Sustained release polymer
View Patent ↗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 flowable composition for a controlled release formulation comprising an organic solvent, a medicament and a polymer of Formula
HO—(P)—C(═O)O—R a —O(O═)C—(P)—OH
wherein:
R 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 a is a linear unsubstituted carbon chain.
5. The flowable composition of claim 1 wherein R 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 α,ω-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 %.