Methods for sterilizing materials containing biologically active agents

• US 8,574,897 B2
• Filed: 06/08/2012
• Issued: 11/05/2013
• Est. Priority Date: 12/20/2007
• Status: Active Grant

• Current Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Original Assignee: DePuy Synthes Products LLC (Johnson & Johnson)
• Inventors: Harmon, Alexander M., Brown, Laura J., Buckle, Charles J., Halperin, Frederick, Bodnar, Stanko
• Primary Examiner(s): Ketter, Jim
• Application Number:
  US13/492,175
• Publication Number:
  US 20120315698A1
• Time in Patent Office: 515 Days
• Field of Search: None
• US Class Current: 435/317.1
• 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. An irradiation-sterilized, stabilizer-free, human umbilical tissue-derived cell (hUTC) lysate composition comprising hUTC lysate sterilized by irradiating with ionizing radiation at a dose in the range of from about 5 kGy to about 25 kGy in an atmosphere comprising at least 95% by volume inert gas and at a temperature of about 4°

C. or lower without the addition of a stabilizer, and wherein the biological activity of the hUTC lysate is retained after sterilization.

2. The composition according to claim 1, wherein said 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.

3. The composition according to claim 1, wherein said composition further comprises a cell derivative selected from the group consisting of a non-hUTC cell lysate, trophic factors, growth factors, cytokines, conditioned media, or any combination thereof.

4. The composition according to claim 1, wherein said composition further comprises a scaffold.

5. The composition according to claim 4, wherein said scaffold comprises collagen, cellulose, fibrin, elastin, gelatin, demineralized bone, hyaluronic acid, poly(lactic acid), poly(glycolic acid), polycaprolactone, polyanhydrides, polyhydroxybutyrates, or any combination thereof.

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

7. The composition according to claim 1, wherein said dose of ionizing radiation is in the range of from about 6 kGy to about 12 kGy.

8. The composition according to claim 1, wherein said dose of ionizing radiation is about 7 kGy.

9. The composition according to claim 1, wherein said inert gas comprises nitrogen.

10. The composition according to claim 1, wherein said atmosphere comprises about 100% by volume nitrogen.

11. The composition according to claim 1, wherein said temperature is about 0°

C.

12. An irradiation-sterilized, stabilizer-free, human umbilical tissue-derived cell (hUTC) lysate composition comprising hUTC lysate sterilized with ionizing radiation in the absence of a stabilizer, and wherein the biological activity of the hUTC lysate is retained after sterilization.

13. The composition according to claim 12, wherein said composition further comprises a cell derivative selected from the group consisting of a non-hUTC cell lysate, trophic factors, growth factors, cytokines, conditioned media, or any combination thereof.

14. The composition according to claim 12, wherein said composition further comprises a scaffold.

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

16. The composition according to claim 12, wherein said 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.