US5455229A
Expired / Lapsed
US
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Method for minimizing and containing ischemic and reperfusion injury
Assignee: Eli Lilly and Co
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Filing: 1992-12-23
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Granted: 1995-10-03
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Expires: 2012-12-23
Abstract
Abstract The present invention is a method for minimizing and containing injury caused when tissue is subject to ischemia and reperfusion. The method comprises administering certain derivatized tripeptide arginal compounds concurent with, or immediately after, reestablishing blood flow to the ischemic tissue. The method is particularly useful for minimizing and containing damage to the heart during evolving myocardial infarction.
Inventors
- 👤 Richard A. Hahn
- 👤 Brian R. MacDonald
- 👤 Robert T. Shuman
- 👤 Gerald F. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 08:14
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/04; C07K5/08; C07K5/0821; A; A61; A61K; A61K38/00; A61K38/04; A61K38/06; C07K5/0802; C07K5/0812
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
113 words
A method of treatment for minimizing and containing reperfusion injury in mammals which comprises administering to a mammal in need of such treatment an effective non-toxic amount of a compound of the general formula: A-Pro-Arg-H wherein substituent A has an α-carbon, the stereochemical configuration of which is either D or L, preferably D, and wherein Pro and Arg are both of the L configuration; ##STR8## Z is C 1 -C 4 alkyl, or H; X is NH 2 , NHZ, t-butyloxycarbonyl-NH, acetyl-NH, or trifluoroacetyl-NH; R is H, OH, halogen, alkoxy, CF 3 , C 1 -C 4 alkyl, NO 2 , or NH 2 ; and, q is CH 2 , or CO.
Claim 2
Independent Claim
113 words
A method of treatment for minimizing and containing reperfusion injury in mammals which comprises administering to a mammal in need of such treatment an effective non-toxic amount of a compound of the general formula: A-Pro-Arg-H wherein substituent A has an α-carbon, the stereochemical configuration of which is either D or L, preferably D, and wherein Pro and Arg are both of the L configuration; ##STR8## Z is C 1 -C 4 alkyl, or H; X is NH 2 , NHZ, t-butyloxycarbonyl-NH, acetyl-NH, or trifluoroacetyl-NH; R is H, OH, halogen, alkoxy, CF 3 , C 1 -C 4 alkyl, NO 2 , or NH 2 ; and, q is CH 2 , or CO.
Claim 3
Dependent Claim
13 words
The method of claim 1 wherein the administering is done by intravenous infusion.
Claim 4
Dependent Claim
19 words
The method of claim 2 wherein the mammal in need of treatment is a mammal experiencing evolving myocardial infarction.
Claim 5
Dependent Claim
12 words
The method of claim 3 wherein the mammal is a human being.
Claim 6
Dependent Claim
17 words
The method of claim 1 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 7
Dependent Claim
17 words
The method of claim 2 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 8
Dependent Claim
17 words
The method of claim 3 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 9
Dependent Claim
17 words
The method of claim 4 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 10
Independent Claim
42 words
A method for minimizing and containing reperfusion injury in mammals which comprises administering to a mammal in need of such treatment an effective non-toxic amount of a compound selected from the group consisting of D-3-Piq-L-Prolyl-L-Arginal, D-7-hydroxyl-1,2,3,4-Tiq-3-carbonyloxy-L-Prolyl-L-Arginal, D-3-Tiq-L-Prolyl-L-Arginal, D-1,2,3,4-Tiq-1-carbonyl-L-Prolyl-L-Arginal, N-Methyl-D-Phenylalanyl-L-Prolyl-L-Arginal, and N.sup.α -t-butyloxycarbonyl-D-Phenylanyl-L-Prolyl-L-Arginal.
Claim 11
Independent Claim
42 words
A method for minimizing and containing reperfusion injury in mammals which comprises administering to a mammal in need of such treatment an effective non-toxic amount of a compound selected from the group consisting of D-3-Piq-L-Prolyl-L-Arginal, D-7-hydroxyl-1,2,3,4-Tiq-3-carbonyloxy-L-Prolyl-L-Arginal, D-3-Tiq-L-Prolyl-L-Arginal, D-1,2,3,4-Tiq-1-carbonyl-L-Prolyl-L-Arginal, N-Methyl-D-Phenylalanyl-L-Prolyl-L-Arginal, and N.sup.α -t-butyloxycarbonyl-D-Phenylanyl-L-Prolyl-L-Arginal.
Claim 12
Dependent Claim
13 words
The method of claim 9 wherein the administering is done by intravenous infusion.
Claim 13
Dependent Claim
19 words
The method of claim 10 wherein the mammal in need of treatment is a mammal experiencing evolving myocardial infarction.
Claim 14
Dependent Claim
12 words
The method of claim 11 wherein the mammal is a human being.
Claim 15
Dependent Claim
17 words
The method of claim 9 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 16
Dependent Claim
17 words
The method of claim 10 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 17
Dependent Claim
17 words
The method of claim 11 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 18
Dependent Claim
17 words
The method of claim 12 wherein the compound is co-administered with an effective, non-toxic amount of aspirin.
Claim 19
Dependent Claim
11 words
The method of claim 1 wherein the administered compound is D-3-Piq-L-Prolyl-L-Arginal.
Claim 20
Dependent Claim
11 words
The method of claim 1 wherein the administered compound is D-7-hydroxyl-1,2,3,4-Tiq-3-carbonyloxy-L-Prolyl-L-Arginal.
Claim 21
Dependent Claim
11 words
The method of claim 1 wherein the administered compound is D-3-Tiq-L-Prolyl-L-Arginal.
Claim 22
Dependent Claim
11 words
The method of claim 1 wherein the administered compound is D-1,2,3,4-Tiq-1-carbonyl-L-Prolyl-L-Arginal.
Claim 23
Dependent Claim
11 words
The method of claim 1 wherein the administered compound is N-Methyl-D-Phenytalanyl-L-Prolyl-L-Arginal.
Claim 24
Dependent Claim
12 words
The method of claim 1 wherein the administered compound is N.sup.α -t-butyloxycarbonyl-D-Phenylanyl-L-Prolyl-L-Arginal.
References Cited (Backward Citations)
US4703036A
Cited
EP0479489A2
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1998-10-02 | 1999-04-03 | 1999-10-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-10-02 | 2003-04-03 | 2003-10-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-10-02 | 2007-04-03 | 2007-10-03 | $7700.00 | Window Closed / Lapsed |