Prolonged release microcapsules

• US 5,480,656 A
• Filed: 01/31/1994
• Issued: 01/02/1996
• Est. Priority Date: 02/13/1990
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Takeda Chemical Industries, Ltd. (Takeda Pharmaceutical Company Limited)
• Inventors: Ogawa, Yasuaki, Okada, Hiroaki, Inoue, Yayoi
• Primary Examiner(s): Griffin, Ronald W.
• Application Number:
  US08/188,918
• Time in Patent Office: 701 Days
• Field of Search: 424/489, 424/461, 424/493, 604/891.1
• US Class Current: 424/493
• CPC Class Codes: A61K 38/066 TRH, thyroliberin, thyrotropin releasing hormone
• CPC Class Codes: A61K 38/09 Luteinising hormone-releasing hormone [LHRH] , i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• 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)

Abstract

This invention provides a microcapsule designed for zero order release of a physiologically active polypeptide over a period of at least two months, which is produced by preparing a water-in-oil emulsion comprising an inner aqueous layer containing about 20 to 70% (w/w) of said polypeptide and an oil layer containing a copolymer or homopolymer having a weight-average molecular weight of 7,000 to 30,000, wherein the composition ratio of lactic acid/glycolic acid in the copolymer or homopolymer is 80/10 to 100/0, and then subjecting said water-in oil emulsion to microencapsulation.

Claims

1. A microcapsule exhibiting zero order release of (pyr)Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-ProNHC₂ H₅ for a period of at least two months upon administration, which is produced by preparing a water-in-oil emulsion comprising an inner aqueous phase free from a drug retaining substance containing 35 to 60% (W/W) of (pyr)Glu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-ProNHC₂ H₅, and an oil phase containing a homopolymer of lactic acid having a weight-average molecular weight of 14,100 to 18,200 and a dispersion degree (ratio of weight-average molecular weight to number-average molecular weight) of 1.5 to 2.5, as the material for forming an outer wall of the microcapsule and then subjecting said water-in-oil emulsion to microencapsulation.

2. A microcapsule according to claim 1, which exhibits zero order release for a period of at least three months upon administration.

3. A microcapsule according to claim 1, wherein the concentration of homopolymer in the oil phase is from 2 to 60% by weight.