摘要
目的制备延胡索乙素磷脂复合物(tetrahydropalmatine phospholipids complex,THP-PC)、延胡索乙素磷脂复合物固体分散体(THP-PC solid dispersion,THP-PC-SD)、延胡索乙素磷脂复合物油制剂(THP-PC oil preparation,THP-PC-OP)和延胡索乙素磷脂复合物纳米混悬剂(THP-PCnanosuspensions,THP-PC-NPs),并分别比较其在SD大鼠体内的药动学行为。方法溶剂挥发法分别制备THP-PC和THP-PC-SD,采用X射线粉末衍射(X-raypowderdiffraction,XRPD)技术分析THP的存在状态。高压均质法制备THP-PC-NPs,测定粒径及ζ电位。以THP混悬液为参考,分别比较THP-PC、THP-PC-SD和THP-PC-NPs体外溶出情况。SD大鼠分别ig给予THP、THP-PC、THP-PC-SD、THP-PC-OP和THP-PC-NPs,HPLC法测定THP血药浓度,计算主要药动学参数。结果THP在THP-PC、THP-PC-SD中均以无定型状态存在。THP-PC-NPs平均粒径为(184.57±10.41)nm,ζ电位为(-31.26±1.93)m V。THP-PC、THP-PC-SD和THP-PC-NPs均在不同程度上提高了THP的溶出度。与THP-PC相比,THP-PC相对生物利用度提高至1.70倍,而THP-PC-SD、THP-PC-NPs和THP-PC-OP的相对生物利用度分别进一步提高至4.11、4.86、4.22倍。结论THP-PC-SD、THP-PC-NPs和THP-PC-OP均可进一步提高THP-PC的生物利用度。
Objective To prepare tetrahydropalmatine phospholipids complex(THP-PC),THP-PC solid dispersion(THP-PC-SD),THP-PC oil preparation(THP-PC-OP),and tetrahydropalmatine phospholipids complex nanosuspensions(THP-PC-NPs),and then compare their pharmacokinetics behavior in SD rats.Methods THP-PC and THP-PC-SD were prepared by solvent volatilization.X-ray power diffraction(XRPD)was employed to study the presence of THP.THP-PC-NPs were prepared by high pressure homogenization method,particle size andζpotential were also determined.Dissolution in vitro of THP-PC,THP-PC-SD and THP-PC-NPs were compared to THP suspension.SD rats in each group were administered intragastrically with THP,THP-PC,THP-PC-SD,THP-PC-OP and THP-PC-NPs,respectively.Plasma concentration of THP was determined by HPLC,and the main pharmacokinetic parameters were calculated.Results The results of XRPD indicated that THP was changed into an amorphous state in THP-PC and THP-PC-SD.Particle size andζpotential of THP-PC-NPs were(184.57±10.41)nm and(-31.26±1.93)mV,respectively.The dissolution of THP was improved by THP-PC,THP-PC-SD and THP-PC-NPs in different degrees.Compared with raw medicine,relative bioavailability of THP-PC was increased to 1.70 times.The relative bioavailability of THP-PC-SD,THP-PC-OP and THP-PC-NPs were enhanced to 4.11,4.86 and 4.22 times,respectively.Conlusion THP-PC-SD,THP-PC-OP and THP-PC-NPs could enhance the oral bioavailability of THP-PC in further.
作者
李君霞
曹亚蕊
王金涛
方晓东
LI Jun-xia;CAO Ya-rui;WANG Jin-tao;FANG Xiao-dong(Henan Provincial Chest Hospital,Zhengzhou 450000,China;School of Materials,Zhengzhou University,Zhengzhou 450000,China;School of Pharmacy,Henan University,Zhengzhou 475001,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第14期4307-4316,共10页
Chinese Traditional and Herbal Drugs
基金
2018年度河南省科技攻关计划项目(2018020561)。
关键词
延胡索乙素
磷脂复合物
固体分散体
油制剂
纳米混悬剂
溶出度
生物利用度
药动学
溶剂挥发法
X射线粉末衍射
高压均质法
tetrahydropalmatine
phospholipids complex
solid dispersion
oil preparation
nanosuspensions
dissolution rate
bioavailability
pharmacokinetics
solvent volatilization
X-ray power diffraction
high pressure homogenization
作者简介
李君霞(1975—),本科,副主任药师,研究方向为医院临床药学。Tel:(0371)65662768 E-mail:lijunxia_henan@126.com;通信作者:王金涛(1969—),博士,副研究员,研究方向为中药新型给药系统。Tel:(0371)67766820 E-mail:jtwangphd@163.com。
