Nonaqueous pressure-sensitive adhesive for medicinal tape preparation for percutaneous absorption, medicinal tape preparation for percutaneous absorption, and process for producing the same

Abstract

A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, and a medicinal tape preparation for percutaneous absorption comprising the adhesive. The nonaqueous pressure-sensitive adhesive may comprise a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers from among other (meth)acrylic monomers without acetoacetyl groups and copolymerizable vinyl monomers, in a nonaqueous solvent. Suitable (meth)acrylic monomers having an acetoacetyl group in the molecule are acetoacetoxyalkyl methacrylates, and especially 2-acetoacetoxyethyl methacrylate. The copolymer nonaqueous pressure-sensitive adhesive of the invention, comprising a (meth)acrylic monomer having an acetoacetyl group as a constituent monomer, is capable of containing large amounts of lipophilic oily substances in the pressure-sensitive adhesive layer, and during heat drying, the acetoacetyl groups undergo self-crosslinking to form a network structure as the solvent evaporates off, so that large amounts of oily substances such as the plasticizer can be included in the network structure. The pressure-sensitive adhesive of the invention uses no polyamine derivatives, isocyanate compounds, polyvalent metal chelate compounds, etc., as crosslinking agents, and therefore toxicity is not a concern and skin is not irritated. A medicinal tape preparation for percutaneous absorption of the invention has superior adhesive strength and cohesive strength, and is highly safe with low skin irritation. It also has excellent drug release and percutaneous absorption properties.

1 . A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption, characterized by comprising a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl acrylate or 2-acetoacetoxyethyl methacrylate,   (ii) one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate and butyl acrylate, and   (iii) one or more (meth)acrylic monomers selected from the group consisting of diacetoneacrylamide, diethyleneglycol dimethacrylate and tetraethyleneglycol dimethacrylate,   
     in a nonaqueous solvent. 
   
   
       2 . A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to  claim 1 , characterized in that the copolymer is a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl methacrylate,   (ii) 2-ethylhexyl acrylate and/or methyl methacrylate, and   (iii) one or more (meth)acrylic monomers selected from the group consisting of diacetoneacrylamide, diethyleneglycol dimethacrylate and tetraethyleneglycol dim ethacrylate.   
   
   
       3 . A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to  claim 1 , characterized in that the copolymer is a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl methacrylate,   (ii) 2-ethylhexyl acrylate and methyl methacrylate, and   (iii) diacetoneacrylamide and tetraethyleneglycol dimethacrylate.   
   
   
       4 . A nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption according to  claim 1 , characterized in that the copolymer has a calculated glass transition temperature (Tg) of between −60° C. and −5° C. 
   
   
       5 . A medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, the medicinal tape preparation for percutaneous absorption being characterized in that said pressure-sensitive adhesive layer is formed by coating a support or release film with a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl acrylate or 2-acetoacetoxyethyl methacrylate,   (ii) one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate and butyl acrylate, and   (iii) one or more (meth)acrylic monomers selected from the group consisting of diacetoneacrylamide, diethyleneglycol dimethacrylate and tetraethyleneglycol dimethacrylate,   
     in a nonaqueous solvent, together with a drug, and heating to dryness. 
   
   
       6 . A medicinal tape preparation for percutaneous absorption according to  claim 5 , characterized in that the copolymer is a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl methacrylate,   (ii) 2-ethylhexyl acrylate and/or methyl methacrylate, and   (iii) one or more (meth)acrylic monomers selected from the group consisting of diacetoneacrylamide, diethyleneglycol dimethacrylate and tetraethyleneglycol dimethacrylate.   
   
   
       7 . A medicinal tape preparation for percutaneous absorption according to  claim 5 , characterized in that the copolymer has a calculated glass transition temperature (Tg) of between −60° C. and −5° C. 
   
   
       8 . A medicinal tape preparation for percutaneous absorption according to  claim 5 , characterized in that the pressure-sensitive adhesive layer further comprises a plasticizer. 
   
   
       9 . A medicinal tape preparation for percutaneous absorption according to  claim 8 , characterized in that the plasticizer is one or more oils selected from the group consisting of fatty acid esters, higher alcohols and castor oil. 
   
   
       10 . A medicinal tape preparation for percutaneous absorption according to  claim 8 , characterized in that the plasticizer content is no greater than 50 wt % of the total weight of said pressure-sensitive adhesive layer. 
   
   
       11 . A medicinal tape preparation for percutaneous absorption according to  claim 9 , characterized in that the plasticizer is one or more fatty acid esters selected from the group consisting of isopropyl myristate, isopropyl palmitate, medium-chain fatty acid triglycerides, diethyl sebacate and diisopropyl adipate. 
   
   
       12 . A medicinal tape preparation for percutaneous absorption according to  claim 11 , characterized in that the plasticizer is isopropyl myristate. 
   
   
       13 . A medicinal tape preparation for percutaneous absorption according to  claim 8 , characterized in that the nonaqueous pressure-sensitive adhesive comprises a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl methacrylate,   (ii) 2-ethylhexyl acrylate and methyl methacrylate, and   (iii) diacetoneacrylamide and tetraethyleneglycol dimethacrylate, in a nonaqueous solvent and, the plasticizer is isopropyl myristate.   
   
   
       14 . A medicinal tape preparation for percutaneous absorption according to  claim 5 , characterized in that the drug is a percutaneously absorbing drug selected from the group consisting of steroid hormones, non-steroidal anti-inflammatory drugs, tranquilizers, anti-hypertensive agents, ischemic heart disease drugs, anti-histamines, antiasthmatic drugs, anti-Parkinson drugs, cerebral circulation improvers, antiemetics, anti-depressants, anti-dementia drugs, Sjogren's syndrome treatments, anti-arrhythmia drugs, anticoagulants, gout suppressants, antifungal agents, narcotic analgesics, beta blockers, β1 agonists, β2 agonists, antitumor agents, diuretics, antithrombotic agents, histamine H1 receptor antagonists, histamine H2 receptor antagonists, anti-allergic agents, serotonin receptor antagonists, anti-hypercholesteremic agents and smoking cessation aids. 
   
   
       15 . A process for production of a medicinal tape preparation for percutaneous absorption comprising (a) a support, (b) a pressure-sensitive adhesive layer containing a drug and a nonaqueous pressure-sensitive adhesive and (c) a release film laminated in that order, the process being characterized by coating the surface of a release film or support with a nonaqueous pressure-sensitive adhesive comprising a copolymer obtained by copolymerization of
 (i) 2-acetoacetoxyethyl acrylate or 2-acetoacetoxyethyl methacrylate,   (ii) one or more (meth)acrylic monomers selected from the group consisting of 2-ethylhexyl acrylate, methyl methacrylate and butyl acrylate, and   (iii) one or more (meth)acrylic monomers selected from the group consisting of diacetoneacrylamide, diethyleneglycol dimethacrylate and tetraethyleneglycol dimethacrylate,   
     in a nonaqueous solvent, with a drug and if necessary with a plasticizer, heating to dryness to form a pressure-sensitive adhesive layer, and then laminating a release film or support thereon and cutting it to a desired size. 
   
   
       16 . A process for production of a medicinal tape preparation for percutaneous absorption according to  claim 15 , characterized in that the pressure-sensitive adhesive layer is formed by heat drying at 40-150° C.