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交联球形聚阳离子吸附剂的合成及其对肝素回收的增强作用。

Synthesis of Cross-Linked Spherical Polycationic Adsorbents for Enhanced Heparin Recovery.

机构信息

Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca 14853, New York, United States.

出版信息

ACS Biomater Sci Eng. 2020 May 11;6(5):2822-2831. doi: 10.1021/acsbiomaterials.0c00299. Epub 2020 Apr 30.

DOI:10.1021/acsbiomaterials.0c00299
PMID:33463302
Abstract

Heparin, as an anticoagulant drug, is almost entirely produced via isolation from mucosal tissues of different animals; therefore, it is it is crucial to maximize its recovery. Adsorption of heparin from this complex biological mixture needs a specialized and highly effective adsorbent that almost separates only heparin from the mixture. In this work, a series of spherical cross-linked polymer bead adsorbents were synthesized via inverse suspension polymerization of water soluble monomers in corn oil, a benign solvent, and their performance for heparin adsorption from a biological sample of porcine mucosa was evaluated. To tune the performance and swelling of the resins, we varied the molar ratio of the monomer(s) to the cross-linker as well as the molar ratio of the monomers. The results of heparin recovery from biological porcine mucosa show that our optimized resin can outperform the commercially available resin in terms of adsorption efficiency of up to 18%. The adsorbed heparin was eluted, isolated, and its anticoagulant potency measured using the standard sheep plasma clotting assay. The isolated heparin samples were also analyzed by H NMR spectroscopy to check the possible impurities, and the results show the presence of chondroitin sulfate and dermatan sulfate, as is the case for the heparin eluted from the commercial resin. Furthermore, the effects of some experimental variables including the adsorbent dosage, pH, time, and recycling on heparin adsorption were studied, and the results show that these resins can be used for efficient recovery of heparin.

摘要

肝素作为一种抗凝药物,几乎完全是通过从不同动物的粘膜组织中分离出来生产的;因此,最大限度地回收肝素至关重要。从这种复杂的生物混合物中吸附肝素需要一种专门的、高效的吸附剂,这种吸附剂几乎只将肝素从混合物中分离出来。在这项工作中,通过在玉米油这种良性溶剂中水溶性单体的反相悬浮聚合,合成了一系列球形交联聚合物珠状吸附剂,并评估了它们从猪粘膜生物样品中吸附肝素的性能。为了调整树脂的性能和溶胀性,我们改变了单体与交联剂的摩尔比以及单体的摩尔比。从生物猪粘膜中回收肝素的结果表明,我们优化的树脂在吸附效率方面可以优于市售树脂,最高可达 18%。吸附的肝素被洗脱、分离,并使用标准的绵羊血浆凝固测定法测量其抗凝效力。通过 H NMR 光谱分析分离得到的肝素样品,以检查可能的杂质,结果表明存在软骨素硫酸盐和硫酸皮肤素,这与从商业树脂洗脱的肝素的情况相同。此外,还研究了一些实验变量,包括吸附剂用量、pH 值、时间和循环利用对肝素吸附的影响,结果表明这些树脂可用于肝素的高效回收。

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