Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, Milan, Italy.
Laboratori Derivati Organici SpA, Trino Vercellese, Italy.
J Pharm Biomed Anal. 2018 Jul 15;156:67-79. doi: 10.1016/j.jpba.2018.04.012. Epub 2018 Apr 15.
Sulodexide is a heparinoid which combines the properties of its components heparin and dermatan sulfate and is used not only for the prophylaxis and treatment of thromboembolic diseases but also for the treatment of diabetic nephropathy. Despite many clinical studies have been conducted to investigate its activity and safety, no data are available on the fine chemical characterization of its components. In this work, the in-depth investigation on the structural features of both the whole mixture and the isolated components was accomplished, involving the analysis of molecular weight distribution and of their mono, di and oligosaccharide composition by HP-SEC/TDA, 2D-NMR and HPLC-MS techniques. Moreover, also the separation of fractions endowed of graded affinity to antithrombin was achieved followed again by detailed structural analysis. The combination of different techniques permits to profile in depth the structural features of such a drug and offers a useful tool for possible analysis of batch production.
舒洛地特是一种类肝素，兼具肝素和硫酸皮肤素的特性，不仅用于预防和治疗血栓栓塞性疾病，也用于治疗糖尿病肾病。尽管已经进行了许多临床研究来研究其活性和安全性，但关于其成分的精细化学特性尚无数据。在这项工作中，深入研究了整个混合物和分离成分的结构特征，涉及通过 HP-SEC/TDA、2D-NMR 和 HPLC-MS 技术分析分子量分布及其单糖、二糖和低聚糖组成。此外，还实现了对具有不同抗凝血酶亲和力的级分的分离，然后再次进行详细的结构分析。不同技术的结合可以深入分析此类药物的结构特征，并为可能的批次生产分析提供有用的工具。
