目的 制备厚朴酚固体分散体、磷脂复合物和固体脂质纳米粒，并分别比较其在SD大鼠体内的药动学行为。方法 溶剂挥发法制备厚朴酚固体分散体和磷脂复合物，采用X射线粉末衍射（X-Ray Powder Diffraction，XRPD）技术分析厚朴酚的存在状态。高压均质法制备厚朴酚固体脂质纳米粒，并测定其粒径分布及Zeta电位。以厚朴酚原料药为参考，分别比较固体分散体、磷脂复合物和固体脂质纳米粒的体外溶出情况。SD大鼠分别ig给予厚朴酚、固体分散体、磷脂复合物和固体脂质纳米粒混悬液，HPLC法测定厚朴酚血药浓度，计算主要药动学参数，并比较药动学行为及相对生物利用度。结果 厚朴酚在固体分散体和磷脂复合物中均以无定型状态存在。厚朴酚固体脂质纳米粒Zeta电位为（-29.16±1.83）mV，平均粒径为（161.37±3.77）nm。厚朴酚原料药在12 h内的累积溶出度为30.6%，而厚朴酚固体分散体、固体脂质纳米粒和磷脂复合物将其12 h内累积溶出度分别提高至96.3%、76.4%、45.9%。ig给药后C_max、AUC_0~t和AUC_0~∞等药动学参数与原料药相比均具有显著提高。其中，磷脂复合物、固体分散体和固体脂质纳米粒将其C_max由（429.67±53.12）ng/mL分别提高至（533.62±59.01）、（721.73±103.44）、（1 063.21±108.22）ng/mL。相对生物利用度分别提高至1.38、2.12、3.45倍。结论 3种制剂均可提高厚朴酚口服吸收生物利用度，但厚朴酚固体脂质纳米粒效果更为明显。

Objective To prepare magnolol solid dispersions (Mag-SD), magnolol phospholipids complex (Mag-PC) and magnolol solid lipid nanoparticles (Mag-SLN), and compare their effects on the pharmacokinetics in vivo. Methods Solvent evaporation method was used to prepare Mag-SD and Mag-PC. Their existential state of Mag in Mag-SD and Mag-PC were analyzed by X-ray power diffraction (XRPD). High pressure homogenization method was employed to prepare Mag-SLN, its particle size and Zeta potential were also studied. The dissolution in vitro of Mag-SD, Mag-PC and Mag-SLN were also studied compared to magnolol suspension. SD rats in each group were administered intragastrically with magnolol, Mag-SD, Mag-PC and Mag-SLN, respectively. The concentration of magnolol in blood was analyzed by HPLC, and the main pharmacokinetic parameters were obtained. The pharmacokinetic behavior and bioavailability of magnolol, Mag-SD, Mag-PC and Mag-SLN were also compared. Results The results of XRPD indicated that magnolol showed an amorphous state in Mag-SD and Mag-PC. The average particle size and Zeta potential of Mag-SLN was (161.37±3.77) nm and (-29.16±1.83) mV, respectively. The results of dissolution in vitro indicated that the cumulative dissolution of magnolol was 30.6% within 12 h. Mag-SD, Mag-PC and Mag-SLN enhanced its cumulative dissolution to 96.3%, 76.4% and 45.9%, respectively. The results of pharmacokinetics in vivo showed that C_max, AUC_0-t and AUC_0-∞ of Mag-SD, Mag-PC and Mag-SLN were enhanced greatly compared to magnolol suspension. Mag-PC, Mag-SD and Mag-SLN increased its C_max from (429.67±53.12) ng/mL to (533.62±59.01), (721.73±103.44) and (1 063.21±108.22) ng/mL, respectively. The bioavailability of Mag-SD, Mag-PC and Mag-SLN were enhanced to 1.38, 2.12 and 3.45 times, respectively. Conclusion Mag-SD, Mag-PC and Mag-SLN could promote the absorption of magnolol in SD rats notably. In addition, Mag-SLN could give a better effect on the bioavailability.

R283.6

国家重大新药创制（2018ZX09210090-002-009）