US5552267A
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Solution for prolonged organ preservation
Assignee: Columbia University
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Filing: 1994-12-05
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Granted: 1996-09-03
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Expires: 2014-12-05
Abstract
Abstract An aqueous solution for organ preservation or maintenance, which contains: a vasodilator in an amount sufficient to maintain vascular homeostasis; D-glucose in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; magnesium ions in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; macromolecules of molecular weight greater than 20,000 daltons in an amount sufficient to maintain endothelial integrity and cellular viability; potassium ions in a concentration greater than about 110 mM; and a buffer in an amount sufficient to maintain the average pH of the organ preservation or maintenance solution during the period of organ preservation at about physiologic pH or above.
Inventors
- 👤 David M. Stern
- 👤 Mehmet C. Oz
- 👤 Roman Nowygrod
- 👤 Shin Koga
- 👤 David J. Pinsky
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 14:56
CPC Classifications
A; A01; A01N; A01N1/00; A01N1/10; A01N1/12; A01N1/122; A01N1/126
Claims Analysis
Total Claims: 48
Claim 1
Independent Claim
115 words
An aqueous solution for organ preservation or maintenance, comprising: a) a phosphodiesterase inhibitor in an amount sufficient to maintain vascular homeostasis; b) D-glucose in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; c) magnesium ions in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; d) macromolecules of molecular weight greater than 20,000 daltons in an amount sufficient to maintain endothelial integrity and cellular viability; e) potassium ions in a concentration greater than about 110 mM; and f) a buffer in an amount sufficient to maintain the average pH of the organ preservation or maintenance solution during the period of organ preservation at about physiologic pH or above.
Claim 2
Dependent Claim
115 words
An aqueous solution for organ preservation or maintenance, comprising: a) a phosphodiesterase inhibitor in an amount sufficient to maintain vascular homeostasis; b) D-glucose in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; c) magnesium ions in an amount sufficient to support intracellular function and maintenance of cellular bioenergetics; d) macromolecules of molecular weight greater than 20,000 daltons in an amount sufficient to maintain endothelial integrity and cellular viability; e) potassium ions in a concentration greater than about 110 mM; and f) a buffer in an amount sufficient to maintain the average pH of the organ preservation or maintenance solution during the period of organ preservation at about physiologic pH or above.
Claim 3
Dependent Claim
26 words
The solution of claim 1, wherein the phosphodiesterase inhibitor is selected from the group consisting of isobutylmethylxanthine, indolidan, rolipram, 2-o-propoxyphenyl-8-azapurin-6-one, trequensin, amrinone, milrinone, aminophylline, and dipyridamole.
Claim 4
Dependent Claim
11 words
The solution of claim 2, wherein the phosphodiesterase inhibitor is indolidan.
Claim 5
Dependent Claim
11 words
The solution of claim 2, wherein the phosphodiesterase inhibitor is rolipram.
Claim 6
Dependent Claim
11 words
The solution of claim 2, wherein the phosphodiesterase inhibitor is 2-o-propoxyphenyl-8-azapurin-6-one.
Claim 7
Dependent Claim
19 words
The solution of claim 1, wherein the concentration of D-glucose ranges from about 50 mM to about 80 mM.
Claim 8
Dependent Claim
20 words
The solution of claim 1, wherein the concentration of magnesium ions ranges from about 2 mM to about 10 mM.
Claim 9
Dependent Claim
26 words
The solution of claim 1, wherein the magnesium ions are derived from compounds selected from the group consisting of magnesium sulfate, magnesium gluconate, and magnesium phosphate.
Claim 10
Dependent Claim
31 words
The solution of claim 1, wherein the macromolecules are selected from the group consisting of macromolecules having a molecular weight greater than about 100,000 daltons, a polysaccharide, and a polyethylene glycol.
Claim 11
Dependent Claim
11 words
The solution of claim 9, wherein the polysaccharide is a dextran.
Claim 12
Dependent Claim
19 words
The solution of claim 10, wherein the dextran is a dextran molecule having a molecular weight of 308,000 daltons.
Claim 13
Dependent Claim
31 words
The solution of claim 1, wherein the potassium ions are derived from compounds selected from the group consisting of potassium sulfate, potassium gluconate, and monopotassium phosphate (KH 2 PO 4 ).
Claim 14
Dependent Claim
20 words
The solution of claim 1, wherein the concentration of potassium ions ranges from about 110 mM to about 140 mM.
Claim 15
Dependent Claim
16 words
The solution of claim 1, wherein the buffer is monopotassium phosphate (KH 2 PO 4 ).
Claim 16
Dependent Claim
28 words
The solution of claim 1, further comprising a vasodilator selected from the group consisting of: adenosine 3',5'-cyclic monophosphate analogues; guanosine 3',5'-cyclic monophosphate analogues; adenosine; nitroglycerin; and pertussis toxin.
Claim 17
Dependent Claim
13 words
The solution of claim 15, wherein the vasodilator is dibutyryl adenosine 3',5'-cyclic monophosphate.
Claim 18
Dependent Claim
22 words
The solution of claim 16, wherein the concentration of dibutyryl adenosine 3',5'-cyclic monophosphate ranges from about 1 mM to about 4 mM.
Claim 19
Dependent Claim
19 words
The solution of claim 15, wherein the concentration of adenosine ranges from about 3 mM to about 20 mM.
Claim 20
Dependent Claim
23 words
The solution of claim 15, wherein the concentration of nitroglycerin ranges from about 0.05 grams per liter to about 0.2 grams per liter.
Claim 21
Dependent Claim
20 words
The solution of claim 1, further comprising impermeant anions in an amount sufficient to maintain endothelial integrity and cellular viability.
Claim 22
Dependent Claim
21 words
The solution of claim 20, wherein the impermeant anions are selected from the group consisting of gluconate anions and lactobionate anions.
Claim 23
Dependent Claim
25 words
The solution of claim 21, wherein the impermeant anions are gluconate anions having a concentration that ranges from about 85 mM to about 105 mM.
Claim 24
Dependent Claim
24 words
The solution of claim 21, wherein the impermeant anions are gluconate anions selected from the group consisting of potassium gluconate and magnesium gluconate compounds.
Claim 25
Dependent Claim
25 words
The solution of claim 1, further comprising an anticoagulant in an amount sufficient to prevent clotting of blood within the capillary bed of the organ.
Claim 26
Dependent Claim
18 words
The solution of claim 24, wherein the anticoagulant is selected from the group consisting of heparin and hirudin.
Claim 27
Dependent Claim
23 words
The solution of claim 25, wherein the anticoagulant is heparin having a concentration that ranges from about 1000 units/l to about 100,000 units/l.
Claim 28
Dependent Claim
22 words
The solution of claim 1, further comprising an antioxidant in an amount sufficient to decrease reperfusion injury secondary to oxygen free radicals.
Claim 29
Dependent Claim
26 words
The solution of claim 27, wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), Vitamin C, and Vitamin E.
Claim 30
Dependent Claim
24 words
The solution of claim 28, wherein the antioxidant is butylated hydroxyanisole (BHA) at a concentration range from about 25 microM to about 100 microM.
Claim 31
Dependent Claim
22 words
The solution of claim 29, further comprising butylated hydroxytoluene (BHT) at a concentration range from about 25 microM to about 100 microM.
Claim 32
Dependent Claim
23 words
The solution of claim 1, further comprising a reducing agent in an amount sufficient to decrease reperfusion injury secondary to oxygen free radicals.
Claim 33
Dependent Claim
17 words
The solution of claim 1, further comprising N-acetylcysteine in an amount sufficient for cells to produce glutathione.
Claim 34
Dependent Claim
19 words
The solution of claim 32, wherein the concentration of N-acetylcysteine ranges from about 0.1 mM to about 5 mM.
Claim 35
Dependent Claim
25 words
The solution of claim 1, further comprising an agent that prevents calcium entry into cells in an amount sufficient to prevent calcium entry into cells.
Claim 36
Dependent Claim
16 words
The solution of claim 34, wherein the agent that prevents calcium entry into cells is verapamil.
Claim 37
Dependent Claim
19 words
The solution of claim 35, wherein the concentration of verapamil ranges from about 2 microM to about 25 microM.
Claim 38
Dependent Claim
17 words
The solution of claim 1, further comprising a bacteriostat in an amount sufficient to inhibit bacterial growth.
Claim 39
Dependent Claim
18 words
The solution of claim 37, wherein the bacteriostat is selected from the group consisting of cefazolin and penicillin.
Claim 40
Dependent Claim
23 words
The solution of claim 38, wherein the bacteriostat is cefazolin having a concentration that ranges from about 0.25 g/l to about 1 g/l.
Claim 41
Dependent Claim
17 words
The solution of claim 1, wherein the osmolarity ranges from about 315 mOSm/l to about 340 mOSm/l.
Claim 42
Dependent Claim
18 words
A method of preserving or maintaining an organ, comprising contacting the organ with the solution of claim 1.
Claim 43
Dependent Claim
14 words
The method of claim 41, wherein the contacting comprises immersion, infusion, flushing, or perfusion.
Claim 44
Dependent Claim
14 words
The method of claim 41, wherein the organ is an organ intended for transplantation.
Claim 45
Dependent Claim
11 words
The method of claim 41, wherein the organ is a heart.
Claim 46
Dependent Claim
13 words
The method of claim 44, wherein the heart is involved in cardiac surgery.
Claim 47
Dependent Claim
11 words
The method of claim 41, wherein the organ is a lung.
Claim 48
Dependent Claim
28 words
The solution of claim 1, wherein the buffer is sufficient to maintain the average pH of the solution at about physiologic pH during the period of organ preservation.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-09-03 | 2000-03-04 | 2000-09-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-09-03 | 2004-03-04 | 2004-09-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-09-03 | 2008-03-04 | 2008-09-03 | $7700.00 | Window Closed / Lapsed |