JPS59199628A - Application drug - Google Patents

Abstract

PURPOSE:An application drug, obtained by laminating a pressure-sensitive adhesive layer, consisting of a copolymer of a methacrylic acid ester or acrylic acid ester and vinylpyrrolidone, and containing a chemical on one surface of a base material sheet, capable of exhibiting drug effect in a short time after the application thereof, and effective for a long term. CONSTITUTION:An application drug obtained by laminating a pressure-sensitive adhesive layer, consisting of a copolymer of a methacrylic acid ester or acrylic acid ester and vinylpyrrolidone, and containing a chemical, e.g. a nitro based compound such as isosorbide dinitrate or nitroglycerol on a base material sheet, e.g. a flexible sheet impermeable to chemicals such as polyethylene, polypropylene or ethylene-vinyl acetate copolymer. The chemical is percutaneously absorbed in a time as short as about 30min, reaches the effective concentration in blood and then is absorbed constantly for about 24hr thereafter. The application drug is well compatible with the skin. The content of the vinylpyrrolidone is preferably 1-60mol% in the above-mentioned copolymer.

Description

[Detailed description of the invention] The present invention relates to a patch.

Conventionally, as a patch that is applied to the body to treat diseased areas of the body's outer skin or to continuously administer drugs to the circulatory system through the skin, one side of the backing member is made of acrylic resin containing the drug.
A laminated adhesive layer (equity 11i1 (52-3)
No. 1405, Japanese Unexamined Patent Publication No. 116011/1983),
A device in which a drug diffusion control layer is provided between a drug storage layer and an adhesive layer (Japanese Patent Publication No. 54-16566) is known.

However, when acrylic adhesives contain drugs such as Adrenal Cortex Yltrumon, the drug migrates in a short period of time after being applied to the skin, and the medicinal effect only lasts for a short period of time. The drawback is that the blood concentration becomes too high and side effects occur, so when an acrylic adhesive contains a drug such as insorbitcinitrate, the blood concentration of the drug decreases even though the pressure is maintained at a constant pressure for a long period of time. It has the disadvantage that it takes a long time with a certain amount of heat, and it cannot be expected to be fast-acting.Also, those with a drug diffusion control layer have the disadvantages that they are difficult to manufacture, are expensive, and cannot be expected to be fast-acting. Ta.

In view of the above-mentioned drawbacks, the present invention has been made with the aim of providing a patch that exhibits its medicinal efficacy within a short period of time after application and is effective for a long period of time. The patch consists of a pressure-sensitive adhesive layer made of an acrylic ester-vinylpyrrolidone copolymer and laminated with a drug-containing pressure-sensitive adhesive layer.

Drug-impermeable sheets are preferred, such as polyethylene, polypropylene, ethylene-acetic acid copolymers, po-IJ
Examples include sheets of vinyl mide, polyvinylidene chloride, vinyl acetate-vinyl chloride copolymer, polyamide, polyester, cellulose acetate, ethyl cellulose, cellophane, etc., metal foils such as aluminum 9mm foil, and laminates thereof. The sheet is preferably subjected to corona discharge treatment in order to improve the adhesive strength with the pressure-sensitive adhesive layer.

In the present invention, a pressure-sensitive adhesive layer is laminated on one surface of the base sheet, and the pressure-sensitive adhesive layer is made of a (meth)acrylic acid ester-vinylpyrrolidone copolymer and is formed by containing a drug. Ru.

means the (meth)acrylic ester or methacrylic ester constituting the (meth)acrylic ester-vinylpyrrolidone copolymer,
For example, methyl acrylate, ethyl acrylate, propyl acrylate, isopropyl acrylate, butyl acrylate, isobutyl acrylate, hexyl acrylate,
Octyl acrylate, 2-ethylhexyl acrylate,
Decyl acrylate, indecyl acrylate, lauryl acrylate, methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate,
Examples include 2-ethylhexyl methacrylate.

In addition, the ratio of (meth)acrylic acid ester and vinylpyrrolidone in the above copolymer is such that when the amount of vinylpyrrolidone added decreases, the initial backwardness decreases, and when the amount increases, the tackiness decreases. Content is 1-60
Preferably it is mole %.

The above drug can be any drug that has been conventionally used in patch preparations, such as insorbitcinitrate,
Examples include nitro compounds such as nitroglycerin, amyl nitride, and benterythritol tetranitrate. In addition, the amount of the drug to be added may be appropriately determined depending on the potency of the drug and the purpose of use; as the amount of the above-mentioned nitro compound added increases, the compatibility decreases and it begins to precipitate on the surface of the adhesive layer.
It is preferable that 5 to 50 layers of the adhesive be added to the adhesive layer.

The structure of the adhesive tape of the present invention is as described above, and since the adhesive layer is formed from a (meth)acrylic acid ester-vinylpyrrolidone copolymer and a drug, the drug can be applied in a short time of about 30 minutes. It is absorbed transdermally, reaches an effective blood concentration, and is absorbed constantly for about 24 hours thereafter, so it is well adapted to skin pressure and can be applied suitably to the body.

Next, examples of the present invention will be described.

Example 1 2-ethylhexyl acrylate 154.69 vinylpyrrolidone 40.09 ethyl acetate
83.49 A mixture having the above composition was heated at 65° C. under nitrogen atmosphere with 100 rnl of an ethyl acetate solution in which 0.65' of azobisin butyronitrile was dissolved.
was added for 20 d at the initial stage, and then polymerized by adding 10 m/m every 25 hours. After the polymerization, ethyl acetate for #station was added to obtain an adhesive composition with a solid content of 19.7%.

To the obtained adhesive composition, 3.39 g of 30% acetone solution of 20PK insorbitinitrate was added, uniformly dispersed and dissolved, and then applied to a polyethylene film with a thickness of 50μ, and heated at 70°C with gear open for 30 minutes. After drying for minutes, a patch having a pressure-sensitive adhesive layer laminated with a thickness of 50 μm was obtained.

Next, samples were prepared by punching out the above patch into a circular shape with a diameter of 36 πm, and the skin transferability and blood concentration over time were measured. The results are shown in Tables 1 and 2.

The test method for skin penetration and the method for measuring blood concentration are as follows.

(2) Transfer to the skin The hair on the back of a male rabbit weighing 2.2 to 25 kg was removed using clippers, and then the hair was completely removed using palicum sulfide, and the above sample was applied to the hair-removed area.

Next, at predetermined intervals [the samples were peeled off from three rabbits, the adhesive layer was dissolved in ethyl acetate, and the weight loss of the drug in the adhesive layer was measured by hydrogen flame detector gas chromatography. It is expressed as a percentage of the amount of drug in the layer. Three samples each of Example 1, Example 2 (described later), and Comparative Example 1 were applied to one rabbit.

■A sample was applied to a hair-depleted cutlet in the same manner as in the blood concentration skin S transfer test, K3me blood was collected at predetermined intervals, and the obtained blood was centrifuged, extracted with n-hexane, and evaporated to dryness. The dry solid content was dissolved in ethyl acetate and measured by electron capture detector gas chromatography.

2-Ethylhexyl methacrylate 24.09 2-ethylhexyl acrylate l 54.69 Vinylpyrrolidone 26.7 Ethyl guacetate
88.09 An adhesive with a solid content of 25.3% was prepared in the same manner as in Example 1 using a formulation having the above composition and 1.00 me of an ethyl acetate solution in which 0.6 F of azobisisobutyronitrile was dissolved. Get the composition.

The obtained adhesive composition 209 VC isosorbo (4.2 hours of idocynitrate 30% acetone solution) was added, a patch was obtained in the same manner as in Example 1, and the skin transfer property and blood concentration were measured. The results are shown in Tables 1 and 2.

Comparative Examples 2-ethylhexyl acrylate 59.69 Butyl methacrylate 143.5 F Ethyl acetate 87. A pressure-sensitive adhesive composition having a solid content of ZtS% was prepared in the same manner as in Example 1 using a formulation having the above composition and 100 me of an ethyl acetate solution in which 0.599% of azobisisobutyronitrile was dissolved. Ta.

To 20 parts of the obtained adhesive composition, 3.6 mI of a 30% acetone solution of insolunoidocynitrate was added, and a patch size J was obtained in the same manner as in Example 1, and the skin transferability and blood The medium concentration was measured and the results are shown in Tables 1 and 2. 7'C.

@Table 1 (Skin migration %) S, E are Skungood error Table 2 (Blood concentration nνml) vague ( ) − [

Claims (1)

[Scope of Claims] L A patch comprising a pressure-sensitive adhesive layer made of a (meth)acrylate ester-vinylpyrrolidone copolymer and containing a drug, laminated on one side of a base sheet. 2. The adhesive patch according to claim 1, wherein the vinylpyrrolidone content of the copolymer is 1 to 60 mol%. 3. Claim 1 in which the drug is a nitro compound
The patch according to item 2 of item id. 4. The adhesive patch according to claim 3, wherein the drug is insorbitcinitrate.