Methods for rejuvenating red blood cells

Patent metadata

Field	Value
Publication number	US-9103842-B2
Application number	US-201313844773-A
Country	US
Kind code	B2
Filing date	Mar 15, 2013
Priority date	Jan 31, 2013
Publication date	Aug 11, 2015
Grant date	Aug 11, 2015

Abstract

Methods for transfusing blood to a mammalian subject. The method includes obtaining a unit of blood, rejuvenating the blood with an enhancement composition, measuring 2,3-DPG concentration of the blood, and delivering the blood to a subject.

First claim

What is claimed is:

1. A method for treating or preventing ischemia in a human or other mammalian subject, comprising:
(a) obtaining a volume of fresh blood from the subject;
(b) performing a separation on the fresh blood, wherein plasma and leukocytes are delivered to the subject, and fresh red blood cells are isolated;
(c) rejuvenating the fresh red blood cells with an enhancement composition to form rejuvenated fresh red blood cells, wherein the rejuvenated fresh red blood cells have adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) levels equal to or greater than ATP and 2,3-DPG levels normally found in the subject's blood; and
(d) delivering the rejuvenated fresh red blood cells to the subject, wherein the performing a separation, rejuvenating and delivering are performed within about 24 hours of the time of obtaining the fresh blood from the subject.

2. The method according to claim 1 , wherein the enhancement composition comprises:
(i) from about 25 g/L to about 30 g/L of inosine;
(ii) from about 0.2 g/L to about 2 g/L of adenine;
(iii) from about 5 g/L to about 15 g/L of pyruvate; and
(iv) from about 17 g/L to about 23 g/L of sodium phosphate.

3. The method according to claim 1 , further comprising performing a diagnostic test on the rejuvenated red blood cells.

4. The method according to claim 3 , wherein the diagnostic test measures the concentrations of 2,3-diphosphoglycerate (2,3-DPG) or adenine triphosphate (ATP) in the rejuvenated red blood cells.

5. The method according to claim 4 , further comprising calculating the volume of rejuvenated blood necessary to dose the subject to obtain normal or higher levels of 2,3-DPG and/or ATP in the subject.

6. The method according to claim 3 , wherein the diagnostic test is performed by a device physically attached to the unit of blood.

7. The method according to claim 3 , wherein the diagnostic test comprises collecting a sample of blood on a tag, a chip, a glass plate, or a pregnancy test-style strip.

8. The method according to claim 1 , wherein the method is performed in anticipation of surgery on the subject.

9. The method according to claim 1 , wherein rejuvenating the red blood cells results in red blood cell 2,3-diphosphoglycerate (2,3-DPG) concentration of greater than about 15 μmol/L/gHb.

10. A method of enhancing the ability of blood to oxygenate tissue in a subject in need thereof comprising:
(a) obtaining a unit of fresh blood;
(b) performing a first diagnostic test on the fresh blood to determine the concentration of a marker selected from 2,3-diphosphoglycerate (2,3-DPG), adenine triphosphate (ATP), or combinations thereof;
(c) contacting the fresh blood with an enhancement composition to form rejuvenated fresh blood;
(d) performing a second diagnostic test on the rejuvenated fresh blood to determine the concentration of the marker;
(e) comparing the concentration of the marker from the first diagnostic test to the concentration of the marker from the second diagnostic test and determining a volume of rejuvenated fresh blood necessary to dose the subject to normal or higher levels of 2,3-DPG and/or ATP in the subject's systemic circulation; and
(f) administering the volume of rejuvenated fresh blood, determined in step (e) to the subject;
wherein the obtaining, performing a first diagnostic test, contacting, performing a second diagnostic test, comparing and administering are performed within about 24 hours of the time of obtaining the fresh blood from the subject.

11. The method according to claim 10 , wherein the unit of blood is autologous to the subject.

12. The method according to claim 10 , wherein the enhancement composition comprises:
(i) from about 25 g/L to about 30 g/L of inosine;
(ii) from about 0.2 g/L to about 2 g/L of adenine;
(iii) from about 5 g/L to about 15 g/L of pyruvate; and
(iv) from about 17 g/L to about 23 g/L of sodium phosphate.

13. The method according to claim 12 , wherein the diagnostic test is performed on a chip.

14. The method according to claim 12 , wherein the subject is in anticipation of surgery.

15. A method of performing a transfusion comprising:
(a) obtaining a unit of fresh blood;
(b) performing a diagnostic test on the unit of fresh blood to determine 2,3-diphosphoglycerate (2,3-DPG) concentration in the blood;
(c) rejuvenating the fresh blood if the 2,3-DPG concentration is lower than about 10 μmol/L/gHb to form rejuvenated fresh blood, wherein the rejuvenating is performed with an enhancement composition comprising, inosine, adenine, pyruvate, and sodium phosphate; and
(d) delivering the rejuvenated fresh blood to a subject in need thereof;

wherein the obtaining, performing a diagnostic test, rejuvenating and delivering are performed within about 24 hours of the time of obtaining the fresh blood from the subject.

16. A method for treating or preventing ischemia in a human or other mammalian subject, comprising:
(a) obtaining a volume of fresh blood from the subject;
(b) performing a separation on the fresh blood, wherein plasma and leukocytes are delivered to the subject, and fresh red blood cells are isolated;
(c) rejuvenating the fresh red blood cells with an enhancement composition to form rejuvenated fresh red blood cells, wherein the concentration of 2,3-diphosphoglycerate (2,3-DPG) concentration in the rejuvenated red blood cells is greater than about 15 μmol/L/gHb; and
(d) delivering the rejuvenated fresh red blood cells to the subject;

wherein the obtaining, performing a separation, rejuvenating, and administering are performed within about 24 hours of the time of obtaining the fresh blood from the subject.

17. The method according to claim 16 , wherein the delivering of the rejuvenated fresh red blood cells is performed within 6 hours after the obtaining of the volume of fresh blood from the subject.

18. The method according to claim 16 , wherein the enhancement composition comprises:
(i) from about 25 g/L to about 30 g/L of inosine;
(ii) from about 0.2 g/L to about 2 g/L of adenine;
(iii) from about 5 g/L to about 15 g/L of pyruvate; and
(iv) from about 17 g/L to about 23 g/L of sodium phosphate.

19. The method according to claim 16 , further comprising performing a diagnostic test on the rejuvenated fresh red blood cells, measuring the concentrations of 2,3-diphosphoglycerate (2,3-DPG) or adenine triphosphate (ATP) in the rejuvenated red blood cells.

20. The method according to claim 16 , wherein the method is performed in anticipation of surgery on the subject.

Assignees

• Biomet Biologics Llc

Inventors

• Gray Alan
• Higgins Joel C
• Landrigan Matthew D
• Cunningham Grant

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/02

  Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title