Synthetic heparin.
Synthetic heparin.
复制标题
DOI：
10.1016/j.coph.2011.12.002
复制
发表时间：
2012-04
影响因子：
4
通讯作者：
Liu, Jian
中科院分区：
文献类型：
--
作者：
Linhardt, Robert J.;Liu, Jian
肝素是一种复杂的基于多糖的抗凝药物，是现代医学实践中必不可少的[1]。用于体外治疗（例如肾透析）、治疗凝血障碍（例如深静脉血栓形成（DVT））以及钝化留置装置（例如导管）的表面，当需要预防或控制血液凝固时，基于肝素的产品是首选。有三种形式的肝素：普通肝素（分子量平均MWavg~ 15 000）、低分子量肝素（LMWH，MWavg~ 6000）和超低分子量肝素（ULMWH，MWavg< 2000）[1-3]。最广泛使用的形式是普通肝素，一种从动物组织中制备的百年药物。尽管它被广泛使用，但它有几个局限性，包括需要静脉给药和副作用，如肝素诱导的血小板减少症（HIT）和出血。在20世纪90年代，LMWH被引入，并且它们已经成功地占据了市场的很大份额，成为治疗DVT的首选抗凝剂。低分子量肝素由动物来源的普通肝素通过受控解聚制备。这些药物的主要优点是皮下生物可利用，半衰期较长，允许门诊使用和/或自我给药。LMWH的一个主要缺点是，与普通肝素不同，其抗凝作用不容易逆转，因此增加了因过量而出血的风险。在过去的十年中，我们已经为我们带来了ULMWH（即磺达肝癸钠），首先由Sinaerol等人合成。[4]，具有良好的药代动力学和药效学控制，不含病毒或朊病毒杂质（可能存在于动物源材料中），具有皮下生物利用度，并按照现行良好生产工艺（cGMP）生产。不幸的是，这些试剂非常昂贵，并且像LMWH一样不容易逆转。
Heparin is a complex polysaccharide-based anticoagulant drug that is essential for the practice of modern medicine [1]. Used in extracorporeal therapies, such as kidney dialysis, in the treatment of coagulation disorders, such as deep vein thrombosis (DVT), and to passivate the surfaces of indwelling devices, such as catheters, a heparin-based product is the first choice whenever blood clotting needs to be prevented or controlled.There are three forms of heparin: unfractionated heparin (molecular weight average MWavg~ 15 000), low molecular weight heparin (LMWH, MWavg~ 6000), and ultra low molecular weight heparin (ULMWH, MWavg< 2000)[1-3]. The most widely used form is unfractionated heparin, a century-old drug prepared from animal tissues. Despite its widespread use it has several limitations including required intravenous administration and side effects such as heparin induced thrombocytopenia (HIT) and bleeding. In the 1990s, LMWHs were introduced and they have successfully captured a large share of the market becoming the anticoagulant of choice to treat DVTs. LMWHs are prepared from animalsourced unfractionated heparin through controlled depolymerization. These have the major advantage of being subcutaneously bioavailable and have a longer half-life allowing their outpatient use and/or self-administration. A major disadvantage of LMWHs is that, unlike unfractionated heparin, their anticoagulant effect is not readily reversible, thus increasing the risk for bleeding due to overdosing. The last decade has brought us ULMWHs (ie, fondaparinux), first synthesized by Sinaÿ et al.[4], which have well controlled pharmacokinetics pharmacodynamics, have no viral or prion impurities (possible in animalsourced materials), are subcutaneously bioavailable, and are manufactured under current good manufacturing process (cGMP). Unfortunately, these agents are very expensive and like LMWHs are not readily reversible.
登录
查看更多内容
DOI：
10.1126/science.1207478
发表时间：
2011-10-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Xu Y;Masuko S;Takieddin M;Xu H;Liu R;Jing J;Mousa SA;Linhardt RJ;Liu J
通讯作者：
Liu J
影响因子：
15
作者：
Zhang, Zhenqing;McCallum, Scott A.;Xie, Jin;Nieto, Lidia;Corzana, Francisco;Jimenez-Barbero, Jesus;Chen, Miao;Liu, Jian;Linhardtt, Robert J.
通讯作者：
Linhardtt, Robert J.
影响因子：
5
作者：
Wang, Zhenyu;Yang, Bo;Zhang, Zhenqing;Ly, Mellisa;Takieddin, Majde;Mousa, Shaker;Liu, Jian;Dordick, Jonathan S.;Linhardt, Robert J.
通讯作者：
Linhardt, Robert J.
从肝素污染中学到的经验教训。
影响因子：
11.9
作者：
Liu H;Zhang Z;Linhardt RJ
通讯作者：
Linhardt RJ
影响因子：
7.3
作者：
Lindahl, U;Li, JP;Casu, B
通讯作者：
Casu, B