EXENDIN-4 DERIVATIVE LINKED HYDROPHOBIC BILE ACID, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

摘要

Provided are an exendin-4 derivative linked by hydrophobic bile acid which forms nanoparticles, improves albumin adsorption activity, and increases the in vivo half-life while it shows identical or similar biological activity to natural exendin-4, a method for the preparation thereof and a pharmaceutical composition comprising the same compound so as to be used for treating disease caused by excessive insulin secretion including diabetes, obesity and irritable colon syndrome. The exendin-4 derivative linked by hydrophobic bile acid in which 12th, 27th or 12th and 27th lysine residues are lined to the hydrophobic bile acid is provided. The method for preparing the exendin-4 derivative linked by hydrophobic bile acid comprises the steps of: (1) reacting bile acid with N-hydroxysuccinimide(NHS) to activate the carboxylic acid group of the bile acid; (2) reacting the activated bile acid-NHS with exendin-4; and (3) separating the exendin-4 derivative linked by hydrophobic bile acid from the reaction mixture.