响应面法优化白芍中芍药苷的超临界流体提取工艺及过程的数学模拟
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摘要
本文先通过响应面优化法优化了白芍中芍药苷的超临界流体萃取工艺条件,然后根据质量衡算规律建立了超临界流体萃取芍药苷的数学模型,最后分析总结了含夹带剂的超临界CO_2萃取传质过程。
根据Box-Behnken的中心组合实验设计原理,在单因素试验的基础上,采用三因素三水平的响应曲面分析法,建立白芍饮片中芍药苷超临界流体提取的二次多项式数学模型,并以芍药苷提取率为响应值作响应面和等高线,考察萃取压力、萃取温度和甲醇浓度对芍药苷超临界流体提取的影响。芍药苷超临界流体提取的优化工艺条件为:萃取压力为18.9MPa,萃取温度为59.9℃,夹带剂甲醇浓度为68.5%,夹带剂流速0.4mL·min~(-1),萃取时间为60min;在此工艺条件下,芍药苷的理论提取率可达7.85mg·g~(-1)。然后在此优化条件下进行验证实验,得到实际芍药苷的提取率为7.48mg·g~(-1),与理论预测值相比,其相对误差约为4.71%。
通过对响应曲面和等高线的分析可以得出芍药苷的超临界流体提取过程中萃取压力与甲醇浓度以及萃取温度和甲醇浓度之间相互影响比较明显,而萃取压力与萃取温度之间的相互作用不明显,说明夹带剂甲醇浓度对整个提取过程影响非常显著。进一步通过与索式提取和超声提取的比较可知,超临界流体提取的效果好、提取率高、时间短,是一种较为优秀的提取方法。
在响应面实验的基础上根据分步萃取传质机理,建立了超临界流体萃取芍药苷的数学模型。通过模拟计算和模型的参数回归得到了不易萃取溶质的浓度x_k=5.243×10~(-4)kg·kg~(-1),样品颗粒表面的外扩散传质系数K_f=8.598×10~(-8)m·s~(-1)以及样品颗粒内部的内扩散传质系数K_s=7.811×10~(-10)m·s~(-1)。通过模型检验得出模型能较好反映萃取的过程,为进一步优化模型参数和工艺研究提供了参考。
This article optimized supercritical fluid extraction process conditions of paeoniflorin by using response surface methodolog at first, and then established the mathematical model of supercritical fluid extraction, finally summarized mass transfer process of supercritical CO_2 extraction containing entrainer.
On the basis of one-factor tests and the Box-Behnken center-united experimental design principle, the method of response surface analysis with 3 factors and 3 levels was adopted. A second order quadratic equation for supercritical fluid extraction of paeoniflorin was built. Response surface and contour were graphed with the extraction rate of paeoniflorin as the response value. Based on the analysis of the response surface plots and their corresponding contour plots, the effects of extraction pressure, extraction temperature, and methanol concentration were explored. By using the new method discussed above, the optimum extraction condition was obtained as follows: extraction pressure 18.9MPa, extraction temperature 59.9℃, methanol concentration 68.5%, the flow rate of cosolvent mehtanol 0.4mL·min~(-1), and extraction time 60min. Under the optimized condition, extraction rate of paeoniflorin on theoretical value was 7.85mg·g~(-1). And the experimental extraction rate was 7.48mg·g~(-1) with relative error 4.71%, compared with the predictive value.
Through the analysis of response surface and contour lines, we can obtain the conclusion that the interaction between methanol concentration and extraction pressure or methanol concentration and extraction temperature is obvious, while is not obvious between pressure and temperature, indicating that methanol concentration has very significant impact on the extraction process. Compared with the soxhlet extraction and ultrasonic extraction, we can see that supercritical fluid extraction is an effective, high extraction rate and shorten time extraction method.
According to fractional mass transfer mechanism on the basis of response surface analysis, established a mathematical model of supercritical fluid extraction about paeoniflorin. Through simulation obtained model parameters such as the solute concentration of difficult extraction x_k=5.243×10~(-4)kg·kg~(-1), the mass transfercoefficient of the outer surface of sample particles K_f=8.598×10~(-8)m·s~(-1), and the mass transfer coefficient of internal surface of sample particles K_s=7.811×10~(-10)m·s~(-1). Through model checking, this model can reflect the process of extraction, it can be use as a reference for further optimizing the model parameters and technology research.
根据Box-Behnken的中心组合实验设计原理,在单因素试验的基础上,采用三因素三水平的响应曲面分析法,建立白芍饮片中芍药苷超临界流体提取的二次多项式数学模型,并以芍药苷提取率为响应值作响应面和等高线,考察萃取压力、萃取温度和甲醇浓度对芍药苷超临界流体提取的影响。芍药苷超临界流体提取的优化工艺条件为:萃取压力为18.9MPa,萃取温度为59.9℃,夹带剂甲醇浓度为68.5%,夹带剂流速0.4mL·min~(-1),萃取时间为60min;在此工艺条件下,芍药苷的理论提取率可达7.85mg·g~(-1)。然后在此优化条件下进行验证实验,得到实际芍药苷的提取率为7.48mg·g~(-1),与理论预测值相比,其相对误差约为4.71%。
通过对响应曲面和等高线的分析可以得出芍药苷的超临界流体提取过程中萃取压力与甲醇浓度以及萃取温度和甲醇浓度之间相互影响比较明显,而萃取压力与萃取温度之间的相互作用不明显,说明夹带剂甲醇浓度对整个提取过程影响非常显著。进一步通过与索式提取和超声提取的比较可知,超临界流体提取的效果好、提取率高、时间短,是一种较为优秀的提取方法。
在响应面实验的基础上根据分步萃取传质机理,建立了超临界流体萃取芍药苷的数学模型。通过模拟计算和模型的参数回归得到了不易萃取溶质的浓度x_k=5.243×10~(-4)kg·kg~(-1),样品颗粒表面的外扩散传质系数K_f=8.598×10~(-8)m·s~(-1)以及样品颗粒内部的内扩散传质系数K_s=7.811×10~(-10)m·s~(-1)。通过模型检验得出模型能较好反映萃取的过程,为进一步优化模型参数和工艺研究提供了参考。
This article optimized supercritical fluid extraction process conditions of paeoniflorin by using response surface methodolog at first, and then established the mathematical model of supercritical fluid extraction, finally summarized mass transfer process of supercritical CO_2 extraction containing entrainer.
On the basis of one-factor tests and the Box-Behnken center-united experimental design principle, the method of response surface analysis with 3 factors and 3 levels was adopted. A second order quadratic equation for supercritical fluid extraction of paeoniflorin was built. Response surface and contour were graphed with the extraction rate of paeoniflorin as the response value. Based on the analysis of the response surface plots and their corresponding contour plots, the effects of extraction pressure, extraction temperature, and methanol concentration were explored. By using the new method discussed above, the optimum extraction condition was obtained as follows: extraction pressure 18.9MPa, extraction temperature 59.9℃, methanol concentration 68.5%, the flow rate of cosolvent mehtanol 0.4mL·min~(-1), and extraction time 60min. Under the optimized condition, extraction rate of paeoniflorin on theoretical value was 7.85mg·g~(-1). And the experimental extraction rate was 7.48mg·g~(-1) with relative error 4.71%, compared with the predictive value.
Through the analysis of response surface and contour lines, we can obtain the conclusion that the interaction between methanol concentration and extraction pressure or methanol concentration and extraction temperature is obvious, while is not obvious between pressure and temperature, indicating that methanol concentration has very significant impact on the extraction process. Compared with the soxhlet extraction and ultrasonic extraction, we can see that supercritical fluid extraction is an effective, high extraction rate and shorten time extraction method.
According to fractional mass transfer mechanism on the basis of response surface analysis, established a mathematical model of supercritical fluid extraction about paeoniflorin. Through simulation obtained model parameters such as the solute concentration of difficult extraction x_k=5.243×10~(-4)kg·kg~(-1), the mass transfercoefficient of the outer surface of sample particles K_f=8.598×10~(-8)m·s~(-1), and the mass transfer coefficient of internal surface of sample particles K_s=7.811×10~(-10)m·s~(-1). Through model checking, this model can reflect the process of extraction, it can be use as a reference for further optimizing the model parameters and technology research.
引文
[1]Kumar K K,Johnston K P.Modeling the Solubility of Solids in Supercritical Fluids with Density as the Independent Variable.Journal of Supercritical Fluids,1998,1(1):15-22
[2]陈维扭.超临界萃取的原理和应用,北京:化学工业出版社,1998
[3]廖传华,黄振仁.超临界CO_2流体萃取技术.工艺开发及其应用,化学工业出版社,2004
[4]B.Mira,M.Blasco,S.Subirats.Journal of Supercritical Fluids,1999,14:95
[5]Stashenko E E,Puertas M A,M Y.Combariza,Journal of Chromatography A,1996,7(52):631
[6]Consuel M,Diaz-MarotoM,Soledad P C,et al.Supercritical carbon-dioxide extraction of volatiles from spices comparison with simultaneous distillation extraction.Journal of Chromatography A,2002,9(47):23-29
[7]Zougagh M,Valcarcel,Rios A.Supercritical fluid extraction:a critical review of its analytical usefulness.Trends in Analytical Chemistry,2004,5(23):399-405
[8]Khaje M.Comparsion of essential oils compositions of ferula assa-foetida obtained by supercritical Cerbon dioxide.extraction and hydrodistillation methods.Food Chemistry,2005,91:639-644
[9]Seied M P,Seiedeh S H.Supercritical fluid extraction in plant essential and volatile oil analysis.Journal of Chromatography A,2007,11(63):2-24
[10]刘福弟.超临界CO_2流体萃取技术在医药中的研究进展,齐齐哈尔医学院学报,2006,27(8):977-979
[11]张莉民,王菊,苏黎红,等.超临界流体萃取技术及在中药提取中的应用概述,齐鲁药事,2007,8(26):487-488
[12]Bahramifar N,Yamini Y,et al.Investigation on the supercritical carbon dioxide extraction of some polar drugs from spiked matrices and tablets.The journal of supercritical fluids,2005,35:205-211.
[13]Walsh J M,Ikonomou G D,Donohue M D,Supercritical phase behavior:the entrainer effect,Fluid Phase Equilibria,1987,33,295-314
[14]Schmitt W J,Reid R C,The use of entrainers in modifying the solubility of phenanthrene and benzoic acid in supercritical carbon dioxide and ethane,Fluid Phase Equilibria,1986,32:77-99
[15]Yutaka,Ikushima,Prediction of mutual solubility curve for t-butylalcohol-water system utilizing salting out phenomenon,Bull Chem Soc Jpn,1987,60:4145-4147
[16]Gonzalez Vila F J,Bautista J M,Gutierrez A J,Supercritical fluid extracting fat from eucalypt leaves,Bichem Biophys Methods,2000,43(1-3):345-351
[17]Baysal T,Ersus S,Starmans D A,Supercritical extraction of vitamins from tomato,J Agric Food Chem,2000,48(11):5507-5511
[18]Kohler M,Haerdi W,Chrustrem P,Extraction of artemisinin and artemisinic acid from artemisia annual using supercritical carbon dioxide,J Chromatogr A,1997,785(1/2):353-360
[19]周泉城,盛桂华.几种携带剂对超临界CO_2萃取维生素E的影响研究.中国粮油学报,2004,19(3):65-68.
[20]Hakuta Y,Hayashi H,Arai K.Fine particle formation using supercritical fluids.Current Opinion in Solid State and Materials Science,2003,7:341
[21]卢明春,包永明,守建国等.超临界CO_2萃取沙棘油工艺条件的优化,大连轻工业学院学报,1999,18(1):48-54
[22]张素华.CO_2超临界萃取沙棘油酸价测定,山西林业科技,2001,2:15-17
[23]银建中,孙献文,原华山等.超临界CO_2萃取沙棘油试验研究,化学工业与工程技术,2001,22(6):9-11
[24]高德永,林春绵.超临界CO_2萃取花生油的研究,浙江大学学报,1998,26(4):288-292
[25]孙爱东,尹卓容,蔡同一等.CO_2超临界萃取技术提取月见草油的工艺研究,中国油脂,1998,23(5):40-42
[26]于恩平,朱美文,方芝蓉等.CO_2超临界萃取月见草油的研究,中草药,1992,23(7):346-348
[27]孙爱东,尹卓容,蔡同一等.CO_2超临界萃取技术提取小麦胚芽油的工艺研究,食品工业科技,1997,5:68-70
[28]马海乐,陈钧,吴守一等.超临界CO_2萃取小麦胚芽油的试验研究,农业工程学报,1996,12(1):182-186
[29]王小梅,陈洪波,黄少烈等.超临界CO_2萃取小麦胚芽油的研究,广东化工,1998.5:16-20
[30]于红宇.亚麻籽油的超临界CO_2萃取及GC-MS分析,中草药,2002,25(4):264
[31]刘明伟,马海乐,李国文.超临界CO_2连续浓缩鱼油EPA和DHA的研究,农业工程学报,2003,19(2):167-170
[32]Ammond DA,Karel M,Klibanov AM,et al.Enzymatic-reactions in supercritical gases.Appl BiochemBiotech,1985,11(5):393-400.
[33]Nakamura K,Chi YM,Yamada Y,et al.Lipase activity and stability in supercritical carbon dioxide.Chem Eng Commun,1986,45(1-6):207-212
[34]包焕升,夏书申.发酵法与超临界CO_2提取法联合生产酒精新技术,中外技术情报,1991,11:3-4.
[35]朱自强.超临界流体技术原理和应用,北京:化学工业出版社,2000
[36]Perrut M,J.Jung,F.Leboeuf.Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes:Part Ⅰ:Micronization of neat particles.Pharma Sciences,2003,13(1):1
[37]宋慧婷,李淑芬.超临界流体技术在中药现代化生产中的研究进展,湖北大学学报(自然科学版),2003,25(3):237
[38]韩布兴等.超临界流体科学与技术,北京:中国石化出版社,2005
[39]陈淑莲,游静,王国俊.超临界流体低压萃取β-榄香烯,色谱,2001,19(2):179-181
[40]Johnston K P,Harrison K L,Clarke M J,et al.Water-in-Carbon Dioxide Microemulsions:An Environment for Hydrophiles Including Proteins.Science,1996,271:624
[41]Beckman E J.Carbon Dioxide Extraction of Biomolecules.Science,1996,271:613
[42]Jimenez-Carmona M M,de Castro M D L.Reverse Micelle Formation for Acceleration of the Supercritical Fluid Extraction of Cholesterol from Food Samples.Anal Chem,1998,70(10):2100
[43]Jimenez-Carmona M M,de Castro M D L.Reverse-micelle formation:a strategy for enhancing CO_2-supercritical fluid extraction of polar analytes.Anal Chimica ACTA,1998,358(1):1
[44]丁雪梅.白芍的特性及栽培技术,新疆农业科技,2008,179(2):35
[45]国家药典委员会.中华人民共和国药典一部,化学工业出版社,2005:68-69
[46]Shibata S,Nakahara M.Paeonoflorin,a glucoside of Chinese paeony root.Chem Pharm Bull,1963,11(3):372-378.
[47]Kaneda M,Iitaka Y,Shibata S.The absolute structures of paeoniflorin,albifloron,oxypaeoniflorin and benzoylpaeoniflorin isolated from Chinese paeony root.Tetrahedron,1972,28:4309-4317.
[48]Kitagawa I,yoshikawa M,Tsunaga K,et al.牡丹皮的成分(日).Shoyakugaku Zasshi,1979,33:171-177.
[49]Murakami N,Saka M,Shimada H,et al.New bioactive monoterpene glycoside from paeoniae radix.Chem Pharm Bull,1996,44(6):1279-1281.
[50]Shimizu M,Hayashi T,Morita N,et al.Paeoniflorigenone,a new monoterpene from paeony roots.Tetrahedron Lett,1981,22:3069-3070.
[51]Shibutani S,agaswa T,Oura H,et al.Effect of extract from paeoniae radix on urea-nitrogen concentration in rat serum.Chem Pharm Bull,1981,29(3):874-878.
[52]Lang HuiYing,Li ShouZhen,T McCabe,et al.A new monoterpene glycoside of Paeonia lactiflora.Planta Medica,1984,50(6):501-504.
[53]郎惠英,李守珍,梁晓天.中药赤芍中化学成分的研究.药学学报,1983,18(7):551-552.
[54]Hayashi T,Shinbo T,Shimizu M,et al.PaeonilactoneA,- B,and - C,new monoterpenoids frompaeony root.Tetrahedron Lett,1985,26:3699-3702.
[55]Kadota S,Terashima S,Basnet P,et al.Palbinone,a novel terpenoid from Paeonia albiflora;Potent inhibitory activity on 3α-hydroxysteroid dehydroxygenase.Chem Pharm Bull,1993,41(3):487-490.
[56]Ikuta A,Kamita K,Satoke T,et al.Triterpenoidsfrom callus tissue cultures of paeonia species.Phytochemistry,1995,38(5):1203-1207.
[57]Kamiya K,Yoshioka K,Saiki Y,et al.Triterpenoids and flavonoids from Paeonia lactiflora.Phytochemistry,1997,44(1):141-144.
[58]张晓燕,李铣.白芍的化学研究进展,沈阳药科大学学报,2002,19(1):70-73.
[59]张树花.芍药中d-儿茶精、没食子酸及其乙酯的含量测定,中草药,1988,19(9):10.
[60]江苏新医学院编.中药大词典上册第一版,上海:上海科学技术出版社,1986:706-709
[61]王兴旺,陈敏珠,徐叔云.白芍总甙对T淋巴细胞亚群的作用,中国药理学通报,1992,8(5):340.
[62]王兴旺,陈敏珠,徐叔云.白芍总甙对免疫系统的影响,中国病理生理杂志,1991,7(6):609-611.
[63]王兴旺,魏伟,陈敏珠等.白芍总甙调节小鼠免疫功能的机理,中国药理学通报,1990,6(6):363-366.
[64]王斌,陈敏珠,徐叔云.白芍总甙对佐剂性关节炎大鼠滑膜细胞功能和脾细胞增殖反应的影响,中国药理学与毒理学杂志,1994,8(2):129-131
[65]王斌,陈敏珠,徐叔云.白芍总甙对大鼠腹腔巨噬细胞产生肿瘤坏死因子的调节机制,中国药理学通报,1997,13(3):255-257
[66]吴曙光.抗炎免疫药理学进展,上海:第二军医大学出版社,1997:162-167
[67]李俊,陈敏珠,徐叔云.白芍总甙对大鼠腹腔巨噬细胞产生前列腺素E2的作用及部分机制的研究,中国药理学通报,1994,10(4):267-270
[68]李俊,赵维中,陈敏珠.白芍总甙对大鼠腹巨噬细胞产生白三烯B4的影响,中国药理学通报,1992,8(1):36-38
[69]吴春福.中芍药总甙的镇静作用,中药通报,1985,10(6):43
[70]王永祥等.白芍总甙的镇痛作用,中国药理学通报,1993,9(1):58
[71]明亮等.白芍总甙对小鼠学习记忆行为的影响,安徽医科大学学报,1993,28(1):1
[72]杨蓁等.中药药理研究方法学,北京:人民卫生出版社,1993:886
[73]黄贤权等.中药白芍在胃双对比造影中的作用,上海中医药杂志,1992:2
[74]杨小军,李建军,轩原清史等.白芍总苷对豚鼠结肠平滑肌M受体作用的研究,南京医科大学学报,2002,22(1):22
[75]戴利明,陈学广,徐叔云.白芍总甙对实验性肝炎的保护作用,中国药理学通报,1993,9(6):449-453
[76]张铭端,黄叔仁,陈敏珠.白芍总甙对内因性葡萄膜炎患者的免疫调节作用,中华眼疾病杂志,1994,3(3):146-148
[77]佘素贞等.白芍等四种中药水溶液提取液对二氨基芴诱导效应的抑制作用,癌症,1992,11(3):250
[78]佘素贞等.白芍总甙的致突变作用,中国医药工业杂志,1990,21(11):496
[79]Kobayashi-M,Ueda-C,Aoki-S,et al.Anticholinergic action of Paeony root and its active constituents.Yakugaku-Zasshi,1990,110(12):964
[80]Kimura-M,Kimura-M,Kimura-I,et al.Blockingeffects of a new component,paeoniflorigenone,in paeony root on neuromuscular junctions of frogs and mice.Jpn-J-Pharmacol,1984,35(1):6
[81]Kang-SS,Shin-KH,Chi-HJ,et al.Galloylpaeoniflorin,a new acylated monoterpene glucoside from paeony root.Arch-Pharm-Res,1991,14(1):52
[82]Watanabe-H.Psychotropic effects of Sino-Japanese traditional medicines.Yakubutsu-Seishin-Kodo,1993,13(2):951
[83]刘芳,杨广德.白芍中芍药苷的提取方法研究,中成药,2003,25(10):792-794
[84]杨士友,孙备,黄世福,吕凌,田军.白芍中白芍苷提取和纯化工艺的研究,安徽医药,2004,8(1):21-23
[85]吴悟贤,李生才,牛之猛.正交试验法优选白芍中芍药苷的提取工艺研究,时珍国医国药,2003,14(7):392-393
[86]吴英华,任凤莲,肖劲,陈胜福.白芍中芍药总苷的提取工艺研究,应用化工,2007,36(7):651-652
[87]贾立革,刘锁兰,李秀青等.中药提取分离新技术的研究进展,解放军药学学报,2004,4(13):21-25
[88]姜峰,赵燕禹,姜梅兰等.功率超声在中药提取过程中的应用,化工进展,2007,26(7):944-948
[89]ZhenShan Zhang,LiJun Wang,Dong Li,et al.Ultrasound-assisted extraction of oil from flaxseed,Separation and Purification Technology,2008,1(16):10-35
[90]刘玉红,陈燕,易进海.不同提取溶剂对白芍中芍药苷含量测定结果的影响,基层中药杂志,2001,15(5):19-20
[91]Ganzler K,Salgo A,Valko K.Microwave extraction.A novel sample preparation method for chromatography.J Chromatogr.1986,371:299-306
[92]黄天辉,沈平,沈永嘉.微波辅助提取白芍的工艺研究,中草药,2006,37(6):878-880
[93]Richter B E,Ezzell J L,et al.An Accelerated Solvent Extraction System for the Rapid Preparation of Environmental Organic Compounds in Soil.American Lab,1995,27(4):26-28
[94]US EPA SW-846.Method 3545.Testmethods for evaluating solid waste.Washington DC:US GPO,1995,7:1-12
[95]郭秀春,陈军辉,郑立等.加速溶剂提取法提取娑罗子中的七叶皂苷,天然产物研究与开发,2007,19:683-687
[96]屈健.加速溶剂萃取技术的原理及应用,中国兽药杂志,2005,39(6):46-48
[97]王乾,刘三康,付春梅,李章万.加速溶剂提取法提取赤芍中的芍药苷,华西药学杂志,2006,21(2):184-186
[98]聂晓玉,王雅亮,张彬,曲海波,王静.大孔吸附树脂法分离白芍中芍药苷和总苷,山东中医药大学学报,2004,28(4):360-310
[99]王爽,侯立强.白芍的提取精制工艺研究,辽宁中医药大学学报,2008,10(1):128
[100]曾宝,黄晓其,易智彪等.芍药苷在生产工艺过程中的含量变化和影响因素研究,中国中药杂志,2007,32(14):1472-1474
[101]慕运动.响应面方法及其在食品工业中的应用,郑州工程学院学报,2001,22(3):91-94
[102]Douglas C Montgomery.实验设计与分析,北京:中国统计出版社,1998:589-592
[103]周纪芗.实用回归分析方法,上海:上海科学技术出版社,1990:77-79
[104]Esquivel M M,Bernardo-Gil M G,King M B.Mathematical models for supercritical extraction of olive husk oil.J Supercrit Fluids,1999,16:43
[105]Bhupesh C.Roy,et.al.Extraction of Ginger Oil with Supercritical Carbon Dioxide:Experiments and Modeling.Industrial & Engineering Chemistry Research,1996,35(2):607-612
[106]朱恩俊.超临界流体萃取固态物料的缩芯萃取模型,江苏理工大学学报,1997,18(5):16-21
[107]E.Reverchon.Mathematical modelling of supercritical extraction of sage oil.AICHE.J,1996,42(6):1765-1771
[108]肖杨,吴元欣,王存文等.超临界CO_2中聚碳酸酯的合成Ⅱ.超临界CO_2密度的计算,天然气化工,2007,33(1):75-77
[2]陈维扭.超临界萃取的原理和应用,北京:化学工业出版社,1998
[3]廖传华,黄振仁.超临界CO_2流体萃取技术.工艺开发及其应用,化学工业出版社,2004
[4]B.Mira,M.Blasco,S.Subirats.Journal of Supercritical Fluids,1999,14:95
[5]Stashenko E E,Puertas M A,M Y.Combariza,Journal of Chromatography A,1996,7(52):631
[6]Consuel M,Diaz-MarotoM,Soledad P C,et al.Supercritical carbon-dioxide extraction of volatiles from spices comparison with simultaneous distillation extraction.Journal of Chromatography A,2002,9(47):23-29
[7]Zougagh M,Valcarcel,Rios A.Supercritical fluid extraction:a critical review of its analytical usefulness.Trends in Analytical Chemistry,2004,5(23):399-405
[8]Khaje M.Comparsion of essential oils compositions of ferula assa-foetida obtained by supercritical Cerbon dioxide.extraction and hydrodistillation methods.Food Chemistry,2005,91:639-644
[9]Seied M P,Seiedeh S H.Supercritical fluid extraction in plant essential and volatile oil analysis.Journal of Chromatography A,2007,11(63):2-24
[10]刘福弟.超临界CO_2流体萃取技术在医药中的研究进展,齐齐哈尔医学院学报,2006,27(8):977-979
[11]张莉民,王菊,苏黎红,等.超临界流体萃取技术及在中药提取中的应用概述,齐鲁药事,2007,8(26):487-488
[12]Bahramifar N,Yamini Y,et al.Investigation on the supercritical carbon dioxide extraction of some polar drugs from spiked matrices and tablets.The journal of supercritical fluids,2005,35:205-211.
[13]Walsh J M,Ikonomou G D,Donohue M D,Supercritical phase behavior:the entrainer effect,Fluid Phase Equilibria,1987,33,295-314
[14]Schmitt W J,Reid R C,The use of entrainers in modifying the solubility of phenanthrene and benzoic acid in supercritical carbon dioxide and ethane,Fluid Phase Equilibria,1986,32:77-99
[15]Yutaka,Ikushima,Prediction of mutual solubility curve for t-butylalcohol-water system utilizing salting out phenomenon,Bull Chem Soc Jpn,1987,60:4145-4147
[16]Gonzalez Vila F J,Bautista J M,Gutierrez A J,Supercritical fluid extracting fat from eucalypt leaves,Bichem Biophys Methods,2000,43(1-3):345-351
[17]Baysal T,Ersus S,Starmans D A,Supercritical extraction of vitamins from tomato,J Agric Food Chem,2000,48(11):5507-5511
[18]Kohler M,Haerdi W,Chrustrem P,Extraction of artemisinin and artemisinic acid from artemisia annual using supercritical carbon dioxide,J Chromatogr A,1997,785(1/2):353-360
[19]周泉城,盛桂华.几种携带剂对超临界CO_2萃取维生素E的影响研究.中国粮油学报,2004,19(3):65-68.
[20]Hakuta Y,Hayashi H,Arai K.Fine particle formation using supercritical fluids.Current Opinion in Solid State and Materials Science,2003,7:341
[21]卢明春,包永明,守建国等.超临界CO_2萃取沙棘油工艺条件的优化,大连轻工业学院学报,1999,18(1):48-54
[22]张素华.CO_2超临界萃取沙棘油酸价测定,山西林业科技,2001,2:15-17
[23]银建中,孙献文,原华山等.超临界CO_2萃取沙棘油试验研究,化学工业与工程技术,2001,22(6):9-11
[24]高德永,林春绵.超临界CO_2萃取花生油的研究,浙江大学学报,1998,26(4):288-292
[25]孙爱东,尹卓容,蔡同一等.CO_2超临界萃取技术提取月见草油的工艺研究,中国油脂,1998,23(5):40-42
[26]于恩平,朱美文,方芝蓉等.CO_2超临界萃取月见草油的研究,中草药,1992,23(7):346-348
[27]孙爱东,尹卓容,蔡同一等.CO_2超临界萃取技术提取小麦胚芽油的工艺研究,食品工业科技,1997,5:68-70
[28]马海乐,陈钧,吴守一等.超临界CO_2萃取小麦胚芽油的试验研究,农业工程学报,1996,12(1):182-186
[29]王小梅,陈洪波,黄少烈等.超临界CO_2萃取小麦胚芽油的研究,广东化工,1998.5:16-20
[30]于红宇.亚麻籽油的超临界CO_2萃取及GC-MS分析,中草药,2002,25(4):264
[31]刘明伟,马海乐,李国文.超临界CO_2连续浓缩鱼油EPA和DHA的研究,农业工程学报,2003,19(2):167-170
[32]Ammond DA,Karel M,Klibanov AM,et al.Enzymatic-reactions in supercritical gases.Appl BiochemBiotech,1985,11(5):393-400.
[33]Nakamura K,Chi YM,Yamada Y,et al.Lipase activity and stability in supercritical carbon dioxide.Chem Eng Commun,1986,45(1-6):207-212
[34]包焕升,夏书申.发酵法与超临界CO_2提取法联合生产酒精新技术,中外技术情报,1991,11:3-4.
[35]朱自强.超临界流体技术原理和应用,北京:化学工业出版社,2000
[36]Perrut M,J.Jung,F.Leboeuf.Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes:Part Ⅰ:Micronization of neat particles.Pharma Sciences,2003,13(1):1
[37]宋慧婷,李淑芬.超临界流体技术在中药现代化生产中的研究进展,湖北大学学报(自然科学版),2003,25(3):237
[38]韩布兴等.超临界流体科学与技术,北京:中国石化出版社,2005
[39]陈淑莲,游静,王国俊.超临界流体低压萃取β-榄香烯,色谱,2001,19(2):179-181
[40]Johnston K P,Harrison K L,Clarke M J,et al.Water-in-Carbon Dioxide Microemulsions:An Environment for Hydrophiles Including Proteins.Science,1996,271:624
[41]Beckman E J.Carbon Dioxide Extraction of Biomolecules.Science,1996,271:613
[42]Jimenez-Carmona M M,de Castro M D L.Reverse Micelle Formation for Acceleration of the Supercritical Fluid Extraction of Cholesterol from Food Samples.Anal Chem,1998,70(10):2100
[43]Jimenez-Carmona M M,de Castro M D L.Reverse-micelle formation:a strategy for enhancing CO_2-supercritical fluid extraction of polar analytes.Anal Chimica ACTA,1998,358(1):1
[44]丁雪梅.白芍的特性及栽培技术,新疆农业科技,2008,179(2):35
[45]国家药典委员会.中华人民共和国药典一部,化学工业出版社,2005:68-69
[46]Shibata S,Nakahara M.Paeonoflorin,a glucoside of Chinese paeony root.Chem Pharm Bull,1963,11(3):372-378.
[47]Kaneda M,Iitaka Y,Shibata S.The absolute structures of paeoniflorin,albifloron,oxypaeoniflorin and benzoylpaeoniflorin isolated from Chinese paeony root.Tetrahedron,1972,28:4309-4317.
[48]Kitagawa I,yoshikawa M,Tsunaga K,et al.牡丹皮的成分(日).Shoyakugaku Zasshi,1979,33:171-177.
[49]Murakami N,Saka M,Shimada H,et al.New bioactive monoterpene glycoside from paeoniae radix.Chem Pharm Bull,1996,44(6):1279-1281.
[50]Shimizu M,Hayashi T,Morita N,et al.Paeoniflorigenone,a new monoterpene from paeony roots.Tetrahedron Lett,1981,22:3069-3070.
[51]Shibutani S,agaswa T,Oura H,et al.Effect of extract from paeoniae radix on urea-nitrogen concentration in rat serum.Chem Pharm Bull,1981,29(3):874-878.
[52]Lang HuiYing,Li ShouZhen,T McCabe,et al.A new monoterpene glycoside of Paeonia lactiflora.Planta Medica,1984,50(6):501-504.
[53]郎惠英,李守珍,梁晓天.中药赤芍中化学成分的研究.药学学报,1983,18(7):551-552.
[54]Hayashi T,Shinbo T,Shimizu M,et al.PaeonilactoneA,- B,and - C,new monoterpenoids frompaeony root.Tetrahedron Lett,1985,26:3699-3702.
[55]Kadota S,Terashima S,Basnet P,et al.Palbinone,a novel terpenoid from Paeonia albiflora;Potent inhibitory activity on 3α-hydroxysteroid dehydroxygenase.Chem Pharm Bull,1993,41(3):487-490.
[56]Ikuta A,Kamita K,Satoke T,et al.Triterpenoidsfrom callus tissue cultures of paeonia species.Phytochemistry,1995,38(5):1203-1207.
[57]Kamiya K,Yoshioka K,Saiki Y,et al.Triterpenoids and flavonoids from Paeonia lactiflora.Phytochemistry,1997,44(1):141-144.
[58]张晓燕,李铣.白芍的化学研究进展,沈阳药科大学学报,2002,19(1):70-73.
[59]张树花.芍药中d-儿茶精、没食子酸及其乙酯的含量测定,中草药,1988,19(9):10.
[60]江苏新医学院编.中药大词典上册第一版,上海:上海科学技术出版社,1986:706-709
[61]王兴旺,陈敏珠,徐叔云.白芍总甙对T淋巴细胞亚群的作用,中国药理学通报,1992,8(5):340.
[62]王兴旺,陈敏珠,徐叔云.白芍总甙对免疫系统的影响,中国病理生理杂志,1991,7(6):609-611.
[63]王兴旺,魏伟,陈敏珠等.白芍总甙调节小鼠免疫功能的机理,中国药理学通报,1990,6(6):363-366.
[64]王斌,陈敏珠,徐叔云.白芍总甙对佐剂性关节炎大鼠滑膜细胞功能和脾细胞增殖反应的影响,中国药理学与毒理学杂志,1994,8(2):129-131
[65]王斌,陈敏珠,徐叔云.白芍总甙对大鼠腹腔巨噬细胞产生肿瘤坏死因子的调节机制,中国药理学通报,1997,13(3):255-257
[66]吴曙光.抗炎免疫药理学进展,上海:第二军医大学出版社,1997:162-167
[67]李俊,陈敏珠,徐叔云.白芍总甙对大鼠腹腔巨噬细胞产生前列腺素E2的作用及部分机制的研究,中国药理学通报,1994,10(4):267-270
[68]李俊,赵维中,陈敏珠.白芍总甙对大鼠腹巨噬细胞产生白三烯B4的影响,中国药理学通报,1992,8(1):36-38
[69]吴春福.中芍药总甙的镇静作用,中药通报,1985,10(6):43
[70]王永祥等.白芍总甙的镇痛作用,中国药理学通报,1993,9(1):58
[71]明亮等.白芍总甙对小鼠学习记忆行为的影响,安徽医科大学学报,1993,28(1):1
[72]杨蓁等.中药药理研究方法学,北京:人民卫生出版社,1993:886
[73]黄贤权等.中药白芍在胃双对比造影中的作用,上海中医药杂志,1992:2
[74]杨小军,李建军,轩原清史等.白芍总苷对豚鼠结肠平滑肌M受体作用的研究,南京医科大学学报,2002,22(1):22
[75]戴利明,陈学广,徐叔云.白芍总甙对实验性肝炎的保护作用,中国药理学通报,1993,9(6):449-453
[76]张铭端,黄叔仁,陈敏珠.白芍总甙对内因性葡萄膜炎患者的免疫调节作用,中华眼疾病杂志,1994,3(3):146-148
[77]佘素贞等.白芍等四种中药水溶液提取液对二氨基芴诱导效应的抑制作用,癌症,1992,11(3):250
[78]佘素贞等.白芍总甙的致突变作用,中国医药工业杂志,1990,21(11):496
[79]Kobayashi-M,Ueda-C,Aoki-S,et al.Anticholinergic action of Paeony root and its active constituents.Yakugaku-Zasshi,1990,110(12):964
[80]Kimura-M,Kimura-M,Kimura-I,et al.Blockingeffects of a new component,paeoniflorigenone,in paeony root on neuromuscular junctions of frogs and mice.Jpn-J-Pharmacol,1984,35(1):6
[81]Kang-SS,Shin-KH,Chi-HJ,et al.Galloylpaeoniflorin,a new acylated monoterpene glucoside from paeony root.Arch-Pharm-Res,1991,14(1):52
[82]Watanabe-H.Psychotropic effects of Sino-Japanese traditional medicines.Yakubutsu-Seishin-Kodo,1993,13(2):951
[83]刘芳,杨广德.白芍中芍药苷的提取方法研究,中成药,2003,25(10):792-794
[84]杨士友,孙备,黄世福,吕凌,田军.白芍中白芍苷提取和纯化工艺的研究,安徽医药,2004,8(1):21-23
[85]吴悟贤,李生才,牛之猛.正交试验法优选白芍中芍药苷的提取工艺研究,时珍国医国药,2003,14(7):392-393
[86]吴英华,任凤莲,肖劲,陈胜福.白芍中芍药总苷的提取工艺研究,应用化工,2007,36(7):651-652
[87]贾立革,刘锁兰,李秀青等.中药提取分离新技术的研究进展,解放军药学学报,2004,4(13):21-25
[88]姜峰,赵燕禹,姜梅兰等.功率超声在中药提取过程中的应用,化工进展,2007,26(7):944-948
[89]ZhenShan Zhang,LiJun Wang,Dong Li,et al.Ultrasound-assisted extraction of oil from flaxseed,Separation and Purification Technology,2008,1(16):10-35
[90]刘玉红,陈燕,易进海.不同提取溶剂对白芍中芍药苷含量测定结果的影响,基层中药杂志,2001,15(5):19-20
[91]Ganzler K,Salgo A,Valko K.Microwave extraction.A novel sample preparation method for chromatography.J Chromatogr.1986,371:299-306
[92]黄天辉,沈平,沈永嘉.微波辅助提取白芍的工艺研究,中草药,2006,37(6):878-880
[93]Richter B E,Ezzell J L,et al.An Accelerated Solvent Extraction System for the Rapid Preparation of Environmental Organic Compounds in Soil.American Lab,1995,27(4):26-28
[94]US EPA SW-846.Method 3545.Testmethods for evaluating solid waste.Washington DC:US GPO,1995,7:1-12
[95]郭秀春,陈军辉,郑立等.加速溶剂提取法提取娑罗子中的七叶皂苷,天然产物研究与开发,2007,19:683-687
[96]屈健.加速溶剂萃取技术的原理及应用,中国兽药杂志,2005,39(6):46-48
[97]王乾,刘三康,付春梅,李章万.加速溶剂提取法提取赤芍中的芍药苷,华西药学杂志,2006,21(2):184-186
[98]聂晓玉,王雅亮,张彬,曲海波,王静.大孔吸附树脂法分离白芍中芍药苷和总苷,山东中医药大学学报,2004,28(4):360-310
[99]王爽,侯立强.白芍的提取精制工艺研究,辽宁中医药大学学报,2008,10(1):128
[100]曾宝,黄晓其,易智彪等.芍药苷在生产工艺过程中的含量变化和影响因素研究,中国中药杂志,2007,32(14):1472-1474
[101]慕运动.响应面方法及其在食品工业中的应用,郑州工程学院学报,2001,22(3):91-94
[102]Douglas C Montgomery.实验设计与分析,北京:中国统计出版社,1998:589-592
[103]周纪芗.实用回归分析方法,上海:上海科学技术出版社,1990:77-79
[104]Esquivel M M,Bernardo-Gil M G,King M B.Mathematical models for supercritical extraction of olive husk oil.J Supercrit Fluids,1999,16:43
[105]Bhupesh C.Roy,et.al.Extraction of Ginger Oil with Supercritical Carbon Dioxide:Experiments and Modeling.Industrial & Engineering Chemistry Research,1996,35(2):607-612
[106]朱恩俊.超临界流体萃取固态物料的缩芯萃取模型,江苏理工大学学报,1997,18(5):16-21
[107]E.Reverchon.Mathematical modelling of supercritical extraction of sage oil.AICHE.J,1996,42(6):1765-1771
[108]肖杨,吴元欣,王存文等.超临界CO_2中聚碳酸酯的合成Ⅱ.超临界CO_2密度的计算,天然气化工,2007,33(1):75-77