US4254145A
Expired / Lapsed
US
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Topical application of prostaglandin hypotensive agents
Assignee: Wyeth Holdings LLC
•
Filing: 1978-08-16
•
Granted: 1981-03-03
•
Expires: 1998-08-16
Abstract
Abstract Pharmaceutical compositions useful as vasodilators whose activity may be restricted to the site of application by control of the dose applied which comprises a prostaglandin selected from the group consisting of the natural and synthetic analogs of the PGE, PGA and PGE.sub.β types in a pharmaceutical carrier. The compositions are applied topically and by local injection to increase peripheral circulation, or to treat peripheral vascular disorders of the arteriospastic and occlusive types. The prostaglandins and pharmaceutical compositions containing them disclosed herein are also administered topically and by local injection to lower the systemic blood pressure of man and warm blooded animals. Systemic action is obtained by the use of an effective dosage greater than that used to induce localized action at the site of application.
Inventors
- 👤 Jay E. Birnbaum
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 13:15
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0014; A61K31/00; A61K31/557; A61K47/00; A61K47/06; A61K47/16; A61K47/18; A61K9/0019; A61P; A61P43/00; A61P9/00; A61P9/08; A61P9/12
Claims Analysis
Total Claims: 76
Claim 1
Independent Claim
182 words
A process of reducing systemic blood pressure comprising the topical application to a warm-blood animal or human of an effective amount of an optically active prostaglandin compound, of the following formula: ##STR10## the mirror image thereof, and the racemic mixture thereof wherein W is selected from the group consisting of: ##STR11## wherein R 3 is selected from the group consisting of hydrogen, hydroxyl and HOCH 2 CH 2 S--; Z is selected from the group consisting of ##STR12## wherein n and m have the value of from 3 to 5 inclusive; R 14 is selected from the group consisting of hydroxyl, C 1 -C 6 alkoxy, --CH 2 OH and --CH 2 OR 15 wherein R 15 is C 2 -C 6 alkanoyl; C 13 -C 14 is ethylene or trans-vinylene; R 7 is a moiety selected from the group consisting of ##STR13## wherein R 8 is selected from the group consisting of ##STR14## wherein R 16 is E-1-propenyl or Z-1-propenyl, R 17 is C 3 to C 7 alkyl; and, when R 14 is hydroxy, the pharmacologically acceptable cationic salts thereof.
Claim 2
Dependent Claim
182 words
A process of reducing systemic blood pressure comprising the topical application to a warm-blood animal or human of an effective amount of an optically active prostaglandin compound, of the following formula: ##STR10## the mirror image thereof, and the racemic mixture thereof wherein W is selected from the group consisting of: ##STR11## wherein R 3 is selected from the group consisting of hydrogen, hydroxyl and HOCH 2 CH 2 S--; Z is selected from the group consisting of ##STR12## wherein n and m have the value of from 3 to 5 inclusive; R 14 is selected from the group consisting of hydroxyl, C 1 -C 6 alkoxy, --CH 2 OH and --CH 2 OR 15 wherein R 15 is C 2 -C 6 alkanoyl; C 13 -C 14 is ethylene or trans-vinylene; R 7 is a moiety selected from the group consisting of ##STR13## wherein R 8 is selected from the group consisting of ##STR14## wherein R 16 is E-1-propenyl or Z-1-propenyl, R 17 is C 3 to C 7 alkyl; and, when R 14 is hydroxy, the pharmacologically acceptable cationic salts thereof.
Claim 3
Dependent Claim
14 words
The process according to claim 1, wherein n is 3 and m is 4.
Claim 4
Dependent Claim
17 words
The process according to claim 2, wherein W is ##STR15## and C 13 -C 14 is trans-vinylene.
Claim 5
Dependent Claim
17 words
The process according to claim 2, wherein W is ##STR16## and C 13 -C 14 is trans-vinylene.
Claim 6
Dependent Claim
17 words
The process according to claim 2, wherein W is ##STR17## and C 13 -C 14 is trans-vinylene.
Claim 7
Dependent Claim
11 words
The process according to claim 3, wherein R 3 is hydroxy.
Claim 8
Dependent Claim
17 words
The process according to claim 3, wherein Z is ##STR18## and R 3 is hydrogen or hydroxyl.
Claim 9
Dependent Claim
24 words
The process according to claim 1, wherein R 7 is selected from the group consisting of ##STR19## wherein R 17 is as previously defined.
Claim 10
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl-9-oxo-11α,16-dihydroxy-16-vinyl-5-cis, 13-trans-prostadienoate.
Claim 11
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadienoic acid.
Claim 12
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-ethynyl-5-cis,13-trans-prostadienoic acid.
Claim 13
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadienoic acid.
Claim 14
Dependent Claim
13 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-methyl-5-cis, 13-trans-prostadienoic acid.
Claim 15
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-5-cis,13-trans-prostadienoic acid.
Claim 16
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-5-cis,13-trans-prostadienoic acid.
Claim 17
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-5-cis,13-trans-prostadienoate
Claim 18
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-13-trans-prostenoic acid.
Claim 19
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-13-trans-prostenoic acid.
Claim 20
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-13-trans-prostenoate.
Claim 21
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-13-trans-prostenoate.
Claim 22
Dependent Claim
13 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadienoate acid.
Claim 23
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadienoic acid.
Claim 24
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadienoate.
Claim 25
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadienoate.
Claim 26
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-nor-13-trans-prostenoic acid.
Claim 27
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-nor-13-trans-prostenoic acid.
Claim 28
Dependent Claim
12 words
The process according to claim 8, wherein said prostglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-nor-13-trans-prostenoate.
Claim 29
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-20-nor-13-trans-prostenoate.
Claim 30
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-ethyl-13-prostadienoate.
Claim 31
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-methyl-5-cis,13-trans-prostadienoic acid.
Claim 32
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-methyl-5-cis,13-trans-prostadienoate.
Claim 33
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-2-methyl-5-cis,13-trans-prostadienoate.
Claim 34
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-methyl-13-trans-prostenoic acid.
Claim 35
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-methyl-13-trans-prostenoic acid.
Claim 36
Dependent Claim
12 words
The process according to claim 8 wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-methyl-13-trans-prostenoate.
Claim 37
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-20-methyl-13-trans-prostenoate.
Claim 38
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-ethyl-13-trans-prostenoic acid.
Claim 39
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-9-oxo-11α,16α-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadienoic acid.
Claim 40
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is methyl 9-oxo-11α,16-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadienoate.
Claim 41
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is nat.-methyl 9-oxo-11α,16α-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadienoate.
Claim 42
Dependent Claim
12 words
The process according to claim 8, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-vinyl-20-ethyl-13-trans-prostenoic acid.
Claim 43
Dependent Claim
35 words
The process according to claim 1, wherein R 14 is selected from the group consisting of ##STR20## wherein R 15 is methyl or ethyl; and wherein Z is selected from the group consisting of ##STR21##
Claim 44
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-13-trans-prostene.
Claim 45
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-5-cis,13-trans-prostadiene.
Claim 46
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-ethyl-5-cis,13-trans-prostadiene.
Claim 47
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-5-cis,13-trans-prostadiene.
Claim 48
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-ethyl-13-trans-prostene.
Claim 49
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-13-trans-prostene.
Claim 50
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadiene.
Claim 51
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-nor-5-cis,13-trans-prostadiene.
Claim 52
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-nor-13-trans-prostene.
Claim 53
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-nor-13-trans-prostene.
Claim 54
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-methyl-5-cis,13-trans-prostadiene.
Claim 55
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-methyl-5-cis,13-trans-prostadiene.
Claim 56
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-methyl-13-trans-prostene.
Claim 57
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-methyl-13-trans-prostene.
Claim 58
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is 1,9-dioxo-1-hydroxymethyl-11α,16-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadiene.
Claim 59
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-ethyl-5-cis,13-trans-prostadiene.
Claim 60
Dependent Claim
11 words
The process according to claim 42, wherein said prostaglandin is nat.-1,9-dioxo-1-hydroxymethyl-11α,16α-dihydroxy-16-vinyl-20-ethyl-13-trans-prostene.
Claim 61
Dependent Claim
11 words
The process according to claim 1, wherein said prostaglandin is methyl-9-oxo-11α,16-dihydroxy-5-cis,13-trans-prostadienoate.
Claim 62
Dependent Claim
12 words
The process according to claim 1, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-methyl-5-cis,13-trans,17-trans-prostatrienoic acid.
Claim 63
Dependent Claim
12 words
The process according to claim 1, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-methyl-5-cis,13-trans-prostadienoic acid.
Claim 64
Dependent Claim
12 words
The process according to claim 1, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-cyclopropyl-5-cis,13-trans-prostadienoic acid.
Claim 65
Dependent Claim
12 words
The process according to claim 1, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-16-(2-propenyl)-5-cis,13-trans-prostadienoic acid.
Claim 66
Dependent Claim
12 words
The process according to claim 1, wherein said prostaglandin is 9-oxo-11α,16-dihydroxy-13-trans-17-trans-prostadienoic acid.
Claim 67
Dependent Claim
29 words
The process according to claim 1, wherein the prostaglandin is contained in an ointment vehicle, wherein the prostaglandin comprises from about 0.3 to 20 weight percent of the composition.
Claim 68
Dependent Claim
47 words
The process according to claim 66, wherein the composition comprises from about 0.95% to 5% by weight prostaglandin, and from about 75% to 95% by weight vehicle, wherein the vehicle includes a solubilizer, wherein the solubilizer comprises from about 5 to 25% by weight of the composition.
Claim 69
Dependent Claim
31 words
The process according to claim 67, wherein the composition includes a prostaglandin selected from the group consisting of PGE 1 and PGE 2 prostaglandins of claim 52 having a 16-vinyl substituent.
Claim 70
Dependent Claim
30 words
The process according to claim 68, wherein the prostaglandin composition comprises about 79% by weight petrolatum, about 20% by weight diisopropyl adipate or polyethylene glycol dioleate, and about 1% prostaglandin.
Claim 71
Dependent Claim
25 words
The process according to claim 68, wherein the prostaglandin composition comprises from about 1% to 5% by weight prostaglandin in an alcohol in Aquatain® vehicle.
Claim 72
Dependent Claim
16 words
The process according to claim 1, wherein the prostaglandin is administered by a sustained release support.
Claim 73
Dependent Claim
13 words
The process according to claim 71, wherein the support includes a hydrophilic polymer.
Claim 74
Dependent Claim
24 words
The process according to claim 1, wherein the effective dosage comprises from about 0.1 mg to 10 mg per kg body weight per day.
Claim 75
Dependent Claim
87 words
The process of reducing systemic blood pressure which comprises the topical application to a hypertensive individual of an effective amount of an optically active compound of the formula: ##STR22## the mirror image thereof, and racemic mixtures thereof, wherein R 1 is selected from the group consisting of hydrogen, methyl and ethyl; R 2 is selected from the group consisting of hydrogen, methyl and ethyl; C 17 -C 18 is selected from the group consisting of ethylene and trans-vinylene; and n is an integer from 0 to 3.
Claim 76
Dependent Claim
87 words
The process of reducing systemic blood pressure which comprises the topical application to a hypertensive individual of an effective amount of an optically active compound of the formula: ##STR22## the mirror image thereof, and racemic mixtures thereof, wherein R 1 is selected from the group consisting of hydrogen, methyl and ethyl; R 2 is selected from the group consisting of hydrogen, methyl and ethyl; C 17 -C 18 is selected from the group consisting of ethylene and trans-vinylene; and n is an integer from 0 to 3.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1984-03-02 | 1984-09-01 | 1985-03-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-03-02 | 1988-09-01 | 1989-03-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-03-02 | 1992-09-01 | 1993-03-03 | $7700.00 | Window Closed / Lapsed |