Tri(n-butyl) phosphate/detergent treatment of licensed therapeutic and experimental blood derivatives.
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 stomatitis 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 serum globulin, haptoglobin, tumor necrosis factor, alpha-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.
D000998:Antiviral Agents; D001769:Blood / Q000382:microbiology*; D001798:Blood Proteins / Q000302:isolation & purification* / Q000627:therapeutic use; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology; D004340:Drug Contamination; D005164:Factor IX / Q000302:isolation & purification; D005169:Factor VIII / Q000302:isolation & purification; D005353:Fibronectins / Q000302:isolation & purification; D006454:Hemoglobins / Q000302:isolation & purification; D006801:Humans; D010755:Organophosphates / Q000494:pharmacology; D013242:Sterilization; D014780:Viruses / Q000187:drug effects
D000998:Antiviral Agents; D001798:Blood Proteins; D002793:Cholic Acids; D005353:Fibronectins; D006454:Hemoglobins; D010755:Organophosphates; D005169:Factor VIII; D005164:Factor IX; C009524:tributyl phosphate; D019826:Cholic Acid