中草药中黄酮类化合物的分离分析
|
摘要
中草药中提取的黄酮类化合物对人类的肿瘤、衰老、心血管病等疾病的治疗和预防有重要的意义，并具有有良好的市场前景。黄酮类化合物是植物代谢过程中产生的一类重要天然有机化合物。特别是近30年来黄酮类化合物一直是国内外研究开发利用的热点，仍是寻找有开发应用前景的先导化合物和生物活性成分的源泉。
本论文以甘草黄酮、葛根异黄酮和银杏黄酮甙为研究对象，对它们的提取方法进行了比较研究及实验优化，进一步对其提取干膏进行了分离分析。另外，还利用定量构谱关系（QSSR）和定量构效关系（QSAR）对黄酮类化合物的核磁共振波谱（13CNMR）进行模拟，并估计和预测其核磁共振的化学位移。并对黄酮类化合物作为酪氨酸抑制剂的pIC50进行了定量分子建模研究。其主要内容和研究结果简要叙述如下：
1．微波辅助提取新工艺提取甘草黄酮、葛根黄酮和银杏黄酮甙。研究和发展了微波辅助提取新工艺和新方法提取甘草黄酮、葛根异黄酮和银杏黄酮甙，并进行了均匀设计、正交设计和中心组合设计实验优化，对实验结果进行了统计分析或直观分析，得到其最优条件下的提取率成倍高于常规的提取法，纯度也得到了大幅度提高，同时大大缩短了提取时间，说明该法显著节省了资源和能源。
2．黄酮类化合物的结构表达及核磁共振碳谱模拟。提出以原子电性距离矢量(VAED)描述19种黄酮醇和21种黄酮中不同等价碳原子的化学微环境，结合碳原子类型，建立核磁共振碳谱(13C NMR)化学位移(CS)的定量构谱关系（QSSR）四参数线性模型, 对于19种黄酮醇285个碳原子其相关系数R=0.796，交互检验R=0.789；对于21种黄酮315个碳原子其相关系数R=0.884，交互检验R=0.880；黄酮醇和黄酮一起建模600个碳原子其相关系数R=0.831，交互检验R=0.828。并综合几种处理方法，找到一种较好的建模方法，作为首次有益的探讨，对黄酮和黄酮醇核磁共振碳谱建模效果尚好。
3．黄酮类化合物作为P56lck蛋白质酪氨酸激酶抑制剂的定量构效关系(QSAR)的研究。提出分子电性距离矢量考察了104个黄酮类化合物分子结构的表征，利用多元线性回归技术，对其生物活性pIC50构建定量线性相关模型，其相关系数R= 0.726，交互检验RCV2=0.427。其结果与状态、拓扑、几何、静电和量化这5组共504种描述子的建模结果相比，结果虽不是最好，但还是比较好，说明我们实验室提出分子电性距离矢量有比较广的普适性。
Extraction off flavonoids from Chinese traditional and herbal drugs was of important significance to cure, treat and prevent tumour, senescence and cardiovascular diseases, which had fairly good market prospect at present. Flavonoids that are important and natural organic compounds were produced during plants metabolization, which has been the potential source of the search of lead biologically active compounds and has also been the emphasis of the research, development and ultilization at home and aboard in the recent 30 years.
In this thesis, flavonoids were extracted from Glycyrrhiza , Pueraria lobata (Willd.) Ohwi and Ginkgo biloba L by several conventional extraction ways and microwave-assisted extraction(MAE) through experimental design and optimization and the flavonoid extracts were further separated and analyzed by chromatography and spectrophotometry. On the other hand, the chemical shift of carbon-13 nuclear magnetic resonance of flavonoids was estimated and predicted through moleculat modeling of quantitative structure-spectrum relationship (QSSR) by the novel atomic electronegative distance vector (AEDV); and molecular modeling for 104 flavonoid derivatives as p56lck protein tyrosine kinase (PTK) inhibitors were quantitatively performed by the new molecular electronegative distance vector (MEDV). The main contents and some conclusions are provided as follows:
1.Glycyrrliza flavonoids, Pueraria lobata (Willd.) Ohwi flavonoids and Ginkgo biloba L flavonoids were extracted by the microwave technique through homogeous / uniform design, the orthogonal experimental design or central composite design. The results indicated that the extraction rate of MAE under the optimal condition obtained through the experiments design was remarkably higher than the one of traditional extraction, the extraction time of MAE was greatly shorten and the purity of flavonoids was obviously enhanced as well..
2.Various chemical shifts of 13CNMR for different chemically equivalent carbon atoms in nineteen natural flavonols and twenty-one natural flavones were estimated and /or predicted by using the novel atomic electronegative distance vector (VAED) with 4 elements parameter: The sample numbers n, correlation coefficients R, standard deviation SD, F-statistic value F, regression quadratic sum and residual quadratic sum.being n= 285, R=0.796, SD=14.734, F=162.315, U=105705.359, Q=60999.156; n= 315, R=0.884,
SD=12.381, F=369.114, U=169745.141, Q=47673.375; N= 600，R=0.831, SD=14.122, F=443.449, U=265310.563 and Q=118859.906, for 19 flavonols, 21 flavones, and all 40 flavonoids, respectively. Finally, cross validation with the leave-one-out (LOO) procedure was made by the QSSR equations for all carbon atoms, with the good results obtained. A relatively reliable correlation model has been developed by the atomic electronegative distance vector, as adjoin structural descriptors. The modeling results were fairly good, but this is preliminary approach to estimation and prediction of chemical shift of carbon-13 nuclear magnetic resonance spectroscopy in flavonoids.
3.Quantitative structure-activity relationship (QSAR) studies on 104 flavonoid derivatives as the p56lck protein tyrosine kinase (PTK) inhibitors were performed, using the newly developed molecular electronegative distance vector(VMED). Multiple linear regression(MLR) and leave-one-out cross validation were applied to generate models to predict of biological activities for binding flavonoids to PTK. The result obtained was compared with modeling results of 504 descriptors that were divided into five groups: constitutional, topological, geometric, electrostatic and quantum-chemical, which was not the best but fairly good. It illustrated that the molecular electronegative distance vector(VMED) could be widely applied, especially.
本论文以甘草黄酮、葛根异黄酮和银杏黄酮甙为研究对象，对它们的提取方法进行了比较研究及实验优化，进一步对其提取干膏进行了分离分析。另外，还利用定量构谱关系（QSSR）和定量构效关系（QSAR）对黄酮类化合物的核磁共振波谱（13CNMR）进行模拟，并估计和预测其核磁共振的化学位移。并对黄酮类化合物作为酪氨酸抑制剂的pIC50进行了定量分子建模研究。其主要内容和研究结果简要叙述如下：
1．微波辅助提取新工艺提取甘草黄酮、葛根黄酮和银杏黄酮甙。研究和发展了微波辅助提取新工艺和新方法提取甘草黄酮、葛根异黄酮和银杏黄酮甙，并进行了均匀设计、正交设计和中心组合设计实验优化，对实验结果进行了统计分析或直观分析，得到其最优条件下的提取率成倍高于常规的提取法，纯度也得到了大幅度提高，同时大大缩短了提取时间，说明该法显著节省了资源和能源。
2．黄酮类化合物的结构表达及核磁共振碳谱模拟。提出以原子电性距离矢量(VAED)描述19种黄酮醇和21种黄酮中不同等价碳原子的化学微环境，结合碳原子类型，建立核磁共振碳谱(13C NMR)化学位移(CS)的定量构谱关系（QSSR）四参数线性模型, 对于19种黄酮醇285个碳原子其相关系数R=0.796，交互检验R=0.789；对于21种黄酮315个碳原子其相关系数R=0.884，交互检验R=0.880；黄酮醇和黄酮一起建模600个碳原子其相关系数R=0.831，交互检验R=0.828。并综合几种处理方法，找到一种较好的建模方法，作为首次有益的探讨，对黄酮和黄酮醇核磁共振碳谱建模效果尚好。
3．黄酮类化合物作为P56lck蛋白质酪氨酸激酶抑制剂的定量构效关系(QSAR)的研究。提出分子电性距离矢量考察了104个黄酮类化合物分子结构的表征，利用多元线性回归技术，对其生物活性pIC50构建定量线性相关模型，其相关系数R= 0.726，交互检验RCV2=0.427。其结果与状态、拓扑、几何、静电和量化这5组共504种描述子的建模结果相比，结果虽不是最好，但还是比较好，说明我们实验室提出分子电性距离矢量有比较广的普适性。
Extraction off flavonoids from Chinese traditional and herbal drugs was of important significance to cure, treat and prevent tumour, senescence and cardiovascular diseases, which had fairly good market prospect at present. Flavonoids that are important and natural organic compounds were produced during plants metabolization, which has been the potential source of the search of lead biologically active compounds and has also been the emphasis of the research, development and ultilization at home and aboard in the recent 30 years.
In this thesis, flavonoids were extracted from Glycyrrhiza , Pueraria lobata (Willd.) Ohwi and Ginkgo biloba L by several conventional extraction ways and microwave-assisted extraction(MAE) through experimental design and optimization and the flavonoid extracts were further separated and analyzed by chromatography and spectrophotometry. On the other hand, the chemical shift of carbon-13 nuclear magnetic resonance of flavonoids was estimated and predicted through moleculat modeling of quantitative structure-spectrum relationship (QSSR) by the novel atomic electronegative distance vector (AEDV); and molecular modeling for 104 flavonoid derivatives as p56lck protein tyrosine kinase (PTK) inhibitors were quantitatively performed by the new molecular electronegative distance vector (MEDV). The main contents and some conclusions are provided as follows:
1.Glycyrrliza flavonoids, Pueraria lobata (Willd.) Ohwi flavonoids and Ginkgo biloba L flavonoids were extracted by the microwave technique through homogeous / uniform design, the orthogonal experimental design or central composite design. The results indicated that the extraction rate of MAE under the optimal condition obtained through the experiments design was remarkably higher than the one of traditional extraction, the extraction time of MAE was greatly shorten and the purity of flavonoids was obviously enhanced as well..
2.Various chemical shifts of 13CNMR for different chemically equivalent carbon atoms in nineteen natural flavonols and twenty-one natural flavones were estimated and /or predicted by using the novel atomic electronegative distance vector (VAED) with 4 elements parameter: The sample numbers n, correlation coefficients R, standard deviation SD, F-statistic value F, regression quadratic sum and residual quadratic sum.being n= 285, R=0.796, SD=14.734, F=162.315, U=105705.359, Q=60999.156; n= 315, R=0.884,
SD=12.381, F=369.114, U=169745.141, Q=47673.375; N= 600，R=0.831, SD=14.122, F=443.449, U=265310.563 and Q=118859.906, for 19 flavonols, 21 flavones, and all 40 flavonoids, respectively. Finally, cross validation with the leave-one-out (LOO) procedure was made by the QSSR equations for all carbon atoms, with the good results obtained. A relatively reliable correlation model has been developed by the atomic electronegative distance vector, as adjoin structural descriptors. The modeling results were fairly good, but this is preliminary approach to estimation and prediction of chemical shift of carbon-13 nuclear magnetic resonance spectroscopy in flavonoids.
3.Quantitative structure-activity relationship (QSAR) studies on 104 flavonoid derivatives as the p56lck protein tyrosine kinase (PTK) inhibitors were performed, using the newly developed molecular electronegative distance vector(VMED). Multiple linear regression(MLR) and leave-one-out cross validation were applied to generate models to predict of biological activities for binding flavonoids to PTK. The result obtained was compared with modeling results of 504 descriptors that were divided into five groups: constitutional, topological, geometric, electrostatic and quantum-chemical, which was not the best but fairly good. It illustrated that the molecular electronegative distance vector(VMED) could be widely applied, especially.
引文
[1] 北京医学院.北京中医学院主编.中草药成分化学.北京:人民卫生出版社.1981.287~292
[2] 姚新生主编.天然药物化学.第二版.北京:人民卫生出版社.1996.191~193.194~195
[3] [日] 米达夫著.植物化学.北京:科学出版社.1985.108~131
[4] Kinoshita T,Firman K.Myricetin 5,7,3',4',5'-pentamethyl ether and other methylated flavonoids from Murraya Paniculata. Phytochemistry. 1997. 45(1):179~181
[5] 孙朋悦,徐颖,文晔,裴玉萍,陈英杰,清水训子,竹田忠泓.朝鲜淫羊藿的化学成分(I).中国药物化学杂志.1998.8(2):122~126
[6] D Agostino M,DE Simone F,Dini A et al.Isolation of 8,3'-Dihydroxy-5,7,4'-Trimethoxy-4-phenyl coumarin from Coutarea hexandra. J Nat Prod.. 990.52(1):161~162
[7] 刘诗平.槲皮素及其衍生物的生物活性研究进展.中草药.1991.22(4):182~184
[8] 张鞍灵,高锦明,王姝清.黄酮类化合物的分布及开发利用.西北林学院学报.2000.15(1):69~74
[9] 郭孝武.一种提取中草药化学成分的方法-超声提取法.天然产物与开发.1999.11(3):37~40
[10] 杨景亮. 中医药工程研究与应用.北京:中国中医药出版社.1992:145~146
[11] 杨景亮.北京:首届中医药工程国际学术论文集. 1992:11~15
[12] 赵兵,王玉春，欧阳藩,伍志春.超声波在植物提取中的应用.中草药.1999.30(9):附1~附3
[13] Brannegan DR, Ashraf-Khorassani M, Taylor L T. Supercritical fluid extraction of ethoxyquin from a beef matrix. Chromatographia. 2001.54(5-6):399~401
[14] Mincher BJ, Fox RV, Holmes RGG, Robbins RA, Boardman C. Supercritical fluid extraction of plutonium and americium from soil using thenoyltrifluoroacetone and tributylphosphate complexation. Radiochimica acta. 2001.89(10):613~617
[15] 李先春,王敦清.超临界二氧化碳流体萃取草珊瑚的工艺研究.天然产物研究与开发.1998.10(4):64~67
[16] 葛发欢,辉国均,李菁,张宝恩,关世欢.中药现代化与超临界流体萃取的应用.天然产物研究与开发.2000.12(3):88~93
[17] 姜继祖,叶开润,廖周坤.超临界CO2流体萃取光菇子中秋水仙碱的研究.中草药.1997.28(3):143~149
[18] 刘锦耀,赵建平,张先俊.从云南小粒啡豆中萃取咖啡因.色谱.1995.13(5):342~345
[19] 李军,冯耀生.超临界CO2萃取茶多酚的研究.天然产物研究与开发.1996.8(3):39~47
[20] 葛发欢.超临界流体萃取法从黄花蒿中提取青蒿素的新工艺.发明专利.ZL 93106143.1
[21] 葛发欢.超临界流体萃取法从薯蓣属植物中提取薯蓣皂素的新工艺.发明专利.98113267.7
[22] J.R.Jocelyn Pare, Jacqueline M.R.Belanger, Sally S. Stafford. Microwave-Assisted Process (MAPTM)a :a new tool for the analytical laboratory. Trends in Analytical Chemistry.1994.13(4):176~184
[23] 黄量,于德泉.紫外光谱在有机化学中的应用.下册.北京:科学出版社.1988.205~207
[24] J.B.Harborne, T.J.Mabry and Helge Mabry编,戴伦凯,谢玉如译.黄酮类化合物. 北京:科学出版社.1983.88~95
[25] Meyer H, Zur Theorie der Alkonarkose I. Welche Eigenschaft der Anaextheticabedingt ihre narkotische Wirkung, Archiv fur Experimentess Pathlolgie und Pharmakologie. 1899.42:109~118
[26] Overton C, Osmotic Properties of Cells in the Bearing on Toxicology and Pharmacy, Zeitxdhrigt fur Physikalisch Chemie. 1897.22:189~209
[27] Ferguson J, The Use of Chemical Potentials as Indices of Toxicity, Proceedings of the Roval Society ser. B..1939. 127: 487~503
[28] Hansch C, Muir M, Fujita T. The Correlation of Biological Activity of Plant Growth Regulators and Chloromycetin Derivatives with Hammett Constants and Partition Coefficients. J, Am. Chem. Soc.. 1963.85:2817~2824
[29] 王连生,韩朔睽等.分子结构、性质与活性.北京:化学工业出版社.1997:155~162
[30] 朱杰,季海涛,张万年.进化算法在定量构效关系研究中的应用.中国药物化学杂志.1999.9(2): 151~156
[31] 张晓晨,周家驹,谢桂荣. 改进的人工神经网络算法在定量构效关系中的应用,计算机与应用化学.1995.12(4):248~254
[32] 张大仁,赵立新.遗传算法对QSAR研究中变量选择的应用.环境科学.2000.19(3):209~213
[33] Miyashita Y, Li ZL, Sasaki S. Chemical pattern recognition and multivariate analysis for QSAR studies. Trend Anal. Chem. TrAC. 1993.12(12): 50~60
[34] 熊国华,邹世春,张展霞.环境分析试样预处理的新方法—微波萃取法.环境科学进展.1997.5(5):58~61
[35] Akhtar, M. Humayoun, Wong, Meeling, Crooks, Steven R. H. ;Sauve Andre.Extraction of incurred sulfamethazine in swine tissue by microwave assisted extraction and quantification without clean up by high performance liquid chromatography following derivatization with dimethylaminozaldehyde. Food Addit. contam. 1998.15(5):542~549
[36] Pare, J. R. Jocelyn, Matni, Gisele, Eelanger Jacqueline M. R. ,Li.Ken, Rule Cari, Thibert Benoit, Yaylayan Varoujan, Liu zhun, Mathe Daniel, Jacquaunt Patrik. Use of the Microwave-Asisted Process in extraction of from meat, dairy and egg products under atmospheric pressure conditions. J. AOAC Int.. 1997.80(4):928~933
[37] Lopez-Avila Viiorica; Young Richard; Benedicto Janet; Ho Pauline; Kim Robert; Beckert Werner F. Extraction of organic Pollutants from Solid Samples Using Microwave Energy. Anal. Chem.. 1995.67(13):2096~2102
[38] Onuska Francis I. Microwave extraction in analytical of pollutants.Polychlorinated biphenyls J. High Resolut Chromatogr..1995.18(7):417~421
[39] Weichbrodt M., Vetter W., Luckas B. Microwave-Assisted Extraction for determination of PCBs(Polychlorinated biphenyls) and chlorine pesticides from fish fat.
Lebensmittelehenie. 1999.53(5):132~141
[40] Dupeyron Stephane, Dadermel Pierre-Michel, Couturier Daniel, Guarini Philippe, Delattre Jean-Marie. Extraxtion of polucuclic aromatic hydrocarbons from soils. Int. J. Environ. Anal. Chem.. 1999.73(3):191~210
[41] Onuska F. I., Terry K. A. Extraction of pesticides from sediments using a microwave technique. Chromatographia. 1993.36:191~194
[42] K. I. Mahan, T. L. Garaz et al. Microwave Digestion Techniques in the Sequential Extraction of Calcium, Iron,Chromiun, Manganese, Lead, and Zinc in Sediments. Anal. Chem..1987.59:938~945
[43] G. Schnitzer, A. Soubelet et al. Comparsion of Open and Closed Microwave Digestion in View of Total Mercury Determination by Cold Vapour Atomic Absorption Spectrometry. Mikrochim. Axta. 1995.119:199~209
[44] Kovacs Agnes; Ganzler Katalin; Simon-Sarkadi Livia. Microwave-Assisted Extraction of free amino acids from foods. I. Lebensm-Unters Forsch. A 1998.207(1):26~30
[45] Zhang Zhanxia, Xiong Guohua, Lie Gongke, He Xiaoqing. Sample pretreatment with microwave-assisted techniques. Anal. Sci.. 2000.16(2):221~224
[46] 陈金传.微波能在医药工业中的应用.中草药.2001.32(9):附1~附2
[47] 南京中药厂,江苏新医学院药学系72年级专题实习组.微波辐射在中药生产中的应用.中草药通讯.1976.7(2):17~18
[48] 林翠英,周晶,赵晶,李辉.芦丁超声提取新技术的再探索.中草药.1999.30(5):350~351
[49] 张代佳,刘传斌,修志龙,昌增益.微波技术在植物胞内有效成分提取中的应用.中草药.2000.31(9):附5~附6
[50] 陈猛,袁东星,许鹏翔.微波萃取法研究进展.分析测试学报.1999.18(2):81~86
[51] Safir O., Fkih-Tetouani S., Soufiaoui M., Bougrin K., Aquino R.. Microwaave extraction of the aerial parts of Iygophyllum gaetulum. Riv. Ital. Eppos. 1998.25:3~10
[52] Pan Xuejun, Liu Huizhou, Jia Guanghe, Shu Younyuen. Microwave -assisted extraction of glycyrrhizic acid from licorice root. Biochem. Eng. J. 2000.5(3):173~177
[53] Carro N., Garcia C. M., Cela R.. Optimization and Comparision of two microwave-assisted extraction procedures of terpenic compounds in Vitis Vinifera must samples. Spectroscopy.1997.13(1):61~70
[54] Mattina M. J. Incorvia, Berger W. A. Iannuci, Denson C. L..Microwave-Assisted Extraction of Tazanes from Taxus Biomass. J. Agric. Food Chem. 1997.45(12):4691~4696
[55] Viorica Lopez-Avila, Janet Benedicto. Microwave-assisted extraction combined with gas ghromatogra-phy and enzyme-linked immynosorbent assay. Trends in Analytical Chemistry. 1996.15(8):334~341
[56] 李嵘,金美芳.微波法提取银杏黄酮甙的新工艺.食品科学.2000.21(2):39~42
[57] 王威,刘传斌,修志龙.高山红景天苷提取新工艺.中草药.1999.30(11):824~826
[58] Vioria Lopez-Avila, Rechard Yong and Wernerf F. Bechet. Microwave-Assisted Extraction of Organic Compounds from Standard reference Soils and Sediments. Anal. Chem. 1994.66:1097~1106
[59] Ian J.Barnabas, John R. Dean, Ian A. Fowlis and Susan P. Owen. Extraction of polycyclic aromatic hydrocarbons from highly contaminated soils using microwave energy. Analyst.1995.120:1897~1905
[60] 陈翠莲,袁东星,陈猛. 微波萃取预混合饲料中的维生素A、D和E及与其它几种提取法的比较.分析科学学报.1990.15(1):36~38
[61] Lopez-Arila Viorica, Young Richard, Teplitsky Nataky. Microwave-assisted extraction as an alternati-ve to Soxhlet, Sonication and Supeicritical fluid extraction. J. AOAC Int. 1996.79(1):142~156
[62] 贾国惠,贾世山.甘草中黄酮的药理作用研究进展.中国中药杂志.1998.33(9):513~515
[63] 《中国药典》1990年版(一部) .415~415
[64] 胡金锋,沈凤嘉.甘草在医药等方面的深度开发及综合利用.中草药.1995.6(1):39~44
[65] 方开泰.均匀设计表.北京:科学出版社.1994:101~105
[66] 孙秀梅,黄树明,王英姿.甘草SBE法与WE法的成分比较.中国中药杂志.1999.24(9):542~544
[67] Molpeceres J, Gtzman M, Aberturas MR, ea. Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement. J Pharm. Sci. 1996.85(2):206~213
[68] Mcleod AD, Lam FC, Gupta PK, et al. Optimized synthesis of polyglutaraldehyde nanoparticles using central composite design. J Pharm. Sci. 1988.77(8):704~710
[69] Abu-lzza KA,Garcia-contreras L, Lu DR, ea. Preparation and evaluation of sustained release AZT-loaded microspheres 1.Optimization of the release characteristics using response surface methodology. J Pharm. Sci. 1996.85(2):144~149
[70] Abu-lzza KA,Garcia-contreras L, Lu DR, ea. Preparation and evaluation of sustained release AZT-loaded microspheres 2.Optimization of the release characteristics using response surface methodology. J Pharm. Sci. 1996.85(6):572~578
[71] Lu B, Wu W. Optimization of preparation of dexamethasone acetate-loaded poly (D,L-lactide) micrcopheres by central composite design. Acta Pharm Sin (in Chinese).1999.34(5):387~391
[72] 宋洪杰,曾明,胡晋红,王大业,张汉明.葛属植物中3种异黄酮成分分析.药物分析杂志.2000.20(4):223~225
[73] 梅全喜,毕焕新. 现代中药药理手册. 北京: 中国中医药出版社.1998:52~53
[74] 刘松林,薛芳芳.葛根素治疗冠心病117例临床分析.湖南中医学院学报.1999.19(4):47~48
[75] 李琰,范璐,孙秀华.葛根提取工艺的考察.北京中医药大学学报.2001.24(4):26~27
[76] 郭建平,孙其荣,周全,赵彤英,高玉田.葛根总黄酮不同提取工艺的探讨.中草药.1995.26(10):537~539
[77] 邵立波,郑文德,何艳贞.葛根中黄酮类化合物的提取.林业科学研究.1996.9(4):400~402
[78] 李石生,邓京振,刘欣,赵守训.野葛藤茎的异黄酮类化学成分.天然产物研究与开发.1999.11(1):31~32
[79] 赵浩如,郜凤香.葛根总黄酮的提取方法研究.中成药.2000.22(11):756~757
[80] 江苏新医学院.中药大辞典:上册.上海:上海科学技术出版社.1986.724~725
[81] 中国科学院中国植物志编辑委员会.中国植物志.北京:科学出版社.1978.18~21
[82] 梁立兴.银杏叶的开发利用及研究进展.世界林业研究.1996.(3):44~51
[83] Bars PLL, Katz MM, Berman N. A placebocontrolled, double-blind, randomized, trial of an extract of Ginkgo biloba for dementia. J Am Med Assoc(Chin Ed).1997.278:1327
[84] 王静,吴晶.银杏叶提取物对老年冠心病患者血液流变学的影响.长春中医学院学报..2001.17(1):11~11
[85] 王成章,郁青,陈祥,谭卫红,沈兆邦.银杏叶黄酮甙浸提工艺的研究.天然产物与开发.1998. 10(2):66~70
[86] 庄向平,虞杏英,杨更生,方涌强.银杏叶中黄酮含量的测定和提取方法.中草药.1992.23(3):122~124
[87] 洪山海.光谱解析法在有机化学中的应用.第二版.北京:科学出版社,1981:97~98
[88] G.D.Christian, J.E. O'Reilly. 王镇浦,王镇棣译.北京:北京大学出版社.1986:176~178
[89] Bergeron R J, Channing M A, Giberly G J, Pillor D M. Disposition requirements for binding in aqueous solution of polar subatrates in the cyclohexaamylose. J. Am. Chem. Soc. 1977.99(15):5146~5151
[90] Schneider H J, Hacket F, Rudiger V, Ikeda H. NMR Studies of Cyclodextrins and cyclodextrin complexes. Chem Rev. 1998.98(5):1755~1785
[91] Naunenko,V. N, Koren, A. O, Gaponik, P.N. Nitrogen-15NMR study of tetrazoles. Magn. Reson. Chem. 1992.30(6):558~559
[92] 刘树深,曹晨忠,余般梅,宫下芳胜,村松由起,李志良.核磁共振碳谱的研究:烷烃分子的化学位移δ与原子分子距边矢量μvλ,原子与分子物理学报.1997.14:606~614
[93] 曹晨忠,刘超,刘树深,李志良.原 子距边矢量,三键数与烷烃的13CNMR化学位移.波谱学杂志.1998.15:347~353
[94] 刘树深,曹晨忠,李志良.Investigation of Carbon-13 nuclear magnetic resonance spectra-structure correlation based on novel atomic distance-edge (ADE) vector. Chin. J. Chem.. 1998.16(2): 126~137
[95] 刘树深,夏之宁,余般梅,李志良,无环醇原子电距矢量及核磁共振碳谱化学位移模拟.波谱学杂志.1999.16(5):429~440
[96] Martin Y C. Qyantitative Drug Design: A Critical Introduction. Dekker: New York. 1978:145~147
[97] 徐文昭.月季花瓣的黄酮类成分的研究.南京中医药学学报.2000.16(4):225~226
[98] 程卫强,隋长惠，袁久志,张红.羽叶千里光黄酮类成分的研究.中草
药.1999.30(10):727~729
[99] 谢忱,徐丽珍,赵保华,杨世林.细梗香草化学成分的研究.中草药.2000.31(2):81~83
[100] 刘银燕,刘丽娟,杨晓虹.分薜葱头化学成分的研究.中草药.2000.31(5):333~334
[101] 成军,赵玉英,崔育新,程铁明.杜仲叶黄酮类化合物的研究.中国中药杂志.2000.25(5):284~285
[102] 邓芹英,丁从梅,张维汉,林永成.艾纳香中黄酮化合物的研究,波谱学杂志.1996.13(5):447~452
[103] 陈凤庭,陆江海,陈祺聪,郭金清,钟世舟,颜星中,祝亚非.厚果鸡血藤化学成分的研究(Ⅰ).中草药.1999.30(1):3~5
[104] 陆江海,曾静星,邝柱庭,陈凤庭.厚果鸡血藤化学成分的研究(Ⅱ).中草药.1999.30(10):721~723
[105] 李石生,Iliya Ⅰ A,邓京振,赵守训.黄独中的黄酮和蒽醌类化学成分的研究.中国中药杂志.2000.25(3):159~160
[106] 张卫东,陈万生,王永红,刘文庸,孔德云,李惠庭.灯战花黄酮类化学成分的研究.中国中药杂志.2000.25(9):536~537
[107] 潘燕.乌拉尔甘草中虎耳草甙的分离和鉴定.中国中药杂志.1999.24(5):295~295
[108] 邵伟艳,祝亚非,关山越,钟世舟,陈凤庭.厚果鸡血藤的化学成分研究.天然产物研究与开发.2001.13(1):1~4
[109] 宣春生,赵晓红,冯福盛,乔本志.山西甘草化学成分的研究.天然产物研究开发.2000.12(2):18~22
[110] 李波,赵映梅,林中文,孙汉董.多舌飞蓬化学成分的研究.中草药.1999.30(8):561~562
[111] 华会明,孙军,李铣.柳穿鱼黄酮成分的研究.中草药.1999.30(5):332~334
[112] 刘延泽,王荩卿,谢兰,贺存恒,谢晶曦.天葵化学成分的研究Ⅰ.天葵苷的结构.中草药.1999.30(1):5~7
[113] 凌云,何板,鲍燕燕,郭秀芳,郑俊华.浮萍的化学成分研究.中草药.1999.30(2):88~89
[114] 周立新,丁怡.水蜡树化学成分的研究.中国中药杂志.2000.25(9):541~543
[115] 杜江,邹永明,张更生.四方蒿中黄酮甙的分离和鉴定.中国中药杂志.1999.24(2)96~98
[116] 陈四保,王立为,高光耀,廖矛川,肖培根.尖萼耧斗菜中黄酮类成分的研究.中国中药杂志.1999.24(3):158~160
[117] 罗晓东,吴少华,马云保,吴大刚.椿叶的化学成分研究.中草药.2001.32(5): 391~393
[118] 苏艳芳,刘建生,果德安,李菁,郭洪祝,郑俊华.金龙胆草黄酮类成分的研究.中草药.2001.32(6):496~497
[119] 官智,潭颂德,苏镜娱,曾陇梅.云南木多木衣黄酮成分研究.天然产物研究与开发.2000.12(3):34~37
[120] 田军,孙汉堇.长管假茉莉的化学成分.天然产物研究与开发.1999.11(3):1~4
[121] 何红平,刘复初.秋水仙花的化学成分.天然产物研究与开发.2000.12(1):12~13
[122] Hunter, T. Protein Modification; Phosphorylation on Tyrosine Residues. Curr. Opin. Cell
Biol.. 1989.1.1168~1181
[123] Ullrich, A., Schlessinger, J. Singal Transduction by Receptors with Tyrosine Kinase Activity. Cell. 1990.61.203~212
[124] Bishop, J. M. The Molecular Genetics of Cancer. Science.1987.235.305~311
[125] Levitzki, A., Gazit, A. Tyrosine Kinase Inhibition, An Approach to Drug Development. Science. 1995.267.1782~1788
[126] Burke, R. T. Protein-Tyrosine Kinase Inhibitors. Drugs Future. 1992.17.119~131
[127] Chang, C., Geahlen, L. R. Protein-Tyrosine Kinase Inhibition; Mechanism-Based Discovery of Antitumor Agents. J. Nat. Prod. 1992.55.1529~1560
[128] Groundwater, P. w.,Solomons, H. R. K., Drewe,A. J.,Munawar,A. M. Protein Tyrosine Kinase Inhibitors. Prog. Med. Chem. 1996.33.323~329
[129] Geahlen, L. R., Mclaughlin, J. L. Piceatannol(3,4,3',5'-tetrahydrocytrans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor.Biochem. Biophys. Res. Commun. 1989.165.241-245
[130] Geahlen, L. R.,Koonchanok, M. N., Mclaughlin, J. L., Patt, D. E. Inhibition of protein-tyrosine kinase activity by flavonoids and related compouds. J. Nat. Prod. 1989.52.982~986
[131] Cushman, M.,Nagarathnam, D.,Geahlen, L. R. Synthesis and Evaluation of Hydroxylated Flavones and Related Compounds as Potential Inhibitors of protein-tyrosine kinase p56. J.Nat.Pred. 1991.54.1345~1352
[132] Cushman, M.,Nagarathnam, D., Burg, L. D., Geahlen, L. R.Synthesis and protein-tyrosine kinase Inhibitory Activities of Flavonoid Analogues. J. Med. Chem. 1994.37.3353~3362
[133] Cushman, M.;Zhu, H.;Geahlen, L. R.;Kraker, J. A.Synthesis and Biochemical Evaluation of a Series of Aminoflavones as Potential Inhibitors of Tyrosine Protein Kinases and Serine / Threonine Protein Kinases p56,EGFr,p60. J.Med.Chem. 1994.37.3353~3362
[134] Hagiwara, M.,Inoue, S., Tanaka, T., Nunlki, K.;Ito, M.; Hidaka, H. Differential Effedts of Flavonoids as Inhibitors of Tyrosine Protein Kinases and Serine / Threonine Protein Kinases.Biochem.Pharmacol. 1988.37.2987~2992
[135] Akiyama, T.Ishida, J.,Nakagawa, S.,Ogawara, H.,Watanabc, S.,Itoh, N.,Shibuya, M.,Fukami, Y. Genistein, A Specific Inhibitor of Tyrosine-Specific Protein Kinases. J,Biol. Chem. 1987.262.5592~5595
[136] M. Oblak, M. Randic, T. Solmajer. Quantitative structure-activity relationship of flavonoid analogues. 3.Inhibition of p56lck protein tyrosine kinase. J. Chem. Inf. Comput. Sci. 2000.40:994~1001
[2] 姚新生主编.天然药物化学.第二版.北京:人民卫生出版社.1996.191~193.194~195
[3] [日] 米达夫著.植物化学.北京:科学出版社.1985.108~131
[4] Kinoshita T,Firman K.Myricetin 5,7,3',4',5'-pentamethyl ether and other methylated flavonoids from Murraya Paniculata. Phytochemistry. 1997. 45(1):179~181
[5] 孙朋悦,徐颖,文晔,裴玉萍,陈英杰,清水训子,竹田忠泓.朝鲜淫羊藿的化学成分(I).中国药物化学杂志.1998.8(2):122~126
[6] D Agostino M,DE Simone F,Dini A et al.Isolation of 8,3'-Dihydroxy-5,7,4'-Trimethoxy-4-phenyl coumarin from Coutarea hexandra. J Nat Prod.. 990.52(1):161~162
[7] 刘诗平.槲皮素及其衍生物的生物活性研究进展.中草药.1991.22(4):182~184
[8] 张鞍灵,高锦明,王姝清.黄酮类化合物的分布及开发利用.西北林学院学报.2000.15(1):69~74
[9] 郭孝武.一种提取中草药化学成分的方法-超声提取法.天然产物与开发.1999.11(3):37~40
[10] 杨景亮. 中医药工程研究与应用.北京:中国中医药出版社.1992:145~146
[11] 杨景亮.北京:首届中医药工程国际学术论文集. 1992:11~15
[12] 赵兵,王玉春，欧阳藩,伍志春.超声波在植物提取中的应用.中草药.1999.30(9):附1~附3
[13] Brannegan DR, Ashraf-Khorassani M, Taylor L T. Supercritical fluid extraction of ethoxyquin from a beef matrix. Chromatographia. 2001.54(5-6):399~401
[14] Mincher BJ, Fox RV, Holmes RGG, Robbins RA, Boardman C. Supercritical fluid extraction of plutonium and americium from soil using thenoyltrifluoroacetone and tributylphosphate complexation. Radiochimica acta. 2001.89(10):613~617
[15] 李先春,王敦清.超临界二氧化碳流体萃取草珊瑚的工艺研究.天然产物研究与开发.1998.10(4):64~67
[16] 葛发欢,辉国均,李菁,张宝恩,关世欢.中药现代化与超临界流体萃取的应用.天然产物研究与开发.2000.12(3):88~93
[17] 姜继祖,叶开润,廖周坤.超临界CO2流体萃取光菇子中秋水仙碱的研究.中草药.1997.28(3):143~149
[18] 刘锦耀,赵建平,张先俊.从云南小粒啡豆中萃取咖啡因.色谱.1995.13(5):342~345
[19] 李军,冯耀生.超临界CO2萃取茶多酚的研究.天然产物研究与开发.1996.8(3):39~47
[20] 葛发欢.超临界流体萃取法从黄花蒿中提取青蒿素的新工艺.发明专利.ZL 93106143.1
[21] 葛发欢.超临界流体萃取法从薯蓣属植物中提取薯蓣皂素的新工艺.发明专利.98113267.7
[22] J.R.Jocelyn Pare, Jacqueline M.R.Belanger, Sally S. Stafford. Microwave-Assisted Process (MAPTM)a :a new tool for the analytical laboratory. Trends in Analytical Chemistry.1994.13(4):176~184
[23] 黄量,于德泉.紫外光谱在有机化学中的应用.下册.北京:科学出版社.1988.205~207
[24] J.B.Harborne, T.J.Mabry and Helge Mabry编,戴伦凯,谢玉如译.黄酮类化合物. 北京:科学出版社.1983.88~95
[25] Meyer H, Zur Theorie der Alkonarkose I. Welche Eigenschaft der Anaextheticabedingt ihre narkotische Wirkung, Archiv fur Experimentess Pathlolgie und Pharmakologie. 1899.42:109~118
[26] Overton C, Osmotic Properties of Cells in the Bearing on Toxicology and Pharmacy, Zeitxdhrigt fur Physikalisch Chemie. 1897.22:189~209
[27] Ferguson J, The Use of Chemical Potentials as Indices of Toxicity, Proceedings of the Roval Society ser. B..1939. 127: 487~503
[28] Hansch C, Muir M, Fujita T. The Correlation of Biological Activity of Plant Growth Regulators and Chloromycetin Derivatives with Hammett Constants and Partition Coefficients. J, Am. Chem. Soc.. 1963.85:2817~2824
[29] 王连生,韩朔睽等.分子结构、性质与活性.北京:化学工业出版社.1997:155~162
[30] 朱杰,季海涛,张万年.进化算法在定量构效关系研究中的应用.中国药物化学杂志.1999.9(2): 151~156
[31] 张晓晨,周家驹,谢桂荣. 改进的人工神经网络算法在定量构效关系中的应用,计算机与应用化学.1995.12(4):248~254
[32] 张大仁,赵立新.遗传算法对QSAR研究中变量选择的应用.环境科学.2000.19(3):209~213
[33] Miyashita Y, Li ZL, Sasaki S. Chemical pattern recognition and multivariate analysis for QSAR studies. Trend Anal. Chem. TrAC. 1993.12(12): 50~60
[34] 熊国华,邹世春,张展霞.环境分析试样预处理的新方法—微波萃取法.环境科学进展.1997.5(5):58~61
[35] Akhtar, M. Humayoun, Wong, Meeling, Crooks, Steven R. H. ;Sauve Andre.Extraction of incurred sulfamethazine in swine tissue by microwave assisted extraction and quantification without clean up by high performance liquid chromatography following derivatization with dimethylaminozaldehyde. Food Addit. contam. 1998.15(5):542~549
[36] Pare, J. R. Jocelyn, Matni, Gisele, Eelanger Jacqueline M. R. ,Li.Ken, Rule Cari, Thibert Benoit, Yaylayan Varoujan, Liu zhun, Mathe Daniel, Jacquaunt Patrik. Use of the Microwave-Asisted Process in extraction of from meat, dairy and egg products under atmospheric pressure conditions. J. AOAC Int.. 1997.80(4):928~933
[37] Lopez-Avila Viiorica; Young Richard; Benedicto Janet; Ho Pauline; Kim Robert; Beckert Werner F. Extraction of organic Pollutants from Solid Samples Using Microwave Energy. Anal. Chem.. 1995.67(13):2096~2102
[38] Onuska Francis I. Microwave extraction in analytical of pollutants.Polychlorinated biphenyls J. High Resolut Chromatogr..1995.18(7):417~421
[39] Weichbrodt M., Vetter W., Luckas B. Microwave-Assisted Extraction for determination of PCBs(Polychlorinated biphenyls) and chlorine pesticides from fish fat.
Lebensmittelehenie. 1999.53(5):132~141
[40] Dupeyron Stephane, Dadermel Pierre-Michel, Couturier Daniel, Guarini Philippe, Delattre Jean-Marie. Extraxtion of polucuclic aromatic hydrocarbons from soils. Int. J. Environ. Anal. Chem.. 1999.73(3):191~210
[41] Onuska F. I., Terry K. A. Extraction of pesticides from sediments using a microwave technique. Chromatographia. 1993.36:191~194
[42] K. I. Mahan, T. L. Garaz et al. Microwave Digestion Techniques in the Sequential Extraction of Calcium, Iron,Chromiun, Manganese, Lead, and Zinc in Sediments. Anal. Chem..1987.59:938~945
[43] G. Schnitzer, A. Soubelet et al. Comparsion of Open and Closed Microwave Digestion in View of Total Mercury Determination by Cold Vapour Atomic Absorption Spectrometry. Mikrochim. Axta. 1995.119:199~209
[44] Kovacs Agnes; Ganzler Katalin; Simon-Sarkadi Livia. Microwave-Assisted Extraction of free amino acids from foods. I. Lebensm-Unters Forsch. A 1998.207(1):26~30
[45] Zhang Zhanxia, Xiong Guohua, Lie Gongke, He Xiaoqing. Sample pretreatment with microwave-assisted techniques. Anal. Sci.. 2000.16(2):221~224
[46] 陈金传.微波能在医药工业中的应用.中草药.2001.32(9):附1~附2
[47] 南京中药厂,江苏新医学院药学系72年级专题实习组.微波辐射在中药生产中的应用.中草药通讯.1976.7(2):17~18
[48] 林翠英,周晶,赵晶,李辉.芦丁超声提取新技术的再探索.中草药.1999.30(5):350~351
[49] 张代佳,刘传斌,修志龙,昌增益.微波技术在植物胞内有效成分提取中的应用.中草药.2000.31(9):附5~附6
[50] 陈猛,袁东星,许鹏翔.微波萃取法研究进展.分析测试学报.1999.18(2):81~86
[51] Safir O., Fkih-Tetouani S., Soufiaoui M., Bougrin K., Aquino R.. Microwaave extraction of the aerial parts of Iygophyllum gaetulum. Riv. Ital. Eppos. 1998.25:3~10
[52] Pan Xuejun, Liu Huizhou, Jia Guanghe, Shu Younyuen. Microwave -assisted extraction of glycyrrhizic acid from licorice root. Biochem. Eng. J. 2000.5(3):173~177
[53] Carro N., Garcia C. M., Cela R.. Optimization and Comparision of two microwave-assisted extraction procedures of terpenic compounds in Vitis Vinifera must samples. Spectroscopy.1997.13(1):61~70
[54] Mattina M. J. Incorvia, Berger W. A. Iannuci, Denson C. L..Microwave-Assisted Extraction of Tazanes from Taxus Biomass. J. Agric. Food Chem. 1997.45(12):4691~4696
[55] Viorica Lopez-Avila, Janet Benedicto. Microwave-assisted extraction combined with gas ghromatogra-phy and enzyme-linked immynosorbent assay. Trends in Analytical Chemistry. 1996.15(8):334~341
[56] 李嵘,金美芳.微波法提取银杏黄酮甙的新工艺.食品科学.2000.21(2):39~42
[57] 王威,刘传斌,修志龙.高山红景天苷提取新工艺.中草药.1999.30(11):824~826
[58] Vioria Lopez-Avila, Rechard Yong and Wernerf F. Bechet. Microwave-Assisted Extraction of Organic Compounds from Standard reference Soils and Sediments. Anal. Chem. 1994.66:1097~1106
[59] Ian J.Barnabas, John R. Dean, Ian A. Fowlis and Susan P. Owen. Extraction of polycyclic aromatic hydrocarbons from highly contaminated soils using microwave energy. Analyst.1995.120:1897~1905
[60] 陈翠莲,袁东星,陈猛. 微波萃取预混合饲料中的维生素A、D和E及与其它几种提取法的比较.分析科学学报.1990.15(1):36~38
[61] Lopez-Arila Viorica, Young Richard, Teplitsky Nataky. Microwave-assisted extraction as an alternati-ve to Soxhlet, Sonication and Supeicritical fluid extraction. J. AOAC Int. 1996.79(1):142~156
[62] 贾国惠,贾世山.甘草中黄酮的药理作用研究进展.中国中药杂志.1998.33(9):513~515
[63] 《中国药典》1990年版(一部) .415~415
[64] 胡金锋,沈凤嘉.甘草在医药等方面的深度开发及综合利用.中草药.1995.6(1):39~44
[65] 方开泰.均匀设计表.北京:科学出版社.1994:101~105
[66] 孙秀梅,黄树明,王英姿.甘草SBE法与WE法的成分比较.中国中药杂志.1999.24(9):542~544
[67] Molpeceres J, Gtzman M, Aberturas MR, ea. Application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement. J Pharm. Sci. 1996.85(2):206~213
[68] Mcleod AD, Lam FC, Gupta PK, et al. Optimized synthesis of polyglutaraldehyde nanoparticles using central composite design. J Pharm. Sci. 1988.77(8):704~710
[69] Abu-lzza KA,Garcia-contreras L, Lu DR, ea. Preparation and evaluation of sustained release AZT-loaded microspheres 1.Optimization of the release characteristics using response surface methodology. J Pharm. Sci. 1996.85(2):144~149
[70] Abu-lzza KA,Garcia-contreras L, Lu DR, ea. Preparation and evaluation of sustained release AZT-loaded microspheres 2.Optimization of the release characteristics using response surface methodology. J Pharm. Sci. 1996.85(6):572~578
[71] Lu B, Wu W. Optimization of preparation of dexamethasone acetate-loaded poly (D,L-lactide) micrcopheres by central composite design. Acta Pharm Sin (in Chinese).1999.34(5):387~391
[72] 宋洪杰,曾明,胡晋红,王大业,张汉明.葛属植物中3种异黄酮成分分析.药物分析杂志.2000.20(4):223~225
[73] 梅全喜,毕焕新. 现代中药药理手册. 北京: 中国中医药出版社.1998:52~53
[74] 刘松林,薛芳芳.葛根素治疗冠心病117例临床分析.湖南中医学院学报.1999.19(4):47~48
[75] 李琰,范璐,孙秀华.葛根提取工艺的考察.北京中医药大学学报.2001.24(4):26~27
[76] 郭建平,孙其荣,周全,赵彤英,高玉田.葛根总黄酮不同提取工艺的探讨.中草药.1995.26(10):537~539
[77] 邵立波,郑文德,何艳贞.葛根中黄酮类化合物的提取.林业科学研究.1996.9(4):400~402
[78] 李石生,邓京振,刘欣,赵守训.野葛藤茎的异黄酮类化学成分.天然产物研究与开发.1999.11(1):31~32
[79] 赵浩如,郜凤香.葛根总黄酮的提取方法研究.中成药.2000.22(11):756~757
[80] 江苏新医学院.中药大辞典:上册.上海:上海科学技术出版社.1986.724~725
[81] 中国科学院中国植物志编辑委员会.中国植物志.北京:科学出版社.1978.18~21
[82] 梁立兴.银杏叶的开发利用及研究进展.世界林业研究.1996.(3):44~51
[83] Bars PLL, Katz MM, Berman N. A placebocontrolled, double-blind, randomized, trial of an extract of Ginkgo biloba for dementia. J Am Med Assoc(Chin Ed).1997.278:1327
[84] 王静,吴晶.银杏叶提取物对老年冠心病患者血液流变学的影响.长春中医学院学报..2001.17(1):11~11
[85] 王成章,郁青,陈祥,谭卫红,沈兆邦.银杏叶黄酮甙浸提工艺的研究.天然产物与开发.1998. 10(2):66~70
[86] 庄向平,虞杏英,杨更生,方涌强.银杏叶中黄酮含量的测定和提取方法.中草药.1992.23(3):122~124
[87] 洪山海.光谱解析法在有机化学中的应用.第二版.北京:科学出版社,1981:97~98
[88] G.D.Christian, J.E. O'Reilly. 王镇浦,王镇棣译.北京:北京大学出版社.1986:176~178
[89] Bergeron R J, Channing M A, Giberly G J, Pillor D M. Disposition requirements for binding in aqueous solution of polar subatrates in the cyclohexaamylose. J. Am. Chem. Soc. 1977.99(15):5146~5151
[90] Schneider H J, Hacket F, Rudiger V, Ikeda H. NMR Studies of Cyclodextrins and cyclodextrin complexes. Chem Rev. 1998.98(5):1755~1785
[91] Naunenko,V. N, Koren, A. O, Gaponik, P.N. Nitrogen-15NMR study of tetrazoles. Magn. Reson. Chem. 1992.30(6):558~559
[92] 刘树深,曹晨忠,余般梅,宫下芳胜,村松由起,李志良.核磁共振碳谱的研究:烷烃分子的化学位移δ与原子分子距边矢量μvλ,原子与分子物理学报.1997.14:606~614
[93] 曹晨忠,刘超,刘树深,李志良.原 子距边矢量,三键数与烷烃的13CNMR化学位移.波谱学杂志.1998.15:347~353
[94] 刘树深,曹晨忠,李志良.Investigation of Carbon-13 nuclear magnetic resonance spectra-structure correlation based on novel atomic distance-edge (ADE) vector. Chin. J. Chem.. 1998.16(2): 126~137
[95] 刘树深,夏之宁,余般梅,李志良,无环醇原子电距矢量及核磁共振碳谱化学位移模拟.波谱学杂志.1999.16(5):429~440
[96] Martin Y C. Qyantitative Drug Design: A Critical Introduction. Dekker: New York. 1978:145~147
[97] 徐文昭.月季花瓣的黄酮类成分的研究.南京中医药学学报.2000.16(4):225~226
[98] 程卫强,隋长惠，袁久志,张红.羽叶千里光黄酮类成分的研究.中草
药.1999.30(10):727~729
[99] 谢忱,徐丽珍,赵保华,杨世林.细梗香草化学成分的研究.中草药.2000.31(2):81~83
[100] 刘银燕,刘丽娟,杨晓虹.分薜葱头化学成分的研究.中草药.2000.31(5):333~334
[101] 成军,赵玉英,崔育新,程铁明.杜仲叶黄酮类化合物的研究.中国中药杂志.2000.25(5):284~285
[102] 邓芹英,丁从梅,张维汉,林永成.艾纳香中黄酮化合物的研究,波谱学杂志.1996.13(5):447~452
[103] 陈凤庭,陆江海,陈祺聪,郭金清,钟世舟,颜星中,祝亚非.厚果鸡血藤化学成分的研究(Ⅰ).中草药.1999.30(1):3~5
[104] 陆江海,曾静星,邝柱庭,陈凤庭.厚果鸡血藤化学成分的研究(Ⅱ).中草药.1999.30(10):721~723
[105] 李石生,Iliya Ⅰ A,邓京振,赵守训.黄独中的黄酮和蒽醌类化学成分的研究.中国中药杂志.2000.25(3):159~160
[106] 张卫东,陈万生,王永红,刘文庸,孔德云,李惠庭.灯战花黄酮类化学成分的研究.中国中药杂志.2000.25(9):536~537
[107] 潘燕.乌拉尔甘草中虎耳草甙的分离和鉴定.中国中药杂志.1999.24(5):295~295
[108] 邵伟艳,祝亚非,关山越,钟世舟,陈凤庭.厚果鸡血藤的化学成分研究.天然产物研究与开发.2001.13(1):1~4
[109] 宣春生,赵晓红,冯福盛,乔本志.山西甘草化学成分的研究.天然产物研究开发.2000.12(2):18~22
[110] 李波,赵映梅,林中文,孙汉董.多舌飞蓬化学成分的研究.中草药.1999.30(8):561~562
[111] 华会明,孙军,李铣.柳穿鱼黄酮成分的研究.中草药.1999.30(5):332~334
[112] 刘延泽,王荩卿,谢兰,贺存恒,谢晶曦.天葵化学成分的研究Ⅰ.天葵苷的结构.中草药.1999.30(1):5~7
[113] 凌云,何板,鲍燕燕,郭秀芳,郑俊华.浮萍的化学成分研究.中草药.1999.30(2):88~89
[114] 周立新,丁怡.水蜡树化学成分的研究.中国中药杂志.2000.25(9):541~543
[115] 杜江,邹永明,张更生.四方蒿中黄酮甙的分离和鉴定.中国中药杂志.1999.24(2)96~98
[116] 陈四保,王立为,高光耀,廖矛川,肖培根.尖萼耧斗菜中黄酮类成分的研究.中国中药杂志.1999.24(3):158~160
[117] 罗晓东,吴少华,马云保,吴大刚.椿叶的化学成分研究.中草药.2001.32(5): 391~393
[118] 苏艳芳,刘建生,果德安,李菁,郭洪祝,郑俊华.金龙胆草黄酮类成分的研究.中草药.2001.32(6):496~497
[119] 官智,潭颂德,苏镜娱,曾陇梅.云南木多木衣黄酮成分研究.天然产物研究与开发.2000.12(3):34~37
[120] 田军,孙汉堇.长管假茉莉的化学成分.天然产物研究与开发.1999.11(3):1~4
[121] 何红平,刘复初.秋水仙花的化学成分.天然产物研究与开发.2000.12(1):12~13
[122] Hunter, T. Protein Modification; Phosphorylation on Tyrosine Residues. Curr. Opin. Cell
Biol.. 1989.1.1168~1181
[123] Ullrich, A., Schlessinger, J. Singal Transduction by Receptors with Tyrosine Kinase Activity. Cell. 1990.61.203~212
[124] Bishop, J. M. The Molecular Genetics of Cancer. Science.1987.235.305~311
[125] Levitzki, A., Gazit, A. Tyrosine Kinase Inhibition, An Approach to Drug Development. Science. 1995.267.1782~1788
[126] Burke, R. T. Protein-Tyrosine Kinase Inhibitors. Drugs Future. 1992.17.119~131
[127] Chang, C., Geahlen, L. R. Protein-Tyrosine Kinase Inhibition; Mechanism-Based Discovery of Antitumor Agents. J. Nat. Prod. 1992.55.1529~1560
[128] Groundwater, P. w.,Solomons, H. R. K., Drewe,A. J.,Munawar,A. M. Protein Tyrosine Kinase Inhibitors. Prog. Med. Chem. 1996.33.323~329
[129] Geahlen, L. R., Mclaughlin, J. L. Piceatannol(3,4,3',5'-tetrahydrocytrans-stilbene) is a naturally occurring protein-tyrosine kinase inhibitor.Biochem. Biophys. Res. Commun. 1989.165.241-245
[130] Geahlen, L. R.,Koonchanok, M. N., Mclaughlin, J. L., Patt, D. E. Inhibition of protein-tyrosine kinase activity by flavonoids and related compouds. J. Nat. Prod. 1989.52.982~986
[131] Cushman, M.,Nagarathnam, D.,Geahlen, L. R. Synthesis and Evaluation of Hydroxylated Flavones and Related Compounds as Potential Inhibitors of protein-tyrosine kinase p56. J.Nat.Pred. 1991.54.1345~1352
[132] Cushman, M.,Nagarathnam, D., Burg, L. D., Geahlen, L. R.Synthesis and protein-tyrosine kinase Inhibitory Activities of Flavonoid Analogues. J. Med. Chem. 1994.37.3353~3362
[133] Cushman, M.;Zhu, H.;Geahlen, L. R.;Kraker, J. A.Synthesis and Biochemical Evaluation of a Series of Aminoflavones as Potential Inhibitors of Tyrosine Protein Kinases and Serine / Threonine Protein Kinases p56,EGFr,p60. J.Med.Chem. 1994.37.3353~3362
[134] Hagiwara, M.,Inoue, S., Tanaka, T., Nunlki, K.;Ito, M.; Hidaka, H. Differential Effedts of Flavonoids as Inhibitors of Tyrosine Protein Kinases and Serine / Threonine Protein Kinases.Biochem.Pharmacol. 1988.37.2987~2992
[135] Akiyama, T.Ishida, J.,Nakagawa, S.,Ogawara, H.,Watanabc, S.,Itoh, N.,Shibuya, M.,Fukami, Y. Genistein, A Specific Inhibitor of Tyrosine-Specific Protein Kinases. J,Biol. Chem. 1987.262.5592~5595
[136] M. Oblak, M. Randic, T. Solmajer. Quantitative structure-activity relationship of flavonoid analogues. 3.Inhibition of p56lck protein tyrosine kinase. J. Chem. Inf. Comput. Sci. 2000.40:994~1001