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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a Continuation application of, and claims benefit of, U.S. patent application Ser. No. 10 / 561,751, filed on Dec. 21, 2005, which was the National Stage of, and claims benefit of, International Application PCT / JP2004 / 008544, filed on Jun. 17, 2004, which claims benefit of, and priority to, Japanese Patent Application No. 2003-179162, filed on Jun. 24, 2003, all of which are herein incorporated by reference.TECHNICAL FIELD

[0002] The present invention relates to a nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption, comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers selected from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, as well as to a medicinal tape preparation for percutaneous absorption prod...

Examples

example 1

Production of Nonaqueous Pressure-Sensitive Adhesive 1

[0046]After charging 157.5 g of 2-ethylhexyl acrylate (hereinafter abbreviated as 2EHA), 35 g of 2-acetoacetoxyethyl methacrylate (hereinafter abbreviated as AAEM), 80.5 g of diacetoneacrylamide (hereinafter abbreviated as DAAM) and 76 g of methyl methacrylate (hereinafter abbreviated as MMA) in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 525 g of ethyl acetate was added as a solvent and the mixture was dissolved to uniformity. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml / min. After holding at 75° C. for 30 minutes, a solution of 0.21 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Subsequently, 300 g of toluene was loaded in portions of 100 g at a time at 3, 5 and 7 hours after adding the initiator. During the polymerization, nitrogen gas was c...

example 2

Production of Nonaqueous Pressure-Sensitive Adhesive 2

[0049]A monomer solution was prepared by uniformly pre-dissolving 78.8 g of 2EHA, 78.8 g of n-butyl acrylate (hereinafter abbreviated as BA), 105 g of AAEM, 87.5 g of MMA and 1.05 g of diethyleneglycol dimethacrylate (hereinafter abbreviated as DEGMA). After adding 100 g of the monomer solution in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 350 g of ethyl acetate was added as a solvent. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml / min, and after holding at 75° C. for 30 minutes, a solution of 0.35 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Upon confirming reflux of the solvent, the remaining monomer solution was loaded continuously for 3 hours. Next, one hour after the initial continuous loading of the monomer solution, 500 g of ethyl aceta...

example 11

Production of Tape Preparation for Percutaneous Absorption 11

[0082]A 36.2 g portion of pressure-sensitive adhesive 7, and then 1.5 g of ketoprofen, were placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 140 mg / 10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape preparation for percutaneous absorption 11. The ketoprofen content of the obtained preparation was 10 w / w %.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application is a Continuation application of, and claims benefit of, U.S. patent application Ser. No. 10 / 561,751, filed on Dec. 21, 2005, which was the National Stage of, and claims benefit of, International Application PCT / JP2004 / 008544, filed on Jun. 17, 2004, which claims benefit of, and priority to, Japanese Patent Application No. 2003-179162, filed on Jun. 24, 2003, all of which are herein incorporated by reference.TECHNICAL FIELD

[0002] The present invention relates to a nonaqueous pressure-sensitive adhesive for a medicinal tape preparation for percutaneous absorption, comprising a copolymer obtained by copolymerization of a (meth)acrylic monomer having an acetoacetyl group in the molecule and one or more monomers selected from among other (meth)acrylic monomers with no acetoacetyl group and copolymerizable vinyl monomers, in a nonaqueous solvent, as well as to a medicinal tape preparation for percutaneous absorption prod...

Examples

example 1

Production of Nonaqueous Pressure-Sensitive Adhesive 1

[0046]After charging 157.5 g of 2-ethylhexyl acrylate (hereinafter abbreviated as 2EHA), 35 g of 2-acetoacetoxyethyl methacrylate (hereinafter abbreviated as AAEM), 80.5 g of diacetoneacrylamide (hereinafter abbreviated as DAAM) and 76 g of methyl methacrylate (hereinafter abbreviated as MMA) in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 525 g of ethyl acetate was added as a solvent and the mixture was dissolved to uniformity. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml / min. After holding at 75° C. for 30 minutes, a solution of 0.21 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Subsequently, 300 g of toluene was loaded in portions of 100 g at a time at 3, 5 and 7 hours after adding the initiator. During the polymerization, nitrogen gas was c...

example 2

Production of Nonaqueous Pressure-Sensitive Adhesive 2

[0049]A monomer solution was prepared by uniformly pre-dissolving 78.8 g of 2EHA, 78.8 g of n-butyl acrylate (hereinafter abbreviated as BA), 105 g of AAEM, 87.5 g of MMA and 1.05 g of diethyleneglycol dimethacrylate (hereinafter abbreviated as DEGMA). After adding 100 g of the monomer solution in a 2-liter four-necked flask equipped with a Dimroth condenser, thermometer, nitrogen gas blow-in tube and stirrer, 350 g of ethyl acetate was added as a solvent. The temperature was raised to 75° C. while blowing in nitrogen gas at flow rate of 100 ml / min, and after holding at 75° C. for 30 minutes, a solution of 0.35 g of benzoyl peroxide as an initiator in 5 g of ethyl acetate was added, and the external temperature was set to 85° C. Upon confirming reflux of the solvent, the remaining monomer solution was loaded continuously for 3 hours. Next, one hour after the initial continuous loading of the monomer solution, 500 g of ethyl aceta...

example 11

Production of Tape Preparation for Percutaneous Absorption 11

[0082]A 36.2 g portion of pressure-sensitive adhesive 7, and then 1.5 g of ketoprofen, were placed in a screw-cap bottle and stirred for more than an hour in the bottle. A coating tester (LTE-S, Wener Mathis AG) was used for coating and drying of the solution onto a support (polyester film) to a dried coating weight of 140 mg / 10 cm2, and then a liner (silicon-treated polyester film) was used to cover it with the silicon side contacting the pressure-sensitive to obtain tape preparation for percutaneous absorption 11. The ketoprofen content of the obtained preparation was 10 w / w %.

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