Engineering absorption of therapeutic compounds via colonic...

A - Human Necessities – 61 – K

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A61K 47/48 (2006.01) A61K 9/22 (2006.01) A61K 31/195 (2006.01) A61K 31/27 (2006.01)

Patent

CA 2473802

Methods of modifying therapeutic compounds such as drugs to be substrates for active transporters expressed in epithelial cells lining the lumen of the human colon are disclosed. The transporters expressed in the human colon include the sodium dependent multi-vitamin transporter (SMVT), and monocarboxylate transporters 1 and 4 (MCT 1 and MCT 4). The modified compounds can themselves be pharmacologically active, or upon cleavage of a chemical moiety after uptake from the colon, can be metabolized to form a compound that is pharmacologically active (e.g., a prodrug). The modified compounds disclosed herein are suitable for use in extended release oral dosage forms, particularly those that release drug over periods of greater than about 2-4 hours following administration.

L'invention concerne des procédés pour modifier des composés thérapeutiques tels que des médicaments devant servir de substrats pour des transporteurs actifs exprimés dans des cellules épithéliales qui recouvrent la lumière du colon humain. Lesdits transporteurs exprimés dans le colon humain comprennent des transporteurs de multi-vitamines dépendant du sodium (SMVT) et des transporteurs de monocarboxylate 1 et 4 (MCT1 et MCT4). Lesdits composés modifiés peuvent être eux-mêmes actifs pharmacologiquement, ou à la suite du clivage d'une fraction chimique après le captage à partir du colon, peuvent être métabolisés de manière à former un composé actif pharmacologiquement (par exemple un promédicament ). Lesdits composés modifiés de l'invention sont conçus pour être utilisés dans des formes de dosages orales à libération étendue, en particulier les formes de dosages dans lesquelles des médicaments sont libérés sur des périodes supérieures à des périodes comprises entre 2 et 4 heures environ suivant l'administration.

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