盐酸小檗碱与七、八元瓜环包合作用的光谱学研究及体外释药行为

目的研究七元瓜环（Q[7]）、八元瓜环（Q[8]）与盐酸小檗碱（BH）的包合作用,以及体系pH值对包合作用的影响,为构建瓜环-盐酸小檗碱药物释放体系提供理论依据。方法紫外可见光谱法和荧光光谱法研究体系包合作用和包合比;荧光光谱法测定包合常数;紫外分光光度法测定包合物的体外药物累积释放。结果七元瓜环-盐酸小檗碱（Q[7]-BH）发生2∶1的包合作用,包合常数为6.71×104L/mol;八元瓜环-盐酸小檗碱（Q[8]-BH）发生1∶2的包合作用,包合常数为1.44×104L/mol。Q[7]、Q[8]对BH均有荧光增敏作用。BH原药400 min在人工肠液（pH 6.8的磷酸盐缓冲溶液）中的累积释放度为94.8%、在人工胃液（pH 1.2）中的累积释放度为29.4%;Q[7]-BH及Q[8]-BH的溶出曲线相似,400 min在人工胃液中的累积释放度分别为63.9%和64.4%,在人工肠液中的累积释放度分别为69.8%和75.7%。结论七、八元瓜环与盐酸小檗碱在酸性和碱性条件下均能形成包合作用,且对盐酸小檗碱有增溶作用和荧光增敏作用。

Spectroscopic Study on the Interaction between Berberine Hydrochloride and Cucurbit[n=7,8]urils and Drug Release Behavior in vitro

Objective To study the interaction of cucurbit[n]urils（Q[n],n=7,8]） with berberine hydrochloride（BH） and the effect of pH on the interaction,provide the theoretical evidence for establishing drug release system of Q[n]-BH.Methods By ultraviolet-visible spectrometry and fluorescence spectrophotometry,the interaction of Q[n]（n=7,8） and BH were studied,inclusion ratio and the stability constants of inclusion was detected.Drug release behavior of inclusion complexes in vitro was detected by ultraviolet spectrometry.Results The experimental results revealed that BH form a 1∶2 complex with Q[7],formation constant of K was found to be 6.71×104L/mol.However,BH form a 2∶1 complex with Q[8],their formation constant of K was 1.44×104L/mol.fluorescent sensitizing effect of Q[7] and Q[8] on BH were both observed.The in vitro dissolution showed that the cumulative release at 400 min of raw BH was 94.8% in the artificial intestinal fluid（pH6.8 phosphate buffer solution） and 29.4% in artificial gastric juice（pH 1.2 hydrochloric acid）.The dissolution curve of Q[7]-BH was similar to that of Q[8]-BH,the cumulative release was 63.9% and 64.4% at 400 min in artificial gastric juice,respectively.In the artificial intestinal fluid at 400min,the cumulative release of Q[7]-BH was 69.8%,and 75.7% for Q[8]-BH.Conclusion Q[7] and Q[8] can form inclusion complex with BH in acidic and alkaline solution,show fluorescent sensitizing effect on BH and solubilization of BH.