PURPOSE: To obtain the subject new derivative useful for treating diffused intravascular coagulation syndrome, capable of being administered by bolus intravenous injection, having prolonged blood half life and anticoagulant action, by modifying an amino group in the molecule with polyethylene glycol by a cross-linking agent.
CONSTITUTION: Activated protein C is reacted with an ethylene glycol derivative of formula I (R1 is a 1-3C alkyl; (n) is an integer of 20-500,), formula II or formula III to give a new human activated protein C derivative which contains at least one amino group modified with a polyethylene glycol through a cross- linking agent in the molecule, not cross-linked with the cross-linking agent between the molecules, is capable of being administered by bolus intravenous injection, has prolonged blood half-life, inhibits activated V factor, activated VIII factor, plasminogen/activator and inhibitor, participating in blood coagulation cascade, manifests anticoagulant action and is useful as a therapeutic agent for diffused intravascular coagulation syndrome (DIC).
MAKINO YUJI
FUJII TAKAO
