目的 制备甲氧苄啶-磺丁基醚-β-环糊精包合物,并对其进行条件优化、表征和分子模拟。方法 采用超声微波-冷冻干燥法制备包合物,使用Box-Behnken响应面法进行条件优化;采用红外光谱法(FT-IR)、差示扫描量热法(DSC)、粉末X衍射法(XRPD)及核磁共振法(1H-NMR)对包合物进行表征;采用分子对接技术,模拟包合物的三维构象及结合能;进行溶出度和稳定性实验。结果 甲氧苄啶-磺丁基醚-β-环糊精包合物的最佳制备工艺为包合温度为52 ℃,包合时间为45 min,投料摩尔比为1.7∶1;红外光谱、差示扫描量热图谱、粉末X衍射图谱和核磁共振图谱均表明TMP/SBE7-β-CD包合物形成;分子模拟的包合物最优构象与表征分析相符,包合物结合能为-9.015 kcal·mol-1;包合物的TMP溶出速率明显增加,但包合物易吸湿。结论 甲氧苄啶-磺丁基醚-β-环糊精包合物制备工艺合理可行,表征方法系统可靠,包合物相对稳定。
Abstract
OBJECTIVE To prepare inclusion complex of SBE7-β-CD with trimethoprim(TMP) and optimize the preparation process, to evaluate the products by structural characterization and molecular simulation. METHODS The TMP/SBE7-β-CD inclusion complex was prepared by the ultrasound-freeze-dry method and the preparation process was optimized by Box-Behnken Design-response surface method(BBD-RSM). Inclusion complex was characterized by FT-IR, DSC, XRPD and 1H-NMR. Molecular docking method was used to simulate 3-dimensional conformations of the inclusion complex and the binding energy was calculated. The dissolution and stability were tested. RESULTS The optimum conditions of TMP/SBE7-β-CD inclusion complex were: temperature(52 ℃), time(45 min), and the ratio of SBE7-β-CD and TMP(mol/mol, 1.7∶1). All characterizations(FT-IR, DSC, XRPD and 1H-NMR) indicated the formation of TMP/SBE7-β-CD inclusion complex. The best 3-dimensional docking conformation was consistent with the characterizations, and the binding energy was -9.015 kcal·mol-1. The TMP dissolution rate of the inclusion complex increased significantly, the hygroscopicity is strong. CONCLUSION The preparation process of TMP/SBE7-β-CD inclusion complex optimized by BBD-RSM is reasonable and feasible. The characterizations of inclusion complex are reliable. The molecular simulation is corresponded to the characterized results and provided reliable theoretical basis for inclusion experiments.
关键词
甲氧苄啶 /
磺丁基醚-β-环糊精 /
包合 /
制备 /
表征 /
分子模拟
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Key words
trimethoprim /
SBE7-β-CD /
inclusion /
preparation /
characterization /
molecular simulation
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中图分类号:
R944
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脚注
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基金
重庆市自然科学基金重点项目资助(cstc2013jjB0011);重庆市应用开发计划项目资助(cstc2013yykfB10013);四川省农业科技成果转化资金项目资助(14NZ0027-1)
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