JPS6320410B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a therapeutic adhesive tape or sheet suitable for treating skin diseases, anti-inflammatory, analgesic, etc. For transdermal absorption of drugs, increasing the water content of the stratum corneum of the skin makes it possible to utilize not only the hair follicle-sebaceous system but also the absorption route that passes directly through the stratum corneum, allowing for effective skin absorption. Can be done. Therefore, as a treatment for skin diseases, occlusive dressing therapy (ODT therapy), which involves applying an external medicine such as an ointment to the skin and covering it with a film to effectively absorb the medicine, has recently become popular. However, with this occlusive bandage therapy, not only is it troublesome to attach the film to the affected area, but it is bulky, easily peels off, and cannot adhere tightly to the affected area when the area of the affected area is large or the shape of the affected area is complex. There were drawbacks such as being difficult. In order to eliminate these drawbacks, therapeutic tapes are commercially available in which a pressure-sensitive adhesive containing a drug is coated on an impermeable film. but,
Pressure-sensitive adhesives used in such tapes must not come off during use and must be easy to remove from the skin after use, so pressure-sensitive adhesives are usually used to balance adhesion. It is necessary to use a suitable crosslinking agent when making the adhesive. However, the use of a cross-linking agent has the disadvantage that the drug's ability to transfer to the skin deteriorates over time, making it impossible to effectively utilize the drug contained in the pressure-sensitive adhesive layer and gradually decreasing the therapeutic effect. . The purpose of the present invention is to solve the above-mentioned drawbacks, and to provide a therapeutic tape that allows the drug contained in the pressure-sensitive adhesive layer to efficiently transfer to the skin, and that transferability does not change over time and always has a stable therapeutic effect. Or to provide seats. The gist of the invention is that on one side of the base material, the general formula CH ₂ =
Acrylic acid ester represented by CHCOOR ₁ (in the formula, R ₁ is an alkyl group having 4 or more carbon atoms) or (and) the general formula

Copolymerization of a methacrylic acid ester represented by the formula (in which R ₂ is an alkyl group having 3 or more carbon atoms) and an α,β-ethylenically unsaturated carboxylic acid having one or two carboxyl groups. The present invention relates to a therapeutic adhesive tape or sheet, characterized in that it is provided with a pressure-sensitive adhesive layer consisting of a combined metal crosslink, magnesium chloride and a prednisolone drug. Next, the therapeutic adhesive tape or sheet of the present invention will be explained in more detail. The base material used in the present invention may be a flammable film or sheet such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, soft polyvinyl chloride, or cellophane, or a film or sheet whose surface has been treated with corona discharge, etc. etc. are preferably used. The thickness of the base material is preferably in the range of 50 to 100 microns. A pressure sensitive adhesive layer is provided on the substrate. The pressure-sensitive adhesive layer has the general formula CH ₂ =CHCOOR ₁ (wherein
R ₁ is an acrylic ester represented by (alkyl group having 4 or more carbon atoms) or (and) a general formula

Copolymerization of a methacrylic acid ester represented by the formula (in which R ₂ is an alkyl group having 3 or more carbon atoms) and an α,β-ethylenically unsaturated carboxylic acid having one or two carboxyl groups. It consists of a combined metal crosslinked product, metal chloride, and a drug. As the acrylic ester, for example, n
-butyl acrylate, iso-butyl acrylate, tert-butyl acrylate, isoamyl acrylate, 2-ethylhexyl acrylate, n
- Octyl acrylate, lauryl acrylate, etc. are preferred. Examples of the methacrylic ester include methyl methacrylate, butyl methacrylate, n
Preferred are -octyl methacrylate, 2-ethylhexyl methacrylate, lauryl methacrylate, and the like. Suitable examples of the α,β-ethylenically unsaturated carboxylic acid include acrylic acid, methacrylic acid, maleic anhydride, and itaconic acid. As the acrylic ester, R ₁ has 4 carbon atoms
Those having the above alkyl group are used, and as the methacrylic acid ester, those having R ₂ having an alkyl group of 3 or more carbon atoms are used.
This is because if the number of carbon atoms in R ₁ and R ₂ is less than these, the adhesive cannot exhibit its performance as a pressure-sensitive adhesive. The copolymer in the present invention includes a copolymer of the acrylic ester and an α,β-ethylenically unsaturated carboxylic acid, and a copolymer of the methacrylic ester and an α,β-ethylenically unsaturated carboxylic acid. A copolymer of the acrylic ester, methacrylic ester, and α,β-ethylenically unsaturated carboxylic acid may be used. Although the copolymer has excellent performance as a pressure-sensitive adhesive, it is too sticky as it is and tends to cause skin irritation when used in the pressure-sensitive adhesive layer of a therapeutic adhesive tape or sheet. . Therefore, in the present invention, by forming a metal crosslinked product of the copolymer, when used as a pressure-sensitive adhesive, it is able to adhere well to the skin and is also easy to peel off from the skin. To obtain the metal crosslinking agent for the copolymer, the copolymer and the metal crosslinking agent are brought into contact in a solution of the metal crosslinking agent. Examples of metal crosslinking agents include oxides of metals such as magnesium, calcium, zinc, barium, aluminum, and tin, hydroxides of these metals, and organic acid salts of these metals such as acetates and stearates. used. The metal crosslinked product of the copolymer serves as a pressure-sensitive adhesive that has both adhesion to the skin and ease of peeling. However, when a therapeutic drug is contained in the metal crosslinked copolymer, the transferability of the drug to the skin tends to deteriorate over time. Prednisolone is used as the drug in the present invention, but this drug uses a metal crosslinked product of the copolymer as a pressure-sensitive adhesive, and when it is included in this, its transferability to the skin tends to gradually deteriorate. . In the present invention, as a result of various studies in view of this point, we found that using magnesium chloride allows the drug to transfer efficiently from the pressure-sensitive adhesive layer to the skin, and that the transferability does not change over time and is stable. I discovered that it can become a thing. It is assumed that the action of magnesium chloride in this case is to coordinate with the functional group of the drug and inhibit its interaction with the metal crosslinking agent, thereby stabilizing the migration of the drug from the pressure-sensitive adhesive layer to the skin. be done. The pressure-sensitive adhesive layer can be formed by applying a solution of the metal crosslinked copolymer, magnesium chloride, and a drug dissolved in a solvent onto the base material, and then drying and removing the solvent. The method will be adopted as appropriate. Furthermore, if the copolymer and the metal crosslinking agent are dissolved in a solvent when forming the pressure-sensitive adhesive layer, a metal crosslinked product of the copolymer will be formed in the solvent. It is not necessary to create a metal bridge. The amount of metal chloride used is determined appropriately depending on the amount of carboxyl groups in the metal crosslinked product of the copolymer and the amount of the drug. The amount of the drug contained in the pressure-sensitive adhesive varies depending on the thickness of the pressure-sensitive adhesive layer, the type of drug, etc., but is 1 μg to 5 mg per 1 cm ² of the pressure-sensitive adhesive layer.
A range of is preferred. The therapeutic adhesive tape or sheet of the present invention is
With the above-described structure, the drug contained in the pressure-sensitive adhesive layer is efficiently transferred to the skin, and its transferability does not change over time, so that it always has a stable therapeutic effect. The present invention will be explained below with reference to Examples. Example 1 475 g of 2-ethylhexyl acrylate, 25 g of acrylic acid, 500 g of ethyl acetate, and 0.3 g of benzoyl peroxide as a polymerization initiator were placed in a separable flask equipped with a stirrer, a thermometer, a cooling tube, and a nitrogen introduction tube, and a nitrogen stream was introduced. Polymerization was carried out at 70°C for 18 hours to obtain a copolymer. The viscosity of this copolymer is 38000
It was centipoise (25℃). For 100 g of the above copolymer, 3 g of a separately prepared magnesium acetate solution (weight ratio of magnesium acetate: methanol = 1:9) and a magnesium chloride solution (weight ratio of magnesium chloride: methanol =
1:9) and 15 g of prednisolone solution (prednisolone:methanol = 1:49 by weight) were added and dissolved, and the pressure-sensitive adhesive was placed on a 60μ thick polyethylene film that was subjected to corona discharge treatment.
It was applied to a thickness of 50μ and dried at 70°C for 20 minutes to obtain a therapeutic adhesive tape. This therapeutic adhesive tape contained 30 μg of prednisolone per cm ² . Immediately after manufacturing of this therapeutic adhesive tape and at 20°C.
When we measured the amount of prednisolone extracted by immersing the sample in physiological saline at 37℃ for 24 hours after leaving it for 6 months, we found that the amount of extracted prednisolone did not change as shown in Table 1. .

[Table] Comparative Example 1 3 g of magnesium acetate solution and 15 g of prednisolone solution were added and dissolved in 100 g of the copolymer obtained in Example 1, and a therapeutic adhesive tape was prepared in the same manner as in Example 1, and the amount extracted was measured. As shown in Table 2, it was observed that the amount of prednisolone extracted was significantly reduced.

[Table] Example 2 A therapeutic adhesive tape was obtained in the same manner as in Example 1 except that butyl methacrylate was used instead of 2-ethylhexyl acrylate. The amount of brednisolone extracted from this therapeutic adhesive tape was measured, and the results were similar to those in Example 1.

Claims (1)

[Scope of Claims] 1. Acrylic ester represented by the general formula CH ₂ =CHCOOR ₁ (in the formula, R ₁ is an alkyl group having 4 or more carbon atoms) or (and) the general formula [Formula] (In the formula, R ₂ is an alkyl group having 3 or more carbon atoms) A metal copolymer of a methacrylic acid ester and an α,β-type ethylenically unsaturated carboxylic acid having one or two carboxyl groups. A therapeutic adhesive tape or sheet, characterized in that it is provided with a pressure-sensitive adhesive layer consisting of a crosslinked product, magnesium chloride and a prednisolone drug. 2. The therapeutic adhesive tape or sheet according to claim 1, wherein the metal chloride is magnesium chloride. 3. The therapeutic adhesive tape or sheet according to claim 1, wherein the metal chloride is calcium chloride. 4. The therapeutic adhesive tape or sheet according to claim 1, wherein the metal chloride is zinc chloride.