Microcapsule formulation and method for producing the same
An object of the present invention is to provide a method for producing a microcapsule formulation using a biodegradable polymer, the method being capable of avoiding direct contact of a peptidic physiologically active substance with an organic solvent layer, and achieving a high encapsulation efficiency of the peptidic physiologically active substance.
1. A method for producing a microcapsule formulation comprising:
step A of adding a basic amino acid to an aqueous solvent containing a heavy metal salt of a peptidic physiologically active substance to obtain an amino acid-containing S/W suspension;
step B of adding a basic amino acid to an organic solvent containing a biodegradable polymer to obtain an amino acid-containing polymer solution;
step C of dispersing the amino acid-containing S/W suspension in the amino acid-containing polymer solution, which is an oil phase, to obtain an S/W/O emulsion;
step D of dispersing the S/W/O emulsion in a water phase to obtain an S/W/O/W emulsion; and
step E of removing the organic solvent from the S/W/O/W emulsion to obtain the microcapsule formulation.
2. The method according to claim 1 , wherein the molar ratio of the basic amino acid contained in the amino acid-containing S/W suspension to the basic amino acid contained in the amino acid-containing polymer solution is 1:5 to 5:1.
3. The method according to claim 1 , wherein the heavy metal salt of the peptidic physiologically active substance has a mean particle size of 1 μm or less and is insoluble in both water and organic solvents.
4. The method according to claim 1 , wherein the peptidic physiologically active substance has an IgG structure.
5. The method according to claim 1 , wherein the peptidic physiologically active substance is TuNEX.
6. The method according to claim 1 , wherein the heavy metal salt is a zinc salt.
7. The method according to claim 1 , wherein the basic amino acid is L-arginine or L-histidine.
8. The method according to claim 1 , further comprising step F of subjecting microcapsules obtained by removing the organic solvent from the S/W/O/W emulsion in step E to freeze-drying or spray-drying to form a powder.
9. The method according to claim 1 , wherein the biodegradable polymer is a polylactic acid, a lactic acid-glycolic acid copolymer, or a mixture thereof.
10. The method according to claim 9 , wherein the molar ratio of lactic acid to glycolic acid (lactic acid:glycolic acid) in the biodegradable polymer is 99:1 to 50:50.
11. The method according to claim 10 , wherein the molar ratio of lactic acid to glycolic acid (lactic acid:glycolic acid) in the biodegradable polymer is 75:25 to 50:50.
12. The method according to claim 1 , wherein the biodegradable polymer has a weight average molecular weight of 3,000 to 200,000.
13. The method according to claim 12 , wherein the biodegradable polymer has a weight average molecular weight of 3,000 to 50,000.
14. The method according to claim 13 , wherein the biodegradable polymer has a weight average molecular weight of 5,000 to 200,000.
15. A microcapsule formulation produced by the method according to claim 1 .