Non-virally inactivated cryoprecipitate prepared by blood banks is still used in the developing world, for the treatment of bleeding disorders such as factor VIII (FVIII) deficiency which induces haemophilia type A. As a consequence, patients receiving cryoprecipitate are at high risk of being infected by plasma-borne viruses, such as hepatitis B (HBV) or C viruses (HCV). Moreover, the high concentration of contaminating proteins in the cryoprecipitate evoked the need for development of a method for production of safe purified freeze-dried FVIII concentrate with increasing stability. In this work, FVIII was fractionated using modified techniques including aluminum hydroxide hydrogel (Al(OH)3) with polyethylene glycol (PEG) 4000 or glycine as precipitating agents with viral inactivation using betapropiolactone (BPL). The highest yield was exposed to accelerated stability using two different polysaccharides trehalose and sucrose. BPL as an inactivant has proved to inactivate Vesicular Stomatitis Virus (VSV) as HCV model, within 60-90 min post treatment at 37 oC and 4 oC in FVIII concentrate respectively. However, it was found to be degradative to FVIII although not affecting the total protein profile. Thus; it can be used for cold sterilization of other factors than FVIII. In this work, lyophilized FVIII concentrate supplemented with 60 mM sucrose or 60 / 90 mM trehalose as stabilizers were subjected for further accelerated stability studies , including forced degradation at 37 ºC for 10 days. Initial Activated Partial Thromboplastin Time (APTT) and percentage activity of the coagulation FVIII were found to be the highest in case of sucrose stabilization indicating a higher stabilizing effect of sucrose than trehalose on FVIII concentrate.
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