of ketoprofen may be used, or two optical isomers may be mixed and used at any ratio.

Pharmaceutically acceptable salts of ketoprofen include inorganic salts such as sodium salts, potassium salts and calcium salts; amine salts such as monoethanolamine and diethanolamine;

The content of ketoprofen in the paste layer is 1.5 to 2.5% by mass, preferably 1.8 to 2.2% by mass, based on the mass of the entire paste layer. When the plaster layer contains a pharmaceutically acceptable salt of ketoprofen, the mass of the salt is converted to the mass of ketoprofen.

Propylene glycol is particularly effective in improving the skin permeability of ketoprofen. The content of propylene glycol in the plaster layer is 3 times or less, 0.5 to 3 times, 0.7 to 3 times, 1 to 3 times, 0.5 to 2 times the content of ketoprofen on a mass basis. 0.5 times, 0.7 to 2.5 times, 1 to 2.5 times, or 1.5 to 2.5 times.

The content of propylene glycol in the paste layer is 1.5 to 6.5% by mass, 2.5 to 6.5% by mass, or 3 to 6% by mass based on the total mass of the paste layer. good too.

A fatty acid alkyl ester may be an ester synthesized from a fatty acid and an alkyl alcohol. Alkyl alcohols can be, for example, alkyl alcohols having from 1 to 10 carbon atoms. As used herein, fatty acid means a saturated or unsaturated alkylcarboxylic acid having 8 to 18 carbon atoms. Examples of fatty acid alkyl esters include caprylic acid alkyl ester, capric acid alkyl ester, lauric acid alkyl ester, myristate alkyl ester, palmitic acid alkyl ester, palmitoleic acid alkyl ester, stearic acid alkyl ester, and oleic acid alkyl ester. be done. Preferred fatty acid alkyl esters are hexyl laurate or isopropyl myristate. Fatty acid alkyl ester may be used individually by 1 type, and may be used in combination of 2 or more type. By containing a fatty acid alkyl ester, the skin permeability of ketoprofen can be improved.

The content of the fatty acid alkyl ester in the base layer may be 1 to 20% by weight, preferably 1 to 15% by weight or 2 to 13% by weight, based on the total weight of the base layer. In particular, the content of hexyl laurate or isopropyl myristate may be 0.5 to 15% by mass or 0.5 to 10% by mass, based on the total mass of the paste layer, and may be 0.5 to 5.5% by mass. It is preferably 0 mass % or 1.0 to 3.5 mass %. When the content of hexyl laurate or isopropyl myristate is 0.5 to 5.0% by mass, the skin permeability of ketoprofen is particularly excellent.

The water content in the paste layer may be 30 to 60% by mass, or may be 35 to 50% by mass, based on the total mass of the paste layer.

The plaster layer may further contain a neutralized polyacrylic acid. The neutralized polyacrylic acid may be a completely neutralized polyacrylic acid, a partially neutralized polyacrylic acid, or a mixture thereof. Examples of neutralized polyacrylic acid include polyacrylic acid salts, and sodium salts, potassium salts, calcium salts, ammonium salts and the like can be used.

As the neutralized polyacrylic acid, a partially neutralized polyacrylic acid is preferable because the initial adhesive strength and the adhesive strength over time are increased. A partially neutralized product of polyacrylic acid is one in which structural units derived from acrylic acid and structural units derived from acrylate are present in an arbitrary ratio in one polymer chain. As the partially neutralized polyacrylic acid, it is preferable to use one in which 50 mol % of the carboxy groups in one polymer chain are neutralized.

The content of the neutralized polyacrylic acid in the plaster layer is preferably 1 to 6% by mass, more preferably 2 to 6% by mass, based on the total mass of the plaster layer. When the content of the neutralized polyacrylic acid is 1% by mass or more, the adhesion of the plaster layer becomes sufficiently high, and the plaster layer becomes difficult to fall off. When the content of the neutralized polyacrylic acid is 6% by mass or less, the moldability and shape retention of the plaster layer are improved.

The plaster layer may further contain polyacrylic acid. By containing polyacrylic acid, the adhesion maintenance performance is maintained at a high level, and the shape retention of the poultice is improved. The content of polyacrylic acid is preferably 1 to 5% by mass based on the mass of the paste layer. When the content of polyacrylic acid is 1% by mass or more, the moldability and shape retention of the plaster layer are improved. When the content of polyacrylic acid is 5% by mass or less, the hardness of the plaster layer does not easily increase, and the adhesiveness to the skin increases. By containing both the neutralized polyacrylic acid and the polyacrylic acid, the adhesiveness, moldability, shape retention and hardness of the poultice are improved in a well-balanced manner.

The plaster layer may further contain poly(methyl acrylate/2-ethylhexyl acrylate) or poly(methacrylic acid/n-butyl acrylate). Poly(methyl acrylate/2-ethylhexyl acrylate) is a copolymer of methyl acrylate and 2-ethylhexyl acrylate. Poly(methacrylic acid/n-butyl acrylate) is a copolymer of methacrylic acid and n-butyl acrylate. The content ratio of each monomer is not particularly limited.

Poly(methyl acrylate/2-ethylhexyl acrylate) or poly(methacrylic acid/n-butyl acrylate) is in the form of an emulsion (aqueous emulsion) dispersed in any solvent such as water or a water-containing organic solvent. good too. Examples of aqueous emulsions of poly(methyl acrylate/2-ethylhexyl acrylate) include Nikasol TS-620 (trade name, manufactured by Nippon Carbide Industry Co., Ltd.). Examples of aqueous emulsions of poly(methacrylic acid/n-butyl acrylate) include Primal N-580NF (trade name, manufactured by Rohm and Haas Co., Ltd.) and Ultrasol W-50 (trade name, manufactured by Aica Kogyo Co., Ltd.). is mentioned. Mixing these copolymers with other ingredients in the form of an aqueous emulsion in preparing the plaster solution facilitates the dispersion of these polymers throughout the plaster solution. By dispersing these copolymers throughout the plaster layer, a more pronounced effect of suppressing a decrease in adhesive force can be obtained, and sufficient adhesive force can be exhibited even after being applied for a long time.

The content of poly(methyl acrylate/2-ethylhexyl acrylate) or poly(methacrylic acid/n-butyl acrylate) is 2.75 to 15.75 mass as a solid content based on the total mass of the paste layer. %, preferably 3.3 to 13.86 mass %, 5.5 to 12.6 mass % or 5.5 to 11.34 mass %.

The content of the aqueous emulsion of poly(methyl acrylate/2-ethylhexyl acrylate) or poly(methacrylic acid/n-butyl acrylate) is 5 to 25 mass% (solid content 2.75 to 15.75% by mass), 6 to 22% by mass (3.3 to 13.86% by mass as solid content), 10 to 20% by mass (5.5 to 12% by mass as solid content .6% by mass) or 10 to 18% by mass (5.5 to 11.34% by mass as solid content). For example, Nikasol TS-620 contains 55-63% poly(methyl acrylate/2-ethylhexyl acrylate) as solids in an aqueous emulsion. When the aqueous emulsion of the above polymer is used to produce a poultice, the water content in the paste layer mentioned above also includes the amount of water added as a medium for the aqueous emulsion.

In the plaster layer, other ingredients such as other chemicals, plant-derived ingredients, animal-derived ingredients, water-soluble polymers, solubilizers, cross-linking agents, moisturizing agents, cooling agents, stabilizers, inorganic powders, coloring agents, etc. Ingredients, flavoring agents, pH adjusters and the like may be added.

Other drugs may be physiologically active substances other than ketoprofen as long as they have percutaneous absorbability. Other drugs include, for example, felbinac, flurbiprofen, diclofenac, diclofenac sodium, methyl salicylate, glycol salicylate, indomethacin, non-steroidal anti-inflammatory drugs such as ketoprofen or their esters, antihistamines such as diphenhydramine, aspirin, aceto Analgesics such as aminophen, ibuprofen, loxoprofen sodium, local anesthetics such as lidocaine, muscle relaxants such as suxamethonium chloride, antifungal agents such as clotrimazole, antihypertensive agents such as clonidine, blood vessels such as nitroglycerin, isosorbide dinitrate, etc. Expanding agents, vitamins such as vitamin A, vitamin E (tocopherol), tocopherol acetate, vitamin K, octothiacin, riboflavin butyrate, prostaglandins, scopolamine, fentanyl, l-menthol, hot pepper extract, nonylic acid vanillylamide, etc. mentioned.

The plant-derived component may be a component extracted from at least a part of a plant (e.g., leaves, roots, skins, fruits) or a hydrolyzate thereof, such as age extract, orange extract, orange juice, raspberry extract, Kiwi extract, cucumber extract, gardenia extract, grapefruit extract, hawthorn extract, Japanese pepper extract, hawthorn extract, juniper extract, sunflower extract, duke extract, tomato extract, grape extract, luffa extract, lime juice, apple extract, apple juice, Examples include fruit-derived components such as lemon extract and lemon juice, and components extracted from various crude drugs such as allantoin, lecithin, amino acids, kojic acid, aloe and licorice. In addition, plant-derived ingredients include Angelica keiskei leaf extract, avocado extract, amacha extract, althea extract, arnica extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, scutellaria root extract, bark extract, barley extract, Dutch mustard extract, seaweed extract, Hydrolyzed elastin, hydrolyzed wheat powder, chamomile extract, wormwood extract, licorice extract, karkade extract, guanosine, kumazasa extract, walnut extract, clematis extract, burdock extract, comfrey extract, cowberry extract, psycho extract, salvia extract, soapwort extract, bamboo shoot extract, hawthorn extract, shiitake extract, rhododendron extract, rhizome extract, linden extract, meadowsweet extract, calamus root extract, white birch extract, horsetail extract, honeysuckle extract, ivy extract, hawthorn extract, elderberry extract, yarrow extract, western Peppermint extract, mallow extract, assembly extract, sunflower extract, thyme extract, clove extract, cinnamon extract, chimp extract, spruce extract, dokudami extract, natto extract, carrot extract, wild rose extract, hibiscus extract, Bakumondou extract, parsley extract, parietalia extract , larvae extract, bisabolol, coltsfoot extract, coltsfoot extract, butterbur extract, bukuryo extract, butcher bloom extract, propolis, peppermint extract, bodaiju extract, hop extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, peach leaf extract, cornflower extract, eucalyptus extract , yuzu extract, mugwort extract, lavender extract, lettuce extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, and the like.

The animal-derived component may be a component extracted from at least a part of an animal (e.g., placenta, umbilical cord), a hydrolyzate thereof, or a component produced by an animal. placenta extract, hydrolyzed silk, honey, royal jelly extract, yeast extract.

The water-soluble polymer is not particularly limited as long as it can retain water in the poultice, and those commonly known to those skilled in the art can be used. Examples of water-soluble polymers include gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, hydroxypropylcellulose, sodium carboxymethylcellulose (carmellose sodium), methylcellulose, and carrageenan. More than one species may be used in combination. Preferred water-soluble polymers are carmellose sodium, gelatin or polyvinyl alcohol. The content of the water-soluble polymer is preferably 3 to 20 mass %, or 3 to 10 mass %, based on the mass of the base layer.

The solubilizing agent is not particularly limited as long as it can dissolve the drug, and examples thereof include crotamiton; N-methylpyrrolidone; polyalkylene glycols such as polyethylene glycol (PEG) and polybutylene glycol; polyethylene glycol monostearate; polyoxyalkylene sorbitan fatty acid esters such as polysorbate 80; and surfactants such as polyoxyethylene hydrogenated castor oil. These solubilizing agents may be used singly or in combination of two or more. The content of the dissolution aid is preferably 0.1 to 10% by mass based on the mass of the paste layer.

The cross-linking agent is a component for adjusting the progress of the cross-linking reaction between the neutralized polyacrylic acid products and the cross-linking reaction between the neutralized polyacrylic acid product and optionally added polyacrylic acid, and is generally used in the art. You can use what is commonly used. Examples of cross-linking agents include aluminum compounds. The content of the cross-linking agent is preferably 0.01 to 6% by mass based on the mass of the paste layer. When the content of the cross-linking agent is within this range, a poultice with superior followability to the skin can be obtained.

The moisturizing agent is not particularly limited as long as it can suppress evaporation of water from the paste layer over time. Examples of moisturizing agents include concentrated glycerin, sorbitol, ethylene glycol, 1,4-butanediol, polyethylene glycol, and polyhydric alcohols such as liquid paraffin. These moisturizing agents may be used singly or in combination of two or more. Concentrated glycerin is preferred as a humectant. The content of the moisturizing agent is preferably 20 to 40% by mass based on the mass of the paste layer.

Cooling agents include, for example, thymol, l-menthol, dl-menthol, l-isopulegol, peppermint oil and the like. A preferred cooling agent is l-menthol. The content of the cooling agent is preferably 0.1 to 3 mass %, or 0.5 to 3 mass %, based on the total mass of the base layer. The content of l-menthol is preferably 0.1 to 0.5% by mass, more preferably 0.2 to 0.4% by mass, based on the total mass of the base layer. . If the content of l-menthol is 0.1% by mass or more, the poultice user can be provided with a sufficient cooling sensation. Further, when the content of l-menthol is 0.5% by mass or less, the storage stability of ketoprofen is more excellent.

Stabilizers include, for example, oxybenzone, dibutylhydroxytoluene (BHT), sodium edetate, UV absorbers (eg, dibenzoylmethane derivatives), and the like. The content of the stabilizer is preferably 0.5 to 3% by mass based on the mass of the paste layer.

The mass of the plaster layer may be 214-1000 g/m ² , 400-1000 g/m ² or 400-650 g/m ² . Preferably, it is 400 to 650 g/m ² to improve the fitting feeling and improve the long-term adhesion. If the mass of the plaster layer is within the above range, the overall thickness of the poultice can be reduced, it is easy to follow the skin, and when it is applied, the difference between the peripheral edge and the edge is small, so it tends to be difficult to peel off. It is in.

The pH of the plaster layer is preferably 4-8, more preferably 4.5-6. By adjusting the pH to 4 or higher, irritation to the skin is reduced, and by adjusting the pH to 8 or lower, the formability and shape retention of the poultice can be improved. In particular, when the support is a woven fabric, especially a knitted fabric, bleeding may occur during formation of the plaster layer, but bleeding is suppressed when the pH is 5 to 6.5. tend to The pH can be measured, for example, by diluting a sample 20-fold with purified water using a glass composite electrode according to the pH measurement method of the Japanese Pharmacopoeia General Test Methods.

The poultice may be provided with a release liner. A release liner is laminated on the side of the paste layer opposite to the support. When a release liner is provided, it is possible to suppress the reduction in the water content of the base layer during storage, and there is a tendency to reduce the adhesion of dust and the like to the base layer.

The material of the release liner is not particularly limited, and liner materials generally known to those skilled in the art can be used. When a woven fabric, nonwoven fabric, knitted fabric, or resin film is used as the support, examples of the release liner material include polyethylene, polypropylene, polybutylene, polyethylene terephthalate, rayon, and polyurethane. may be used, or two or more may be used in combination. A polypropylene film is preferable as the material for the release liner.

The cataplasm may be stored inside the pouch. By storing it inside the pouch, it is possible to suppress a decrease in the water content of the paste layer and reduce the adhesion of dust and the like to the paste layer.

A poultice is prepared by, for example, mixing ketoprofen, propylene glycol, and water, adding the optional ingredients described above to obtain a plaster solution, spreading this plaster solution evenly on a release liner, and applying a support thereon. can be manufactured by laminating the

The present invention provides a poultice comprising a base layer containing ketoprofen or a pharmaceutically acceptable salt thereof on a support, wherein the base layer contains propylene glycol in a mass not more than three times the mass of ketoprofen. It also has an aspect of a method for stabilizing ketoprofen.

EXAMPLES The present invention will be described in detail below using examples and test examples, but the present invention is not limited by the examples. In addition, the numbers shown in Tables 1, 3 and 5 represent % by mass unless otherwise specified.

Examples 1-4 and Comparative Examples 1-6
(1) Production of poultice Each component shown in Table 1 was mixed for a certain period of time to obtain a plaster. The resulting plaster solution was spread evenly on a release liner so that the mass of the plaster per patch (140 mm x 100 mm) was 6 g, and then immediately laminated with a knitted fabric (backing). Then, a poultice was manufactured.

(2) Evaluation of Storage Stability The poultice obtained was stored at 60° C. for 2 weeks. After the stored poultice was cut so that the application area was 35 cm ² (5 cm×7 cm), the release liner was removed, and the plaster layer was extracted with 30 mL of methanol to obtain a sample solution. The content of ketoprofen and the total content of esters of ketoprofen (esters of glycerin, propylene glycol, menthol, or ethylhexyl of ketoprofen) in the sample solution were calculated based on the peak areas by a high performance liquid chromatography (HPLC) method. .

Table 2 shows the results. The total amount of ketoprofen ester was calculated as a relative value (mol %) when the amount of ketoprofen at the time of production of the poultice was taken as 100. The amount of ketoprofen in each example was 95% or more based on the content of ketoprofen at the time of production of the poultice. On the other hand, the amount of ketoprofen ester was 2.2% or more in Comparative Examples 1-6, but less than 2.1% in Examples 1-4. The poultices of Examples 3 and 4 containing hexyl laurate had even lower total esters.

Examples 5-10 and Comparative Examples 7-13
(1) Production of poultice Each component shown in Table 3 was mixed for a certain period of time to obtain a plaster. The resulting plaster solution was spread evenly on a release liner so that the mass of the plaster per patch (140 mm x 100 mm) was 6 g, and then immediately laminated with a knitted fabric (backing). Then, a poultice was manufactured.

(2) Evaluation of Storage Stability According to the method described above, the content of ketoprofen and the total content of esters of ketoprofen in the sample solution were calculated based on the peak area by high performance liquid chromatography (HPLC).

Table 4 shows the results. The amount of ketoprofen in each example was 95% or more based on the content of ketoprofen at the time of production of the poultice. On the other hand, the amount of ketoprofen ester was 2.29% or more in Comparative Examples 7-13, but less than 2.1% in Examples 5-10.

Example 11 and Comparative Examples 14-15
(1) Production of poultice Each component shown in Table 5 was mixed for a certain period of time to obtain a plaster. The resulting plaster solution was spread evenly on a release liner so that the mass of the plaster per patch (140 mm x 100 mm) was 6 g, and then immediately laminated with a knitted fabric (backing). Then, a poultice was manufactured.

(2) Evaluation of Storage Stability According to the method described above, the content of ketoprofen and the total content of esters of ketoprofen in the sample solution were calculated based on the peak area by high performance liquid chromatography (HPLC).

Table 6 shows the results. In Comparative Examples 14-15, the total amount of esters of ketoprofen was 2.5% or more. Moreover, in Example 11, it was 2% or less.

Claims (4)

A poultice comprising a plaster layer on a support,
The plaster layer comprises ketoprofen or a pharmaceutically acceptable salt thereof, propylene glycol, l-menthol, water, poly(methyl acrylate/2-ethylhexyl acrylate) and poly(methacrylic acid/acrylic acid). n-butyl) and
The mass of propylene glycol in the paste layer is 3 times or less the mass of ketoprofen,
A poultice in which the content of l-menthol is 0.1 to 0.5% by mass based on the total mass of the plaster layer. The poultice according to claim 1, wherein the plaster layer further contains a fatty acid alkyl ester. A method for stabilizing ketoprofen in a poultice comprising a plaster layer on a support, comprising:
Ketoprofen or a pharmaceutically acceptable salt thereof, l-menthol, water, at least one of poly(methyl acrylate/2-ethylhexyl acrylate) and poly(methacrylic acid/n-butyl acrylate), and mass of ketoprofen Mixing propylene glycol with a mass of 3 times or less of the
spreading the paste onto a release liner to form a paste layer;
A method for stabilizing ketoprofen, wherein the content of l-menthol is 0.1 to 0.5% by mass based on the total mass of the paste layer. 4. The method of claim 3, wherein said salve further comprises a fatty acid alkyl ester.