[关键词]
[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-PC nanosuspensions，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-ray powder diffraction，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）mV。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。
[Key word]
[Abstract]
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 and ζ potential 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 and ζ potential 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.
[中图分类号]
R283.6
[基金项目]
2018年度河南省科技攻关计划项目(2018020561)
