高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (02): 282.doi: 10.3969/j.issn.0251-0790.2012.02.012

• 有机化学 • 上一篇    下一篇

七、八元瓜环对盐酸雷尼替丁的包合作用及缓释性能

李立凡, 林友文, 黄智文, 罗红斌   

  1. 福建医科大学药学院, 福州 350004
  • 收稿日期:2011-03-22 出版日期:2012-02-10 发布日期:2012-01-13
  • 通讯作者: 林友文, 男, 教授, 主要从事生物医用材料研究. E-mail: linhumor@sina.com E-mail:linhumor@sina.com
  • 基金资助:

    福建省自然科学基金(批准号: 2011J01289)、福建省科技计划重点项目(批准号: 2011Y0031)和福建医科大学教授学术发展基金计划(批准号: JS09004)资助.

Interaction of Cucurbit[n=7,8] uril with Ranitidine Hydrochloride and Slow Release Properties

LI Li-Fan, LIN You-Wen, HUANG Zhi-Wen, LUO Hong-Bin   

  1. School of Pharmacy, Fujian Medical University, Fuzhou 350004, China
  • Received:2011-03-22 Online:2012-02-10 Published:2012-01-13
  • Contact: You-Wen LIN E-mail:linhumor@sina.com

摘要: 研究了七元瓜环(Q[7])和八元瓜环(Q[8])与盐酸雷尼替丁(RH)的包合作用及包合物的体外药物缓释性能. 采用紫外-可见光谱法测定了体系的包合比、包合稳定常数和药物累积释放度; 用 1H NMR技术考察了体系主-客体的包合作用. 结果表明, Q[7]和Q[8]与RH在酸性及中性条件下均能发生1∶1包合作用, 包合稳定常数分别为1.21×104和2.06×104 L/mol; 在碱性条件下则不发生包合作用. 原药RH, Q[7]-RH及Q[8]-RH包合物在人工胃液(pH=1.2)中的60 min累积释放度分别为89.1%, 56.6%和38.4%; 而在人工肠液(pH=6.8)中三者的60 min累积释放度分别为90.2%, 58.7%和38.0%. 实验结果表明, Q[7]及Q[8]包合对RH有明显的体外缓释作用.

关键词: 盐酸雷尼替丁, 瓜环, 包合作用, 缓释性能

Abstract: Cucurbit[n]urils(Q[n]) has hydrophobic central cavity and negatively charged carbonyl portals, can bind to a variety of cationic organic guest molecules and neutral species with high affinity, and therefore show great promise as a drug delivery system. In this work, interaction of cucurbit[n=7,8]urils with ranitidine hydrochloride(RH) which is a histamine H2 receptor antagonists were investigated by means of 1H NMR and UV-Vis spectroscopy, and the drug slow-release properties of inclusion complexes were observed in vitro. The effect of pH value on the interaction was studied; the inclusion ratio m, formation constant Ka and the drugs cumulative release of inclusion complexes in vitro were determined. The results reveal that RH form a 1∶1 complex with the Q[n](n=7,8). Formation constant of Ka was found to be 1.21×104 and 2.06×104 L/mol for Q[7]-RH and Q[8]-RH systems, respectively. RH can both form inclusion complexes with Q[7] and Q[8] in acidic, neutral conditions respectively, but they can't form inclusion complexes in alkaline conditions. The cumulative release rate in vitro of RH, Q[7]-RH and Q[8]-RH in artificial gastric juice(pH=1.2) at 60 min were 89.1%, 56.6% and 38.4%, respectively; and in artificial intestinal fluid(pH=6.8) at 60 min were found to be 90.2%, 58.7% and 38.0%, respectively. The drug release rates of Q[7]-RH and Q[8]-RH were obviously slower than that of RH. Q[7]-RH and Q[8]-RH had obviously sustained-release in vitro.

Key words: Ranitidine hydrochloride, Cucurbi[n]turil, Inclusion interaction, Slow release property

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