JPH09255566A - Supporter for dermal administration agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a supporter for a dermal administration agent excellent in stretchability and penetration-diffusion preventability of the medicine. SOLUTION: This supporter is composed of a film comprising at least one kind of fluorine rubber and fluorine-based elastomer and having a thickness within the range of 10-200μm, preferably 50-100μm, As the fluorine rubber, vinylidene fluoride-hexafluoropropylene-tetrafluoroethylene terpolymer rubber, readily processed to film by a casting method, is exemplified. As the fluorine- based elastomer, a thermoplastic elastomer comprising an ethylene- tetrafluoroethylene copolymer and a vinylidene fluoride-hexafluoropropylene- tetrafluoroethylene copolymer is exemplified. The supporter for a dermal administration agent is obtained by molding with an extrusion molding method, etc. The film can be coated with a tackifier added with a medicine and made to be a dermal administration agent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a support for medicinal agents for transdermal administration, which is excellent in stretchability and drug permeation and diffusion prevention properties.

[0002]

2. Description of the Related Art A drug for transdermal administration comprises a drug contained in an adhesive layer, and the adhesive layer is coated on a support. This transdermal drug is used for the purpose of treatment by applying it to the skin, mucous membranes, etc. and absorbing the drug directly from the skin, mucous membranes, etc., for example, anti-inflammatory analgesics, skin disease tapes, antipruritic patches, wounds. Widely used as an agent. These have been used as local therapeutic agents, but recently, a transdermal therapeutic system (TTS) has been developed as a systemic therapeutic agent.

Examples of such applications include motion sickness agents, anginal agents, and menopausal agents. Since the range of treatment is expanding in this way, the requirements for supports used for transdermal drugs are becoming strict, and in particular, a product that has both elasticity and prevention of permeation and diffusion of drugs is desired. It is rare.

Elasticity is a characteristic required to follow the movement of the skin when it is applied to the skin, and if it is insufficient, it easily peels off or is applied to places with high movement such as the skin of the waist. There is a problem that it cannot be used. In addition, when the drug diffuses and permeates, there are drawbacks such as swelling of the support and reduction of the drug in the adhesive to impair a predetermined therapeutic effect.

[0005]

Examples of the currently used supports for medicinal preparations for transdermal administration include soft polyvinyl chloride film, polyethylene film, polyethylene terephthalate film, polyurethane film, aluminum vapor deposition film, non-woven fabric, and woven fabric. be able to. this house,
Soft polyvinyl chloride film, polyurethane film,
Polyethylene films and the like are excellent in flexibility, but have drawbacks such as easy penetration and diffusion of drugs. On the other hand, polyethylene terephthalate film, aluminum vapor deposition film and the like are excellent in preventing drug diffusion and penetration, but have drawbacks such as lack of elasticity.

In view of the above, it is an object of the present invention to provide a support for transdermal drug administration which is free from permeation and diffusion of the drug and is excellent in elasticity.

[0007]

The gist of the present invention resides in that the support for percutaneous administration is formed of a film having a thickness of 10 to 200 μm and made of at least one of fluororubber and fluoroelastomer.

The film made of at least one of the above-mentioned fluorine rubber and fluorine-based thermoplastic elastomer has a thickness of 10 to 200 μm. If it is less than 10 μm, it is thin and lacks strength and does not function as a support.
When it exceeds m, elasticity is insufficient, so the range is limited to the above range. It is preferably 50 to 100 μm.

The above-mentioned fluororubber is preferably one which can be easily processed into a film by a casting method. For example, vinylidene fluoride-6 propylene fluoride-4 ethylene fluorinated terpolymer rubber (Daiel G-manufactured by Daikin Industries, Ltd.) 90
1, G-902), propylene-4 fluoroethylene copolymer rubber (manufactured by Japan Synthetic Rubber Co., Ltd., Aflas 150c), and the like.

The above-mentioned fluorine-based elastomer is, for example, a thermoplastic elastomer composed of ethylene-4 fluoroethylene copolymer and vinylidene fluoride-hexafluoropropylene-tetrafluoroethylene copolymer (Dayer Thermoplastic T-530). , T-550, manufactured by Daikin Industries, Ltd.) and the like.

The film made of at least one of the fluororubber and the fluoroelastomer of the present invention may be made of one or more of the above fluororubbers, or one of the above fluoroelastomers. It may be composed of two or more kinds, or may be composed of one or more kinds of the above-mentioned fluororubber and one or more kinds of the above-mentioned fluorine-based elastomer.

The method for producing the transdermal drug carrier of the present invention includes, for example, a molding method by an extrusion method, a casting method by dissolving at least one of the fluororubber and the fluoroelastomer in an organic solvent. A method of forming a film can be mentioned.

The transdermal drug carrier of the present invention is prepared by applying a drug-containing adhesive to a film made of at least one of the above-mentioned fluororubber and fluoroelastomer to prepare a transdermal drug. You can

The drug is not particularly limited as long as it is percutaneously absorbed into the body and exerts a pharmacological effect. For example, anti-inflammatory agents, analgesics, local stimulants, antihistamines, local anesthetics, blood circulation. Examples thereof include accelerating agents, hypnotic sedatives, tranquilizers, antihypertensive agents, antibacterial agents and coronary vasodilators. At least one of these can be selected and used according to the purpose of treatment.

The anti-inflammatory agent and analgesic agent are not particularly limited, and examples thereof include indomethacin, ketoprofen, flurbiprofen, salicylic acid monoglycol ester, and methyl salicylate. The coronary vasodilator is not particularly limited, and examples thereof include nitroglycerin, nitroglycol, pentaerythritol tetranitrate, and isosorbide dinitrate. The antihistamine is not particularly limited, and examples thereof include diphenhydramine hydrochloride, isothibenzyl hydrochloride, and chlorpheniramine.

The polymer used as the main component of the pressure-sensitive adhesive is not particularly limited, and examples thereof include natural rubber, polyisoprene, polyisobutylene, silicone rubber, styrene-
Examples thereof include isoprene block copolymer, acrylic acid ester, methacrylic acid ester and the like. Further, as an additive, a tackifier, a softening agent, a filler, an antioxidant and the like may be added.

As a method for applying the pressure-sensitive adhesive containing the above drug, a method of dissolving in a solvent and applying and drying, a method of melting and extruding into a sheet form from an extruder, and the like can be used. By these methods, the support may be directly coated, or the release paper may be coated and then bonded to the support.

The drug has a functional group such as a hydroxyl group or an ester bond, which easily causes intermolecular interaction in the molecule, whereas the support for transdermal drug administration of the present invention has the above-mentioned constitution. By being formed from carbon and hydrocarbon, it is difficult for the drug to interact with these drugs, the permeation and diffusion of the drug in the adhesive into the support is suppressed, and the drug can be stably retained.

[0019]

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

Example 1 Daier Thermoplastic T-530 (manufactured by Daikin Industries, Ltd.) was molded into a film having a thickness of 80 μm by a T-die extruder to obtain a support for transdermal drug delivery.

Evaluation (1) Elasticity (i) 10% Modulus Tensile modulus was measured by performing a tensile test according to JIS K 6732 “Agricultural polyvinyl chloride film”. ○ Less than 1.0 N △ 1.0 N or more and less than 2.0 N × 2.0 N or more

(Ii) Residual elongation A Dematcher flexural fatigue tester (described in JIS K 6301) was used to give 75% elongation 10,000 times with JIS No. 1 dumbbell-shaped sample pieces. The elongation of the sample piece was measured 30 seconds after the load applied to the sample piece was made zero (the chuck fixing the bottom of the sample was removed). ○ Less than 10% △ 10 to less than 15% × 15% or more

(2) Drug Penetration and Diffusion Prevention Property A pressure-sensitive adhesive containing a drug was applied to the barrier film side of the support film. The adhesive was prepared according to the following formulation. To 100 parts by weight of natural rubber, 10 parts by weight of hydrogenated rosin acid ester was added to toluene, and
It was dissolved so as to be 0% by weight, and further, monoglycol salicylate was dissolved so as to be 2% by weight. This drug-containing pressure-sensitive adhesive toluene solution was applied to a silicone-surface-treated release paper so that the thickness of the pressure-sensitive adhesive after drying would be 15 μm, and the solvent was removed by drying. A support-adhesive laminate is prepared by adhering it to the barrier film surface of the support, and the laminate is allowed to stand at 40 ° C. for 6 months, after which the monoglyceryl salicylate in the adhesive is quantified and left. I checked the quantity. ○ 85% or more and 100% or less △ 70% or more and less than 85% × less than 70% These evaluation results are shown in Table 1.

Example 2 The same procedure as in Example 1 was carried out using Daiel Thermoplastic T-550 (manufactured by Daikin Industries, Ltd.) to obtain a support for transdermal drug delivery. Table 1 shows the evaluation results.

Example 3 100 parts by weight of a methyl ethyl ketone solution of Daier G-902 (manufactured by Daikin Industries, Ltd.) having a solid content of 30% by weight was added to triallyl isocyanurate (TAIC, manufactured by Nippon Kasei Co., Ltd.).
0.8 parts by weight and peroxide (Perhexa 25B,
0.3 parts by weight of Nippon Oil & Fats Co., Ltd. was mixed and dissolved, and coated with a bar coater on a release paper having one surface treated with silicon so that the thickness after drying was 50 μm, and methyl ethyl ketone was removed by drying. After that, attach it to the release paper and
It was pressurized with a hot roll at 50 ° C. and further vulcanized at 180 ° C. for 6 hours in an oven to obtain a support for transdermal administration. Table 1 shows the evaluation results.

Example 4 100 parts by weight of tetrahydrofuran / methyl ethyl ketone (weight ratio 5/5) solution of Aflas 150c (manufactured by Japan Synthetic Rubber Co., Ltd.) having a solid content of 20% by weight was added to triallyl isocyanurate (TAIC, manufactured by Nippon Kasei Co., Ltd.). 1.0 part by weight and peroxide (Perhexa 25B, manufactured by NOF CORPORATION)
A transdermal drug support was obtained in the same manner as in Example 3 except that 1 part by weight was mixed and dissolved and vulcanized at 200 ° C. for 4 hours in an oven. Table 1 shows the evaluation results.

Comparative Example 1 Polyester plasticizer 7 having a molecular weight of 2000 as a plasticizer
A polyvinyl chloride resin (PVC) containing 0% by weight was melted by a roll at a temperature of 160 ° C. to prepare a sheet having a thickness of 80 μm, which was used as a support for medicinal agents for transdermal administration. Table 1 shows the evaluation results.

Comparative Example 2 Polyurethane-polyvinyl chloride composite (PU-PVC)
100 parts by weight of Dominus K-650F (manufactured by Tosoh Corporation) was added with 1.5 parts by weight of Ca-Zn stabilizer, and a 100 μm film was formed by a calender roll, which was used as a support for transdermal drug delivery. Table 1 shows the evaluation results.

Comparative Example 3 In the PU-PVC film of Comparative Example 2, 100 parts by weight of UD417 (solid content 25%, manufactured by Seiko Kasei) and 2 parts by weight of an isocyanate curing agent U-4000 (manufactured by Seiko Kasei). The added material is coated by a gravure coater so that the thickness after drying is 1 μm, and dried.
A 3.5 μm-thick polyethylene terephthalate film (manufactured by Toray Industries, Inc.) was laminated, and this was used as a support for transdermal administration. The evaluation of the drug permeation / diffusion preventing property was performed by providing an adhesive layer on the polyethylene terephthalate surface. Table 1 shows the evaluation results.

Comparative Example 4 A urethane type thermoplastic elastomer film (manufactured by Nisshinbo Co., Ltd., thickness 40 μm) was used as a support for medicinal agents for transdermal administration. Table 1 shows the evaluation results.

[0031]

[Table 1]

[0032]

EFFECTS OF THE INVENTION Since the support for transdermal drug delivery of the present invention has the above-mentioned constitution, it is possible to obtain a transdermal drug which is excellent in stretchability and drug permeation / diffusion prevention property.

Claims (1)

[Claims] 1. A support for transdermal drug delivery, which comprises a film having a thickness of 10 to 200 μm and made of at least one of fluororubber and a fluoroelastomer.