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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(magnolol,MN)及和厚朴酚(honokiol,HN)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=25MPa、喷嘴孔径d=100μm;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4.7μm,粒子中总酚含量为91.2%。在15%甲醇中90min内厚朴SCF-CO2萃取物超微颗粒的溶出度为14.77mg.L-1,显著高于厚朴SCF-CO2萃取物原料粒子的溶出度6.37mg.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HN和MN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HN、MN的AUC0-t值[(5.41±0.63)和(7.24±0.83)mg.h.L-1]和Cmax值[(2.31±0.17)和(2.84±0.21)mg.L-1]均显著高于原料粒子组中HN、MN的AUC0-t值[(4.23±0.36)和(5.46±0.57)mg.h.L-1]和Cmax值[(1.55±0.22)和(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、AUC和Cmax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。
The supercritical carbon dioxide (SCF-CO2) extract ultrafine particles were prepared by supercritical rapid expansion technology (RESS), and the feasibility and superiority of this technology in the field of traditional Chinese medicine were discussed. The average phenolic content of magnolol (MN) and honokiol (HN) were used as indexes to investigate the influence of RESS on the SCF-CO2 extraction of Magnolia officinalis by orthogonal experiment L9 (33) Ultrafine particles (extraction temperature, extraction pressure, nozzle diameter) were optimized, and the evaluation indexes of the particles were investigated by scanning electron microscopy, HPLC, combined dissolution and in vivo animal experiments. The optimum conditions of this method were as follows: extraction temperature T = 50 ℃, extraction pressure P = 25MPa, nozzle diameter d = 100μm; under these conditions, gray-white particles were observed under the electron microscope. The average particle size Was 4.7 μm and the total phenolic content in the particles was 91.2%. The dissolution rate of ultrafine particles of Magnaporthia SCF-CO2 in 90% methanol for 14min was 14.77mg.L-1, which was significantly higher than that of Magnolia officinalis SCF-CO2 extract for 6.37mg.L-1 ( P <0.01). After the two groups of rats were respectively fed with the suspension of raw material particles and RESS particles, the plasma concentration of HN and MN was measured at different time to obtain the mean plasma concentration-time curve of HN and MN, and calculated by WINNONLN software The pharmacokinetic parameters were calculated and t test was performed on the pharmacokinetic parameters of the two groups. The results showed that the AUC0-t values of HN and MN in RESS particles [(5.41 ± 0.63) and (7.24 ± 0.83) mg.hL-1] and The Cmax values [(2.31 ± 0.17) and (2.84 ± 0.21) mg.L-1] were significantly higher than the AUC0-t values of HN and MN [(4.23 ± 0.36) and (5.46 ± 0.57) mg, respectively. hL-1] and Cmax [(1.55 ± 0.22) and (2.35 ± 0.14) mg.L-1], respectively (P <0.05). RESS technology can be used to prepare ultrafine particles of Magnolia officinalis SCF-CO2 extract. The obtained particles have small particle size and uniform distribution, and their dissolution, AUC and Cmax values are obviously higher than those of Magnolia officinalis extract prepared by the conventional process. Low temperature, simple process, no pollution to the environment and no residual organic solvents.