| 摘要 |
The present invention provides a novel albumin-free preparation of Factor VIII has a high amount of salt and a low concentration of sugar and of glycine. The high salt provides stability and an elegant cake structure as the major crystalline component. The sugar and glycine provide a complex amorphous matrix together with some amorphous non-crystallized salt for stabilization of Factor VIII. This formulation is suitable for B-domain deleted Factor VIII that requires a high ionic strength environment for stability. The addition of low amount of glycine to the sucrose prevents the crystallization of salt. This results in an amorphous matrix comprising of glycine, sucrose, and salt. This amorphous matrix provides a stabilizing environment where Factor VIII is protected by three stabilizers; amino acid (glycine), sugar (sucrose or trehalose), and salt (NaCl). Such an amorphous matrix that can stabilize the Factor VIII across lyophilization and during storage as a lyophile. |
