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目的研究双嘧达莫(Dip)大鼠消化道在体吸收情况。方法采用HPLC测定各溶液中Dip的含量,测定不同pH溶液中Dip的溶解度,分别进行原位胃吸收、十二指肠、空肠、回肠、结肠单向灌流实验,并用SPSS进行统计学考察。结果Dip在盐酸溶液(9→1000)、pH2.5,4.5,6.8,7.4磷酸盐缓冲液和Krebs-Ringer缓冲液中的溶解度分别为(79096±329)、(1530±91)、(294.7±7.0)、(10.21±0.61)、(9.43±0.69)和(10.57±0.28)mg.L-1,溶解度和pH值近似满足如下关系S(mg.L-1)=450773.pH-5.3781(r=0.99);大鼠消化道各部位吸收速率常数分别为:胃(0.91±0.36)h-1、十二指肠(2.80±0.80)h-1、空肠(2.95±0.47)h-1、回肠(1.05±0.28)h-1、结肠(2.95±0.80)h-1。结论在胃液中Dip的溶解度显著高于其他肠段,且药物在消化道各段均有吸收,适合制成胃漂浮/滞留缓控释制剂。
Objective To study the in vivo absorption of digestive tract in Dip rats. Methods The content of Dip in each solution was determined by HPLC. The Dip solubility in different pH solutions was determined. In situ gastric perfusion, duodenum, jejunum, ileum and colon unilateral perfusion experiments were performed, and SPSS was used for statistical analysis. Results The solubilities of Dip in hydrochloric acid solution (9 → 1000), pH 2.5, 4.5, 6.8, 7.4 phosphate buffer and Krebs-Ringer buffer were (79096 ± 329), (1530 ± 91), (294.7 ± (10.21 ± 0.61), (9.43 ± 0.69) and (10.57 ± 0.28) mg.L-1, respectively. The solubility and pH value approximately satisfy the following relationship: S mg.L-1 = 450773.pH-5.3781 r = 0.99). The absorption rate constants of various parts of the digestive tract in rats were: gastric (0.91 ± 0.36) h-1, duodenal (2.80 ± 0.80) h- (1.05 ± 0.28) h-1, colon (2.95 ± 0.80) h-1. Conclusions The solubility of Dip in gastric juice is significantly higher than that of other intestinal segments, and the drugs are absorbed in all sections of the digestive tract, making it suitable for gastric floating / retention controlled release formulations.