Patent ID: 7087246

Claim:
A controlled release preparation of insulin containing microparticles having a volume average diameter of 10 μm or less obtained by microencapsulation of insulin microcrystals having a volume average diameter which is less than the volume average diameter of the microparticles, wherein the insulin microcrystals are formed by varying the pH of an acidic insulin solution, which is at an isoelectric point or below, up to within the range 9 to 10.5 to form insulin seeds that can act as nuclei of crystal; and lowering the solubility of insulin in the solution by lowering the pH of the solution, wherein the microencapsulation is performed by double emulsion method comprising suspending the insulin microcrystals in a solution of pH 4.5 to 6.5, which is. an isoelectric precipitation zone; adding the suspended solution to a biodegradable polymer solution to make a primary emulsion; adding an emulsifier to the primary emulsion to make a secondary emulsion; and stirring the secondary emulsion to form microparticles.