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Determination of indicators allowing to evaluating the hemostatic activity of chitosan without a biological experiment
Journal of Bioactive and Compatible Polymers ( IF 2.1 ) Pub Date : 2021-07-18 , DOI: 10.1177/08839115211030607
Oksana Vladimirovna Kadyseva 1 , Vladimir Nikolaevich Bykov 2 , Olga Yurievna Strelova 1 , Alexander Nikolaevich Grebenyuk 1
Affiliation  

The biopolymer chitosan is widely used for the development of local hemostatic agents. However, the physicochemical parameters of chitosan that determine its hemostatic properties have not yet been determined. Standard quality control of chitosan-containing raw materials and medical products on its basis do not allow us to make a conclusion about the effectiveness of their use for stopping bleeding. The most reliable method for assessing hemostatic activity remains in vivo experiment on large animals. The aim of this study was to determine additional physicochemical parameters of chitosan, which would make it possible to predict its hemostatic activity without conducting a biological experiment. In this work, using the methods of nuclear magnetic resonance spectroscopy, spectrophotometry and viscometry, it has been shown that the ability to initiate hemostasis is depending of the molecular weight and degree of deacetylation of chitosan, but not enough linearly. The hemostatic properties in vitro increases in a series of samples with a relatively constant molecular weight with an increase in the degree of deacetylation. As well as in a series with the same degree of deacetylation with an increase in molecular weight. However, at molecular weight values more than 300 kDa, the viscosity of the polymer causes the opposite effect: with an increase in the degree of deacetylation, the hemostatic activity decreases. The best ability to initiate hemostasis have chitosan samples with a degree of deacetylation of 90.0%–97.4% and molecular weight 145.7–284.7 kDa, in which at pH of solution close to physiological, a significant part of the molecules transitioned from conformation state rigid rod to state globule. It was accompanied by an abrupt change in light transmission of the solution. It was concluded, that it is possible to study conformational states by spectrophotometry to assess the hemostatic activity of chitosan samples without performing biological experiment.



中文翻译:

无需生物实验即可评价壳聚糖止血活性的指标的测定

生物高分子壳聚糖被广泛用于局部止血剂的开发。然而,决定其止血特性的壳聚糖的理化参数尚未确定。含壳聚糖的原材料和医疗产品的标准质量控制在此基础上不允许我们对它们用于止血的有效性做出结论。评估止血活性最可靠的方法仍然是大型动物的体内实验。这项研究的目的是确定壳聚糖的其他理化参数,这将使预测其止血活性成为可能,而无需进行生物实验。在这项工作中,利用核磁共振波谱、分光光度法和粘度测定法,已经表明,启动止血的能力取决于壳聚糖的分子量和脱乙酰度,但线性不够。在一系列具有相对恒定分子量的样品中,体外止血特性随着脱乙酰化程度的增加而增加。以及在一系列具有相同脱乙酰度且分子量增加的情况下。然而,当分子量值超过 300 kDa 时,聚合物的粘度会产生相反的效果:随着脱乙酰度的增加,止血活性降低。启动止血的最佳能力是脱乙酰度为 90.0%–97.4% 且分子量为 145.7–284.7 kDa 的壳聚糖样品,其中溶液的 pH 值接近生理,大部分分子从构象状态刚性棒转变为状态球。伴随着溶液透光率的突然变化。结论是,可以通过分光光度法研究构象状态来评估壳聚糖样品的止血活性,而无需进行生物实验。

更新日期:2021-07-19
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