Modification of polypeptide drugs to increase...

C - Chemistry – Metallurgy – 07 – K

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C07K 1/107 (2006.01) A61K 38/00 (2006.01) A61N 1/30 (2006.01) C07K 14/535 (2006.01) C07K 14/60 (2006.01) C07K 14/635 (2006.01) C12N 9/00 (2006.01) A61K 9/00 (2006.01)

Patent

CA 2220146

Methods of modifying polypeptide drugs in order to enhance their transdermal electrotransport flux are provided. The polypeptide is modified by substituting a histidine residue (HIS) for one or more glutamine (Gln), threonine (Thr) and/or aspargine (Asn) residue(s). The HIS for Gln substitution is particularly preferred from the standpoint of retaining biological activity of the parent polypeptide. Compositions containing the modified polypeptide, which are useful for transdermal electrotransport delivery, are also provided.

Procédés de modification de médicaments polypeptidiques, destinés à augmenter leur flux d'électrotransport transdermique. On modifie le polypeptide en remplaçant au moins un reste glutamine (Gln), thréonine (Thr) et/ou aspargine par un reste histidine (HIS). La substitution de Gln par HIS est particulièrement préférée dans la mesure où l'on veut maintenir l'activité biologique du polypeptide parent. Des compositions contenant le polypeptide modifié, utiles pour l'administration par électrotransport transdermique, sont également décrites.

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