Lyophilization of red blood cells

• US 4,874,690 A
• Filed: 08/26/1988
• Issued: 10/17/1989
• Est. Priority Date: 08/26/1988
• Status: Expired due to Fees

• Current Assignee: Cobe Cardiovascular Incorporated (LivaNova Plc)
• Original Assignee: Cryopharm Corp.
• Inventors: Weiner, Murray, Goodrich, Raymond P. Jr., Williams, Christine M., Franco, Robert S.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US07/237,588
• Time in Patent Office: 417 Days
• Field of Search: 435/2, 424/101
• US Class Current: 435/2
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61P 7/08 Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04

Abstract

A process and medium are disclosed for the lyophilization of red blood cells which comprises the use of solutions including monosaccharide hexoses and pentoses, biocompatible polymers and polyanions to permit the reconstitution of viable red blood cells.

Claims

1. A process for the lyophilization of erythrocytes, comprising immersing a plurality of erythrocytes in a buffered solution which includes:

a monosaccharide which is present in the solution in a concentration of from about 7.0 to 37.5%;

a polymer having a molecular weight of from about 5K to about 80K which is present in a concentration of from about 0.7% up to saturation in the solution;

a polyanion which is present in a concentration of from 0.01 weight percent up to saturation in the solution;

freezing the solution; and

drying the erythrocytes by sublimation of the water.

2. The process of claim 1 wherein the monosaccharide is selected from the group consisting of pentoses and hexoses.

3. The process of claim 1 wherein the monosaccharide is selected from the group consisting of xylose, glucose, ribose, mannose and fructose.

4. The process of claim 1, 2 or 3 wherein the polymer is selected from the group consisting of polyvinylpyrrolidone, dextran and gelatin.

5. The process of claim 1, 2 or 3 wherein the polyanion is a compound having anionic groups which are phosphate, sulfate or carboxylate groups.

6. The process of claim 4 wherein the polyanion is a compound having anionic groups which are phosphate, sulfate or carboxylate groups.

7. The process of claim 1, 2 or 3 wherein the polyanion is selected from the group consisting of pyrophosphate, tripolyphosphate, phosphorylated inositols, 2,3 diphosphoglycerate, adenosine triphosphate, phosphorylated dextran, heparin and polycarboxylic acids.

8. The process of claim 4 wherein the polyanion is selected from the group consisting of pyrophosphate, tripolyphosphate, phosphorylated inositols, 2,3 diphosphoglycerate, adenosine triphosphate, phosphorylated dextran, heparin and polycarboxylic acids.

9. A process for the lyophilization of erythrocytes having a cell membrane, comprising:

immersing a plurality of erythrocytes in a buffered solution which includes

(a) monosaccharide selected from the group consisting of xylose, glucose, ribose, mannose and fructose, the monosaccharide being present in the solution in a concentration of from about 7.0 to 37.5%;

(b) a biocompatible polyanion selected from the group consisting of pyrophosphate, tripolyphosphate, phosphorylated inositols, 2,3 diphosphoglycerate, adenosine triphosphate, phosphorylated dextran, heparin and polycarboxylic acids, the polyanion being present in the solution in a concentration of at least 0.01 weight percent;

(c) a polymer selected from the group consisting of polyvinylpyrrolidone and dextran, the polymer being present in the solution in a concentration of at least 0.7%;

freezing the solution, and

drying the erythrocytes by sublimation of the water.