US4704282A
Expired / Lapsed
US
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Transdermal therapeutic system having improved delivery characteristics
Assignee: Alza Corp
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Filing: 1984-06-29
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Granted: 1987-11-03
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Expires: 2004-06-29
Abstract
Abstract A transdermal therapeutic system using a subsaturated matrix is provided having improved approved release characteristics. Reinforcing means preferably in the form of a fabric are embedded in the upper surface of the subsaturated matrix. At least a portion of the reinforcing means is selected such that the active agent to be delivered to the skin has a solubility, C r therein which is lower than the initial solubility C o of the agent in the matrix. In addition, the relationship between the diffusion coefficients of the agent in the matrix D m and the portion of reinforcing means D r and the solubilities is given by the relationship: D r ·C r <D m ·C o . In operation the agent dissolved in the reinforcing means acts as a secondary reservoir improving the release characteristics of the system. Specific embodiments of the invention are particularly adapted for scrotal and labial delivery of drugs such as testosterone and progesterone.
Inventors
- 👤 Patricia S. Campbell
- 👤 James B. Eckenhoff
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 14:02
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/70; A61K9/7023; A61K9/703; A61K9/7038; A61K9/7046; A61K9/7053; A61K9/7069; Y; Y10; Y10S; Y10S424/00; Y10S424/14
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
143 words
A subsaturated transdermal therapeutic system having improved release characteristics comprising, in combination: (a) a matrix containing an active agent to be dispensed therefrom at an initial concentration, C o , no greater than the saturation concentration of the agent in the matrix; (b) reinforcing means within the matrix, at least a portion of said reinforcing means being a solvent for said agent, said portion of said reinforcing means having a solubility for said agent, C r , less than the initial concentration of the agent in the matrix and wherein the diffusion coefficient of said agent in said matrix is D m , the diffusion coefficient of said agent in the solvent portion of said reinforcing means is D r and the values of D m , D r , C o and C r are selected such that: D.sub.r ·C.sub.r <D.sub.m ·C.sub.o.
Claim 2
Dependent Claim
143 words
A subsaturated transdermal therapeutic system having improved release characteristics comprising, in combination: (a) a matrix containing an active agent to be dispensed therefrom at an initial concentration, C o , no greater than the saturation concentration of the agent in the matrix; (b) reinforcing means within the matrix, at least a portion of said reinforcing means being a solvent for said agent, said portion of said reinforcing means having a solubility for said agent, C r , less than the initial concentration of the agent in the matrix and wherein the diffusion coefficient of said agent in said matrix is D m , the diffusion coefficient of said agent in the solvent portion of said reinforcing means is D r and the values of D m , D r , C o and C r are selected such that: D.sub.r ·C.sub.r <D.sub.m ·C.sub.o.
Claim 3
Dependent Claim
23 words
The transdermal therapeutic system of claim 1 wherein D r ·C r is at least 10% less than D m ·C o .
Claim 4
Dependent Claim
23 words
The transdermal therapeutic system of claim 2 wherein said reinforcing means comprises a fabric imbedded in the body distal portion of the system.
Claim 5
Dependent Claim
23 words
The transdermal therapeutic system of claim 3 wherein the overall thickness of said system is in the range of from about 2-10 mils.
Claim 6
Dependent Claim
72 words
A transdermal therapeutic system according to claim 1 particularly adapted for application to sensitive skin surfaces for an extended time period wherein said reinforcing means comprises fibrous means imbedded in the body distal surface of said matrix and said matrix is adherent to said sensitive skin surfaces with a peel strength sufficiently high to maintain said system in place for said extended time period and sufficiently low to be removed without discomfort.
Claim 7
Dependent Claim
21 words
The system of claim 5 wherein the peel strength of said material from skin is in the range of 1-20 gm/cm.
Claim 8
Dependent Claim
19 words
The system of claim 5 wherein the overall thickness of the system is in the range of 2-10 mils.
Claim 9
Dependent Claim
44 words
The system of claim 7 wherein said agent is selected from the group consisting of testosterone and progesterone and and said matrix comprises an ethylene/vinyl acetate copolymer containing from about 40 to 60% vinyl acetate and said system is from about 2-10 mils thick.
Claim 10
Dependent Claim
43 words
A method of transdermal administration of an agent which comprises applying a system according to claim 7 to the scrotum of a male subject or the labia of a female subject and maintaining said system in place for an extended period of time.
Claim 11
Dependent Claim
43 words
A method of transdermal administration of an agent which comprises applying a system according to claim 8 to the scrotum of a male subject or the labia of a female subject and maintaining said system in place for an extended period of time.
Claim 12
Dependent Claim
15 words
The transdermal therapeutic system of claim 1 wherein said reinforcing means comprise fibrous reinforcing means.
Claim 13
Dependent Claim
22 words
The transdermal therapeutic system of claim 11 wherein said fibrous reinforcing means are imbedded in the skin distal surface of said matrix.
Claim 14
Dependent Claim
25 words
The transdermal therapeutic system of claim 11 wherein the solvent portion of said reinforcing means is a coating on the fibers forming said reinforcing means.
Claim 15
Dependent Claim
24 words
The transdermal therapeutic system of claim 12 wherein the solvent portion of said reinforcing means is a coating on fibers forming said reinforcing means.
Claim 16
Dependent Claim
11 words
This system according to claim 8 wherein said agent is testosterone.
Claim 17
Dependent Claim
10 words
The system of claim 8 wherein said agent is progesterone.
Claim 18
Dependent Claim
15 words
The transdermal therapeutic system of claim 8 wherein said reinforcing means comprises fibrous reinforcing means.
Claim 19
Dependent Claim
22 words
The transdermal therapeutic system of claim 17 wherein said fibrous reinforcing means are imbedded in the skin distal surface of said matrix.
Claim 20
Dependent Claim
25 words
The transdermal therapeutic system of claim 18 wherein the solvent portion of said reinforcing means is a coating on the fibers forming said reinforcing means.
Claim 21
Dependent Claim
180 words
A transdermal therapeutic system particularly adapted for application to sensitive skin surfaces for an extended time period comprising, in combination: (a) a matrix containing an active agent to be dispensed therefrom at an initial concentration, C o , no greater than the saturation concentration of said agent in the matrix and having a diffusion coefficient of said agent in said matrix, D m ; (b) fibrous reinforcing means imbedded in the body distal surface of said matrix, at least the exterior portion of said fibrous reinforcing means being a solvent for said agent having a solubility for said agent, C r , less than C o , and having a diffusion coefficient for said agent in said portion, D r ; (c) said agent, matrix and exterior portion of said fibrous reinforcing means are selected such that: D.sub.r ·C.sub.r <D.sub.m ·C.sub.o ; and (d) said matrix being adherent to said sensitive skin surface with a peel strength sufficiently high to allow said system to remain in place for said extended time period and sufficiently low to the removed without discomfort.
Claim 22
Dependent Claim
180 words
A transdermal therapeutic system particularly adapted for application to sensitive skin surfaces for an extended time period comprising, in combination: (a) a matrix containing an active agent to be dispensed therefrom at an initial concentration, C o , no greater than the saturation concentration of said agent in the matrix and having a diffusion coefficient of said agent in said matrix, D m ; (b) fibrous reinforcing means imbedded in the body distal surface of said matrix, at least the exterior portion of said fibrous reinforcing means being a solvent for said agent having a solubility for said agent, C r , less than C o , and having a diffusion coefficient for said agent in said portion, D r ; (c) said agent, matrix and exterior portion of said fibrous reinforcing means are selected such that: D.sub.r ·C.sub.r <D.sub.m ·C.sub.o ; and (d) said matrix being adherent to said sensitive skin surface with a peel strength sufficiently high to allow said system to remain in place for said extended time period and sufficiently low to the removed without discomfort.
Claim 23
Dependent Claim
23 words
The transdermal therapeutic system of claim 20 wherein D r ·C r is at least 10% less than D m ·C o .
Claim 24
Dependent Claim
21 words
The transdermal therpeutic system of claim 20 wherein the overall thickness of said system is in the range of 2-10 mils.
Claim 25
Dependent Claim
28 words
The transdermal therapeutic system of claim 20 wherein said matrix is selected from the group consisting of ethylene/vinyl acetate copolymer, natural rubbers, synthetic rubbers, and low density polyethylene.
Claim 26
Dependent Claim
25 words
The transdermal therapeutic system for claim 21 wherein said exterior portion of said reinforcing means is selected form the group consisting of polyolefins and polyarylamides.
Claim 27
Dependent Claim
21 words
The transdermal therapeutic system of claim 22 wherein said agent is selected from the group consisting of progesterone, testosterone and hydrocortisone.
Claim 28
Dependent Claim
41 words
The transdermal therapeutic system of claim 23 wherein said matrix is selected from the group consisting of ethylene/vinyl acetate copolymers and styrene-butadiene block copolymers, said exterior portion of said reinforcing means is selected from the group consisting of polyolefins and polyarylamides.
Claim 29
Dependent Claim
21 words
The transdermal therapeutic system of claim 26 wherein said agent is selected from the group consisting of progesterone, testosterone and hydrocortisone.
Claim 30
Dependent Claim
25 words
The transdermal therapeutic system of claim 26 wherein said matrix is an ethylene/vinyl acetate copolymer and said exterior portion of said reinforcing means is polyethylene.
Claim 31
Dependent Claim
26 words
The transdermal therapeutic system of claim 26 wherein said matrix is a styrene-butadiene block copolymer and said exterior portion of said reinforcing means is a polyarylamide.
Claim 32
Dependent Claim
25 words
The transdermal therapeutic system of claim 27 wherein said matrix is an ethylene/vinyl acetate copolymer and said exterior portion of said reinforcing means is polyethylene.
Claim 33
Dependent Claim
26 words
The transdermal therapeutic system of claim 27 wherein said matrix is a styrene-butadiene block copolymer and said exterior portion of said reinforcing means is a polyarylamide.
Claim 34
Dependent Claim
11 words
The transdermal therapeutic system claim 30 wherein said agent is progesterone.
Claim 35
Dependent Claim
12 words
The transdermal therapeutic system of claim 30 wherein said agent is testosterone.
Claim 36
Dependent Claim
12 words
The transdermal therapeutic system of claim 31 wherein said agent is hydrocortisone.
Claim 37
Dependent Claim
12 words
The transdermal therapeutic system of claim 8 wherein said agent is testosterone.
Claim 38
Dependent Claim
12 words
The transdermal therapeutic system of claim 1 wherein said agent is testosterone.
Claim 39
Dependent Claim
40 words
A method for testosterone replacement in hypogonadic males which comprises applying the system of claim 35 to the scrotum of a hypogonadic male and maintaining said system in testosterone transfering relationship to said scrotum for at least about 8 hours.
Claim 40
Dependent Claim
40 words
A method for testosterone replacement in hypogonadic males which comprises applying the system of claim 36 to the scrotum of a hypogonadic male and maintaining said system in testosterone transfering relationship to said scrotum for at least about 8 hours.
Claim 41
Dependent Claim
31 words
The method of claim 37 wherein said system is maintained in place for about 24 hours and is replaced with a fresh system upon removal whereby continuous testosterone replacement is obtained.
Claim 42
Dependent Claim
31 words
The method of claim 38 wherein said system is maintained in place for about 24 hours and is replaced with a fresh system upon removal whereby continuous testosterone replacement is obtained.
Claim 43
Dependent Claim
24 words
The system of claim 20 wherein said agent is testosterone and said matrix is an ethylene/vinyl acetate copolymer having from about 40%-60% vanyl acetate.
Claim 44
Dependent Claim
40 words
A method for testosterone replacement in hypogonadic males which comprises applying the system of claim 41 to the scrotum of a hypogonadic male and maintaining said system in testosterone transfering relationship to said scrotum for at least about 8 hours.
Claim 45
Dependent Claim
31 words
The method of claim 42 wherein said system is maintained in place for about 24 hours and is replaced with a fresh system upon removal whereby continuous testosterone replacement is obtained.
References Cited (Backward Citations)
US3813466A
Cited
US3598122A
Cited
US3598122B1
Cited
US4069307A
Cited
US3742951B1
Cited
US3742951A
Cited
US3923939A
Cited
US4144317A
Cited
US4262003A
Cited
GB1594389A
Cited
US4201211A
Cited
GB2030860A
Cited
US4243656A
Cited
JPS5699410A
Cited
US4286592A
Cited
GB2086224A
Cited
US4379454A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1990-11-02 | 1991-05-04 | 1991-11-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1994-11-02 | 1995-05-04 | 1995-11-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1998-11-02 | 1999-05-04 | 1999-11-03 | $7700.00 | Window Closed / Lapsed |