Blood-contacting materials with good mechanical property, excellent anticoagulant function and promoting effect on endothelialization are in great demand for clinical application such as vascular grafts in treating cardiovascular diseases. In this study, electrospinning nanofiber scaffolds of polycaprolactone (PCL) were functionalized by oxidative self-polymerization of dopamine (PDA) on the surface followed by the modification of anticoagulant recombinant hirudin (rH) molecules. The morphology, structure, mechanical property, degradation behavior, cellular compatibility and blood compatibility of the multifunctional PCL/PDA/rH nanofiber scaffolds were evaluated. The diameter of the nanofibers was between 270-1030 nm. The ultimate tensile strength of the scaffolds was around 4 MPa and the elastic modulus increased with the amount of rH. The degradation tests in vitro indicated that the nanofiber scaffolds began to crack on the 7th day, but still maintained the nanoscale architecture within a month. The cumulative release of rH from the nanofiber scaffold was up to 95.9 % at 30th day. The functionalized scaffolds promoted the adhesion and proliferation of endothelial cells, while resisting platelet adhesion and enhancing anticoagulation effects. The hemolysis ratios of all scaffolds were <2 %. The nanofiber scaffolds are promising candidates for vascular tissue engineering.

2021-07-01·Critical care clinics3区 · 医学

Antithrombotic and Antiplatelet Drug Toxicity

3区 · 医学

Review

作者: Mullins, Michael E ; Liss, David B

Anticoagulant and antiplatelet drugs target a specific portion of the coagulation cascade or the platelet activation and aggregation pathway. The primary toxicity associated with these agents is hemorrhage. Understanding the pharmacology of these drugs allows the treating clinician to choose the correct antidotal therapy. Reversal agents exist for some of these drugs; however, not all have proven patient-centered outcomes. The anticoagulants covered in this review are vitamin K antagonists, heparins, fondaparinux, hirudin derivatives, argatroban, oral factor Xa antagonists, and dabigatran. The antiplatelet agents reviewed are aspirin, adenosine diphosphate antagonists, dipyridamole, and glycoprotein IIb/IIIa antagonists. Additional notable toxicities are also reviewed.

2020-11-01·Journal of biotechnology3区 · 工程技术

Enhanced anticoagulant activity of hirudin-i analogue co-expressed with arylsulfotransferase in periplasm of E. coli BL21(DE3)

3区 · 工程技术

Article

作者: Yang, Junqing ; Wang, Xingang ; Liang, Yunlong ; Sun, Yue ; Chu, Xiaohui ; Rai, Kamal ; Bao, Zixian ; Xian, Mo ; Nian, Rui

Hirudin, a blood anticoagulant, is the most potent natural thrombin inhibitor of leech origin. Its application is limited because it is difficult to obtain abundant natural hirudin directly from the leech. Although some bioengineering methods can significantly increase the production of hirudin, the reduced efficacy of recombinant hirudin (rH) remains a critical shortcoming. The lack of sulfation of tyrosine 63 in rH is an important cause of its inadequate performance. This article is the first report of periplasmic co-expression of an rH-I analogue with arylsulfotransferase (ASST) in E. coli BL21(DE3). Co-expressed rH-I analogue with sulfate donor substrate (p-nitrophenyl sulfate potassium) showed anticoagulant (rabbit and goat serum) activity twice more than rH-I analogue expressed without ASST, indicating its potential periplasmic sulfation. Moreover, purified rH-I analogue showed above 4.5 times higher anticoagulant activity compared to therapeutic anti-thrombotic heparin (HE). At the same time, pH-dependent differential solubility was employed to purify rH analogues from fermentation broth, which is a simple, fast and inexpensive purification technology, and can potentially be used for larger scale purification. This will also greatly improve the application of rH in clinical treatment.

项与重组水蛭素 (华润昂德生物) 相关的新闻（医药）

2022-12-31

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全球畅销药「利伐沙班」分析报告

血栓病是高发病之一。临床上将血栓产生、血栓梗塞这两种病变过程引起的疾病称为血栓病。临床上针对血栓的治疗药物主要有三类：溶血栓类、抗凝血类、抗血小板类。本文主要阐述抗凝血药。图1 抗凝药物发展历程根据作用机制，抗凝药主要分为凝血酶直接抑制剂、凝血酶间接抑制剂、维生素K拮抗剂及Xa因子抑制剂：（1）凝血酶直接抑制剂：达比加群酯、比伐卢定、阿加曲班、重组水蛭素（来匹卢定）等；（2）凝血酶间接抑制剂：肝素、低分子肝素等；（3）维生素K拮抗剂（VKA）：华法林等；（4）Xa因子抑制剂：利伐沙班、阿哌沙班、艾多沙班、磺达肝癸钠等。本文重点探讨选择性Ⅹa因子抑制剂-利伐沙班：数据来源：药智数据，药智咨询整理2022年，拜耳的利伐沙班在中国获批，用于18岁以下且体重30kg-50kg及50kg以上的儿童和青少年静脉血栓栓塞症（VTE）患者经过初始口服抗凝治疗至少5天后的VTE治疗及预防VTE复发。拜耳的利伐沙班片是目前中国唯一拥有儿童VET治疗及预防复发适应症的抗凝药物。利伐沙班同靶点在研药品情况利伐沙班的靶点为Coagulation factor X，该靶点药物主要适应症在治疗静脉血栓形成、房颤等。表1 全球上市及在研的同靶点药品数据来源：药智数据，药智咨询整理利伐沙班的全球上市情况利伐沙班由拜耳和杨森联合开发，2008年9月16日获加拿大卫生部批准上市，同年9月30日获欧洲药物管理局（EMA）批准上市；2011年7月1日获美国食品药品监督管理局（FDA）批准上市。在加拿大和欧洲由拜耳上市销售，在美国由杨森上市销售，商品名均为Xarelto。利伐沙班口服Ⅹa因子抑制剂，有10、15、20mg三种规格的片剂。批文数量德国、欧盟、韩国最多，居前三（详见图3）。图2 利伐沙班上市时光轴（部分展示）数据来源：药智数据，药智咨询整理图3 全球上市的利伐沙班批文数量数据来源：药智数据，药智咨询整理利伐沙班的中国上市情况国内上市的利伐沙班有片剂和干混悬剂。利伐沙班干混悬剂上市产品只有拜耳1家，注册批文数量为2，利伐沙班片的生产厂家有32家，注册批文数为67。国内已有30余家企业布局利伐沙班仿制药，主要包括正大天晴、石药、瑞阳制药、扬子江药业、江苏二叶制药等。图4 中国上市的利伐沙班各剂型的批文数量占比图数据来源：药智数据，药智咨询整理利伐沙班的市场情况全球范围内利伐沙班的销售处于增长状态，2017年的销售额为420.6亿元，2021年的销售额增长到537.6亿元，年复合增长率6.3%。2017-2021年间，利伐沙班的销售额在同比5%-9%的范围内持续增长（图5）。图5 2017-2021年利伐沙班全球销售情况数据来源：药智数据，药智咨询整理利伐沙班近年来在中国的销售额增长也较为迅速，从2017年的9.7亿元，增长到2021年的37.0亿元，年复合增长率39.6%（图6）。推测利伐沙班在中国的增长较为迅速的原因有三点：1.我国抗凝观念的推广和普及，推动抗凝药市场份额的逐步提升；2.我国心脑血管疾病患病人数的增加；2.PCI（冠状动脉介入）手术量的增加：为改善早期临床预后和预防介入治疗部位的并发症，PCI手术的术前、术中、术后均需使用抗凝血药或抗血小板药进行针对性抗栓治疗。2021年6月利伐沙班片被纳入第五批集采，推测后续利销售额或有小幅下降。图6 2017-2021年利伐沙班中国销售情况数据来源：药智数据，药智咨询整理表2 利伐沙班第五批国家集采情况数据来源：药智数据，药智咨询整理声明：本内容为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | Summer转载开白 | 马老师 18323856316（同微信）— Tips —长按/扫码入读者群交流投稿请联系：马老师电话/微信：18323856316邮箱：maxuelian@yaozh.com 阅读原文，是受欢迎的文章哦

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