Sustained release polymer
A polymer and a method for its preparation are provided. The polymer comprises poly(lactide), poly(lactide/glycolide) or poly(lactic acid/glycolic acid) segments bonded by ester linkages to both ends of an alkanediol core unit. The polymer is for use in a controlled release formulation for a medicament, preferably leuprolide acetate. The controlled release formulation is administered to a patient as a subcutaneous depot of a flowable composition comprising the polymer, a biocompatible solvent, and the medicament. Controlled release formulations comprising the polymer release leuprolide for treatment of prostate cancer patients over periods of 3-6 months.
1. A method to reduce serum testosterone levels in a human patient, comprising administering to the patient a flowable controlled release composition,
wherein the flowable controlled release composition comprises:
a. an organic solvent,
b. leuprolide or a pharmaceutically acceptable salt thereof, and
c. a biodegradable polymer comprising the structure of:
R1=H or CH 3
R2=alkyl group
wherein the polymer has substantially no titratable carboxylic acid groups, and
wherein the composition when administered once per about six months reduces the serum testosterone level of the patient to 20 ng/dL or lower.
2. The method of claim 1 , wherein the biodegradable polymer has a weight average molecular weight of between about 15 kD to about 45 kD.
3. The method of claim 1 , wherein the biodegradable polymer has a weight average molecular weight of about 21 kD.
4. The method of claim 1 , wherein the biodegradable polymer comprises about 35 to about 60 wt. % of the flowable controlled release composition.
5. The method of claim 1 , wherein the biodegradable polymer is a poly(lactide/glycolide) (PLG) copolymer.
6. The method of claim 5 , wherein the ratio of lactide/glycolide is about 85/15.
7. The method of claim 1 , wherein the biodegradable polymer is a poly(lactic acid/glycolic acid) (PLGA) copolymer.
8. The method of claim 7 , wherein the ratio of lactic acid/glycolic acid is about 85/15.
9. The method of claim 1 , wherein the solvent is selected from N-methyl-2-pyrrolidone, 2-pyrrolidone, N, N-dimethylformamide, dimethyl sulfoxide, propylene carbonate, caprolactam, triacetin, or any combination thereof.
10. The method of claim 1 , wherein the solvent is N-methyl-2-pyrrolidone.
11. A method to treat prostate cancer in a human patient, comprising administering a flowable controlled release composition subcutaneously to the human patient, the composition comprising:
a. an organic solvent,
b. leuprolide or a pharmaceutically acceptable salt thereof, and
c. a biodegradable polymer comprising the structure of:
R1=H or CH 3
R2=alkyl group
wherein the polymer has substantially no titratable carboxylic acid groups, and
wherein the composition when administered once per about six months reduces the serum testosterone level of the patient to 20 ng/dL or lower.
12. The method of claim 11 , wherein the biodegradable polymer is an 85/15 poly(lactide/glycolide) (PLG) copolymer.
13. The method of claim 11 , wherein the biodegradable polymer is an 85/15 poly(lactic acid/glycolic acid) (PLGA) copolymer.
14. The method of claim 11 , wherein the biodegradable polymer has a weight average molecular weight of between about 15 kD to about 45 kD.
15. A syringe comprising a flowable controlled release composition consisting essentially of:
a. an organic solvent,
b. leuprolide or a pharmaceutically acceptable salt thereof, and
c. a biodegradable polymer comprising the structure of:
R1=H or CH 3
R2=alkyl group
wherein the polymer has substantially no titratable carboxylic acid groups, and
wherein the composition when administered once per about six months reduces the serum testosterone level of the patient to 20 ng/dL or lower.
16. The syringe of claim 15 , wherein the biodegradable polymer is an 85/15 poly(lactide/glycolide) (PLG) copolymer.
17. The syringe of claim 15 , wherein the biodegradable polymer is an 85/15 poly(lactic acid/glycolic acid) (PLGA) copolymer.
18. The syringe of claim 15 , wherein the biodegradable polymer has a weight average molecular weight of between about 15 kD to about 45 kD.
19. A method to reduce serum testosterone levels in a human patient, comprising administering a flowable controlled release composition subcutaneously to the human patient, the composition comprising:
a. N-methyl-2-pyrrolidone,
b. leuprolide or a pharmaceutically acceptable salt thereof, and
c. a biodegradable polymer comprising the structure of:
R1=H or CH 3
R2=alkyl group
wherein the polymer has substantially no titratable carboxylic acid groups; and
wherein the biodegradable polymer is selected from the group consisting of 85/15 poly(lactide/glycolide) (PLG) copolymer and 85/15 poly(lactic acid/glycolic acid) (PLGA) copolymer; and
wherein the composition when administered once per about six months reduces the serum testosterone level of the patient to 20 ng/dL or lower.
20. The method of claim 19 , wherein the biodegradable polymer has a weight average molecular weight of between about 15 kD to about 45 kD.