Pharmaceutical formulation comprising a peptide angiogenesis inhibitor
Parenteral formulations of peptides which are useful for sustained release are disclosed. Also disclosed are methods of preparation for the formulations.
1. A pharmaceutical composition comprising:
(a) N-Ac-Gly-Val-D-alloIle-Ser-Gln-Ile-Arg-ProNHCH 2 CH 3 or a pharmaceutically acceptable salt thereof;
(b) poly(lactide-co-glycolide); and
(c) an organic solvent.
2. The pharmaceutical composition of claim 1 wherein the pharmaceutically acceptable salt is selected from the group consisting of acetate, pivalate, valproate, and octanoate.
3. The pharmaceutical composition of claim 1 which comprises between about 1% and about 15% (w/w) of N-Ac-Gly-Val-D-alloIle-Ser-Gln-Ile-Arg-ProNHCH 2 CH 3 or a pharmaceutically acceptable salt thereof.
4. The pharmaceutical composition of claim 1 which comprises between about 3% and about 6% (w/w) of N-Ac-Gly-Val-D-alloIle-Ser-Gln-Ile-Arg-ProNHCH 2 CH 3 or a pharmaceutically acceptable salt thereof.
5. The pharmaceutical composition of claim 1 which comprises between about 25% and about 45% (w/w) poly(lactide-co-glycolide).
6. The pharmaceutical composition of claim 5 which comprises about 35% (w/w) poly(lactide-co-glycolide).
7. The pharmaceutical composition of claim 1 wherein the poly(lactide-co-glycolide) has a weight of between about 6 and about 60 KD.
8. The pharmaceutical composition of claim 7 wherein the poly(lactide-co-glycolide) has a weight of between about 13 and about 24 KD.
9. The pharmaceutical composition of claim 1 wherein the organic solvent is N-methyl-2-pyrrolidinone.
10. The pharmaceutical composition of claim 1 wherein the organic solvent is triacetin.
11. The pharmaceutical composition of claim 1 wherein the organic solvent is a mixture of N-methyl-2-pyrrolidinone and triacetin.
12. The pharmaceutical composition of claim 11 wherein the N-methyl-2-pyrrolidinone and the triacetin are in a weight ratio of from about 1:2 to about 6:1.
13. The pharmaceutical composition of claim 11 wherein the N-methyl-2-pyrrolidinone and the triacetin are in a weight ratio of about 2:1.
14. The pharmaceutical composition of claim 11 wherein the N-methyl-2-pyrrolidinone and the triacetin are in a weight ratio of about 1:1.
15. A pharmaceutical composition comprising:
(a) about 3% (w/w) of N-Ac-Gly-Val-D-alloIle-Ser-Gln-Ile-Aw-ProNHCH 2 CH 3 (formula Id), or a pharmaceutically acceptable salt thereof;
(b) about 34% (w/w) poly(lactide-co-glycolide); and
(c) about a 2:1 (w/w) mixture of N-methylpyrrolidinone and triacetin.
16. The pharmaceutical composition of claim 15 wherein the therapeutically acceptable salt is selected from the group consisting of acetate, pivalate, valproate, and octanoate.