| 主权项 |
1. A process for the synthesis of copolymer-1 having a molecular weight below 20 KDa and acid content of less than 1%, the process comprising:
a) dissolving N-carboxyanhydrides (NCA) of tyrosine, alanine, γ-benzyl glutamate and Nε-trifluoroacetyllysine in a solvent; b) polymerizing the NCA by initiating with a polymer-supported dialkylamine or a polymer-supported trialkylamine or both, followed by stirring at room temperature to obtain copolymer 1; c) pouring the copolymer-1 as obtained in step b) into water, filtering the product followed by washing with water and drying; d) suspending the dried copolymer-1 as obtained in step c) in acetic acid, adding HBr in acetic acid, stirring at room temperature, decanting the acetic acid and evaporating; e) dispersing the copolymer-1 as obtained in step d) in water, adding 1 M piperidine, stirring for a time period in the range of 20-28 hrs at room temperature to form a solution; f) dialyzing the solution as obtained in step e) at room temperature to achieve pH=8; g) dialyzing the solution as obtained in step f) against acid followed by water to achieve pH=5.5-6 followed by concentrating the solution to obtain concentrated copolymer-1; h) lyophilizing the solution as obtained in step g) to dryness. |
