Development of a Protamine Hollow-Fiber Device for Extracorporeal Heparin Removal

Abstract

Protamine was covalently coupled to a cellulose hollow fiber (cuprophan membrane) through epichlorohydrin-activated hydroxyl groups on the hollow fiber. An immobilization efficiency of as much as 15 mg protamine/g fiber could be achieved under optimal reacting conditions. Compared to a protamine hollow-fiber device produced using cyanogen bromide as an activator, the protamine hollow-fiber device using epichlorohydrin as an activator shows very high resistance to hydrolysis. Both in vitro and in vivo experiments showed that such a protamine hollow-fiber device had high heparin-removal capacity and efficiency, suggesting that this device may be suitable for various clinical applications in extracorporeal heparin removal.