JPH07196505A - Percutaneous absorption preparation - Google Patents

Abstract

PURPOSE:To obtain a percutaneous preparation which can release indomethacin effectively and permit efficient absorption through skin into the living body. CONSTITUTION:The percutaneous absorption preparation is produced by coating the substrate with a layer comprising a rubber base of at least one of natural or synthetic rubber, a tackifier resin, indomethacin and isopropyl myristate on its one surface where the amount of isopropyl myristate is 5 to 500 pts.wt. per 100 pts.wt. of the base.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a percutaneous absorption preparation excellent in skin absorbability.

[0002]

2. Description of the Related Art A percutaneous absorption preparation has an adhesive layer containing a drug and a support, and is devised so that the drug present in the adhesive layer can be transdermally absorbed into the body. ing. The method for improving this skin absorbability is generally described in the following 2
There are two methods.

The first means is a method of improving the affinity of the drug for the skin, and specifically, a method of adding a skin migrating substance capable of improving the drug solubility in the skin to the adhesive layer. For example, Tokuhyodaira 3-50583
Japanese Patent Publication No. 5 discloses a technique of improving the skin absorbability of a drug by modifying the stratum corneum with an enzyme preparation such as papain. Further, Japanese Patent Publication No. 20886/1992 discloses a technique for improving the skin absorbability of a drug by perturbing the cell membrane with a cell membrane perturbing compound such as myristyl alcohol.

However, the above-mentioned means cannot eliminate side effects such as skin irritation such as erythema that may occur as a result of skin-transferring substances degenerating the stratum corneum or disturbing cell membranes. Absent.

The second means is a method of improving the release of the drug from the transdermal preparation, and specifically, a non-skin transfer substance that improves the distribution of the drug to the skin is added to the adhesive layer. In order to increase the physical mobility of the drug in the pressure-sensitive adhesive layer, a liquid component is added to soften the pressure-sensitive adhesive layer. The above-mentioned means is an effective method when the release rate of the drug from the pressure-sensitive adhesive layer is the rate-limiting absorption, but for indomethacin, there has been no effective method by the above-mentioned means until now.

[0006]

SUMMARY OF THE INVENTION In view of the above, an object of the present invention is to provide a transdermal preparation capable of effectively releasing indomethacin and efficiently absorbing it through the skin into the body.

[0007]

The gist of the present invention is to provide a percutaneous absorption preparation on one surface of a support, a base comprising at least one of natural rubber and synthetic rubber, a tackifying resin, indomethacin, and A pressure-sensitive adhesive layer made of isopropyl myristate is laminated, and the amount of isopropyl myristate is 5 to 500 with respect to 100 parts by weight of the base.
It exists in the weight part.

Although the above-mentioned support is flexible, it gives self-supporting properties to the transdermal preparation, prevents volatilization and migration of the drug,
Further, it is not particularly limited as long as it has conformability to the skin surface, and examples thereof include a drug-impermeable film, sheet, foam, woven fabric made of natural or synthetic fibers, non-woven fabric, paper, or The thing etc. which laminate | stack these suitably are mentioned.

Examples of the material of the support include polyethylene, ethylene-vinyl acetate copolymer, polyurethane, polypropylene, polyvinyl chloride, polyvinylidene chloride, cellulose acetate, ethyl cellulose, polyethylene terephthalate, vinyl acetate-vinyl chloride copolymer. Coalescing,
Nylon, polyester, polyolefin, rayon,
Examples thereof include polyamide, aluminum, cotton, suf, and the like.
Among these, polyethylene terephthalate, polyester, polyolefin, rayon, etc. are non-migratory agents,
It is particularly preferable because it has chemical resistance, moisture resistance, dimensional stability, dyeability and the like as a support and has a relatively low price.

In order to improve the adhesion between the support and the pressure-sensitive adhesive layer, the support may be subjected to corona treatment, plasma discharge treatment, or the like, or an anchor coating agent may be applied.

If the thickness of the above-mentioned support is too thin, the self-supporting property of the percutaneous absorption preparation is insufficient and it becomes difficult to handle, and if it is too thick, the flexibility of the percutaneous absorption preparation is insufficient and the skin feels uncomfortable. The range of 0.01 to 7 mm is preferable.

The base is made of at least one of natural rubber and synthetic rubber. The synthetic rubber is not particularly limited, for example, styrene-isoprene block copolymer, styrene-isoprene-styrene block copolymer and other styrene-isoprene block copolymer; styrene-butadiene block copolymer, Styrene-butadiene-styrene block copolymer, styrene-
Examples thereof include styrene-butadiene block copolymers such as ethylene-butadiene-styrene block copolymers. Among these, styrene-isoprene-styrene block copolymers are particularly preferable because they have appropriate rubber elasticity.

When the above-mentioned base is composed of a styrene-isoprene-styrene block copolymer, the solution viscosity of the styrene-isoprene-styrene block copolymer is too low or too high, the indomethacin releasing property is lowered. ,
700 to 1500 cps (25 ° C., 25 wt% toluene solution) is preferable. The solution viscosity is measured according to JISK
7117 can be performed.

As the styrene-isoprene-styrene block copolymer, a commercially available styrene-isoprene-styrene block copolymer such as Califlex TR series manufactured by Shell Chemical Co. can be used. A polymer may be added, and in some cases, a plurality of polymers may be mixed so as to have a specified viscosity.

The tackifying resin is not particularly limited, and examples thereof include a rosin resin, a polyterpene resin, a coumarone-indene resin, a petroleum resin, a terpene-phenol resin, and an alicyclic saturated hydrocarbon resin. . Among them, the alicyclic saturated hydrocarbon resin is preferably used because it exhibits the tackifying effect without excessively reducing the cohesive force of the base.

If the amount of the base and the tackifying resin is too small, the cohesive force and the adhesive force will be insufficient and the indomethacin release property will be lowered. If the amount is too large, the cohesive force will be excessive and the adhesive force will be insufficient. Further, since the release of indomethacin is reduced, the tackifying resin 6 is added to 100 parts by weight of the base material.
0 to 400 parts by weight is preferable. More preferably 80-2
The amount is 50 parts by weight, more preferably 100 to 230 parts by weight, and even more preferably 115 to 130 parts by weight.

The above-mentioned indomethacin has anti-inflammatory and analgesic effects, and is a drug generally used as a medicine. If the amount of the indomethacin added is too small, the skin absorption will be insufficient, and if it is too large, crystals will precipitate in the pressure-sensitive adhesive layer and the adhesive strength will be insufficient, so the total amount of the base, the tackifying resin and isopropyl myristate is 100% by weight. It is preferably 0.2 to 10 parts by weight with respect to parts. It is more preferably 0.2 to 1 part by weight.

The above-mentioned isopropyl myristate functions as a softening agent and at the same time promotes release of the drug from the adhesive layer. The amount of isopropyl myristate added is 1
It is 5 to 500 parts by weight with respect to 00 parts by weight. If it is too small, drug release is insufficient and a sufficient amount of skin absorption cannot be expected, and if it is too large, the cohesive force of the base decreases and so-called adhesive residue phenomenon or adhesiveness is insufficient, so add isopropyl myristate. The amount is limited to the above range. It is preferably 10 to 250 parts by weight, more preferably 15 to 1
The amount is 60 parts by weight, more preferably 40 to 50 parts by weight.

In addition to the above-mentioned indomethacin, 1-menthol may be added to the above-mentioned pressure-sensitive adhesive layer, if necessary, to impart a cooling sensation, or pepper extract or the like may be added to impart a warming sensation. If the added amount of these additives is too large, it affects the efficacy of the main component drug, so 10 parts by weight or less is preferable for 100 parts by weight of the base.

If necessary, the pressure-sensitive adhesive layer further contains
Liquid paraffin, isopropyl palmitate, liquid polybutene, mineral oil, lanolin, liquid polyisoprene, liquid polyacrylate and other softeners other than isopropyl myristate according to the present invention; antioxidants such as dibutylhydroxytoluene; fillers such as titanium oxide. Etc. may be added. These components are preferably added in an amount within a range that does not impair the cohesive force and the adhesive force, and usually, a range of 0.1 to 30 parts by weight is preferable with respect to 100 parts by weight of the base, and more preferably filling. It is 1 to 10 parts by weight for the agent and 1 to 20 parts by weight for the softening agent.

The transdermal preparation of the present invention can be obtained by spreading the above-mentioned pressure-sensitive adhesive layer on one surface of a support to form a layer. If the thickness of the pressure-sensitive adhesive layer is too thin, the skin absorption amount and adhesive strength of indomethacin are insufficient, and if it is too thick, the transdermal absorption formulation lacks flexibility and the skin feels uncomfortable.
The range of 0.01 to 1 mm is preferable.

In order to protect the surface of the adhesive layer of the percutaneous absorption preparation of the present invention until use, it is usually preferable that the adhesive surface has a release paper. As the release paper, those obtained by subjecting a polyethylene terephthalate film to silicon treatment, those obtained by subjecting paper to polyethylene lamination and then subjecting it to silicon treatment, and the like are preferably used. The thickness of the release paper is generally 1000 μm or less, preferably 20 to 200 μm.

As a method for producing the percutaneous absorption preparation of the present invention, a usual method for producing an adhesive tape can be applied. For example, typical methods such as a solvent coating method and a hot melt coating method, an emulsion coating method, a method by electron beam cross-linking and the like can be mentioned.
To produce the percutaneous absorption preparation of the present invention by a solvent coating method, for example, a base, a tackifying resin, a drug, a softening agent and various other compounding agents are dissolved or dispersed in an appropriate solvent, and the resulting solution or dispersion is obtained. The liquid is directly applied to the surface of the support and dried to form an adhesive layer. This adhesive layer is brought into close contact with a protective release paper to obtain the desired indomethacin-containing transdermal preparation. In addition, this solution or dispersion may be applied on a release paper and the adhesive layer obtained after drying may be adhered to a support.

To apply the percutaneous absorption preparation of the present invention by the hot melt method, for example, a base, a tackifying resin, a drug, a softening agent, and various other compounding ingredients are heated and melted and then mixed. The melt is directly applied to the surface of the support and solidified by cooling to form an adhesive layer. This adhesive layer is brought into close contact with a protective release paper to obtain the desired indomethacin-containing transdermal preparation. Alternatively, the melt may be applied onto release paper and the pressure-sensitive adhesive layer obtained after cooling and solidification may be brought into close contact with the support.

[0025]

When the percutaneous absorption preparation of the present invention is applied to the skin, indomethacin is absorbed into the skin more easily than before. Once absorbed by the skin, indomethacin is readily absorbed by the body through the skin. Since the saturated dissolution concentration of indomethacin in each component constituting the pressure-sensitive adhesive layer of the transdermal preparation of the present invention is overwhelmingly high for isopropyl myristate, most of indomethacin contained in the pressure-sensitive adhesive layer is dissolved in isopropyl myristate. It takes a form that does not easily transfer to other ingredients. Isopropyl myristate maintains a fluid state as a liquid component in the pressure-sensitive adhesive layer, and indomethacin contained therein also has a high thermodynamic activity. On the other hand, at the interface between the adhesive layer and the skin, indomethacin is considered to be directly absorbed by the skin via isopropyl myristate, but since the mobility of indomethacin itself is high, it is effectively absorbed by the skin. .

[0026]

The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.

Example 1 100 parts by weight of styrene-isoprene-styrene block copolymer (Califlex 1107P, Shell Chemical Co.), 200 parts by weight of alicyclic saturated hydrocarbon resin (Alcon P85, Arakawa Chemical Co., Ltd.), myristin Isopropyl acid (manufactured by NOF CORPORATION) 15.6 parts by weight, titanium oxide (A100,
Ishihara Sangyo Co., Ltd.) 9.4 parts by weight and dibutylhydroxytoluene (Orient BHT, Orient Chemical Co., Ltd.)
3.1 parts by weight was stirred and mixed under nitrogen substitution at 150 ° C. to obtain a pressure-sensitive adhesive layer component. Next, 0.375 parts by weight of indomethacin (manufactured by Daiwa Pharmaceutical Co., Ltd.) and 0.035 parts by weight of capsicum extract (manufactured by Daiichi Pharmaceutical Co., Ltd.) were added to the above-mentioned pressure-sensitive adhesive layer components to make 100 parts by weight as a whole, and under nitrogen substitution, 130 Mix and stir at ℃,
A polyethylene terephthalate film having a thickness of 0.035 mm is treated with silicon to give a release paper having a thickness of 0.2.
After being uniformly coated so as to have a thickness of mm, it was cooled and solidified to obtain an adhesive layer. Then, on the pressure-sensitive adhesive layer, a polyethylene foam having a thickness of 3 mm (Sekisui Softlon IF30025,
Sekisui Chemical Co., Ltd.) has a basis weight of 60 g / m ² and a thickness of 0.
25mm polyester / polyolefin non-woven fabric (ED
-6, manufactured by Japan Vilene Co., Ltd.) was laminated by a thermal lamination method on the non-woven fabric surface of the support to obtain a percutaneous absorption preparation.

With respect to each of the obtained transdermal preparations, the performance in the following items was evaluated. (1) Skin Permeability of Mice Permeability test of indomethacin to the excised skin of mice was performed. That is, the Franz-type diffusion cell (a) shown in FIG. 1 has a bottomed cylindrical receptor tank (b).
And a bottomed cylindrical donor tank (c) placed on top of this
Consists of. An opening (d) is provided in the center of the lower wall of the donor tank (c), and an upper flange (e) is provided at the lower end of the donor tank (c) and the upper end of the receptor tank (b), respectively.
And a lower flange (f). The receptor tank (b) is provided with a laterally projecting sampling port (g) on its side, and a magnetic stirrer (h) is placed inside the receptor tank.

After hairless mice (7-week-old, male) were sacrificed by cervical dislocation, their back skin was immediately removed to remove subcutaneous fat and muscular layer to obtain a removed skin piece of about 5 cm × 5 cm. This skin piece is sandwiched between the upper flange (e) and the lower flange (f) of the diffusion cell (a), and the opening (d) of the donor tank (c) is completely closed with the skin piece (i). I did it. A circular tape-shaped percutaneous absorption preparation test piece (j) punched out in an area of 3.14 cm ² was attached to the upper surface of the skin piece (i). The receptor tank was filled with a receptor solution composed of a phosphate buffer solution having a pH of 7.2. Next, the diffusion cell (a) was placed in a constant temperature bath of 37 ° C., and the receptor liquid was stirred by a magnetic stirring device. 2 from the start of the test
After 4 hours, the receptor liquid was collected from the sampling port (g), the concentration of indomethacin in the collected receptor liquid was measured by high performance liquid chromatography, and the permeation amount of indomethacin per cm ^{2 of} the test piece was determined. The number of repetitions of the test was 3.

(2) Adhesiveness An adhesive strength test was conducted based on JIS Z 0273. That is, the release paper of the transdermal absorption preparation having a width of 5 cm and a length of 20 cm was removed, and the adhesive surface was fixed upward on a slope of 30 degrees with respect to the horizontal so that the tip of the sample was in contact with the upper end of the slope.
The upper portion of 10 cm and the lower portion of 5 cm were covered with an appropriate paper, and an adhesive surface having a width of 5 cm and a length of 5 cm was left in the central portion. The steel ball was rolled from the upper end of the slope, and the Japanese Pharmacopoeia standard number of the ball stopped at the central adhesive surface was used as the measured value. The number of repetitions of the test was 3. Generally, no. When 4 or more balls stop, it is evaluated as having a good adhesive force. The results of the above test are shown in Table 1.

Example 2 Styrene-isoprene-styrene block copolymer 10
0 part by weight, alicyclic saturated hydrocarbon resin 182.4 parts by weight,
A percutaneous absorption preparation was prepared in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 32.4 parts by weight of isopropyl myristate, 8.8 parts by weight of titanium oxide, and 2.9 parts by weight of dibutylhydroxytoluene. Obtained and evaluated. The results are shown in Table 1.

Example 3 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 166.7 parts by weight of alicyclic saturated hydrocarbon resin,
50 parts by weight of isopropyl myristate, titanium oxide 8.
A transdermal preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 3 parts by weight and 2.8 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 4 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 100 parts by weight of alicyclic saturated hydrocarbon resin, 37.5 parts by weight of isopropyl myristate, titanium oxide 6.
A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 3 parts by weight and 2.1 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 5 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 102.9 parts by weight of alicyclic saturated hydrocarbon resin,
A transdermal absorption preparation was prepared in the same manner as in Example 1 except that 42.9 parts by weight of isopropyl myristate, 37.1 parts by weight of titanium oxide, and 2.9 parts by weight of dibutylhydroxytoluene were used to obtain an adhesive layer component. Obtained and evaluated. The results are shown in Table 1.

Example 6 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 111.4 parts by weight of alicyclic saturated hydrocarbon resin,
A transdermal absorption preparation was prepared in the same manner as in Example 1 except that 42.9 parts by weight of isopropyl myristate, 28.6 parts by weight of titanium oxide, and 2.9 parts by weight of dibutylhydroxytoluene were used to obtain an adhesive layer component. Obtained and evaluated. The results are shown in Table 1.

Example 7 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, alicyclic saturated hydrocarbon resin 120 parts by weight, isopropyl myristate 42.9 parts by weight, titanium oxide 20
A transdermal preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 1 part by weight and 2.9 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 8 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, alicyclic saturated hydrocarbon resin 120 parts by weight, isopropyl myristate 37.1 parts by weight, titanium oxide 2
A transdermal preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained using 5.7 parts by weight and 2.9 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 9 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, saturated alicyclic hydrocarbon resin 120 parts by weight, isopropyl myristate 48.6 parts by weight, titanium oxide 1
A transdermal absorption preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 4.3 parts by weight and 2.9 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 10 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 120 parts by weight of alicyclic saturated hydrocarbon resin, 54.3 parts by weight of isopropyl myristate, titanium oxide 8.
A transdermal preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 6 parts by weight and 2.9 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Example 11 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 125.7 parts by weight of alicyclic saturated hydrocarbon resin,
A percutaneous absorption preparation was prepared in the same manner as in Example 1 except that 42.9 parts by weight of isopropyl myristate, 11.4 parts by weight of titanium oxide and 2.9 parts by weight of dibutylhydroxytoluene were used to obtain an adhesive layer component. Obtained and evaluated. The results are shown in Table 1.

Example 12 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 134.3 parts by weight of alicyclic saturated hydrocarbon resin,
A transdermal preparation was prepared in the same manner as in Example 1 except that 42.9 parts by weight of isopropyl myristate, 5.7 parts by weight of titanium oxide, and 2.9 parts by weight of dibutylhydroxytoluene were used to obtain a pressure-sensitive adhesive layer component. Obtained and evaluated. The results are shown in Table 1.

Example 13 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, alicyclic saturated hydrocarbon resin 152.6 parts by weight,
A transdermal preparation was prepared in the same manner as in Example 1 except that 65.8 parts by weight of isopropyl myristate, 7.9 parts by weight of titanium oxide, and 2.6 parts by weight of dibutylhydroxytoluene were used to obtain a pressure-sensitive adhesive layer component. Obtained and evaluated. The results are shown in Table 1.

Example 14 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, alicyclic saturated hydrocarbon resin 97.7 parts by weight, isopropyl myristate 152.3 parts by weight, titanium oxide 9.1 parts by weight, and dibutylhydroxytoluene 2.3 parts by weight are used to form an adhesive layer component. A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 1 except that the above was obtained. The results are shown in Table 1.

Example 15 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 84.3 parts by weight of alicyclic saturated hydrocarbon resin, 131.4 parts by weight of isopropyl myristate, 7.8 parts by weight of titanium oxide, and 3.9 parts by weight of dibutylhydroxytoluene were used to form an adhesive layer component. A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 1 except that the above was obtained. The results are shown in Table 1.

Comparative Example 1 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 115.9 parts by weight of alicyclic saturated hydrocarbon resin,
A transdermal preparation was obtained in the same manner as in Example 1 except that the adhesive layer component was obtained by using 97.7 parts by weight of liquid paraffin, 9.1 parts by weight of titanium oxide, and 4.5 parts by weight of dibutylhydroxytoluene. ,evaluated. The results are shown in Table 1.

Comparative Example 2 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, alicyclic saturated hydrocarbon resin 340 parts by weight, isopropyl myristate 73.3 parts by weight, titanium oxide 20
A transdermal preparation was obtained and evaluated in the same manner as in Example 1 except that the pressure-sensitive adhesive layer component was obtained by using 1 part by weight and 6.7 parts by weight of dibutylhydroxytoluene. The results are shown in Table 1.

Comparative Example 3 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 57.1 parts by weight of alicyclic saturated hydrocarbon resin, 15.7 parts by weight of isopropyl myristate, 4.3 parts by weight of titanium oxide, 1.4 parts by weight of dibutylhydroxytoluene were used to form the adhesive layer component. A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 1 except that the above was obtained. The results are shown in Table 1.

Comparative Example 4 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 102.2 parts by weight of alicyclic saturated hydrocarbon resin,
Isopropyl myristate 183.3 parts by weight, titanium oxide 13.3 parts by weight, dibutylhydroxytoluene 6.7
Example 1 except that the pressure-sensitive adhesive layer component was obtained using parts by weight.
A percutaneous absorption preparation was obtained and evaluated in the same manner as. The results are shown in Table 1.
It was shown to.

Comparative Example 5 Styrene-isoprene-styrene block copolymer 10
0 parts by weight, 200 parts by weight of alicyclic saturated hydrocarbon resin, 5 parts by weight of isopropyl myristate, 9.4 parts by weight of titanium oxide, 3.1 parts by weight of dibutylhydroxytoluene except that a pressure-sensitive adhesive layer component was obtained. Was obtained and evaluated in the same manner as in Example 1. The results are shown in Table 1.

[0050]

[Table 1]

Example 16 As a styrene-isoprene-styrene block copolymer, 50 parts by weight of Califlex TR1112 manufactured by Shell Chemical Co., Ltd. and 50 parts by weight of Califlex TR1117 (styrene in the above-mentioned styrene-isoprene-styrene block copolymer were used). -Including 34 parts by weight of isoprene block copolymer), the viscosity is set to a value shown in Table 2, 130 parts by weight of an alicyclic saturated hydrocarbon resin, and 40 parts of isopropyl myristate.
An adhesive layer component was obtained by using 6 parts by weight of liquid paraffin (manufactured by Nikko Co., Ltd.), 6 parts by weight of titanium oxide, and 3 parts by weight of dibutylhydroxytoluene, and the obtained adhesive layer component was indomethacin (manufactured by Daiwa Pharmaceutical Co., Ltd.). ) A transdermal preparation was obtained in the same manner as in Example 1 except that 0.375 parts by weight was added to make 100 parts by weight.

With respect to each of the obtained percutaneous absorption preparations, the skin permeability of mice was evaluated in the same manner as in Example 1. The results are shown in Table 2. In the table, IPM represents isopropyl myristate.

Example 17 100 califlex TR1112 manufactured by Shell Chemical Co., Ltd. was used as a styrene-isoprene-styrene block copolymer.
By weight (including 35 parts by weight of the styrene-isoprene block copolymer in the styrene-isoprene-styrene / block copolymer), the viscosity is set to the value shown in Table 2, and 123 parts by weight of the alicyclic saturated hydrocarbon resin is used. A transdermal preparation was prepared in the same manner as in Example 16 except that the adhesive layer component was obtained by using 45 parts by weight of isopropyl myristate, 16 parts by weight of liquid paraffin, 8 parts by weight of titanium oxide, and 3 parts by weight of dibutylhydroxytoluene. Was obtained and evaluated. The results are shown in Table 2.

Example 18 As a styrene-isoprene-styrene block copolymer, 100 Kaliflex TR1111 manufactured by Shell Chemical Co., Ltd. was used.
Parts by weight (styrene-isoprene block copolymer 1 in the above styrene-isoprene-styrene block copolymer 1
(Including 7 parts by weight), the viscosity is as shown in Table 2, 120 parts by weight of alicyclic saturated hydrocarbon resin, 42 parts by weight of isopropyl myristate, 8 parts by weight of liquid paraffin, 6 parts by weight of titanium oxide, dibutylhydroxytoluene. A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that the adhesive layer component was obtained by using 3 parts by weight. The results are shown in Table 2.

Example 19 As a styrene-isoprene-styrene block copolymer, 34 parts by weight of Califlex TR1111 manufactured by Shell Chemical Co., Ltd. and 66 parts by weight of Califlex TR1107 (styrene in the styrene-isoprene-styrene block copolymer were used). (Including 18 parts by weight of isoprene block copolymer), the viscosity is set to a value shown in Table 2, 115 parts by weight of alicyclic saturated hydrocarbon resin, 50 parts by weight of isopropyl myristate, 9 parts by weight of liquid paraffin, and 9 parts by weight of titanium oxide. Department,
A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that the pressure-sensitive adhesive layer component was obtained using 3 parts by weight of dibutylhydroxytoluene. The results are shown in Table 2.

COMPARATIVE EXAMPLE 6 As a styrene-isoprene-styrene block copolymer, 100 Kaliflex TR1117 manufactured by Shell Chemical Co., Ltd. was used.
Using parts by weight (including 33 parts by weight of the styrene-isoprene-styrene block copolymer in the styrene-isoprene-styrene block copolymer), the viscosity is set to the value shown in Table 2, and 123 parts by weight of the alicyclic saturated hydrocarbon resin are used. A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 16, except that 45 parts by weight of isopropyl myristate, 16 parts by weight of liquid paraffin, 8 parts by weight of titanium oxide, and 3 parts by weight of dibutylhydroxytoluene were used. The results are shown in Table 2.

Comparative Example 7 100 as a styrene-isoprene-styrene block copolymer, Califlex TR1107 manufactured by Shell Chemical Co., Ltd.
Parts by weight (styrene-isoprene block copolymer 1 in the above styrene-isoprene-styrene block copolymer 1
(Including 8 parts by weight), the viscosity is as shown in Table 2, 123 parts by weight of alicyclic saturated hydrocarbon resin, 45 parts by weight of isopropyl myristate, 16 parts by weight of liquid paraffin, 8 parts by weight of titanium oxide, dibutylhydroxytoluene. A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that 3 parts by weight was used. The results are shown in Table 2.

Comparative Example 8 Califlex TR1112 manufactured by Shell Kagaku Co., Ltd. as a styrene-isoprene-styrene block copolymer was used.
Parts by weight (styrene-isoprene block copolymer 3 in the styrene-isoprene-styrene block copolymer)
(Including 5 parts by weight), the viscosity is as shown in Table 2, 80 parts by weight of alicyclic saturated hydrocarbon resin, 46 parts by weight of isopropyl myristate, 9 parts by weight of liquid paraffin, 6 parts by weight of titanium oxide, dibutylhydroxytoluene. A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that 3 parts by weight was used. The results are shown in Table 2.

Comparative Example 9 Califlex TR1112 manufactured by Shell Kagaku Co., Ltd. as a styrene-isoprene-styrene block copolymer was used.
Parts by weight (styrene-isoprene block copolymer 3 in the styrene-isoprene-styrene block copolymer)
(Including 5 parts by weight), the viscosity is as shown in Table 2, 150 parts by weight of alicyclic saturated hydrocarbon resin, 40 parts by weight of isopropyl myristate, 3 parts by weight of liquid paraffin, 9 parts by weight of titanium oxide, dibutylhydroxytoluene. A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that 3 parts by weight was used. The results are shown in Table 2.

Comparative Example 10 As a styrene-isoprene-styrene block copolymer, 100 is Califlex TR1112 manufactured by Shell Chemical Co.
Parts by weight (styrene-isoprene block copolymer 3 in the styrene-isoprene-styrene block copolymer)
(Including 5 parts by weight), the viscosity is set to the value shown in Table 2, 123 parts by weight of alicyclic saturated hydrocarbon resin, 30 parts by weight of isopropyl myristate, 10 parts by weight of liquid paraffin, 9 parts by weight of titanium oxide, dibutylhydroxytoluene. A transdermal preparation was obtained and evaluated in the same manner as in Example 16 except that 3 parts by weight was used. The results are shown in Table 2.

Comparative Example 11 100 as a styrene-isoprene-styrene block copolymer, Califlex TR1112 manufactured by Shell Chemical Co., Ltd.
By weight (including 35 parts by weight of the styrene-isoprene block copolymer in the styrene-isoprene-styrene / block copolymer), the viscosity is set to the value shown in Table 2, and 123 parts by weight of the alicyclic saturated hydrocarbon resin is used. A percutaneous absorption preparation was obtained and evaluated in the same manner as in Example 16 except that 60 parts by weight of isopropyl myristate, 1 part by weight of liquid paraffin, 10 parts by weight of titanium oxide and 3 parts by weight of dibutylhydroxytoluene were used. The results are shown in Table 2.

[0062]

[Table 2]

As is clear from the results shown in Tables 1 and 2,
The percutaneous absorption preparation of the present invention showed a significantly higher skin permeation amount of indomethacin than the percutaneous absorption preparation containing no isopropyl myristate. In particular, it has been clarified that the skin permeation amount of indomethacin is remarkably increased by adding a styrene-isoprene-styrene copolymer having a specific viscosity, a tackifying resin and isopropyl myristate.

[0064]

Since the percutaneous absorption preparation of the present invention is constituted as described above, it is possible to provide a percutaneous absorption preparation having indomethacin which is better in skin absorbability than ever before. In particular, styrene-isoprene-styrene copolymer of specific viscosity, tackifying resin and isopropyl myristate are blended in a specific ratio, so that the skin absorbability of indomethacin is not changed with the conventional base and composition or properties. An excellent percutaneous absorption preparation can be provided.

[Brief description of drawings]

FIG. 1 is a perspective view showing a Franz diffusion cell.

[Explanation of symbols]

 a Diffusion cell b Receptor tank c Donor tank e Flange g Sampling port h Magnetic stirrer i Skin piece j Transdermal absorption test piece

Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location A61K 47/14 E

Claims (3)

[Claims] 1. A percutaneous absorption preparation in which a pressure-sensitive adhesive layer made of at least one of natural rubber and synthetic rubber, a tackifying resin, indomethacin, and isopropyl myristate is laminated on one surface of a support. And the amount of the isopropyl myristate is 5 to 500 parts by weight based on 100 parts by weight of the base, a transdermal preparation. 2. The percutaneous absorption preparation according to claim 1, wherein the base is a styrene-isoprene-styrene block copolymer. 3. A percutaneous absorption preparation in which a base comprising a styrene-isoprene-styrene block copolymer, a tackifying resin, indomethacin and an adhesive layer comprising isopropyl myristate are laminated on one side of a support. And the solution viscosity of the styrene-isoprene-styrene block copolymer is 700 to 1500 cps (25 ° C., 25 wt% toluene solution), and the amount of the tackifying resin is 115 with respect to 100 parts by weight of the base. To 130 parts by weight, and the amount of isopropyl myristate is 40 to 50 parts by weight, a percutaneous absorption preparation.