Patent ES-8602858-A1 (ES)
Title: Continuous release formulations.
IPC: A61K47/00
Filed: 1984-08-13
Abstract: EP--92918 A Compsn. comprises (1) a pharmacologically active polypeptide (I) and (2) an acceptable, amphipathic, non-crosslinked copolymer (linear, branched or graft) (II) of min. wt. average mol. wt. 5000. The hydrophobic component of (II) is biodegradable or hydrolysable under physiological conditions, and the hydrophilic component is opt. biodegradable. When introduced into the body the compsn. forms a hydrogel. - (II) are claimed as new esp. they are linear block copolymers Am(BA)n or Bm(AB)n or graft or branched block copolymers ABn or BAn (A is a hydrophobic and B a hydrophilic polymer n is an integer and m is 0 or 1). The compsns. continuously release (I) over a long period when implanted or introduced by intramuscular or subcutaneous injection. (I) are pref. relatively hydrophilic e.g. oxytocin, vasopressin, insulin, interferon, endomorphins, monoclonal antibodies, soluble vaccines or esp. the LH-RH analogue Pyroglu-His-Trp-Ser-Tyr-D-Ser (Ot.Bu)-Leu-Arg-Pro-Azgly.NH2. More generally (II) are also useful for sustained release of non-peptide drugs. (0/0) EPAB- EP--92918 B Compsn. comprises (1) a pharmacologically active polypeptide (I) and (2) an acceptable, amphipathic, non-crosslinked copolymer (linear, branched or graft) (II) of min. wt. average mol. wt. 5000. The hydrophobic component of (II) is biodegradable or hydrolysable under physiological conditions, and the hydrophilic component is opt. biodegradable. When introduced into the body the compsn. forms a hydrogel. - (II) are claimed as new esp. they are linear block copolymers Am(BA)n or Bm(AB)n or graft or branched block copolymers ABn or BAn (A is a hydrophobic and B a hydrophilic polymer n is an integer and m is 0 or 1). The compsns. continuously release (I) over a long period when implanted or introduced by intramuscular or subcutaneous injection. (I) are pref. relatively hydrophilic e.g. oxytocin, vasopressin, insulin, interferon, endomorphins, monoclonal antibodies, soluble vaccines or esp. the LH-RH analogue Pyroglu-His-Trp-Ser-Tyr-D-Ser (Ot.Bu)-Leu-Arg-Pro-Azgly.NH2. More generally (II) are also useful for sustained release of non-peptide drugs. (27pp Dwg.No.0/0) - EP--92918 B A pharmaceutical composition comprising a pharmacologically useful polypeptide and a pharmaceutically or veterinarily acceptable, amphipathic, non-cross-linked linear, branched or graft block copolymer, which has a minimum weight average molecular weight of 5,000, in which the hydrophobic component is biodegradable or hydrolytically unstable under normal physiological conditions, and the hydrophilic component may or may not be biodegradable, the composition being capable of absorbing water to form a hydrogel when placed inwater or an aqueous physiological-type environment in an animal body, but excluding such compositions in which the hydrophobic component is derivable from at least one cyclic (thio) ether. (14pp)l USAB- US4526938 A New compsn. comprises amphipathic non-crosslinked linear branched or graft copolymer, MW 5000 +, with hydrophobic component biodegradable or hydrolytically unstable and hydrophilic component opt. biodegradable. The amphipathic copolymer absorbs water to form hydrogel in body, and is of formula Am (BA)n or Bm (AB)n wherein n is 0 or 1 and n is an integer, with A a hydrophobic and B a hydrophilic polymer. Or it is a graft or branched block copolymer of formula ABm or BAn with A or B a backbone polymer with n units of monomer or polymer A or B respectively grafted on. - Esp. copolymer is oxyethylene:lactic:glycol of 2:1:1. Mfr. is by copolymerising A and B. - A is selected from D-, L and DL lactic acids or lactides, polyglycolic acid, polyglycolide, polycaprolactone, poly-hydroxybutyric acid non-therapeutic hydrophobic polypeptides, polyacetals, polycarbonates or polyorthoesters. B is selected from PVA, polyvinylpyrrolidone, polyethyleneglycol, polyacrylamide, polymethacrylamide, dextran, alginic acid, sodium alginate, gelatin, copolymers of 2 or more monomers, polyoxyethylene-polyoxypropylene block copolymers.