Claims
- 1. A method for treating a disease or medical disorder which can be ameliorated by delivery of NO or its biological equivalent to tissues affected by the disease or medical disorder, in an animal or human, comprising administering to the animal or human a therapeutically effective amount of a composition comprising nitrosylhemoglobin, nitrosyl-heme, a substituted form of hemoglobin in which a different metal is substituted for the heme iron, or a substituted form of hemoglobin in which a nitrosyl-porphyrin is substituted for the heme.
- 2. The method of claim 1 wherein the nitrosyl-heme-containing donor of NO is nitrosylhemoglobin.
- 3. Method for making stable nitrosyl-deoxyhemoglobin comprising adding NO to deoxyhemoglobin in an aqueous solution such that the ratio of added NO:heme is less than about 1:100 or greater than about 0.75.
- 4. Method for making SNO-oxyhemoglobin, comprising adding NO to an aqueous solution of oxyhemoglobin and buffer having a pK of at least about 9.4, at a concentration of approximately 10 mM to 200 mM, at pH 7.4.
- 5. Method for making nitrosyl-oxyhemoglobin comprising adding NO to oxyhemoglobin in an aqueous solution such that the ratio of NO:hemoglobin is less than about 1:30.
- 6. Hemoglobin conjugated to an NO-donor.
- 7. Hemoglobin of claim 6, wherein the NO-donor is selected from the group consisting of: diazeniumdiolates, nitroprusside, nitroglycerin and nitrosothiol.
- 8. A composition comprising hemoglobin and one or more NO-donors.
- 9. A method for treating or preventing a disease or medical disorder which can be ameliorated by delivery of NO or its biological equivalent to tissues affected by the disease or medical disorder, in an animal or human, comprising administering a heme-based blood substitute and inhaled NO to the animal or human.
- 10. A method for delivering CO to the tissues in an animal or human, comprising administering CO-derivatized hemoglobin to the animal or human.
- 11. A method of treating or preventing a disease or medical disorder which can be ameliorated by delivery of NO or its biological equivalent to tissues affected by the disease or medical disorder in an animal or human, comprising administering CO-derivatized hemoglobin and a nitrosated hemoglobin to the animal or human.
- 12. Nitrosylhemoglobin conjugated to one or more electron acceptors.
- 13. Nitrosylhemoglobin of claim 12, wherein the electron acceptor is selected from the group consisting of: superoxide dismutase, stable nitroxide radicals, and oxidized forms of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, flavin adenine dinucleotide, flavin mononucleotide, ascorbate and dehydroascorbate.
- 14. A composition comprising nitrosylhemoglobin and one or more electron acceptors.
- 15. Hemoglobin conjugated to nitric oxide synthase.
- 16. Hemoglobin of claim 15, wherein the nitric oxide synthase is nitric oxide synthase of neurons.
- 17. A composition comprising hemoglobin and nitric oxide synthase.
- 18. A method for making isolated erythrocytes comprising nitrosylhemoglobin, comprising incubating deoxygenated erythrocytes in a solution comprising NO.
- 19. Isolated erythrocytes comprising nitrosylhemoglobin.
- 20. A method for treating shock in an animal or human comprising administering hemoglobin α-chains to the animal or human.
- 21. A method for treating or preventing a disease or medical disorder which can be ameliorated by delivery of NO or its biological equivalent to tissues affected by the disease or medical disorder, in an animal or human, comprising administering hemoglobin β-chains to the animal or human.
- 22. A method for assessing oxygen delivery to a site in the body, comprising determining S-nitrosohemoglobin and nitrosylhemoglobin values in a blood sample from the site, and using said values to assess oxygen delivery.
- 23. The method of claim 22, further comprising determining an oxygen value in the blood sample and using said value to assess oxygen delivery.
- 24. A method for treating ischemic injury in a mammal, said method comprising administering to the mammal a nitrosyl-heme-containing donor of NO.
- 25. A method for treating hypertension in a mammal, said method comprising administering to the mammal a therapeutically effective amount of a composition comprising nitrosylhemoglobin, nitrosyl-heme, a substituted form of hemoglobin in which a different metal is subsituted for the heme iron, or a substituted form of hemoglobin in which a nitrosyl-porphyrin is substituted for the heme.
- 26. A method for treating angina in a mammal, said method comprising administering to the mammal a nitrosyl-heme-containing donor of NO.
- 27. A method for delivering NO or its biologically active form to tissues in a mammal, said method comprising administering to the animal or human a therapeutically effective amount of a composition comprising nitrosylhemoglobin, nitrosyl-heme, a substituted form of hemoglobin in which a different metal is substituted for the heme iron, or a substituted form of hemoglobin in which a nitrosyl-porphyrin is substituted for the heme.
- 28. A method for delivering NO or its biologically active form to tissues in an animal or human, said method comprising administering to the animal or human a therapeutically effective amount of a composition comprising nitrosylhemoglobin.
- 29. A method for treating a disease or medical disorder which can be ameliorated by delivery of NO or its biological equivalent to tissues affected by the disease or medical disorder, in an animal or human, comprising administering to the animal or human a therapeutically effective amount of a composition comprising nitrosylhemoglobin or nitrosyl-heme.
- 30. A method for treating hypertension in a mammal, said method comprising administering to the mammal a therapeutically effective amount of a composition comprising nitrosylhemoglobin, nitrosyl-heme, or hemoglobin in which a nitrosyl-porphyrin is substituted for the heme.
- 31. A method for treating hypertension, ischemic injury or angina in a mammal, said method comprising administering to the mammal a therapeutically effective amount of a composition comprising nitrosylhemoglobin, nitrosyl-heme, or hemoglobin in which a nitrosyl-porphyrin is substituted for the heme.
- 32. A method for treating hypertension in a mammal, said method comprising administering to the mammal a therapeutically effective amount of a composition comprising nitrosylhemoglobin or nitrosyl-heme.
- 33. A method for treating hypertension, ischemic injury or angina in a mammal, said method comprising administering to the mammal a therapeutically effective amount of a composition comprising nitrosylhemoglobin.
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser. No. 09/369,966 filed on Aug. 6, 1999, which is a continuation of PCT/U.S.98/02383 filed on Feb. 5, 1998, which is a continuation-in-part of U.S. application Ser. No. 08/874,992 filed on Jun. 12, 1997, which is a continuation-in-part of U.S. application Ser. No. 08/796,164 filed on Feb. 6, 1997, which is a continuation-in-part of PCT/U.S.96/14659 filed on Sep. 13, 1996, which is a continuation of U.S. application Ser. No. 08/667,003 filed on Jun. 20, 1996, which is a continuation-in-part of U.S. application Ser. No. 08/616,371 filed on Mar. 15, 1996, which claims the benefit of U.S. Provisional Application No. 60/003,801 filed on Sep. 15, 1995. The teachings of all of the above applications are each incorporated herein by reference in their entirety.
GOVERNMENT SUPPORT
[0002] This invention was made with government support under Grant Nos. HL52529 and HR59130 awarded by the National Institutes of Health. The government has certain rights in the invention.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60003801 |
Sep 1995 |
US |
Continuations (3)
|
Number |
Date |
Country |
Parent |
09369966 |
Aug 1999 |
US |
Child |
10638969 |
Aug 2003 |
US |
Parent |
PCT/US98/02383 |
Feb 1998 |
US |
Child |
09369966 |
Aug 1999 |
US |
Parent |
08667003 |
Jun 1996 |
US |
Child |
08874992 |
|
US |
Continuation in Parts (4)
|
Number |
Date |
Country |
Parent |
08874992 |
Jun 1997 |
US |
Child |
PCT/US98/02383 |
Feb 1998 |
US |
Parent |
08796164 |
Feb 1997 |
US |
Child |
08874992 |
Jun 1997 |
US |
Parent |
PCT/US96/14659 |
Sep 1996 |
US |
Child |
08796164 |
Feb 1997 |
US |
Parent |
08616371 |
Mar 1996 |
US |
Child |
08667003 |
Jun 1996 |
US |