IMMOBILIZED ACTIVITY STABILIZED LHRH ANTAGONIST COMPLEXES, METHOD FOR THE PRODUCTION THEREOF

摘要

The invention relates to a retard system for LHRH antagonists, specially cetrorelix, based on complexation with suitable biophile carriers enabling targeted release of the active substance over a period of several weeks. Acidic polyamino acids, polyasparaginic acids and polyglutaminic acids are selected for complexation with cetrorelix. The cetrorelix polyamino acid complexes are produced from aqueous solutions by combining the solutions and precipitating the complexes which are subsequently centrifuged off and vacuum dried by P2O5, lyophilization proving to be a suitable method. The acidic polyamino, polyglutaminic and polyasparaginic acids display good retarding properties in a static liberation system depending on the hydrophobicity and the molar mass of the polyamino acids. Animal testing demonstrates the principal efficacy of the cetrorelix polyamino acid complexes as a depot system. By complexation of cetrorelix with polyamino acids, testosterone suppression can be achieved in male rats over a period of 600 hours. Active substance release can thus be controlled according to polymer type and molar mass.