JPS58152564A - Medical adhesive tape or sheet - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] The present invention relates to therapeutic adhesive tapes or sheets.

A therapeutic adhesive tape or sheet, which has a thin layer of pressure-sensitive adhesive layer mixed with a therapeutic drug on the base material, is applied to the skin as an adherend, and the drug is released from the pressure-sensitive adhesive layer. 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 that it does not cause excessive adhesion to the skin when removed. There is no mutual chemical interaction between the pressure-sensitive adhesive and the drug, and the drug can be easily and economically extracted from the adhesive to the surface so that sufficient medicinal effects can be obtained.

Conventionally, pressure-sensitive adhesives for this purpose have been made by copolymerizing acrylic acid ester with monomers having chemically active groups such as acrylic acid, methacrylic acid, glycol monoacrylate, glycol methacrylate, and glycidyl methacrylate. In addition, chemical crosslinking is created using Schiff's compounds, diisocyanates, dicarboxylic acids, glycols, alkylated melamines, organic polyvalent metal compounds, etc., and the adhesive strength and internal cohesive strength that are insufficient with acrylic ester polymers alone are achieved. is supplementing.

However, in therapeutic adhesive tapes or sheets provided with the pressure-sensitive adhesive layer, the drug may react with the chemically active groups in the pressure-sensitive adhesive, impairing its efficacy, and even if the drug does not react with the chemically active groups, the chemical Due to chemical affinity, the compatibility between the drug and the pressure-sensitive adhesive is excessively improved, and the drug enters the adhesive. As a result, the adhesion strength improves as time passes after application, resulting in pain and discomfort when peeled off.

The present invention solves the above-mentioned drawbacks, and provides a therapeutic device that allows the drug contained in the pressure-sensitive adhesive layer to effectively transfer to the skin, and that the transferability does not change over time, providing a stable therapeutic effect at all times. The purpose is to provide adhesive tapes or sheets.

The gist of the present invention is to provide a therapeutic adhesive tape or sheet in which a base material is provided with a pressure-sensitive adhesive layer containing a drug, in which the pressure-sensitive adhesive is a captive acrylic ester or (
and) a methacrylic acid ester and (a) a copolymerization component of one or more polyfunctional monomers selected from polyfunctional vinyl monomers, polyfunctional allyl phosphors, and polyfunctional amide monomers. A therapeutic adhesive tape or sheet comprising a copolymer containing:

Next, the bromination of the therapeutic adhesive tape or sheet of the present invention will be explained in detail.

The base material used in the present invention is preferably made of a flexible material such as polyethylene, polypropylene, ethylene-vinyl acetate copolymer, soft vinyl chloride, or cellophane. The thickness of the base material is 0.02
The range of α15 to α15 is preferable.

The base material is subjected to corona discharge treatment, plasma treatment, primer coating, etc., as necessary, in order to increase the adhesion with the pressure-sensitive adhesive layer.

The pressure-sensitive adhesive is selected from methacrylic esters or (and) acrylic esters (co-forming ingredients) and polyfunctional vinyl monomers, polyfunctional allyl monomers, polyfunctional amide monomers. one or more polyfunctional monomers (copolymer components)
B)).

The reason why pressure-sensitive adhesives contain acrylic esters or (and) methacrylic esters as copolymer components is that they do not have chemically active groups and therefore do not interact chemically with drugs, thereby impairing their medicinal efficacy. This is because there is no oxidation, the delivery of the drug is good, and there is no strong irritation to the skin.

Examples of ester residues in the acrylic ester or (and) methacrylic ester that become the copolymerization component of the copolymer include methyl group, ethyl group, propyl group, isopropyl group, n-butyl group, isobutyl group, n- Pentyl group, isopentyl group, 2-methylbutyl group, n-
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., and are particularly preferred. Examples of acrylic esters include ethyl acrylate, n-butyl acrylate, isobutyl acrylate, isoamyl acrylate, 2-ethylhexyl acrylate, n-octyl acrylate, lauryl acrylate, etc., and methacrylic esters include methyl methacrylate, butyl acrylate, etc. These include methacrylate, 2-ethylhexyl acrylate, n-octyl methacrylate, and lauryl methacrylate.

By the way, when the positive pressure adhesive is a polymer made only of acrylic ester, it has the necessary internal cohesive force and adhesive strength to the skin to prevent the pressure-sensitive adhesive from transferring to the skin or from shifting its position. However, a polymer consisting only of methacrylic acid ester can provide internal cohesive strength, but does not exhibit adhesive strength to the skin. In addition, the copolymer of acrylic acid ester and methacrylic acid ester has only a small amount of K.
Since the cohesive force is partially insufficient, it is necessary to improve the internal cohesive force by the amount that is insufficient.

For this reason, in the present invention, the pressure-sensitive adhesive is a copolymer containing the above-mentioned copolymer molecule and copolymer component tB).

As a copolymerization component, one or more polyfunctional monomers selected from polyfunctional vinyl monomers, polyfunctional allyl monomers, and polyfunctional a(d) monomers are used. The polyfunctional vinyl monomer is a compound having two or more 17) H=A groups in one molecule, and includes, for example, divinylbenzene, divinyltoluene, and the like.

A polyfunctional allyl monomer is a compound having an allyl group of 21v or more in one molecule, such as diallyl phthalate,
Examples include diallyl maleate, diallyl adipate, diallyl glycolate, triallyl isocyanurate, diethylene glycol vinylyl carbonate, and the like.

Further, the polyfunctional amide monomer is a compound having two or more amide groups in one molecule, and includes, for example, methylenebisacrylamide. Copolymer component (Bl is 0 in the copolymer)
．． It participates in the copolymerization in a range of 0.01 to 1 mole. This is because when the copolymer synthesis molecule Bl is less than K (LO1 mole 4") in the copolymer, the resulting copolymer has a small internal cohesive force as an adhesive, and it does not stick to the skin when it is peeled off from the skin. Adhesion tends to occur, and if the amount is more than 1 mol%, gelation may occur during the polymerization reaction to obtain the copolymer, making coating difficult. .

In the present invention, when the pressure-sensitive adhesive is composed of a copolymer containing a copolymerization component and a copolymerization component), a copolymer containing a copolymerization molecule and a copolymerization component) is used. In addition, other polymerizable monomers that can be copolymerized with these and do not have chemically active groups (copolymerizable component 1c)), that is, other polymerizable monomers that are not likely to interact with the drug. This includes the case where it is used as a copolymerization component. Copolymer component C) is used, for example, when it is expected to have the effect of controlling the crystallization of the drug, precipitation on the surface, or elution of the drug by controlling its compatibility with the drug. Examples of the copolymer component C) include vinyl acetate, vinyl chloride, styrene, α-methylstyrene, vinyltoluene, and acrylonide! These include dibutyl maleate, butadiene, isoprene, etc.

When manufacturing a positive adhesive, solution polymerization, emulsion polymerization, suspension polymerization, etc. can be carried out using ordinary radical polymerization catalysts such as azobis compounds and peroxide compounds. Considering the drug mixing and dissolving steps involved in the process, solution polymerization is optimal.

For example, each component constituting the copolymer and a solvent such as ethyl acetate are added to a reaction vessel to form a solution with a concentration of approximately 60% by weight, the atmosphere inside the reaction vessel is replaced with nitrogen gas, and the mixture is allowed to rise while stirring. Then, at a temperature of 60 to 80°C, a solution of the radical generating catalyst dissolved in the same solvent is added dropwise, but the viscosity is suppressed by adding only the solvent according to the increase in viscosity. Polymerization is completed in hours. After the pressure-sensitive adhesive solution is prepared in this manner, the drug is added either neat or dissolved in a suitable solvent.

As a drug, hydrocortisone, ell human.

Corticosteroids such as cortisone, prednisolone, dexamethasone, betamethacin, fluocinoacetonide;
Anti-inflammatory analgesics such as methyl salicylate and monoglycol salicylate; antihistamines; antifungal agents and the like are used as appropriate depending on the purpose.

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 it is preferably in the range of 1 μ2 to 5 μm per layer. .

The pressure-sensitive adhesive is applied to a base material and dried, and is formed to a thickness of, for example, QO2 to (12 m), and then a releasable sheet is pressed through a roll or the like, or a KWIk pressure contact is applied to the surface of the VC releasable sheet. A therapeutic adhesive tape or sheet with a protected pressure-sensitive adhesive layer is obtained by applying the adhesive, drying it, and pressing the adhesive surface of the substrate through a roll.

According to the therapeutic adhesive tape or sheet of the present invention, not only the exudation of the drug from the pressure-sensitive adhesive layer is excellent, but also there is no need to perform post-crosslinking etc. on the copolymer constituting the pressure-sensitive adhesive. It is difficult to cause drug deterioration, and since there are no residual chemically active groups, irritation to the skin is minimal. w'lfr economical N111
Example 1: 2 ho moles of 2-ethylhexyl methacrylate, 10 moles of butyl acrylate, divinylbenzene. 5 x 10
-3 moles of each component were placed in a reaction vessel, azobisisobutyronitrile 3X1G''E-k was added as a catalyst, ethyl acetate was added as an illumination agent, and solution polymerization was carried out at 70'C until the solid content reached 20% by weight. A copolymer solution was obtained.Next, 06 parts by weight of a 20% methanol solution of prednisolone was added per 100 parts by weight of the copolymer solution, and a polyethylene sheet having a thickness of QO5 and subjected to corona discharge treatment was prepared. It was applied and dried so that the thickness of the adhesive layer was QO5m.

Test pieces were punched out from the thus obtained therapeutic adhesive sheets, and the test pieces were immersed in ion-exchanged water for 24 hours for 24 hours, and the amount of the extracted drug was measured. When measured, the amount extracted was 9996 for the product immediately after production, while it was 989 M for the product left at 60° C. for 1 day, and it was found that there was almost no change. When this therapeutic adhesive sheet was applied to the skin for 24 hours, there was no peeling from the edges, no transfer of the pressure sensitive adhesive to the skin upon peeling, no skin irritation, etc.

Example 2 In Example 1, divinylbenzene 5×10-”
Polymerization reaction was carried out in the same manner as in Example 1 except that 5×10 ” mole (diallylphthale) was used, and after incorporating the drug, it was applied to the base material and dried to obtain a therapeutic adhesive sheet. Next, evaluation was carried out in the same manner as in Example 1, and it was observed that the amount of drug extracted hardly changed.Also, when the skin 11 was attached, there was no peeling from the edges, and when peeled off, there was no peeling. There was no transfer of the pressure-sensitive adhesive to the skin, no skin irritation, etc.

Example 3 5 moles of 2-ethylhexyl methacrylate, 0.5 moles of butyl methacrylate, 4.0 moles of butyl acrylate, and woos moles of methylenebisacrylamide were placed in a reaction vessel, and a polymerization reaction was carried out in the same manner as in Example 1. After applying the drug to the base material and drying it, a therapeutic adhesive sheet was obtained. Next, evaluation was carried out in the same manner as in Example 1, but the amount of extracted drug was hardly affected. There was no peeling from the edges when applied to the skin, no transfer of pressure sensitive adhesive to the skin when peeled off, no skin irritation, etc.

Example 4 2-ethylhexyl methacrylate 2hol, butyl acrylate 20mol, methylenebisacrylamide 0.
0.006 moles of each component were placed in a reaction vessel, a polymerization reaction was carried out in the same manner as in Example 1, and a drug-containing adhesive sheet was applied to a substrate and dried to obtain a therapeutic adhesive sheet. Evaluation was carried out in the same manner as in Example 1, but the extracted amount of the drug hardly changed. When applied to the skin, peeling from the edges, transfer of the pressure sensitive adhesive to the skin during #U#, skin irritation, etc. did not occur.

Comparative Example 1 3.5 moles of 2-ethylhexyl acrylate, 10 moles of butyl acrylate, and 5 moles of methacrylic acid were solution polymerized at 70°C using 3 x 10" moles of azobisisobutyronitrile in ethyl acetate, and the solid content was A copolymer solution weighing approximately 34% by weight was obtained. 111 mol of KL4-dioxytetramethylene dihexamethylene diisocyanate was added to this copolymer solution and reacted at 80° C. for 8 hours to perform post-crosslinking to a slight degree. A pressure sensitive adhesive was obtained.

Next, evaluation was carried out in the same manner as in Example 1, and the amount of extracted drug was 72 g6 immediately after production, whereas it was 11 g6 when left at 60° C. for 10 days, and a significant decrease was observed.

Furthermore, after it was applied to the skin, the adhesive transferred to the skin when it was peeled off.

patent applicant Sekisui Chemical Co., Ltd. Representative: Mototoshi Fuji Numa

Claims (1)

[Scope of Claims] 1. A therapeutic adhesive tape or sheet in which a pressure-sensitive adhesive layer containing a drug is provided on a base material, wherein the pressure-sensitive adhesive is a captive acrylic ester or (and) a methacrylic ester. , (B) A copolymer containing as a copolymerization component one or more polyfunctional monomers selected from polyfunctional vinyl monomers, polyfunctional allyl monomers, and polyfunctional 7-mide monomers. Therapeutic adhesive tape or sheet 'L's pressure adhesive is characterized by a combination of a captive acrylic ester or (and) a methacrylic ester, and (B) a polyfunctional vinyl monomer, a polyfunctional allyl ester, and (B) a polyfunctional vinyl monomer, a polyfunctional allyl In addition to one or more polyfunctional monomers selected from monomers and polyfunctional amide monomers, () other polymerizable monomers that are copolymerizable with these monomers and do not have chemically active groups; The therapeutic adhesive tape or sheet according to claim IP1, characterized in that the therapeutic adhesive tape or sheet is made of a copolymer containing a polymer as a copolymer component.