Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
Sci Rep. 2016 Oct 18;6:35619. doi: 10.1038/srep35619.
Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations.
尽管来源不同的肝素在药理学上存在差异，但一直以来都被认为是有效的抗凝和抗血栓药物。我们在此对从猪肠、牛肠和牛肺中获得的几批医药级肝素的物理化学性质、二糖组成、体外抗凝活性以及体内抗血栓和出血作用进行了系统分析。这三种肝素类型在化学结构、物理化学性质和/或止血作用方面都存在明显差异。我们还制备了这些肝素的衍生物，它们的分子量相似，但二糖组成不同。猪肠和牛肺肝素的衍生物在结构上彼此更为相似，因此具有相似的抗凝活性，而牛肠肝素的衍生物则含有更高比例的 6-去硫酸化α-葡萄糖胺单位，抗凝活性约为前者的一半。我们的研究结果合理地表明，来自不同动物来源的医药级肝素制剂构成了不同的药物，因此需要特定的监管规则和治疗评估。
