复方丹参双相胶囊体内外评价研究

In vitro and in vivo evaluation of Fufang Danshen Biphasic Capsules

目的 对比研究复方丹参双相胶囊(Fufang Danshen Biphasic Capsules,FDBC)与复方丹参胶囊(Fufang Danshen Capsules,FDC),证实复方丹参双相胶囊可降低冰片挥发损失且不会影响其他有效成分的体内外释药行为。方法 采用GC法测定FDBC与FDC处于高温、高湿、光照及加速实验条件后冰片的含量;以pH 1.2盐酸溶液、pH 4.5醋酸缓冲液、pH 6.8磷酸盐缓冲液和纯水为溶出介质,采用小杯法测定FDBC和FDC中丹参酮ⅡA、丹酚酸B、三七皂苷R1、人参皂苷Rg1和人参皂苷Rb1在不同时间点的累积溶出率,绘制溶出曲线;采用盐酸异丙肾上腺素(isoprenalinehydrochloride,ISO)制备大鼠急性心肌缺血模型,预防给药7 d后监测大鼠心电图ST段变化,HE染色观察心肌组织病理损伤,并利用试剂盒测定大鼠血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactic dehydrogenase,LDH)、心肌肌钙蛋白-T(cardiac troponin-T,cTn-T)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malonaldehyde,MDA)、肿瘤坏死因子-α(tumornecrosis factor-α,TNF-α)和白细胞介素-6(interleukin-6,IL-6)水平。结果 FDBC在高温、高湿、光照条件下及加速实验条件下冰片含量均保持在94.61%以上,而FDC中冰片含量显著降低;FDBC与FDC的体外溶出曲线相似;FDBC可以改善ISO致心肌缺血大鼠心电图ST段改变,减少血清中心肌酶的含量,保持心肌细胞结构完整,具有明显的抗心肌缺血作用,与FDC具有相同的抗心肌缺血作用。结论 与FDC相比,FDBC可以显著减少冰片挥发损失,且不会影响其他成分的体外释放和药理作用,显示出FDBC的优越性。

Objective In order to confirm that Fufang Danshen Biphasic Capsules(FDBC,复方丹参双相胶囊)can reduce the mass loss caused by volatilization of borneol without affecting the in vitro and in vivo drug release behavior of other active ingredients,a comparative study was conducted between FDBC and Fufang Danshen Capsules(FDC,复方丹参胶囊).Methods GC method was used to determine the content of borneol in FDBC and FDC under high temperature,high humidity,bright light and accelerated experimental conditions.Using pH 1.2 hydrochloric acid solution,pH 4.5 acetate buffer,pH 6.8 phosphate buffer and pure water as the dissolution medium,the cumulative dissolution rate of tanshinone IIA,salvianolic acid B,notoginsenoside R1,ginsenoside Rg1 and ginsenoside Rb1 at different time points was adopted by the small cup method,then the dissolution curve was drawn.The rat model of acute myocardial ischemia was prepared by isoprenaline hydrochloride(ISO).After 7 days of prophylactic administration,the changes of ST segment of the rat's electrocardiogram were monitored,the pathological damage of myocardial tissue was observed by hematoxylin-eosin staining,and the levels of creatine kinase(CK),lactic dehydrogenase(LDH),cardiac troponin-T(cTn-T),superoxide dismutase(SOD),malonaldehyde(MDA),tumornecrosis factor-α(TNF-α)and interleukin-6(IL-6)in rat serum were determined with kits.Results The content of borneol in FDBC remained above 94.61%under high temperature,high humidity,bright light conditions and accelerated experimental conditions,while the content of borneol in FDC decreased significantly.The dissolution profiles of FDBC and FDC were similar.FDBC could improve the changes of ST segment of ECG in rats with myocardial ischemia induced by ISO,reduce the content of myocardial enzymes in serum,keep the structure of myocardial cells intact,and have obvious anti-myocardial ischemia effect.FDC had the same anti-myocardial ischemia effect.Conclusion Compared with FDC,FDBC can significantly reduce the mass loss caused by volatilization of borneol without affecting the in vitro release and pharmacological effects of other components,showing the advantages of FDBC.