Method for improving oxygen transport by stored red blood cells

• US 20030049232A1
• Filed: 09/10/2001
• Published: 03/13/2003
• Est. Priority Date: 09/10/2001
• Status: Active Grant

• Current Assignee: Hemoglobin Oxygen Therapeutics LLC
• Original Assignee: Bio Pure Technology Limited
• Inventors: Jacobs, Edward E. Jr., Page, Thomas C., Light, William R.
• Granted Patent: US 6,811,778 B2
• Time in Patent Office: Days
• US Class Current: 424/93.7
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61K 38/42 Haemoglobins; Myoglobins
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

A method of treatment of a patient includes administering to the patient stored red blood cells and a hemoglobin solution. The stored red blood cells and the hemoglobin solution can be administered to the patient simultaneously. Alternatively, the hemoglobin solution can be administered to the patient prior to administrating the stored red blood cells or the stored red blood cells can be administered to the patient prior to administering the hemoglobin solution. A composition of the invention includes stored red blood cells and a hemoglobin solution.

Claims

1. A method of treating a patient, comprising administering to the patient stored red blood cells and a hemoglobin solution.

2. The method of claim 1, wherein the hemoglobin solution is administered prior to administering the stored red blood cells.

3. The method of claim 2, wherein the stored red blood cells are administered within about thirty-six hours of administering the hemoglobin solution.

4. The method of claim 3, wherein the stored red blood cells are administered within about twenty-four hours of administering the hemoglobin solution.

5. The method of claim 4, wherein the stored red blood cells is administered within about eight hours of administering the hemoglobin solution.

6. The method of claim 1, wherein the stored red blood cells are administered simultaneously with or before administering the hemoglobin solution.

7. The method of claim 6, wherein the hemoglobin solution is administered within about eight hours of administering the stored red blood cells.

8. The method of claim 1, wherein the ratio of hemoglobin of the hemoglobin solution to hemoglobin of the stored red blood cells is in a range of between about 1:

9 and about 1;

1 by weight.

9. The method of claim 1, wherein the stored red blood cells have been stored for greater than about 48 hours.

10. The method of claim 7, wherein the stored red blood cells have been stored for greater than about seven days.

11. The method of claim 7, wherein the stored red blood cells have been stored for greater than about thirty-five days.

12. The method of claim 7, wherein the stored red blood cells have been stored for greater than about forty-two days.

13. The method of claim 1, wherein hemoglobin of the stored red blood cells has a P₅₀ of less than about 15 mm Hg.

14. The method of claim 1, wherein hemoglobin of the stored red blood cells has a P₅₀ of less than about 20 mm Hg.

15. The method of claim 1, wherein the hemoglobin of the stored red blood cells has a P₅₀ of less than about 25 mm Hg.

16. The method of claim 1, wherein the hemoglobin of the hemoglobin solution is polymerized.

17. The method of claim 16, wherein the hemoglobin is polymerized with glutaraldehyde.

18. The method of claim 16, wherein the polymerized hemoglobin solution has

a) a methemoglobin content less than about fifteen percent by weight;

b) an endotoxin concentration less than about 0.5 endotoxin units per milliliter;

c) less than, or equal to, about fifteen percent by weight polymerized hemoglobin with molecular weight greater than about 500,000 Daltons; and

d) less than, or equal to, about ten percent by weight polymerized hemoglobin with a molecular weight less than or equal to about 65,000 Daltons.

19. A method of treating a patient, comprising the steps of;

a) administering a hemoglobin solution to the patient; and

thereafter

b) administering stored red blood cells,

wherein the hemoglobin solution comprises polymerized hemoglobin and wherein the stored red blood cells have been stored for greater than

20. The method of claim 19, wherein the stored red blood cells have been stored for at least about 48 hours.

21. The method of claim 19, wherein hemoglobin of the hemoglobin solution has a P₅₀ of at least about 25 mm Hg.

22. The method of claim 19, wherein hemoglobin of the hemoglobin solution has been polymerized with glutaraldehyde.

23. A method of treating a patient, comprising the steps of;

a) administering stored red blood cells to the patient; and

thereafter

b) administering a hemoglobin solution to the patient,

wherein the hemoglobin solution comprises polymerized hemoglobin.

24. The method of claim 23, wherein the hemoglobin solution, is administered to the patient within about eight hours of administering the stored red blood cells.

25. The method of claim 24, wherein the stored red blood cells have been stored for at least about 48 hours.

26. The method of claim 23, wherein the hemoglobin has a P₅₀ of at least about 25 mm Hg.

27. The method of claim 23, wherein the hemoglobin has been polymerized with glutaraldehyde.

28. A composition comprising a hemoglobin solution and stored red blood cells, wherein the hemoglobin solution comprises polymerized hemoglobin and wherein the stored red blood cells have been stored for more than about 48 hours.

29. The composition of claim 28, wherein the hemoglobin has been polymerized with glutaraldehyde.

30. The composition of claim 28, wherein the stored red blood cells have been stored for greater than about seven days.

31. The composition of claim 30, wherein the stored red blood cells have been stored for greater than about thirty-five days.

32. The composition of claim 31, wherein the stored red blood cells have been stored for greater than about forty-two days.