METHOD FOR STABILISING BLOOD PLASMA COMPONENTS IN A LYOPHILISATE

• US 20100159023A1
• Filed: 02/15/2008
• Published: 06/24/2010
• Est. Priority Date: 02/15/2007
• Status: Active Grant

• Current Assignee: Octapharma AG (Octapharma Nordic AB)
• Original Assignee: Octapharma AG (Octapharma Nordic AB)
• Inventors: Svae, Tor-Einar, Roemisch, Juergen, Gruber, Gerhard, Kern, Martin, Schuetz, Raimund, Bjornstrup, Kim, Sachse, Hans, Heger, Andrea
• Granted Patent: US 8,518,452 B2
• Time in Patent Office: Days
• US Class Current: 424/530
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• 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

Process for the stabilization of blood plasma components in a lyophilizate, wherein

• • in a freeze-drying process, said blood plasma components were in a solution containing at least two different pH-lowering substances causing a predetermined pH value range to be adjusted in the solution formed upon reconstitution.

Claims

1. A process for the stabilization of blood plasma components in a lyophilizate, wherein

in a freeze-drying process, said blood plasma components were in a solution containing at least two different pH-lowering substances causing a predetermined pH value range to be adjusted in the solution formed upon reconstitution.

2. The process according to claim 1, wherein:

the lyophilizate is obtained by having the blood plasma components in an essentially aqueous solution and filling it in a container which at least partially consists of a sterile material that is impermeable to water, but permeable to water vapor; and

the uptake of water vapor beyond a predetermined residual moisture content of the lyophilizate is prevented after the freeze drying process has been completed.

3. The process according to claim 2, wherein said sterile material that is impermeable to water, but permeable to water vapor is provided on a support material.

4. The process according to claim 1, wherein said at least two different substances prevent the pH value from being adjusted into ranges that negatively affect the structure of the blood plasma components, such as proteins, in the lyophilizate by an at least partial loss of activity and/or nativity, denaturing, fragmentation, aggregation, chemical modification, such as oxidation.

5. The process according to claim 1, wherein said at least two substances are selected from the group of buffer substances, such as salts of mineral or organic acids, especially by introducing CO₂, di- or monohydrogenphosphates, hydrogencarbonates, sulfates, hydrogensulfates, salts of organic acids or bases, tris(hydroxymethylamino)methane and/or amino acids.

6. The process according to claim 1, wherein said blood plasma components are selected from the group consisting of biopolymers, such as proteins, polysaccharides, nucleic acids, lipids and their mixtures.

7. The process according to claim 1, wherein said blood plasma components are proteins from blood, plasma or serum.

8. The process according to claim 1, wherein stabilizers such as sugar, polysaccharides, oligosaccharides, polyols, amino acids or combinations thereof are present in the lyophilizate or in a reconstitution solution.

9. The process according to claim 1 wherein said blood plasma components, especially the biopolymers, are contained in biological sources, such as body fluids, for example, blood or blood plasma, fractions of transgenic or recombinantly prepared proteins.

10. The process according to claim 2, wherein said sterile material permeable to water vapor consists of fluorinated plastic materials, polyester or polyethylene.

11. The process according to claim 3, wherein said support material consists of polypropylene, polyethylene, ethyl vinyl acetate, polyurethane, multilayer polymers, such as block polymers of the type styrene/butadiene/styrene, styrene/isoprene/styrene, styrene/ethylene/butylene/styrene, styrene/ethylene/propylene/styrene or combinations thereof.

12. The process according to claim 1, wherein a freeze-drying process is applied that includes first and second steps, wherein a lower input of desorption energy into the freeze-drying process occurs in the second step of the freeze-drying process as compared to the first step.

13. The process according to claim 2, wherein said container permeable to water vapor is placed into a container impermeable to water vapor which consists of plastic materials or aluminum foil.

14. The process according to claim 1, wherein the reconstitution of the lyophilizate is effected in an aqueous solution containing physiologically acceptable acidic-hydrolyzing salts or physiologically acceptable acids.

15. The process according to claim 1, wherein the reconstitution is effected with essentially neutral water for injection if the freeze drying of the blood plasma components is done in a solution containing substances that cause a predetermined pH range to be adjusted in the solution formed during the reconstitution.

16. Use of a container in a process according to claim 2, wherein the container for lyophilization has walls (10), connection elements (21, 22), and the walls (10) at least partially consist of a sterile material (15) that is impermeable to water, but permeable to water vapor.