| 摘要 |
PURPOSE:To prepare a new mitomycin derivative having enhanced lymph migration characteristics and an increased retention time in blood and unsusceptible to enzymatic degradation, by bonding mitomycin to polysaccharide through a spacer. CONSTITUTION:(1) An aliphatic acid having a terminal amino group, e.g., epsilon- amino-n-caproic acid, etc., as a spacer is added to an aqueous solution (pH=9) of an activated polysaccharide, e.g. dextran, etc., and reacted at room temperature for preferably 12-48 hr; and dialyzed, etc. to give a polysaccharide intermediate bonded to the spacer. (2) The intermediate is reacted with mitomycin and a binding agent, e.g. 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, etc., at pH 5-6 and at room temperature. The reaction mixture is ultrafiltrated, washed, concentrated and recrystallized with acetone to give the desired mitomycin derivative. The activation of the polysaccharide is accomplished by adding a halogenated cyanide, e.g. chlorocyanide, etc., to an aqueous solution of the polysaccharide and adjusting pH to 10.7 with sodium hydroxide. |
