JPH0363530B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to therapeutic adhesive tapes or sheets. A therapeutic adhesive tape or sheet, which is a plaster with a thin layer of pressure-sensitive adhesive mixed with a therapeutic drug mixed into the base material, is applied to the skin, and the drug oozes from the pressure-sensitive adhesive layer for local treatment. is attracting attention as a new treatment method to replace the conventional occlusive dressing therapy (ODT therapy). The performance required for such therapeutic adhesive tapes or sheets is that the pressure-sensitive adhesive does not cause strong irritation to the skin, and that it is easy to apply to the skin and does not cause pain due to adhesive residue or excessive adhesive force when removed. In addition, there is no mutual chemical interaction between the pressure-sensitive adhesive and the drug, and the drug easily oozes out from the adhesive to the surface so that a sufficient medicinal effect can be obtained. Conventionally, pressure-sensitive adhesives used for this purpose,
A copolymer consisting of a monomer having a carboxyl group and an acrylic ester or (and) a methacrylic ester is used, and this pressure-sensitive adhesive layer contains a drug. If an acidic and unstable substance is used, the drug will deteriorate extremely quickly due to heat, and if it is a colored drug, discoloration may be observed, and the internal cohesive force may be insufficient, making it difficult to peel off the drug after it has been applied. When doing so, there was a risk that the pressure-sensitive adhesive would adhere to the adhesive surface (adhesive residue). The present invention has been made with the aim of eliminating such drawbacks, and its gist is to provide a therapeutic plaster that has a pressure-sensitive adhesive layer containing a drug on the base material. In the adhesive tape or sheet, the pressure-sensitive adhesive is (A) an α,β unsaturated carboxylic acid having 1 or 2 carboxyl groups;
A water-insoluble copolymer containing 0.1 to 20% by weight of (B) an acrylic ester or (and) a methacrylic ester as a copolymerization component, wherein the carboxyl group in the copolymer contains an alkali metal or (and) ) A therapeutic adhesive tape or sheet characterized by being a salt of an alkali metal. Next, the therapeutic adhesive tape or sheet of the present invention will be explained in more detail. The base material in the present invention includes polyethylene,
Flexible materials such as polypropylene, ethylene-vinyl acetate copolymer, soft polyvinyl chloride, and cellophane are suitable, and the thickness of the base material is
A range of 0.02 to 0.15 mm is preferred. If necessary, the base material is subjected to corona discharge treatment, plasma treatment, primer coating, etc. in order to increase the adhesion with the pressure-sensitive adhesive. The pressure-sensitive adhesive has (A) 1 to 2 carboxyl groups.
It consists of a water-insoluble copolymer containing an individual α,β unsaturated carboxylic acid and (B) an acrylic ester or (and) a methacrylic ester as copolymerization components. As the component (A), for example, acrylic acid, methacrylic acid, crotonic acid, maleic acid, itaconic acid, etc. are suitable, and the copolymerization amount is 0.1 to 1.
It is said to be 20% by weight. Component (B) includes ester residues such as methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, n-
Those having a hexyl group, 2-methylpentyl group, 3-methylpentyl group, 2-ethylbutyl group, n-octyl group, isooctyl group, 2-ethylhexyl group, nonyl group, n-decyl group, lauryl group, etc. are used. Ru. Particularly suitable acrylic esters include ethyl acrylate, n-butyl acrylate,
Isobutyl acrylate, isoamyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, lauryl acrylate, etc., and methacrylic acid esters include methyl methacrylate, butyl methacrylate, 2-ethylhexyl methacrylate, n-octyl methacrylate, lauryl methacrylate, etc. . In addition to components (A) and (B), the copolymer may contain (C) another monomer copolymerizable with these components as a copolymerization component. As the component (C), for example, acrylamide,
Vinyl acetate, acrylonitrile, styrene, vinyl chloride, vinylidene chloride, ethylene, propylene, butadiene, isoprene, and the like are suitable for use. A copolymer containing the components (A) and (B) as copolymerization components,
Alternatively, in order to obtain a copolymer containing, in addition to components (A) and (B), (C) another monomer copolymerizable with these components, a common radical polymerization catalyst such as azobis Although solution polymerization, emulsion polymerization, suspension polymerization, etc. may be carried out by using a peroxide-based compound or a peroxide-based compound, solution polymerization is optimal in consideration of the subsequent steps of mixing and dissolving the drug. For example, add the above (A), (B) components and optionally (C) component into a reaction container, add a solvent such as ethyl acetate, and add about 60% by weight.
Prepare a concentrated solution, replace the atmosphere in the reaction vessel with nitrogen gas, raise the temperature while stirring, and at a temperature of 60 to 80°C, drop or divide a solution in which the radical generating catalyst is dissolved in the same solvent. Polymerization is completed in 10 to 20 hours by adding only the solvent as the viscosity increases and controlling the viscosity. The copolymers thus obtained are only unsatisfactory as pressure-sensitive adhesives for therapeutic adhesive tapes or sheets. The reason is,
Such copolymers lack internal cohesive strength, which may cause the pressure-sensitive adhesive to stick to the adhesive surface (adhesive residue) when the adhesive is peeled off after application. Copolymers that are acidic and unstable are often used, but since copolymers have carboxyl groups, they have problems such as being easily altered by heat of about 60 to 80 degrees Celsius, and easily discoloring with colored drugs. This is because it has. For this purpose, in the present invention, the carboxyl group in the copolymer is an alkali metal or/and an alkali metal salt. Examples of the alkali metals and alkali metals used include sodium, potassium, magnesium, and calcium. In addition, to form a salt of an alkali metal or (and) an alkali metal, the copolymer may be added with, for example, lithium hydroxide, sodium ethylate, sodium hydroxide, potassium hydroxide, magnesium hydroxide, magnesium oxide, hydroxide. Calcium or the like may be contacted under appropriate heating conditions. Preferably, 80 mol% or more of the carboxyl groups in the copolymer are salts of alkali metals and/or alkali metals. If the amount is less than 80 mol%, if the drug is acid-unstable, it may discolor when exposed to heat, or the colored drug may discolor. This is because the internal cohesive force of the copolymer tends to be insufficient. Examples of drugs include sodium salicylate,
Mefenamic acid, flufenamic acid, acetylsalicylic acid, indomethacin, etc. are used. The amount of drug varies depending on the thickness of the pressure-sensitive adhesive layer, the type of drug, etc., but is 1 μg or more per 1 cm ² of the pressure-sensitive adhesive layer.
A range of 5 mg is preferred. The pressure-sensitive adhesive is applied to the base material and dried, and then a releasable sheet is pressed through a roll or the like, or a solution of the pressure-sensitive adhesive is first applied onto the surface of the releasable sheet, dried, and then the pressure-sensitive adhesive is applied through a roll. By pressing the substrate onto the adhesive surface, a therapeutic adhesive tape or sheet with a protected pressure-sensitive adhesive layer is obtained. According to the present invention, the pressure-sensitive adhesive is a copolymer containing the components (A) and (B) as copolymerization components, and the carboxyl group in the copolymer is an alkali metal or (and) an alkali metal. Since it is a salt of a similar metal, the pressure-sensitive adhesive has an appropriate internal cohesive force, does not leave adhesive residue on the adhesive surface, and has good exudation properties of the drug.
Furthermore, even if a chemical that is unstable to acids is used, deterioration or discoloration due to heat is prevented, and the chemical does not precipitate on the surface of the pressure-sensitive adhesive layer. Example 1 2-ethylhexyl methacrylate 55g n-butyl acrylate 38g ethyl acrylate 4g acrylic acid 2.5g The above components were placed in a reaction vessel, 0.5g of azobisisobutyronitrile was added as a catalyst, and ethyl acetate was added as a solvent, and the mixture was heated at 70°C. Solution polymerization was performed to obtain a copolymer solution with a solid content of 40% by weight. Next, add ethyl acetate to 100 g of the above copolymer solution.
Add 50g and dissolve uniformly, add 0.898g of sodium ethylate, 10g of ethyl acetate, and ethanol.
The uniformly dispersed mixture was added to 10 g of the mixed liquid. Next, stirring was performed while heating at 70° C. for 1 hour, and 10 g of a 0.68% by weight ethyl acetate-ethanol solution of sodium ethylate was added dropwise. After continuing stirring for 30 minutes, 10 ml of water was added and the pH value was measured and found to be 7.77. In addition, more than 80 mol% of the carboxyl groups in the copolymer were sodium salts. Then this pressure sensitive adhesive solution (solids content 25.4%)
2.54 g of indomethacin was mixed as a drug, and the resulting solution was applied onto a polyethylene film.
It was dried at 70°C for 20 minutes to obtain a therapeutic adhesive tape.
The pressure-sensitive adhesive layer of this therapeutic adhesive tape had a thickness of 63.5 μm, and when it was applied to the skin, it did not peel off, nor did it cause any pain when it was removed after being applied. This therapeutic adhesive tape can be used immediately after manufacturing and at 60°C.
Table 1 shows the results of determining the presence or absence of discoloration of the drug after being left for 7 days, the compatibility of the drug with the pressure-sensitive adhesive, and the presence or absence of deterioration in the quality of the drug exuded from the pressure-sensitive adhesive layer. . The presence or absence of discoloration of the drug was determined from the change in color tone of the pressure-sensitive adhesive layer. In addition, drug exudation was determined by punching a circular test piece with a diameter of 66 mm from a therapeutic adhesive tape and immersing it in a mixture of 25 ml of methanol and 25 ml of water for 24 hours.
The drug was extracted, and the amount of the extracted drug was determined by liquid chromatography. The presence or absence of deterioration of the drug was determined by whether it had the same peak as the standard drug in liquid chromatography.

【table】

[Table] Comparative Example 1 Using the same components as in Example 1, a copolymer solution with a solid content of 40% by weight was obtained in the same manner as in Example 1. Next, using this copolymer solution, 2.54 g of indomethacin was mixed in the same manner as in Example 1, and this solution was applied onto a polyethylene film and dried at 70° C. for 20 minutes to obtain a therapeutic adhesive tape. The drug in this therapeutic adhesive tape is 7°C at 60°C.
Discoloration was observed after being left for one day, as the color tone of the pressure-sensitive adhesive layer changed to dark brown. Furthermore, when the drug was extracted in the same manner as in Example 1 and this extract was measured using liquid chromatography, there was no difference from the standard drug peak immediately after manufacture, but after leaving it at 60°C for 7 days. In the case of , the sample peaks were at two locations, and it was confirmed that the quality had clearly changed.

Claims (1)

[Scope of Claims] 1. A therapeutic adhesive tape or sheet that is a plaster having a pressure-sensitive adhesive layer containing a drug on a base material, wherein the pressure-sensitive adhesive has (A) 1 to 2 carboxyl groups. alpha, beta unsaturated carboxylic acid
A water-insoluble copolymer containing 0.1 to 20% by weight of (B) an acrylic ester or (and) a methacrylic ester as a copolymerization component, wherein the carboxyl group in the copolymer contains an alkali metal or (and) ) Therapeutic adhesive tape or sheet 2, characterized in that it is a salt of an alkali metal. In addition to the above-mentioned components (A) and (B), (C) the copolymer is copolymerizable with these. Therapeutic adhesive tape or sheet 3 according to claim 1, characterized in that other monomers are copolymerized components. 80 mol% of carboxyl groups in the copolymer.
The therapeutic adhesive tape or sheet according to claim 1 or 2, characterized in that the above is an alkali metal or/and a salt of an alkali metal.