US4690683A — Transdermal varapamil delivery device

Claim 1

Independent Claim 112 words

A transdermal drug delivery device comprising: a permeable polymer matrix comprising a silicone elastomer corresponding to the formula: ##STR2## wherein R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000; said permeable polymer matrix having an effective cardiovascular affecting amount of 5-[-(3,4-dimethoxyphenyl) methylamino]-2-(3,4-dimethoxyphenly)-2-isopropylvaleronitrile and an effective release promoting amount of a first transport enhancing agent dispersed therein, and a bioacceptable adhesive layer covering one face of said polymer matrix, said adhesive having an effective drug transport promoting amount of a second transport enhancing agent dispersed therein; wherein said second agent is different from said first agent.

Claim 2

Dependent Claim 112 words

A transdermal drug delivery device comprising: a permeable polymer matrix comprising a silicone elastomer corresponding to the formula: ##STR2## wherein R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000; said permeable polymer matrix having an effective cardiovascular affecting amount of 5-[-(3,4-dimethoxyphenyl) methylamino]-2-(3,4-dimethoxyphenly)-2-isopropylvaleronitrile and an effective release promoting amount of a first transport enhancing agent dispersed therein, and a bioacceptable adhesive layer covering one face of said polymer matrix, said adhesive having an effective drug transport promoting amount of a second transport enhancing agent dispersed therein; wherein said second agent is different from said first agent.

Claim 3

Dependent Claim 60 words

A transdermal drug delivery device as recited in claim 1, wherein said first and second transport enhancing agents are independently selected from the group consisting of lower alkyl esters of saturated and unsaturated fatty acids, mineral oil, dialkylsulfoxides, N,N-dialkylamides, N-alkyl azacyclo ketones, thioglycolate salts, fatty alcohols, saturated and unsaturated fatty acids, glycol monoesters of fatty acids, and fatty acid monoglycerides.

Claim 4

Dependent Claim 21 words

A transdermal drug delivery device as recited in claim 2, wherein said first and second transport enhancing agents are the same.

Claim 5

Dependent Claim 25 words

A transdermal drug delivery device as recited in claim 2, wherein said adhesive has a pH in the range from about 5 to about 7.

Claim 6

Dependent Claim 18 words

A transdermal drug delivery device according to claim 4, wherein the pH of said adhesive is about 6.

Claim 7

Dependent Claim 26 words

A transdermal drug delivery device as recited in claim 2, wherein said adhesive layer comprises from about 1 to about 30 weight percent transport enhancing agent.

Claim 8

Dependent Claim 26 words

A transdermal drug delivery device as recited in claim 6, wherein said adhesive layer comprises from about 5 to about 25 weight percent transport enhancing agent.

Claim 9

Dependent Claim 19 words

A transdermal drug delivery device as recited in claim 2, wherein said second transport enhancing agent comprises isopropyl myristate.

Claim 10

Dependent Claim 18 words

A transdermal drug delivery device as recited in claim 2, wherein said first transport enhancing agent comprises N,N-diethyl-m-toluamide.

Claim 11

Dependent Claim 18 words

A transdermal drug delivery device as recited in claim 2, wherein said adhesive comprises a bioacceptable silicone elastomer.

Claim 12

Dependent Claim 45 words

A transdermal drug delivery device comprising a permeable bioacceptable lipophilic polymer matrix having an effective cardiovascular affecting amount of 5-[-(3,4-dimethoxyphenyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said polymer matrix being substantially electroneutral with respect to said 5-[-(3,4-dimethoxyphenylethyl )methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.

Claim 13

Dependent Claim 45 words

A transdermal drug delivery device comprising a permeable bioacceptable lipophilic polymer matrix having an effective cardiovascular affecting amount of 5-[-(3,4-dimethoxyphenyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said polymer matrix being substantially electroneutral with respect to said 5-[-(3,4-dimethoxyphenylethyl )methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.

Claim 14

Dependent Claim 50 words

A transdermal drug delivery device as recited in claim 11 wherein said polymer matrix comprises a silicone elastomer corresponding to the formula: ##STR3## wherein R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000.

Claim 15

Dependent Claim 56 words

A transdermal drug delivery device as recited in claim 11 wherein said transport enhancing agent is selected from the group consisting of lower alkyl esters of saturated and unsaturated fatty acids, mineral oil, dialkylsulfoxides, N,N-dialkylamides, N-alkyl azacyclo ketones, thioglycolate salts, fatty alcohols, saturated and unsaturated fatty acids, glycol monoesters of fatty acids, and fatty acid mono-glycerides.

Claim 16

Dependent Claim 28 words

A transdermal drug delivery device as recited in claim 13, wherein said transport enhancing agent comprises from about 2 to about 50 weight percent of said polymer matrix.

Claim 17

Dependent Claim 28 words

A transdermal drug delivery device as recited in claim 14, wherein said transport enhancing agent comprises from about 5 to about 30 weight percent of said polymer matrix.

Claim 18

Dependent Claim 68 words

A unit-dose package comprising a transdermal drug delivery device comprising a permeable bioacceptable lipophilic polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, and means for pretreating the skin of a patient with a skin permeation enhancing agent prior to application of said transdermal drug delivery device to the skin of the patient.

Claim 19

Dependent Claim 68 words

A unit-dose package comprising a transdermal drug delivery device comprising a permeable bioacceptable lipophilic polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, and means for pretreating the skin of a patient with a skin permeation enhancing agent prior to application of said transdermal drug delivery device to the skin of the patient.

Claim 20

Dependent Claim 55 words

A unit-dose package as recited in claim 16, wherein said skin permeation enhancing agent is selected from the group consisting of lower alkyl esters of saturated and unsaturated fatty acids, mineral oil, dialkylsulfoxides, N,N-dialkylamides, N-alkyl azacyclo ketones, thioglycolate salts, fatty alcohols, saturated and unsaturated fatty acids, glycol monoesters of fatty acids, and fatty acid monoglycerides.

Claim 21

Dependent Claim 126 words

A transdermal drug delivery device comprising: a permeable polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said drug delivery device having one surface disposable adjacent the skin of a patient in use; a protective layer covering said one surface prior to use of said drug delivery device and strippable therefrom when it is desired to use said drug delivery device, and a supply of skin permeation enhancing agent disposed between said one surface and said protective layer such that when said protective layer is stripped from said device and said one surface is disposed adjacent a patient's skin, the skin is directly contacted by said supply of skin permeation enhancing agent.

Claim 22

Dependent Claim 126 words

A transdermal drug delivery device comprising: a permeable polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said drug delivery device having one surface disposable adjacent the skin of a patient in use; a protective layer covering said one surface prior to use of said drug delivery device and strippable therefrom when it is desired to use said drug delivery device, and a supply of skin permeation enhancing agent disposed between said one surface and said protective layer such that when said protective layer is stripped from said device and said one surface is disposed adjacent a patient's skin, the skin is directly contacted by said supply of skin permeation enhancing agent.

Claim 23

Dependent Claim 50 words

A transdermal drug delivery device as recited in claim 18, wherein an adhesive layer is provided over said polymer matrix to secure the polymer matrix to the skin of a patient and said supply of skin permeation enhancing agent is disposed between said adhesive layer and the strippable protective layer.

Claim 24

Dependent Claim 35 words

A transdermal drug delivery device as recited in claim 19, wherein said supply of skin permeation enhancing agent comprises a removable absorbent layer covering said adhesive layer and impregnated with said skin permeation enhancing agent.

Claim 25

Dependent Claim 33 words

A transdermal drug delivery device as recited in claim 18, further comprising an occlusive backing covering the surface of said matrix opposite said surface which is disposable adjacent the skin of a patient.

Claim 26

Dependent Claim 50 words

A transdermal drug delivery device as recited in claim 18 wherein said polymer matrix comprises a silicone elastomer corresponding to the formula: ##STR4## wherein R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000.

Claim 27

Dependent Claim 57 words

A transdermal drug delivery device as recited in claim 18 wherein said skin permeation enhancing agent is selected from the group consisting of lower alkyl esters of saturated and unsaturated fatty acids, mineral oil, dialkylsulfoxides, N,N-dialkylamides, N-alkyl azacyclo ketones, thioglycolate salts, fatty alcohols, saturated and unsaturated fatty acids, glycol monoesters of fatty acids, and fatty acid monoglycerides.

Claim 28

Dependent Claim 65 words

A transdermal drug delivery device comprising: a permeable lipiphilic polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile dispersed therein, and a bioacceptable adhesive layer covering a face of said polymer matrix, said adhesive having an effective drug transport promoting amount of a transport enhancing agent dispersed therein and having a pH at which said 5-(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile exists as an electrically neutral species.

Claim 29

Dependent Claim 65 words

A transdermal drug delivery device comprising: a permeable lipiphilic polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile dispersed therein, and a bioacceptable adhesive layer covering a face of said polymer matrix, said adhesive having an effective drug transport promoting amount of a transport enhancing agent dispersed therein and having a pH at which said 5-(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile exists as an electrically neutral species.

Claim 30

Dependent Claim 21 words

A transdermal drug delivery device according to claim 24, wherein said adhesive further comprises a buffering agent for maintaining said pH.

Claim 31

Dependent Claim 135 words

A transdermal drug delivery device comprising: a permeable silicone elastomer matrix corresponding to the formula: ##STR5## in which R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000 and having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a first transport enhancing agent intimately dispersed therein, and a bioacceptable adhesive layer having an effective drug transport promoting amount of a second transport enhancing agent dispersed therein, said adhesive layer having a first face disposed in contiguous face to face contact with a face of said matrix and a second face opposite said first face disposable in contact with skin of a person to whom it is desired to transdermally administer 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.

Claim 32

Dependent Claim 135 words

A transdermal drug delivery device comprising: a permeable silicone elastomer matrix corresponding to the formula: ##STR5## in which R represents an alkoxy, alkyl, alkenyl or aryl group containing 1 to 7 carbon atoms and wherein n, m and p are each 100 to 5,000 and having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a first transport enhancing agent intimately dispersed therein, and a bioacceptable adhesive layer having an effective drug transport promoting amount of a second transport enhancing agent dispersed therein, said adhesive layer having a first face disposed in contiguous face to face contact with a face of said matrix and a second face opposite said first face disposable in contact with skin of a person to whom it is desired to transdermally administer 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile.

Claim 33

Dependent Claim 26 words

A transdermal drug delivery device according to claim 26, wherein said adhesive layer has a pH at which 5-[(3,4-dimethoxyphenethyl) methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile exists as an electrically neutral species.

Claim 34

Dependent Claim 18 words

A transdermal drug delivery device as recited in claim 27, wherein said first transport enhancing agent comprises N,N-diethyl-m-toluamide.

Claim 35

Dependent Claim 106 words

A transdermal drug delivery device comprising: a permeable polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said polymer matrix having one surface disposable adjacent the skin of a patient, and a supply of skin permeation enhancing agent adjacent said one polymer matrix surface such that when said one surface is disposed adjacent a patient's skin, the skin is directly contacted by said supply of skin permeation enhancing agent, wherein said supply of skin permeation enhancing agent comprises a film of skin permeation enhancing agent on the surface of an adhesive layer.

Claim 36

Dependent Claim 106 words

A transdermal drug delivery device comprising: a permeable polymer matrix having an effective cardiovascular affecting amount of 5-[(3,4-dimethoxyphenethyl)-methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropylvaleronitrile and an effective release promoting amount of a transport enhancing agent dispersed therein, said polymer matrix having one surface disposable adjacent the skin of a patient, and a supply of skin permeation enhancing agent adjacent said one polymer matrix surface such that when said one surface is disposed adjacent a patient's skin, the skin is directly contacted by said supply of skin permeation enhancing agent, wherein said supply of skin permeation enhancing agent comprises a film of skin permeation enhancing agent on the surface of an adhesive layer.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1990-08-31	1991-03-02	1991-09-01	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1994-08-31	1995-03-02	1995-09-01	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1998-08-31	1999-03-02	1999-09-01	$7700.00	Window Closed / Lapsed

Transdermal varapamil delivery device

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