JPH05148145A - Plaster for percutaneously absorbing estradiol - Google Patents

Abstract

PURPOSE:To provide a plaster percutaneously absorbing estradiol continuously releasing the estradiol and not causing flares, rashes, etc., by adding the estradiol as an active ingredient to a base agent component containing an elastic polymer. CONSTITUTION:The objective plaster contains an (A-B)n-A type elastic polymer (A is monovinyl-substituted aromatic compound polymer block; B is conjugated diolefin copolymer block; (n) is 3-7), polyethylene glycol, a fatty acid ester and a water-absorbing polymer as essential components, and also estradiol as an active ingredient. The plaster contains preferably 5-50wt.% of the elastic polymer (e.g. styrene-isoprene-styrene block copolymer), 1-10wt.% of the polyethylene glycol (e.g. polyethylene glycol 200), 1-10wt.% of the fatty acid ester (e.g. ethyl oleate), 1-20wt.% of the water-absorbing polymer (e.g. traded name: Sumikagel SP-520) and 0.01-10wt.% of the estradiol.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a transdermal estradiol patch suitable for sustained release of estradiol.

[0002]

2. Description of the Related Art Estradiol is an estrogen secreted by the ovaries during a female reproductive period. Therefore, pre- and post-menopausal women are mainly deficient in estradiol, and symptoms such as menopause and abnormal menstruation occur. Currently, treatments such as oral agents are being carried out for the purpose of improving these symptoms, but since they are rapidly metabolized and inactivated by the gastrointestinal and other gastrointestinal tracts and the liver, etc. Must take high doses of estradiol. Further, since the dose is high, side effects may be more likely to occur.

Therefore, an administration method for transdermal administration that does not pass through the digestive tract, liver, etc. has been studied. For example, JP-A-57-154122 discloses a method for controlling the release of estradiol dissolved in a gel of hydroxypropylcellulose-ethanol with an ethylene-vinyl acetate film, and JP-A-60-152413 discloses a method. Only a percutaneous absorption preparation containing menthol as a skin absorption enhancer is disclosed, and no mention is made of a patch.

JP-A-61-17513 describes a pharmaceutical composition using a drug permeation enhancer obtained by mixing propylene glycol and glycerin in a specific ratio. In JP-A-61-155321, an adhesive resin material (polyterpene resin, hydrocarbon resin, etc.), natural rubber or synthetic rubber (polyisobutylene, styrene-butylene polymer, styrene-isoprene polymer) is used as an adhesive base. Styrene-ethylene-butylene polymer, 1,4
-Polyisoprene, etc.) and galactomannan-based patches based on polymers capable of swelling in water are disclosed. Japanese Unexamined Patent Publication No. 63-233916 discloses a patch for a device consisting of a 7-layer laminate.

[0005]

The estradiol percutaneous absorption patch which has been variously studied as described above is
First of all, because of its complicated structure, it requires a special process to manufacture it, and the manufacturing equipment becomes expensive. On the other hand, the active substance contained is utilized only in a limited proportion and the bioavailability is low. Furthermore, the addition of absorption enhancers such as ethanol is problematic in terms of skin irritation from the viewpoint of transdermal administration. In view of the above problems, the present inventors 1) have a simple structure 2) improve the bioavailability 3) have diligently studied for the purpose of providing an estradiol transdermal patch with reduced skin irritation As a result of continuing the above, the present invention has been completed.

[0006]

Means for Solving the Problems That is, the estradiol percutaneous absorption patch of the present invention comprises: (1) a (A-B) n-A type elastic polymer as a base of the preparation [wherein A is substantially monovinyl-substituted]; Aromatic compound polymer block, B is a substantially conjugated diolefin copolymer block, n represents an integer of 3 to 7] 2) Polyethylene glycol 3) Fatty acid ester 4) Water-absorbing polymer, as an essential component To do. The estradiol used in the present invention has a general name of estra-1.3.
5 (10) triene-3.17β-diol, represented by the structural formula:

[0007]

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

The (A-B) n-A type elastic polymer used as a formulation base in the present invention is specifically a styrene-butadiene-styrene block copolymer manufactured by Shell Chemical Co., Ltd. which is easily available as a commercial product. (Califlex TR-1101), styrene-isoprene-styrene block copolymers (Califlex TR-1107, Califlex TR-1111), styrene-isoprene-styrene block copolymer (JS) manufactured by Japan Synthetic Rubber Co., Ltd.
R5000), Quintac 3421 manufactured by Zeon Corporation
Etc., but a styrene-isoprene-styrene block copolymer is particularly preferably used. By using such an (AB) n-A type elastic polymer as a formulation base, the release of estradiol and the bioavailability can be significantly improved.

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, diisopropyl adipate. Used.

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

The water-absorbing polymer used in the present invention absorbs 10 times or more of its own weight of water and gels and swells,
It is preferably a fine powder, for example, polyacrylic acid and a metal salt thereof, for example, a sodium salt, carboxymethylated polyvinyl alcohol, carboxymethyl cellulose and a metal salt thereof, or a carboxymethyl polymer into which a slight cross-linking bond is introduced, or Starch acrylonitrile graft saponified metal salt or the like is used, and fine powders thereof are preferably used.

Specifically, Sanyo Kasei Co., Ltd. sun wet [IM-300, IM-1000, IM-1000MP
S, etc.], Aqua Keep [4S, 4SH]
Etc.], Sumika Gel Co., Ltd. [SP-520, S
P-540, N-100, NP-1020, NP-10
40 etc.], Arasorb made by Arakawa Chemical Co., Ltd. [800, 80
0F, etc.] is used.

By using these base materials containing the elastic body, polyethylene glycol, fatty acid ester, and water-absorbing polymer as essential components, the utilization rate is improved and the redness caused by stuffiness caused by perspiration during sticking, irritation of drugs, etc. , The feeling can be greatly reduced.

The preferred contents of the (AB) nA type elastic polymer, polyethylene glycol, fatty acid ester and water-absorbing polymer in the estradiol transdermal absorption 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 formulation.
It is 0 to 99% by weight, more preferably 30 to 60% by weight. In addition, the content of each component in the formulation (AB)
nA type elastic polymer 5 to 50% by weight, more preferably 10 to 20% by weight, polyethylene glycol 1 to 15% by weight, further preferably 3 to 10% by weight, fatty acid ester 1 to 15% by weight, further preferably 3 The content is 10 to 10% by weight, the water-absorbing polymer is 1 to 20% by weight, and more preferably 2 to 10% by weight, and the combination in this range exhibits the effect of the present invention most.

The estradiol percutaneous absorption preparation of the present invention contains, in addition to the above-mentioned essential components, a conventionally known compounding amount of a softening agent such as liquid paraffin, a tackifier, and an inorganic filler. Further, as the support of the preparation of the present invention, it is desirable that it has excellent flexibility without affecting the release of the drug, and it is selected from a film or woven fabric such as polyester, polypropylene and polyethylene, or an aluminum foil, or these are laminated. Composite materials such as flexible plastic films or woven fabrics are desirable.

Next, a method for producing the transdermal preparation of estradiol of the present invention will be described. First, the base component is heated and dissolved, and then the drug, polyethylene glycol, and fatty acid ester are added, spread on the above support, covered with a liner, and cut into a desired shape to give a cut product. After the plaster is applied to the applied film, it can be used as a transfer pressure-bonded product on an appropriate support. The estradiol percutaneous absorption patch of the present invention thus obtained enhances the release of the contained drug estradiol, improves the bioavailability, and significantly reduces skin irritation in continuous administration and long-term administration. It has the effect of reducing heat.

[0019]

EXAMPLES The present invention will be described in more detail with reference to examples and test examples. In the examples, comparative examples and reference examples,
All references to "parts" refer to parts by weight.

Example 1 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 part This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

Example 2 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 parts This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

Example 3 Styrene-isoprene-styrene block copolymer 30.00 parts (trade name Califlex 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 production method and cut into a desired size to give an estradiol transdermal patch.

Example 4 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

Example 5 Styrene-isoprene-styrene block copolymer 20.00 parts (trade name Califlex TR-1107) Liquid paraffin 47.50 parts Polyethylene glycol 1000 5.00 parts Butyl stearate 7.00 parts Water absorption Polymer (trade name: AQUAKEEP 4SH) 20.00 parts Estradiol 0.50 part This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

Example 6 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 part This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

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

Example 8 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

Example 9 Styrene-isoprene-styrene block copolymer 35.00 parts (trade name Califlex 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 This formulation was prepared according to the above production method and cut into a desired size to give an estradiol transdermal patch.

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

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

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

Example 13 Styrene-isoprene-styrene block copolymer 27.00 parts (Califlex TR-1107, trade name) Liquid paraffin 38.50 parts Polyethylene glycol 300 2.00 parts Butyl stearate 2.00 parts Water absorption Polymer (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Produced with this formulation according to the above manufacturing method and desired. It was cut into a size to give a transdermal patch for estradiol.

Example 14 Styrene-isoprene-styrene block copolymer 26.50 parts (trade name Califlex TR-1107) Liquid paraffin 36.00 parts Polyethylene glycol 300 5.00 parts Myristyl myristate 5.00 parts Water absorbency Polymer (Brand name Sunwet IM-1000MPS) 2.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Made according to the above manufacturing method with this formulation, and desired It was cut into a size to give a transdermal patch for estradiol.

Example 15 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name Califlex TR-1107) Liquid paraffin 32.50 parts Polyethylene glycol 400 5.00 parts Octyldodecyl myristate 7.00 parts Water absorption Polymer (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Made with this formulation according to the above manufacturing method, desired It was cut into the size of 1 to prepare an estradiol transdermal patch.

Example 16 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name Califlex TR-1107 liquid paraffin 30.00 parts Polyethylene glycol 400 7.00 parts Cholesteryl stearate 5.00 parts High water absorbency Molecules (trade name Sunwet IM-1000MPS) 10.00 parts Tackifier (rosin ester) 25.00 parts (trade name KE-311) Estradiol 0.50 parts Produced with this formulation according to the above production method to obtain a desired size. It was cut into pieces to give a transdermal patch of estradiol.

Example 17 Styrene-isoprene-styrene block copolymer 22.50 parts (Califlex TR-1107, trade name) Liquid paraffin 27.00 parts Polyethylene glycol 600 10.00 parts Diisopropyl adipate 10.00 parts Water absorption Polymer (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Produced with this formulation according to the above manufacturing method and desired. It was cut into a size to give a transdermal patch for estradiol.

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

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

Example 20 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name Califlex 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 (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (Brand name Alcon P-100) Estradiol 0.50 parts This formulation was prepared according to the above production method and cut into a desired size to give an estradiol percutaneous absorption patch.

Example 21 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name Califlex TR-1111) polyisobutylene 5.00 parts liquid paraffin 32.00 parts polyethylene glycol 1500 6.00 parts butyl stearate 4.00 parts Water-absorbent polymer (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (alicyclic saturated hydrocarbon resin) 25.00 parts (Brand name Alcon P-100) Estradiol 0.50 parts This formulation was prepared according to the above production method and cut into a desired size to give an estradiol percutaneous absorption patch.

Example 22 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name Califlex TR-1111) Liquid paraffin 29.50 parts Polyethylene glycol 1500 7.00 parts Myristyl myristate 8.00 parts Water absorption Polymer (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Produced with this formulation according to the above manufacturing method and desired. It was cut into a size to give a transdermal patch for estradiol.

Example 23 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name Califlex 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 (Brand name Sunwet IM-1000MPS) 5.00 parts Tackifier (rosin ester) 25.00 parts (Brand name KE-311) Estradiol 0.50 parts Production as described above with this formulation It was prepared according to the method and cut into a desired size to give an estradiol transdermal patch.

Example 24 Styrene-isoprene-styrene block copolymer 22.50 parts (trade name Califlex 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 The above-mentioned production with this formulation. It was prepared according to the method and cut into a desired size to give an estradiol transdermal patch.

Comparative Example 1 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name Califlex 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 parts Estradiol percutaneous absorption patch prepared according to the above production method with this formulation and cut into desired size And

Comparative Example 2 Styrene-isoprene-styrene block copolymer 25.00 parts (trade name Califlex TR-1107) Polyisobutylene 5.00 parts Liquid paraffin 39.50 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 Estradiol transdermally produced by this formulation according to the above production method and cut into a desired size. It was used as an absorption patch.

Reference Example 1 Acrylic resin solvent-based pressure-sensitive adhesive 93.16 parts (Brand name NISSETSU PE-300 solid content 40%) (84.47 parts after drying) Polyethylene glycol 300 2.21 parts (5 after drying) 0.01 part) Ethyl oleate 2.21 part (after drying 5.01 part) Water-absorbing polymer (trade name Sumikagel SP-520) 2.21 part (after drying 5.01 part) Estradiol 0.22 part (dry) 0.50 part later) After mixing with this formulation, spread on the above-mentioned support or liner so that the plaster thickness after solvent evaporation becomes the same as in the example, and thereafter prepare according to the above-mentioned manufacturing method It was cut into the size of 1 to prepare an estradiol transdermal patch.

Reference Example 2 Silicone adhesive 80.50 parts (trade name: Shirasucon 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 0.50 parts of estradiol After mixing with this formulation, spread on the above-mentioned support or liner so that the plaster thickness becomes the same as in the example, and thereafter prepare according to the above-mentioned manufacturing method and cut into the desired size. It was used as a transdermal patch for estradiol.

Test Example 1 (Hairless Mouse Skin Permeation Test 1) A hairless mouse skin permeation test was conducted using Example 2 and Reference Examples 1 and 2, and the test results are shown in FIG. As shown in the test results, Example 2 shows that the release of estradiol is clearly higher than those of Reference Examples 1 and 2. This is because the formulation of the present invention is 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 the hairless mouse skin permeation test of Examples 15, 17, 23 and Comparative Example 2, the results are shown in FIG. As shown in the test results, Examples 15, 17, and 23 are Comparative Example 2
In comparison with, the release of estradiol is clearly higher. This is because the preparation of the present invention uses polyethylene glycol and fatty acid ester. That is, it supports the usefulness of the present invention.

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

[0051]

[Table 1] The skin irritation criteria are as follows. No change; -Weak redness; ± Clear redness; + Severe rash; ++

Test Example 4 (Rabbit Blood Concentration Measurement Test) Using Examples 15, 17, 23 and Comparative Example 2, the rabbit blood concentration measurement was carried out. The hair on the back of the Japanese White House rabbit was removed, and the estradiol concentration in blood was measured over time.
The test results are shown in FIG. As shown in the test results, Examples 15, 17, and 23 are superior to Comparative Example 2 in all of rise in blood concentration, release amount, and sustainability. That is, it supports the usefulness of the present invention.

[0053]

As described above, (AB) n-A
The estradiol percutaneous absorption 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 the release of estradiol, exhibits sufficient medicinal effect, and has a redness, It is very useful industrially as a very ideal estradiol transdermal patch without rash.

[Brief description of drawings]

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

FIG. 2 is a hairless mouse skin permeation test 2.

FIG. 3 is a rabbit blood concentration measurement test.

[Explanation of symbols]

 In FIG. 1, ○: Estradiol transdermal patch of Example 2 □: Estradiol transdermal patch of Reference Example Δ: Estradiol transdermal patch of Reference Example 2 and FIG. 3, ○: Implementation Estradiol transdermal patch of Example 23 □: Estradiol transdermal patch of Example 17 Δ: Estradiol transdermal patch of Example 15 ●: Estradiol transdermal patch of Comparative Example 2

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Akira Nakagawa Akira Nakagawa 408 Tadaishiro-machi, Tosu City, Saga Prefecture Hisamitsu Pharmaceutical Co., Ltd.

Claims (2)

[Claims] 1. In an estradiol percutaneous absorption preparation, the base component is an (AB) nA 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,
An estradiol percutaneous absorption patch containing a fatty acid ester and a water-absorbing polymer as essential components and containing estradiol as a medicinal component. 2. As a base component, 5 to 50% by weight of (AB) n-A type elastic polymer and polyethylene glycol 1 to 1
The transdermal patch of estradiol according to claim 1, which contains 0% by weight, 1 to 10% by weight of a fatty acid ester, 1 to 20% by weight of a water-absorbing polymer, and 0.01 to 10% by weight of estradiol as a medicinal component. Agent.