溴吡斯的明新型纳米乳体外释放和大鼠在体胃肠吸收

摘要

Aim To prepare the novel pyridostigmine bromide nanoemusion(PPNE)and study its release in vitro, and to investigate the intestinal absorption. Methods Pyridostigmine bromide (PB)and PPNE were tested by HPLC in pH 1 .2 HCl,pH 6.8,pH 7.4,pH 7.8 PBS.Rat single pass intestinal perfusion method was employed to investigate the absorption mechanism of PB and PPNE.Results PB release rate was faster than PB in the four release media;the intes-tinal absorption rate constant(Ka )and apparent perme-ability coefficient(Papp)of PPNE were increased in the duodenum,jejunum,ileum and colon segments.PB and PPNE had significant difference in the duodenum, jejunum,ileum and colon segments by t test (P <0.05).Conclusions PPNE can improve the bioavail-ability of drugs,increase the drugs permeability,sig-nificantly improve the absorption of the drugs in the in-testinal segments. PPNE has obviously sustained effects.%目的：制备油包水型溴吡斯的明新型纳米乳（novel pyridostigmine bromide nanoemulsion，PPNE），研究其体外释放规律及各胃肠段吸收动力学特征。方法选用3种不同浓度 pH 6.8、pH 7.4、pH 7.8的 PBS 以及 pH 1.2的 HCl 作为释药介质，测定并绘制其体外释药曲线；并采用在体单向肠灌流实验模型，比较溴吡斯的明（pyridostigmine bromide， PB）和 PPNE 在胃肠道的吸收行为。结果在4种释放介质中，PB 释放速率较快，而 PPNE 释放速率相对减缓；PPNE 的吸收速率常数（Ka ）和表观渗透系数（Papp ）较 PB 在十二指肠、空肠、回肠、结肠段中均增加。经 t 检验，PB 和 PPNE 在4个肠段均有统计学意义（P ＜0.05）。结论PPNE 可提高药物的生物利用度，明显提高其药物在体肠段的吸收；体外释放中有良好的缓释效果。