左氧氟沙星多组分晶体的制备与性能研究

摘要以左氧氟沙星为模型药物,采用偏最小二乘回归模型预测了可能与左氧氟沙星形成多组分晶体的配体,以指导左氧氟沙星多组分晶体样品的制备,并探究了样品的稳定性和体外抗菌活性。结果表明,所选17种配体中,7种配体成功与左氧氟沙星形成多组分晶体,其中5种配体被预测模型命中。各预测模型中,汉森溶解度参数/COSMO-RS双参数预测模型的准确率最高,对实验体系的总体准确率和阳性准确率分别为82.4%和83.3%。其中5种多组分晶体样品的稳定性与稳定性良好的原料药相当,且所制备的7种多组分晶体样品的抗菌活性均明显提高,预期在实现与原料药同等抗菌活性的前提下,可有效降低给药剂量,减少不良反应。

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	陈武
	顾振东
	郑智勇
	梁小小
	刘诗苑
	江燕斌

关键词：左氧氟沙星多组分晶体配体筛选制备性能

Abstract： Multi-component crystal is an effective way to improve the physicochemical and biochemical properties of drugs. Levofloxacin (LEV) is an antibacterial and anti-infective drug with high solubility and high antibacterial activity, but still exists some adverse effects. In this study, LEV was selected as the model drug, and partial least squares regression (PLS) models were used to predict the co-formers that might form multi-component crystals with levofloxacin. Guided by the prediction results, LEV multi-component crystals were prepared, then the stability and in vitro antibacterial activity of the samples were investigated. The results show that 7 of the 17 selected co-formers are successfully prepared as multi-component crystals with LEV, and 5 co-formers are successfully hit by the prediction results. Among the prediction models, the Hansen solubility parameter/COSMO-RS two-parameter prediction model has the highest accuracy, with an overall accuracy of 82.4% and a positive accuracy of 83.3% for the experimental systems, respectively. The stability of 5 multi-component crystal samples prepared is not significantly altered compared to the stable raw LEV, and the antibacterial activity against E. coli and S. aureus of all 7 prepared multi-component crystal samples is obviously improved. While achieving the same antibacterial activity as the raw LEV, it is expected that the prepared multi-component crystals would be effective in reducing the dose of the drug and reducing adverse effects.

Keywords： levofloxacin multi-component crystal co-former screening preparation property

Received 2023-07-03;

Fund:国家自然科学基金(22178121)。

Corresponding Authors: 郑智勇,硕士,E-mail:876176775@qq.com。 Email: 876176775@qq.com

About author: 陈武(1968—),男,高级工程师,现从事生物制药方面的研究。

引用本文:

陈武, 顾振东, 郑智勇, 梁小小, 刘诗苑, 江燕斌.左氧氟沙星多组分晶体的制备与性能研究[J]. 化学工业与工程, 2024,41(6): 136-148

CHEN Wu, GU Zhendong, ZHENG Zhiyong, LIANG Xiaoxiao, LIU Shiyuan, JIANG Yanbin.Preparation and property study of levofloxacin multi-component crystals[J]. Chemcial Industry and Engineering, 2024,41(6): 136-148

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