Comparative Pharmacological Profiles of Various Bovine, Ovine, and Porcine Heparins
Comparative Pharmacological Profiles of Various Bovine, Ovine, and Porcine Heparins
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DOI：
10.1177/1076029619889406
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发表时间：
2019-11-28
影响因子：
2.9
通讯作者：
Fareed, Jawed
中科院分区：
文献类型：
--
作者：
Kouta, Ahmed;Jeske, Walter;Fareed, Jawed
普通肝素是第一种抗凝药物，已成功应用于临床80多年。肝素及其类似物在手术和透析过程中使用，通常用于涂覆留置导管和其他暴露血管系统的装置。临床上使用的肝素大部分来源于猪肠粘膜。然而，肝素也可以从其他哺乳动物物种（例如牛和羊）的组织中制造。最近，人们尝试生产生物工程肝素以克服污染和抗原性问题。目前，由于猪肝素广泛用于低分子肝素的生产，因此存在一些短缺问题。此外，由于一些国家的文化和宗教原因，需要肝素的替代来源。美国食品和药物管理局和其他监管机构已考虑使用肝素的替代来源来替代猪肝素，目前正在审查此事。正在进行大量研究来了解这些不同肝素的结构-活性关系。在本文中，对不同动物来源的肝素进行了研究，以确定它们之间的生物相似性程度。对于这些研究，对牛粘膜肝素 (BMH)、绵羊粘膜肝素 (OMH) 和猪粘膜肝素 (PMH) 各 10 个批次进行了研究。这些研究表明 OMH 和 PMH 具有相当的抗凝血和抗蛋白酶活性。然而，在功能测定中，与 OMH 和 PMH 相比，BMH 的效力稍低。
Unfractionated heparin is the first anticoagulant drug and has been successfully used clinically for over 80 years. Heparin and its analogues are used during surgery and dialysis and are often used to coat indwelling catheters and other devices where the vascular system is exposed. Most of the heparins used clinically are derived from porcine intestinal mucosa. However, heparins have also been manufactured from tissues of other mammalian species such as cows and sheep. Recently there have been attempts to generate bioengineered heparin in order to overcome contamination and antigenicity problems. Currently there are some concerns about the shortage of the porcine heparins as they are widely used in the manufacturing of the low-molecular-weight heparins. Moreover, due to cultural and religious reasons in some countries, alternative sources of heparins are needed. The Food and Drug Administration and other regulatory agencies have considered alternative sourcing of heparin for potential substitution of porcine heparin and are currently reviewing this matter. Numerous studies are ongoing to understand the structure-activity relationships of these various heparins. In this article, heparins from different animal sources were studied to determine the extent of biosimilarity between them. For these investigations, 10 batches each of bovine mucosal heparin (BMH), ovine mucosal heparin (OMH), and porcine mucosal heparin (PMH) were studied. These studies have demonstrated that OMH and PMH have comparable anticoagulant and antiproteases activities. However, BMH exhibited somewhat a lower potency compared to OMH and PMH in functional assays.