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 polymer for use in manufacture of a controlled release formulation for a drug, comprising a structure of Formula I:
wherein:
R a is an alkane diradical comprising about 4 to about 8 carbon atoms;
R b is hydrogen or methyl with the proviso that both R b groups are identical;
R c is independently hydrogen or methyl with the proviso that both R c groups are identical;
each L/G independently comprises a lactide/glycolide copolymer segment;
the polymer has substantially no titratable carboxylic acid groups, and
the polymer has a weight average molecular weight of from about 6 kD to about 200 kD.
2. The polymer of claim 1 wherein L/G comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 45/55 to about 99/1.
3. The polymer of claim 1 wherein L/G comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 70/30 to about 90/10.
4. The polymer of claim 1 wherein L/G comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 85/15.
5. The polymer of claim 1 wherein the weight average molecular weight is about 9 kD to about 100 kD.
6. The polymer of claim 1 wherein the weight average molecular weight is about 25 kD to about 45 kD.
7. The polymer of claim 1 in combination with a drug wherein the combination is a controlled release formulation.
8. The polymer combination of claim 7 wherein the drug is leuprolide.
9. A method of treatment of prostate cancer in a human male patient comprising treating the patient with an effective dose of the polymer combination of claim 8 .
10. A method of treatment of claim 9 wherein the treatment s accomplished once every 3 months, 4 months or 6 months.
11. The polymer combination of claim 8 further including an organic solvent which is N-methyl pyrrolidone, N,N-dimethyl formamide or N,N-dimethyl acetamide.
12. The polymer combination of claim 11 wherein the organic solvent is N-methyl pyrrolidone.
13. A method of treatment of prostate cancer in a human male patient comprising administration to the patient an effective dose of a polymer combination of claim 12 .
14. A method of treatment of claim 13 wherein the administration is accomplished once every 3 months, 4 months or 6 months.