中文摘要：比利时自2018年起批准将噬菌体掺入用于人体的主要制剂中。这些制剂的稳定性对于保证整个治疗过程的质量和功效非常重要。本文评估了四种噬菌体在两种浓度（9和7log pfu/mL）和4℃条件下，医学和生物技术生产中常用的五种不同缓冲液和输液溶液中，对三种细菌种类保持感染活性的能力。与其溶液相比，不含Ca2+和Mg2+的DPBS是最佳选择。噬菌体浓度为7log pfu/mL的悬浮液不适合，因为即使在4℃储存一周，它们的活性也降至有效治疗剂量（6-9log pfu/mL）以下。噬菌体之间的变化很大，但鲍曼不动杆菌噬菌体Acibel004在五种不同溶液的四种中稳定性好。还研究了冻干葡萄球菌噬菌体ISP的长期储存，发现当用蔗糖和海藻糖作稳定剂时，滴度可以在近8年的时间内保持。将冻干的ISP噬菌体在盐水中复水后，溶液在4℃下可保持稳定126天。
外文摘要：In Belgium, the incorporation of phages into magistral preparations for human application has been permitted since 2018. The stability of such preparations is of high importance to guarantee quality and efficacy throughout treatments. We evaluated the ability to preserve infectivity of four different phages active against three different bacterial species in five different buffer and infusion solutions commonly used in medicine and biotechnological manufacturing processes, at two different concentrations (9 and 7 log pfu/mL), stored at 4 degrees C. DPBS without Ca2+ and Mg2+ was found to be the best option, compared to the other solutions. Suspensions with phage concentrations of 7 log pfu/mL were unsuited as their activity dropped below the effective therapeutic dose (6-9 log pfu/mL), even after one week of storage at 4 degrees C. Strong variability between phages was observed, with Acinetobacter baumannii phage Acibel004 being stable in four out of five different solutions. We also studied the long term storage of lyophilized staphylococcal phage ISP, and found that the titer could be preserved during a period of almost 8 years when sucrose and trehalose were used as stabilizers. After rehydration of the lyophilized ISP phage in saline, the phage solutions remained stable at 4 degrees C during a period of 126 days.
外文关键词：phage；API；magistral preparation；buffers；infusion solutions；infectivity; titer；storage；lyophilization
作者：Duyvejonck, H；Merabishvili, M；Vaneechoutte, M；de Soir, S；Wright, R；Friman, VP；Verbeken, G；De Vos, D；Pirnay, JP；Van Mechelen, E；Vermeulen, SJT
作者单位：Univ Coll Ghent；Queen Astrid Mil Hosp；Univ York；Univ Manchester
期刊名称：VIRUSES-BASEL
期刊影响因子：3.816
出版年份：2021
出版刊次：5
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