Synergistic effects of amlodipine and atorvastatin...

A - Human Necessities – 61 – K

Patent

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A61K 31/40 (2006.01) A61K 31/44 (2006.01) A61K 31/4418 (2006.01)

Patent

CA 2370639

The combination of amlodipine with either atorvastatin or atorvastatin metabolite shows a synergistic antioxidant effect on lipid peroxidation in human low-density lipoproteins and membrane vesicles enriched with polyunsaturated fatty acids. Inhibition of oxy-radical damage by this drug combination was observed at therapeutic levels in a manner that could not be reproduced by the combination of amlodipine with other statins or the natural antioxidant, vitamin E. The basis for this potent activity is attributed to the chemical structures of these compounds and their molecular interactions with phospholipid molecules, as determined by x-ray diffraction analyses. This combination therapy can be used to treat cardiovascular disorders, especially coronary artery disease, by increasing the resistance of low-density lipoproteins and vascular cell membranes against oxidative modification.

La combinaison d'amlodipine avec de l'atorvastatine ou un métabolite d'atorvastatine produit un effet antioxydant synergique sur la peroxydation lipidique dans les lipoprotéines de basse densité et les vésicules membranaires humaines enrichies avec des acides gras polyinsaturés. On a observé que cette combinaison médicamenteuse inhibait l'activité nuisible des radicaux hydroxy à des niveaux thérapeutiques, propriété impossible à reproduire par la combinaison d'amlodipine avec d'autres statines ou avec la vitamine E, antioxydant naturel. On attribue cette puissante activité aux structures chimiques de ces composés et à leurs interactions moléculaires avec des molécules phospholipidiques, comme l'ont montré les analyses par diffraction de rayons X. Cette polythérapie peut servir à traiter les troubles cardiovasculaires, et notamment la coronaropathie, grâce à l'augmentation de la résistance des lipoprotéines de basse densité et des membranes cellulaires vasculaires aux modifications oxydatives.

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