Treatment of red blood cells

Patent metadata

Field	Value
Publication number	US-9572833-B2
Application number	US-201214356221-A
Country	US
Kind code	B2
Filing date	Nov 6, 2012
Priority date	Nov 7, 2011
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

Compositions and methods for treating red blood cells are disclosed. The methods include contacting a red blood cell sample ex vivo with an amount of nitric oxide or a nitric oxide-releasing compound sufficient to convert at least a portion of the extracellular ferrous hemoglobin present in the red blood cell sample to ferric hemoglobin. Red blood cells administered to a mammal following the ex vivo treatment have reduced adverse effects on the mammal to which they are administered.

First claim

What is claimed is:

1. A method of treating a red blood cell sample, the method comprising contacting a red blood cell sample ex vivo with an amount of nitric oxide or a nitric oxide-releasing compound sufficient to convert at least 20% of extracellular ferrous hemoglobin present in the red blood cell sample to ferric hemoglobin, wherein less than 20% of hemoglobin present in red blood cells in the red blood cell sample is converted to methemoglobin.

2. The method of claim 1 , wherein the red blood cell sample has been subjected to hemodialysis, intraoperative blood salvage, or cardiotomy suction ex vivo prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

3. The method of claim 1 , wherein the red blood cell sample has been subjected to one or more of a pump, a membrane, or air bubbles ex vivo prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

4. The method of claim 1 , wherein the red blood cell sample has been stored ex vivo for at least 24 hours after removal from a donor and prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

5. The method of claim 1 , wherein the red blood cell sample has been stored ex vivo for at least 7 days after removal from a donor and prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

6. The method of claim 1 , wherein the red blood cell sample has been stored ex vivo for at least 14 days after removal from a donor and prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

7. The method of claim 1 , wherein the red blood cell sample has been stored ex vivo for at least 28 days after removal from a donor and prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

8. The method of claim 1 , wherein the red blood cell sample has been stored ex vivo for at least 42 days after removal from a donor and prior to being contacted with nitric oxide or the nitric oxide-releasing compound.

9. The method of claim 1 , wherein the red blood cell sample is contacted with a therapeutic gas comprising gaseous nitric oxide.

10. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is at least 20 ppm.

11. The method of claim 9 , wherein the red blood cell sample is contacted with the therapeutic gas for fewer than 5 seconds.

12. The method of claim 1 , wherein the red blood cell sample is contacted with a nitric oxide-releasing compound.

13. The method of claim 1 , wherein the method is performed under sterile conditions.

14. The method of claim 1 , wherein at least 50% of extracellular ferrous hemoglobin present in the red blood cell sample is converted to ferric hemoglobin.

15. The method of claim 1 , wherein at least 80% of extracellular ferrous hemoglobin present in the red blood cell sample is converted to ferric hemoglobin.

16. The method of claim 1 , wherein less than 15% of hemoglobin present in red blood cells in the red blood cell sample is converted to methemoglobin.

17. The method of claim 1 , wherein less than 10% of hemoglobin present in red blood cells in the red blood cell sample is converted to methemoglobin.

18. The method of claim 1 , wherein less than 5% of hemoglobin present in red blood cells in the red blood cell sample is converted to methemoglobin.

19. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is at least 40 ppm.

20. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is at least 80 ppm.

21. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is in the range of 100 ppm to 800 ppm.

22. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is in the range of 40 ppm to 200 ppm.

23. The method of claim 9 , wherein the concentration of gaseous nitric oxide in the therapeutic gas is in the range of 40 ppm to 3,000 ppm.

24. The method of claim 9 , wherein the red blood cell sample is contacted with the therapeutic gas for at least 15 minutes.

25. The method of claim 9 , wherein the red blood cell sample is contacted with the therapeutic gas for at least one hour.

26. The method of claim 9 , wherein the red blood cell sample is contacted with the therapeutic gas for at least two hours.

27. The method of claim 12 , wherein the nitric oxide-releasing compound comprises nitrite.

28. The method of claim 12 , wherein the nitric oxide-releasing compound is an ultra-short-acting nitric oxide-releasing compound.

29. The method of claim 28 , wherein the ultra-short-acting nitric oxide-releasing compound is 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate or (Z)-1-[N-Methyl-N-[6-(N-methylammoniohexyl)amino]]diazen-1-ium-1,2-diolate.

Assignees

• Massachusetts Gen Hospital

Inventors

• Zapol Warren M
• Yu Binglan

Classifications

• A61M1/0281

  Apparatus for treatment of blood or blood constituents prior to transfusion, e.g. washing, filtering or thawing · CPC title

• A61M2202/0429

  Red blood cells; Erythrocytes · CPC title

• A61K33/00 Primary

  Medicinal preparations containing inorganic active ingredients · CPC title

• A61K35/18 Primary

  Erythrocytes (haemoglobin A61K38/42) · CPC title

• A61M2202/0275

  Nitric oxide [NO] · CPC title