根皮素前体脂质体制备及其体内药动学研究  

Preparation and in vivo pharmacokinetics of phloretin proliposomes

作　　者：禹瑞 杨璞 崔晓鸽 陈四清[2] YU Rui;YANG Pu;CUI Xiao-ge;CHEN Si-qing(Zhengzhou Shuqing Medical College,Zhengzhou 450064,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]郑州澍青医学高等专科学校,河南郑州450064 [2]河南中医药大学,河南郑州450046

出　　处：《中成药》2023年第10期3173-3179,共7页Chinese Traditional Patent Medicine

基　　金：2023年河南省科技攻关项目(232102310384)。

摘　　要：目的 制备根皮素前体脂质体,并考察其体内药动学。方法 载体沉积法制备根皮素前体脂质体。以磷脂与胆固醇比例、脂(磷脂+胆固醇)药比、载(乳糖)脂比为影响因素,包封率为评价指标,Box-Behnken响应面法优化处方,测定体外释药、稳定性,进行晶型分析。12只大鼠随机分为2组,分别灌胃给予根皮素及其前体脂质体的PBS缓冲液(40 mg/kg),于不同时间点采血,HPLC法测定根皮素血药浓度,计算主要药动学参数。结果 最佳处方为根皮素用量20 mg,磷脂与胆固醇比例4.8∶1,脂药比16.5∶1,载脂比4.2∶1。所得前体脂质体呈球形或椭圆形,平均包封率为83.06%,粒径为216.84 nm, Zeta电位为-22.76 mV。原料药以无定形状态存在于前体脂质体中。前体脂质体在模拟胃液、模拟肠液中的累积释放度明显高于原料药,在90 d内稳定性良好。与原料药比较,前体脂质体tmax缩短(P<0.05),Cmax、AUC0~t、AUC0~∞升高(P<0.01),相对生物利用度增加至2.44倍。结论 前体脂质体可促进根皮素体外释放、体内吸收。AIM To prepare phloretin proliposomes and to investigate their in vivo pharmacokinetics.METHODS Carrier deposition method was adopted in the preparation of proliposomes.With phospholipids-cholesterol ratio,lipid(phospholipids+cholesterol)-drug ratio and carrier(lactose)-lipid ratio as influencing factors,encapsulation efficiency as an evaluation index,the formulation was optimized by Box-behnken response surface method,after which the in vitro drug release and stability were determined,and crystalline form analysis was made.Twelve rats were randomly assigned into two groups and given intragastric administration of the PBS buffers of phloretin and its proliposomes(40 mg/kg),respectively,after which blood collection was made at different time points,HPLC was adopted in the plasma concentration determination of phloretin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 20 mg for phloretin consumption,4.8∶1 for phospholipids-cholesterol ratio,16.5∶1 for lipid-drug ratio,and 4.2∶1 for carrier-lipid ratio.The obtained spherical or oval proliposomes demonstrated the average encapsulation efficiency,particle size and Zeta potential of 83.06[WTB4]%[WTBZ],216.84 nm and-22.76 mV,respectively.Raw medicine existed in the proliposomes in an amorphous state.The accumulative release rates of proliposomes in simulated gastric juice and simulated intestinal juice were obviously higher than those of raw medicine,whose stability was good within 90 d.Compared with raw medicine,the proliposomes displayed shortened t max(P<0.05)and increased C max,AUC 0-t,AUC 0-∞(P<0.01),the relative bioavailability was enhanced to 2.44 times.CONCLUSION Proliposomes can promote the in vitro release and in vivo absorption of phloretin.

关 键 词：根皮素 前体脂质体 制备 体内药动学 载体沉积法 HPLC 

分 类 号：R944[医药卫生—药剂学]