Stabilization and storage of biological pharmaceutical compositions
The present invention relates to compositions and methods for the preparation, stabilization, and/or storage of active agents, particularly therapeutic proteins and polypeptides such as Interleukin-2.
1. A parenterally injectable pharmaceutical composition comprising:
(a) from 0.01 to 40 weight percent choline dihydrogen phosphate;
(b) an added base included in an amount not greater than 40 weight percent, wherein said added base is choline hydroxide;
(c) at least 60 weight percent water; and
(d) from 0.01 to 10 weight percent active compound selected from the group consisting of Interleukin-2, gelsolin, antibodies, erythropoietin, interferon, human growth hormone, follicle stimulating hormone, and granulocyte colony stimulating factor;
said composition having a pH of from 6 up to 8;
said composition packaged in a sterile container.
2. The composition of claim 1 , wherein said active compound is included in an amount of not more than 5 weight percent.
3. The composition of claim 1 , wherein said water is included in an amount up to 99 weight percent.
4. The composition of claim 1 , wherein said choline dihydrogen phosphate is included in an amount of not more than 40 weight percent.
5. The composition of claim 1 , wherein said base and said choline dihydrogen phosphate are included together in a combined amount not more than 50 weight percent.
6. The composition of claim 1 , wherein said composition is a single phase liquid solution.
7. The composition of claim 1 , wherein said composition has an osmolality of 100 to 3,000 milliOsmoles per kilogram of water.
8. The composition of claim 1 , wherein said active compound is Interleukin-2.
9. The composition of claim 8 , wherein said Interleukin-2 is human Interleukin-2.
10. The composition of claim 8 , wherein said Interleukin-2 is aldesleukin.
11. The composition of claim 1 , wherein said active compound is gelsolin.
12. The composition of claim 11 , wherein said gelsolin is human gelsolin.
13. The composition of claim 1 , wherein said active compound is recombinant.
14. The composition of claim 1 , wherein said active compound is non-glycosylated.
15. The composition of claim 1 having a shelf life of from 2 days to 2 years at 37° C.
16. The composition of claim 1 , wherein said active compound is Interleukin-2 and said composition has a shelf life of 2 days to 2 months at 37° C.
17. A method comprising administering a composition of claim 1 to a subject in need thereof.
18. The composition of claim 1 , wherein:
said active compound is included in an amount of not more than 5 weight percent;
said water is included in an amount up to 99 weight percent;
said choline dihydrogen phosphate is included in an amount of not more than 40 weight percent;
said base and said choline dihydrogen phosphate are included together in a combined amount not more than 50 weight percent;
said composition is a single phase liquid solution;
said composition has an osmolality of 100 to 3,000 milliOsmoles per kilogram of water; and
said active agent is Interleukin-2.
19. The composition of claim 1 having a shelf life of from 2 weeks to 2 years at 37° C.
20. The composition of claim 1 having a shelf life of at least 2 weeks at 37° C.
21. The composition of claim 1 having a shelf life of at least 1 month at 37° C.
22. The composition of claim 1 having a shelf life of at least 1 year at 37° C.
23. The composition of claim 1 , further comprising from 0.01 to 50 weight percent of at least one osmolyte.