Methods for in vivo reduction of iron levels and...

A - Human Necessities – 61 – K

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A61K 31/44 (2006.01) A61K 31/27 (2006.01) A61K 31/325 (2006.01) A61K 31/33 (2006.01) A61K 31/40 (2006.01)

Patent

CA 2263686

In accordance with the present invention, there are provided methods for the in vivo reduction of free iron ion levels in a mammalian subject. The present invention employs a scavenging approach whereby free iron ions are bound in vivo to a suitable physiologically compatible scavenger. The resulting complex renders the free iron ions harmless, and is eventually excreted in the urine of the host. Further in accordance with the present invention, there are provided compositions and formulations useful for carrying out the above- described methods. An exemplary scavenger contemplated for use in the practice of the present invention is a dithiocarbamate-containing composition. This material binds to free iron ions, forming a stable, water-soluble dithiocarbamate-iron complex. Thus, the present invention relates to methods for reducing in vivo levels of free iron ions as a means of treating subjects afflicted with iron overload and non-iron overload diseases and/or conditions, such as thalassemia, anemia, hereditary hemochromatosis, hemodialysis, stroke and rheumatoid arthritis. Dithiocarbamate-containing scavengers are administered to a host in need of such treatment; these scavengers interact in vivo with free iron ions, thereby forming a stable dithiocarbamate-metal complex, which is then filtered through the kidneys, concentrated in the urine, and eventually excreted by the subject, thus reducing in vivo levels of free iron ions.

Dans la présente invention, on décrit des procédés de réduction in vivo des taux d'ions de fer libres chez un mammifère, procédés dans lesquels on met en oeuvre une approche d'épuration consistant à fixer in vivo les ions de fer libres sur un épurateur compatible physiologiquement. Le complexe résultant rend inoffensifs les ions de fer libres, et il est éventuellement éliminé dans l'urine du patient. En outre, l'invention concerne des compositions et formulations utiles pour exécuter les procédés ci-dessus décrits. A titre d'exemple d'épurateur dont l'utilisation peut être envisagée dans la mise en oeuvre de l'invention, on peut citer une composition contenant un dithiocarbamate, lequel se fixe sur les ions de fer libres, et forme un complexe dithiocarbamate/fer, stable et hydrosoluble. Ainsi, la présente invention concerne des procédés de réduction in vivo des taux d'ions de fer libres en tant que moyen de traitement de sujets souffrant d'états et/ou de pathologies liés à une surcharge en fer ou non en fer, tels que la thalassémie, l'anémie, hémochromatose héréditaire, l'hémodialyse, l'ictus et la polyarthrite rhumatoïde. On administre à un patient nécessitant un tel traitement des épurateurs contenant du dithiocarbamate, lesquels interagissent in vivo avec les ions de fer libres, formant ainsi un complexe stable dithiocarbamate/métal, lequel est ensuite filtré par les reins, concentré dans l'urine et éventuellement éliminé par le patient, ce qui permet de réduire in vivo les taux d'ions de fer libres.

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