JPH07101853A - Percutaneously absorbable plaster - Google Patents

Abstract

PURPOSE:To provide a percutaneously absorbable plaster excellent in adhesivity and not giving irritation to skins and also pain to the skins when peeled. CONSTITUTION:An self-adhesive layer comprising 100 pts.wt. of a self-adhesive agent, 10-40 pts.wt. of a medicinal substance (e.g. 17-beta-estradiol), if necessary, furthermore a tackifying resin and a percutaneous absorption-accelerating agent is laminated to one side of a support. The self-adhesive agent comprises 5-20 pts.wt. of a polyvinyl pyrrolidone having a mol.wt. of 1000000-5000000 and 100 pts.wt. of either of a silicone adhesive and an acrylic adhesive agent comprising the acrylic copolymer of one or more methacrylate compounds selected from dodecyl methacrylate and octyl methacrylate with one or more acrylate compounds selected from dodecyl acrylate and octyl acrylate. The medicinal substance is contained in the self-adhesive agent in a supersaturated state exceeding the solubility of the self-adhesive agent, and the supersaturated state can stably be maintained for a long period.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a transdermal patch.

[0002]

2. Description of the Related Art Percutaneous absorption patches absorb a drug into the body by distributing the drug from the base of the patch or the drug reservoir to the skin, diffusing, and transferring into the blood. Therefore, it is known that the amount of the drug transferred to the skin varies depending on the presence state of the drug in the base. In particular, the higher the concentration of the drug with respect to the saturated solubility in the adhesive base, the higher the drug transfer rate to the skin, and further, when the drug concentration in the adhesive base is higher than the saturated solubility, that is, in the supersaturated state, It is known that the transmission performance is improved.

For the above reasons, a transdermal patch has been proposed in which the drug concentration in the adhesive base is increased to precipitate drug crystals, or the drug is placed in a supersaturated state in which the saturated solubility is exceeded (Japanese Patent Laid-Open Publication No. S60-187242). 60-16916, JP-A-60-1
85713, JP-A-63-35521, and JP-A-63-93714).

However, a supersaturated transdermal patch has a problem that the supersaturated state of the patch decreases during distribution.
There is a problem that drug crystals are deposited and the permeation performance is lowered. In addition, the patch on which drug crystals are deposited requires the drug to be contained in the adhesive base at a supersaturated concentration or higher, which increases the amount of drug per formulation and increases the cost.
A patch which is slowly deposited after the supersaturated concentration level has a problem that it takes a long time to deposit, resulting in a marked decrease in production efficiency.

Regarding the method for producing a percutaneous absorption preparation in which a drug having a saturated concentration or more is dispersed in an adhesive base, in addition to the above-mentioned patent publications, JP-A-62-273913 and JP-A-63.
Although it is described in Japanese Patent Publication No. -273913, all of them have the following problems.

In the method of precipitating the drug after containing the drug in a supersaturated state in the base, it takes a long time to precipitate the crystal. Therefore, when the crystal is precipitated before distribution, the production time is very long, and In the case of precipitating crystals in the distribution stage, there is a problem that when the crystals are deposited in the user's hands, some crystals are precipitated and some are not. In the method of precipitating drug crystals in a dispersed state, it is extremely difficult to uniformly disperse the crystals when the viscosity of the adhesive base or the adhesive base solution is high, and it is difficult to produce a preparation of uniform quality. was there.

Further disclosed is an estradiol-containing patch in which the pressure-sensitive adhesive layer is made of an acrylic pressure-sensitive adhesive containing estradiol and polyvinylpyrrolidone, and a cloth is laminated on the side of the pressure-sensitive adhesive layer opposite to the skin-contacting surface. (Japanese Patent Laid-Open No. 2-2379268). This contains crystallization of estradiol by containing a predetermined amount of polyvinylpyrrolidone.

However, when the pressure-sensitive adhesive contains 2-ethylhexyl acrylate as a main component as described in Examples, there is a problem that the skin irritation caused by exfoliation of the keratin is caused because the pressure-sensitive adhesive strength is too strong. However, there is a problem that drug permeability is significantly reduced due to the use of a breathable cloth material.

[0009]

The present invention has been made in view of the above-mentioned drawbacks, and an object thereof is to contain a drug in a supersaturated state in which the solubility of the pressure-sensitive adhesive exceeds the solubility. The object of the present invention is to provide a percutaneous absorption patch that can maintain its supersaturated state stably for a long period of time, has excellent adhesiveness, and does not cause skin irritation or pain during peeling.

[0010]

[Means for Solving the Problems]

The transdermal patch of the present invention has a pressure-sensitive adhesive layer composed of a pressure-sensitive adhesive and a drug, which is laminated on one surface of a support.

Examples of the above-mentioned support include cellulose acetate, ethyl cellulose, polyethylene, polypropylene, polyvinyl chloride, vinyl acetate-vinyl chloride copolymer, ethylene-vinyl acetate copolymer, ethylene-vinyl acetate- Carbon monoxide copolymer, ethylene-butyl acrylate-carbon monoxide copolymer, polyvinylidene chloride, polyurethane, nylon, polyethylene terephthalate, resin film such as polybutylene terephthalate, aluminum sheet, etc. These may be laminated sheets, and may be laminated with a woven fabric or a non-woven fabric.

The above-mentioned pressure-sensitive adhesive comprises one of a silicon-based pressure-sensitive adhesive and an acrylic pressure-sensitive adhesive, and polyvinylpyrrolidone. As the above-mentioned silicone-based pressure-sensitive adhesive, "Silascon 355" manufactured by Dow Corning Co., Ltd. is a commercially available product.

The acrylic adhesive is selected from the group consisting of dodecyl methacrylate and octyl acrylate, and one or more methacrylate compounds selected from the group consisting of dodecyl methacrylate and octyl methacrylate. And an acrylic copolymer having one or more acrylate compounds as constituents.

The octyl methacrylate is n
-Octyl methacrylate and 2-ethylhexyl methacrylate can be mentioned, and examples of the octyl acrylate include n-octyl acrylate and 2-ethylhexyl acrylate.

In the above acrylic copolymer, when the amount of one or more methacrylate compounds selected from the group consisting of dodecyl methacrylate and octyl methacrylate decreases, the adhesive strength increases and skin irritation occurs.
It is preferably 0 mol% or more.

When the molecular weight of the polyvinylpyrrolidone is small, the supersaturated state of the drug in the pressure-sensitive adhesive is destroyed, so that the skin permeation amount of the drug is reduced, and when it is large, the diffusion of the drug in the pressure-sensitive adhesive layer is hindered. 10,000-50
Limited to 0,000.

When the amount of polyvinylpyrrolidone is small, the supersaturated state of the drug cannot be maintained, and when it is large, the diffusion of the drug is hindered. Therefore, it is limited to 5 to 20 parts by weight per 100 parts by weight of the adhesive. To be done.

To prepare the pressure-sensitive adhesive used in the present invention, usually, solution polymerization of the required monomer is carried out in the presence of a polymerization initiator. However, the polymerization form is not limited to this. The polymerization reaction conditions are appropriately selected mainly depending on the type of monomer.

When solution polymerization is carried out, for example, ethyl acetate or other general polymerization solvent is added to a predetermined amount of the required monomer, and the azobis type, peroxide is added in a reactor equipped with a stirrer and a cooling reflux device. The reaction may be performed at 70 to 90 ° C. for 8 to 40 hours in a nitrogen atmosphere in the presence of a polymerization initiator such as an oxide type. The monomer and the solvent may be added all at once, or may be added separately in appropriate portions. It is preferable to add the polymerization initiator appropriately in divided portions according to the progress of the reaction.

Examples of the azobis-based polymerization initiator include 2,2'-azobis-iso-butyronitrile,
1,1′-azobis (cyclohexane-1-carbonitrile), 2,2′-azobis- (2,4-dimethylvaleronitrile) and the like can be mentioned. Examples of the peroxide type polymerization initiator include peroxides. Lauroyl, benzoyl peroxide,
Examples thereof include di (ter-butyl) peroxide.

The constitution of the pressure-sensitive adhesive used in the present invention is as described above, but a tackifying resin may be added if necessary. Examples of the tackifying resin include rosin-based resins, rosin-based resin derivatives, terpene resins, terpene phenol resins, aliphatic petroleum resins, aromatic petroleum resins, alicyclic petroleum resins, coumarone indene resins, and alkylphenol resins. , Xylene resin and the like.

As the rosin-based resin, a resin containing a mixed melt of a monovalent carboxylic acid having an alkylhydrophenanthrene nucleus as a main component is preferably used. Further, as the rosin-based resin derivative, hydride, disproportionate, dimerized product, esterified product, etc. of the rosin-based resin are preferably used, and commercially available esterified products include ester gum H.
(Arakawa Chemical Co., Ltd.) and the like.

Examples of the terpene resin include α-
Those containing a cyclic terpene as a main component such as pinene, β-pinene, camphor and dipentene are preferably used, and commercially available products include YS resin A, YS resin PX (all manufactured by Yasuhara Yushi Co., Ltd.), Picolite A and Picolite. S (all manufactured by Hercules) and the like can be mentioned.

As the terpene phenol resin, those obtained by binding phenol to the above terpene resin by Friedel-Crafts reaction or further condensing with formalin are preferably used. As a commercial product, Tamanol 800 (Arakawa Chemical Co., Ltd.) is used. Manufactured by Yasuhara Yushi Co., Ltd., Sumilite PR-12603 (manufactured by Sumitomo Duretz), and the like.

The above-mentioned aliphatic petroleum resin is a tackifying resin whose main component is an aliphatic compound derived from petroleum, and commercially available products include Escoletz (Tonen Petrochemical Co., Ltd.) and Hiletz (Mitsui Petrochemical Co., Ltd.). ), Quinton (manufactured by Zeon Corporation), Tacky Roll (manufactured by Sumitomo Chemical Co., Ltd.) and the like.

The above-mentioned aromatic petroleum resin is a tackifying resin containing an aromatic compound derived from petroleum as a main component, and commercially available products include petrozine (manufactured by Mitsui Petrochemical Co., Ltd.) and neopolymer (Nippon Synthetic Resin Co., Ltd.). Manufactured by Toho Petrochemical Co., Ltd., and PETOL (manufactured by Tosoh Corp.).

The above alicyclic petroleum resin is a tackifying resin whose main component is an alicyclic compound made from petroleum, and examples of commercially available products include Alcon (manufactured by Arakawa Chemical Co., Ltd.) and the like.

The above-mentioned coumarone indene resin is a resin mainly obtained by copolymerizing coumarone or indene, and as commercial products, there are coumarone NG (manufactured by Nippon Steel Chemical Co., Ltd.), coumarone RG (manufactured by Nippon Steel Co., Ltd.) and the like. Can be mentioned.

The above alkylphenol resin is pt-
Butylphenol and acetylene are condensed, and as commercial products, Tamanol 101, 130 (manufactured by Arakawa Chemical Co., Ltd.), Hitanol-1501 (manufactured by Hitachi Chemical Co., Ltd.),
Tacky rolls 101 and 103 (produced by Sumitomo Chemical Co., Ltd.) and the like can be mentioned.

The above-mentioned xylene resin is obtained by polymerizing a resin containing xylene as a main component, and commercially available products include Nikanol A-70, HP-70 (manufactured by Mitsubishi Gas Chemical Co., Inc.), and national xylene (Matsushita Electric Works, Ltd.). Manufactured) and the like.

Of the above tackifying resins, ester gum and YS resin are particularly preferable.

In the above-mentioned pressure-sensitive adhesive layer, when the amount of the tackifying resin is small, a sufficient initial pressure-sensitive adhesive force is not developed, and when the amount is too large, the cohesive force is reduced to cause adhesive residue and the skin is soiled at the time of peeling. 10 to 40 parts by weight is preferable with respect to 100 parts by weight.

The drug is not particularly limited as long as it has a steroid skeleton as a main skeleton, and examples of such drugs include estradiol, progesterone, norethisterone, corticosteroid, testosterone, norgestrel, desogestrel and the like. Can be mentioned. As the drug, 17-β-estradiol and norethisterone acetate are particularly preferable. The term "main skeleton" as used herein means that the sum of the molecular weights of the side chain portions is smaller than the molecular weight of the portion forming the steroid skeleton.

When the amount of the above-mentioned drug added is small, the required amount of permeation through the skin cannot be obtained and the medicinal effect is lost. 3 to 7 parts by weight is preferable for 100 parts by weight of the adhesive.

If necessary, a transdermal absorption enhancer such as N-lauroyl sarcosine and maleic acid may be added to the pressure-sensitive adhesive layer. When the amount of the above-mentioned percutaneous absorption enhancer is small, the effect is not exhibited, and when the amount is large, the adhesiveness of the pressure-sensitive adhesive is reduced, and it easily peels off during perspiration, and further, it may peel to the stratum corneum during peeling due to excessive transfer to the skin. Therefore, 3 to 5 parts by weight is preferable for 100 parts by weight of the adhesive.

The thickness of the pressure-sensitive adhesive layer is not particularly limited, but if it becomes thin, it cannot contain the necessary amount of drug, and if it becomes thick, the drug contained in the pressure-sensitive adhesive layer near the support is effective. 30-200μ because it will not be used for
m is preferred.

The composition of the percutaneous absorption patch of the present invention is as described above, and its production can be carried out by a conventionally known method for producing an adhesive tape. A typical example thereof is a solvent coating method, and other examples include a hot melt coating method and an emulsion coating method. When performing solvent coating, for example, a method of dissolving or dispersing a predetermined amount of a pressure-sensitive adhesive, a drug and a percutaneous absorption enhancer in a solvent such as ethyl acetate, coating the resulting liquid on a support, and drying, peeling A method of applying on paper and drying and then transferring it onto a support is preferably used. This release paper may be used to protect the adhesive layer of the patch until use.

The above-mentioned percutaneous absorption patch is cut into a predetermined shape and stored and stored in a packaging material. As the packaging material, a material which does not permeate oxygen or hardly permeates oxygen is preferable. 0 to 100 [cc / m ² · atm · 24hrs] (25
C) materials are preferred. Examples of such a material include an aluminum foil whose surface is coated with polyethylene terephthalate or polyethylene, and a laminated film of polyvinylidene chloride and polyvinyl chloride.

Further, in order to enhance the stability of the drug content, it is preferable to enclose an oxygen absorber in the packaging material. As the oxygen scavenger, iron-based, hydrosulfide-based, ascorbic acid-based, BHT (butylhydroxytoluene) -based ones can be used, and commercially available products such as Agerace (manufactured by Mitsubishi Gas Chemical Co., Inc.) and freshness preserving agent F (topographic printing plate) (Manufactured by Printing Co.) and the like.

When the transdermal absorption patch of the present invention has insufficient adhesive strength and is difficult to apply, the patch may be fixed with an adhesive tape after application. Examples of such an adhesive tape include Japanese Pharmacopoeia adhesive plaster, Micropore Tape (manufactured by 3M Company), and Utokuban (manufactured by Yutoku Pharmaceutical Co., Ltd.).

[0042]

EXAMPLES Next, examples of the present invention will be described. Hereinafter, "part" means "part by weight". (Example 1) Dodecyl methacrylate (hereinafter referred to as DMA) 69.5 parts (10 mol%), 2-ethylhexyl acrylate (hereinafter referred to as EHA) 46 parts (10 mol%)
And 2-ethylhexyl methacrylate (hereinafter referred to as EHM) 396 parts (80 mol%) were supplied to a separable flask equipped with a stirrer and a cooling device, and ethyl acetate was gradually added to this solution under nitrogen atmosphere to 70%.
The temperature was raised to 2 ° C and 2 parts of lauroyl peroxide was added to 1 part of cyclohexane.
The solution dissolved in 00 parts was divided into 10 parts, and 1 was added to a separable flask to initiate polymerization. 5 after initiation of polymerization
From the time, the remaining 9 was added at 1-hour intervals, and the reaction was continued for 19 hours after the addition was completed. After the reaction was started to adjust the viscosity, 27 parts of ethyl acetate was added 5 times every 5 hours for polymerization for a total of 40 hours, and the solid content was 50% by weight.
An acrylic copolymer solution of was obtained.

15 parts by weight of 17-β-estradiol and 10 parts by weight of polyvinylpyrrolidone having an average molecular weight of 1.2 million were added to 100 parts by weight of the solid content of the acrylic copolymer, and mixed uniformly by a dissolver. By doing so, a mixed solution was obtained. The obtained mixed liquid was applied on a silicon-treated polyethylene terephthalate film (thickness 40 μm) and dried at 60 ° C. for 30 minutes to form a pressure-sensitive adhesive layer having a thickness of 60 μm, and then a thickness of 50 μm.
The adhesive layer was transferred onto the ethylene-vinyl acetate copolymer layer of the polyethylene terephthalate / ethylene-vinyl acetate copolymer laminated film of m to obtain the transdermal patch of the present invention.

Example 2 Polyvinylpyrrolidone was added to 100 parts by weight of the solid content of the acrylic copolymer of Example 1 so that the concentration in the solid content was 7 parts by weight to obtain a mixed solution. A transdermal patch was obtained in the same manner as in Example 1.

Example 3 Example 1 was repeated except that polyvinylpyrrolidone was added to 17 parts by weight to 100 parts by weight of the solid content of the acrylic copolymer of Example 1 to obtain a mixed solution. Similarly, a transdermal absorption patch was obtained.

(Example 4) To 100 parts by weight of the solid content of the acrylic copolymer of Example 1, 10 parts by weight of norethithrone acetate was added instead of 17-β-estradiol to obtain a mixed solution. A transdermal patch was obtained in the same manner as in Example 1 except for the above.

Example 5 Except that polyvinylpyrrolidone having an average molecular weight of 4 million was added to the acrylic copolymer solution of Example 1 instead of polyvinylpyrrolidone having an average molecular weight of 1.2 million to obtain a mixed solution. A transdermal patch was obtained in the same manner as in Example 1.

Example 6 A silicone-based pressure-sensitive adhesive (“Silascon 355” manufactured by Dow Corning) was used as a pressure-sensitive adhesive, and 4 parts by weight of 17-β-estradiol was added to obtain a mixture, except that a mixture was obtained. A transdermal patch was obtained in the same manner as in Example 1.

(Comparative Example 1) The procedure of Example 1 was repeated except that polyvinylpyrrolidone having an average molecular weight of 600,000 was added to the acrylic copolymer solution of Example 1 instead of polyvinylpyrrolidone having an average molecular weight of 1.2 million to obtain a mixed solution. A transdermal patch was obtained in the same manner as in Example 1.

(Comparative Example 2) Polyvinylpyrrolidone having an average molecular weight of 6 million was added to the acrylic copolymer solution of Example 1 instead of polyvinylpyrrolidone having an average molecular weight of 1.2 million to obtain a mixed solution. A transdermal patch was obtained in the same manner as in Example 1.

Comparative Example 3 A transdermal patch was prepared in the same manner as in Example 1 except that 1 part by weight of polyvinylpyrrolidone was added to the acrylic copolymer solution of Example 1 to obtain a mixed solution. Got

Comparative Example 4 A transdermal patch was prepared in the same manner as in Example 1 except that 25 parts by weight of polyvinylpyrrolidone was added to the acrylic copolymer solution of Example 1 to obtain a mixed solution. Obtained.

Comparative Example 5 A transdermal patch was obtained in the same manner as in Comparative Example 1 except that 10 parts by weight of norethithrone acetate was added in place of 17-β-estradiol to obtain a mixed solution.

Comparative Example 6 A transdermal patch was obtained in the same manner as Comparative Example 2 except that 10 parts by weight of norethithrone acetate was added in place of 17-β-estradiol to obtain a mixed solution.

Comparative Example 7 A transdermal patch was obtained in the same manner as Comparative Example 3 except that 10 parts by weight of norethithrone acetate was added in place of 17-β-estradiol to obtain a mixed solution.

Comparative Example 8 A transdermal patch was obtained in the same manner as in Comparative Example 4 except that 10 parts by weight of norethithrone acetate was added in place of 17-β-estradiol to obtain a mixed solution.

(Comparative Example 9) 97.4 parts of 2-ethylhexyl acrylate, 2.6 parts of methacrylate, 0.1 part of polyethylene glycol dimethacrylate, 1.0 part of benzoyl peroxide and 100 parts of ethyl acetate were stirred and cooled. The polymer was supplied to a separable flask equipped with a device, heated to 60 ° C. under a nitrogen atmosphere, and polymerized for 9 hours to obtain a polymer.
Further, 500 parts of ethyl acetate was added to this polymer to adjust the solid content concentration to 20% by weight to prepare an adhesive solution. After adding 5 parts by weight of polyvinylpyrrolidone having an average molecular weight of 1.2 million and 2.5 parts by weight of 17-β-estradiol to the above adhesive solution, a siliconized polyethylene terephthalate film (thickness 40 μm
m) coated on it, dried at 60 ° C for 30 minutes, and thickness of 60 μm
Of the polyethylene terephthalate / ethylene-vinyl acetate copolymer laminated film having a thickness of 50 μm, and then the adhesive layer is transferred onto the ethylene-vinyl acetate copolymer layer of the polyethylene terephthalate / ethylene-vinyl acetate copolymer laminated film to be percutaneously absorbed. A patch was obtained.

Skin Permeation Test The percutaneous absorption patches obtained in Examples 1 to 6 and Comparative Examples 1 to 9 just before production and stored in packaging for 1 year are used as samples and shown in FIG. The skin permeation amount (μg) was measured with the diffusion cell 1. The diffusion cell 1 is composed of a bottomed cylindrical receptor tank 2 and a bottomed cylindrical donor tank 3 arranged on the tank 2. An opening 4 is provided at the center of the bottom wall of the donor tank 3, and the bottom wall is provided with a flange 5 extending in the circumferential direction. Receptor tank 2
Is provided with a flange 6 on the upper side thereof, and a side wall is provided with a sampling port 7 protruding laterally. The flange 5 and the flange 6 are overlapped facing each other, and the donor tank 3 and the receptor tank 2 are stacked in an airtight and concentric manner. A magnetic stirring bar 9 is placed inside the receptor tank 2.

A hairless mouse (6 weeks old, ♂) was sacrificed by cervical dislocation, and immediately the back skin was peeled off to remove subcutaneous fat and muscle layer to obtain a skin piece 8 of about 5 cm × 5 cm.
The obtained skin piece 8 was sandwiched between the flange 5 and the flange 6 of the diffusion cell 1, and the opening 4 of the donor layer 3 was completely closed by the skin piece 8. The obtained sample is circular (3.14 cm ² )
Cut into pieces 8 so that the adhesive layer contacts the pieces 8.
Attached to the central part of.

The receptor layer 2 was filled with the receptor solution, placed in a constant temperature bath maintained at a temperature of 37 ° C., and the magnetic stirrer 9 was rotated by the magnetic stirrer to stir the mixture. Twenty-four hours after the start of the test, 1 ml of the receptor solution was sampled from the sampling port 7, and the amount of 17-β-estradiol in the sampled receptor solution was measured by high performance chromatography. The results are shown in Table 1. When collecting the receptor liquid, the receptor liquid was replenished after the collection. Further, the test was conducted at n = 3, and the average value was calculated.

The receptor liquid was NaH ₂ PO ₄ 5 × 10 ^-4.
1N of NaOH in an aqueous solution in which mol, Na ₂ HPO ₄ 2 × 10 ^-4 mol, NaCl 1.5 × 10 ^-1 mol and gentamicin 10 ppm were dissolved.
It was obtained by dissolving 20 parts of polyethylene glycol 400 in 80 parts of an aqueous solution adjusted to pH 7.2 by adding an aqueous solution.

Skin Adhesion Test Using the patches obtained in Examples 1 to 6 and Comparative Examples 1 to 9 and the Japanese Pharmacopoeia plaster (standard patch), the following tests were carried out on 10 healthy men. After that, evaluation was performed according to the following criteria, and the results are shown in Tables 2 and 3. [Test method] The above patch was applied to the left and right upper arm portions in 5 mm square, and the application state was maintained for 48 hours without bathing, and then the application property (peeling state) at the time of application, 24 hours and 48 hours after application was visually observed. evaluated. [Judgment Criteria] 5: No peeling was observed in all the subjects (less than 20% of the peeling area was acceptable) 4: 1 to 3 subjects had a peeling area of 20% or more 3: Half of subjects having a peeling area of 20% or more (Stripping 1
No more than 2) 30-80% of subjects with peeling area of 20% or more (3 or less peeling) 1: All subjects with peeling area of 20% or more (7 or less peeling) 0: 8 or more peeling was observed Was

Skin irritation test Using the transdermal patches obtained in Examples 1 to 6 and Comparative Examples 1 to 9 and the Japanese Pharmacopoeia plaster (standard patch), the following was applied to 10 healthy men. Was performed and evaluated according to the following criteria (based on the Draize method and erythema criteria), and the results of the mode values are shown in the table. [Test method] The above patch was applied to the left and right upper arms in a 5 mm square, and the patch was applied for 48 hours without bathing (4 hours after application, 12
After each hour, 30 minutes of load exercise was performed to perspire), and the skin condition 30 minutes after peeling and 24 hours after peeling was visually observed. [Criteria] 0: no erythema, 1: very slight erythema (finally noticeable), 2: clear erythema, 3: moderate to strong erythema

[0064]

[Table 1]

[0065]

The composition of the transdermal absorption patch of the present invention is as described above, and the adhesive contains a drug in a supersaturated state exceeding the solubility of the adhesive, and the supersaturated state is stable over a long period of time. It can be maintained, has excellent adhesiveness, and does not cause skin irritation or pain during peeling.

[0066]

[Brief description of drawings]

FIG. 1 is a perspective view of a diffusion cell used in a skin permeability test.

[Explanation of symbols]

 1 Diffusion Cell 2 Receptor Tank 3 Donor Tank 4 Opening 5,6 Flange 7 Sampling Port 8 Skin Piece

Claims (1)

[Claims] 1. A percutaneous absorption patch in which an adhesive layer comprising an adhesive and a drug is laminated on one surface of a support, wherein the adhesive is selected from the group consisting of dodecyl methacrylate and octyl methacrylate. One or more selected methacrylates
Any one of an acrylic pressure-sensitive adhesive and a silicon-based pressure-sensitive adhesive composed of an acrylic copolymer composed of one or more acrylate compounds selected from the group consisting of dodecyl acrylate and octyl acrylate. A transdermal patch, which comprises 100 parts by weight and 5 to 20 parts by weight of polyvinylpyrrolidone having a molecular weight of 1 to 5 million.