贺帅, 雷正杰, 张守尧, 张忠义 . 超临界快速膨胀法制备厚朴SCF-CO2萃取物超微颗粒及其溶出度和药动学考察J. 药学学报, 2009,44(5): 532-539.
引用本文: 贺帅, 雷正杰, 张守尧, 张忠义 . 超临界快速膨胀法制备厚朴SCF-CO2萃取物超微颗粒及其溶出度和药动学考察J. 药学学报, 2009,44(5): 532-539.
HE Shuai, LEI Zheng-Jie, ZHANG Shou-Yao, ZHANG Zhong-Xi- . Micronization of magnolia bark extract by RESS as well as dissolution and pharmacokinetics evaluationJ. 药学学报, 2009,44(5): 532-539.
Citation: HE Shuai, LEI Zheng-Jie, ZHANG Shou-Yao, ZHANG Zhong-Xi- . Micronization of magnolia bark extract by RESS as well as dissolution and pharmacokinetics evaluationJ. 药学学报, 2009,44(5): 532-539.

超临界快速膨胀法制备厚朴SCF-CO2萃取物超微颗粒及其溶出度和药动学考察

Micronization of magnolia bark extract by RESS as well as dissolution and pharmacokinetics evaluation

  • 摘要:

    应用超临界快速膨胀技术 (RESS) 制备中药厚朴超临界CO2 (SCF-CO2) 萃取物超微颗粒,初步探讨该技术应用于中药领域的可行性和优越性。以平均粒径、厚朴酚 (magnololMN) 及和厚朴酚 (honokiolHN) 的总酚含量为考察指标, 采用L9(33) 正交实验,对影响RESS制备厚朴SCF-CO2萃取物超微颗粒的因素 (萃取温度、萃取压力、喷嘴孔径)进行优选,并通过扫描电镜、HPLC、结合溶出度及体内动物实验对粒子各评价指标进行考察。该法最佳制备条件为:萃取温度T = 50 ℃、萃取压力P = 25 MPa、喷嘴孔径d = 100 μm;此条件下得到灰白色粒子, 电镜下观察为不规则的片状或块状,平均粒径为4.7 μm,粒子中总酚含量为91.2%。在15%甲醇中90 min内厚朴SCF-CO2萃取物超微颗粒的溶出度为14.77 mg·L−1,显著高于厚朴SCF-CO2萃取物原料粒子的溶出度6.37 mg·L−1  (P < 0.01);两组大鼠分别灌胃原料粒子混悬液和RESS粒子混悬液后,于不同时间测定血药浓度,得HNMN的平均血药浓度-时间曲线,采用WINNONLN软件计算求得药动学参数,对两组药动学参数进行t检验,结果表明RESS粒子中HNMNAUC0−t (5.41 ± 0.63) (7.24 ± 0.83) mg·h·L−1Cmax (2.31 ± 0.17) (2.84 ± 0.21) mg·L−1 均显著高于原料粒子组中HNMNAUC0−t (4.23 ± 0.36) (5.46 ± 0.57) mg·h·L−1 Cmax (1.55 ± 0.22) (2.35 ± 0.14) mg·L−1 (P < 0.05)RESS技术可用于厚朴SCF-CO2萃取物超微粒子的制备,得到的粒子粒径小,分布均匀,其溶出度、AUCCmax值均明显高于普通工艺制备的厚朴提取物粒子,且操作温度低、工艺流程简单、对环境无污染及无有机溶剂残留。

     

    Abstract:

    The purpose of this study is to explore the feasibility and superiority of using rapid expansion of supercritical solution (RESS) technology in the field of traditional Chinese medicine.  The extract of magnolia bark (EMB) was obtained by supercritical carbon dioxide (SCF-CO2) extraction technology.  Microparticles of EMB were manufactured by RESS technology.  The effects of operating temperature and pressure on the   contents of the active ingredient in the particles were evaluated by HPLC.  The effect of expansion conditions on the particle size distribution of EMB particles was investigated.  The smallest sample (mean size: 4.7 μm) was obtained under the RESS condition: pressure of 25 MPa, temperature of 50 ℃ and a nozzle size of 100 μm.  The characteristics of microparticles were also studied by differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and image analysis.  The dissolution rate study showed that microparticles had a   significantly faster dissolution rate than normal material particles.  After oral raw EMB suspension, the mean areas under the plasma concentration-time curves (AUC0−t) of honokiol and magnolol were found to be (4.23 ± 0.36) and (5.46 ± 0.57) mg·h·L−1, respectively, which were increased significantly, i.e. (5.41 ± 0.63) and (7.24 ± 0.83) mg·h·L−1 when micronized EMB suspension was administered orally in SD rats (P < 0.05).  Similarly, the mean maximum plasma concentrations of honokiol and magnolol increased from (1.55 ± 0.22) and (2.35 ± 0.14) mg·L−1 (raw EMB) to (2.31 ± 0.17) and (2.84 ± 0.21) mg·L−1 (micronized EMB), respectively.  The results of t-test demonstrated that AUC0−t and Cmax value for honokiol and magnolol was significantly increased with the micronization compared to raw EBM (P < 0.05).  This study demonstrated that the RESS was applicable for preparing microparticles of EMB at low operating temperature.  The process was simple, free of environment pollution and without residual solvent.

     

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