Composition and microsphere for controlled-release of exendin, and method of preparing the same

A controlled-release microsphere with a coating layer comprising

• a core comprising an exendin as an active ingredient, and a biodegradable polymer, and
• a coating layer that coats the core with a coating material,
• wherein the biodegradable polymer is a polymer selected from the group consisting of polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), polyorthoester, polyanhydride, polyhydroxybutyric acid, polycaprolactone, and polyalkylcarbonate;
• a copolymer or a simple mixture of two or more selected the polymer group;
• a copolymer of the polymer and polyethylenglycol (PEG);
• or a polymer-sugar complex where a sugar is coupled with the polymer or the copolymer,
• the coating material is one or more selected from the group consisting of basic amino acids, polypeptides, and organic nitrogen compounds, where the basic amino acid is one or more selected from the group consisting of arginine, lysine, and histidine, the polypeptide comprises 2 to 10 amino acids wherein one or more basic amino acids selected from the group consisting of arginine, lysine, and histidine are comprised, and the number of basic amino acid is more than that of acidic amino acids, and the organic nitrogen compound is one or more selected from the group consisting of creatine, creatinine, and urea.

A method of preparing an exendin-containing controlled-release microsphere with a coating layer comprising the steps of:

• mixing an exendin and a biodegradable polymer to prepare a W/O type emulsion or a homogeneous mixture;
• and
• emulsifying by adding the emulsion or the homogeneous mixture to an aqueous solution of a coating material, to form a coating layer,
• wherein the biodegradable polymer is a polymer selected from the group consisting of polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), polyorthoester, polyanhydride, polyhydroxybutyric acid, polycaprolactone, and polyalkylcarbonate, a copolymer or a simple mixture of two or more selected the polymer group, a copolymer of the polymer and polyethylenglycol (PEG), or a polymer-sugar complex where a sugar is coupled with the polymer or the copolymer, and
• the coating material is one or more selected from the group consisting of basic amino acids, polypeptides, and organic nitrogen compounds, where the basic amino acid is one or more selected from the group consisting of arginine, lysine, and histidine, the polypeptide comprises 2 to 10 amino acids wherein one or more basic amino acids selected from the group consisting of arginine, lysine, and histidine are comprised, and the number of basic amino acid is more than that of acidic amino acids, and the organic nitrogen compound is one or more selected from the group consisting of creatine, creatinine, and urea.

A method of preparing exendin-containing controlled-release microspheres with a coating layer comprising the steps of:

• mixing an exendin and a biodegradable polymer to form an emulsion or a homogeneous mixture;
• solidifying the obtained emulsion or homogeneous mixture to prepare primary microspheres;
• and
• suspending the obtained primary microspheres in an aqueous solution of a coating material, to form a coating layer on each microsphere,
• wherein the biodegradable polymer is a polymer selected from the group consisting of polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), polyorthoester, polyanhydride, polyhydroxybutyric acid, polycaprolactone, and polyalkylcarbonate, a copolymer or a simple mixture of two or more selected from the polymer group, a copolymer of the polymer and polyethylenglycol (PEG), or a polymer-sugar complex where a sugar is coupled with the polymer or the copolymer, and
• the coating material is one or more selected from the group consisting of basic amino acids, polypeptides, and organic nitrogen compounds, where the basic amino acid is one or more selected from the group consisting of arginine, lysine, and histidine, the polypeptide comprises 2 to 10 amino acids wherein one or more basic amino acids selected from the group consisting of arginine, lysine, and histidine are comprised, and the number of basic amino acids is more than that of acidic amino acids, and the organic nitrogen compound is one or more selected from the group consisting of creatine, creatinine, and urea.