Heparin in Acid and Alkaline Environments—A Study of the Correlations between Hydrodynamic Properties and Desulphation

Aleksandra M Kozlowski, Vlad Dinu, Thomas E MacCalman, Alan M. Smith, J. Roubroeks, E. Yates, S. Harding, G. Morris
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Abstract

This work evaluated the hydrodynamic properties of heparin hydrolysed at temperatures ranging from 40 °C to 80 °C in buffered acid and alkaline environments. The correlation between hydrodynamic parameters led to the conclusion that polymer conformational changes appeared to be minimal until chain depolymerisation, initiated at pH 1 and 80 °C. However, the synergy of conformational changes, even if minimal, and sulphate loss observed at pH 1, pH 3 and pH 12 (various temperatures) resulted in a loss of the antifactor Xa activity. Therefore, the ‘contribution’ of conformational changes should be added to the generally recognized effect of desulphation towards the activity of heparin. This is of significance as the processing of medical heparin is complex, and requires adjustment of several physical and chemical factors, including pH and temperature.
酸碱性环境下的肝素——水动力学性质与脱硫关系的研究
这项工作评估了在缓冲酸和碱性环境中,在40°C至80°C的温度范围内水解的肝素的水动力学性质。水动力参数之间的相关性得出结论,聚合物构象变化似乎很小,直到在pH 1和80°C下开始链解聚。然而,构象变化的协同作用,即使是最小的,以及在pH 1、pH 3和pH 12(不同温度)下观察到的硫酸盐损失导致抗因子Xa活性的损失。因此,构象变化的“贡献”应该加入到公认的脱硫对肝素活性的影响中。这是有意义的,因为医用肝素的加工是复杂的,需要调整几个物理和化学因素,包括pH和温度。
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