Pharmaceutical formulations for the sustained release of...

A - Human Necessities – 61 – K

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Details

A61K 38/21 (2006.01) A61K 9/10 (2006.01) A61K 9/14 (2006.01) A61K 38/20 (2006.01) A61K 47/42 (2006.01) A61K 47/48 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2546677

The invention relates to novel pharmaceutical formulations based on fluids and stable aqueous colloidal suspensions for the sustained release of interferon IFN- (and one or more other optional active principles), and to the applications, particularly the therapeutic applications, of said formulations. The invention aims to provide a fluid pharmaceutical formulation for the sustained release of interferon(s) (and one or more other optional active principles), such that, following parenteral injection, the in vivo interferon release time is increased significantly, while the plasma concentration peak thereof is lowered. Moreover, said formulation must be storage stable and, in addition, biocompatible, non-toxic biodegradable, non-immunogenic and well tolerated locally. According to the invention, the formulation is a low-viscosity aqueous colloidal suspension of submicronic particles of water-soluble, biodegradable polymer PO bearing hydrophobic groups (GH). The aforementioned particles are noncovalently associated with at least one interferon (and one or more other optional active principles) and form a gelled deposit on the injection site, said gelling being caused by a protein present in the physiological medium.

La présente invention concerne de nouvelles formulations pharmaceutiques à base de suspensions colloïdales aqueuses stables et fluides pour la libération prolongée d~interféron -IFN- (et un ou plusieurs autres principe(s) actif(s) éventuels), ainsi que les applications, notamment thérapeutiques, de ces formulations. Le but de l~invention est de proposer une formulation pharmaceutique fluide pour la libération prolongée d'interféron(s) (et un ou plusieurs autres principe(s) actif(s) éventuels), permettant après injection par voie parentérale d'accroître significativement la durée de libération in vivo des interférons, tout en diminuant le pic de concentration plasmatique de cet IFN, ladite formulation se devant par ailleurs d'être stable à la conservation et de surcroît biocompatible, biodégradable non-toxique, non- immunogène et bien tolerée localement. La formulation selon l'invention est une suspension colloïdale aqueuse de basse viscosité, de particules submicroniques de polymère PO biodégradable, hydrosoluble et porteur de groupements hydrophobes (GH), lesquelles particules étant associées de façon non covalente avec au moins un interféron (et un ou plusieurs autres principe(s) actif(s) éventuels) et formant un dépôt gélifié sur le site d'injection, cette gélification étant provoquée par une protéine présente dans le milieu physiologique.

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