Polymer-based sustained release device

The composition of for sustained release of biologically active polypeptide consisting of a biocompatible polymer, exendin-4 at about 3% w/w or more and sucrose at about 2% w/w or more of the weight of the composition, wherein the ratio of Cmax to Cave is about 3 or less and wherein the biocompatible polymer is selected from poly(lactides), poly(glycolides), poly(lactide-co-glycolides), poly(lactic acid)s, poly(glycolic acid)s, poly(lactic acid-co-glycolic acid)s and blends and copolymers thereof.

A method of treating a patient suffering from Type 2 diabetes comprising administering a therapeutically effective amount of a sustained release composition consisting essentially of a biocompatible polymer, a biologically active agent selected from the group consisting of an exendin, exendin analog, derivative, or agonist, and a sugar wherein the ratio of Cmax to Cave is 3 or less.

An injectable composition suitable for passage through a 23 gauge needle comprising, a sustained release composition comprising a 50:50 DL PLG 4A polymer, 3 to 5% (w/w) exendin-4, and 2% (w/w) sucrose, wherein the ratio of Cmax to Cave is about 3 or less and the total pore volume of the composition is about 0.1 mL/g or less, suspended in an injection vehicle comprising sodium carboxymethylcellulose at 3.0% (w/v), sodium chloride at 0.9% (w/v), and Polysorbate 20, NF (Tween 20) at 0.1% (v/v) in water.

An injectable composition suitable for passage through a 23 gauge needle comprising, a sustained release composition comprising a 50:50 DL PLG 4A polymer, about 3 to 5% (w/w) exendin-4 having an amino substitution of leucine for methionine at position 14, and about 2% (w/w) sucrose, wherein the ratio of Cmax to Cave is about 3 or less and the total pore volume of the composition is about 0.1 mL/g or less, suspended in an injection vehicle comprising sodium carboxymethylcellulose at 3.0% (w/v), sodium chloride at 0.9% (w/v), and Polysorbate 20, NF (Tween 20) at 0.1% (v/v) in water.

A kit for making an injectable composition suitable for passage through a 23 gauge needle comprising, a vial comprising a therapeutically effective dose of a dry sustained release composition comprising a 50:50 DL PLGA 4A polymer, 5% (w/w) exendin-4, and 2% (w/w) sucrose, wherein the ratio of Cmax to Cave is about 3 or less and the total pore volume of the composition is about 0.1 mL/g or less, and a vial comprising an injection vehicle comprising sodium carboxymethylcellulose at 3.0% (w/v), sodium chloride at 0.9% (w/v), and Polysorbate 20, NF (Tween 20) at 0.1% (v/v) in water, wherein there is sufficient injection vehicle to suspend the sustained release composition to at least 30 mg/ml, and instructions.

A pharmaceutically acceptable composition for the sustained release of biologically active polypeptide consisting essentially of a purified 50:50 DL PLG 4A polymer having dispersed therein exendin-4 at about 5% (w/w) or more and sucrose at about 2% (w/w) or more of the weight of the composition, wherein said composition has an absence of ammonium sulfate and a Cmax to Cave ratio of about 3 or less;

• the total pore volume of the composition is about 0.1 mL/g or less;
• and said composition is suitable for administration to a human for the treatment of diabetes mellitus.

A method of treating a patient suffering from diabetes mellitus comprising administering an amount effective to therapeutically lower blood glucose to a patient with diabetes mellitus of a sustained release pharmaceutically acceptable composition for the sustained release of biologically active polypeptide consisting essentially of a purified 50:50 DL PLG 4A polymer having dispersed therein exendin-4 at about 5% (w/w) or more and sucrose at about 2% (w/w) or more of the weight of the composition, wherein said composition has an absence of ammonium sulfate and a Cmax to Cave ratio of about 3 or less;

• the total pore volume of the composition is about 0.1 mL/g or less.