Health Sciences Division, Cardiovascular Research Institute, Loyola University Chicago, Maywood, IL, USA.
Ronnsi Pharma Co, Suzhou, China.
Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619889406. doi: 10.1177/1076029619889406.
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.
未分级肝素是第一种抗凝药物,已成功临床应用 80 余年。肝素及其类似物在手术和透析期间使用,常用于涂覆留置导管和其他暴露于血管系统的器械。临床上使用的大多数肝素来源于猪肠黏膜。然而,肝素也已从牛和羊等其他哺乳动物的组织中制造出来。最近,人们试图生成生物工程肝素,以克服污染和抗原性问题。目前,由于广泛用于低分子量肝素的制造,人们对猪肝素的短缺存在一些担忧。此外,由于一些国家的文化和宗教原因,需要替代来源的肝素。食品和药物管理局和其他监管机构已经考虑了肝素的替代来源,以潜在替代猪肝素,并正在对此事进行审查。目前正在进行大量研究,以了解这些不同肝素的结构-活性关系。在本文中,研究了来自不同动物来源的肝素,以确定它们之间的生物相似性程度。为此,对 10 批牛黏膜肝素(BMH)、羊黏膜肝素(OMH)和猪黏膜肝素(PMH)进行了研究。这些研究表明,OMH 和 PMH 在抗凝和抗蛋白酶活性方面具有可比性。然而,在功能测定中,BMH 的效价略低于 OMH 和 PMH。