Polymer-based sustained release device
AssigneeAlkermes Pharma Ireland Limited
InventorsSteven G. Wright, Troy Christensen, Thean Yeoh, Michael E. Rickey, Joyce M. Hotz, Rajesh Kumar, Henry R. Costantino
Life of this patent
Estimating the term…
Abstract
This invention relates to compositions for the sustained release of biologically active polypeptides, and methods of forming and using said compositions, for the sustained release of biologically active polypeptides. The sustained release compositions of this invention comprise a biocompatible polymer having dispersed therein, a biologically active polypeptide and a sugar.
Claims20
A method of preparing a composition for the sustained release of a polypeptide comprising the steps of:
- a) forming a mixture by combining an aqueous phase comprising a sugar and a water soluble polypeptide with an oil phase comprising a biocompatible polymer and a solvent for the polymer;
- b) forming a water-in-oil emulsion of the mixture from step a), wherein the inner emulsion droplet size is less than about 0.5 microns;
- c) adding a coacervation agent to the mixture to form embryonic microparticles, wherein said coacervation agent is silicone oil added in an amount sufficient to achieve a silicone oil to polymer solvent ratio of from about 0.75:1 to about 2:1;
- d) transferring the embryonic microparticles to a quench solvent to harden the microparticles;
- e)collecting the hardened microparticles;
- and
- f) drying the hardened microparticles.
A method of preparing a composition for the sustained release of exendin-4 comprising the steps of:
- a) forming a mixture by combining an aqueous phase comprising water soluble exendin-4 polypeptide and sucrose with an oil phase comprising a biocompatible 50:50 PLGA 4A polymer in methylene chloride;
- b) forming a water-in-oil emulsion of the mixture from step a), herein the inner emulsion droplet size is less than about 0.5 microns;
- c) adding a coacervation agent to the mixture to form embryonic microparticles, wherein said coacervation agent is silicone oil added in an amount sufficient to achieve a silicone oil to polymer solvent ratio of from about 0.75:1 to about 2:1, and wherein the silicone oil is added to the water-in-oil emulsion in from about 3 minutes to about 5 minutes and the coacervation mixture is held for less than or about 1 minute;
- d) transferring the embryonic microparticles to a quench solvent to harden the microparticles, wherein the quench solvent is a heptane/ethanol mixture and the transfer time is less than or about 3 minutes;
- e) collecting the hardened microparticles;
- and
- f) drying the hardened microparticles.
A method of preparing a composition for the sustained release of a polypeptide comprising the steps of:
- a) forming a mixture by combining an aqueous phase comprising a sugar and a water soluble polypeptide with an oil phase comprising a biocompatible polymer and a solvent for the polymer, wherein the polypeptide has a concentration of about 30 g to about 45 g per 600 g water;
- b) homogenizing the mixture of step a) to form a water-in-oil emulsion of the mixture, wherein an inner emulsion is formed having a droplet size of about 0.4 microns;
- c) adding a coacervation agent to the mixture to form embryonic microparticles, wherein said coacervation agent is silicone oil added in an amount sufficient to achieve a silicone oil to polymer solvent ratio of from about 0.75:1 to about 2:1;
- d) transferring the embryonic microparticles to a quench solvent to harden the microparticles;
- e) collecting the hardened microparticles;
- and
- f) drying the hardened microparticles.
Dependencies are inferred from the claim text.