染料木素纳米混悬剂制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of genistein nanosuspensions

作　　者：寇应琳[1] 徐向宇[2] 孙宁[2] KOU Ying-lin;XU Xiang-yu;SUN Ning(Zhengzhou Railway Vocational&Technical College,Zhengzhou 450052,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]郑州铁路职业技术学院,河南郑州450052 [2]河南中医药大学,河南郑州450046

出　　处：《中成药》2023年第4期1045-1051,共7页Chinese Traditional Patent Medicine

基　　金：河南省二○二二年科技发展计划项目(222102310628)。

摘　　要：目的制备染料木素纳米混悬剂,并考察其体内药动学。方法采用高压均质法制备纳米混悬剂,单因素试验分析稳定剂(大豆卵磷脂+PVP K30)用量、大豆卵磷脂与PVP K30比例、均质压力、均质次数对粒径、PDI的影响。以蔗糖-甘露醇(1∶2)为冻干保护剂制备冻干粉,测定溶解度、体外溶出度。18只大鼠随机分为3组,分别灌胃给予染料木素、物理混合物、染料木素纳米混悬剂的0.5%CMC-Na混悬液(40 mg/kg),于0.25、0.5、1、1.5、2、3、4、6、8、12 h采血,HPLC法测定染料木素血药浓度,计算主要药动学参数。结果最佳处方工艺为染料木素用量20 mg,稳定剂用量50 mg,大豆卵磷脂与PVP K30比例2∶3,均质压力100 MPa,均质次数10次,平均粒径为184.63 nm,PDI为0.090,Zeta电位为-33.69 mV。纳米混悬剂在不同pH值介质中的溶解度、累积溶出度明显高于原料药、物理混合物。与原料药、物理混合物比较,纳米混悬剂t_(max)缩短(P<0.01),t_(1/2)延长(P<0.01),C_(max)、AUC_(0~t)、AUC_(0~∞)升高(P<0.01),相对生物利用度增加至4.60倍。结论纳米混悬剂可促进染料木素体外溶出,改善其口服吸收。AIM To prepare genistein nanosuspensions,and to investigate their in vivo pharmacokinetics.METHODS The nanosuspensions were prepared by high-pressure homogenization method,after which single factor test was applied to analyzing the effects of stabilizer(soybean lecithin+PVP K30)consumption,soybean lecithin-PVP K30 ratio,homogenization pressure and homogenization frequency on particle size and PDI.The lyophilized powder was prepared with saccharose-mannitol(1∶2)as lyoprotectant,along with the determination of solubility and in vitro dissolution rate.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of tilianin,physical mixture and genistein nanosuspensions(40 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,1.5,2,3,4,6,8,12 h,HPLC was adopted in the plasma concentration determination of genistein,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation process was determined to be 20 mg for genistein consumption,50 mg for stabilizer consumption,3∶2 for soybean lecithin-PVP K30 ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,the average particle size,PDI and Zeta potential were 184.63 nm,0.090 and-33.69 mV,respectively.The nanosuspensions demonstrated obviously higher solubility and in vitro dissolution rate in different pH media than raw medicine and physical mixture.Compared with raw medicine and physical mixture,the nanosuspensions displayed shortened t_(max)(P<0.01)and increased C_(max),AUC_(0-t),AUC_(0-∞)(P<0.01),the relative bioavailability was enhanced to 4.60 times.CONCLUSION Nanosuspensions can promote the in vitro dissolution of genistein and improve its oral absorption.

关 键 词：染料木素 纳米混悬剂 制备 体内药动学 高压均质法 HPLC 

分 类 号：R944[医药卫生—药剂学]