The invention discloses a preparation method of medicinal 6-arm-
polyethylene glycol-
succinimide glutaric acid ester (amido bond), which comprises the following steps: reacting 6-arm-
polyethylene glycol-amino with
glutaric anhydride to obtain a reaction solution 1; adding an
organic solvent B into the reaction liquid 1, stirring, pulping, filtering and
drying to obtain 6-arm-
polyethylene glycol-
glutaric acid (amido bond); mixing 6-arm-
polyethylene glycol-
glutaric acid (amido bond) with a condensing agent, dropwise adding organic alkali, and reacting to obtain reaction liquid 2; adding N-hydroxysuccinimide, and reacting to obtain a reaction solution 3; concentrating under reduced pressure, dropwise adding n-
hexane into the filtrate to separate out
solid, stirring and pulping to obtain pulp; and filtering, washing a
filter cake with n-
hexane, and
drying to obtain the medicinal 6-arm-
polyethylene glycol-
succinimide glutaric acid ester (amido bond). The method has the advantages of mild
reaction conditions, high
reaction rate, few byproducts and high yield, the content is more than 99.0%, the
acid value is less than 0.10, and the quality indexes all meet the standards of pharmaceutical enterprises.