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| 丹红注射液在正常和寒凝血瘀大鼠中的药代动力学 |
| 陈勇勇1,贾璞1,董娟妮2,杨璐萌1,马晓毅1,王世祥1,肖超妮1,王晓雯3,张鹏3,郑晓晖1* |
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(1. 西北大学生命科学学院, 西安 710069;
2. 西安医学院第一附属医院药剂科, 西安 710077;
3. 陕西省人民医院药剂科, 西安 710068
*通信作者) |
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| 摘要: |
| 目的 建立同时测定血浆中丹参素(DSS)、原儿茶酸(PA)及羟基红花黄色素A(HSYA)的HPLC分析方法,研究丹红注射液主要酚酸类成分DSS、PA以及HSYA在正常和寒凝血瘀大鼠中药代动力学行为. 方法 正常及寒凝血瘀模型大鼠各6只,尾静脉注射丹红注射液.采用HPLC法检测给药后2、5、10、15、20、25、30、40、50、60、90 min时血浆中DSS、PA以及HSYA的浓度,流动相为0.2 %甲酸水(A)-甲醇(B),梯度洗脱,梯度波长检测:280 nm(0~40 min),402 nm(40~60 min).DAS 3.0软件计算药代动力学参数. 结果 DSS和PA呈现二室开放模型,HSYA呈现三室模型.与正常组相比,模型大鼠体内DSS、PA和HSYA的达峰浓度Cmax、DSS的分布半衰期t1/2α、PA和HSYA的消除半衰期t1/2α(t1/2γ) 和药时曲线下面积AUC以及总表观分布容积V均增大(P <0.05);PA和HSYA的分布半衰期t1/2α和DSS药时曲线下面积AUC均降低(P <0.05). 结论 在寒凝血瘀病理模型下,DSS在体内分布减慢,生物利用度降低;PA和HSYA的分布加快,消除减慢,表观分布容积增大,生物利用度增加,更能发挥好疗效. |
| 关键词: 丹红注射液 高压液相色谱法 药代动力学 寒凝血瘀 |
| DOI：10.3724/SP.J.1008.2015.00755 |
| 投稿时间：2014-11-30修订日期：2015-02-11 |
| 基金项目:国家科技支撑计划课题(2008BAI51B01),教育部长江学者和创新团队发展计划(IRT1174),陕西省重点科技创新团队计划(2013KCT-24),陕西省中医管理局资助项目(13-JC030),陕西省自然科学基金(2013JC2-07). |
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| Pharmacokinetics of Danhong Injection in normal and cold-coagulation and blood-stasis rats |
| CHEN Yong-yong1,JIA Pu1,DONG Juan-ni2,YANG Lu-meng1,MA Xiao-yi1,WANG Shi-xiang1,XIAO Chao-ni1,WANG Xiao-wen3,ZHANG Peng3,ZHENG Xiao-hui1* |
(1. College of Life Sciences, Northwest University, Xi'an 710069, Shaanxi, China;
2. Department of Pharmacy, The First Affiliated Hospital of Xi'an Medical University, Xi'an 710077, Shaanxi, China;
3. Department of Pharmacy, The People's Hospital of Shaanxi Province, Xi'an 710068, Shaanxi, China
*Corresponding author) |
| Abstract: |
| Objective To establish an HPLC method for simultaneous analysis of danshensu (DSS), protocatechuic acid (PA) and hydroxysafflor yellow A (HSYA) in plasma samples, and to study the pharmacokinetics of DSS, PA and HSYA in Danhong Injection in normal and cold-coagulation and blood-stasis model rats. Methods The cold-coagulation and blood-stasis rat models (n=6) were made by continuous stimulation with ice water for 20 days; another 6 normal rats served as controls. The concentrations of DSS, PA and HSYA in the plasma were determined by RP-HPLC (0.2% formic acid water[A]-methanol[B], gradient elution, wavelength detection: 280 nm [0-40 min] and 402 nm [40-60 min] ) at 2, 5, 10, 15, 20, 25, 30, 40, 50, 60, and 90 min after administration of Danhong Injection via the tail vein. The pharmacokinetic parameters were calculated with DAS 3.0 software. Results DSS and PA had an open two compartment model and HSYA had an open three compartment model. Compared with the normal groups, the model group had significantly increased maximum plasma concentration (Cmax) of DSS, PA and HSYA, the distribution half-life time (t1/2α) of DSS, and elimination half-life time (t1/2α, t1/2γ), area under curve (AUC), and apparent volume (V) of PA and HSYA (P <0.05); it also had significantly reduced distribution half-life time (t1/2α) of PA and HSYA and area under curve (AUC) of DSS(P <0.05). Conclusion DSS has a lower distribution and bioavailability under the condition of cold-coagulation and blood-stasis, while PA and HSYA show a faster distribution, slower elimination, increased apparent volume and bioavailability, indicating a better clinical effect. |
| Key words: Danhong Injection high pressure liquid chromatography pharmacokinetics cold coagulation and blood stasis |
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