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Preparation of low molecular weight heparins from bovine and ovine heparins using nitrous acid degradation
Carbohydrate Polymers ( IF 10.7 ) Pub Date : 2018-05-25 , DOI: 10.1016/j.carbpol.2018.05.070
Shaoshuai Xie , Yudong Guan , Peipei Zhu , Fei Li , Mengqi Yu , Robert J. Linhardt , Lianli Chi , Lan Jin

Low molecular weight heparins (LMWHs) are important anticoagulant drugs. Nitrous acid degradation is a major approach to produce LMWHs, such as dalteparin. Due to the foreseeable shortage of porcine intestinal mucosa heparin and other potential risks, expansion of other animal tissues for heparin preparation is necessary. Heparins from different tissues differ in structure and bioactivity potency, and these variations may be carried over to the LMWH products. Sophisticated analytical techniques have been applied to compare various versions of dalteparins produced from porcine intestinal, bovine lung and ovine intestinal heparins to elucidate the effects of different animal tissues starting materials and processing conditions on the properties of final dalteparin products. With adjusted depolymerization conditions, versions of dalteparins that qualify under the European Pharmacopeia (EP) specifications were manufactured using non-porcine heparins. Dissimilarities among the three interspecies animal tissue heparin-derived dalteparins regarding fine structures are also disclosed, and their origins are discussed.



中文翻译:

用亚硝酸降解从牛肝和绵羊肝素制备低分子量肝素

低分子量肝素(LMWHs)是重要的抗凝药物。亚硝酸降解是生产LMWH(例如达肝素)的主要方法。由于可预见的猪肠粘膜肝素短缺和其他潜在风险,肝素制备需要扩大其他动物组织。来自不同组织的肝素在结构和生物活性效力方面有所不同,这些变化可能会延续到LMWH产品中。已应用复杂的分析技术来比较从猪肠,牛肺和绵羊肠肝素生产的多种形式的达肝素,以阐明不同动物组织起始原料和加工条件对最终达肝素产品性能的影响。调整解聚条件后,使用非猪肝素生产符合欧洲药典(EP)规范要求的达肝素版本。还公开了三种种间动物组织肝素来源的达肝素在精细结构方面的差异,并讨论了它们的起源。

更新日期:2018-05-27
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