METHODS FOR STERILIZING MATERIALS CONTAINING BIOLOGICALLY ACTIVE AGENTS

• US 20090166178A1
• Filed: 12/17/2008
• Published: 07/02/2009
• Est. Priority Date: 12/20/2007
• Status: Active Grant

• Current Assignee: Depuy Synthes Products Incorporated (Johnson & Johnson)
• Original Assignee: Ethicon Incorporated (Johnson & Johnson)
• Inventors: Halperin, Frederick, Buckle, Charles J., Bodnar, Stanko, Harmon, Alexander M., Brown, Laura J.
• Granted Patent: US 8,236,538 B2
• Time in Patent Office: Days
• US Class Current: 204/158.210
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0035 Gamma radiation
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36

Abstract

Provided are methods for sterilizing a material comprising a biologically-active agent comprising irradiating said material with ionizing radiation at a dose of about 5 kGy to about 25 kGy while maintaining said material in an atmosphere comprising at least 95% by volume inert gas and at a temperature of about 4° C. or lower. Also provided are sterilized materials comprising a biologically-active agent, wherein said materials exhibit substantially the same amount of biological activity as a non-sterilized control.

Claims

1. A method for sterilizing a material comprising a biologically-active agent comprising:

irradiating said material with ionizing radiation at a dose of about 5 kGy to about 25 kGy while maintaining said material in an atmosphere comprising at least 95% by volume inert gas and at a temperature of about 4°

C. or lower.

2. The method according to claim 1 wherein said ionizing radiation comprises X-rays, gamma radiation, or electron beams.

3. The method according to claim 1 wherein said dose of ionizing radiation is about 6 kGy to about 12 kGy.

4. The method according to claim 1 wherein said dose of ionizing radiation is about 7 kGy.

5. The method according to claim 1 wherein said inert gas comprises nitrogen.

6. The method according to claim 1 wherein said atmosphere comprises about 100% by volume nitrogen.

7. The method according to claim 1 wherein said temperature is about 0°

C.

8. The method according to claim 1, wherein said material is contained within a vessel, and wherein said method further comprises purging the ambient air from said vessel by flushing with said inert gas prior to irradiating said material.

9. The method according to claim 1 wherein said biologically active agent comprises cells, cell derivatives, growth factors, or any combination thereof.

10. The method according to claim 9 wherein said biologically active agent comprises cells comprising epithelial cells, bone marrow cells, adipocytes, stem cells, keratinocytes, melanocytes, dermal fibroblasts, keratinocytes, vascular endothelial cells, myoblasts, myocytes, hepatocytes, smooth muscle cells, striated muscle cells, stromal cells, other soft tissue cells or progenitor cells, chondrocytes, osteoblasts, islet cells, nerve cells, placenta-derived cells, human umbilical tissue derived cells (hUTC), human kidney derived cells, or any combination thereof.

11. The method according to claim 9 wherein said biologically active agent comprises a cell derivative comprising cell lysate, trophic factors, growth factors, cytokines, conditioned media, or any combination thereof.

12. The method according to claim 9 wherein said biologically active agent comprises hUTC lysate.

13. The method according to claim 9 wherein said biologically active agent comprises a growth factor comprising PDGF-BB, bFGF, TGF-beta, HGF, VEGF, GDF-5, or any combination thereof.

14. The method according to claim 1 wherein said material further comprises a scaffold composition.

15. The method according to claim 14 wherein said scaffold composition comprises collagen, cellulose, fibrin, elastin, gelatin, demineralized bone, hyaluronic acid, poly(lactic acid), poly(glycolic acid), polycaprolactone, polyanhydrides, polyhydroxybutyrates, or any combination thereof.

16. A sterilized material comprising a biologically-active agent, wherein said material exhibits substantially the same amount of biological activity as a non-sterilized control.

17. The sterilized material according to claim 16 wherein said amount of biological activity is assessed according to a cell proliferation assay, transmigration assay, angiogenesis assay, cytotoxicity assay, matrix deposition assay, lymphocyte activation assay, or apoptosis assay.

18. The sterilized material according to claim 16, wherein said material been sterilized by irradiating said material with ionizing radiation at a dose of about 5 kGy to about 25 kGy while maintaining said material in an atmosphere comprising at least 95% by volume inert gas and at a temperature of about 4°

C. or lower.

19. The sterilized material according to claim 16 wherein said biologically active agent comprises cells, cell derivatives, or any combination thereof.

20. The sterilized material according to claim 19 wherein said biologically active agent comprises cells comprising epithelial cells, bone marrow cells, adipocytes, stem cells, keratinocytes, melanocytes, dermal fibroblasts, keratinocytes, vascular endothelial cells, myoblasts, myocytes, hepatocytes, smooth muscle cells, striated muscle cells, stromal cells, other soft tissue cells or progenitor cells, chondrocytes, osteoblasts, islet cells, nerve cells, placenta-derived cells, human umbilical tissue derived cells, human kidney derived cells, or any combination thereof.

21. The sterilized material according to claim 19 wherein said biologically active agent comprises a cell derivative comprising cell lysate, trophic factors, growth factors, cytokines, conditioned media, or any combination thereof.

22. The sterilized material according to claim 18 wherein said biologically active agent comprises hUTC lysate.

23. The sterilized material according to claim 19 wherein said biologically active agent comprises a growth factor comprising PDGF-BB, bFGF, TGF-beta, HGF, VEGF, GDF-5, or any combination thereof.

24. The sterilized material according to claim 19 wherein said material further comprises a scaffold composition.

25. The sterilized material according to claim 24 wherein said scaffold composition comprises collagen, cellulose, fibrin, elastin, gelatin, demineralized bone, hyaluronic acid, poly(lactic acid), poly(glycolic acid), polycaprolactone, polyanhydrides, polyhydroxybutyrates, or any combination thereof.