Method for improving the adhesive layer of a poultice

Abstract

To provide a method for improving an adhesive layer in a plaster, capable of improving the adhesiveness of the adhesive layer to the skin and suppressing stickiness after peeling.SOLUTION: A method for improving an adhesive layer in a plaster that comprises a support layer and an adhesive layer containing a drug and a water-soluble polymer improves the adhesiveness of the adhesive layer and suppresses stickiness after peeling, and is characterized by comprising further incorporating, into the adhesive layer, silicic anhydride having a particle diameter D50 of 0.2 to 9.0 μm at which the cumulative volume in the particle size distribution becomes 50%.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for improving the adhesive layer of a poultice, and more particularly, to a method for improving the adhesive layer of a poultice that improves the adhesion of the adhesive layer to the skin and suppresses the occurrence of stickiness after peeling.

Background Art

[0002] A poultice is an adhesive patch having an adhesive layer containing a water-soluble polymer and water, and is widely used as a preparation that can be expected to have a cooling effect and a warming stimulation effect in addition to the medicinal effect of a drug.

[0003] Therefore, as a poultice, as a drug, for example, a poultice containing a drug having an anti-inflammatory action such as diclofenac, loxoprofen, indomethacin, etc. is mainly known. As such a poultice, for example, in Japanese Patent Application Laid-Open No. 9-208462 (Patent Document 1), a self-adhesive type poultice in which polybutene and gelatin are added to a poultice in which diclofenac sodium, water, and fatty acid dialkylolamide are blended in a poultice base is described.

[0004] In addition, various other poultices have been developed. For example, Japanese Patent Application Laid-Open No. 4-29927 (Patent Document 2) describes an adhesive patch in which an adhesive layer contains an adhesive base, a compound having a plasticizing action on the adhesive base, anhydrous silicic acid, a drug, and a water-absorbing filler. Further, for example, Japanese Patent Application Laid-Open No. 6-145049 (Patent Document 3) describes a patch in which anhydrous silicic acid is blended in a crosslinked hap (patch) base mainly composed of polyacrylic acid and / or polyacrylate.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

[0006] Since the poultice contains water as described above, generally, compared with non-aqueous tape agents and the like, it has a drawback of inferior adhesiveness to the skin and being easily peeled off during sticking. Therefore, when the present inventors further examined the adhesiveness of the poultice to the skin, they found that when trying to improve the adhesiveness to the skin, a phenomenon in which an adhesive layer or a part of the adhesive layer or a part of the components contained in the adhesive layer remains on the skin when peeled off from the skin, that is, "stickiness" may occur.

[0007] Furthermore, it is known that an inorganic filler is contained in the adhesive layer of the poultice for the purpose of improving its shape retention property and the like. As such an inorganic filler, conventionally, anhydrous silicic acid having a small particle size and bulk density, such as Aerosil A-200 (manufactured by Nippon Aerosil Co., Ltd.) described in Patent Document 2, has been preferably used from the viewpoint of excellent uniformity when mixed with other components. However, since such an inorganic filler having a small particle size and bulk density is difficult to handle during production, such as being prone to generate dust, when the present inventors further examined the inorganic filler of the poultice, they found that depending on its type and particle size, aggregates are likely to be generated during production, making it difficult to obtain an adhesive layer with a uniform appearance. Furthermore, it has also been found that depending on the type and particle size of such an inorganic filler, problems such as a decrease in the adhesiveness to the skin and stickiness may occur.

[0008] The present invention has been made in view of the problems of the above prior art, and an object of the present invention is to provide a method for improving an adhesive layer that can improve the adhesiveness of the adhesive layer of a poultice to the skin and suppress the occurrence of stickiness after peeling. Means for Solving the Problems

[0009] As a result of intensive research conducted by the present inventors to achieve the above object, it has been discovered that a cataplasm comprising a support layer and an adhesive layer has a particle diameter D 50 It has been found that by containing silicic anhydride having a specific range, the adhesion to the skin is sufficiently improved and the occurrence of stickiness after peeling is sufficiently suppressed. Furthermore, the present inventors have found that by using such a specific silicic anhydride, it is possible to suppress the generation of dust from silicic anhydride during production compared to the case of using silicic anhydride having a small particle size and bulk density, which has been conventionally used, and also that the generation of aggregates is sufficiently suppressed, making it possible to easily obtain a pressure-sensitive adhesive layer with a uniform appearance, and have completed the present invention. The aspects of the present invention obtained based on such findings are as follows.

[0010] [1] A method for improving an adhesive layer in a cataplasm comprising a support layer and an adhesive layer, the adhesive layer containing a drug and a water-soluble polymer, the method improving the adhesiveness of the adhesive layer and suppressing stickiness after peeling, Particle diameter D at which the cumulative volume in the particle size distribution reaches 50% 50 The pressure-sensitive adhesive layer further contains silicic anhydride having a particle size of 0.2 to 9.0 μm. Method for improving adhesive layer.

[0011] [2] The method for improving a pressure-sensitive adhesive layer according to [1], wherein the silicic anhydride is incorporated into the pressure-sensitive adhesive layer so that the content of the silicic anhydride relative to the total mass of the pressure-sensitive adhesive layer is 0.1 to 6.0 mass %.

[0012] [3] The method for improving a pressure-sensitive adhesive layer according to [1] or [2], wherein the pressure-sensitive adhesive layer further contains at least one selected from the group consisting of carboxymethylcellulose and pharma-ceutically acceptable salts thereof.

[0013] [4] The method for improving the pressure-sensitive adhesive layer according to [3], wherein the anhydrous silicic acid is contained in the pressure-sensitive adhesive layer so that the mass ratio of the content in terms of the sodium salt of at least one selected from the group consisting of carboxymethyl cellulose and its pharmaceutically acceptable salts in the pressure-sensitive adhesive layer to the content of anhydrous silicic acid (content in terms of the sodium salt of carboxymethyl cellulose and / or its pharmaceutically acceptable salt: content of anhydrous silicic acid) is 1:2 to 6:0.5.

[0014] [5] The method for improving the pressure-sensitive adhesive layer according to [3] or [4], wherein the content of at least one selected from the group consisting of carboxymethyl cellulose and its pharmaceutically acceptable salts in the pressure-sensitive adhesive layer is 1.0 to 4.0% by mass in terms of the sodium salt based on the total mass of the pressure-sensitive adhesive layer containing the anhydrous silicic acid.

[0015] [6] The method for improving the pressure-sensitive adhesive layer according to any one of [1] to [5], wherein the drug is at least one selected from the group consisting of diclofenac, loxoprofen, indomethacin, salicylic acid ester, lidocaine, glycyrrhetinic acid, felbinac, ketoprofen, and their pharmaceutically acceptable salts. [Advantages of the Invention]

[0016] According to the present invention, it is possible to provide a method for improving a pressure-sensitive adhesive layer that can improve the adhesion of the pressure-sensitive adhesive layer to the skin and suppress the occurrence of stickiness after peeling in a patch. [Embodiments for Carrying Out the Invention]

[0017] Hereinafter, the present invention will be described in detail according to its preferred embodiments. The method for improving a pressure-sensitive adhesive layer of the present invention (hereinafter, sometimes simply referred to as "the method of the present invention") is a method for improving a pressure-sensitive adhesive layer that includes a support layer and a pressure-sensitive adhesive layer, and in a patch in which the pressure-sensitive adhesive layer contains a drug and a water-soluble polymer, and improves the adhesion of the pressure-sensitive adhesive layer and suppresses the occurrence of stickiness after peeling. The particle diameter D at which the cumulative volume in the particle size distribution is 50% 50A method including a step of further incorporating anhydrous silicic acid having a particle size of 0.2 to 9.0 μm into the pressure-sensitive adhesive layer.

[0018] (Patch) The patch according to the present invention, that is, the patch which is the object of the method of the present invention includes a support layer. The support layer according to the present invention is not particularly limited as long as it can support the pressure-sensitive adhesive layer described later, and those known as the support layer of the patch can be appropriately adopted. Examples of the material of the support layer according to the present invention include polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymer, vinyl acetate-vinyl chloride copolymer, polyvinyl chloride, etc.; polyamides such as nylon; polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate, and polyethylene naphthalate; cellulose derivatives; synthetic resins such as polyurethane, and metals such as aluminum. Examples of the support layer according to the present invention include films, sheets, fabrics, foils, and laminates thereof. Among them, it is preferable to use a fabric made of the fibers of the above materials, and as the fabric, it is more preferable to use a woven fabric or a non-woven fabric processed by a method such as knitting, intertwining, heat fusion, pressure bonding, or binder adhesion of the fibers.

[0019] As such a support layer, for example, it is preferable to use a non-woven fabric made of polyester fibers, and the basis weight of the non-woven fabric is more preferably 2 50 to 200 g / m. When the basis weight of the non-woven fabric is less than the lower limit, problems such as easy breakage when peeling off the patch may occur, or a phenomenon called "bleeding", that is, the components contained in the pressure-sensitive adhesive layer seeping out on the back surface of the support layer, may occur, leading to deterioration of the appearance and usability of the patch. On the other hand, when it exceeds the upper limit, the stretchability and flexibility of the support layer are insufficient, so the patch tends to be easily peeled off.

[0020] As the patch according to the present invention, for the purpose of covering and protecting the surface of the pressure-sensitive adhesive layer until the patch is used, etc., a release liner may be further provided on the surface of the pressure-sensitive adhesive layer opposite to the support layer. The material of the release liner is not particularly limited, and examples include polyolefins such as polyethylene and polypropylene; ethylene-vinyl acetate copolymer, vinyl acetate-vinyl chloride copolymer, polyvinyl chloride, etc.; polyamides such as nylon; polyesters such as polyethylene terephthalate; cellulose derivatives; synthetic resins such as polyurethane, and aluminum and paper. Examples of the release liner include films, sheets, and laminates thereof made of the above materials. Further, as the release liner, it is preferably one that has been subjected to a release treatment such as a silicone compound coating or a fluorine-containing compound coating on the surface in contact with the pressure-sensitive adhesive layer so that it can be easily peeled off from the pressure-sensitive adhesive layer. Among these, as the release liner, it is preferable to use a film made of polyethylene terephthalate or polypropylene. Also, the thickness of such a release liner is not particularly limited, but for example, it is preferably 20 to 150 μm.

[0021] The patch according to the present invention includes a pressure-sensitive adhesive layer on the surface (usually one surface) of the support layer. The pressure-sensitive adhesive layer according to the present invention is not particularly limited, but the mass per unit area (the area of the adhesion surface) is preferably 430 to 1900 g / m 2 and more preferably 665 to 1500 g / m 2 and even more preferably 900 to 1100 g / m 2 The area of the adhesion surface of the pressure-sensitive adhesive layer according to the present invention is not particularly limited because it can be appropriately adjusted according to the type and content of the drug, the purpose of treatment, the application target, etc., but usually ranges from 70 to 280 cm 2 .

[0022] (Drug) In the present invention, the pressure-sensitive adhesive layer contains a drug. The drug contained in the pressure-sensitive adhesive layer according to the present invention is not particularly limited, and a drug that can be contained in the pressure-sensitive adhesive layer of a patch can be appropriately employed. Examples of such drugs include non-steroidal anti-inflammatory drugs such as diclofenac, felbinac, flurbiprofen, salicylate, indomethacin, ketoprofen, and ibuprofen; antihistamines such as diphenhydramine and chlorpheniramine; analgesics such as aspirin, acetaminophen, ibuprofen, and loxoprofen; local anesthetics such as lidocaine and dibucaine; muscle relaxants such as succinylcholine chloride; antifungal agents such as clotrimazole; antihypertensive agents such as clonidine; vasodilators such as nitroglycerin and isosorbide nitrate; vitamins such as vitamin A, vitamin E, vitamin K, octothiocin, and riboflavin butyrate; prostaglandins; glycyrrhetinic acid, scopolamine, fentanyl, capsicum extract, capsaicin, and nonyl vanillylamide; and pharmaceutically acceptable salts thereof when these can form salts, and these may be one kind or a combination of two or more kinds. Examples of the pharmaceutically acceptable salts include inorganic base salts such as sodium salt, potassium salt, calcium salt, and ammonium salt; organic base salts such as epolamine salt (1-(2-hydroxyethyl)pyrrolidine salt); inorganic acid salts such as hydrochloride, nitrate, and phosphate; and organic acid salts such as acetate, lactate, and benzenesulfonate.

[0023] Among these, from the viewpoint of being suitable for a cataplasm, the drug according to the present invention is preferably at least one of diclofenac, loxoprofen, indomethacin, salicylate, lidocaine, glycyrrhetinic acid, felbinac, ketoprofen, and pharmaceutically acceptable salts thereof.

[0024] For example, diclofenac is a non-steroidal analgesic and anti-inflammatory drug and is included in the Japanese Pharmacopoeia as well as the pharmacopoeias of various countries around the world. In the present invention, when diclofenac is contained in the adhesive layer, its form may be either the free form or a pharmaceutically acceptable salt thereof, and it may be a product in which a pharmaceutically acceptable salt of diclofenac is desalted to the free form during production and / or in the produced preparation, and it may be one of these or a combination of two or more thereof. Among these, from the viewpoint that the stability of the drug is improved and the skin irritation caused by acid and the decrease in the physical properties (strength, elasticity, durability, water retention, etc.) of the adhesive layer can be more suppressed, the form of diclofenac contained in the adhesive layer according to the present invention is preferably a pharmaceutically acceptable salt of diclofenac, and more preferably the sodium salt.

[0025] Also, for example, salicylate esters are also non-steroidal analgesic and anti-inflammatory drugs, and examples of the salicylate ester according to the present invention include methyl salicylate and glycol salicylate. Among these, glycol salicylate is preferred as the salicylate ester contained in the adhesive layer according to the present invention from the viewpoint of having less odor.

[0026] In the present invention, the drug content in the adhesive layer (when there are two or more drugs, their total content, the same hereinafter) is appropriately adjusted according to its effects, purposes, etc., and thus cannot be generally stated, but it is preferably 0.2 to 10.0% by mass based on the total mass of the adhesive layer. In the present specification, the "total mass of the adhesive layer" refers to the total mass of the adhesive layer in the cataplasm to which the method of the present invention is applied, that is, the adhesive layer containing also anhydrous silicic acid according to the present invention.

[0027] For example, when the pressure-sensitive adhesive layer according to the present invention contains at least one selected from the group consisting of diclofenac and its pharmaceutically acceptable salts (hereinafter, sometimes referred to as "diclofenac and / or its pharmaceutically acceptable salts"), the content of diclofenac and / or its pharmaceutically acceptable salts (the content of diclofenac or the content of the pharmaceutically acceptable salt of diclofenac, or when both are contained, their total content, the same hereinafter) is preferably 0.5 to 3.0% by mass, more preferably 0.75 to 2.5% by mass, and even more preferably 1.0 to 2.0% by mass in terms of sodium salt of diclofenac based on the total mass of the pressure-sensitive adhesive layer.

[0028] Also, for example, when the pressure-sensitive adhesive layer according to the present invention contains a salicylic acid ester, the content of the salicylic acid ester (when two or more salicylic acid esters are contained, their total content, the same hereinafter) is preferably 0.5 to 3.0% by mass, more preferably 0.75 to 2.5% by mass, and even more preferably 1.0 to 2.0% by mass in terms of glycol salicylate based on the total mass of the pressure-sensitive adhesive layer.

[0029] If the content of these drugs is less than the above lower limit, the analgesic and anti-inflammatory effects tend to decrease. On the other hand, if it exceeds the above upper limit, side effects tend to occur easily.

[0030] (Water-soluble polymer) In the present invention, the pressure-sensitive adhesive layer contains a water-soluble polymer. The water-soluble polymer according to the present invention is not particularly limited, and a water-soluble polymer known as a water-soluble polymer contained in the pressure-sensitive adhesive layer of a conventional patch can be appropriately employed. In the present invention, for convenience, the "water-soluble polymer" does not include the following carboxymethyl cellulose and / or its pharmaceutically acceptable salts.

[0031] Examples of the water-soluble polymer (a water-soluble polymer other than carboxymethyl cellulose and / or a pharmaceutically acceptable salt thereof) according to the present invention include neutralized polyacrylic acid, polyacrylic acid, carboxyvinyl polymer, methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, crystalline cellulose, gelatin, casein, pullulan, agar, dextran, dextrin, sodium alginate, soluble starch, carboxylated starch, polyvinyl alcohol, polyethylene oxide, polyacrylamide, polyvinyl pyrrolidone, polyvinyl ether-maleic anhydride copolymer, methoxyethylene-maleic anhydride copolymer, isobutylene-maleic anhydride copolymer, polyethyleneimine, sodium hyaluronate, guar gum, xanthan gum, gellan gum, carrageenan, locust bean gum, and pectin. It may be one of these or a combination of two or more thereof.

[0032] Among these, from the viewpoint of further improving the shape retention of the pressure-sensitive adhesive layer, the water-soluble polymer according to the present invention is preferably at least one selected from the group consisting of neutralized polyacrylic acid, polyacrylic acid, gelatin, agar, sodium alginate, polyvinyl alcohol, polyvinyl pyrrolidone, sodium hyaluronate, guar gum, xanthan gum, gellan gum, carrageenan, locust bean gum, and pectin, and more preferably contains at least neutralized polyacrylic acid.

[0033] In the present invention, the "neutralized polyacrylic acid" includes the completely neutralized polyacrylic acid and the partially neutralized polyacrylic acid, and indicates that all or part of the polyacrylic acid is neutralized by an alkali metal such as sodium or potassium or an ammonium ion. Examples of the neutralized polyacrylic acid include sodium polyacrylate, potassium polyacrylate, ammonium polyacrylate, etc. It may be one of these or a combination of two or more. However, from the viewpoint that the shape retention property of the resulting pressure-sensitive adhesive layer tends to be higher, the partially neutralized polyacrylic acid is preferred, and sodium polyacrylate is preferred. The neutralization rate of the neutralized polyacrylic acid is not particularly limited, but for example, it is preferably 30 to 100%, more preferably 35 to 65%, and even more preferably 40 to 60%.

[0034] In the present invention, the content of the water-soluble polymer in the pressure-sensitive adhesive layer (when there are two or more water-soluble polymers, their total content, the same applies hereinafter) is preferably 5.0 to 15.0% by mass based on the total mass of the pressure-sensitive adhesive layer, and more preferably 8.5 to 9.0% by mass. When the content of the water-soluble polymer is less than the lower limit, the shape retention property of the pressure-sensitive adhesive layer tends to decrease. On the other hand, when it exceeds the upper limit, the effect of improving the adhesion to the skin in the pressure-sensitive adhesive layer tends to decrease easily. Further, when the pressure-sensitive adhesive layer according to the present invention contains the neutralized polyacrylic acid, the content (when there are two or more neutralized polyacrylic acids, their total content, the same applies hereinafter) is preferably 1.0 to 10.0% by mass based on the total mass of the pressure-sensitive adhesive layer from the same viewpoint, more preferably 2.0 to 7.0% by mass, and even more preferably 3.0 to 4.0% by mass.

[0035] (Water) In the present invention, the pressure-sensitive adhesive layer also contains water. The water is preferably water that has been purified by ion exchange, distillation, filtration, etc. For example, "purified water" described in the Japanese Pharmacopoeia (the 18th revised Japanese Pharmacopoeia) can be preferably used. The water content in the pressure-sensitive adhesive layer is preferably 20 to 70% by mass based on the total mass of the pressure-sensitive adhesive layer. When the water content is outside this range, the shape retention of the pressure-sensitive adhesive layer tends to decrease, and the effect of improving the adhesion to the skin tends to decrease.

[0036] (Carboxymethyl cellulose and pharmaceutically acceptable salts thereof) In the present invention, the pressure-sensitive adhesive layer preferably further contains at least one selected from the group consisting of carboxymethyl cellulose and pharmaceutically acceptable salts thereof (hereinafter sometimes referred to as "carboxymethyl cellulose and / or pharmaceutically acceptable salts thereof" in this specification).

[0037] Carboxymethyl cellulose is a derivative of cellulose, also known as carmellose, and has a structure in which carboxymethyl groups (-CH2-COOH) are ether-bonded to some of the hydroxy groups of cellulose. The degree of etherification is theoretically 0 to 3, but the carboxymethyl cellulose according to the present invention preferably has a degree of etherification of 0.5 to 1.5.

[0038] In addition, the carboxymethyl cellulose according to the present invention is not particularly limited, but for example, the viscosity measured at 25°C in a 1.0% aqueous solution and at a rotation speed of 60 rpm is preferably 10 to 15,000 mPa·s, more preferably 10 to 6,000 mPa·s, and even more preferably 10 to 3,000 mPa·s.

[0039] In the present invention, the form of carboxymethyl cellulose in the pressure-sensitive adhesive layer may be a free form or a pharmaceutically acceptable salt thereof, and may be a pharmaceutically acceptable salt of carboxymethyl cellulose that has been desalted to a free form during production and / or in the produced preparation. It may be one of these or a combination of two or more. Examples of pharmaceutically acceptable salts of carboxymethyl cellulose include sodium salts, calcium salts, potassium salts, and ammonium salts, and it may be one of these salts or a combination of two or more. Among these, the carboxymethyl cellulose contained in the pressure-sensitive adhesive layer according to the present invention is preferably a salt of carboxymethyl cellulose, and more preferably a sodium salt.

[0040] In addition, as the carboxymethyl cellulose and / or its pharmaceutically acceptable salt, for example, commercially available products such as CMC Daicel series (manufactured by Daicel Miraiz Co., Ltd.), Aqualon CMC series (manufactured by Ashland), Blanose CMC series (manufactured by Ashland), Serogen series (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), and TPT series (manufactured by Gode Chemical Co., Ltd.) can be appropriately used.

[0041] When the pressure-sensitive adhesive layer according to the present invention contains carboxymethyl cellulose and / or its pharmaceutically acceptable salt, the content (the content of carboxymethyl cellulose or the content of the pharmaceutically acceptable salt of carboxymethyl cellulose, or the total content when both are contained, the same hereinafter) is preferably 1.0 to 4.0% by mass, more preferably 1.5 to 3.5% by mass, and even more preferably 2.0 to 3.0% by mass in terms of the sodium salt of carboxymethyl cellulose based on the total mass of the pressure-sensitive adhesive layer. If the content of carboxymethyl cellulose and / or its pharmaceutically acceptable salt is less than the above lower limit, stickiness after peeling from the skin tends to occur easily, while if it exceeds the above upper limit, the effect of improving the adhesion to the skin in the pressure-sensitive adhesive layer tends to decrease easily.

[0042] (Polyhydric alcohol) As the pressure-sensitive adhesive layer according to the present invention, from the viewpoint of functioning as a wetting agent and further improving the adhesion to the skin, it is preferable to further contain a polyhydric alcohol. Such polyhydric alcohols are not particularly limited, and examples thereof include glycerin; alkylene glycols such as methylene glycol, ethylene glycol, propylene glycol, and butylene glycol; polyalkylene glycols such as polyethylene glycol; alkanediols such as 1,3-propanediol and 1,4-butanediol; and sorbitol. It may be one of these or a combination of two or more thereof.

[0043] Among these, as the polyhydric alcohol, from the viewpoint that the adhesion of the pressure-sensitive adhesive layer to the skin tends to be further improved, it is preferably at least one selected from the group consisting of glycerin and alkylene glycol, and more preferably contains at least glycerin.

[0044] When the pressure-sensitive adhesive layer according to the present invention contains the polyhydric alcohol, the content (when there are two or more polyhydric alcohols, the total content thereof, the same applies hereinafter) is preferably 10 to 50% by mass based on the total mass of the pressure-sensitive adhesive layer, and more preferably 35 to 45% by mass. When the content of the polyhydric alcohol is less than the lower limit, the effect of improving the adhesion tends not to be sufficiently exhibited. On the other hand, when it exceeds the upper limit, the shape retention of the pressure-sensitive adhesive layer tends to decrease. When the pressure-sensitive adhesive layer according to the present invention contains glycerin, the content is preferably 20 to 50% by mass, more preferably 25 to 43% by mass, and even more preferably 30 to 35% by mass from the same viewpoint.

[0045] (Chelating agent) As the pressure-sensitive adhesive layer according to the present invention, from the viewpoint that it tends to more suppress the uneven spreading of the pressure-sensitive adhesive layer, it is preferable to further contain a chelating agent. Such a chelating agent is not particularly limited, and examples thereof include edetate (EDTA), pyrophosphate, hexametaphosphate, and gluconate, and it may be one of these or a combination of two or more thereof. Among these, sodium edetate is preferable as the chelating agent.

[0046] When the pressure-sensitive adhesive layer according to the present invention contains the chelating agent, the content thereof (when there are two or more chelating agents, the total content thereof, the same applies hereinafter) is preferably 0.01 to 1% by mass, more preferably 0.01 to 0.1% by mass, based on the total mass of the pressure-sensitive adhesive layer. When the content of the chelating agent is less than the lower limit, the effect of suppressing uneven spreading of the pressure-sensitive adhesive layer is not sufficiently exhibited and the appearance tends to be impaired. On the other hand, when it exceeds the upper limit, the shape retention of the pressure-sensitive adhesive layer tends to decrease.

[0047] (Crosslinking agent) As the pressure-sensitive adhesive layer according to the present invention, from the viewpoints that the shape retention of the pressure-sensitive adhesive layer tends to be more improved and the uneven spreading can be more suppressed, it is preferable to further contain a crosslinking agent. Such a crosslinking agent is not particularly limited, and examples thereof include potassium aluminum sulfate (alum), calcium chloride, magnesium chloride, aluminum hydroxide, and dihydroxyaluminum aminoacetate, and it may be one of these or a combination of two or more thereof. Among these, potassium aluminum sulfate is preferable as the crosslinking agent.

[0048] When the pressure-sensitive adhesive layer according to the present invention contains the crosslinking agent, the content thereof (when there are two or more crosslinking agents, the total content thereof, the same applies hereinafter) is preferably 0.1 to 1.0% by mass, more preferably 0.2 to 0.5% by mass, based on the total mass of the pressure-sensitive adhesive layer. When the content of the crosslinking agent is less than the lower limit, the effect of improving the shape retention of the pressure-sensitive adhesive layer tends not to be sufficiently exhibited. On the other hand, when it exceeds the upper limit, the effect of suppressing uneven spreading of the pressure-sensitive adhesive layer is not sufficiently exerted, and the appearance tends to be impaired.

[0049] Further, when the pressure-sensitive adhesive layer according to the present invention contains both the chelating agent and the crosslinking agent, the mass ratio of the content of the chelating agent to the content of the crosslinking agent (content of chelating agent: content of crosslinking agent) is preferably 1:0.7 to 1:10, more preferably 1:4 to 1:9. When the content of the crosslinking agent relative to the content of the chelating agent is less than the lower limit, bleeding tends to occur, or the effect of improving the shape retention of the pressure-sensitive adhesive layer tends not to be sufficiently exhibited. On the other hand, when it exceeds the upper limit, the effect of suppressing uneven spreading of the pressure-sensitive adhesive layer is not sufficiently exerted, the appearance tends to be impaired, or the adhesive strength of the pressure-sensitive adhesive layer tends to decrease.

[0050] (pH adjuster) The pressure-sensitive adhesive layer according to the present invention preferably further contains a pH adjuster in order to adjust its pH. Examples of such a pH adjuster include organic acids such as acetic acid, lactic acid, oxalic acid, citric acid, and tartaric acid; inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid; pharmaceutically acceptable salts of the organic acids and the inorganic acids; amines such as monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, and diisopropanolamine; and salts of hydroxides such as sodium hydroxide, potassium hydroxide, and magnesium hydroxide. It may be one of these or a combination of two or more. Further, the pH of the pressure-sensitive adhesive layer according to the present invention is preferably 7.0 to 9.0, more preferably 7.0 to 8.5.

[0051] (Adhesion enhancer) As for the pressure-sensitive adhesive layer according to the present invention, from the viewpoint that the adhesiveness of the pressure-sensitive adhesive layer to the skin tends to be further improved, it is preferable to further contain an adhesion enhancer. Such an adhesion enhancer is not particularly limited, and examples thereof include acrylic ester copolymers such as aminoalkyl methacrylate copolymer E; methyl acrylate / 2-ethylhexyl acrylate copolymer. It may be one of these or a combination of two or more. Among these, from the viewpoint that the effect is likely to be achieved with a small amount of addition, aminoalkyl methacrylate copolymer E is preferable as the adhesion enhancer.

[0052] When the pressure-sensitive adhesive layer according to the present invention contains the adhesion enhancer, its content (when there are two or more adhesion enhancers, the total content thereof, the same applies hereinafter) is preferably 0.1 to 1.0% by mass, more preferably 0.4 to 0.6% by mass, based on the total mass of the pressure-sensitive adhesive layer. When the content of the adhesion enhancer is less than the lower limit, the effect of improving the adhesiveness of the pressure-sensitive adhesive layer to the skin tends not to be sufficiently achieved. On the other hand, when it exceeds the upper limit, pain tends to occur when peeling the pressure-sensitive adhesive layer from the skin.

[0053] (Other additives) As for the pressure-sensitive adhesive layer according to the present invention, in addition, it may further contain additives such as an emulsifier, a cooling agent, a stabilizer (antioxidant), a preservative, and a filler other than the silicic anhydride according to the present invention.

[0054] Examples of the emulsifier include polyalkylene glycol monooleate (such as polyethylene glycol monooleate, polypropylene glycol monooleate, polyethylene polypropylene glycol monooleate, etc.), polyethylene glycol monostearate, and polyoxyethylene sorbitan monooleate. It may be one of these or a combination of two or more.

[0055] Examples of the cooling agent include thymol, l-menthol, dl-menthol, dl-camphor, l-isopulegol, and peppermint oil, and it may be one of these or a combination of two or more thereof.

[0056] Examples of the stabilizer include sodium sulfite, butylhydroxyanisole, dibutylhydroxytoluene, nordihydroguaiaretic acid, tocopherol, tocopherol acetate, citric acid, ascorbic acid, and propyl gallate, and it may be one of these or a combination of two or more thereof.

[0057] Examples of the preservative include methyl paraben, ethyl paraben, propyl paraben, butyl paraben, 1,2-pentanediol, benzoic acid and its salts, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, 4-isopropyl-3-methylphenol, 2-isopropyl-5-methylphenol, phenol, hinokitiol, cresol, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarbanilide, chlorobutanol, benzalkonium chloride, and benzethonium chloride, and it may be one of these or a combination of two or more thereof.

[0058] As the filler other than the silicic anhydride according to the present invention, in addition to the silicic anhydride having a particle size different from that of the silicic anhydride according to the present invention described below, for example, inorganic fillers such as titanium oxide, aluminum silicate, kaolin, talc, bentonite, magnesium aluminometasilicate, etc. may be mentioned, and one of these or a combination of two or more thereof may be used. However, as the adhesive layer according to the present invention, it is preferably substantially free of fillers other than the silicic anhydride according to the present invention, and even when it contains or allows the inclusion of such fillers, the content (in the case of two or more fillers, the total content thereof, the same shall apply hereinafter) is preferably 3.0% by mass or less, more preferably 1.0% by mass or less, still more preferably 0.1% by mass or less, and particularly preferably 0.05% by mass or less with respect to the total mass of the adhesive layer.

[0059] (Silicic anhydride) In the method of the present invention, the adhesive layer is further made to contain silicic anhydride. Silicic anhydride is also referred to as silica and is an oxide of silicon represented by SiO2.

[0060] As the particle size of the silicic anhydride according to the present invention, the particle size D at which the cumulative volume in the particle size distribution becomes 50% 50 is required to be 0.2 to 9.0 μm, and the particle size D 50 is preferably 0.5, 1.0, 2.0, 3.0, 4.0, 4.5, or 4.8 μm or more, and is preferably 5.2, 6.0, 7.0, or 8.0 μm or less. The upper limit and the lower limit of the particle size D 50 can be appropriately combined. For example, it is preferably 2.0 to 8.0 μm, more preferably 4.0 to 8.0 μm, and particularly preferably 4.8 to 7.7 μm. When the particle size D of the silicic anhydride 50 is less than the lower limit, the effect of suppressing the occurrence of stickiness after peeling the adhesive layer from the skin tends to decrease, or the handling during production tends to become difficult. On the other hand, when it exceeds the upper limit, the effect of improving the adhesion of the adhesive layer to the skin tends to decrease, or particles remain in the adhesive layer, resulting in poor appearance.

[0061] In the present invention, the particle diameter D of the anhydrous silicic acid 50 represents the particle diameter measured by the laser diffraction / scattering method of Japanese Industrial Standard JIS.Z8825:2013. More specifically, as a measurement sample, a 3 mass% aqueous dispersion of the anhydrous silicic acid to be measured is prepared, and the following measurement conditions: Measuring instrument: Laser diffraction particle size distribution measuring device (for example, SALD-2300 manufactured by Shimadzu Corporation, high-concentration sample measurement mode) Refractive index: 1.55 are used to measure the particle diameter in the sample and obtain a particle size distribution curve. The particle diameter at which the cumulative volume becomes 50% in the obtained particle size distribution curve is defined as the particle diameter D of the anhydrous silicic acid in the present invention 50 [μm]. For example, the inventors measured the particle diameter D of Aerosil A-200 (manufactured by Nippon Aerosil Co., Ltd.) described in Patent Document 2 by this measurement method (more specifically, the method described in the following examples). 50 As a result, it was 0.055 μm (n = 3, first time: 0.055 μm, second time: 0.055 μm, third time: 0.055 μm).

[0062] In the method of the present invention, the amount of the anhydrous silicic acid contained in the pressure-sensitive adhesive layer is preferably an amount such that the content with respect to the total mass of the pressure-sensitive adhesive layer is 0.1 to 6.0 mass%, more preferably an amount such that it is 0.2 to 5.0 mass%, still more preferably an amount such that it is 0.7 to 4.5 mass%, and particularly preferably an amount such that it is 1.0 to 4.0 mass%. When the content of the anhydrous silicic acid is outside the above range, the effect of improving the adhesion of the pressure-sensitive adhesive layer to the skin tends to decrease, or the effect of suppressing the occurrence of stickiness after peeling the pressure-sensitive adhesive layer from the skin tends to decrease.

[0063] In addition, when the pressure-sensitive adhesive layer according to the present invention contains carboxymethyl cellulose and / or a pharmaceutically acceptable salt thereof, the mass ratio of the sodium salt equivalent content of the carboxymethyl cellulose and / or the pharmaceutically acceptable salt thereof in the pressure-sensitive adhesive layer to the content of the silicic anhydride (content of the carboxymethyl cellulose and / or the pharmaceutically acceptable salt thereof in terms of sodium salt equivalent: content of silicic anhydride) is preferably 1:2 to 6:0.5, more preferably 1:1.5 to 6:0.9, still more preferably 1:1.5 to 6:1, and particularly preferably 1:1.4 to 3:1. When the content of the silicic anhydride relative to the content of the carboxymethyl cellulose and / or the pharmaceutically acceptable salt thereof in terms of sodium salt equivalent is less than the lower limit, the effect of improving the adhesiveness tends to decrease, and the effect of suppressing the stickiness after peeling the pressure-sensitive adhesive layer from the skin tends to decrease. On the other hand, when it exceeds the upper limit, the effect of suppressing the stickiness after peeling the pressure-sensitive adhesive layer from the skin tends to decrease.

[0064] As a method for further incorporating the silicic anhydride according to the present invention into the pressure-sensitive adhesive layer, for example, in a method for producing a poultice, a method of adding silicic anhydride to a pressure-sensitive adhesive layer composition containing a drug and a water-soluble polymer can be mentioned.

[0065] As a method of the present invention, more specifically, for example, the following method: A step of mixing the drug, the water-soluble polymer, water, and the silicic anhydride to obtain a pressure-sensitive adhesive layer composition; A step of spreading the pressure-sensitive adhesive layer composition to obtain the pressure-sensitive adhesive layer; A method including these steps can be mentioned. Thereby, the pressure-sensitive adhesive layer of the obtained poultice is improved as compared with the case where the pressure-sensitive adhesive layer does not contain the silicic anhydride, and the pressure-sensitive adhesive layer has excellent adhesiveness to the skin and appearance, and the stickiness after peeling is suppressed.

[0066] In the step of obtaining the pressure-sensitive adhesive layer composition, the drug, the water-soluble polymer, water, and the anhydrous silicic acid, and, if necessary, at least one selected from the group consisting of carboxymethyl cellulose and pharmaceutically acceptable salts thereof, the polyhydric alcohol, the chelating agent, the crosslinking agent, the pH adjuster, the tackifier, and the additive, etc. are mixed to obtain a pressure-sensitive adhesive layer composition. At this time, the blending amounts of the respective components to be mixed are as described for the contents of the respective components in the above-described pressure-sensitive adhesive layer, including their preferred embodiments.

[0067] The mixing method is not particularly limited, and a method known in the conventional method for producing a cataplasm or a method analogous thereto can be appropriately employed. For example, a method of mixing using a mixer such as a propeller mixer, a paddle mixer, an anchor mixer, a planetary mixer, a V-type mixer, a Henschel mixer, etc. can be mentioned. The mixing conditions are also not particularly limited, and can be appropriately adjusted to conventionally known conditions or conditions analogous thereto.

[0068] Next, in the step of obtaining the pressure-sensitive adhesive layer, the pressure-sensitive adhesive layer composition obtained above is spread to form a pressure-sensitive adhesive layer of the cataplasm. The spreading method is not particularly limited, and a method known in the conventional method or a method analogous thereto can be appropriately employed. For example, the pressure-sensitive adhesive layer composition can be spread on the surface (usually one surface) of the support layer with a predetermined thickness to form a cataplasm having the pressure-sensitive adhesive layer on the support layer. In this case, if necessary, the release liner can be bonded to the surface of the pressure-sensitive adhesive layer opposite to the support layer to form a cataplasm in which the support layer, the pressure-sensitive adhesive layer, and the release liner are laminated in this order.

[0069] As another embodiment of the spreading method, for example, the pressure-sensitive adhesive layer composition is first spread on one surface of the release liner with a predetermined thickness to form the pressure-sensitive adhesive layer, and then the support layer is bonded to the surface of the pressure-sensitive adhesive layer opposite to the release liner, whereby a cataplasm in which the support layer, the pressure-sensitive adhesive layer, and the release liner are laminated in this order can be obtained.

[0070] Furthermore, as the method of the present invention, it may further include a step of cutting the poultice into a predetermined shape as needed, a step of enclosing it in a storage packaging container (for example, an aluminum packaging bag) to form a package, and the like.

Examples

[0071] Hereinafter, the present invention will be described more specifically based on examples and comparative examples, but the present invention is not limited to the following examples. In addition, the particle size measurement of anhydrous silicic acid or magnesium aluminometasilicate used in each example and comparative example, and the adhesion evaluation, stickiness evaluation, and appearance evaluation of the adhesive layer of the poultices obtained in each example and comparative example were each carried out by the methods shown below.

[0072] (Particle size measurement) The particle size of anhydrous silicic acid or magnesium aluminometasilicate was measured by the laser diffraction / scattering method of Japanese Industrial Standard JIS.Z8825:2013 under the following measurement conditions: Measuring instrument: Laser diffraction particle size distribution measuring device SALD-2300 manufactured by Shimadzu Corporation Measurement mode: High-concentration sample measurement mode Sample concentration: 3 mass% Dispersion medium: Purified water Refractive index: 1.55 The particle size in the sample was measured under these conditions to obtain a particle size distribution curve. From the obtained particle size distribution curve, the particle size D 50 (μm) at which the cumulative volume is 50% was determined. The measurement was performed three times for each anhydrous silicic acid sample or magnesium aluminometasilicate sample, and the average was taken as the particle size of the anhydrous silicic acid or magnesium aluminometasilicate (particle size D 50 [μm]).

[0073] (Adhesion evaluation) First, six patches were prepared for each of the same examples or comparative examples. The release liners were peeled off from each patch and applied to the elbows of six subjects, respectively. Next, the arms of the subjects were flexed and extended (bent and stretched), and the peeling state of the adhesive layer from the skin after 40 flexions and extensions was observed. The peeling state was scored based on the criteria in Table 1 below, and the adhesion was evaluated based on the average value (average score) of the scores of the six subjects. The adhesion evaluation of the patch can be judged to be "B" or above, and the adhesion to the skin is excellent enough to be fully acceptable as a preparation.

[0074]

Table 1

[0075] (Stickiness evaluation) After the above adhesion evaluation, each patch was peeled off from the skin, and the stickiness situation was observed when touching the site where the patch was applied with the fingertips. The stickiness situation was scored based on the criteria in Table 2 below, and the stickiness evaluation was determined based on the average value (average score) of the scores of the six subjects. The stickiness evaluation of the patch can be judged to be "B" or above, and the occurrence of stickiness to the skin is suppressed to a level that is fully acceptable as a preparation.

[0076]

Table 2

[0077] (Appearance evaluation of the adhesive layer) The release liner was peeled off from the patch immediately obtained in the example or comparative example, and the surface of the adhesive layer was visually observed. If aggregates or unevenness were confirmed on the surface of the adhesive layer and it was difficult to use as a preparation, it was evaluated as "N". If no aggregates or unevenness were confirmed on the surface of the adhesive layer and it was uniform, it was evaluated as "Y".

[0078] (Example 1) First, 3.0 parts by mass of silicic anhydride, 1.0 part by mass of diclofenac sodium, 8.8 parts by mass of a water-soluble polymer (gelatin:sodium polyacrylate (partial neutralization product of polyacrylic acid):polyvinyl alcohol = 1.8:3.5:3.5 (mass ratio)), 3.0 parts by mass of sodium carboxymethyl cellulose (degree of etherification: 0.8 to 1.0, viscosity (25 °C, 1.0% aqueous solution, 60 rpm): 13 mPa·s), 39.2 parts by mass of a polyhydric alcohol (glycerin:alkylene glycol = 31.6:7.6 (mass ratio)), 0.05 part by mass of a chelating agent (sodium edetate hydrate), 0.41 part by mass of a cross-linking agent (potassium aluminum sulfate, dry), 1.9 parts by mass of a pH adjuster (diethanolamine), 0.5 part by mass of a tackifier (aminoalkyl methacrylate copolymer E), 2.72 parts by mass of other additives (emulsifier, cooling agent, and stabilizer), and 39.42 parts by mass of purified water were mixed to prepare a pressure-sensitive adhesive layer composition. The particle diameter of the silicic anhydride measured by the above particle diameter measurement was particle diameter D 50 : 4.8 μm.

[0079] Next, the obtained pressure-sensitive adhesive layer composition was uniformly spread on a release liner (polypropylene film) so as to be 14 g per patch (140 mm × 100 mm), and a support layer (non-woven polyester fabric, basis weight: 100 g / m 2 ) was laminated thereon to obtain a patch. The composition of the obtained pressure-sensitive adhesive layer is shown in Table 3 below.

[0080] (Examples 2 to 3) Each patch was obtained in the same manner as in Example 1 except that the amount of silicic anhydride was 0.5 part by mass (Example 2) or 1.0 part by mass (Example 3), and the composition of the pressure-sensitive adhesive layer was the composition shown in Table 3 below, respectively.

[0081] (Example 4) Particle diameter D 50 : Instead of silicic anhydride having a particle diameter D 50 of 4.8 μm, a patch was obtained in the same manner as in Example 1 except that silicic anhydride having a particle diameter D 50It was measured by the above particle size measurement. The composition of the obtained pressure-sensitive adhesive layer is shown in Table 3 below.

[0082] (Example 5) Particle size D 50 : Instead of silicic anhydride with a particle size D of 4.8 μm, silicic anhydride with a particle size D 50 of 3.1 μm was used, and a cataplasm was obtained in the same manner as in Example 1 except that glycol salicylate was used instead of diclofenac sodium. The particle size D of silicic anhydride 50 was measured by the above particle size measurement. The composition of the obtained pressure-sensitive adhesive layer is shown in Table 3 below.

[0083] (Example 6) Particle size D 50 : Instead of 3.0 parts by mass of silicic anhydride with a particle size D of 4.8 μm, 4.0 parts by mass of silicic anhydride with a particle size D 50 of 7.7 μm was used, and a cataplasm was obtained in the same manner as in Example 1 except that the composition of the pressure-sensitive adhesive layer was made the composition shown in Table 3 below.

[0084] (Comparative Example 1) A cataplasm was obtained in the same manner as in Example 1 except that silicic anhydride was not used and the composition of the pressure-sensitive adhesive layer was made the composition shown in Table 3 below.

[0085] (Comparative Examples 2 to 3) Particle size D 50 : Instead of silicic anhydride with a particle size D of 4.8 μm, each cataplasm was obtained in the same manner as in Example 1 except that silicic anhydride with a particle size D 50 of 0.12 μm (Comparative Example 2) or 9.6 μm (Comparative Example 3) was used. The particle size D of silicic anhydride 50 was measured by the above particle size measurement. The composition of the obtained pressure-sensitive adhesive layer is shown in Table 3 below.

[0086] (Comparative Example 4) Particle size D 50 : Instead of silicic anhydride with a particle size D of 4.8 μm, a cataplasm was obtained in the same manner as in Example 1 except that magnesium aluminometasilicate with a particle size D 50 of 3.8 μm was used. The particle size D of magnesium aluminometasilicate50 It was measured by the above particle size measurement. The composition of the obtained adhesive layer is shown in Table 3 below.

[0087] The results of the adhesion evaluation, stickiness evaluation, and adhesive layer appearance evaluation for the patches obtained in each Example and Comparative Example are shown in Table 3 below together with the composition of each adhesive layer. Note that for the patch obtained in Comparative Example 4, since the result of the adhesive layer appearance evaluation was N and it was difficult to use as a preparation, the adhesion evaluation and stickiness evaluation were not carried out.

[0088]

Table 3

[0089] As is clear from the results shown in Table 3, in the patches to which the method of the present invention was applied (for example, Examples 1 to 3), by containing silicic anhydride, it was confirmed that all of the adhesion evaluation, stickiness evaluation, and adhesive layer appearance evaluation were sufficiently excellent as patches. On the other hand, in the patches that do not contain silicic anhydride (for example, Comparative Examples 1 and 4), at least one of the adhesion evaluation, stickiness evaluation, and adhesive layer appearance evaluation was inferior, and it was confirmed that they were not sufficient as the adhesive layer of the patch.

[0090] Furthermore, as is clear from the results shown in Table 3, in the patches (for example, Examples 1 and 4 to 6) to which the method of the present invention was applied and the particle size of the silicic anhydride contained in the adhesive layer was within a specific range (for example, 2.0 to 8.0 μm), both the adhesion evaluation and the stickiness evaluation were sufficiently excellent. In contrast, when the particle size of the silicic anhydride contained in the adhesive layer was outside the above range (for example, Comparative Examples 2 to 3), at least one of the adhesion evaluation and the stickiness evaluation was inferior, and it was confirmed that they were not sufficient as the adhesive layer of the patch. 50

Industrial Applicability

[0091] ​As described above, according to the present invention, it is possible to provide a method for improving an adhesive layer that can improve the adhesion of the adhesive layer to the skin and suppress the occurrence of stickiness after peeling in a poultice.

Claims

1. In a patch comprising a support layer and an adhesive layer, wherein the adhesive layer contains a drug and a water-soluble polymer, a method for improving the adhesive layer, which improves the adhesiveness of the adhesive layer and suppresses the stickiness after peeling, The particle diameter D at which the cumulative volume in the particle size distribution becomes 50% ５０ The method further includes a step of further incorporating anhydrous silicic acid having a particle diameter of 0.2 to 9.0 μm at which the cumulative volume in the particle size distribution becomes 50% into the pressure-sensitive adhesive layer. characterized in that it is a method for improving the adhesive layer.

2. The method for improving the adhesive layer according to claim 1, characterized in that the silicic anhydride is contained in the adhesive layer so that the content thereof with respect to the total mass of the adhesive layer is 0.1 to 6.0% by mass.

3. The method for improving the adhesive layer according to claim 1 or 2, characterized in that the adhesive layer further contains at least one selected from the group consisting of carboxymethyl cellulose and pharmaceutically acceptable salts thereof.

4. The method for improving the adhesive layer according to claim 3, characterized in that the silicic anhydride is contained in the adhesive layer so that the mass ratio (content in terms of sodium salt of at least one selected from the group consisting of carboxymethyl cellulose and pharmaceutically acceptable salts thereof: content of silicic anhydride) is 1:2 to 6:0.

5.

5. The method for improving the adhesive layer according to claim 3, characterized in that the content of at least one selected from the group consisting of carboxymethyl cellulose and pharmaceutically acceptable salts thereof in the adhesive layer is 1.0 to 4.0% by mass in terms of sodium salt with respect to the total mass of the adhesive layer containing the silicic anhydride.

6. The method for improving the adhesive layer according to claim 1 or 2, characterized in that the drug is at least one selected from the group consisting of diclofenac, loxoprofen, indomethacin, salicylate, lidocaine, glycyrrhetinic acid, felbinac, ketoprofen, and pharmaceutically acceptable salts thereof.

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