Studies on the Stability and Oral Administration of the Factor VIII and IX Concentrates

Abstract

This study was intended to improve the stability of F. VIII and IX and to examine the effectiveness of oral administration using these preparations. Two modification methods were used; F. VIII and IX were entrapped in liposome and coated by the intestinally digestive capsules (lipo-VIII and IX) and F. VIII and IX were modified with polythyleneglycole (PEG-VIII and IX). The following results were obtained: 1) 40% of the native F. VIII and IX were entrapped in liposome and aprotinin was necessary to protect the degradation of lipo-VIII and IX. 2) F. VIII: C increased varyingly from 2% to 23% when lipo-VIII 1,000 or 1,200 units was administered orally to the patients with hemophilia A and vWD. 3) After the administration of lipo-IX to dogs, rapid adsorption of F. IX, II and X were observed. 4) PEG-VIII was stable against plasmin and activated protein C, but it showed almost the same change against thrombin compared with native F. VIII. 5) F. VIII and IX increased significantly after the administration of PEG-VIII and IX. These results suggest that oral administration of F. VIII and IX is hopeful if F. VIII and IX are purified precisely and exact mechanism of adsorption and security of liposome and PEG are established.