JP2971224B2 - Estradiol transdermal patch - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an estradiol transdermal patch suitable for sustained release of estradiol.

[0002]

2. Description of the Related Art Estradiol is an estrogen (estrogens) secreted from the ovaries when a woman can reproduce. Thus, pre- and postmenopausal women mainly develop estradiol deficiency and develop symptoms such as menopause and menstrual abnormalities. At present, treatment with oral preparations is used to improve these symptoms, but it is rapidly metabolized and inactivated by the gastrointestinal tract such as the gastrointestinal tract and the liver. Must take high doses of estradiol. In addition, the expression of side effects may be increased due to the high dose.

[0003] Therefore, an administration method for transdermal administration that does not pass through the digestive tract, liver, or the like has been studied. For example, JP-A-57-154122 discloses a method of controlling the release of estradiol dissolved in a gel of hydroxypropylcellulose-ethanol by using an ethylene-vinyl acetate membrane, and JP-A-60-152413 discloses a method of controlling the release. Only a transdermal absorption preparation containing menthol as a skin absorption enhancer is disclosed, but nothing is described about patches.

JP-A-61-17513 describes a pharmaceutical composition using a drug permeation enhancer obtained by mixing propylene glycol and glycerin in a specific ratio. JP-A-61-155321 discloses an adhesive base material comprising an adhesive resin material (polyterpene resin, hydrocarbon resin, etc.), natural rubber or synthetic rubber (polyisobutylene, styrene-butylene polymer, styrene-isoprene polymer, Styrene-ethylene-butylene polymer, 1,4
-Patches based on water-swellable polymers such as polyisoprene) and galactomannan are disclosed. JP-A-63-233916 discloses a patch for a device comprising a seven-layer laminate.

[0005]

The estradiol transdermal patches which have been studied variously as described above are:
In the end, due to the complicated structure, a special process is required for its production, and the production equipment is expensive. On the other hand, the active substances contained are only utilized in a limited proportion and have low bioavailability. Furthermore, the addition of an absorption enhancer such as ethanol has a problem in terms of skin irritation in terms of transdermal administration. In view of the above problems, the inventors of the present invention have eagerly studied to provide 1) a simple structure, 2) an improvement in bioavailability, and 3) an estradiol transdermal patch with reduced skin irritation. As a result, the present invention has been completed.

[0006]

The estradiol transdermal patch of the present invention comprises: 1) an (AB) nA type elastic polymer (where A is substantially monovinyl substituted) Aromatic compound polymer block, B is substantially a conjugated diolefin copolymer block, n represents an integer of 3 to 7] 2) polyethylene glycol 3) fatty acid ester 4) water-absorbing polymer, as essential components Is what you do. Estradiol used in the present invention has a general name of estra-1.3.
5 (10) triene-3.17β-diol, which is represented by the following structural formula.

[0007]

Embedded image The content of this estradiol in the estradiol transdermal patch is 0.01 to 10% by weight, preferably 0.05 to 5% by weight, and more preferably 0.1 to 1% by weight.

In the present invention, the (AB) nA type elastic polymer used as a preparation base is specifically a styrene-butadiene-styrene block copolymer manufactured by Shell Chemical Co., which is easily available as a commercial product. Styrene-isoprene-styrene block copolymer (JS) manufactured by Nippon Synthetic Rubber Co., Ltd. such as (Califlex TR-1101), styrene-isoprene-styrene block copolymer (Cariflex TR-1107, Califflex TR-1111).
R5000), Quintac 3421 manufactured by Zeon Corporation
And the like. In particular, a styrene-isoprene-styrene block copolymer is preferably used. By using such an (AB) nA type elastic polymer as a preparation base, the release of estradiol and a significant improvement in bioavailability can be achieved.

The polyethylene glycol used in the present invention is specifically polyethylene glycol 200,
Polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 150
0, polyethylene glycol 1540 and polyethylene glycol 4000 are preferably used.

The fatty acid ester used in the present invention is preferably ethyl oleate, isopropyl myristate, isopropyl palmitate, butyl stearate, myristyl myristate, octyldodecyl myristate, cholesteryl stearate, or diisopropyl adipate. Used.

The combination of polyethylene glycol and fatty acid ester used in the present invention greatly improves the solubility of estradiol, release from the preparation, transdermal absorption, and the like. In addition, there is no example in which polyethylene glycol and a fatty acid ester are blended in an (AB) nA type elastic polymer base preparation as a solubilizer and an absorption enhancer for estradiol, and there is no known literature suggesting this.

Absorbent polymer used in the [0012] present invention is intended to absorb and gel swell more than 10 times its weight in water, preferably those of the fine powder, such as polyacrylic acid and metal salts thereof, For example, sodium salts, carboxymethylated polyvinyl alcohol, carboxymethylcellulose and metal salts thereof, those obtained by introducing a lightly cross-linked bond into a carboxymethyl polymer or the like, or starch acrylonitrile graft saponified metal salts are used. Fine powder is used.

More specifically, a sun wet [IM-300, IM-1000, IM-1000MP, manufactured by Sanyo Chemical Co., Ltd.]
S, etc.), Aqua keep [4S, 10S , manufactured by Tekko Chemical Co., Ltd.]
H, etc.], Sumika Gel [SP-520, manufactured by Sumitomo Chemical Co., Ltd.]
SP-540, N-100, NP-1020, NP-1
040 etc.], Arakawa Chemical Co., Ltd. Arasorp [800, 8
00F etc.] are used.

[0014] By using these base materials containing an elastic body, polyethylene glycol, a fatty acid ester, and a water-absorbing polymer as essential components, the utilization rate can be improved, and stuffiness due to sweating at the time of application and irritation of drugs can be caused. Significant reduction in redness and touch can be achieved.

The preferred contents of the (AB) nA type elastic polymer, polyethylene glycol, fatty acid ester, and water-absorbing polymer in the estradiol transdermal patch of the present invention are as follows.

That is, the total content of the essential components consisting of (AB) nA type elastic polymer, polyethylene glycol, fatty acid ester and water-absorbing polymer is 2% in the preparation.
The content is 0 to 99% by weight, more preferably 30 to 60% by weight. Further, the content of each component is determined in the preparation (AB).
5 to 50% by weight, more preferably 10 to 20% by weight, polyethylene glycol 1 to 15% by weight, more preferably 3 to 10% by weight, fatty acid ester 1 to 15% by weight, more preferably 3 to 5% by weight of the nA type elastic polymer 10 wt%, water-absorbing polymer 20% by weight, more preferably 2 to 10
%, And the combination in this range exhibits the effect of the present invention most.

The percutaneously absorbable estradiol preparation of the present invention contains, in addition to the above essential components, conventionally known softeners such as liquid paraffin, tackifiers, and inorganic fillers in appropriate amounts. Further, as the support of the preparation of the present invention, those having excellent flexibility without affecting the release of the drug are desirable, and are selected from films or woven fabrics of polyester, polypropylene, polyethylene, or the like, or are laminated with these. Composite materials such as flexible plastic films or woven fabrics are desirable.

Next, a method for producing the estradiol transdermal preparation of the present invention will be described. First, after heating and dissolving the base component, a drug, polyethylene glycol, and a fatty acid ester are added, plastered on the above support, covered with a liner, and cut into a desired shape into a cut product, or once subjected to a release treatment. After plastering on the applied film, it can be formed into a transfer-compression-bonded product on a suitable support. The thus obtained estradiol transdermal patch of the present invention enhances the release of the contained drug estradiol, improves the bioavailability, and significantly reduces skin irritation during continuous administration and long-term administration. It has the effect of reducing it.

[0019]

The present invention will be described below in more detail with reference to examples and test examples. In Examples, Comparative Examples and Reference Examples,
All parts are parts by weight.

Example 1 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 57.99 parts Polyethylene glycol 200 1.00 parts Ethyl oleate 1.00 parts Water absorption Polymer (Sumikagel SP-520) 5.00 parts Estradiol 0.01 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to give an estradiol transdermal absorption patch.

Example 2 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 51.50 parts Polyethylene glycol 300 5.00 parts Ethyl oleate 3.00 parts Water absorption Polymer (Sumikagel SP-520) 5.00 parts Estradiol 0.50 part Estradiol was prepared according to the above-mentioned method in accordance with the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal absorption patch.

Example 3 Styrene-isoprene-styrene block copolymer 30.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 35.00 parts Polyethylene glycol 400 10.00 parts Isopropyl myristate 10.00 parts Water absorption Polymer (Sumikagel SP-520) 5.00 parts Estradiol 10.00 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal absorption patch.

Example 4 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 53.50 parts Polyethylene glycol 600 6.00 parts Isopropyl palmitate 4.00 parts Water absorption Polymer (trade name: Aquakeep 4SH) 1.00 part Estradiol 0.50 part Estradiol was prepared according to the above-mentioned method according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal absorption patch.

Example 5 Styrene-isoprene-styrene block copolymer 20.00 parts (trade name: Califrex TR-1107) Liquid paraffin 47.50 parts Polyethylene glycol 1000 5.00 parts Butyl stearate 7.00 parts Water absorption high Molecule (trade name: Aquakeep 10SH ) 20.00 parts Estradiol 0.50 part Estradiol was prepared in accordance with the above-mentioned method and cut into a desired size to obtain an estradiol transdermal patch.

Example 6 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 45.50 parts Polyethylene glycol 1500 7.00 parts Myristyl myristate 7.00 parts Water absorption Polymer (trade name: Arasorb 800F) 5.00 parts Estradiol 0.50 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal patch.

Example 7 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 49.50 parts Polyethylene glycol 200 4.00 parts Octyldodecyl myristate 6.00 parts Water absorption Water-soluble polymer (trade name: Arasorb S-100F) 5.00 parts Estradiol 0.50 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal patch.

Example 8 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 51.50 parts Polyethylene glycol 300 5.00 parts Cholesteryl stearate 3.00 parts Water absorption Polymer (trade name: Sunwet IM-300MPS) 5.00 parts Estradiol 0.50 part Estradiol was prepared according to the above-mentioned method according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal absorption patch.

Example 9 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 45.50 parts Polyethylene glycol 400 7.00 parts Diisopropyl adipate 7.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Estradiol 0.50 part Estradiol was prepared according to the above-mentioned method and cut into a desired size to obtain an estradiol transdermal patch.

Example 10 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 34.50 parts Polyethylene glycol 600 5.00 parts Ethyl oleate 5.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts The above-mentioned production using this formulation It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 11 Styrene-isoprene-styrene block copolymer 5.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 42.50 parts Polyethylene glycol 1000 4.00 parts Isopropyl myristate 8.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 35.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts The above-mentioned production using this formulation It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 12 Styrene-isoprene-styrene block copolymer 50.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 22.00 parts Polyethylene glycol 1500 7.00 parts Isopropyl palmitate 3.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 12.50 parts (trade name: Alcon P-100) Estradiol 0.50 part The above-described production using this formulation It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 13 Styrene-isoprene-styrene block copolymer 27.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 38.50 parts Polyethylene glycol 300 2.00 parts Butyl stearate 2.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name: KE-311) Estradiol 0.50 parts It was cut into a size to give an estradiol transdermal patch.

Example 14 Styrene-isoprene-styrene block copolymer 26.50 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 36.00 parts Polyethylene glycol 300 5.00 parts Myristyl myristate 5.00 parts Water absorbency Polymer (Sunwet IM-1000MPS) 2.00 parts Tackifier (rosin ester) 25.00 parts (KE-311) Estradiol 0.50 part It was cut into a size to give an estradiol transdermal patch.

Example 15 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 32.50 parts Polyethylene glycol 400 5.00 parts Octyldodecyl myristate 7.00 parts Water absorption Functional polymer (trade name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name KE-311) Estradiol 0.50 part And cut into estradiol transdermal patches.

Example 16 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: Califrex TR-1107 Liquid paraffin 30.00 parts Polyethylene glycol 400 7.00 parts Cholesteryl stearate 5.00 parts Water absorption high Molecule (trade name: Sunwet IM-1000MPS) 10.00 parts Tackifier (rosin ester) 25.00 parts (trade name: KE-311) Estradiol 0.50 parts Then, it was cut into an estradiol transdermal patch.

Example 17 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 27.00 parts Polyethylene glycol 600 10.00 parts Diisopropyl adipate 10.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name: KE-311) Estradiol 0.50 parts It was cut into a size to give an estradiol transdermal patch.

Example 18 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1107) Liquid paraffin 33.50 parts Polyethylene glycol 600 8.00 parts Ethyl oleate 3.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts The above-mentioned production using this formulation It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 19 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1111) Liquid paraffin 34.50 parts Polyethylene glycol 1000 2.00 parts Isopropyl myristate 8.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts The above-mentioned production using this formulation It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 20 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: CARIFLEX TR-1107) polyisobutylene 5.00 parts liquid paraffin 29.00 parts polyethylene glycol 1000 10.00 parts isopropyl palmitate 3.00 parts Water-absorbing polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal patch.

Example 21 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: CARIFLEX TR-1111) Polyisobutylene 5.00 parts Liquid paraffin 32.00 parts Polyethylene glycol 1500 6.00 parts Butyl stearate 4.00 parts Water-absorbing polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (trade name: Alcon P-100) Estradiol 0.50 parts This formulation was prepared according to the above-mentioned production method and cut into a desired size to obtain an estradiol transdermal patch.

Example 22 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1111) Liquid paraffin 29.50 parts Polyethylene glycol 1500 7.00 parts Myristyl myristate 8.00 parts Water absorption Polymer (trade name: Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name: KE-311) Estradiol 0.50 parts It was cut into a size to give an estradiol transdermal patch.

Example 23 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: CARIFLEX TR-1107) Polyisobutylene 5.00 parts Liquid paraffin 32.00 parts Polyethylene glycol 300 3.00 parts Ethyl oleate 7.00 parts Water-absorbing polymer (trade name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (brand name KE-311) Estradiol 0.50 part It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Example 24 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name: CARIFLEX TR-1111) Polyisobutylene 5.00 parts Liquid paraffin 32.00 parts Polyethylene glycol 400 5.00 parts Isopropyl myristate 5.00 parts Water-absorbing polymer (trade name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name KE-311) Estradiol 0.50 parts It was prepared according to the method and cut into a desired size to obtain an estradiol transdermal patch.

Comparative Example 1 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1107) polyisobutylene 5.00 parts liquid paraffin 32.50 parts polyethylene glycol 300 5.00 parts myristyl myristate 7.00 parts Tackifier (rosin ester) 25.00 parts (trade name KE-311) Estradiol 0.50 part Estradiol transdermal patch prepared with this formulation according to the above-mentioned production method, cut into a desired size, and cut to a desired size. And

Comparative Example 2 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name: CARIFLEX TR-1107) polyisobutylene 5.00 parts liquid paraffin 39.50 parts water-absorbent polymer (trade name Sunwet IM) 5.00 parts Tackifier (rosin ester) 25.00 parts (trade name: KE-311) Estradiol 0.50 part Estradiol percutaneous cut according to the above-mentioned manufacturing method, cut into a desired size, and cut to a desired size. It was an absorption patch.

Reference Example 1 93.16 parts of an acrylic resin-based solvent-type pressure-sensitive adhesive (trade name: NISSETSU PE-300, solid content: 40%) (84.47 parts after drying) 2.21 parts of polyethylene glycol 300 (5 after drying) .01 parts) Ethyl oleate 2.21 parts (5.01 parts after drying) Water absorbent polymer (trade name: Sumikagel SP-520) 2.21 parts (5.01 parts after drying) Estradiol 0.22 parts (dry) After mixing with this formulation, the mixture was spread on the above-mentioned support or liner so that the paste thickness after evaporation of the solvent would be the same as in the example, and thereafter, it was prepared according to the above-mentioned production method, and was then prepared. And cut into estradiol transdermal patches.

Reference Example 2 80.50 parts of silicone pressure-sensitive adhesive (trade name: Silascon 355 Medical Adhesive) polyethylene glycol 300 5.00 parts ethyl oleate 7.00 parts water-absorbing polymer (trade name: Sumikagel SP-520) 7.00 parts Estradiol 0.50 parts After mixing with this formulation, plaster on the above-mentioned support or liner so that the plaster thickness becomes the same as in the example, then prepare according to the above-mentioned production method and cut to desired size Estradiol was used as a transdermal patch.

Test Example 1 (Hairless Mouse Skin Permeation Test 1) A hairless mouse skin permeation test was performed using Example 2, Reference Examples 1 and 2, and the test results are shown in FIG. As shown in the test results, Example 2 clearly shows higher estradiol release than Reference Examples 1 and 2. This is because the preparation of the present invention can be used as a base component or (AB) n-
This is due to the use of the A-type elastic polymer, polyethylene glycol and fatty acid ester. That is, it supports the usefulness of the present invention.

Test Example 2 (Hairless Mouse Skin Permeation Test 2) Using Examples 15, 17, 23 and Comparative Example 2, a hairless mouse skin permeation test was carried out, and the results are shown in FIG. As shown in the test results, Examples 15, 17, and 23 were Comparative Examples 2
Shows that the release of estradiol is clearly higher than that of This is due to the fact that the preparation of the present invention uses polyethylene glycol and a fatty acid ester. That is, it supports the usefulness of the present invention.

Test Example 3 (Skin irritation test) Using Examples 14 to 16, 23 and Comparative Example 1, the skin was adhered to the chest of 15 healthy adult males for 3.5 days, and the condition of the skin was observed. As shown in Table 1, Examples 14 to 16, 23
Compared with Comparative Example 1, the skin irritation is clearly less and the effect of blending the water-absorbing polymer appears. That is, it supports the usefulness of the present invention.

[0051]

[Table 1] The criteria for determining skin irritation are as follows. No change;-slight redness; ± distinct redness; + severe rash; ++

Test Example 4 (Rabbit blood concentration measurement test) Using Examples 15, 17, 23 and Comparative Example 2, rabbit blood concentration measurement was performed. The hair on the back of a Japanese white rabbit was removed, and the estradiol concentration in the blood was measured over time.
The test results are shown in FIG. As shown in the test results, Examples 15, 17, and 23 are higher than those in Comparative Example 2 in all of the rise in the blood concentration, the release amount, and the sustainability. That is, it supports the usefulness of the present invention.

[0053]

As described above, (AB) n-A
The estradiol transdermal patch of the present invention containing a type elastic polymer, polyethylene glycol, a fatty acid ester, and a water-absorbing polymer as essential components is a formulation most suitable for releasing estradiol, exhibits a sufficient medicinal effect, and exhibits redness, It is very useful industrially as an ideal estradiol transdermal patch with no rash.

[Brief description of the drawings]

FIG. 1 is a skinless mouse skin permeation test 1.

FIG. 2 shows Hairless Mouse Skin Permeation Test 2.

FIG. 3 is a rabbit blood concentration measurement test.

[Explanation of symbols]

 In FIG. 1, ○: Estradiol transdermal absorption patch of Example 2 □: Estradiol transdermal absorption patch of Reference Example 1 Δ: Estradiol transdermal absorption patch of Reference Example 2 In FIGS. Estradiol transdermal absorption patch of Example 23 □: Estradiol transdermal absorption patch of Example 17 Δ: Estradiol transdermal absorption patch of Example 15 ●: Estradiol transdermal absorption patch of Comparative Example 2

──────────────────────────────────────────────────の Continuation of the front page (56) References JP-A-63-255217 (JP, A) JP-A-3-502700 (JP, A) JP-A-2-500740 (JP, A) JP-T-3- 502925 (JP, A) Special Table 57-500980 (JP, A) International Publication No. 91/17752 (WO, A1) (58) Fields investigated (Int. Cl. ⁶ , DB name) A61K 31/565 A61K 9 / 70 A61K 47/10 A61K 47/14 A61K 47/32

Claims (2)

(57) [Claims] 1. The estradiol percutaneous absorption preparation, wherein the base component is (AB) nA type elastic polymer [wherein,
A is a substantially monovinyl-substituted aromatic compound polymer block, B is a substantially conjugated diolefin copolymer block,
n represents an integer of 3 to 7] and polyethylene glycol;
Fatty acid esters and the water-absorbing polymer as essential components, estradiol transdermal patches agent comprising estradiol as the medicinal ingredient. 2. As a base component, 5 to 50% by weight of (AB) nA type elastic polymer and polyethylene glycol 1 to 1
0 wt%, a fatty acid ester from 1 to 10 wt%, water-absorbing polymer 20% by weight and estradiol percutaneous absorption according to claim 1, characterized in that it contains estradiol 0.01 to 10 wt% is medicinal ingredient Patch.