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用于治疗铁和铜过载的螯合剂:从低分子量化合物向聚合物的转变

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers.

作者信息

Hruby Martin, Martínez Irma Ivette Santana, Stephan Holger, Pouckova Pavla, Benes Jiri, Stepanek Petr

机构信息

Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic Heyrovského Náměstí 2, 162 06 Prague, Czech Republic.

Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research Bautzner Landstraße 400, 01328 Dresden, Germany.

出版信息

Polymers (Basel). 2021 Nov 17;13(22):3969. doi: 10.3390/polym13223969.

Abstract

Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson's disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

摘要

铁和铜是每个细胞正常功能所需的必需微量营养素。然而,这些元素过量时具有毒性,因为它们可能会引起氧化应激,导致肝脏和其他器官受损。这可能由于中毒、地中海贫血输注治疗的副作用或由于遗传性疾病血色素沉着症或威尔逊氏病而发生。目前治疗铁和铜过载的金标准是使用这些元素的低分子量螯合剂。然而,这些药物存在严重的副作用,通常价格昂贵且具有不良的药代动力学,因此限制了这种治疗方法的可用性。新兴的概念是用于肠胃外或口服的聚合物支持的铁和铜螯合疗法,其显示出在保持低分子量药物治疗效果的同时避免其缺点,尤其是副作用的显著潜力。对这种新的聚合物方法进行批判性评估是这篇综述文章的目的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcf7/8618197/710766165822/polymers-13-03969-g001.jpg

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