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The evolution of recombinant thrombolytics: Current status and future directions.重组溶栓剂的演变:现状与未来方向。
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Pulmonary embolism thrombolysis: Do we need another agent?肺栓塞溶栓治疗:我们还需要另一种药物吗?
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How should intravenous thrombolytic agents for acute myocardial infarction be selected?急性心肌梗死的静脉溶栓药物应如何选择?
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本文引用的文献

1
PEGylation of Truncated Streptokinase Leads to Formulation of a Useful Drug with Ameliorated Attributes.截短链激酶的聚乙二醇化导致具有改善特性的有用药物的配方。
PLoS One. 2016 May 18;11(5):e0155831. doi: 10.1371/journal.pone.0155831. eCollection 2016.
2
Natural Products Towards the Discovery of Potential Future Antithrombotic Drugs.天然产物助力未来潜在抗血栓药物的发现。
Curr Pharm Des. 2016;22(20):2926-46. doi: 10.2174/1381612822666160307150454.
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Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain.大齿拟凤梨、巴兰西凤梨和希氏凤梨(凤梨科)果实的蛋白水解提取物对纤维蛋白原、纤维蛋白和血液凝固的影响与菠萝蛋白酶的比较
Blood Coagul Fibrinolysis. 2016 Jun;27(4):441-9. doi: 10.1097/MBC.0000000000000531.
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Liposomal nanocarriers for plasminogen activators.载脂蛋白纳米载体的纤溶酶原激活剂。
J Control Release. 2016 Apr 10;227:45-57. doi: 10.1016/j.jconrel.2016.02.019. Epub 2016 Feb 12.
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High level production of active streptokinase in Pichia pastoris fed-batch culture.在毕赤酵母分批补料培养中高效生产活性链激酶。
Int J Biol Macromol. 2016 Feb;83:50-60. doi: 10.1016/j.ijbiomac.2015.11.062. Epub 2015 Nov 26.
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How it all starts: Initiation of the clotting cascade.这一切是如何开始的:凝血级联反应的启动。
Crit Rev Biochem Mol Biol. 2015;50(4):326-36. doi: 10.3109/10409238.2015.1050550. Epub 2015 May 28.
7
Safety and efficacy of desmoteplase given 3-9 h after ischaemic stroke in patients with occlusion or high-grade stenosis in major cerebral arteries (DIAS-3): a double-blind, randomised, placebo-controlled phase 3 trial.急性缺血性脑卒中发病 3-9 小时内颅内大动脉闭塞或重度狭窄患者给予地特酶溶栓的安全性和有效性(DIAS-3):一项双盲、随机、安慰剂对照 3 期试验。
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8
Effects of organic extracts and their different fractions of five Bangladeshi plants on in vitro thrombolysis.五种孟加拉植物的有机提取物及其不同馏分对体外溶栓的作用。
BMC Complement Altern Med. 2015 Apr 23;15:128. doi: 10.1186/s12906-015-0643-2.
9
Biochemical characterization of a new glycosylated protease from Euphorbia cf. lactea latex.从乳浆大戟乳汁中分离得到一种新糖基化蛋白酶的生化特性分析。
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10
Comparative effects of PEG-containing liposomal formulations on in vivo pharmacokinetics of streptokinase.含聚乙二醇脂质体制剂对链激酶体内药代动力学的比较作用。
Arch Pharm Res. 2015 Oct;38(10):1822-9. doi: 10.1007/s12272-015-0594-7. Epub 2015 Apr 8.

重组溶栓剂的演变:现状与未来方向。

The evolution of recombinant thrombolytics: Current status and future directions.

作者信息

Khasa Yogender Pal

机构信息

a Department of Microbiology , University of Delhi South Campus , New Delhi , India.

出版信息

Bioengineered. 2017 Jul 4;8(4):331-358. doi: 10.1080/21655979.2016.1229718. Epub 2016 Oct 3.

DOI:10.1080/21655979.2016.1229718
PMID:27696935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5553328/
Abstract

Cardiovascular disorders are on the rise worldwide due to alcohol abuse, obesity, hypertension, raised blood lipids, diabetes and age-related risks. The use of classical antiplatelet and anticoagulant therapies combined with surgical intervention helped to clear blood clots during the inceptive years. However, the discovery of streptokinase and urokinase ushered the way of using these enzymes as thrombolytic agents to degrade the fibrin network with an issue of systemic hemorrhage. The development of second generation plasminogen activators like anistreplase and tissue plasminogen activator partially controlled this problem. The third generation molecules, majorly t-PA variants, showed desirable properties of improved stability, safety and efficacy with enhanced fibrin specificity. Plasmin variants are produced as direct fibrinolytic agents as a futuristic approach with targeted delivery of these drugs using liposome technlogy. The novel molecules from microbial, plant and animal origin present the future of direct thrombolytics due to their safety and ease of administration.

摘要

由于酗酒、肥胖、高血压、血脂升高、糖尿病以及与年龄相关的风险,心血管疾病在全球范围内呈上升趋势。在早期,使用经典的抗血小板和抗凝疗法并结合手术干预有助于清除血栓。然而,链激酶和尿激酶的发现开创了将这些酶用作溶栓剂以降解纤维蛋白网络的方法,但存在全身出血问题。第二代纤溶酶原激活剂如茴香酰化纤溶酶原链激酶复合物和组织纤溶酶原激活剂的开发部分控制了这个问题。第三代分子,主要是组织纤溶酶原激活剂变体,表现出稳定性、安全性和有效性提高以及纤维蛋白特异性增强等理想特性。纤溶酶变体作为直接溶栓剂生产,是一种未来的方法,可使用脂质体技术靶向递送这些药物。来自微生物、植物和动物来源的新型分子因其安全性和易于给药而展现出直接溶栓剂的未来前景。