姜黄素纳米混悬剂在大鼠体内药代动力学考察

In vivo Pharmacokinetics Investigation of Curcumin Nanosuspensions in Rats

摘要:

目的: 探讨姜黄素纳米混悬剂在大鼠体内的药代动力学过程。方法: 将同等剂量的姜黄素原料药与姜黄素纳米混悬剂分别灌胃给2组大鼠,于灌胃后20,40 min和1,2,4,6,8,12,24 h眼底静脉丛取血,采用HPLC测定血浆姜黄素含量,Xterra C₁₈色谱柱(4.6 mm×250 mm,5 μm),C₁₈预柱(4.0 mm×2.0 mm),柱温35℃,流动相甲醇-1%乙酸水溶液(78:22),流速1.0 mL·min^-1,进样量20 μL,计算姜黄素最低定量限,同时测定血浆中姜黄素原料药与姜黄素纳米混悬剂的药代动力学参数。结果: 血浆中姜黄素的定量限15 μg·L^-1(S/N>10),低、中、高质量浓度的提取回收率(x±s,n=5)分别为(91.3±5.7)%,(93.0±4.1)%,(93.3±5.2)%。姜黄素纳米混悬剂的Cmax和AUC均显著高于姜黄素原料,Cmax分别为(863.1±390.4),(91.8±22.9) μg·L^-1;原料药和混悬剂的Tmax分别为(4.4±2.2),(4.8±4.4) h,t1/2分别为(4.6±3.2),(5.4±3.7) h,均无显著性变化。结论: 建立的HPLC分析条件稳定可靠,纳米混悬剂能明显促进姜黄素的吸收,提高其生物利用度,但吸收和代谢速度无明显差异。

Abstract:

Objective: To investigate in vivo pharmacokinetics and oral bioavailability of curcumin nanosuspensions in rats. Method: The same dose of curcumin bulk drugs and curcumin nanosuspensions were orally administered to two groups of rats,After gavage 20,40 min,1,2,4,6,8,12,24 h,0.3 mL blood from retinal venous plexus was obtained to measure plasma curcumin concertration ny HPLC analysis,Xterra C₁₈ column(4.6 mm×250 mm,5 μm),C₁₈ pre-column(4.0 mm×2.0 mm),column temperature 35℃,mobile phase of methanol-1% acetic acid aqueous solution(78:22),flow rate 1.0 mL·min^-1,injection volume 20 μL.The lowest limit of quantitation of curcumin and other pharmacokinetic parameters of curcumin and curcumin nanosuspensions were determined. Result: Quantification limit of curcumin in plasma was 15 μg·L^-1(S/N>10),extraction recoveries of low,medium and high concentration were (91.3±5.7)%,(93.0±4.1)%,(93.3±5.2)%,respectively.Cmax and AUC of curcumin nanosuspensions were higher than that of curcumin bulk drugs,Cmax were (863.1±390.4),(91.8±22.9) μg·L^-1;Tmax of curcumin bulk drugs and curcumin nanosuspensions were (4.4±2.2) h and (4.8±4.4) h,t1/2 were (4.6±3.2) h and (5.4±3.7) h,there was no significant change of these two parameters. Conclusion: Established HPLC analysis was reliable and stable,curcumin nanosuspensions could significantly promote absorption of curcumin and improve its bioavailability,but no significant differences were found in both absorption and metabolic.