大黄酸纳米混悬剂的制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of rhein nanosuspensions

作　　者：张亚林[1] 喻海洋 黄涛[1] ZHANG Ya-lin;YU Hai-yang;HUANG Tao(Huanghe Science&Technology College,Zhengzhou 450005,China;Henan Provincial People’s Hospital,Zhengzhou 450011,China)

机构地区：[1]黄河科技学院,河南郑州450005 [2]河南省人民医院,河南郑州450011

出　　处：《中成药》2020年第11期2829-2834,共6页Chinese Traditional Patent Medicine

基　　金：郑州市医药创新科技服务平台项目(02031346)。

摘　　要：目的制备大黄酸纳米混悬剂,并考察其体内药动学。方法高压均质法制备纳米混悬剂。在单因素试验基础上,以PVP K30用量、均质压力、均质次数为影响因素,粒径为评价指标,正交试验优化制备工艺,检测纳米混悬剂形态、载药量、粒径、Zeta电位、体外释药。大鼠随机分为2组,分别灌胃给予大黄酸及其纳米混悬剂的0.5%CMC-Na混悬液(50 mg/kg),于0.083、0.167、0.25、0.5、1.0、2.0、4.0、6.0、8.0、10.0、12.0 h采血,HPLC法测定大黄酸血药浓度,计算主要药动学参数。结果最佳条件为PVP K30用量75 mg,均质压力100 MPa,均质次数15次,所得纳米混悬剂中纳米粒呈球形,分布均匀,无粘连,平均载药量为(32.14±0.92)%,Zeta电位为(-31.90±1.34)mV,粒径为(170.86±3.07)nm,40 min内累积溶出度为95.73%。纳米混悬剂t1/2、Cmax、AUC0~t、AUC0~∞高于原料药(P<0.01),相对生物利用度提高至2.02倍。结论纳米混悬剂可改善大黄酸体内吸收,提高其口服生物利用度。AIM To prepare rhein nanosuspensions and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high pressure homogenization method.With PVP K30 consumption,homogenization pressure and homogenization frequency as influencing factors,particle size as an evaluation index,the preparation process was optimized by orthogonal test on the basis of single factor test,after which the morphology,drug loading,particle size,Zeta potential,and in vitro drug release of nanosuspensions were detected.Rats were randomly assigned into two groups and given intragastric administration of the 0.5%CMC-Na suspensions of rhein and its nanosuspensions(50 mg/kg),respectively,after which blood collection was performed at 0.083,0.167,0.25,0.5,1.0,2.0,4.0,6.0,8.0,10.0,12.0 h.HPLC was adopted in the plasma concentration determination of rhein,and the main pharmacokinetic parameters were calculated.RESULTS The optimal conditions were determined to be 75 mg for PVP K30 consumption,100 MPa for homogenization pressure,and 15 times for homogenization frequency,the spherical nanoparticles demonstrated uniform distribution without adhesion,whose average drug loading,Zeta potential,particle size and accumulative release rate within 40 min were(32.14±0.92)%,(-31.90±1.34)mV,(170.86±3.07)nm and 95.73%,respectively.The nanosuspensions displayed higher t1/2,Cmax,AUC0-t and AUC0-∞than the raw medicine(P<0.01),and the relative bioavailability was increased to 2.02 times.CONCLUSION Nanosuspensions can improve the in vivo absorption of rhein and enhance its oral bioavailability.

关 键 词：大黄酸 纳米混悬剂 制备 体内药动学 高压均质法 正交试验 HPLC 

分 类 号：R944[医药卫生—药剂学]