JPH04360827A - Precutaneously absorbable cataplasm - Google Patents

Abstract

PURPOSE:To provide the title cataplasm high in the dermal penetrability per unit area of norethisterone and/or its ester, leading to enabling adequate drug delivery with smaller area. CONSTITUTION:The objective cataplasm can be obtained by providing (A) one surface of a substrate with (B) an ointment layer containing (1) 1-20wt.% of a medicine consisting of norethisterone and/or its ester and (2) an acrylic tack agent consisting of a copolymer from 45-80mol% of 2-ethylhexyl acrylate and 20-55mol% of N-vinyl-2-pyrrolidone.

Description

[Detailed description of the invention]

0001

[Field of Industrial Application] The present invention relates to a transdermal patch used to administer a required drug to the body's circulatory system via a biological membrane by applying it to the skin, and more specifically, The present invention relates to a transdermal patch that contains norethisterone and/or its ester as a medicinal ingredient and also contains a transdermal absorption enhancer, has excellent adhesiveness and adhesion, and absorbs a drug at a stable blood concentration over time.

0002

[Prior art] Norethisterone (chemical name: 17-α-
Hydroxy-19-norpregn-4-en-20-yn-3-one) and/or its esters are known as synthetic progestin agents, and their administration shows contraceptive effects in women and is effective against menopausal symptoms and osteoporosis. Reduction and
It is known to be effective in treating menstrual abnormalities. Preparations containing this drug are widely known; for example, Japanese Patent Application Laid-Open No. 61-93119 describes a synergistic contraceptive containing benzamide that increases prolactin, norethisterone that is a progestogen, and in some cases estrogen. Pharmaceutical compositions are disclosed. Also, JP-A-62
-153219 also discloses a contraceptive kit containing norethindrone acetate and ethinyl estradiol. Further, compositions of norethisterone and norethisterone acetate used for the above purpose are also disclosed in JP-A-62-205024 and JP-B-1-132523.

However, this drug is heavily metabolized by the liver, placing a heavy burden on the liver, and also has a low bioavailability, so when administered orally, large doses must be administered at once. However, long-term use can cause cancer and cardiovascular disease. Therefore,
Oral administration of this drug is not preferred. Therefore, there is a strong need for a sustained-release preparation that can control the blood concentration of hormones over a long period of time without raising the blood concentration to a high level all at once.

[0004] Transdermal absorption-type preparations are particularly preferred formulations that can avoid hepatic metabolism, are easy to administer, and can withstand long-term administration, and can meet the above requirements. As such a preparation, for example, West German Published Patent Application No. DE-3333240 discloses a transdermal absorption preparation containing a steroid hormone such as norethisterone acetate in the form of fine particles in silicone gel.

[0005] However, since the skin has a biological defense function that prevents foreign substances from entering the body, it is said to be difficult to transdermally administer a sufficient amount of a drug to exert the desired medicinal effect. To solve this problem, measures have been taken such as increasing the area of application and incorporating transdermal absorption enhancers into the base.

As a formulation intended to improve transdermal absorption, for example, a transdermal treatment system having a subsaturated drug reservoir matrix has been proposed in Japanese Patent Application Laid-open No. 25569/1983. According to this document, stable and uniform drug supply is possible by using a drug supply source that is in a subsaturated state. Such multilayered patch-like transdermal preparations have a stable drug delivery rate;
It has the following problems. That is, since the preparation has a multilayer structure, the tape is extremely thick, which causes a great discomfort when worn on the skin. Furthermore, since the dosage form is complicated, the manufacturing equipment and manufacturing process become complicated.

Furthermore, JP-A-2-500740 discloses that levonorgestrel or norethindrone as a progestin is contained dispersedly in a polymer matrix made of a silicone polymer or a copolymer along with 17-β-estradiol or ethinyl estradiol as an estrogen, Furthermore, a transdermal fertility regulating system is disclosed which contains one selected from isopropyl myristate, a straight chain fatty acid containing an alkyl group of 4 to 18 carbon atoms, and decyl methyl sulfoxide as a skin penetration enhancer.

[0008] In this preparation, the polymer matrix is a single layer, so it has the advantage of being easy to manufacture, but the above-mentioned skin penetration enhancer does not have sufficient release and transfer to obtain the necessary blood concentration. You can't get speed. Therefore,
In order to obtain the desired dosage, it is still necessary to produce a formulation with a fairly large area.

[0009]

The present invention has been devised to solve the above-mentioned problems of the prior art, and its purpose is to reduce the amount of norethisterone and/or its ester per unit area in the skin. The object of the present invention is to provide a transdermal patch that has high permeability and, as a result, can be used in a smaller area and can provide sufficient drug delivery.

0010

[Means for Solving the Problems] The transdermal absorption patch of the present invention has been devised to achieve the above object, and it is said that the use of a specific acrylic adhesive significantly improves the skin permeability of drugs. It has been completed by gaining knowledge.

That is, the transdermal patch according to the present invention is a patch comprising a support and a plaster layer containing a drug and an adhesive on one side, in which the adhesive contains 45 to 80 moles of 2-ethylhexyl acrylate. % and 20 to 55 mol% of N-vinyl-2-pyrrolidone, and contains norethisterone and/or as drugs.
Or it contains 1 to 20% by weight of its ester.

[0012] The transdermal patch according to the present invention may contain oxycarboxylic acids having 2 to 10 carbon atoms and salts thereof, dicarboxylic acids having 2 to 10 carbon atoms, and salts thereof, and compounds selected from the group consisting of N-acylsarcosine and salts thereof.

[0013] In addition, in the transdermal patch according to the present invention, if necessary, a material having a carbon number of 10 is added to the plaster layer as an adhesion improving agent.
Contains a higher fatty acid ester of ~18 higher fatty acids and an alcohol having 1 to 20 carbon atoms.

In its preferred mode, the transdermal patch according to the present invention contains 2-ethylhexyl acrylate 5
5 to 70 mol%, and 30 to 70 mol% of N-vinyl-2-pyrrolidone.
Preferably 2 to 15% by weight, more preferably 4 to 10% by weight of norethisterone acetate is contained in an adhesive base made of an acrylic adhesive made of a copolymer with 45 mol% of norethisterone acetate. Lactic acid, fumaric acid and/or N-lauroylsarcosine are used as accelerators, preferably from 1 to
15% by weight, more preferably 2 to 5% by weight, and/or preferably 1 to 15% by weight, more preferably 2 to 7% by weight of isopropyl myristate as an adhesion improving agent.
Contains % by weight.

[0015] Each component of the transdermal patch according to the present invention will be explained in detail below.

a) In the transdermal patch according to the present invention, the adhesive forming the main body of the plaster layer is composed of 45 to 80 mol% of 2-ethylhexyl acrylate and 20 to 55 mol% of N-vinyl-2-pyrrolidone. This is an acrylic adhesive made of copolymer.

If the proportion of 2-ethylhexyl acrylate, which is the main component of the copolymer, is less than 45 mol%, the tackiness will be significantly reduced, and if this proportion exceeds 80 mol%, it will not dissolve in the drug base. Since the solubility of the drug decreases, drug crystals precipitate, resulting in a decrease in adhesion and a decrease in skin permeability of the drug, which is not preferable in either case. A particularly preferred copolymer is 55 to 70 mole % of 2-ethylhexyl acrylate and 30 to 70 mole percent of N-vinyl-2-pyrrolidone.
It is a copolymer with 45 mol%.

[0018] A polyfunctional monomer may be further added to the acrylic pressure-sensitive adhesive, if necessary. The addition of this polyfunctional monomer causes very slight crosslinking between the resulting polymers, thereby increasing the internal cohesive strength of the adhesive. Therefore, the so-called adhesive residue phenomenon when the patch is removed can be almost eliminated, regardless of the properties of the skin to which it is applied or the amount of perspiration. Moreover, the addition of this polyfunctional monomer does not have any adverse effect on drug release properties or low skin irritation. Examples of such polyfunctional monomers include di(meth)
Examples include, but are not limited to, acrylate, tri(meth)acrylate, and tetra(meth)acrylate. More specifically, polymethylene glycols such as hexamethylene glycol and octamethylene glycol (
Di(meth)acrylate obtained by bonding with meth)acrylic acid; Di(meth)acrylate obtained by bonding polyalkylene glycols such as polyethylene glycol or polypropylene glycol with (meth)acrylic acid; Trimethylolpropane Tri(meth)acrylates such as tri(meth)acrylate and glycerin tri(meth)acrylate; and tetra(meth)acrylates such as pentaerythritol tetra(meth)acrylate. These polyfunctional monomers may be used in combination of two or more types. The polyfunctional monomer is used in an amount of 0.005 to 0.5% by weight based on the total monomers used in the production of the adhesive. No amount of polyfunctional monomer used
．． If the amount is less than 0.05% by weight, the effect of improving internal cohesive force due to crosslinking will be small, and if it exceeds 0.5% by weight, the adhesive obtained by polymerization will tend to gel, and the diffusion and release of the drug will also be affected. appear.

[0019] To prepare an acrylic adhesive, usually
Solution polymerization of the required monomers is carried out in the presence of a polymerization initiator. However, the polymerization form is not limited to this. Further, the polymerization reaction conditions are appropriately selected.

b) The drug of the transdermal patch according to the present invention is norethisterone and/or its ester. Examples of the ester of norethisterone include acetate, valerate, and benzoate.

The content of the drug in the plaster layer is preferably in the range of 1 to 20% by weight, more preferably 2 to 15% by weight, most preferably 4 to 10% by weight. If the drug content is too low, the necessary and sufficient amount of drug permeable through the skin will not be obtained; if the content is too high, crystals will precipitate, resulting in decreased adhesive properties and a decrease in the amount of drug permeable through the skin.

c) The support for the transdermal patch according to the present invention is flexible but provides self-supporting properties to the transdermal patch, and prevents volatilization and migration of the drug in the plaster layer. Those that serve the purpose are used. Materials for the support include cellulose acetate, ethyl cellulose, polyethylene terephthalate, plasticized vinyl acetate-vinyl chloride copolymer, nylon, ethylene-vinyl acetate copolymer, plasticized polyvinyl chloride, polyurethane, polyethylene, polyvinylidene chloride, Examples include 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 a support,
A material made of a material that has conformability to the skin surface is preferably used, and a laminate film of polyethylene terephthalate and ethylene-vinyl acetate copolymer is particularly preferred. The thickness of the support is 500 μm or less, preferably 5 to 150 μm.

d) The absorption enhancer used as necessary in the transdermal absorption patch according to the present invention has a carbon number of 2 to
10 oxycarboxylic acids and their salts, carbon number 2~
10 dicarboxylic acids and salts thereof, and N-acylsarcosine and salts thereof.

Examples of the oxycarboxylic acid having 2 to 10 carbon atoms include lactic acid, glyceric acid, tartaric acid, citric acid, tropic acid, and benzylic acid.

As the dicarboxylic acid having 2 to 10 carbon atoms,
Examples include oxalic acid, malonic acid, fumaric acid, maleic acid, malic acid, succinic acid, glutaric acid, adipic acid, phthalic acid, isophthalic acid, and terephthalic acid.

Examples of N-acylsarcosine include N-lauroylsarcosine, coconut oil fatty acid sarcosine, N-stearoylsarcosine, oleoylsarcosine, and palmitoylsarcosine.

Examples of the above acid salts and N-acylsarcosine salts include sodium salts, potassium salts, magnesium salts, calcium salts, and aluminum salts.

Most preferably as absorption enhancers, lactic acid, maleic acid, fumaric acid and N-lauroylsarcosine or their salts are used alone or in combination of two or more.

The absorption enhancer is preferably contained in the plaster layer at a concentration of 0.
It is contained in a proportion of 1 to 30% by weight, more preferably 1 to 15% by weight, most preferably 2 to 5% by weight. If the content of the above-mentioned absorption enhancer is too small, a sufficient transdermal absorption promoting effect of the drug cannot be obtained, and if it is too large, the compatibility between the absorption enhancer and the adhesive decreases, resulting in a decrease in adhesive properties.

e) The adhesion improving agent that is optionally used in the transdermal patch according to the present invention is a higher fatty acid ester obtained from a higher fatty acid having 10 to 18 carbon atoms and an alcohol having 1 to 20 carbon atoms. It is.

Examples of fatty acids having 10 to 18 carbon atoms include myristic acid, palmitic acid, lauric acid, stearic acid, palmitoleic acid, oleic acid, vaccenic acid, linoleic acid, and linolenic acid. Examples of the alcohol having 1 to 20 carbon atoms include methanol, ethanol, propanol, isopropanol, butanol, hexanol, pentanol, heptanol, octanol, decanol, and cetanol.

Isopropyl myristate and/or isopropyl palmitate are preferably used as the higher fatty acid ester.

[0033] These higher fatty acid esters have the effect of promoting the transdermal absorption promoting effect of the above-mentioned absorption enhancer and also improving the adhesiveness and applicability of the patch. These higher fatty acid esters are preferably contained in the plaster layer.
．． It is contained in a proportion of 1 to 30% by weight, more preferably 1 to 15% by weight, and most preferably 2 to 7% by weight. If the content of the higher fatty acid ester is too low, the intended effect of adding the higher fatty acid ester will not be sufficiently exhibited, and if the content is too high, the compatibility between the higher fatty acid ester and the adhesive will decrease and crystals will precipitate. Furthermore, it causes a decrease in adhesiveness and adhesion.

f) A transdermal patch usually has a release paper on its application surface to protect the surface of the plaster layer until use. As the release paper, a material obtained by siliconizing a polyethylene terephthalate film is often used, but the release paper is not limited to this. The thickness of the release paper is 100 μm or less, preferably 5 to 50 μm.

g) In the preparation of a transdermal patch,
A normal adhesive tape manufacturing method can be applied to form the plaster layer. A typical example thereof is a solvent coating method, and other methods such as a hot melt coating method and an electron beam curing emulsion coating method are also used. To form a plaster layer using a solvent coating method, for example, the drug, absorption enhancer, higher fatty acid ester, and other additives as required are dissolved or dispersed in a suitable solvent, and the resulting solution or dispersion is mixed. Apply directly to one side of the support and dry to form a plaster layer of the required thickness. Also,
This solution or dispersion may be applied onto a protective release paper, and after drying, the obtained plaster layer may be brought into close contact with the support. The thickness of the plaster layer varies depending on the purpose of use, but is usually 30 to 2
It is in the range of 00 μm. If the thickness is less than 30 μm, the required amount of drug cannot be contained and the adhesiveness is insufficient. If the thickness exceeds 200 μm, the drug contained in the plaster layer near the support will not be sufficiently diffused, resulting in a decrease in drug release properties.

[0036]

[Function] In the transdermal patch according to the present invention, an acrylic adhesive is used as an adhesive, which is made of a copolymer of 45 to 80 mol% of 2-ethylhexyl acrylate and 20 to 55 mol% of N-vinyl-2-pyrrolidone. Since noresterone and/or its ester is dissolved in the plaster layer at a high concentration, the release properties of these drugs are excellent, and a large effective dose can be obtained from a fixed area of application.

[0037] Furthermore, when the plaster layer contains an absorption enhancer and/or an adhesion improver, a marked improvement in drug transfer to the skin is observed. This is because carboxylic acids and/or their salts, N-acyl sarcosine and/or its salts, which are included as absorption enhancers, and higher fatty acid esters, which are included as patch improvers, form a structure in the plaster layer or skin. It may be based on bringing about a change or physical or chemical interaction. That is, the above substance changes the behavior of the drug in the plaster layer, which changes the distribution coefficient of the drug between the skin and the plaster layer,
Alternatively, it is considered that the skin migration and drug release properties of the drug are dramatically improved by changing the diffusion rate of the drug in the plaster layer.

[0038]

[Example] Next, in order to specifically explain the present invention,
Examples illustrating an example of the present invention and several comparative examples illustrating comparison therewith will be listed, and performance test results of each patch obtained will also be shown.

Example 1 65 mol% 2-ethylhexyl acrylate (302.
0 g), 35 mol% (98.0 g) of vinylpyrrolidone, and 0.02 wt% (40.0 mg) of hexamethylene glycol dimethacrylate were placed in a separable flask.
70.6 g of ethyl acetate was added so that the monomer concentration at the initial stage of polymerization was 85% by weight. This solution was heated to 60°C under nitrogen atmosphere, and 3.5g of lauroyl peroxide was added to 330°C.
A polymerization initiator solution prepared by dissolving 1 g of ethyl acetate was added little by little, and a polymerization reaction was carried out over 32 hours. After the polymerization reaction was completed, 340 g of ethyl acetate was added to obtain a 35% by weight solution of the polymer in ethyl acetate.

A tetrahydrofuran solution of norethisterone acetate as a drug was added to the obtained ethyl acetate solution of the polymer so that the solid content (sum of the weight of the polymer and drug) was 30% by weight. The solution was added so that the medium concentration was 8% by weight, and the solution was uniformly mixed using a dissolver.

The obtained coating solution was applied onto a release paper made of silicone-treated polyethylene terephthalate film so that the thickness of the plaster layer after drying was 60 μm, and the applied layer was placed in an oven at 60°C. Dry for 30 minutes. Thereafter, a support consisting of a polyethylene terephthalate-ethylene/vinyl acetate copolymer laminate film having a thickness of 50 μm was laminated on the obtained plaster layer.

[0042] A patch was thus prepared.

Example 2 In addition to norethisterone acetate, lactic acid was added as an absorption enhancer to an ethyl acetate solution of the acrylic polymer obtained in the same manner as in Example 1, so that the concentration in solid content was 3% by weight. Other operations were similar to those in Example 1 to produce a patch.

Example 3 2-ethylhexyl acrylate 50 mol% (249.
6g), vinylpyrrolidone 50mol% (150.4g)
and trimethylolpropane triacrylate 0.0
Norethisterone acetate was added to the acrylic polymer obtained in the same manner as in Example 1 using 1 wt % (40.0 mg), and lactic acid was further added to the solid content so that the solid content was 8 wt %. were added so that the amount was 3% by weight. Other operations were the same as in Example 1 to produce a patch.

Example 4 A patch was prepared in the same manner as in Example 2 except that lactic acid in Example 2 was replaced with 3% by weight of maleic acid.

Example 5 A patch was prepared in the same manner as in Example 2, except that lactic acid was replaced with 3% by weight of N-lauroylsarcosine.

Example 6 The same procedure as in Example 2 was carried out, except that lactic acid in Example 2 was replaced with 3% by weight of N-lauroylsarcosine, and isopropyl myristate was added so that the concentration in solid content was 5% by weight. A patch was made.

Comparative Example 1 Silascon 3, a silicone resin adhesive, was used as a paste.
55 (manufactured by Dow Corning) with a solid content equivalent of 90.
0 g, and 10.0 g of tetrahydrofuran and 8.0 g of norethisterone acetate were added thereto, and this liquid was mixed uniformly using a dissolver. Other operations were similar to those in Example 1 to produce a patch.

Comparative Example 2 In Comparative Example 1, the solid content of Silascon 355 was changed to 85
．． A patch was prepared in the same manner as in Comparative Example 1, except that the amount was changed to 0 g and 5.0 g of isopropyl myristate was added.

Comparative Example 3 In Comparative Example 2, the solid content of Silascon 355 was changed to 82
．． A patch was produced in the same manner as in Comparative Example 1, except that the amount of oleic acid was changed to 0g and 3.0g of oleic acid was added.

Comparative Example 4 The amount of 2-ethylhexyl acrylate was 30 mol% (1
29.2g), the amount of vinylpyrrolidone was added to 70 mol% (
181.6 g) and the amount of hexamethylene glycol dimethacrylate to 0.02% by weight (62.2 mg)
By the same operation as in Example 1, except for changing each to
A patch was made.

Comparative Example 5 The amount of 2-ethylhexyl acrylate was 90 mol% (1
93.7g), the amount of vinylpyrrolidone was added to 10 mol% (
A patch was prepared in the same manner as in Example 1, except that the amount of hexamethylene glycol dimethacrylate was changed to 13.0 g) and 0.02% by weight (41.3 mg).

i) Skin permeability test evaluation examples 1 to 6
and a test piece consisting of the adhesive patch obtained in Comparative Examples 1 to 5 (applied surface area: 10 cm2, plaster layer thickness: 60 μm,
Performance tests were conducted using the method described below.

First, a Franz type diffusion cell (1) shown in the attached FIG. 1 was prepared. The diffusion cell (1) consists of a lower cylindrical receptor tank (2) with a bottom and a bottomed cylindrical donor tank (3) placed above this. An opening (4) is provided in the center of the bottom wall of the donor tank (3), and an upper flange (5) and a lower flange (6) are provided at the lower end of the donor tank (3) and the upper end of the receptor tank (2), respectively. ) is provided. By stacking the upper flange (5) and the lower flange (6) facing each other, the donor tank (3) and receptor tank (2) are stacked airtightly and concentrically. A laterally protruding sampling port (7) is attached to the side of the receptor tank (2), and a magnetic stirrer (9) is placed inside the receptor tank (2).

[0055] After a hairless mouse (6 weeks old, male) was sacrificed by cervical dislocation, the back skin was immediately peeled off, the subcutaneous fat and muscle layer were removed, and a skin piece of about 4 cm x 4 cm was obtained. This piece of skin (8) is sandwiched between the upper flange (5) and the lower flange (6) of the diffusion cell (1), and the opening (4) of the donor tank (3) is connected to the piece of skin (8). I tried to close it completely.

A test piece was pressed onto the upper surface of the skin piece (8). The receptor tank (2) was filled with a receptor liquid having the composition shown in Table 1.

[0057]

[Table 1]

[0058] Next, the diffusion cell (1) was placed in a constant temperature bath maintained at a temperature of 37°C, and the receptor liquid was stirred using a magnetic stirring device. Over the course of 24 hours after the start of the test, 1 ml of the receptor fluid was collected from the sampling port (7) at the required time intervals, the receptor fluid was replenished immediately after that, and the amount of drug permeated into the collected receptor fluid was measured using high performance liquid chromatography. It was measured. The number of samples for each patch was three.

The amount of norethisterone acetate permeated over time in each test piece is shown in the graphs of FIGS. 2 and 3.

As is clear from these graphs, the test pieces of each Example, especially those of Examples 2 and 4 to 6, exhibit superior permeability compared to the test pieces of Comparative Examples. This indicates that the patch of Example shows the same permeability as the patch of Comparative Example even if the area is considerably smaller.

ii) Adhesion test The adhesion test was conducted using the same test piece as used in the skin permeability test using the method described below.

That is, test strips were pasted on the upper arms of 10 test subjects (healthy, male), and after 72 hours, the degree of adhesion of the test strips was judged on a four-point scale as shown in Table 2. Table 3 shows the number of people applicable to each level of adhesion.

[0063]

[Table 2]

[0064]

[Table 3]

As is clear from Table 3, the adhesion properties of the patches of Examples (particularly Example 6) are superior to those of Comparative Examples. This is due to the effect of isopropyl myristate added as an adhesion improving agent. On the other hand, the patch of Comparative Example 4 had poor adhesion properties, and was almost peeled off or peeled off to the point of being peeled off during the test period.

iii) Drug migration test After the above-mentioned adhesion test, the remaining drugs in each test piece removed from the skin were extracted with methanol, and the remaining amount of each drug was determined by high performance liquid chromatography. It was measured. Among these, the difference between the initial content and the measured content for those with an adhesion degree of 3 or higher was defined as the daily skin transfer amount of the drug. The results are shown in Table 4.

[0067]

[Table 4]

As is clear from Table 4, although the test piece of the example and the test piece of the comparative example have the same area and the same dosage, the former is superior to the latter in terms of drug transferability. shows.

[0069]

[Effects of the Invention] Since the transdermal absorption patch according to the present invention is constructed as described above, it can exhibit the following effects.

(1) It is possible to provide a transdermal patch that dissolves noresterone and/or its ester at a high concentration and has excellent release properties for these drugs. A transdermal patch that can be administered at an effective dose can be provided.

(2) By reducing the application area, it is possible to provide a transdermal patch with low skin irritation.

(3) When an absorption enhancer is blended into the base, drug transfer to the skin is dramatically improved. Therefore, the drug blood concentration per fixed area of application can be maintained at a higher level compared to conventional products. In this way, by incorporating an absorption enhancer, excellent medicinal efficacy can be expressed with a smaller application area, and as a result, erythema that can occur in people who are sensitive to the skin irritation of the plaster layer can be reduced as much as possible.

(4) Because the desired medicinal effect can be expressed even with a small application area, and because the plaster layer also serves as a drug-containing layer, it is possible to provide a thin tape-shaped pharmaceutical product, and therefore , it is possible to reduce the discomfort of wearing it on the skin.

(5) Since the pasting area is small, the pasting operation can be simplified.

(6) Even if the plaster layer also serves as a drug-containing layer, the desired medicinal effect can be expressed, so the structure can be simplified, and therefore manufacturing management, storage and storage of the patch can be simplified. Management can be simplified.

(7) Since volatile components are not contained in the plaster layer, storage and management of the patch is easy.

(8) Furthermore, when an adhesion improving agent is blended, the degree of adhesion can be greatly improved and the drug transfer to the skin can be improved. Therefore, the above-mentioned (1) to (
7) The effect of 7) can be further enhanced.

[Brief explanation of drawings]

FIG. 1 is a perspective view of a Franz type diffusion cell.

FIG. 2 is a graph showing the amount of norethisterone acetate permeated over time.

FIG. 3 is a graph showing the amount of norethisterone acetate permeated over time.

Claims (3)

[Claims] Claim 1: A patch comprising a support and a plaster layer containing a drug and an adhesive on one side, wherein the adhesive is 2-
It is an acrylic adhesive consisting of a copolymer of 45 to 80 mol% of ethylhexyl acrylate and 20 to 55 mol% of N-vinyl-2-pyrrolidone, and contains 1 to 20% by weight of norethisterone and/or its ester as a drug. Skin-absorbable patch. [Claim 2] The plaster layer contains 2 carbon atoms as an absorption enhancer.
~10 oxycarboxylic acids and their salts, carbon number 2
~10 dicarboxylic acids and their salts, and N-
The patch according to claim 1, comprising a compound selected from the group consisting of acylsarcosine and salts thereof. 3. The patch according to claim 1, wherein the plaster layer contains a higher fatty acid ester of a higher fatty acid having 10 to 18 carbon atoms and an alcohol having 1 to 20 carbon atoms as an adhesive improving agent.