Prolonged release microcapsule and its production

• US 4,652,441 A
• Filed: 11/01/1984
• Issued: 03/24/1987
• Est. Priority Date: 11/04/1983
• Status: Expired due to Term

• Current Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Yashiki, Takatsuka, Okada, Hiroaki, Ogawa, Yasuaki
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US06/667,096
• Time in Patent Office: 873 Days
• Field of Search: 264/4.6, 428/402.2, 424/19, 424/35, 514/963
• US Class Current: 424/497
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 38/33 derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
• CPC Class Codes: A61K 38/37 Factors VIII
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/1694 resulting in granules or microspheres of the matrix type containing more than 5% of excipient
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50
• CPC Class Codes: B01J 13/125 by evaporation of the solvent apparatus therefor B01J13/043
• CPC Class Codes: Y10S 424/15 Suppositories
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]

Abstract

A microcapsule produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing said water-soluble drug and a drug retaining substance therefor and an oil layer containing a polymer substance, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centiposes and finally subjecting the resulting emulsion to in water drying gives prolonged release of water-soluble drug.

Claims

1. A prolonged release microcapsule having an average diameter of about 2 to 200μ

m for injection, which is produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing a biologically active polypeptide, a drug retaining substance therefor selected from a member of the group consisting of gelatin, albumin, pectin and agar and an oil layer containing a polymer substance of lactic acid-glycolic acid copolymer or lactic acid polymer, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centipoises and finally admixing the resulting emulsion with a third aqueous layer to give a water/oil/water ternary layer emulsion and then desorbing the solvent in the oil layer.

2. A microcapsule as claimed in claim 1, wherein the biologically active polypeptide is (Pyr) Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NH-C₂ H₅.

3. A microcapsule as claimed in claim 1, wherein the drug retaining substance is gelatin.

4. A microcapsule as claimed in claim 1, wherein the polymer substance in the oil layer is a copolymer of lactic acid and glycolic acid.

5. A microcapsule as claimed in claim 4, wherein the ratio of lactic acid:

glycolic acid is 75;

25.

6. A microcapsule as claimed in claim 1, wherein the polymer substance in the oil layer is polylactic acid.

7. A microcapsule as claimed in claim 1, wherein the inner aqueous layer is thickened to a viscosity not less than about 10,000 centipoises.

8. A microcapsule as claimed in claim 1, wherein the inner aqueous layer is solidified.

9. A method for producing a prolonged release microcapsule having an average diameter of about 2 to 200 μ

m for injection, which comprises preparing a water-in-oil emulsion comprising an inner aqueous layer containing a biologically active polypeptide, a drug retaining substance therefor selected from a member of the group consisting of gelatin, albumin, pectin and agar and an oil layer containing a polymer substance of lactic acid-glycolic acid copolymer or lactic acid polymer, then thickening or solidifying said inner aqueous layer to a viscosity of not lower than about 5000 centipoises and finally admixing the resulting emulsion with a third aqueous layer to give a water/-oil/water ternary layer emulsion and then desorbing the solvent in the oil layer.