七、八元瓜环对盐酸雷尼替丁的包合作用及缓释性能

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

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.

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 cucurbiturils 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.