Method for extending the useful shelf-life of refrigerated red blood cells by nutrient supplementation

a technology nutrient supplementation, which is applied in the field of extending the useful shelf life of refrigerated red blood cells by nutrient supplementation, can solve the problems of periodic shortage of blood, limited liquid blood supply, and patients currently cannot collect and store with current technology

Inactive Publication Date: 2003-08-14
TRUSTEES OF BOSTON UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012] The present invention provides methods and compositions for extending the useful shelf-life of red blood cells. The method of the invention comprises adding a metabolic supplement to packed red blood cells, adding an additive solution, preferably an oxygen-free additive solution, to said red blood cells, and storing said red blood cells at a temperature above freezing, preferably 4.degree. C., under conditions of oxygen-depletion. Metabolic supplement compositions of the invention comprise pyruvate, inosine, adenine, monobasic and dibasic phosphate salts at a pH from about 5 to about 8. Rejuvesol, or modification thereof, may be used as a metabolic supplement solution. Oxygen depletion may be effected by flushing the red blood cells with an inert gas as described with oxygen depleted refrigerated storage in U.S. Pat. No. 5,624,794 and U.S. Pat. No. 6,162,396. Preferred oxygen-free additive solutions comprise modifications of EAS61 (Hess et al., Transfusion 40: 1007-1011), and OFAS1 (U.S. Pat. No. 5,789,151). A preferred oxygen-free additive solution is OFAS3. The present invention extends the useful shelf life of refrigerated packed red blood cells from the current approximately 6 week limit to about 12 to about 20 weeks.

Problems solved by technology

By way of background, currently the supplies of liquid blood are limited by storage.
There are periodic shortages of blood that occur due to donation fluctuation, emergencies and other factors.
Patients currently cannot collect and store with current technology enough autologous blood for certain pre-planned surgeries, including hip replacement, organ transplantation and the like.
Storage of frozen blood is known in the art but such frozen blood has limitations.
However, frozen blood is difficult to handle.
It must be thawed which makes it impractical for emergency situations.

Method used

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  • Method for extending the useful shelf-life of refrigerated red blood cells by nutrient supplementation
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  • Method for extending the useful shelf-life of refrigerated red blood cells by nutrient supplementation

Examples

Experimental program
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Effect test

example 2

OFAS3: Effect of pH and Oxygen Depletion on % of Cells Exposing Phosphotidylserine

[0031] Results of experimentation to determine the effect of pH and oxygen depletion on the % of red blood cells exposing phosphotidylserine with samples containing oxygen-free additive solution (OFAS3) are presented in FIG. 2. Data were obtained by flow cytometer measurements using FITC-Annexin IV probe. Each point on the graph is the average of 6 subjects. There is a significant reduction in exposed phosphotidylserine after 10 weeks when pH 8.3 and pH 6.5 blood samples, both oxygen depleted, are compared.

example 3

OFAS3: Effect of pH and Oxygen Depletion on Red Blood Cell Hemolysis

[0032] Results of experimentation to determine the effect of pH and oxygen depletion on red blood cell hemolysis with blood samples containing oxygen-free additive solution (OFAS3) are presented in FIG. 3. Each point on the graph is the average of 6 subjects. Three different pH's were tested, pH 6.5, pH 7.4, and pH 8.3, with control cultures that were not oxygen-depleted. At week 16, the pH 6.5 oxygen-depleted refrigerated red blood cell storage system has the lowest extent of hemolysis.

example 4

Addition of Metabolic Supplements During Refrigerated Oxygen-Depleted Red Blood Cell Storage: Effect of Metabolic Supplements Added at Different pH's in the Presence or Absence of Oxygen on Cellular ATP Levels

[0033] Results of experimentation to determine the effect of addition of metabolic supplements added during refrigerated, oxygen-depleted storage of red blood cells at different pH's in the presence or absence of oxygen on cellular ATP levels, are graphically presented in FIG. 4. Two different pH's were tested, pH 6.5 and pH 8.3, with control cultures that are not oxygen depleted. Metabolic supplement, Rejuvesol, was added to cultures as indicated by the arrows in FIG. 4, which correspond approximately to additions during cold storage at 9, 14, and 21 weeks respectively. These data show that ATP levels are significantly increased each time the cold fuel / metabolic supplement is added. The highest ATP levels are sustained with pH 6.5 additive solution under oxygen depleted condit...

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Abstract

There is provided methods and compositions for the storage of red blood cells. The compositions are metabolic supplements which are preferably added to refrigerated red blood cells suspended in an additive solution. Red blood cells are preferably stored under conditions of oxygen-depletion. Metabolic compositions comprises pyruvate, inosine, adenine, and optionally dibasic sodium phosphate and / or monobasic sodium phosphate.

Description

[0001] This application claims priority from U.S. Provisional Application No. 60 / 332,409, filed Nov. 16, 2001.[0002] The present invention relates to the preservation of blood in liquid form. More particularly, the present invention relates to enhancement of the shelf-life of oxygen-depleted refrigerated storage of red blood cells. Still more particularly, compositions and methodology involving nutrient or metabolic supplementation of red blood cells stored in liquid form in oxygen-depleted refrigeration are provided. This invention was made with partial support by the United States Office of Naval Research, Contract No. N00014-98-1-0451. The Government has certain rights in the invention.DESCRIPTION OF THE PRIOR ART[0003] By way of background, currently the supplies of liquid blood are limited by storage. Stored blood expires after about 42 days of refrigerated storage. Red blood cells may, for example, be stored under refrigeration at a temperature above freezing (4.degree. C.) as...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N1/04A01N1/02A61K35/18A61P43/00C12N5/00C12N5/02C12N5/07C12N5/078
CPCA01N1/0226A01N1/02A61P43/00
Inventor BITENSKY, MARK W.YOSHIDA, TATSURO
Owner TRUSTEES OF BOSTON UNIV
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