JPH06239752A - Aspirin-containing percutaneous absorption preparation - Google Patents

Abstract

PURPOSE:To obtain a percutaneous absorption preparation having excellent release of aspirin, capable of effectively absorbing aspirin through skin into body. CONSTITUTION:In this percutaneous absorption preparation obtained by providing a tacky agent layer containing a medicine and a medicine release promoter, the tacky agent is a copolymer (a) having tack at normal temperature obtained by copolymerizing >=50wt.% (meth)acrylic acid alkyl ester with 1-35wt.% N- vinyl-2-pyrrolidone as essential components and its content is 70-99wt.% and the medicine release promoter is a copolymer (b) prepared by copolymerizing 40-80wt.% (meth)acrylic acid alkyl ester with 20-60wt.% (meth)acrylate and its content is 1-3wt.%. The medicine as a percutaneous absorption preparation is characterized by containing aspirin as the effective medicine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a percutaneous absorption preparation containing aspirin as a medicinal ingredient. More specifically, the release of aspirin is improved by incorporating a drug release promoter into the adhesive. Percutaneous absorption preparation.

[0002]

2. Description of the Related Art A transdermal drug preparation is a drug which allows a drug to be absorbed into the body through the skin to exhibit a desired drug effect.
Transdermal administration of such a drug has the following advantages over conventional oral administration methods. For example, when a drug is orally administered, most of the drug absorbed in the intestine is metabolized in the liver before reaching the affected area and exerting a drug effect, and thus the drug must be administered in an amount more than necessary. Furthermore, since the drug is absorbed in large quantities in a short time, side effects are likely to occur.

On the other hand, in transdermal administration, unlike the above-mentioned oral administration, the drug absorbed through the skin reaches the affected area before being metabolized in the liver. For transdermal administration,
It is unlikely to cause gastrointestinal disorders as seen with oral administration. Further, by adjusting the amount of drug released by transdermal administration, side effects caused by the drug being absorbed in large amounts in a short time can be reduced. Furthermore, if a constant drug release rate can be maintained over a long period of time, the frequency of drug administration can be reduced.

However, at present, the drugs that can be used in transdermal preparations having various advantages are very limited at present. That is, many drugs originally have a property of being difficult to penetrate the skin, and thus transdermal administration often fails to administer a sufficient amount of the drug. For example,
The stratum corneum on the surface of the skin has a barrier function for preventing the invasion of foreign substances into the body, and thus necessarily tries to prevent the absorption of the drug through the skin.

Several attempts have been made to solve the drawbacks of such transdermal preparations. These attempts are generally carried out by adding an absorption enhancer having a function of weakening the barrier function of the stratum corneum to a preparation to facilitate absorption of the drug (for example, JP-A-59-95212,
Tokuhei Hei 3-505835, Tokuhei 4-20886),
It is roughly divided into two methods, namely, a method of increasing the amount of drug released from a transdermal preparation and efficiently absorbing the drug.

[0006]

However, in the former method, the absorption enhancer, which generally has a large absorption promoting effect, causes greater damage to the keratin, and therefore has a large irritating effect on the skin, resulting in such absorption. The application of the patch using the accelerator is limited.

The present invention is intended to solve the above-mentioned conventional problems, and an object thereof is to improve transdermal absorption of aspirin, which can be effectively absorbed into the body through the skin. To provide a formulation.

[0008]

The present invention has been devised to solve the above problems. Aspirin can be effectively released by including a drug release promoter in a certain range in the adhesive layer. It was completed with the knowledge that a transdermal preparation can be provided.

That is, the percutaneous absorption preparation according to the present invention is a transdermal absorption preparation comprising a support and an adhesive layer containing a drug and a drug release accelerating agent provided on the support.
A copolymer (a) which is obtained by copolymerizing 50% by weight or more of a (meth) acrylic acid alkyl ester and 1 to 35% by weight of N-vinyl-2-pyrrolidone as an essential component and has an adhesive property at room temperature. , Its content is 70 to 99% by weight, and the drug release-promoting agent is (meth) acrylic acid alkyl ester 40 to 80% by weight and (meth) acrylic acid 20 to 6
A copolymer (b) obtained by copolymerizing 0% by weight, the content of which is 1 to 30% by weight, and the drug is aspirin.

The constituents of the percutaneous absorption preparation according to the present invention and the preparation method thereof will be described in detail below.

(1) Acrylic pressure-sensitive adhesive The composition of the acrylic pressure-sensitive adhesive used in the present invention is not particularly limited as long as it has pressure-sensitive adhesiveness capable of sticking to the skin for a long time at room temperature. Preferably, a copolymerization product obtained by copolymerizing an ester obtained from an aliphatic alcohol having 1 to 18 carbon atoms and (meth) acrylic acid and N-vinyl-2-pyrrolidone as a functional monomer as essential components Coalescence (a) is used.

Examples of the (meth) acrylic acid alkyl ester include methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate, and acrylic. Decyl acid,
Isodecyl acrylate, lauryl acrylate, stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate, isodecyl methacrylate, lauryl methacrylate , Stearyl methacrylate and the like.

The ratio of alkyl (meth) acrylic acid ester in all monomers used for preparing the copolymer (a) is 5
0% by weight or more, preferably 65% by weight or more, N-
The proportion of vinyl-2-pyrrolidone is 1 to 35% by weight. If the proportion of (meth) acrylic acid alkyl ester in all the monomers is less than 50% by weight or the proportion of N-vinyl-2-pyrrolidone exceeds 35% by weight, the adhesiveness of the adhesive layer at room temperature is insufficient. On the contrary, when the proportion of N-vinyl-2-pyrrolidone is less than 1% by weight, the effect of promoting the release of aspirin is not sufficiently exhibited.

The copolymer (a) is obtained by copolymerizing an alkyl (meth) acrylate and N-vinyl-2-pyrrolidone with another functional monomer in an amount of 49% by weight or less. Good.

Examples of such another functional monomer include a monomer having a hydroxyl group, a monomer having an amide group, a monomer having an amino group, and other copolymerizable monomers. Examples of the monomer having a hydroxyl group include hydroxyalkyl (meth) acrylates such as 2-hydroxyethyl (meth) acrylate and hydroxypropyl (meth) acrylate. Examples of the monomer having an amide group include alkyl (meth) acrylamides such as acrylamide, dimethyl acrylamide and diethyl acrylamide, N-alkoxymethyl (meth) acrylamides such as N-butoxymethyl acrylamide and N-ethoxymethyl acrylamide, and diacetone acrylamide. It is illustrated. Examples of the monomer having an amino group include dimethylaminoethyl acrylate. Other copolymerizable monomers include vinyl acetate, vinyl alcohol, styrene,
α-methylstyrene, vinyl chloride, acrylonitrile,
Ethylene, propylene, butadiene, etc. can also be used.

If necessary, a polyfunctional monomer is added to the monomer component for producing the acrylic pressure-sensitive adhesive,
It may be copolymerized with the above-mentioned monomer component. The addition of this polyfunctional monomer causes only slight cross-linking between the resulting polymers, which increases the internal cohesive strength of the adhesive. Therefore, the so-called adhesive residue phenomenon at the time of peeling off the patch can be almost eliminated irrespective of the property of the applied skin and the amount of perspiration. Moreover, the addition of this polyfunctional monomer does not have any adverse effect on drug release and low skin irritation.

Examples of such polyfunctional monomers include, but are not limited to, di (meth) acrylate, tri (meth) acrylate, tetra (meth) acrylate and the like. More specifically, di (meth) acrylate obtained by reacting polymethylene glycols such as hexamethylene glycol and octamethylene glycol with (meth) acrylic acid; polyalkylene glycols such as polyethylene glycol and polypropylene glycol Di (meth) acrylate obtained by combining with (meth) acrylic acid; tri (meth) acrylate such as trimethylolpropane tri (meth) acrylate or glycerin tri (meth) acrylate; and pentaerythritol tetra (meth) acrylate. The tetra (meth) acrylate of is exemplified. You may use these polyfunctional monomers in combination of 2 or more types.

The polyfunctional monomer is the total amount of the monomers other than the polyfunctional monomer used in the preparation of the copolymer (a).
It is used in a proportion of 0.005 to 0.5 parts by weight with respect to 0 parts by weight. If the amount of the polyfunctional monomer used is less than 0.005 parts by weight, the effect of improving the internal cohesive force due to crosslinking is small, and if it exceeds 0.5 parts by weight, the pressure-sensitive adhesive obtained by polymerization easily causes gelation. It also affects the diffusion and release of aspirin.

If necessary, a tackifier may be added to the acrylic pressure-sensitive adhesive to adjust the tackiness. Examples of the tackifier include rosin-based resins, terpene-based resins, petroleum resins, coumarone-indene resins, terpene-phenol resins, and the like, and preferably rosin-based resins such as hydrogenated rosin esters are used.

To prepare the acrylic copolymer (a),
Usually, solution polymerization of required monomers 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 kind of the monomer.

(2) Drug Release Accelerator The percutaneous absorption preparation of the present invention contains a drug release enhancer in order to improve the aspirin release property and ensure a sufficient blood concentration. As the drug release accelerator, a copolymer composed of 40-80% by weight of (meth) acrylic acid alkyl ester and 20-60% by weight of (meth) acrylic acid
(b) is used.

Used for Preparation of Copolymer (b) (Meth)
The acrylic acid alkyl ester preferably has 1 to 1 carbon atoms.
It is an ester obtained from 18 aliphatic alcohols and (meth) acrylic acid.

Examples of the (meth) acrylic acid alkyl ester include methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, hexyl acrylate, octyl acrylate, 2-ethylhexyl acrylate, isooctyl acrylate, and acrylic. Decyl acid,
Isodecyl acrylate, lauryl acrylate, stearyl acrylate, methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, isooctyl methacrylate, decyl methacrylate, isodecyl methacrylate, lauryl methacrylate , Stearyl methacrylate and the like.

Among the drug release accelerators obtained by copolymerizing these (meth) acrylic acid alkyl esters and (meth) acrylic acid, there are some which do not have tackiness at room temperature, but There is no particular problem within the range of 1 to 30% by weight of the blending ratio of the copolymer (b) to the polymer (a).

The proportion of alkyl (meth) acrylate in all monomers used for preparing the copolymer (b) is 4
0 to 80% by weight, the proportion of (meth) acrylic acid is 20 to 6
It is 0% by weight. When the proportion of (meth) acrylic acid alkyl ester in all the monomers is less than 40% by weight (the proportion of (meth) acrylic acid exceeds 60% by weight), the copolymer (a) and the copolymer (b) are When the proportion of (meth) acrylic acid alkyl ester exceeds 80% by weight (the proportion of (meth) acrylic acid is less than 20% by weight), the effect of promoting the release of aspirin is decreased. Not fully exerted.

Specific examples of the copolymer (b) include a methacrylic acid-ethyl acrylate copolymer (Eudragit L
30D-55, L100-55, Laem Pharma (R
ohmPharma Gmbh), methacrylic acid-methyl acrylate / copolymer (Eudragit L100, manufactured by Rehm Pharma), methacrylic acid-methyl methacrylate / copolymer (Eudragit S100, manufactured by Reem Pharma), and the like. To be done. Among these, methacrylic acid-
Methyl acrylate / copolymer (Eudragit L10
0) and a methacrylic acid-methyl methacrylate copolymer (Eudragit S100) are preferably used.

The blending ratio of the copolymer (a) and the copolymer (b) is 70 to 99% by weight of the copolymer (a), and
(b) 1 to 30% by weight. The proportion of copolymer (a) is 70
If it is less than 30% by weight (the proportion of the copolymer (b) is 30% by weight)
When the proportion of the copolymer (a) exceeds 99% by weight (when the proportion of the copolymer (b) is less than 1% by weight). , The effect of promoting the release of aspirin is not sufficiently exerted.

To prepare the acrylic copolymer (b),
Usually, solution polymerization of required monomers 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 kind of the monomer.

(3) Drug The drug used in the antithrombotic transdermal preparation according to the present invention is aspirin, that is, acetylsalicylic acid. Aspirin exerts various actions such as analgesia, antipyretic, antirheumatic and anticoagulation of platelets.

The content of aspirin in the pressure-sensitive adhesive layer is preferably 1 to 50% by weight. If the content is more than 50% by weight, aspirin may be precipitated in the pressure-sensitive adhesive layer or the pressure-sensitive adhesive layer may have insufficient tackiness at room temperature. Further, if the content is less than 1%, effective drug effect cannot be secured.

(4) Support The support of the percutaneous absorption preparation according to the present invention is flexible, but imparts self-supporting property to the percutaneous absorption preparation and prevents volatilization and migration of the drug in the adhesive layer. Those that fulfill the role of being used are used. As the material of the support, cellulose acetate,
Examples thereof include ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, polyvinylidene chloride and aluminum. These materials are used, for example, as a single layer sheet or film or a laminate of two or more sheets. Materials other than aluminum may be used as woven or non-woven fabrics. As the support, one made of a material having a proper conformability to the skin surface is preferably used, and a laminated film of polyethylene terephthalate and ethylene-vinyl acetate copolymer is particularly preferable.

An adhesive layer having a certain thickness is formed on the surface of such a support to obtain the transdermal preparation of the present invention. Further, in order to improve the adhesion between the support and the pressure-sensitive adhesive layer, the support may be subjected to corona treatment, plasma discharge treatment, or coated with an anchor coating agent. The thickness of the support is 500 μm or less, preferably 5 to 1
It is 50 μm.

(5) Release Paper The percutaneous absorption preparation according to the present invention is usually provided with a release paper on its sticking surface in order to protect the surface of the pressure-sensitive adhesive layer until use. As the release paper, a polyethylene terephthalate film treated with silicon is often used, but the release paper is not limited to this. The thickness of the release paper is 1
The thickness is 000 μm or less, preferably 20 to 200 μm.

(6) Preparation method In order to prepare the percutaneous absorption preparation according to the present invention, a usual method for producing an adhesive tape can be applied. A typical example thereof is a solvent coating method, and in addition to this, a hot melt coating method, an electron beam curing emulsion coating method and the like are used. To form the percutaneously absorbable preparation according to the present invention by a solvent coating method, for example, an adhesive, a drug release-promoting agent, a drug, and an additive optionally added are dissolved or dispersed in an appropriate solvent. Then, the obtained solution or dispersion is directly applied to the surface of the support and dried to form a pressure-sensitive adhesive layer having a required thickness. This adhesive layer is brought into close contact with a protective release paper to obtain the desired tape-shaped percutaneous absorption preparation. Further, this solution or dispersion may be coated on a protective release paper, and the pressure-sensitive adhesive layer obtained after drying may be brought into close contact with the support.

To prepare the percutaneously absorbable preparation according to the present invention by the hot melt method, for example, an adhesive, a drug release accelerator, a drug and, if necessary, various compounding ingredients are heated and melted and then mixed. The melt is applied directly to the surface of the support and cooled to solidify to form an adhesive layer. This adhesive layer is brought into close contact with a protective release paper to obtain a desired percutaneous absorption preparation. Alternatively, the melt may be applied onto release paper and the pressure-sensitive adhesive layer obtained after cooling and solidification may be brought into close contact with the support.

Although the thickness of the pressure-sensitive adhesive layer varies depending on the purpose of use, it is usually about 10 to about 1000 μm, preferably 20 to.
It is in the range of 200 μm. Thickness of adhesive layer is about 10 μm
If the amount is less than the range, the effect of protecting the wound is insufficient, the required amount of the drug cannot be contained, and the adhesiveness is insufficient. On the contrary, if the thickness exceeds 1000 μm, the flexibility of the pressure-sensitive adhesive layer may be impaired.

[0037]

When the transdermal preparation according to the present invention is applied to the skin surface, the contained aspirin is easily absorbed into the body through the skin. The detailed mechanism is not clear,
It can be considered as follows. That is, the copolymer (b) constituting the drug release-promoting agent compounded in the pressure-sensitive adhesive layer is more hydrophilic than the copolymer (a) constituting the pressure-sensitive adhesive and absorbs water. Have a property of swelling but not substantially swelling with aspirin. Therefore, when the transdermal absorption preparation according to the present invention is applied to the skin surface, the drug release-promoting agent absorbs moisture such as sweat and swells, and acts to remove aspirin from the adhesive layer. By the action of this drug release accelerator, aspirin is effectively released from the adhesive layer and absorbed into the body through the skin.

[0038]

EXAMPLES Next, in order to specifically explain the present invention, some examples of the present invention and some comparative examples showing a comparison therewith are given, and further various transdermal preparations obtained The performance test results of are shown.

(1) Preparation of percutaneous absorption preparation Example 1 (a) Preparation of acrylic adhesive 2-ethylhexyl acrylate 75% by weight (187,
5 g), 25% by weight of N-vinyl-2-pyrrolidone (6
2.5 g) was charged into a separable flask, and ethyl acetate 2 was added so that the monomer concentration at the initial stage of polymerization was 50% by weight.
50 g was added. This solution was heated to 80 ° C. under a nitrogen atmosphere, and a solution prepared by dissolving 1 g of lauroyl peroxide in 100 ml of ethyl acetate as a polymerization initiator was added little by little to carry out a polymerization reaction for 8 hours.

Thus, an ethyl acetate solution of an acrylic pressure-sensitive adhesive having a solid content concentration of 41.7% by weight was obtained.

(B) Preparation of coating liquid Methyl methacrylate and methacrylic acid as a drug release accelerator were copolymerized at a weight ratio of 2: 1 with an ethyl acetate solution of the above-mentioned acrylic pressure-sensitive adhesive to prepare a copolymer. Methacrylic acid-methyl methacrylate copolymer (Eudragit S100, manufactured by Reem Pharma Co.) having an average content of methacrylic acid in the range of 25 to 34.5% by weight in total solid content of 2% by weight. And aspirin, which is the drug, are dissolved so that the concentration in the total solid content is 16.2% by weight (saturated solubility in the total solid content) to prepare a drug release-promoting agent and a drug-containing coating liquid. did.

(C) Preparation of percutaneous absorption preparation Polyethylene terephthalate (PET) having a thickness of 35 μm
After applying the above-mentioned coating liquid on a release paper obtained by treating the above film with silicon, it is dried at 60 ° C. for 30 minutes to give a thickness of 80.
An adhesive layer having a thickness of μm was formed. Then, the pressure-sensitive adhesive layer was adhered to the PET film side of a support having a thickness of 35 μm formed by laminating a PET film and an ethylene-vinyl acetate copolymer (EVA) film. Thus, a tape-shaped percutaneous absorption preparation was obtained.

Example 2 In step (b) of Example 1, a methacrylic acid-methyl methacrylate copolymer (Eudragit S100) was added to an ethyl acetate solution of an acrylic pressure-sensitive adhesive at a concentration of 5 in the total solid content.
Except that the drug release accelerator and the drug-containing coating solution were prepared by dissolving aspirin so that the concentration in the total solid content would be 16% by weight (saturated solubility in the total solid content), respectively. A percutaneous absorption preparation was prepared in the same manner as in Example 1.

Example 3 In the step (b) of Example 1, a methacrylic acid-methyl methacrylate copolymer (Eudragit S100) was added to an ethyl acetate solution of an acrylic pressure-sensitive adhesive at a concentration of 1 in the total solid content.
0% by weight and aspirin were dissolved so that the concentration in the total solid content was 15.7% by weight (saturated solubility in the total solid content), and the drug release accelerator and the drug-containing coating liquid were dissolved. A transdermal preparation was prepared in the same manner as in Example 1 except that the preparation was performed.

Example 4 In the step (b) of Example 1, a methacrylic acid-methyl methacrylate copolymer (Eudragit S100) was added to an ethyl acetate solution of an acrylic pressure-sensitive adhesive at a concentration of 2 in the total solid content.
0% by weight and aspirin were dissolved so that the concentration in the total solid content was 15.0% by weight (saturated solubility in the total solid content), and the drug release accelerator and the drug-containing coating liquid were dissolved. A transdermal preparation was prepared in the same manner as in Example 1 except that the preparation was performed.

Example 5 In step (b) of Example 1, methyl acrylate and methacrylic acid were copolymerized with a solution of an acrylic pressure-sensitive adhesive in ethyl acetate at a weight ratio of 1: 1. Of methacrylic acid-methyl acrylate copolymer (Eudragit L100) having an average methacrylic acid content of 38 to 52% by weight in total solid content of 2% by weight and total aspirin content. The same operation as in Example 1 except that the drug release accelerator and the drug-containing coating liquid were prepared by dissolving each of them so that the concentration in the solid content was 16.2 wt% (saturated solubility in the total solid content). A percutaneous absorption preparation was prepared by

Example 6 In the step (b) of Example 1, a methacrylic acid-methyl acrylate / copolymer (Eudragit L100) was added to an ethyl acetate solution of an acrylic pressure-sensitive adhesive at a concentration of 20 in the total solid content.
To prepare a drug release-promoting agent and a drug-containing coating liquid by dissolving aspirin in a concentration of 15.0% by weight in total solid content (saturated solubility in total solid content). A percutaneous absorption preparation was prepared in the same manner as in Example 1 except for the above.

Comparative Example 1 In the step (b) of Example 1, a drug release accelerating agent was not added to the ethyl acetate solution of the acrylic adhesive base, and only aspirin was contained in the total solid content at 16.3% by weight. A percutaneous absorption preparation was prepared in the same manner as in Example 1 except that the drug-mixing coating solution was prepared by dissolving so as to have a saturated solubility in the total solid content.

Comparative Example 2 In the step (b) of Example 1, Eudragit S100 was added to a solution of an acrylic adhesive base in ethyl acetate so that the concentration of the Eudragit S100 in the total solid content was 40% by weight, and aspirin was added in the total solid content. Transdermal by the same procedure as in Example 1 except that the medium concentration was 13.7% by weight (saturated solubility in the total solid content) to prepare a drug release-promoting agent and a drug-containing coating solution. An absorption preparation was prepared.

Comparative Example 3 In the step (b) of Example 1, Eudragit L100 was added to an ethyl acetate solution of an acrylic adhesive base so that the concentration of the total solid content was 40% by weight, and aspirin was added to the total solid content. Transdermal by the same procedure as in Example 1 except that the medium concentration was 13.7% by weight (saturated solubility in the total solid content) to prepare a drug release-promoting agent and a drug-containing coating solution. An absorption preparation was prepared.

(2) Performance Evaluation of Percutaneous Absorption Formulations The performance of the following items was examined for each transdermal absorption formulation obtained in Examples and Comparative Examples.

(A) Human skin migration test of drug 3.14 cm ² circular tape-shaped percutaneous absorption preparation was adhered to the chest of 5 spontaneous test subjects (healthy person, male) after removing the release paper. Then, after 24 hours, this was peeled and collected, and the residual amount of aspirin in this test piece was quantified by the following method. The difference between the initial aspirin content of the percutaneous absorption preparation and the residual amount after the test was used as the amount transferred to the skin for 24 hours.

The amount of aspirin in the adhesive layer was determined by the following method.
I went there. That is, 3.14 cm ²Round tape
Percutaneous absorption preparation with a fixed amount of ethyl parahydroxybenzoate
Immersed in 5 ml of tetrahydrofuran containing
The layers were allowed to dissolve. Add isopropanol-water mixture to this solution
50 ml of (1: 1) was added to precipitate the adhesive. this
Collect the supernatant and use high performance liquid chromatography to
Aspirin in the adhesive was quantified by the internal standard method.

(B) Adhesiveness test of transdermal absorption preparation A circular tape-shaped transdermal absorption preparation of 3.14 cm ² was removed from the release paper and then applied to the chest of five spontaneous test subjects (healthy persons, males). It was applied and peeled off after 24 hours, and a sensory test was conducted on the peeling resistance of the test piece and the amount of adhesive residue on the skin after peeling. The degree of tackiness was evaluated according to the following three criteria.

◯: There is sufficient resistance at the time of peeling, and the skin feels pulled.

Δ: The resistance to peeling is insufficient and the skin does not feel pulled.

X: There is no resistance to peeling and adhesive residue may occur.

The results of the above tests (a) and (b) are shown in Table 1.

[0059]

[Table 1] As is clear from the above table, the percutaneous absorption preparations of Examples belonging to the scope of the present invention have significantly higher aspirin-releasing properties as compared with the percutaneous absorption preparations containing no drug release promoter, It is recognized as a percutaneous absorption preparation with expected higher drug efficacy. Further, the percutaneous absorption preparations of Examples belonging to the scope of the present invention have good adhesiveness as compared with the percutaneous absorption preparations excessively containing the drug release promoter.

[0060]

EFFECTS OF THE INVENTION Since the transdermal preparation according to the present invention is constituted as described above, it has a better aspirin-releasing property than conventional products, and effectively absorbs aspirin through the skin into the body. A percutaneous absorption preparation to be obtained can be provided.

Claims (1)

[Claims] 1. A percutaneous absorption preparation comprising a support and a pressure-sensitive adhesive layer containing a drug and a drug release accelerating agent, wherein the pressure-sensitive adhesive comprises 50% by weight or more of a (meth) acrylic acid alkyl ester and N-. Vinyl-2-pyrrolidone 1-35% by weight
Is a copolymer (a) having an adhesive property at room temperature and having a content of 70 to 99.
The drug release accelerating agent is a copolymer (b) obtained by copolymerizing 40 to 80% by weight of (meth) acrylic acid alkyl ester and 20 to 60% by weight of (meth) acrylic acid, The content thereof is 1 to 30% by weight, and the drug is aspirin.