COMPLEXES OF DABIGATRAN AND ITS DERIVATIVES, PROCESS FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

The present invention relates to pharmaceutically acceptable complex formulae comprising complexes of Dabigatran, its esters, preferably Dabigatran etexilate, its salts, preferably 5 Dabigatran etexilate mesylate, or derivatives thereof and complexation agents and pharmaceutically accepted excipients, process for the preparation thereof and pharmaceutical compositions containing them. The complex formulae of the present invention have improved physicochemical properties and enhanced biological performance and are useful in the treatment and/or prophylaxis of diseases, in particular thrombotic diseases, stroke, cardiac infarction and/or atrial fibrillation and cardiac arrhythmia, as well as oncological diseases of any pathogenesis. More specifically, the complex of the present invention possesses increased apparent solubility in the whole physiologically relevant pH range resulting in increased absorption and higher overall bioavailability. This allows the reduction of dose which delivers significantly less anticoagulant to the GI tract. Furthermore, the complex composition of the present invention contains no tartaric acid or any other acid which further decreases the incidence of GI tract bleeding. This also makes the bioavailability of the compound independent of the way it is administered; the final dosage form is not sensitive to being broken, chewed, or opened. Overall, the complex Dabigatran composition of the present invention allows safer administration of a lower dose from the active ingredient. La présente invention concerne des formules de complexes pharmaceutiquement acceptables comprenant des complexes de dabigatran, ses esters, de préférence l'étexilate de dabigatran, ses sels, de préférence le mésylate d'étexilate de dabigatran, ou des dérivés de ceux-ci et des agents de complexation et des excipients pharmaceutiquement acceptables, un procédé pour leur préparation et des compositions pharmaceutiques les contenant. Les formules de complexes de la présente invention ont des propriétés physico-chimiques améliorées et des performances biologiques renforcées et sont utiles dans le traitement et/ou la prophylaxie de maladie, en particulier des maladies thrombotiques, un accident vasculaire cérébral, un infarctus cardiaque et/ou une fibrillation auriculaire et une arythmie cardiaque, ainsi que des maladies oncologiques de pathogenèse quelconque. Plus spécifiquement, le complexe de la présente invention possède une solubilité apparente augmentée da