JPH07215844A - Skin cataplasm sheet - Google Patents

Abstract

PURPOSE:To obtain a skin cataplasm sheet having both medicinal migration and dermal irritancy preventabilities, also leaving no paste on the skin after applied. CONSTITUTION:This skin cataplasm sheet is obtained by laminating one side of a substrate composed of, a polystyrene film of 30-200mum thickness consisting of a styrene homopolymer 1-18g/10min in melt flow rate with a tack agent layer containing a medicine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a skin patch sheet which has both drug transfer preventive property and skin irritation preventive property and does not cause adhesive residue after application.

[0002]

2. Description of the Related Art In recent years, for the purpose of administering a drug into the body, attention has been paid to a skin patch that is easy to use and has a long lasting pharmacological effect, and various skin patch sheets have been used. The skin patch sheet is composed of a support for maintaining a sheet-like form and an adhesive layer containing a drug. The support needs to follow the movement of the skin, and the pressure-sensitive adhesive layer needs to have good adhesiveness when attached to the skin, compatibility with the skin, and appropriate elasticity.

It is known that a vinyl chloride resin is used for the support and a diene copolymer, particularly a diene block copolymer, is used for the pressure-sensitive adhesive layer in order to have the above characteristics. (JP-A-54-138124).

Regarding the skin patch sheet, in addition to the above-mentioned properties, drug transfer preventing property, skin irritation preventing property and adhesive property between the support and the pressure-sensitive adhesive layer are important. If the drug transfer preventive property is not sufficient, there arises a problem that the drug permeates and diffuses into the support, causing the support to swell and deteriorate. Further, when the drug migrates from the pressure-sensitive adhesive layer to the support during storage or application, the drug diffusively moves in the support and the drug is leached from the surface opposite to the pressure-sensitive adhesive layer, or the drug content is reduced. It may occur and a therapeutically effective amount of the drug may not be released, which is a fatal defect for the skin patch sheet.

If the skin irritation prevention property is not sufficient, an infant, due to irritation of the skin surface to be applied such as stuffiness or rash of the skin,
It is difficult to use for people with weak skin such as old people. Further, if the adhesive strength between the support and the pressure-sensitive adhesive layer is not sufficient, the adhesive remains on the skin when peeled off after application, that is, so-called adhesive residue occurs, and the product value is significantly reduced.

As a means for obtaining the drug transfer preventing property, there is a method of providing a drug transfer preventing layer (barrier layer) on the support surface, and for example, polyethylene terephthalate (PET).
Aluminum foil is used as a barrier layer. Further, Japanese Patent Application Laid-Open No. 2-29081 discloses a technique using a polyolefin film such as polyethylene or polypropylene which has been subjected to a fluorine treatment.
Japanese Patent No. 915 discloses a technique using a fluororesin (polychlorotrifluoroethylene copolymer).

However, when PET or aluminum foil is used for the barrier layer, the flexibility is insufficient and there is a problem in use. The one using a fluorine-treated polyolefin film has a thin treatment layer and a rough treatment density, so that the drug transfer preventing property is not sufficient. Further, the one using a fluororesin has a disadvantage that the support is not sufficiently flexible, the adhesive force between the pressure-sensitive adhesive layer and the barrier layer is low, and the adhesive remains on the skin.

As means for obtaining skin irritation prevention, Japanese Patent Application Laid-Open No. 62-230720 discloses a technique in which a support having moisture permeability is used and the support is subjected to perforation treatment or porosity treatment. . However, with these methods, the skin irritation preventive property can be obtained, but at the same time the drug transfer preventive property cannot be obtained.

[0009]

In view of the above, the present invention has both drug transfer prevention properties and skin irritation prevention properties,
Moreover, it is an object of the present invention to provide a skin patch sheet which does not cause adhesive residue after application.

[0010]

The gist of the present invention is to provide a skin patch sheet which is a homopolymer of styrene and has a melt flow rate (hereinafter referred to as "MFR") of 1 to 18 g / 10.
The adhesive layer containing a drug is laminated on one side of a support made of a polystyrene film having a thickness of 30 to 200 μm.

The polystyrene film constituting the support of the skin patch sheet according to the present invention is a homopolymer of styrene. Styrene-butadiene rubber (SBR) and butadiene rubber (BR) having a rubber component called impact-resistant (HI) polystyrene cannot be used in the present invention because they are inferior in drug transfer prevention property. Among the diene block copolymers which are the main components of the adhesive layer, styrene-isoprene-styrene triblock copolymer (SIS) and styrene-ethylene / butylene-styrene block copolymer (SEBS) are typical. Since the main component of these is styrene, the polystyrene film has good affinity with these pressure-sensitive adhesive layers.

The MFR of the polystyrene film is J
It is in the range of 1 to 18 g / 10 minutes as measured according to IS K 7210 at 200 ° C. and 5 kg. If the MFR is smaller than this range, the film processability and texture will be poor, and if it is larger than this range, the effect of preventing drug migration will be poor, so the range is limited to the above range. Preferably 1.0-10 g
/ 10 minutes.

In the polystyrene film according to the present invention, due to the above MFR limitation, the gap between polystyrene molecules is
Although it is too small for the drug molecules to pass through, it has a size that allows water molecules to pass through, so that it has excellent drug transfer prevention properties and also has moisture permeability.

The thickness of the polystyrene film is 30 to
It is 200 μm. If the thickness is less than 30 μm, the strength will be insufficient,
If it is thicker than 200 μm, the flexibility is insufficient, and thus the range is limited. It is preferably 50 to 150 μm.

The polystyrene film is extruded using a T-die to obtain a cylinder temperature of 180 to 22.
It can be easily prepared at 0 ° C. and a T-die temperature of 200 to 220 ° C.

The pressure-sensitive adhesive used in the pressure-sensitive adhesive layer of the present invention is not particularly limited, and examples thereof include styrene-isoprene-styrene block copolymer rubber, styrene-butadiene-styrene block copolymer rubber, styrene-butadiene rubber, polybutene rubber. Rubber-based materials such as polyisoprene rubber, butyl rubber, silicone rubber, natural rubber, and synthetic isoprene rubber; poly (meth) acrylic, polyvinyl ether,
Examples thereof include synthetic resin-based materials such as polyurethane, polyester, polyamide, and ethylenic copolymer. Also,
A tackifier resin, a liquid rubber, a softening agent or the like may be added to these to adjust the glass transition temperature, and those having desired adhesive properties and drug diffusion mobility can be used.

The drug contained in the pressure-sensitive adhesive layer of the present invention is not particularly limited as long as it is a drug suitable for transdermal administration, and examples thereof include anti-inflammatory analgesics, hypnotic sedatives, tranquilizers, antihypertensive agents, antihypertensive diuretics. Agents, antibiotics, anesthetics, antibacterial substances, antifungal substances,
Vitamins, antiepileptics, coronary vasodilators, antihistamines, antitussives, sex hormones, antidepressants, cerebral circulation improving agents,
Antiemetics, antitumor agents, biopharmaceuticals (polypeptides, etc.) and the like can be mentioned. According to the present invention, among these drugs, nandrolone decanoate (a steroidal anti-inflammatory drug), nitroglycerin (a coronary vasodilator), and propatil nitrate (the same drugs that are easily volatilized or sublimated during storage). ), Isosorbide dinitrate (same), salicylic acid (anti-inflammatory analgesic), methyl salicylate (same), 1-menthol (same)
Etc. can also be used.

The drug content in the pressure-sensitive adhesive layer varies depending on the type of drug, the type of pressure-sensitive adhesive and the disease to be treated, but is preferably in the range of 0.1 to 30% by weight in the pressure-sensitive adhesive. The thickness of the pressure-sensitive adhesive layer is 5 to 500 μm, preferably 10 to 30 in consideration of skin adhesiveness, continuous release of the drug to the skin surface, and the like.
The range of 0 μm is preferable.

[0019]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. Example 1 MFR 7.5 g / 10 min polystyrene (Styron 666 manufactured by Asahi Chemical Industry Co., Ltd.) was extruded at a cylinder temperature of 180 to 220 ° C. and a T die temperature of 220 ° C. using a uniaxial extruder equipped with a T die. It was wound up to obtain a polystyrene film having a thickness of 40 μm. The adhesive containing a drug is a styrene-isoprene-styrene block copolymer (Califlex TR1107 manufactured by Shell Chemical Co.) 3
0 parts by weight, terpene resin (YSHARA CHEMICAL CO., LTD.
35 parts by weight of resin 115, 10 parts by weight of liquid paraffin, and 5 parts by weight of 1-menthol were mixed and obtained. Next, the adhesive (containing a drug) was applied to a release paper to a thickness of 10 μm and attached to a film to prepare a skin patch sheet.

Examples 2 to 4 The thickness of the polystyrene film is shown in Table 1 (μm).
A skin patch sheet was prepared in the same manner as in Example 1 except for the above.

Example 5 Same as Example 1 except that polystyrene having a MFR of 16 g / 10 min (HF-55, manufactured by Mitsubishi Kasei Polytech Co., Ltd.) was used at a cylinder temperature of 170 to 210 ° C. and a T die temperature of 210 ° C. Then, a skin patch sheet was prepared.

Example 6 Polystyrene (Styron G8259 manufactured by Asahi Kasei Corporation) having a MFR of 1.1 g / 10 min was used, and the cylinder temperature was 18.
A skin patch sheet was prepared in the same manner as in Example 1 except that the temperature was 0 to 230 ° C and the T-die temperature was 230 ° C.

Comparative Examples 1-2 A skin patch sheet was prepared in the same manner as in Example 1 except that the thickness of the polystyrene film was changed to that shown in Table 1.

Comparative Example 3 A skin patch sheet was prepared in the same manner as in Example 5 except that polystyrene having a MFR of 20 g / 10 min (679R manufactured by Asahi Kasei Corporation) was used. Comparative Example 4 Polystyrene blended with a rubber component (4 manufactured by Asahi Kasei Corporation)
A skin patch sheet was prepared in the same manner as in Example 6 except that 75D) was used.

COMPARATIVE EXAMPLE 5 100 μm thickness with 40 parts by weight of DOP added as a plasticizer
A skin patch sheet was prepared in the same manner as in Example 1 except that the PVC film of m was used. Comparative Example 6 PE having a thickness of 75 μm was used instead of the polystyrene film.
Other than using T film (Toray Lumirror),
A skin patch sheet was prepared in the same manner as in Example 1.

The skin patch sheet obtained as described above was evaluated, and the results are also shown in Table 1. The measurement method and evaluation method were as follows. The unit of thickness in Table 1 is μm. (1) MFR is 2 according to JIS K 7210.
It was measured at 00 ° C. and 5 kg. The unit is g / 10 minutes. (2) The drug transfer prevention property is as follows. A sheet coated with a drug-containing adhesive is sealed with aluminum foil and left at 40 ° C. for 6 months.
The adhesive was peeled off and the drug concentration was measured by gas chromatography. When 90% or more of the drug remained in the adhesive layer, it was evaluated as ◯, and when not remained, it was evaluated as x. (3) For skin irritation prevention, the skin patch sheet obtained in each of the examples and comparative examples was cut into a size of 3 cm in diameter, stuck on the inner side of the upper arm for 24 hours, and then peeled off, and 8 hours after peeling The skin surface at that time was visually evaluated, and the results are shown by x when erythema was present and by o when it was not.

(4) Adhesiveness with the adhesive is evaluated as follows: when the sheet is placed on a Bakelite plate and peeled off after 1 hour, the adhesive is not marked with ∘, a slight residue is marked with Δ, and the adhesive residue is marked with ×. Indicated by. (5) The strength is measured according to JIS K 6871, and x is less than 1500 N / m, 1500 to 300
△ for 0 N / m, ○ for over 3000 N / m
Indicated by. (6) For flexibility, cut into a size of 2 cm in diameter, affixed to the upper arm, observe the state of the sheet after 8 hours of daily life, and ○ when peeling and no floating, Δ when only floating, The case where there was peeling was indicated by x.

[0028]

[Table 1]

[0029]

According to the present invention, it is possible to obtain a skin patch sheet which has both drug transfer preventive property and skin irritation preventive property and does not cause adhesive residue after application.

Claims (1)

[Claims] 1. A styrene homopolymer having a melt flow rate of 1 to 18 g / 10 minutes and a thickness of 30 to 20.
A skin patch sheet comprising a support made of a polystyrene film having a thickness of 0 μm and a pressure-sensitive adhesive layer containing a drug laminated on one surface of the support.