Details for Patent: 8,470,359

Title:	Sustained release polymer
Abstract:	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.
Inventor(s):	Dunn; Richard L. (Fort Collins, CO)
Assignee:	QLT USA, Inc. (Willmington, DE)
Filing Date:	Aug 31, 2006
Application Number:	11/469,392
Claims:	1. A flowable composition for a controlled release formulation comprising an organic solvent, a medicament and a polymer of Formula HO--(P)--C(.dbd.O)O--R.sup.a--O(O.dbd.)C--(P)--OH wherein: R.sup.a is an alkane diradical comprising about 4 to about 8 carbons and is a residue of an alkane diol, P is a polymeric segment of repeating units of lactide, lactic, co(lactide-glycolide) or co(lactic-glycolic) moieties, the polymer is substantially insoluble in water and body fluid, the polymer has substantially no titratable carboxylic acid groups, and the polymer has a weight average molecular weight from about 10 kD to about 50 kD, and the polymer in neat form is a solid at ambient temperature, the organic solvent is a polar, aprotic organic solvent having at least some water solubility. 2. The flowable composition of claim 1 wherein P comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 45/55 to about 99/1. 3. The flowable composition of claim 1 wherein P comprises a lactide/glycolide copolymer segment with a lactide/glycolide ratio of about 70/30 to about 90/10. 4. The flowable composition of claim 1 wherein R.sup.a is a linear unsubstituted carbon chain. 5. The flowable composition of claim 1 wherein R.sup.a is a linear unsubstituted carbon chain of 6 carbon atoms. 6. The flowable composition of claim 1 wherein the polymer has a polydispersity of about 1.2 to about 2.0. 7. The flowable composition of claim 6 wherein the polymer has a polydispersity of about 1.4 to about 1.7. 8. The flowable composition of claim 1 wherein the polymer has an inherent viscosity of about 0.20 dL/gm to about 0.60 dL/gm. 9. The flowable composition of claim 1 wherein the polymer has an inherent viscosity of about 0.25 dL/gm to about 0.40 dL/gm. 10. A flowable composition of claim 1 comprising an organic solvent, a medicament and a polymer prepared by a method comprising contacting an alkanediol, and a polymerizable unit selected from the group consisting of glycolide, lactide, lactate, glycolate and a combination thereof, and a catalyst, the catalyst being adapted to catalyze ring-opening polymerization of polymerizable unit initiated by the alkanediol; wherein the alkanediol comprises an .alpha.,.omega.-diol of about 4 to about 8 carbon atoms. 11. The flowable composition of claim 1, wherein the organic solvent is N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, triacetin, propylene carbonate, or ethyl acetate. 12. The flowable composition of claim 1 wherein the medicament is leuprolide or a pharmaceutically acceptable salt thereof. 13. Method for use of the flowable composition of claim 1 for treatment of a malcondition in a patient in need thereof, comprising implantation of the flowable composition comprising an effective amount of a medicament, into body tissue of the patient. 14. The use of claim 13, wherein the malcondition is prostate cancer. 15. The use of claim 13, wherein the composition comprises leuprolide or a pharmaceutically acceptable salt thereof. 16. A flowable composition according to claim 1 wherein the weight percentage of alkane diol relative to the total weight of alkane diol and the starting materials forming the repeating units of the polymer P is from about 0.05 wt % to about 2 wt %.