Biochemical, molecular and preclinical characterization of a double-virus-reduced human butyrylcholinesterase preparation designed for clinical use
Biochemical, molecular and preclinical characterization of a double-virus-reduced human butyrylcholinesterase preparation designed for clinical use
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DOI：
10.1111/j.1423-0410.2010.01415.x
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发表时间：
2011-04-01
期刊：
影响因子：
2.7
通讯作者：
Schwarz, H. P.
中科院分区：
文献类型：
--
作者：
Weber, A.;Butterweck, H.;Schwarz, H. P.
背景与目的介绍了一种工业化生产的人血浆源性丁基胆碱酯酶制剂。材料和方法采用免疫和电泳方法对人丁基胆碱酯酶（hBChE）产物的纯度进行了广泛的研究，并采用糖蛋白组学方法对其进行了表征。一个全面的临床前测试方案解决安全性和药代动力学参数补充生化表征。结果制备的高纯度hBChE为四聚体，具有较高的比活性和蛋白骨架的分子完整性。急性毒性研究和体内血栓形成性研究为人类使用提供了足够的安全范围的证据。结论广泛的临床前安全性和药代动力学试验证实，该hBChE制剂可在适当的动物模型和最终在人体中作为有毒有机磷化合物的生物清除剂进行进一步的功效测试。
Background and ObjectivesA human plasma-derived butyrylcholinesterase preparation manufactured on the industrial scale is described.Material and MethodsThe human butyrylcholinesterase (hBChE) product was extensively investigated for its purity using immunological and electrophoretic methods and characterized by thorough glycoproteomic approaches. A comprehensive preclinical testing programme addressing safety and pharmacokinetic parameters supplemented the biochemical characterization.ResultsThe high-purity hBChE preparation is tetrameric and has high specific activity and molecular integrity of the protein backbone. Acute toxicity studies and in vivo thrombogenicity studies provided evidence of a sufficient safety margin for use in humans.ConclusionExtensive preclinical safety and pharmacokinetic testing confirmed that this hBChE preparation can be used for further efficacy testing as a bioscavenger for toxic organophosphate compounds in appropriate animal models and ultimately in humans.