厚朴酚共晶抑菌活性研究  

Study on the Antibacterial Activity of Magnolol Co-Crystals

作　　者：曾金石 陈晓锋 廖龙凤 谢月辉 朱丽康 ZENG Jinshi;CHEN Xiaofeng;LIAO Longfeng;XIE Yuehui;ZHU Likang(Ganxian District People′s Hospital,Ganzhou,Jiangxi,China 341100;National Research Institute for Family Planning,Beijing,China 100018)

机构地区：[1]江西省赣州市赣县区人民医院,江西赣州341100 [2]国家卫生健康委科学技术研究所,北京100018

出　　处：《中国药业》2024年第24期51-54,共4页China Pharmaceuticals

基　　金：国家卫生健康委科学技术研究所科技创新基金面上项目[2019GJM02]。

摘　　要：目的进一步提高厚朴酚(MAG)的抑菌活性。方法应用研磨法分别制备厚朴酚-L-脯氨酸(MAG-PRO)和厚朴酚-甜菜碱(MAG-BET)共晶,采用粉末X-射线衍射(PXRD)法、热失重分析(TG)法、差示扫描量热(DSC)法、傅里叶红外光谱(FT-IR)法鉴定共晶;对共晶粉末样品进行PXRD表征以观察其稳定性;采用高效液相色谱法测定MAG及其2种共晶在10 mL水、pH 2.0盐酸缓冲液、pH 4.5和6.8磷酸盐缓冲液4种溶出介质中的平衡溶解度;采用微量肉汤稀释法检测MAG及其2种共晶不同质量浓度(50,100,200μg/mL)下对大肠埃希菌的抑菌活性。结果4种鉴定方法确定了共晶形成;PXRD表征结果显示样品未发生晶型改变,稳定性较好;MAG及其2种共晶在4种溶出介质中的平衡溶解度存在显著差异,且均在pH 6.8条件下最高,pH 4.5条件下最低。菌悬液在不同MAG质量浓度下,共晶的抑菌率均高于MAG,且质量浓度为200μg/mL时,MAG及其共晶均表现出抑菌作用(抑菌率>50%)。结论MAG-PRO和MAG-BET的抑菌活性较单体更高。该结论可为MAG进一步的药用研发提供参考。Objective To increase the antibacterial activity of magnolol(MAG).Methods Magnolol-L-proline(MAG-PRO)co-crystal and magnolol-betaine(MAG-BET)co-crystal were prepared by the grinding method.The co-crystals were identified by the powder X-ray diffraction(PXRD),thermogravimetric analysis(TG),differential scanning calorimetry(DSC),and Fourier transform infrared spectroscopy(FT-IR)methods.PXRD characterization was performed to observe the stability of co-crystals.The equilibrium solubilities of the MAG and its two co-crystals in four dissolution media[10 mL water,hydrochloric acid buffer(pH 2.0),phosphate buffer(pH 4.5,pH 6.8)]were determined by the high-performance liquid chromatography(HPLC)method.The antibacterial activity of the MAG and its two co-crystals at different mass concentrations(50,100,200μg/mL)against Escherichia coli was detected by the broth microilution method.Results The co-crystals were confirmed by the above four identification methods.The PXRD characterization showed that the samples did not have any crystal form change and showed good stability.The equilibrium solubilities of MAG and its two co-crystals in four dissolution media were significantly different,with the highest in phosphate buffer(pH 6.8)and lowest in phosphate buffer solution(pH 4.5).At different concentrations of MAG,the antibacterial rate of co-crystals was higher than that of MAG;and when the concentration of MAG was 200μg/mL,all MAG and its co-crystals showed antibacterial activity(antibacterial rate>50%).Conclusion MAG-PRO and MAG-BET have higher antibacterial activity compared to monomer,which can provide a reference for further pharmaceutical research and development of MAG.

关 键 词：厚朴酚 L-脯氨酸 甜菜碱 共晶 鉴定 稳定性 平衡溶解度 抑菌活性 

分 类 号：R965[医药卫生—药理学] R285[医药卫生—药学]