POLYMERIC DELIVERY FORMULATIONS OF LEUPROLIDE WITH IMPROVED EFFICACY
The present invention is directed to a flowable composition that is suitable for use as a controlled release implant. The flowable composition includes a biodegradable thermoplastic polyester that is at least substantially insoluble in aqueous medium or body fluid. The flowable composition also includes a biocompatible polar aprotic solvent. The biocompatible polar aprotic solvent is miscible to dispersible in aqueous medium or body fluid. The flowable composition also includes leuprolide acetate.
1 - 46 . (canceled)
47 . A flowable composition suitable for use to form an in situ, single body controlled release implant, the composition comprising a non-aqueous, liquid solution of: (a) a biodegradable thermoplastic chain extended copolymer of lactide and glycolide including hexane diol as a chain extender; (b) N-methyl-2-pyrrolidone; and (c) leuprolide acetate; wherein,
the copolymer has a weight average molecular weight of about 15,000 to about 45,000, and is present in the composition at about 30 wt % to about 50 wt %;
the N-methyl-2-pyrrolidone is present in the composition at about 45 wt % to about 70 wt %; and,
the leuprolide acetate is present in the composition at least at about 2 wt %.
48 . A flowable composition according to claim 47 wherein the leuprolide acetate is present in the composition in an amount sufficient to reduce serum testosterone levels in a male patient.
49 . a flowable composition according to claim 47 wherein the leuprolide acetate is present in the composition at about 2 wt % to about 8 wt %.
50 . A flowable composition according to claim 47 wherein the sum of the weight percentages of the copolymer, N-methyl-2-pyrrolidone and leuprolide acetate is about 100%.
51 . A flowable composition according to claim 49 wherein the sum of the weight percentages of the copolymer, N-methyl-2-pyrrolidone and leuprolide acetate is about 100%.
52 . A flowable composition according to claim 47 wherein the composition is formulated for administration to a male patient about once per three months, once per four months or once per six months and produces in situ the single body implant.
53 . A flowable composition according to claim 52 wherein the in situ implant reduces serum testosterone levels in the male patient.
54 . A biodegradable implant formed in situ, in a male patient, by the steps comprising: (a) injecting about 0.2 to about 0.5 ml of the flowable composition of claim 47 within the body of the patient; and (b) allowing the N-methyl-2-pyrrolidone to dissipate to produce a solid, monolithic biodegradable implant of a microporous matrix of a core surrounded by a skin.
55 . A method of reducing serum testosterone levels in a male human comprising injecting subcutaneously into the male human about 0.2 ml to about 0.5 ml of a flowable composition comprising a non-aqueous, liquid solution of: (a) a biodegradable thermoplastic chain extended copolymer of lactide and glycolide including hexane diol as the chain extender; (b) N-methyl-2-pyrrolidone; and (c) leuprolide acetate; wherein
the chain extended copolymer has a weight average molecular weight of about 15,000 to about 45,000 and is present in the composition at about 30 wt % to about 50 wt %;
the N-methyl-2-pyrrolidone is present in the composition at about 45 wt % to about 70 wt %; and,
the leuprolide acetate is present in the composition at least at about 2 wt %;
the flowable composition forms in situ a monolithic solid implant of a microporous matrix of a core surrounded by a skin within a body tissue of the male human.
56 . A method according to claim 55 wherein the leuprolide acetate is present in the composition in an amount sufficient to reduce serum testosterone levels in a the male human;
57 . A method according to claim 55 wherein the leuprolide acetate is present in the composition at about 2 wt % to about 8 wt %.
58 . A method according to claim 55 wherein the solid implant is formed by diffusion of the N-methyl-2-pyrrolidone into the body fluid of the male human and precipitation of the chain extended copolymer.
59 . A flowable composition according to claim 47 wherein the leuprolide acetate is present in the composition in an amount sufficient to reduce LHRH levels in a human.