A method of extending the dose range of vitamin d compounds

A - Human Necessities – 61 – K

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A61K 31/59 (2006.01) A61K 31/565 (2006.01) A61K 31/593 (2006.01) A61K 45/06 (2006.01)

Patent

CA 2497828

Inhibitors of bone calcium resorption are administered to allow high doses of vitamine D compounds or mimetics to be given the intent of treating non- calcium related diseases such as cancer, psoriasis, and autoimmune disease without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG or the soluble RANKL receptor known as sRANK, and function to block the availabilite of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of 1.alpha.,25- dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene-19-nor(20S)-1.alpha.,25 dihydroxyvitamin D3.

Cette invention concerne des inhibiteurs de la résorption osseuse du calcium administrés dans le but d'augmenter le dosage de composés à base de vitamine D ou de mimétiques prescrits dans le traitement de maladies non associées au calcium telles que le cancer, le psoriasis et les maladies auto-immunes, ceci sans risques de calcification des reins, du coeur et de l'aorte. Ces inhibiteurs de la résorption osseuse du calcium tels que les bis-phosphonates, l'ostéoprotégérine ou le récepteur RANKL soluble connu sous le sigle sRANK, ont pour effet de bloquer la disponibilité du calcium de provenance osseuse et donc d'empêcher une hypercalcémie et la calcification des tissus mous qui en résulte. Ainsi, il est possible d'utiliser des doses élevées de 1?,25-dihydroxyvitamine D¿3? (1,25-(OH)¿2?D¿3?), analogues, promédicaments ou mimétiques avec un risque minime pour le patient. Spécifiquement, il apparaît que l'alendronate bloque l'activité de mobilisation osseuse du calcium tant de 1,25-(OH)¿2?D¿3? que de son très puissant analogue, la 2-méthylène-19-nor(20S)-1?,25 dihydroxyvitamine D¿3?.

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