Methods and compositions for lipidization of hydrophilic...

C - Chemistry – Metallurgy – 07 – D

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C07D 213/71 (2006.01) C07C 323/59 (2006.01) C07D 473/18 (2006.01) C07H 19/06 (2006.01) C07H 19/16 (2006.01) C07H 21/00 (2006.01) C07J 43/00 (2006.01) C07K 5/093 (2006.01) C07K 14/585 (2006.01) A61K 9/127 (2006.01)

Patent

CA 2267179

Fatty acid derivatives of disulfide-containing compounds (for example, disulfide-containing peptides or proteins) comprising fatty acid-conjugated products with a disulfide linkage are employed for delivery of the compounds to mammalian cells. This modification markedly increases the absorption of the compounds by mammalian cells relative to the rate of absorption of the unconjugated compounds, as well as prolonging blood and tissue retention of the compounds. Moreover, the disulfide linkage in the conjugate is quite labile in vivo and thus facilitates intracellular or extracellular release of the intact compounds from the fatty acid moieties.

Cette invention se rapporte à des dérivés acides gras de composés contenant du disulfure (par exemple des peptides ou des protéines contenant du disulfure), qui comprennent des produits modifiés par conjugaison avec des acides gras, présentant une liaison disulfure, ces dérivés étant utilisés pour administrer les composés à teneur en disulfure dans des cellules de mammifères. La modification ainsi apportée augmente considérablement l'absorption desdits composés par les cellules de mammifères par rapport à la vitesse d'absorption de tels composés non conjugués, et elle prolonge la rétention de ces composés dans le sang et les tissus. En outre, la liaison disulfure du conjugué est très labile in vivo et elle facilite par conséquent la libération intracellulaire ou extracellulaire des composés intacts à partir des fractions d'acides gras.

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