槟榔炒制“火候”量化及其规律研究
|
摘要
目的本课题以槟榔炒制为研究对象,‘提出中药炮制、“火候”判别客观量化研究方法和炒制动力学研究思路,分别从宏观(性状)和微观(主要药效成分的动态变化规律)两个角度出发进行槟榔炒制火候“度”的量化把握研究,探讨炒制过程中的动态变化规律,为解决槟榔炒制工艺与“火候”相关的关键共性问题提供新思路新方法。
方法中药炮制“火候”判别客观量化研究方法是在全国范围内采集槟榔及其炮制品,应用色彩色差计和电子鼻采集其颜色特征参数和气味特征参数,通过统计分析总结全国老药工炮制经验,建立“火候”判别的数学预测模型和90%参考值范围。
炒制动力学研究是以在线式非接触红外测温系统采集炒制过程中的温度和时间参数,以槟榔中的槟榔碱、槟榔次碱和去甲基槟榔次碱为指标成分,建立其高效液相色谱含量测定方法,测定在不同炒制程度时以上化合物在饮片中的含量,收集时间、温度、含量等数据进行数学拟合,建立动力学数学模型,同时结合药效学实验,共同探讨药材中化学成分在炒制过程中的动态变化规律。
结果建立了基于L*a*b*色度空间的槟榔炒制火候判断的数学判别模型,其判别符合率为100%和双侧90%参考值范围分别为生品：L*(50.07-55.03)；a*(4.136～6.906),b*(6.65～8.82)；炒品：L*(43.874～47.998),a*(3.816～6.732),b*(3.786～6.558)；焦品：L*(38.744～40.616),a*(1.11～3.01), b*(-1.434～0.538)；电子鼻采集不同炮制品的气味数据,通过线性判别分析(LAD)和主成分分析(PCA),证明不同炮制程度的槟榔气味存在显著区别,建立了基于气味特征参数的“火候”判别数学模型。
在炒制动力学研究中,分别通过拟合药材、槟榔碱、槟榔次碱和去甲基槟榔次碱在炒制过程中的收得率—时间回归直线方程,求得质量下降速率常数Ks,证明由于槟榔碱、槟榔次碱和去甲基槟榔次碱的物理化学性质不同,其在炒制过程中的动态变化规律各有不同,在炒制过程中槟榔碱在炒制品中的含量为先缓慢下降后快速下降；槟榔次碱在炒制品中的含量为先上升后快速降低；去甲基槟榔次碱在炒制品中的含量为随着炒制程度的加深而匀速下降的变化规律,同时参考Yoshioka模型基于消除率(X)和时间(t)分别对槟榔碱、槟榔次碱和去甲基槟榔次碱的量在整个炒制过程中的动态变化进行了动力学模型拟合,其动态变化规律可用以下数学模型进行描述,分别为槟榔碱：LnX=0.6283 t0.6834,R=0.9920;槟榔次碱：LnX=0.0011 t2.8607,R=0.9994;去甲基槟榔次碱：LnX=0.8831 t0.5779,R=0.9920,求出动力学参数,证明炒制动力学能较好的揭示各化学成分在炒制过程中的动态变化规律,结合药效学实验结果,可初步判断通过炒制后槟榔中的槟榔碱和去甲基槟榔次碱降低到1217.7μg/g 结论通过实验证明基于色泽特征参数和气味特征常数均可区分不同炮制程度的槟榔样品,证明采用色彩色差计和电子鼻从宏观的角度判别中药炮制的“火候”具有一定的可行性。同时通过对动力学参数的分析,证明炒制动力学能有效的揭示药材中化学成分在炒制过程中的动态变化规律,可一定程度的为“火候”的不及、适中和太过进行定量分析,能为炒制原理的阐述和炒制工艺的建立提供一种定量研究的新思路新方法。
Objective:To introduce a series of new detection technologies and raise a new quantitative study method for studying on the processing of Chinese medicine.
Method:In studying of discriminating processed Betel nut's degree of stir-frying and quantizing empirical index Based on the Color Difference Meter and Electronic Nose Fingerprint Analyzer, the color's and the smell's characteristic parameters of belet nut and its processed products were measured by the color difference meter and electronic nose fingerprint Analyzer and set up huohou's math discrimination modules and 90% reference value scale by SPSS. In Stir-baking Kinetic Studies on the Alkaloids from Areca Catechu during Stir-baking Processing, the residual concentration of arecoline, arecaidine and guvacine in the processed products that were processed by stir-baking to different degree, were measured with a RP-HPLC method. At the same time, temperature's and time's parameters during.the stir-baking processing were determined by NCITS. The reduction rate constant, Ks could be obtained from a linear regerssion method in different phase and the degradation ratio, X at the whole stage could be correlated to time by the equation LnX=kt~n, where k and n are parameters.
Result:The huohou's math discrimination module was set up and its discrimination coincidence is 100% base on L*a*b*. The 90% reference value range respectively is Shengpin:L*(50.07～55.03), a*(4.136～6.906), b*(6.65～8.82); Chaopin: L*(43.874～47.998), a*(3.816～6.732),6*(3.786～6.558); Jiaopin:L*(38.744-40.616), a*(1.11～3.01), b*(-1.434～0.538). At the same time, a huohou's math discrimination module base on smell's characteristic parameters was founded too. The reduction of arecoline, arecaidine and guvacine could be described as retention ratio-time linear regerssion method in different phase. The whole dynamic state of arecoline, arecaidine and guvacine in the continuous stir-baking processing could be described as Arecoline:LnX=0.6283 t0.6834, R=0.9920; Arecaidine:LnX=0.0011 t2.8607, R=0.9994 and Guvacine:LnX=0.8831 t0.5779, R=0.9920, respectively. To combinate kinetics equations with results of pharmacodynamic test and conclude the best proportion of arecoline, arecaidine and guvacine in the baked products for increasing animal gastronitestinal contractile activity respectively is 1217.7μg/g Conclusion:Color characteristic parameters and smell characteristic parameters of belet nut and its processed products could availably discriminate different degree of processing and the stir-baking kinetics can effectively reveal regularity of kinetic transmutation of betel nut's chemical composition in a continuous processing and can quantitatively anlysis Huohou's inferior, appropriate and excessive degrees.
方法中药炮制“火候”判别客观量化研究方法是在全国范围内采集槟榔及其炮制品,应用色彩色差计和电子鼻采集其颜色特征参数和气味特征参数,通过统计分析总结全国老药工炮制经验,建立“火候”判别的数学预测模型和90%参考值范围。
炒制动力学研究是以在线式非接触红外测温系统采集炒制过程中的温度和时间参数,以槟榔中的槟榔碱、槟榔次碱和去甲基槟榔次碱为指标成分,建立其高效液相色谱含量测定方法,测定在不同炒制程度时以上化合物在饮片中的含量,收集时间、温度、含量等数据进行数学拟合,建立动力学数学模型,同时结合药效学实验,共同探讨药材中化学成分在炒制过程中的动态变化规律。
结果建立了基于L*a*b*色度空间的槟榔炒制火候判断的数学判别模型,其判别符合率为100%和双侧90%参考值范围分别为生品：L*(50.07-55.03)；a*(4.136～6.906),b*(6.65～8.82)；炒品：L*(43.874～47.998),a*(3.816～6.732),b*(3.786～6.558)；焦品：L*(38.744～40.616),a*(1.11～3.01), b*(-1.434～0.538)；电子鼻采集不同炮制品的气味数据,通过线性判别分析(LAD)和主成分分析(PCA),证明不同炮制程度的槟榔气味存在显著区别,建立了基于气味特征参数的“火候”判别数学模型。
在炒制动力学研究中,分别通过拟合药材、槟榔碱、槟榔次碱和去甲基槟榔次碱在炒制过程中的收得率—时间回归直线方程,求得质量下降速率常数Ks,证明由于槟榔碱、槟榔次碱和去甲基槟榔次碱的物理化学性质不同,其在炒制过程中的动态变化规律各有不同,在炒制过程中槟榔碱在炒制品中的含量为先缓慢下降后快速下降；槟榔次碱在炒制品中的含量为先上升后快速降低；去甲基槟榔次碱在炒制品中的含量为随着炒制程度的加深而匀速下降的变化规律,同时参考Yoshioka模型基于消除率(X)和时间(t)分别对槟榔碱、槟榔次碱和去甲基槟榔次碱的量在整个炒制过程中的动态变化进行了动力学模型拟合,其动态变化规律可用以下数学模型进行描述,分别为槟榔碱：LnX=0.6283 t0.6834,R=0.9920;槟榔次碱：LnX=0.0011 t2.8607,R=0.9994;去甲基槟榔次碱：LnX=0.8831 t0.5779,R=0.9920,求出动力学参数,证明炒制动力学能较好的揭示各化学成分在炒制过程中的动态变化规律,结合药效学实验结果,可初步判断通过炒制后槟榔中的槟榔碱和去甲基槟榔次碱降低到1217.7μg/g
Objective:To introduce a series of new detection technologies and raise a new quantitative study method for studying on the processing of Chinese medicine.
Method:In studying of discriminating processed Betel nut's degree of stir-frying and quantizing empirical index Based on the Color Difference Meter and Electronic Nose Fingerprint Analyzer, the color's and the smell's characteristic parameters of belet nut and its processed products were measured by the color difference meter and electronic nose fingerprint Analyzer and set up huohou's math discrimination modules and 90% reference value scale by SPSS. In Stir-baking Kinetic Studies on the Alkaloids from Areca Catechu during Stir-baking Processing, the residual concentration of arecoline, arecaidine and guvacine in the processed products that were processed by stir-baking to different degree, were measured with a RP-HPLC method. At the same time, temperature's and time's parameters during.the stir-baking processing were determined by NCITS. The reduction rate constant, Ks could be obtained from a linear regerssion method in different phase and the degradation ratio, X at the whole stage could be correlated to time by the equation LnX=kt~n, where k and n are parameters.
Result:The huohou's math discrimination module was set up and its discrimination coincidence is 100% base on L*a*b*. The 90% reference value range respectively is Shengpin:L*(50.07～55.03), a*(4.136～6.906), b*(6.65～8.82); Chaopin: L*(43.874～47.998), a*(3.816～6.732),6*(3.786～6.558); Jiaopin:L*(38.744-40.616), a*(1.11～3.01), b*(-1.434～0.538). At the same time, a huohou's math discrimination module base on smell's characteristic parameters was founded too. The reduction of arecoline, arecaidine and guvacine could be described as retention ratio-time linear regerssion method in different phase. The whole dynamic state of arecoline, arecaidine and guvacine in the continuous stir-baking processing could be described as Arecoline:LnX=0.6283 t0.6834, R=0.9920; Arecaidine:LnX=0.0011 t2.8607, R=0.9994 and Guvacine:LnX=0.8831 t0.5779, R=0.9920, respectively. To combinate kinetics equations with results of pharmacodynamic test and conclude the best proportion of arecoline, arecaidine and guvacine in the baked products for increasing animal gastronitestinal contractile activity respectively is 1217.7μg/g
引文
[1]原思通.挖掘传承、研究提高,努力开创中药炮制发展新局面——中药炮制分会第二届委员会工作报告[C].中华中医药学会中药炮制分会第二届第五次学术研究会论文集,2007,1.
[2]汪新久,孟宪纾,王学农,等.山楂炮制品的工艺及质量研究[J].沈阳药学院学报,1993,10(4)：263.
[3]陈青莲,彭洁,艾卫涛.不同烘制温度对山楂有机酸含量及胃肠推进功能的影响[J].湖北中
医学院学报,2000,1(2)：46-48.
[4]陈青莲,江雪萍.山楂不同炮制品对小鼠胃排空作用的影响[J].中药材,2001,12(24)：887-889.
[5]蔡少芬,江海燕,欧艳萍.山楂不同炮制品有机酸含量测定[J].中成药,2000,12(22)：841-843.
[6]南云生,马春亮,王洪波.山楂炮制研究.中成药,1992,14(4)：765.
[7]张林丽,陈国佩,韦凤.槟榔不同炮制品中槟榔碱含量的比较[J].中药材,2002,6(25)：404-406.
[8]黄敏琪.槟榔几种不同炮制品含量测定的研究[J].广西中医学院报,2000,3(17)：84.
[9]惠秋沙,孙立立.炮制对槟榔化学成分的影响[J].中成药,2007,9(29)：1331-1333.
[10]孔祥田,孟凡鹏,张迎.“三仙”炒焦增效质疑[J].贵阳中医学院学报,1999,4(21)：50-51.
[11]王亚红.麦芽在临床应用说略[J].河南中医,2003,1(23)：60.
[12]薛玲,谭鹏,吕文海.莱菔子不同炮制品对消化系统作用及其急性毒性研究[J].山东中医药大学学报,2006,1(30)：74-75.
[13].黄春燕,吴纯洁,陈文文,等.中药炮制“火力”与“火候”研究现状及展望[J].世界科学技术-中医药现代化,2006,8(5)：73-75.
[14]陈楚明,吴纯洁,黄春燕,等.红外非接触测温在中药加工炮制中的应用[J].中国中药杂志.2005,30(7)：629.
[15]陈楚明,吴纯洁,黄学思,等.NOITM技术在中药炮制中的应用探讨[C].炮制会议论文集,2006.
[16]陈楚明,吴纯洁,黄春燕,等.在线式红外测温炒药机的构建[C].炮制会议论文集,2007.
[17]陈楚明,吴纯洁,孙灵根,等.中药饮片有关色泽客观量化表达的构建[J],世界科学技术—中医药现代化,2007,9(4)：2225.
[18]李文敏,吴纯洁,艾利,等.电子舌和电子鼻技术及其在中药炮制研究中应用的展望[C].炮制会议论文集,2007.
[19]张慧慧,吴纯洁,黄学思,等.“电子眼”在中药炮制中应用构想[C].炮制会议论文集,2007.
[20]李文敏,吴纯洁,艾利,等.基于电子鼻、电子舌技术实现中药性状气味客观化表达的构想[J].中国科技论文在线.2007.
[21]张利伟,付玉梅.不同炮制方法的山楂药材指纹特征[J].江西中医学院学报,2006,5(18)：47-48.
[22]龚千锋.中药炮制学[M].中国中医药出版社,2007.
[23]Frey,A.H.A, Review of the nature of odor perception and human response[J],Indoor Environ.2005.
[24]Gardner J.W, Bartlett P.N, A brief history of electronic nose[J],Sensors and Actuators,2004.
[25]Keller P.E, Kangas L.J etc., Electronic nose and their applications,Neural network application studies workshop in the IEEE orthicon, USA,1995.
[26]Craven M.A, Gardner J.W, Electronic nose development and future prospect[J],Trends in analytical chemistry,1996(21):486-493.
[27]Fengchun Tian,Simon X.Yang,and Kevin Dong, Circuit and Noise Analysis of Odorant Gas Sensors in an E-Nose[J],Sensors 2005(5):85-96.
[28]Hsin-Ti chneh, John V.hatfield, A real-time data acquisitions system for a hand-held electronic nose(H2EN)[J],Sensors and Actuators,2002(8):262-269.
[29]Pardo M,Sberveglieri G,Sisk B,Lewis N, Classifier comparison and sensor selection for
e-noses[J], Sensors,2003.
[30]Dutta R, Hines E. L. and Gardner J. W. Tea quality prediction using a tin oxide-based electronic nose:an artificial intelligence approach[J].Sensors and Actuators B,2003.94:228-237.
[31]Bhattacharvya N.. Seth s.. and Tudu B. Detection of optimum fermentation time for black tea manufacturing using electronic nose [J]. Sensors and Actuators B,2007,122:627-634.
[32]Vernat-Rossi V., Garcia C.and Talon R. Rapid discrimination of meat products and bacterial strains using semiconductor gas sensors. Sensors and Actuators B,2006,37:43-48.
[33]Rossi V., Garcia C. and Talon R. Rapid discrimination of meat products and bacterial strains using semiconductor gas sensors. Proceedings of Bioflavour 95. Dijon.2005,85-89.
[34]Moy L.,Vasic G and Berdague J.L. Transient signal modeling for fast odour classification. Proceedings of Bioflavour 95[J].Dijon.1995,55-58.
[35]Jonsson A.,Winquist F. and Schnurer J. Electronic nose for microbial quality classification of grains[J]. International journal of food microbiology,1997,35:187-193.
[36]Rella R.,Siciliano P. and Capone S. Air quality monitoring by mean of sol-gel integrated tin oxide thin films [J]. Sensors and Actuators B.1999.58:283-288.
[37]Ulmer H.,Mitrovies J. and Neotzel G.Odors and flavours identified with hybrid modular sensor systems [J]. Sensors and Actuators B.1997,43:24-33.
[38]Sayago L,Horrillo M C. and Getino J. Discrimination of grape juice and fermated wine using a tin oxide multisensor [J].Sensors and Actuators B.1999,57:249-254.
[39]Natale C D, macagnaro A. and Davide F. An electronic nose for food analysis [J]. Sensor and Actuators B.1991.44:521-526.
[40]Simon Haykin, Neural Networks, A comprehensive Foundation[M].Beijing:Tsinghua University Press,2001,2th Edition.
[41]Martin T.Hagan,Howard B. Demuth, Mark Beale. Neural Network Design [M]. Beijing: China Machine Press,2002.
[42]Fagging,F.,VLSI Implementation of Neural Networks,Tutorial Notes, International Joint Conference on Neural Networks[C],Seattle 1991.
[43]McCulloch W. C.,Pitts W.. Bulletin of Mathematical Biophysics,1943,5:115-113.
[44]Hebb D.O..The Organization of Behavior[M],John Wiley, New York,1949.
[45]Rosenbaltt F., Psychological Review.1958,65:386-408.
[46]Widrow B.,Hoff E.. IRE WESCON Convention Record. Part 4[J], Computers Man-Machine Systems.1960,96-104.
[47]Minkey M.,Papert S.. Perceptrons[M].MIT Press,1969.
[48]Hopfield J.,et al. Biological Cybernetics.1985,52:141-152.
[49]Rumelhart D. E.,et al. Parallel Data Processing[M].Cambridge:the MIT press 1989,1, Chapter 8:318-362.
[50]Hecht-hielsen R.Counter Propagation Networks[J].Applied Optics.1987,26:4979-4984.
[51]王孝涛.历代中药炮制法汇典(古代)[M].南昌：江西科学技术出版社,1986：336.
[52]Y.-T.Jin,S.-T.Tsai,T.-Y.Wong,et al.Dtudies on Promoting Activity of Taiwan Betel Quid Ingredients in Hamster Buccal Pouch Carcinogenesis[J].Oral Oncol, EurJ Cancer, 1996,32(5):343-346.
[53]W.Harvey,A.Scutt,S.Meghji,et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31 (1):45-49.
[54]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[55]G.A.R.Johnston, P.Krogsgaard-Larsen, A.Stephanson. Betel nut constituents as inhibitors of y-aminobutyric acid uptake[J].Nature,1975,(258):627-628.
[56]曾琪,李忠海,袁列江,等.槟榔生物碱的研究现状及展望[J]FOOD&MACHINERY,2006,22(6)：158-161.
[57]赵云霞,于蕾,季宇彬,等.槟榔的毒理研究进展[J].药品评价,2006,3(6)：158-161.
[58]Ching HL,Ruey HL,et al. Mutualinte actions among ingredients of betel quia in inducing genotoxicity on Chinese hamster ovary cells[J]. MutatR.es,1999(367):99.
[59]Anupam C,Shampa DE. Genotoxic efect of arecoline giveneither by the peritoneal or oral route in murine bone martowcels and the inuence of Nacetylcysteine [J]. CancerLett,1999(139):23-31.
[60]Wang CK,Peng CH. The mutagenicities of alkaloids and N-nitrosog-uvacoline from betel quid[J]. Mutat Res,1996(360):165-171.
[61]Chang BE,Liao MH,Kuo YP, et al. Developmental Toxicityof Arecoline,the Major Alkaloid in Betel Nuts,in ZebratlshEmbryos[J]. Birth Defects Research(Part A),2004(70):28-36.
[62]张春江,吕飞杰,陶海腾.槟榔活性成分及其功能作用的研究进展[J].中国食品与营养,2008,6：50-53.
[63]惠秋沙,孙立立.炮制对槟榔化学成分的影响[J].中成药,2007,9(29)：1331-1333.
[64]张林丽,陈国佩,韦风.槟榔不同.炮制品中槟榔碱含量的比较[J].中药材,2002,25(6)：404-405.
[65]黄敏琪.槟榔几种不同炮制品含量测定的研究[J]广西中医学院报,2000,3(17)：84.
[66]孙立立,惠秋莎,孙立靖,等.中药槟榔饮片炮制工艺研究[J].中成药,2000,22(5)：345-348.
[67]王广基.药物代谢动力学[M],北京：化学工业出版社,2005.
[68]Gallarate,M.;Carlotti,M.E.;Trotta,M.;Bovo.S.int.PHarm.1999,188,233.
[69]Midhat,V.;Sabira,H.;Fatima,S.;Amina,H.;Elvedina,V.;Ediba,H.Int. J.PHarm.2003,256,109.
[70]Seonggyun Shin,Santi R.Bhowmik.Thermal Kinetics of color changes in Pea Puree[J].J Food Engineering,1995:77-86.
[71]Ohlsson,T.Temperature dependence of sensory quality changes during thermal processine[J].J.Food Sci.,1980,45:836.
[72]Bhowmik,S.R,Shin,S.Thermal sterilization of conduction-heated foods in plastic cylindrical cans using a convective boundary condition[J].J.Food Sci.,1991,56(3):827-830.
[73]Garrett,E.R.J.Am.PHarm.Assoc.,1956,45:171.
[74]Gupte,S.M.,Francis,F.J.Effect of pH adjustment and high-temperature short-time processing on color and pigment retention in spinach puree[J].Food Technol.,18,1645.
[75]江觉民,杜薇,王春焰.蜜炙甘草烘法炮制的动力学研究[J].贵阳中医学院学报,1992,4(14)：58-60.
[76]黄学思,吴纯洁,贾晶等.中药炒制过程动力学研究的可行性分析[J].中国科技论文在线,www.paper.edu.cn,2009,2.
[77]周庆华,李秋红,曲丽莉,等.何首乌炮制动力学方程建立研究[J].中医药学报,2005,3(33)：7-9.
[78]倪依东,王建洪,王汝俊.槟榔的药理研究进展[J].中药新药与临床药理,2004,15(3)：224-225.
[79]蔡宝昌.中药炮制学[M].北京：中国中医药出版社,2008,110.
[80]黄玉林,王铭,张欣英,等.槟榔果中活性物质的研究进展[J].农产品加工学刊,2007,(7)：16-18.
[81]曾琪,李钟海,袁列江,等.槟榔生物碱的研究现状及展望[J].食品与机理,2006,6：158-160.
[82]吕圭源.药理学[M].北京：中国中医药出版社,2003.
[83]W.Harvey, A.Scutt, S.Meghji, et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31(1):45-49.
[84]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[85]Venkatesh S, Lipper RA:Role of the development scientist in compound lead selection and optimization[J]. J PHarm Sci 2000,89:145-154.
[86]Rodrigues AD, Lin JH:Screening of drug candidates for their drug-drug interaction potential[J]. Curr Opin Chem Biol 2001,5:396-401.
[87]Van de WateAeemd H, Smith DA, Beaumont K, Walker DK:Property-based design: optimization of drug absorption and PHafmacokinetics[J]. J Med Chem 2001,44:1313-1333.
[88]Lipinski CA:Drug-like properties and the causes of poor solubility and poor permeability[J]. J PHarm Tox Methods 2000,44:235-249.
[89]Lipinski CA, Lombardo F, Dominy BW, Feeney PJ:Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J].Adv Drug Delivery Rev 2001,46:3-26.
[90]Avdeef A:PHysicochemical profiling (solubility, permeability and charge state)[J]. Curr Topics Med Chem 2001,1:277-351.
[91]Masimirembwa CM, Thompson R, Andersson TB:In vitro high throughput screening of compounds for favorable metabolic properties in drug discovery[J]. Comb Chem High Throughput Screen 2001,4:245-263.
[92]Janiszewski JS, Rogers KJ, Whalen KM, Cole MJ, Liston TE,Duchoslav E, Fouda HG:A high-capacity LC/MS system for the bioanalysis of samples generated from plate-based metabolic screening[J]. Anal Chem 2001,73:1495-1501.
[93]Clark DE:Computational methods for the prediction of ADME and toxicity[J]. Adv Drug Deliv Rev 2002,54:253-254.
[94]Han van de Waterbeemd and Eric Gifford.ADMET in silico modelling:towards prediction paradise?[J].Nature,2003,2:192-204. Walter J.Moore.Basic PHysical Chemistry[M].Prentice-Hall,INC.,1983,218-221.
[95]Leeson LJ and Mattocks AM. Decomposition of aspirin in the solid state[J]. J Am PHarm Assoc Sci Ed,1958,47(5):329.
[96]Prout EG and Tompkins FC. The thermal decomposition of potassium permanganate. Trans Faraday Soc[J],1944,40:488.
[97]Yoshioka S,Shibazaki T and Ejima A. Stability of solid dosage form s. I. Hydrolysis of meclofenoxate hydrochloride in the solid state. Chem PHarm Bull[J],1982,30(10):3734.
[98]Y.-T.Jin, S.-T.Tsai, T.-Y.Wong,et al.Dtudies on Promoting Activity of Taiwan Betel Quid Ingredients in Hamster Buccal Pouch. Carcinogenesis[J].Oral Oncol, EurJ Cancer, 1996,32(5):343-346.
[99]GA.R.Johnston, P.Krogsgaard-Larsen, A.StePHanson. Betel nut constituents as inhibitors of γ-aminobutyric acid uptake[J].Nature,1975,(258):627-628.
[100]W.Harvey, A.Scutt, S.Meghji, et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31(1):45-49.
[101]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[102]D.K.Holdsworth, R.A.Jones and R.Self. Volatile Alkaloids from Areca Catechu[J]. PHytochemistry,1998,48(3):581-582.
[103]John A.Dean. Lange's Handbook of Chemistry[M]. McGRAW-HILL,INC.1999.
[1]邹洁明,王力生.中药炮制的现状浅析[J].中成药,2005,4(36)：620-622.
[2]袁俊贤,邵依因,仵培坚.酒炙黄芪炮制工艺的研究[J]中成药.1994,16(2)：22.
[3]刘玉东.银花炭的最佳炮制温度探讨[J].山东中医杂志.1993,12(1)：43.
[4]崔学义,马英丽,孔琪,等.淫羊藿炮制工艺研究[J]中国中药杂志.1996,21(7)：408.
[5]张启伟,周钟鸣,阴健.温度对决明子化学成分和药理作用的影响[J].中国中药杂志.1996,21(11)：663.
[6]黄建东.浅谈清炒王不留行的火候选择[J].时珍国药研究.1996,7(5)：315.
[7]王桂英,田宇.硫熏法加工中药材的利弊浅析[J].华西药学杂志,1997,(12)4：262-263
[8]刘钟栋.食品添加剂原理及应用技术[M].中国轻工业出版社.2000,168-170.
[9]刘志敏.对《中国药典》1995年版一部硫磺熏法加工药材的看法[J].中国中药杂志,1997(22)7：412
[10]陈国盛.浅谈药材加工、保管中的硫磺熏制法[J].中药材,1998(21)11：571
[11]李宏宇,戴跃进,谢成科.中药白芷硫熏前后香豆素成分含量比较[J].中国中药杂志,1991,(16)：27.
[12]刘斌.中医系学生应开设《中药炮制学》课[J].中医教育.1999,13,(1)：46.
[2]汪新久,孟宪纾,王学农,等.山楂炮制品的工艺及质量研究[J].沈阳药学院学报,1993,10(4)：263.
[3]陈青莲,彭洁,艾卫涛.不同烘制温度对山楂有机酸含量及胃肠推进功能的影响[J].湖北中
医学院学报,2000,1(2)：46-48.
[4]陈青莲,江雪萍.山楂不同炮制品对小鼠胃排空作用的影响[J].中药材,2001,12(24)：887-889.
[5]蔡少芬,江海燕,欧艳萍.山楂不同炮制品有机酸含量测定[J].中成药,2000,12(22)：841-843.
[6]南云生,马春亮,王洪波.山楂炮制研究.中成药,1992,14(4)：765.
[7]张林丽,陈国佩,韦凤.槟榔不同炮制品中槟榔碱含量的比较[J].中药材,2002,6(25)：404-406.
[8]黄敏琪.槟榔几种不同炮制品含量测定的研究[J].广西中医学院报,2000,3(17)：84.
[9]惠秋沙,孙立立.炮制对槟榔化学成分的影响[J].中成药,2007,9(29)：1331-1333.
[10]孔祥田,孟凡鹏,张迎.“三仙”炒焦增效质疑[J].贵阳中医学院学报,1999,4(21)：50-51.
[11]王亚红.麦芽在临床应用说略[J].河南中医,2003,1(23)：60.
[12]薛玲,谭鹏,吕文海.莱菔子不同炮制品对消化系统作用及其急性毒性研究[J].山东中医药大学学报,2006,1(30)：74-75.
[13].黄春燕,吴纯洁,陈文文,等.中药炮制“火力”与“火候”研究现状及展望[J].世界科学技术-中医药现代化,2006,8(5)：73-75.
[14]陈楚明,吴纯洁,黄春燕,等.红外非接触测温在中药加工炮制中的应用[J].中国中药杂志.2005,30(7)：629.
[15]陈楚明,吴纯洁,黄学思,等.NOITM技术在中药炮制中的应用探讨[C].炮制会议论文集,2006.
[16]陈楚明,吴纯洁,黄春燕,等.在线式红外测温炒药机的构建[C].炮制会议论文集,2007.
[17]陈楚明,吴纯洁,孙灵根,等.中药饮片有关色泽客观量化表达的构建[J],世界科学技术—中医药现代化,2007,9(4)：2225.
[18]李文敏,吴纯洁,艾利,等.电子舌和电子鼻技术及其在中药炮制研究中应用的展望[C].炮制会议论文集,2007.
[19]张慧慧,吴纯洁,黄学思,等.“电子眼”在中药炮制中应用构想[C].炮制会议论文集,2007.
[20]李文敏,吴纯洁,艾利,等.基于电子鼻、电子舌技术实现中药性状气味客观化表达的构想[J].中国科技论文在线.2007.
[21]张利伟,付玉梅.不同炮制方法的山楂药材指纹特征[J].江西中医学院学报,2006,5(18)：47-48.
[22]龚千锋.中药炮制学[M].中国中医药出版社,2007.
[23]Frey,A.H.A, Review of the nature of odor perception and human response[J],Indoor Environ.2005.
[24]Gardner J.W, Bartlett P.N, A brief history of electronic nose[J],Sensors and Actuators,2004.
[25]Keller P.E, Kangas L.J etc., Electronic nose and their applications,Neural network application studies workshop in the IEEE orthicon, USA,1995.
[26]Craven M.A, Gardner J.W, Electronic nose development and future prospect[J],Trends in analytical chemistry,1996(21):486-493.
[27]Fengchun Tian,Simon X.Yang,and Kevin Dong, Circuit and Noise Analysis of Odorant Gas Sensors in an E-Nose[J],Sensors 2005(5):85-96.
[28]Hsin-Ti chneh, John V.hatfield, A real-time data acquisitions system for a hand-held electronic nose(H2EN)[J],Sensors and Actuators,2002(8):262-269.
[29]Pardo M,Sberveglieri G,Sisk B,Lewis N, Classifier comparison and sensor selection for
e-noses[J], Sensors,2003.
[30]Dutta R, Hines E. L. and Gardner J. W. Tea quality prediction using a tin oxide-based electronic nose:an artificial intelligence approach[J].Sensors and Actuators B,2003.94:228-237.
[31]Bhattacharvya N.. Seth s.. and Tudu B. Detection of optimum fermentation time for black tea manufacturing using electronic nose [J]. Sensors and Actuators B,2007,122:627-634.
[32]Vernat-Rossi V., Garcia C.and Talon R. Rapid discrimination of meat products and bacterial strains using semiconductor gas sensors. Sensors and Actuators B,2006,37:43-48.
[33]Rossi V., Garcia C. and Talon R. Rapid discrimination of meat products and bacterial strains using semiconductor gas sensors. Proceedings of Bioflavour 95. Dijon.2005,85-89.
[34]Moy L.,Vasic G and Berdague J.L. Transient signal modeling for fast odour classification. Proceedings of Bioflavour 95[J].Dijon.1995,55-58.
[35]Jonsson A.,Winquist F. and Schnurer J. Electronic nose for microbial quality classification of grains[J]. International journal of food microbiology,1997,35:187-193.
[36]Rella R.,Siciliano P. and Capone S. Air quality monitoring by mean of sol-gel integrated tin oxide thin films [J]. Sensors and Actuators B.1999.58:283-288.
[37]Ulmer H.,Mitrovies J. and Neotzel G.Odors and flavours identified with hybrid modular sensor systems [J]. Sensors and Actuators B.1997,43:24-33.
[38]Sayago L,Horrillo M C. and Getino J. Discrimination of grape juice and fermated wine using a tin oxide multisensor [J].Sensors and Actuators B.1999,57:249-254.
[39]Natale C D, macagnaro A. and Davide F. An electronic nose for food analysis [J]. Sensor and Actuators B.1991.44:521-526.
[40]Simon Haykin, Neural Networks, A comprehensive Foundation[M].Beijing:Tsinghua University Press,2001,2th Edition.
[41]Martin T.Hagan,Howard B. Demuth, Mark Beale. Neural Network Design [M]. Beijing: China Machine Press,2002.
[42]Fagging,F.,VLSI Implementation of Neural Networks,Tutorial Notes, International Joint Conference on Neural Networks[C],Seattle 1991.
[43]McCulloch W. C.,Pitts W.. Bulletin of Mathematical Biophysics,1943,5:115-113.
[44]Hebb D.O..The Organization of Behavior[M],John Wiley, New York,1949.
[45]Rosenbaltt F., Psychological Review.1958,65:386-408.
[46]Widrow B.,Hoff E.. IRE WESCON Convention Record. Part 4[J], Computers Man-Machine Systems.1960,96-104.
[47]Minkey M.,Papert S.. Perceptrons[M].MIT Press,1969.
[48]Hopfield J.,et al. Biological Cybernetics.1985,52:141-152.
[49]Rumelhart D. E.,et al. Parallel Data Processing[M].Cambridge:the MIT press 1989,1, Chapter 8:318-362.
[50]Hecht-hielsen R.Counter Propagation Networks[J].Applied Optics.1987,26:4979-4984.
[51]王孝涛.历代中药炮制法汇典(古代)[M].南昌：江西科学技术出版社,1986：336.
[52]Y.-T.Jin,S.-T.Tsai,T.-Y.Wong,et al.Dtudies on Promoting Activity of Taiwan Betel Quid Ingredients in Hamster Buccal Pouch Carcinogenesis[J].Oral Oncol, EurJ Cancer, 1996,32(5):343-346.
[53]W.Harvey,A.Scutt,S.Meghji,et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31 (1):45-49.
[54]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[55]G.A.R.Johnston, P.Krogsgaard-Larsen, A.Stephanson. Betel nut constituents as inhibitors of y-aminobutyric acid uptake[J].Nature,1975,(258):627-628.
[56]曾琪,李忠海,袁列江,等.槟榔生物碱的研究现状及展望[J]FOOD&MACHINERY,2006,22(6)：158-161.
[57]赵云霞,于蕾,季宇彬,等.槟榔的毒理研究进展[J].药品评价,2006,3(6)：158-161.
[58]Ching HL,Ruey HL,et al. Mutualinte actions among ingredients of betel quia in inducing genotoxicity on Chinese hamster ovary cells[J]. MutatR.es,1999(367):99.
[59]Anupam C,Shampa DE. Genotoxic efect of arecoline giveneither by the peritoneal or oral route in murine bone martowcels and the inuence of Nacetylcysteine [J]. CancerLett,1999(139):23-31.
[60]Wang CK,Peng CH. The mutagenicities of alkaloids and N-nitrosog-uvacoline from betel quid[J]. Mutat Res,1996(360):165-171.
[61]Chang BE,Liao MH,Kuo YP, et al. Developmental Toxicityof Arecoline,the Major Alkaloid in Betel Nuts,in ZebratlshEmbryos[J]. Birth Defects Research(Part A),2004(70):28-36.
[62]张春江,吕飞杰,陶海腾.槟榔活性成分及其功能作用的研究进展[J].中国食品与营养,2008,6：50-53.
[63]惠秋沙,孙立立.炮制对槟榔化学成分的影响[J].中成药,2007,9(29)：1331-1333.
[64]张林丽,陈国佩,韦风.槟榔不同.炮制品中槟榔碱含量的比较[J].中药材,2002,25(6)：404-405.
[65]黄敏琪.槟榔几种不同炮制品含量测定的研究[J]广西中医学院报,2000,3(17)：84.
[66]孙立立,惠秋莎,孙立靖,等.中药槟榔饮片炮制工艺研究[J].中成药,2000,22(5)：345-348.
[67]王广基.药物代谢动力学[M],北京：化学工业出版社,2005.
[68]Gallarate,M.;Carlotti,M.E.;Trotta,M.;Bovo.S.int.PHarm.1999,188,233.
[69]Midhat,V.;Sabira,H.;Fatima,S.;Amina,H.;Elvedina,V.;Ediba,H.Int. J.PHarm.2003,256,109.
[70]Seonggyun Shin,Santi R.Bhowmik.Thermal Kinetics of color changes in Pea Puree[J].J Food Engineering,1995:77-86.
[71]Ohlsson,T.Temperature dependence of sensory quality changes during thermal processine[J].J.Food Sci.,1980,45:836.
[72]Bhowmik,S.R,Shin,S.Thermal sterilization of conduction-heated foods in plastic cylindrical cans using a convective boundary condition[J].J.Food Sci.,1991,56(3):827-830.
[73]Garrett,E.R.J.Am.PHarm.Assoc.,1956,45:171.
[74]Gupte,S.M.,Francis,F.J.Effect of pH adjustment and high-temperature short-time processing on color and pigment retention in spinach puree[J].Food Technol.,18,1645.
[75]江觉民,杜薇,王春焰.蜜炙甘草烘法炮制的动力学研究[J].贵阳中医学院学报,1992,4(14)：58-60.
[76]黄学思,吴纯洁,贾晶等.中药炒制过程动力学研究的可行性分析[J].中国科技论文在线,www.paper.edu.cn,2009,2.
[77]周庆华,李秋红,曲丽莉,等.何首乌炮制动力学方程建立研究[J].中医药学报,2005,3(33)：7-9.
[78]倪依东,王建洪,王汝俊.槟榔的药理研究进展[J].中药新药与临床药理,2004,15(3)：224-225.
[79]蔡宝昌.中药炮制学[M].北京：中国中医药出版社,2008,110.
[80]黄玉林,王铭,张欣英,等.槟榔果中活性物质的研究进展[J].农产品加工学刊,2007,(7)：16-18.
[81]曾琪,李钟海,袁列江,等.槟榔生物碱的研究现状及展望[J].食品与机理,2006,6：158-160.
[82]吕圭源.药理学[M].北京：中国中医药出版社,2003.
[83]W.Harvey, A.Scutt, S.Meghji, et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31(1):45-49.
[84]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[85]Venkatesh S, Lipper RA:Role of the development scientist in compound lead selection and optimization[J]. J PHarm Sci 2000,89:145-154.
[86]Rodrigues AD, Lin JH:Screening of drug candidates for their drug-drug interaction potential[J]. Curr Opin Chem Biol 2001,5:396-401.
[87]Van de WateAeemd H, Smith DA, Beaumont K, Walker DK:Property-based design: optimization of drug absorption and PHafmacokinetics[J]. J Med Chem 2001,44:1313-1333.
[88]Lipinski CA:Drug-like properties and the causes of poor solubility and poor permeability[J]. J PHarm Tox Methods 2000,44:235-249.
[89]Lipinski CA, Lombardo F, Dominy BW, Feeney PJ:Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings[J].Adv Drug Delivery Rev 2001,46:3-26.
[90]Avdeef A:PHysicochemical profiling (solubility, permeability and charge state)[J]. Curr Topics Med Chem 2001,1:277-351.
[91]Masimirembwa CM, Thompson R, Andersson TB:In vitro high throughput screening of compounds for favorable metabolic properties in drug discovery[J]. Comb Chem High Throughput Screen 2001,4:245-263.
[92]Janiszewski JS, Rogers KJ, Whalen KM, Cole MJ, Liston TE,Duchoslav E, Fouda HG:A high-capacity LC/MS system for the bioanalysis of samples generated from plate-based metabolic screening[J]. Anal Chem 2001,73:1495-1501.
[93]Clark DE:Computational methods for the prediction of ADME and toxicity[J]. Adv Drug Deliv Rev 2002,54:253-254.
[94]Han van de Waterbeemd and Eric Gifford.ADMET in silico modelling:towards prediction paradise?[J].Nature,2003,2:192-204. Walter J.Moore.Basic PHysical Chemistry[M].Prentice-Hall,INC.,1983,218-221.
[95]Leeson LJ and Mattocks AM. Decomposition of aspirin in the solid state[J]. J Am PHarm Assoc Sci Ed,1958,47(5):329.
[96]Prout EG and Tompkins FC. The thermal decomposition of potassium permanganate. Trans Faraday Soc[J],1944,40:488.
[97]Yoshioka S,Shibazaki T and Ejima A. Stability of solid dosage form s. I. Hydrolysis of meclofenoxate hydrochloride in the solid state. Chem PHarm Bull[J],1982,30(10):3734.
[98]Y.-T.Jin, S.-T.Tsai, T.-Y.Wong,et al.Dtudies on Promoting Activity of Taiwan Betel Quid Ingredients in Hamster Buccal Pouch. Carcinogenesis[J].Oral Oncol, EurJ Cancer, 1996,32(5):343-346.
[99]GA.R.Johnston, P.Krogsgaard-Larsen, A.StePHanson. Betel nut constituents as inhibitors of γ-aminobutyric acid uptake[J].Nature,1975,(258):627-628.
[100]W.Harvey, A.Scutt, S.Meghji, et al.Stimulation of Human Buccal Mucosa Fibroblasts in vitro by Betel-nut Alkaloids[J]. Arechs oral Biol,1986,31(1):45-49.
[101]E.Boyland and R.Nery.Mercapturic Acid Formation During the Metabolism of Arecoline and Arecaidine in the Rat[J].Biochem.J.,1969,113:123-130.
[102]D.K.Holdsworth, R.A.Jones and R.Self. Volatile Alkaloids from Areca Catechu[J]. PHytochemistry,1998,48(3):581-582.
[103]John A.Dean. Lange's Handbook of Chemistry[M]. McGRAW-HILL,INC.1999.
[1]邹洁明,王力生.中药炮制的现状浅析[J].中成药,2005,4(36)：620-622.
[2]袁俊贤,邵依因,仵培坚.酒炙黄芪炮制工艺的研究[J]中成药.1994,16(2)：22.
[3]刘玉东.银花炭的最佳炮制温度探讨[J].山东中医杂志.1993,12(1)：43.
[4]崔学义,马英丽,孔琪,等.淫羊藿炮制工艺研究[J]中国中药杂志.1996,21(7)：408.
[5]张启伟,周钟鸣,阴健.温度对决明子化学成分和药理作用的影响[J].中国中药杂志.1996,21(11)：663.
[6]黄建东.浅谈清炒王不留行的火候选择[J].时珍国药研究.1996,7(5)：315.
[7]王桂英,田宇.硫熏法加工中药材的利弊浅析[J].华西药学杂志,1997,(12)4：262-263
[8]刘钟栋.食品添加剂原理及应用技术[M].中国轻工业出版社.2000,168-170.
[9]刘志敏.对《中国药典》1995年版一部硫磺熏法加工药材的看法[J].中国中药杂志,1997(22)7：412
[10]陈国盛.浅谈药材加工、保管中的硫磺熏制法[J].中药材,1998(21)11：571
[11]李宏宇,戴跃进,谢成科.中药白芷硫熏前后香豆素成分含量比较[J].中国中药杂志,1991,(16)：27.
[12]刘斌.中医系学生应开设《中药炮制学》课[J].中医教育.1999,13,(1)：46.