目的  验证和评价人抗凝血酶Ⅲ（human antithrombin Ⅲ，AT-Ⅲ）生产工艺中有机溶剂/去污剂（solvent/detergent，S/D）法联合纳米膜过滤法灭活／去除病毒的可行性。方法  采用S/D法作为AT-Ⅲ病毒灭活工艺，纳米膜过滤法（20 nm孔径）作为其病毒去除工艺，分析病毒灭活／去除工艺对AT-Ⅲ活性的影响；以伪狂犬病毒、辛德毕斯病毒、猪细小病毒、脑心肌炎病毒作为指示病毒，对上述工艺进行病毒灭活／去除工艺效果的验证。结果   S/D法联合纳米膜过滤法可有效灭活／去除脂包膜病毒和非脂包膜病毒，指示病毒滴度下降均>4 lg；且AT-Ⅲ的生物活性及其他各项指标未发生明显改变，活性变化<10%。结论  研究建立的S/D法联合纳米膜过滤法可有效灭活／去除AT-Ⅲ中的指示病毒，该方法为凝血因子类制品的病毒灭活验证工艺提供了参考。

Objective  To verify and evaluate the feasibility of the solvent/detergent (S/D) method combined with nanomembrane filtration method in the preparation of human plasma antithrombin Ⅲ (AT-Ⅲ) to inactivate/remove the virus. Methods  S/D method was used as the AT-Ⅲ virus inactivation process in human plasma, and the nanomembrane filtration method (20 nm pore size) was used as the virus removal process. The effect of virus inactivation/removal process on AT-Ⅲ activity was analyzed. Pseudorabies virus, Sindbis virus, porcine parvovirus and encephalomyocarditis virus were used as indicate viruses to verify the virus inactivation/removal effect of the above process. Results  The method of S/D combined with nanomembrane filtration effectively inactivated/removed lipid-enveloped as well as non-lipid-enveloped viruses, with all indicate viruses titers decreases >4 lg. The biological activity of AT-Ⅲ and other indicators did not change significantly, with activity changes <10%. Conclusion  S/D combined with nanomembrane filtration method established in this study can effectively inactivate/remove viruses in AT-Ⅲ, providing a reference for the virus inactivation of the coagulation factor products.