JP3749766B2 - Support for transdermal drug delivery - Google Patents

Description

【００３２】
【発明の効果】
本発明の経皮投与薬用支持体は上述の構成からなり、薬物の浸透拡散防止性に優れ、粘着剤層中の薬物を安定して保持することができ、投与量を高い精度で制御することができ、また、皮膚の動きに追従することができる柔軟性を有しているので、粘着剤の粘着力を大きくする必要がなく、剥離時に皮膚を傷めない経皮投与薬を提供することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a support for a drug for transdermal administration, which is excellent in flexibility and prevention of penetration and diffusion of a drug.
[0002]
[Prior art]
A transdermal drug is formed by applying a pressure-sensitive adhesive layer containing a drug to a support. Such a transdermal drug can be treated by adsorbing the drug directly from the skin, mucous membrane, etc. by pasting it on the skin, mucous membrane, etc., and has been conventionally treated with anti-inflammatory analgesics, skin disease tapes, antipruritics. It has been used as a local therapeutic agent such as a patch and a wound agent. However, in recent years, transdermal therapeutic systems (TTS) have been developed, and their use as systemic therapeutic agents such as motion sickness medicine, angina pectoris, climacteric medicine, vasodilator, asthma medicine, etc. has increased. ing.
[0003]
With the spread of such a therapeutic field, the demand for a support used for a transdermal drug is becoming strict, and in particular, both flexibility and ability to prevent the diffusion of a drug into a support can be achieved. Things are strongly sought after.
[0004]
Flexibility is a characteristic that is necessary for the ability to follow the movement of the skin when a transdermal drug is applied to the skin. The administered drug will easily peel off the skin. In order to prevent this, there are methods such as increasing the adhesive force of the adhesive layer to the skin. However, the pressure-sensitive adhesive layer having an increased adhesive force has a problem in that when the drug for transdermal administration is peeled off, the stratum corneum is peeled off to cause inflammation on the skin.
[0005]
In TTS, for example, drugs with strong side effects such as angina pectoris and vasodilators may be administered. The administration of such a drug needs to be controlled with high accuracy. However, if the support does not have sufficient drug permeation and diffusion preventing properties, the amount of the drug in the pressure-sensitive adhesive is required for the drug to permeate and diffuse into the support. However, it may be difficult to control the dose surely, causing side effects due to overdose, and causing problems related to human life such as insufficient treatment due to insufficient administration.
[0006]
[Problems to be solved by the invention]
At present, an aluminum vapor-deposited film, a polyethylene terephthalate (PET) film, and the like having high chemical resistance and gas barrier properties are used as a support for a drug for transdermal administration having excellent drug penetration prevention properties. However, since they do not have the flexibility to follow the movement of the skin, there are problems such as easy peeling after being attached to the skin.
[0007]
Examples of the film excellent in drug penetration prevention and drug retention include polyacrylonitrile film, nylon film, liquid crystal polymer film, polyvinyl alcohol film, etc., but these are in the molecule. Since it has an aromatic functional group and a polar functional group, and has high molecular cohesion and crystallinity, there are problems such as small elongation and poor flexibility.
[0008]
On the other hand, as a support for a medicinal agent for transdermal administration with improved flexibility, there is one obtained by laminating a soft polyvinyl chloride (soft PVC) film on a PET film having a thickness of 1.5 to 3.5 μm. However, although the flexibility of the PET film increases as it becomes thinner, there are problems such as a decrease in mechanical strength and a decrease in laminate processability.
[0009]
Moreover, although the support body which has the outstanding softness | flexibility can be obtained from soft PVC, polyethylene, a polypropylene, a polyurethane, etc., since these have the low penetration prevention property of a drug, they cannot be used for TTS.
[0010]
In view of the above, it is an object of the present invention to provide a support for a transdermal drug that is excellent in flexibility and drug penetration prevention property.
[0011]
[Means for Solving the Problems]
The gist of the present invention resides in that the support for a drug for transdermal administration is composed of an ethylene-tetrafluoroethylene copolymer film having a thickness of 5 to 50 μm.
The present invention is described in detail below.
[0012]
The ethylene-tetrafluoroethylene copolymer (ETFE) film used in the present invention has a thickness of 5 to 50 μm. When the thickness is less than 5 μm, handling becomes difficult, and when it exceeds 50 μm, the flexibility becomes insufficient, so the range is limited. Preferably, it is 15-30 micrometers. Examples of the ETFE film include a film manufactured by Daikin Industries, Ltd., a film manufactured by Asahi Glass Co., Ltd., and a film manufactured by Mitsui DuPont Fluorochemical Co., Ltd.
[0013]
The support for a drug for transdermal administration of the present invention can be made into a drug for transdermal drug application, for example, by applying an adhesive layer containing a drug on the surface of the ETFE film.
The drug is not particularly limited as long as it is percutaneously absorbed into the body and exhibits a medicinal effect. For example, an anti-inflammatory agent, an analgesic agent, a local stimulant, an antihistamine, a local anesthetic, blood circulation promotion Agents, hypnotic sedatives, tranquilizers, antihypertensive agents, antibacterial agents, coronary vasodilators, and the like.
[0014]
The anti-inflammatory agent and analgesic are not particularly limited, and examples include indomethacin, ketoprofen, flurbiprofen, salicylic acid monoglycol ester, isosorbide dinitrate, and the like.
The antihistamine is not particularly limited, and examples thereof include diphenhydramine hydrochloride, isothibenzil hydrochloride, chlorpheniramine and the like.
The coronary vasodilator is not particularly limited, and examples thereof include nitroglycerin, nitroglycol, pentaerythritol tetranitrate, and isosorbide dinitrate.
[0015]
The polymer used as the main component of the pressure-sensitive adhesive of the pressure-sensitive adhesive layer is not particularly limited. For example, natural rubber, polyisoprene, polyisobutylene, silicon rubber, styrene-isoprene block copolymer, acrylic acid ester, methacrylic acid Examples include esters.
In the present invention, additives such as a tackifier, a softener, a filler, and an antioxidant may be added to the polymer.
[0016]
The method for applying the adhesive layer containing the drug is not particularly limited. For example, the method for applying the adhesive layer containing the drug by dissolving it in a solvent, the adhesive containing the drug Examples thereof include a method of coating after melting the agent layer and extruding it from the extruder into a sheet. The pressure-sensitive adhesive layer containing the drug may be applied directly to the support for a transdermal drug, for example, or may be applied to a release paper. When the adhesive layer containing the drug is applied to a release paper, a transdermal drug can be obtained by pasting the release paper after coating to the support for a transdermal drug. .
[0017]
The second gist of the present invention is that the support for a drug for transdermal administration consists of a film in which an ethylene-tetrafluoroethylene copolymer film having a thickness of 5 to 50 μm and a soft plastic film are laminated. There is a place to do.
[0018]
The ethylene-tetrafluoroethylene copolymer (ETFE) film has a thickness of 5 to 50 μm. When the thickness is less than 5 μm, handling becomes difficult, and when it exceeds 50 μm, the flexibility becomes insufficient, so the range is limited. Preferably, it is 5-15 micrometers. When it is less than 5 μm, it becomes easy to cut and it becomes difficult to bond with a soft plastic film, and when it exceeds 15 μm, the flexibility becomes insufficient.
[0019]
The soft plastic film is not particularly limited. For example, soft polyvinyl chloride (soft PVC), polyurethane, low-density polyethylene, polyolefin-based thermoplastic elastomer, styrene-based thermoplastic elastomer, urethane-based thermoplastic elastomer, soft polyurethane-poly A vinyl chloride graft copolymer (PU-PVC) etc. can be mentioned. Preferred are olefin-based thermoplastic elastomers, styrene-based thermoplastic elastomers, PU-PVC and the like because they are excellent in flexibility.
[0020]
Since the ETFE film used in the present invention is a fluororesin having a low polarity and has low compatibility with hydrocarbon compounds, the support for transdermal drug delivery of the present invention has a drug penetration prevention property, drug retention property. Etc.
[0021]
In addition, the fluorine resin has higher flexibility than a film made of a crystalline polymer such as PET, and examples of such a fluorine resin include polytetrafluoroethylene (PTFE) and polychlorotrimethyl. Fluoroethylene (PCTFE), polyvinylidene fluoride (PVDF), and the like can be mentioned. Among them, the ETFE film is a copolymer and is particularly difficult to form a crystal structure. The support for transdermal drug delivery is excellent in flexibility.
[0022]
【Example】
Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
[0023]
Example 1
A 25 μm ETFE film (manufactured by Daikin Industries, Ltd.) was used as a support for transdermal drug delivery.
[0024]
Evaluation (1) Flexibility According to JIS K 6732 “Agricultural polyvinyl chloride film”, a tensile test was performed and a 10% modulus was measured.
○: Less than 2.5 N / m Δ: 2.5 N / m or more, less than 4.0 N / m ×: 4.0 N / m or more
(2) A drug-containing adhesive was applied to the support film for preventing drug penetration and diffusion, and allowed to stand at 50 ° C. for 1 week in a sealed glass container, and then the residual amount of glycolic salicylate in the adhesive was measured. . The pressure-sensitive adhesive was prepared according to the following formulation.
What added 10 weight part of hydrogenated rosin acid ester to 100 weight part of natural rubber was dissolved in toluene so that it might become 20 weight%. Furthermore, the salicylate glycol was dissolved to 2% by weight. This drug-containing pressure-sensitive adhesive solution was applied onto a release paper so that the thickness after drying was 15 μm, and the solvent was removed by drying.
○: 95% or more, 100% or less Δ: 90% or more, 95% or less ×: less than 90% Evaluation results are shown in Table 1.
[0026]
Example 2
ETFE film (Daikin Kogyo Co., Ltd.) is biaxially stretched and bonded to a film with a thickness of 12 μm and a soft plastic film with a thickness of 80 μm formed from an olefinic thermoplastic elastomer (manufactured by Nippon Synthetic Rubber Co., Ltd.). Created the body.
The above olefinic thermoplastic elastomer film was prepared by a T-die extruder. On the ETFE film, an adhesive (AG-9014A manufactured by Asahi Glass Co., Ltd.) was coated so that the thickness after drying was 3 μm, and bonded to the olefinic thermoplastic elastomer film. It was placed and the reaction of the adhesive was promoted to obtain the intended support for transdermal drug delivery.
Evaluation was performed in the same manner as in the method described in Example 1. In the evaluation of the drug penetration diffusion preventing property, the drug-containing pressure-sensitive adhesive was applied to the surface of the ETFE film. The evaluation results are shown in Table 1.
[0027]
Comparative Example 1
A polyurethane-polyvinyl chloride graft copolymer (PU-PVC) film and a 3.5 μm thick PET film (manufactured by Toray Industries, Inc.) were bonded together to obtain a support for transdermal drug delivery.
The PU-PVC film was molded so that 1.5 parts by weight of a Ca—Zn stabilizer was added to 100 parts by weight of Dominus K-650F (manufactured by Tosoh Corporation) and the thickness was 90 μm with a calender roll. After drying the adhesive on the PET film with a gravure coater so as to have a thickness of 1 to 2 μm and drying, the PU-PVC film was bonded. The above adhesive was prepared by adding 2 parts by weight of an isocyanate curing agent U-4000 (manufactured by Seiko Kasei Co.) to 100 parts by weight of UD 417 (solid content 25%, manufactured by Seiko Kasei Co., Ltd.). Evaluation was performed in the same manner as in the method described in Example 1. In the evaluation of the drug penetration diffusion preventing property, the drug-containing pressure-sensitive adhesive was applied to the surface of the ETFE film. The evaluation results are shown in Table 1.
[0028]
Comparative Example 2
A film for transdermal administration was prepared and evaluated in the same manner as in Comparative Example 1 using a nylon film (made by Teijin Limited) having a thickness of 5 μm instead of the PET film having a thickness of 3.5 μm in Comparative Example 1.
[0029]
Comparative Example 3
The olefinic thermoplastic elastomer film of Example 1 was used as a support for a transdermal drug. The evaluation results are shown in Table 1.
[0030]
Comparative Example 4
A urethane-based thermoplastic elastomer film (Nisshinbo Co., Ltd., thickness 40 μm) was used as a support for a transdermal drug. The evaluation results are shown in Table 1.
[0031]
[Table 1]

[0032]
【The invention's effect】
The support for a drug for transdermal administration of the present invention has the above-described configuration, is excellent in preventing penetration of the drug, can stably hold the drug in the pressure-sensitive adhesive layer, and can control the dosage with high accuracy. It is possible to provide a transdermal drug that does not need to increase the adhesive strength of the adhesive and does not damage the skin when it is peeled off because it has the flexibility to follow the movement of the skin. it can.

Claims (2)

A support for a drug for transdermal administration, comprising an ethylene-tetrafluoroethylene copolymer film having a thickness of 5 to 50 µm. A support for transdermal drug delivery, comprising a film in which an ethylene-tetrafluoroethylene copolymer film having a thickness of 5 to 50 µm and a soft plastic film are laminated.