Horowitz B, Piët M P, Prince A M, Edwards C A, Lippin A, Walakovits L A
New York Blood Center, N.Y.
Vox Sang. 1988;54(1):14-20. doi: 10.1111/j.1423-0410.1988.tb01606.x.
Virus sterilization of blood plasma derivatives by addition of several naturally occurring fatty acids was evaluated using vesicular stomatitis virus and Sindbis virus as markers for lipid-enveloped virus inactivation and human immunodeficiency virus (HIV). Inactivation of greater than or equal to 10(4) tissue culture infectious doses (TCID50) of marker viruses added to antihemophilic factor (AHF) concentrates, with 60-100% retention of AHF activity, was achieved with oleic, 11-eicosenoic, linoleic, linolenic, palmitoleic and arachidonic acids. Elaidic, gamma-linolenic, palmitic, and arachidic acids and another fat-soluble compound previously reported to inactivate virus, butylated hydroxytoluene, were less effective. A long chain mono- but not a di- or triglyceride also displayed virucidal properties. Evaluation of the inactivation of HIV added to an immune globulin solution on exposure to 0.033% sodium oleate for 20 min indicated inactivation of greater than or equal to 10(3.4) TCID50. The degree of virus inactivation depended on the sample composition. A favorable balance was achieved between degree of virus inactivation and retention of protein function for AHF concentrate, prothrombin complex concentrate, antithrombin III concentrate, and immune globulin solution on incubation with 0.033% (w/v) sodium oleate at 24 degrees C for 4-6 h. Virus inactivation in whole plasma and plasma cryoprecipitate was not complete despite use of higher concentrations of sodium oleate and/or incubation at 37 degrees C. Reduced virus kill in these less purified derivatives probably is a consequence of their endogenous lipid and/or albumin.
以水泡性口炎病毒和辛德毕斯病毒作为脂包膜病毒灭活的标志物以及人类免疫缺陷病毒(HIV),评估了添加几种天然存在的脂肪酸对血浆衍生物进行病毒灭活的效果。向抗血友病因子(AHF)浓缩物中添加大于或等于10⁴组织培养感染剂量(TCID₅₀)的标志物病毒,使用油酸、11-二十碳烯酸、亚油酸、亚麻酸、棕榈油酸和花生四烯酸可实现60 - 100%的AHF活性保留,同时使标志物病毒失活。反油酸、γ-亚麻酸、棕榈酸、花生酸以及先前报道的另一种能灭活病毒的脂溶性化合物丁基化羟基甲苯效果较差。一种长链单甘油酯而非二甘油酯或三甘油酯也具有杀病毒特性。评估添加到免疫球蛋白溶液中的HIV在暴露于0.033%油酸钠20分钟后的灭活情况,结果表明大于或等于10³.⁴TCID₅₀的病毒被灭活。病毒灭活程度取决于样品组成。在24℃下将AHF浓缩物、凝血酶原复合物浓缩物、抗凝血酶III浓缩物和免疫球蛋白溶液与0.033%(w/v)油酸钠孵育4 - 6小时,在病毒灭活程度和蛋白质功能保留之间实现了良好的平衡。尽管使用了更高浓度的油酸钠和/或在37℃下孵育,但全血和血浆冷沉淀中的病毒灭活并不完全。这些纯度较低的衍生物中病毒杀灭率降低可能是其内源脂质和/或白蛋白的结果。