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喷雾干燥乳剂提高一氧化氮供体药物ZLR-8大鼠在体肠吸收的研究

Enhancement of in situ intestinal absorption of an insoluble NO-donating drug ZLR-8 in rats by spray-dried emulsion

  • 摘要: 目的 : 考察难溶性一氧化氮供体药物ZLR-8大鼠在体肠吸收特征及喷雾干燥乳剂对ZLR-8肠吸收的促进作用。 方法 : 采用大鼠在体小肠回流装置,以UV法和HPLC法分别测定酚红和ZLR-8的含量,计算ZLR-8在各肠段的吸收速率常数,考察ZLR-8浓度、肠循环液pH对肠吸收的影响,并对ZLR-8混悬液与ZLR-8喷雾干燥乳剂的肠吸收进行比较。 结果 : 以喷雾干燥乳剂给药,大鼠十二指肠﹑空肠﹑回肠﹑结肠1 h后对ZLR-8的吸收百分率分别为(23.54±1.40)%,(15.95±0.09)%,(12.30±0.74)%,(3.98±0.12)%,吸收速率常数分别为(0.248 6±0.046 0),(0.143 7±0.036 0),(0.069 2±0.001 3),(0.020 8±0.000 4) h-1,各肠段吸收特性有极显著性差异。ZLR-8浓度对吸收速率常数无显著影响,但吸收量与浓度线性相关;肠循环液pH显著影响肠吸收,ZLR-8在pH 5.4~7.4时有较好吸收;与混悬液相比,喷雾干燥乳剂极显著性增加大鼠肠吸收。 结论 : ZLR-8混悬液仅在小肠有微弱吸收,在其他肠段无明显吸收;喷雾干燥乳剂在各肠段均有明显吸收,吸收机制为被动扩散,极显著性地提高了ZLR-8的肠吸收。

     

    Abstract: Aim :To explore the in situ intestinal absorption in rats of ZLR-8,an insoluble NO-donor drug,and to compare the intestinal absorption enhancement by spray-dried emulsion. Methods :Intestine of rats was cannulated for in situ perfusion.UV and HPLC methods were used to monitor phenolsulfonphthalein and ZLR-8, respectively.The effects on ZLR-8 absorption of the intestinal segments,the concentration of ZLR-8 and the pH of the circulating perfusate were studied.The absorption of ZLR-8 suspension was compared to that of the spray-dried emulsion. Results :1-h in situ intestinal perfusion of the spray-dried emulsion allowed the estimation of the absortion percentage to be (23.54±1.40) %,(15.95±0.09) %,(12.30±0.74) %,(3.98±0.12) %,respectively;the absorption rate constants in duodenum,colon,jejunum and ileum to be (0.248 6±0.046 0) h-1,(0.143 7±0.036 0) h-1,(0.069 2±0.001 3) h-1,(0.020 8±0.000 4) h-1,respectively.Significant differences in absorption characteristics were found among intestinal segments.In the range of 3.4-9.4,pH of the perfuate had significant influence on the absorption of ZLR-8,and better absorption appeared at pH of 5.4 to 7.4.It was found that the absorption rate constant was unaffected by ZLR-8 concentration.However,the absorption amount was proportional to ZLR-8 concentration.Compared to the ZLR-8 suspension,the in situ intestinal absorption of ZLR-8 in rats given the spray-dried emulsion increased significantly. Conclusion :It was only found that ZLR-8 administered in suspension has minor absorption in rat duodenum while no apparent absorption occurred in other segemnts.ZLR-8 in spray-dried emulsion was fairly absorbed in the rat intestinal segments.Passive diffusion was invloved in the absorption of ZLR-8.Spray-dried emulsion significantly enhanced the intestinal absorption of ZLR-8 in rats.