Non-aqueous polar aprotic peptide formulations

• US 5,932,547 A
• Filed: 06/13/1997
• Issued: 08/03/1999
• Est. Priority Date: 07/03/1996
• Status: Expired due to Term

• Current Assignee: Horatio Washington Depot Technologies, LLC
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Stevenson, Cynthia L., Prestrelski, Steven J.
• Primary Examiner(s): DAVENPORT, AVIS MICHELLE
• Application Number:
  US08/874,233
• Time in Patent Office: 781 Days
• Field of Search: 530/328, 530/313, 514/15
• US Class Current: 514/10.3
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• 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: A61P 13/08 of the prostate
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 7/23 Luteinising hormone-releasing hormone [LHRH]; Related peptides

Abstract

This invention relates to stable non-aqueous polar aprotic formulations of peptide compounds. These stable formulations comprise peptide in non- aqueous polar aprotic solvent. They may be stored at elevated temperatures for long periods of time and are especially useful in implantable delivery devices for long term delivery of drug.

Claims

1. A stable non-aqueous formulation of a peptide compound comprising:

a) at least one peptide compound; and

b) at least one polar aprotic solvent,

wherein said peptide compound is an LHRH-related compound.

2. The formulation of claim 1 which comprises at least about 10% (w/w) peptide compound.

3. The formulation of claim 1 which comprises at least about 30% (w/w) peptide compound.

4. The formulation of claim 1 wherein said peptide compound is selected from the group consisting of leuprolide, LHRH, nafarelin and goserelin.

5. The formulation of claim 1 of which is stable at 80°

C. for at least 2 months.

6. The formulation of claim 1 which is stable at 37°

C. for at least 3 months.

7. The formulation of claim 1 which is stable at 37°

C. for at least one year.

8. The formulation of claim 1 which is adapted for use in an implantable drug delivery device.

10. The formulation of claim 1 wherein said polar aprotic solvent is selected from the group consisting of DMSO and DMF.

11. The formulation of claim 1 wherein said polar aprotic solvent provides an anti-gellant effect.

12. The formulation of claim 1 which consists essentially of about 30% to about 50% (w/w) of the LHRH-related compound leuprolide acetate in DMSO.

13. The formulation of claim 1 which consists essentially of leuprolide and DMSO in the proportions of 370 mg leuprolide in 1 ml DMSO.

14. The formulation of claim 1 which is stable after irradiation.

9. A stable non-aqueous formulation of a peptide compound comprising:

a) at least one peptide compound;

b) at least one polar aprotic solvent; and

c) a non-aqueous protic solvent.

16. The formulation of claim 9 which comprises at least about 10% (w/w) peptide compound.

17. The formulation of claim 9 which comprises at least about 30% (w/w) peptide compound.

18. The formulation of claim 9 of which is stable at 80°

C. for at least 2 months.

19. The formulation of claim 9 which is stable at 37°

C. for at least 3 months.

20. The formulation of claim 9 which is stable at 37°

C. for at least one year.

21. The formulation of claim 9 which is adapted for use in an implantable drug delivery device.

22. The formulation of claim 9 wherein said polar aprotic solvent is selected from the group consisting of DMSO and DMF.

23. The formulation of claim 9 wherein said polar aprotic solvent provides an anti-gellant effect.

24. The formulation of claim 9 which is stable after irradiation.

25. The formulation of claim 9 wherein said peptide is an LHRH-related compound.

15. A stable non-aqueous formulation of a peptide compound comprising:

(a) at least one peptide compound; and

(b) at least one polar aprotic solvent,

wherein said peptide compound is selected from the group consisting of glucagon, glucagon like peptide-1 and glucagon like peptide-2.

26. The formulation of claim 15 which comprises at least about 10% (w/w) peptide compound.

27. The formulation of claim 15 which comprises at least about 30% (w/w) peptide compound.

28. The formulation of claim 15 of which is stable at 80°

C. for at least 2 months.

29. The formulation of claim 15 which is stable at 37°

C. for at least 3 months.

30. The formulation of claim 15 which is stable at 37°

C. for at least one year.

31. The formulation of claim 15 which is adapted for use in an implantable drug delivery device.

32. The formulation of claim 15 wherein said polar aprotic solvent is selected from the group consisting of DMSO and DMF.

33. The formulation of claim 15 wherein said polar aprotic solvent provides an anti-gellant effect.

34. The formulation of claim 15 which is stable after irradiation.