Transdermal drug delivery device

Claim 2

A flexible and compliant medical device for the transdermal administration of a biological agent through intact skin at sensitive body locations comprising, in combination: (a) an agent reservoir comprising said agent dispersed through a non-aqueous, nonadhesive polymeric carrier permeable to said agent, said reservoir having a body contacting surface through which said agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) a flexible bonding agent substantially less permeable to said agent than the polymeric carrier forming said reservoir, said bonding agent coating substantially all of said body distal surface of said reservoir; and (c) fibrous reinforcing means imbedded in said bonding means to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said bonding means, said imbedded fibrous reinforcing means forming the body distal surface of said device; whereby said bonding agent bonds said fibrous reinforcing means to said reservoir, substantially impedes the transfer of said agent from the body distal surface of said device to other surfaces and the body distal surface of said device retains a fibrous texture.

Claim 3

The device of claim 1 wherein said agent is selected from the group consisting of testosterone, progesterone, estradiol, acyclovir, interferon, cortisone and phenolphthalein, cyproterone, LHRH, their active metabolites, and their prodrugs.

Claim 4

A method of transdermal administration of an agent which comprises applying a device according to claim 1 to a body site selected from the group consisting of the scrotum, the labia, the penis or the breast, and maintaining said system in place for an extended period of time.

Claim 5

The device of claim 1 further comprising a removable agent impermeable liner disposed on the body contacting surface to protect the device in storage.

Claim 6

The device of claim 1 wherein said reinforcing means comprises a fabric web which is non-elastically deformable in at least one direction.

Claim 7

The device of claim 5 wherein said fabric is anisotropically deformable.

Claim 8

The device of claim 5 wherein said fabric is isotropically deformable.

Claim 9

The device of claim 1 wherein said reinforcing means comprises a spun-bonded fabric.

Claim 10

The device of claim 1 wherein said carrier is an ethylene/vinyl acetate copolymer having a vinyl acetate content of about 28-61%.

Claim 11

The device of claim 9 wherein said vinyl acetate content is in the range of about 40-60%.

Claim 12

The device of claim 1 wherein said agent is dispersed within said carrier at a concentration less than saturation.

Claim 13

The device of claim 1 wherein said device has a thickness of about 2-10 mils.

Claim 14

The device of claim 1 wherein said bonding material is polyisobutylene.

Claim 15

The device of claim 1 wherein said device has an extension modulus at 15% elongation in at least one dimension in the range of 1000 to 15,000 gm/cm 2 .

Claim 16

The device of claim 14 wherein said device has a stress decay from 15% elongation after 5 minutes in the range of 25-45%.

Claim 17

The device of claim 15 wherein a 2 cm wide strip required an elongation force of 30-300 gm to produce a 15% elongation.

Claim 18

The device of claim 16 wherein said modulus is in the range of about 1000-5000 gm/cm 2 , said elongation force is in the range of about 50-150 gm.

Claim 19

A flexible and compliant medical device particularly adapted for the transdermal administration of a biological agent through the skin of the human genitalia, said device having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) an agent reservoir comprising said agent dispersed through a non-aqueous, nonadhesive polymeric carrier permeable to said agent, said reservoir having a body contacting surface through which said agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) a flexible bonding agent substantially less permeable to said agent than the polymeric carrier forming said reservoir, said bonding agent coating substantially all of said body distal surface of said reservoir; and (c) fibrous reinforcing means imbedded in said bonding means to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said bonding means, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby said bonding agent bonds said fibrous reinforcing means to said reservoir, substantially impedes the transfer of said agent from the body distal surface of said device to another surface, the body distal surface of said device retains a fibrous texture and said device will be capable of clinging to irregular skin surfaces after application thereto.

Claim 20

A flexible and compliant medical device particularly adapted for the transdermal administration of a biological agent through the skin of the human genitalia, said device having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) an agent reservoir comprising said agent dispersed through a non-aqueous, nonadhesive polymeric carrier permeable to said agent, said reservoir having a body contacting surface through which said agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) a flexible bonding agent substantially less permeable to said agent than the polymeric carrier forming said reservoir, said bonding agent coating substantially all of said body distal surface of said reservoir; and (c) fibrous reinforcing means imbedded in said bonding means to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said bonding means, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby said bonding agent bonds said fibrous reinforcing means to said reservoir, substantially impedes the transfer of said agent from the body distal surface of said device to another surface, the body distal surface of said device retains a fibrous texture and said device will be capable of clinging to irregular skin surfaces after application thereto.

Claim 21

The device of claim 18 wherein said agent is selected from the group consisting of testosterone, progesterone, estradiol, acyclovir, interferon, cortisone, phenolphthalein, cyproterone, LHRH, their active metabolites and their prodrugs.

Claim 22

The device of claim 18 wherein said device is from 2-10 mils thick.

Claim 23

The device of claim 18 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content in the range of about 28-61%.

Claim 24

A flexible and compliant medical device for the transdermal administration of testosterone through the skin of the human male genitalia, said device being from 2-10 mils thick and having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) a testosterone reservoir comprising testosterone dissolved in a non-aqueous, nonadhesive polymeric carrier permeable to said testosterone, said reservoir having a body contacting surface through which testosterone is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) a flexible bonding agent substantially less permeable to testosterone than the polymeric carrier forming said reservoir, said bonding agent coating substantially all of said body distal surface of said reservoir; and (c) fibrous reinforcing means imbedded in said bonding means to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said bonding means, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby said bonding agent bonds said fibrous reinforcing means to said reservoir, substantially impedes the transfer of testosterone from the body distal surface of said device to another surface, the body distal surface of said device retains a fibrous texture and said device is capable of non-adhesively clinging to the skin of the male genitalia in testosterone transmitting relationship thereto.

Claim 25

A flexible and compliant medical device for the transdermal administration of testosterone through the skin of the human male genitalia, said device being from 2-10 mils thick and having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) a testosterone reservoir comprising testosterone dissolved in a non-aqueous, nonadhesive polymeric carrier permeable to said testosterone, said reservoir having a body contacting surface through which testosterone is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) a flexible bonding agent substantially less permeable to testosterone than the polymeric carrier forming said reservoir, said bonding agent coating substantially all of said body distal surface of said reservoir; and (c) fibrous reinforcing means imbedded in said bonding means to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said bonding means, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby said bonding agent bonds said fibrous reinforcing means to said reservoir, substantially impedes the transfer of testosterone from the body distal surface of said device to another surface, the body distal surface of said device retains a fibrous texture and said device is capable of non-adhesively clinging to the skin of the male genitalia in testosterone transmitting relationship thereto.

Claim 26

The device of claim 22 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content in the range of about 28-61%.

Claim 27

The device of claim 23 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content in the range of about 40-60%.

Claim 28

The device of claim 22 wherein said reinforcing means is isotropically non-elastically deformable.

Claim 29

A method of testosterone replacement in hypogonadal males which comprises applying a device according to claim 22 to the genitalia of a hypogonadal male and maintaining said device in testosterone transmitting relationship thereto for at least about 8 hours.

Claim 30

The method of claim 26 wherein said device is replaced with a fresh device on a daily basis.

Claim 31

The device of claim 24 wherein said device is free of undissolved testosterone and contains testosterone at a loading of from about 5-15 mg.

Claim 32

The device of claim 23 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 33

The device of claim 23 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 34

A method for testosterone replacement in hypogonadic males which comprises applying the device of claim 22 to the scrotum of a hypogonadic male and maintaining said system in testosterone transferring relationship to said scrotum for at least about 8 hours.

Claim 35

The method of claim 31 wherein said system is maintained in place for up to about 24 hours and is replaced with a freshsystem after removal whereby continuous testosterone replacement is obtained.

Claim 36

The method of claim 31 wherein said device is stretched in application to the scrotum whereby the device conforms to and clings to the scrotal skin.

Claim 37

The device of claim 9 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 38

The device of claim 21 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 39

The device of claim 23 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 40

The device of claim 10 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 41

The device of claim 24 wherein said bonding agent comprises a polyisobutylene polymer.

Claim 42

The device of claim 1 wherein said tack is in the range of 100-300 g/cm 2 at 35° C.

Claim 43

The device of claim 18 wherein said tack is in the range of 100-300 g/cm 2 at 35° C.

Claim 44

The device of claim 22 wherein said tack is in the range of 100-300 g/cm 2 at 35° C.

Claim 45

The device of claim 21 wherein said fibrous reinforcing means is a polyester fabric.

Claim 46

The device of claim 18 wherein said fibrous reinforcing means is a polyester fabric.

Claim 47

A flexible and compliant medical device particularly adapted for the transdermal administration of a biological agent through intact skin at sensitive body locations said device being from 2-10 mils thick and having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) an agent reservoir comprising said agent dispersed through a non-aqueous, nonadhesive polymeric carrier permeable to said agent, said reservoir having a body contacting surface through which agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) fibrous reinforcing means imbedded in said reservoir to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said reservoir, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby the body distal surface of said device retains a fibrous texture and said device is capable of non-adhesively clinging to the skin at sensitive body locations in agent transmitting relationship thereto.

Claim 48

A flexible and compliant medical device particularly adapted for the transdermal administration of a biological agent through intact skin at sensitive body locations said device being from 2-10 mils thick and having an extension modulus at 15% elongation in at least one direction in the range of 1000 to 15,000 gm/cm 2 , a stress decay from 15% elongation at 5 minutes in the range of 25-45%, a 2 cm wide strip of said device requiring an elongation force of from 30-300 gm to produce said 15% elongation, said device comprising, in combination: (a) an agent reservoir comprising said agent dispersed through a non-aqueous, nonadhesive polymeric carrier permeable to said agent, said reservoir having a body contacting surface through which agent is released to the skin and a body distal surface opposite said body contacting surface, the body contacting surface of said reservoir having a tack in the range of about 50-500 g/cm 2 at 35° C.; (b) fibrous reinforcing means imbedded in said reservoir to a depth that does not penetrate through said body contacting surface and does not submerge said reinforcing means in said reservoir, said imbedded fibrous reinforcing means forming the body distal surface of said device; said fibrous reinforcing means being being non-elastically deformable in at least one direction; whereby the body distal surface of said device retains a fibrous texture and said device is capable of non-adhesively clinging to the skin at sensitive body locations in agent transmitting relationship thereto.

Claim 49

The device of claim 44 wherein said reservoir comprises an ethylene/vinyl acetate copolymer having a vinyl acetate content in the range of about 40-60%.

Claim 50

The device of claim 45 wherein said reinforcing means comprises a polyester fabric.

Claim 51

A method of testosterone replacement in hypogonadal males which comprises applying a device according to claim 44 in which said agent is testosterone to the genitalia of a hypogonadal male and maintaining said device in testosterone transmitting relationship thereto for at least about 8 hours.

Claim 52

The method of claim 47 wherein said device is replaced with a fresh device on a daily basis.

Claim 53

The device of claim 45 wherein said agent is testosterone, said device is free of undissolved testosterone and contains testosterone at a loading of from about 5-15 mg.

Claim 54

A method for testosterone replacement in hypogonadic males which comprises applying the device of claim 44 in which said agent is testosterone to the scrotum of a hypogonadic male and maintaining said system in testosterone transferring relationship to said scrotum for at least about 8 hours.

Claim 55

The method of claim 50 wherein said system is maintained in place for up to about 24 hours and is replaced with a fresh system after removal whereby continuous testosterone replacement is obtained.

Claim 56

The method of claim 50 wherein said device is stretched in application to the scrotum whereby the device conforms to and clings to the scrotal skin.

Claim 57

The device of claim 44 wherein said tack is in the range of 100-300 g/cm 2 at 35° C.

Claim 58

The device of claim 46 wherein said tack is in the range of 100-300 g/cm 2 at 35° C.