GLP-1 DERIVATIVE LINKED BIOTIN AND BIOTIN-POLYETHYLENE GLYCOL, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

摘要

The GLP-1 derivatives that one biotin is connected with biotin polyethylene glycol are arranged to be the glucose decline for being efficiently used for preventing or curing the disease as caused by the excessive secretion of insulin, in the plasma, the inhibition of stomach or bowel movement, the inhibition or food intake of primary empty stomach or intestines, the inhibition of type 2 diabetes, hypertrophy and irritable colon syndrome. Wherein biotin and biotin-polyethylene glycol are selectively attached to No. 26 tyrosine residues, the GLP-1 derivatives that No. 34 tyrosine residues are indicated by formula (2), wherein biotin-polyethylene glycol is indicated by formula (1), with 3,400 molecular weight. A kind of method is used to prepare GLP-1 derivatives and includes the following steps: :(a) increases biotin, biotin-polyethylene glycol and GLP to a buffer solution and an organic solvent to be susceptible to react; (b) reaction mixture that (a) is obtained the step of from certain period of time under certain temperature is stored; (c) unreacted reaction product is removed after the reaction of step (b) is completed; (d) isolated GLP-1, wherein biotin and the product of biotin-polyethylene glycol never reactor product removal are connected and clean them. A pharmaceutical composition or treating diabetes or the loose GLP-1 derivatives connected including biotin with biotin polyethylene glycol for preventing.