Freeze-dried blood cells, stem cells and platelets, and manufacturing method for the same

• US 5,656,498 A
• Filed: 02/21/1995
• Issued: 08/12/1997
• Est. Priority Date: 02/22/1994
• Status: Expired due to Fees

• Current Assignee: Nippon Telegraph and Telephone Corporation
• Original Assignee: Nippon Telegraph and Telephone Corporation
• Inventors: Ishii, Yoshikazu, Funakoshi, Nobuhiro, Iijima, Tetsuo, Okada, Keiji
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US08/390,957
• Time in Patent Office: 903 Days
• Field of Search: 436/8, 436/10, 435/2, 435/260, 34/304
• US Class Current: 436/10
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0221 Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/19 Platelets; Megacaryocytes
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/101666 Particle count or volume standard or control [e.g., platelet count standards, etc.]

Abstract

The present invention provides a method for manufacturing freeze-dried blood cells, stem cells and platelets comprising the steps of: pre-treating a liquid selected from the group consisting of blood including blood cells, bone marrow fluid (hemopoietic stem cells), and platelets in blood plasma, with a solution containing at least one substance selected from the group consisting of saccharide, biopolymer, acid and acid salt; conducting granulation of the aforementioned pre-treated liquid into a granules of a predetermined size; performing rapid cooling of the granules; and drying the resultant frozen material by sublimation of the water content contained therein.

Claims

1. A method for manufacturing freeze-dried blood cells, stem cells, and platelets, the method comprising the steps of:

pre-treating a liquid selected from the group consisting of blood including blood cells, bone marrow fluid (hemopoietic stem cells), and platelets in blood plasma, with a solution containing saccharide, biopolymer, and acid and/or acid salt;

conducting granulation of said pre-treated liquid to yield granules of a first predetermined size, wherein the granulation is conducted by means of mixed spraying with a gas;

performing rapid cooling of said granules of the first predetermined size into a frozen product of a second predetermined size; and

drying said frozen product by sublimation of a water content therein.

2. Method according to claim 1, wherein said first predetermined size is several microns to several hundred microns.

3. Method according to claim 2, wherein said first predetermined size is 10 μ

m to 200 μ

m.

4. Method according to claim 1, wherein said second predetermined size is 1 mm or less.

5. Method according to claim 4, wherein said second predetermined size is 100 μ

m to several hundred microns.

6. Method according to claim 1, wherein said rapid cooling is performed by means of spraying said blood into a gas at a temperature below the freezing point.

7. Method according to claim 1, wherein said saccharide is at least one saccharide selected from the group consisting of mannose, xylose, glucose, trehalose, sucrose and maltose.

8. Method according to claim 1, wherein said biopolymer is at least one biopolymer selected from the group consisting of dextran, phosphate, polyvinylpyrolidone and albumin.

9. Method according to claim 8, wherein said albumin is at least one type of albumin selected from the group consisting of human albumin, bovine albumin and egg white albumin.

10. Method according to claim 1, wherein said acid or acid salt is at least one substance selected from the group consisting of phytinic acid, pyrophosphate, adenosine triphosphate and 2,3-diphosphoglyceric acid.

11. Method according to claim 1, wherein said solution for use in pre-treating has a pH between 4 and 9.

12. Method according claim 11, wherein said solution for use in pre-treating has a pH between 7 and 8.

13. Method according to claim 1, wherein said rapid cooling is performed at a rate of 10³ °

C./second to 10⁶ °

C./second.

14. Freeze-dried product of a solution containing saccharide, biopolymer, an acid and/or acid salt and a liquid selected from the group consisting of blood including blood cells, bone marrow fluid (hemopoietic stem cells), and platelets suspended in blood plasma;

said freeze-dried product being formed from porous clusters possessing a size of 100 microns to several hundred microns and comprising from about 10 to approximately several hundred granules possessing a size of 10 microns to 200 hundred microns.

15. A method for manufacturing freeze-dried blood cells, stem cells, and platelets, the method comprising the steps of:

pre-treating a material selected from the group consisting of blood including cells, bone marrow fluid (hemopoietic stem cells), and platelets in blood plasma, with a solution containing saccharide, biopolymer, and acid and/or acid salt to yield a pre-treated liquid;

conducting granulation of said pre-treated liquid to yield granules of a first predetermined size, wherein the granulation is conducted by means of mixed spraying with a gas;

performing rapid cooling of said granules of a first predetermined size to produce clusters of a second predetermined size to yield a frozen product; and

drying said frozen product by sublimation of a water contained therein.

16. A method for manufacturing freeze-dried blood cells, stem cells, and platelets, the method comprising the steps of:

preparing a container having a wall;

preparing a pre-treatment solution containing saccharide, biopolymer, and acid and/or acid salt;

pre-treating a material selected from the group consisting of blood including cells, bone marrow fluid (hemopoietic stem cells), and platelets in blood plasma, with the pre-treatment solution to yield a pre-treated liquid;

conducting granulation of said pre-treated liquid in the container to yield granules of a first predetermined size, wherein the granulation is conducted by means of mixed spraying with a gas;

performing rapid cooling of said granules of a first predetermined size in the container to produce clusters of a second predetermined size on the wall of the container to yield a frozen product; and

drying said frozen product in the container by sublimation of a water contained in said frozen product.