Pharmaceutical formulations targeting specific regions of...

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A61K 31/706 (2006.01) A61K 9/14 (2006.01) A61K 9/22 (2006.01) A61K 9/26 (2006.01) A61K 9/28 (2006.01) A61K 9/30 (2006.01) A61K 9/32 (2006.01) A61K 9/34 (2006.01) A61K 9/40 (2006.01) A61K 9/42 (2006.01) A61K 31/4745 (2006.01) A61K 31/7052 (2006.01)

Patent

CA 2503150

Oral formulations of pharmaceuticals are provided with enhanced bioavailability by targeting specific regions of the gastrointestinal tract. Particularly, water soluble and acid-labile drugs such as cytidine analogs (e.g., decitabine) and 2'-deoxyadenosine analogs (e.g., pentostatin) are formulated with pH-sensitive polymers so that these drugs are preferably absorbed in the upper regions of the small intestine, such as the jejunum. In addition, drugs with poor oral bioavailability such as camptothecin compounds (e.g., 9~ nitro-camptothecin) can also be formulated using similar strategies in order to significantly improve their oral bioavailability. These formulations can be used to treat a wide variety of diseases or conditions, such hematological disorders, benign tumors, cancer, restenosis, inflammatory diseases, and autoimmune diseases.

L'invention concerne des formulations orales de produits pharmaceutiques de biodisponibilité améliorée par ciblage de régions spécifiques du tractus gastro-intestinal. En particulier, des médicaments hydrosolubles et acido-labiles tels que des analogues de cytidine (par exemple, la décitabine) et des analogues de 2'-déoxyadénosine (par exemple la pentostatine) sont formulés avec des polymères sensibles au pH de façon que ces médicaments soient de préférence absorbés dans les régions supérieures du petit intestin, comme le jéjunum. De plus, les médicaments de pauvre biodisponibilité orale tel que les composés de la camptothécine (par exemple la 9- nitro-camptothécine) peuvent aussi être formulés au moyen de stratégies similaires de façon à améliorer de façon importante leur biodisponibilité orale. On peut utiliser ces formulations afin de traiter une grande variété de maladies ou de troubles, tells que des troubles hématologique, des tumeurs bénignes, le cancer, la resténose, des maladies inflammatoires et des maladies auto-immunes.

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