Incubation of an AHF concentrate with 0.3% tri(n-butyl)phosphate (TNBP) and 0.2% sodium cholate was shown to inactivate at least 10,000 infectious doses of lipid-enveloped viruses, including hepatitis B and non-A, non-B viruses and HTLV-III [Prince et al., Lancet i, pp. 706-710, 1986]. The use of TNBP/detergent combinations for virus sterilization was evaluated further to determine its effect on the structure and function of a wide variety of blood proteins. Vesicular stormatitis and Sindbis viruses were used as markers of virus inactivation. TNBP/detergent treatment did not significantly alter the function of AHF, factor VII, factor IX, factor X, fibrinogen, factor XIII, fibronectin, anti-HBsAg and anti-HA in normal immune serum globulin, haptoglobin, tumor necrosis factor, a-interferon, and both native and chemically polymerized stroma-free hemoglobin. As compared with partially purified derivatives, the extent of virus sterilization of plasma and component cryoprecipitate with 0.3% TNBP and 0.2% sodium cholate at ambient temperature could be improved by raising the TNBP concentration and temperature. Virus sterilization by TNBP/detergent mixtures appears to be generally applicable to blood protein derivatives.

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