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| 光谱法研究γ-环糊精及其两种衍生物与罗库溴铵和维库溴铵的相互作用 |
| 陈梦心1,张文婷1,闻俊1,赵鑫1,范国荣1*,漆又毛2,揭清2 |
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(1. 第二军医大学药学院药物分析学教研室, 上海市药物(中药)代谢产物研究重点实验室, 上海 200433
2. 杭州奥默医药股份有限公司, 杭州 310011
*通信作者) |
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| 摘要: |
| 目的 研究γ-环糊精(γ-CD)及其两种衍生物与罗库溴铵、维库溴铵的相互作用。方法 采用等温滴定量热法研究γ-CD及其衍生物奥美克松钠Aom0498-16(HS-7)、舒更葡糖(Sugammadex)与罗库溴铵、维库溴铵的相互作用, 测定其热力学常数及结合常数。采用紫外-可见分光光度法测定γ-CD与罗库溴铵、维库溴铵的包合比与结合常数, 并采用核磁共振谱二维相关谱和氢谱表征γ-CD及其两种衍生物与罗库溴铵、维库溴铵的结合力大小。结果 等温滴定量热法结果显示 Sugammadex 与HS-7均以1:1结合罗库溴铵、维库溴铵, γ-CD以2:1结合罗库溴铵;HS-7与罗库溴铵的结合常数k=(3.44±2.18)×107 L/mol、与维库溴铵的结合常数k=(5.80±1.83)×106 L/mol, Sugammadex与罗库溴铵的结合常数k=(1.04±0.34)×107 L/mol、与维库溴铵的结合常数k=(2.53±1.07)×106 L/mol, γ-CD与罗库溴铵的结合常数k=(2.84±3.41)×104 L/mol。紫外-可见分光光度法结果表明γ-CD以2:1结合罗库溴铵、维库溴铵, γ-CD与罗库溴铵的结合常数k=6.93×104 L/mol, 与维库溴铵的结合常数k=5.17×104 L/mol。核磁共振法结果显示HS-7对罗库溴铵、维库溴铵的包合作用强于 Sugammadex 和γ-CD。结论 HS-7包合肌松药的能力大于Sugammadex及γ-CD。等温滴定量热法、紫外-可见分光光度法和核磁共振谱二维相关谱和氢谱法3种方法从不同的侧面表征了包合物的性质。 |
| 关键词: γ-环糊精类 罗库溴铵 维库溴铵 磁共振波谱学 等温滴定量热法 紫外光谱法 |
| DOI：10.3724/SP.J.1008.2015.00507 |
| 投稿时间：2015-04-01修订日期：2015-04-20 |
| 基金项目: |
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| Spectroscopy study on the interaction of γ-cyclodextrin and its two derivatives with rocuronium and vecuronium |
| CHEN Meng-xin1,ZHANG Wen-ting1,WEN Jun1,ZHAO Xin1,FAN Guo-rong1*,QI You-mao2,JIE Qing2 |
(1. Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, Shanghai Key Laboratory for Pharmaceutical (Chinese Materia Medica) Metabolite Research, Shanghai 200433, China;
2. Hangzhou Adamerck Pharmlabs Inc., Hangzhou 310011, Zhejiang, China
*Corresponding author) |
| Abstract: |
| Objective To study the interaction of γ-cyclodextrin (γ-CD) and its two derivatives with rocuronium and vecuronium. Methods The interactions of γ-CD and its two derivatives HS-7, Sugammadex with rocuronium and vecuronium were characterized by Isothermal Titration Calorimetry (ITC), and the thermodynamic constant and the binding constant was determined. The binding constant and inclusion ratio of γ-CD with rocuronium and vecuronium was observed by ultraviolet-visible spectrophotometry; the binding ability of three cyclodextrins with rocuronium and vecuronium was analyzed by nuclear magnetic resonance spectroscopy COSY and 1HNMR. Results The results of ITC showed that HS-7, Sugammadex combined with rocuronium and vecuronium in a 1:1 molar ratio, and γ-CDs combined with rocuronium in a 2:1 molar ratio, with the binding constant of HS-7 and rocuronium being (3.44±2.18)×107 L/mol, HS-7 and vecuronium being (5.80±1.83)× 106 L/mol, Sugammadex and rocuronium being (1.04±0.34)× 107 L/mol, Sugammadex and vecuronium being (2.53±1.07)×106 L/mol, and γ-CD and rocuronium being (2.84±3.41)×104L/mol. The results of ultraviolet-visible spectrophotometry revealed that γ-CDs combined with rocuronium and vecuronium in a 2:1 molar ratio, with the binding constant of γ-CD and rocuronium being 6.93×104L/mol, and of γ-CD and vecuronium being 5.17×104 L/mol. The results of nuclear magnetic resonance spectroscopy suggested that the binding ability of HS-7 with rocuronium and vecuronium was stronger than that of Sugammadex and γ-CD. Conclusion The binding ability of HS-7 with rocuronium and vecuronium is stronger than that of Sugammadex and γ-CD, and the three methods used in this study (ITC, ultraviolet-visible spectrophotometry and nuclear magnetic resonance spectroscopy) can characterize the inclusion complex from different perspectives. |
| Key words: gamma-cyclodextrins rocuronium vecuronium magnetic resonance spectroscopy isothermal titration calorimetry ultraviolet-visible spectrophotometry |
