长春西汀及其共晶盐分子间相互作用的分析研究

Analysis and Study on the Interaction between Vinpocetine and Its Eutectic Salt Molecules

摘要: 药物固体形式的选择直接影响药物的稳定性和生物利用度。目前文献报道了4种长春西汀的共晶盐型，但理论上缺乏深刻剖析，系统分析晶体结构中分子间相互作用对于理解各盐型化学和物理特性的关系具有重要意义。本文应用分子间相互作用能计算，探讨了长春西汀形成共晶盐后性质变化的内在机制。结果显示，将长春西汀制成共晶可以改变分子间作用力，药物溶解度和熔点有所提高。Hirshfeld表面分析结果表明，在以长春西汀分子为中心3.8 Å距离范围内，长春西汀分子与形成盐型的酸根存在不同的相互作用能，加深了对长春西汀及其共晶盐分子间相互作用的深刻理解。本研究对探索长春西汀制成不同共晶盐可以改善何种理化性质和生物利用度具有一定的理论指导和应用价值。

Abstract: The choice of drug solid form directly affects the stability and bioavailability of the drug. Currently, four eutectic salt forms of vinpocetine have been reported in the literature, but there is a lack of in-depth analysis in theory. Systematic analysis of the intermolecular interactions in the crystal structure is of great significance for understanding the relationship between the chemical and physical properties of each salt form. This article applies the calculation of intermolecular interaction energy. These results showed that eutectic formation of vinpocetine can alter intermolecular forces and increase drug solubility and melting point. Through Hirshfeld surface analysis, it was found that within a distance range of 3.8 Å from the center of vinpocetine molecules, there are different interaction energies between vinpocetine molecules and salt forming acid groups, which deepens our understanding of the interactions between vinpocetine and its eutectic salt molecules. This study has certain theoretical guidance and application value for exploring the improvement of physical and chemical properties and bioavailability of vinpocetine by making different eutectic salts.