Asta Medica, Aktiengesellschaft

Wolfgang Deger

Jurgen Engel

Dieter Sauerbier

Elisabeth Wolf-Heuss

Giancarlo Camuglia

Thomas Reissmann

Gunter Losse

Wolfgang Naumann

Sandra Murgas

In this invention, a release-delaying system is to be developed for LHRH antagonists, in particular for cetrorelix, which allows the active compound to be released in a controlled manner over several weeks by complexation with suitable biophilic carriers. The acidic polyamino acids polyglutamic acid and polyaspartic acid were selected for complexation with cetrorelix. The cetrorelix polyamino acid complexes are prepared from aqueous solutions by combination of the solutions and precipitation of the complexes, which are subsequently centrifuged off and dried over P.sub.2 O.sub.5 in vacuo. If complexes having a defined composition are to be obtained, lyophilization proves to be a suitable method. The cetrorelix-carboxylic acid complexes were also prepared from the aqueous solutions. In the random liberation system, the acidic polyamino acids poly-Glu and poly-Asp showed good release-delaying properties as a function of the hydrophobicity and the molecular mass of the polyamino acid. In animal experiments, it was possible to confirm the activity of the cetrorelix-polyamino acid complexes as a depot system in principle. It is thus possible by complexation of cetrorelix with polyamino acids to achieve testosterone suppression in male rats over 600 hours. The release of active compound here can be controlled by the nature and the molecular mass of the polymers.

Process for the preparation of immobilized and activity-stabilized

Immobilized and activity-stabilized complexes of LHRH antagonists and

Injectable mesna solutions having a pH value higher than 7.5. The solutions have increased storage stability.

Container for injectable mesna solutions

Injectable mesna solutions

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Frankfurt-am-Main, Germany

Wolfgang Deger