雷公藤有效成分的制备分离及优化分离方法的建立
|
摘要
本文首先以近年来国内外天然产物研究取得的成果为例，概述了天然产物化学在研究策略与方向、资源保护、分离技术、生物与化学合成等主要领域的研究现状，并对雷公藤提取制备方法、检测技术等方面的研究现状加以综述。
研究了几种天然产物有效成分如生物碱类化合物、萜内酯类化合物、糖类化合物及甙类化合物的提取制备工艺。建立了雷公藤内酯醇、雷公藤内酯酮等二萜内酯类化合物柱色谱制备分离方法；建立了雷公藤生物碱类化合物如雷公藤次碱、雷公藤定碱的柱色谱制备分离方法。
建立了雷公藤二萜内酯类化合物高效毛细管电泳优化分离分析方法。考察了此方法的回收率、精密度、线性和检测限，讨论了缓冲溶液的组成中，硼砂及磷酸二氢钠的浓度、表面活性剂的浓度和pH值等因素对分离的影响，其优化分离的缓冲溶液组成为10mM磷酸二氢钠20mM硼砂加入20mM SDS，pH值为8.62，采用此方法分离雷公藤二萜内酯类化合物，可得到较好的分离效果。
建立了中成药雷公藤多甙片有效成分高效毛细管电泳优化分离分析方法。在熔融硅胶毛细管(60.2cm有效柱长52.6cm，内径为75μm)柱上，施加20kV电压，温度298K，进样时间5s，214nm紫外检测，缓冲体系包括10 mM硼砂中加入20 mM十二烷基硫酸钠(SDS)作表面活性剂，用硼酸调节pH=7.30。优化分离条件下有效成分可达基线分离，有良好的线性关系，方法简便快速。
建立了雷公藤生物碱类化合物非水相毛细管电泳优化分离分析方法。优化条件是：操作电压15kV，温度保持301K，进样时间5s，运行介质为20mM醋酸铵和3mM氨水加到甲醇媒介中。实验结果证明此方法是可行的。
建立了手性药物佐米曲坦毛细管电泳优化分离分析方法，其优化分离的缓冲溶液组成为84mM Tris—H_3PO_4中加入30 mM磺化—β—环糊精作手性拆分剂，pH=4.10；分离通道为未涂层熔硅弹性石英毛细管，内径50μm，柱长60cm，有效柱长52cm；分离条件是温度298K，运行电压为18kV，紫外检测波长设在214nm，进样时间为5s。
Based on the current achievement on natural product, a general review of
natural product chemistry and its application on investigation protocol, resources
protection, analysis technology, biology and chemistry synthesis was made. Further
more, this review also covers the preparation and detection of Tripterygium \vilfordii.
First, several extraction and preparation technologies of the alkaloid compounds, the diterpenoid triepoxides compounds and the saccharide compounds were studied. Two column chromatography methods for the separation wilforine and wilfordine , the triptolide and triptonide were developed, respectively.
Second, a micellar electrokinetic capillary chromatography (MEKC) method has been established for the identification and determination of diterpenoid triepoxides in Chinese herb Tripterygium wilfordii Hook F and its preparations. The detailed investigations of the influence of SDS concentration, pH, boric acidand borax concentration were carried out. From the experiments, the MEKC was found to exhibit good accuracy, precision and repeatability.
A capillary electrophoresis method has been established for the determination of triptonide and triptolide in Multi-glycosides Tripterygium wilfordii tablets. Capillary separation was carried out by using 0.01mol L-1 borax + + 0.02mol L-1 SDS (pH =7.3) as the buffer, 20kV applied voltage and 301K temperature.
A method for the separation of wilforine and wilfordine in Tripterygium wilfordii Hook F based on nonaqueous capillary eletrophoresis has been developed. The optimum separation conditions are as follows: voltage 15kV, the temperature was kept at 301K and the running medium consisted of 20mM ammonium acetate and 3mM ammonium hydroxide in methanol. The feasibility of this method was demonstrated by the determination of wilforine and wilfordine in Tripterygium wilfordii Hook F.
A capillary electrophoresis method has been established for the zolmitriptan of chiral drug.
研究了几种天然产物有效成分如生物碱类化合物、萜内酯类化合物、糖类化合物及甙类化合物的提取制备工艺。建立了雷公藤内酯醇、雷公藤内酯酮等二萜内酯类化合物柱色谱制备分离方法；建立了雷公藤生物碱类化合物如雷公藤次碱、雷公藤定碱的柱色谱制备分离方法。
建立了雷公藤二萜内酯类化合物高效毛细管电泳优化分离分析方法。考察了此方法的回收率、精密度、线性和检测限，讨论了缓冲溶液的组成中，硼砂及磷酸二氢钠的浓度、表面活性剂的浓度和pH值等因素对分离的影响，其优化分离的缓冲溶液组成为10mM磷酸二氢钠20mM硼砂加入20mM SDS，pH值为8.62，采用此方法分离雷公藤二萜内酯类化合物，可得到较好的分离效果。
建立了中成药雷公藤多甙片有效成分高效毛细管电泳优化分离分析方法。在熔融硅胶毛细管(60.2cm有效柱长52.6cm，内径为75μm)柱上，施加20kV电压，温度298K，进样时间5s，214nm紫外检测，缓冲体系包括10 mM硼砂中加入20 mM十二烷基硫酸钠(SDS)作表面活性剂，用硼酸调节pH=7.30。优化分离条件下有效成分可达基线分离，有良好的线性关系，方法简便快速。
建立了雷公藤生物碱类化合物非水相毛细管电泳优化分离分析方法。优化条件是：操作电压15kV，温度保持301K，进样时间5s，运行介质为20mM醋酸铵和3mM氨水加到甲醇媒介中。实验结果证明此方法是可行的。
建立了手性药物佐米曲坦毛细管电泳优化分离分析方法，其优化分离的缓冲溶液组成为84mM Tris—H_3PO_4中加入30 mM磺化—β—环糊精作手性拆分剂，pH=4.10；分离通道为未涂层熔硅弹性石英毛细管，内径50μm，柱长60cm，有效柱长52cm；分离条件是温度298K，运行电压为18kV，紫外检测波长设在214nm，进样时间为5s。
Based on the current achievement on natural product, a general review of
natural product chemistry and its application on investigation protocol, resources
protection, analysis technology, biology and chemistry synthesis was made. Further
more, this review also covers the preparation and detection of Tripterygium \vilfordii.
First, several extraction and preparation technologies of the alkaloid compounds, the diterpenoid triepoxides compounds and the saccharide compounds were studied. Two column chromatography methods for the separation wilforine and wilfordine , the triptolide and triptonide were developed, respectively.
Second, a micellar electrokinetic capillary chromatography (MEKC) method has been established for the identification and determination of diterpenoid triepoxides in Chinese herb Tripterygium wilfordii Hook F and its preparations. The detailed investigations of the influence of SDS concentration, pH, boric acidand borax concentration were carried out. From the experiments, the MEKC was found to exhibit good accuracy, precision and repeatability.
A capillary electrophoresis method has been established for the determination of triptonide and triptolide in Multi-glycosides Tripterygium wilfordii tablets. Capillary separation was carried out by using 0.01mol L-1 borax + + 0.02mol L-1 SDS (pH =7.3) as the buffer, 20kV applied voltage and 301K temperature.
A method for the separation of wilforine and wilfordine in Tripterygium wilfordii Hook F based on nonaqueous capillary eletrophoresis has been developed. The optimum separation conditions are as follows: voltage 15kV, the temperature was kept at 301K and the running medium consisted of 20mM ammonium acetate and 3mM ammonium hydroxide in methanol. The feasibility of this method was demonstrated by the determination of wilforine and wilfordine in Tripterygium wilfordii Hook F.
A capillary electrophoresis method has been established for the zolmitriptan of chiral drug.
引文
1 Cragg G M, Newman D J, Weiss, R, Coral reefs, forests, and thermal vents: the worldwide exploration of nature for novel antitumor agents, J Nat Prod, 1997,60: 52
2 Cheng X M, In annual reports of medicinal chemistry, American Chemistry Society,Washington D C., 2001, 29(34): 331
3 Lowis J A, In human medicinal agents from plants, ACS Symposium Series 534,American Chemical Society, Washington D C., 1993, 48
4 王德心，药物开发的新策略：并联有机合成及库筛选，药学学报，1995，30(8)：627—640
5 嵇汝运，庆祝中国药学会成立九十周年大会论文集。北京：中国药学会，1997，39
6 Cordell G A., Natural products as medicinal and biological agents, potentiating the resources of the rain forest, Phytochemistry, 1995, 50: 1585
7 Phillipson J D, Anderson L A, Plants as sources of new medicines, J Ethnopharmacol, 1989, 25: 61
8 Vance N C, Kelsey R G, Sabin, T. E, Seasonal and tissue variation in taxane concentrations of taxus brevifolia, Phytochemistry, 1994, 36: 1241
9 Elsohly H N, Croom E M, El-kashoury, Elsayeda, Taxol content of stored fresh and dried taxus clippings, J Nat Prod, 1994, 57: 1025
10 Hostettmann K, Hostettmann M, Marston A, Preparative chromatography techniques, applications in natural product isolation, Phytochemical Anal, 1990, 1: 3
11 Giddings J C, Molecular genetics and immunoanalysis in blood coagulation, J Chromatogr, 1989, 480: 21
12 罗国安，王义明，周国华，毛细管电泳的原理及应用—毛细管电泳在氨基酸、肽及蛋白分析中的应用，色谱，1997，15(4)：305—309
13 王义明，罗国安，魏伟，关燕华，毛细管电泳的原理及应用—毛细管电泳在医药领域中的应用，色谱，1997，15(6)：494—498
14 李方，顾峻岭，傅若农，毛细管电色谱法的研究进展，色谱，1997，15(5)：392—395
15 彭清涛，胡文祥，谭生建，药物对映体HPLC分离测定研究新进展，药学学报，1998，(10)：793—800
16 Zare R N, Gassman E, Kuo J E, Laser excitation fluorescence detection electrokinetic separation, Science, 1985, 230: 813
17 Gozel P, Gassman E, Michelsen H, Zare R N, Electrokinetic resolution of amino acid enantiomers with copper(Ⅱ) aspartame support electrolyte, Anal Chem., 1989,61: 413
18 Kuhn R, Hoffsttter-Kuhn S, Chiral separation by capillary electrophoresis,Chromatographia, 1992, 34: 505
19 Kuhn R, StoeeKlin F, Enri F, Chiral separation by host-guest complexation with cyclodextrin and crown ether in capillary zone electrophoresis, Chromatographia,1992, 33: 32
20 Kuhn R, Enri F, Bereuter T, Hansler J, Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis, Anal Chem., 1992, 64: 2815
21 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary electrophoresis, Ⅰ Initial evaluation of a model, J Chromatogra., 1992, 603: 235
22 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary, electrophoresis, Ⅱ The role of organic solvent, J Chromatogra., 1992, 609: 363
23 Quang C, Khaladi MG, Chiral separations of acidic compounds by dextrin mediated capillary zone electrophoresis, J High Resolut Chromatogra, 1994, 17(8): 609-612
24 Quang C, Khaladi MG, Extending the scope of chiral separation of basic compounds by cyclodextrin-mediated capillary zone electrophoresis, J Chromatogra. A, 1995, 692: 253-265
25 Peterson T E, Trowbridge D, Quantitation of L-epinephrine and determination of
D-/L-epinephrine enantiomer ratio in a pharmaceutical formulation by capillary electrophoresis, J Chromatogra., 1992, 603: 298
26 Peterson T E, Separation of drug stereoisomers by capillary electrophoresis with cyclodextrins, J Chromatogra., 1992, 630: 353
27 Fanali S, Bocek P, Resolution of racemic tryptophan and determination of the enantiomer composition of commercial pharmaceutical epinephrine,Electrophoresis, 1990, 11: 757
28 Quang C, Khaladi MG, Improved chiral separation of basic compounds in capillary electrophoresis using β-cyclodextrin and tetralkylammonium reagents, Anal Chem.,1993, 65: 3354
29 Quang C, Khaladi MG, Direct separation of the enantiomers of β-blockers by cyclodextrin-mediated capillary zone electrophoresis, HRC., 1994, 17: 99
30 Bernreuther A, Krammer G, Full G, Pabst A, Schreier P, Chiral analysis of natural flavor compounds, Riv. Ital. Eppos, 1993, 4: 18-32
31 Miyashita Y, Terabe S, Separation of dansyl DL-amino acid by micellar electrokinetic capillary chromatography with and without cyclodextrins using P/ACE system 2000, Chromatographia, 1990, 11(2): 6
32 Jiang Z Z, Boyer M T, Sen A, Chiral and steric recognition in optically active,isotactic, alternating α-olefin-carbon monoxide copolymers, effect on physical properties and chemical reactivity, J AM. Chem. Soc., 1995, 117(26): 7037-7038
33 Penn S G etal, Differential binding of tioconazole enantiomers to hydroxypropyl β-cyclodextrin studied capillary electrophoresis, J Chrornatogra., 1993, 636: 149
34 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary electrophoresis, Ⅲ Application to β-blockers, J Chromatogra. 1993, 635: 113
35 Nielen M W F, Chiral separation of basic drugs using cyclodextrin-mediated capillary zone electrophoresis, Anal Chem. 1993, 65: 885
36 Schutzner W, Fanali S, Enantiomers resolution in capillary zone electrophoresis by using cyclodextfins, Electrophoresis, 1992, 13: 687
37 Palmarsdottir S, Edholm L E, Capillary zone electrophoresis for separation of drug
enantiomers using cyclodextrins as chiral selectors, influence of experimental parameters on separation, J Chromatogr. 1994, 666: 337
38 Nardi A, Eliseev A, Bocek P, Fanali S, Use of charged and neutral cyclodextrins in capillary zone electrophoresis enantiomeric resolution of some 2-hydroxy acids,119: 151379
39 Nardi A, Ossicini L, Fanali S, Use of cyclodextrins in capillary zone electrophoresis for the separation of optical isomers, resolution of racemic tryptophan derivatives, 117: 19580
40 Gahm K H, Stalcup A M, Capillary zone electrophoresis study of naphthylethyl-carbarnoylated β-cyclodextrin, Anal Chem., 1995, 67: 19
41 Nishi H, Fukuyama T, Matsuo M, Terabe S, Separation and determination of the ingredients of a cold melicine by micellar electrokinetic chromatography with bile salts, J Microcol Sep., 1989, 1: 234
42 Nishi H, Fukuyama T, Matsuo M, Terabe S, Chiral separation of trimeto-quinol hydrochloride and related compounds by micellar electrokinetic chromatography using sodium taurodeoxycholate solutions and application to optical purity determination, Anal Chem Acta., 1990, 236: 281
43 Nishi H, Fukuyama T, Matsuo M, Terabe S, Chiral separation of diltiazem, trimeto-quinol and related compounds by micellar electrokinetic chromatography with bile salts, J Chromatogra., 1990, 515: 233
44 Cole R O, Sepaniak M J, Hinze W L, Gorse J, Bile salt surfactants in micellar electrokinetic capillary chromatography, application to hydrophobic molecule separations, J Chromatogra., 1991, 557(1-2): 113-123
45 Wolfender J L, Maillard M, Hostettmann K, Thermospray liquid chromatographymass spectrometry in phytochemical analysis, Phytochemical Anal, 1994, 5: 153
46 Breyn L T, Detection isolation and structure determinatio, Bioactive Natural Products, CRC, 1993, 75
47 Wolfender J L, Hostettmann K, Nagao T, Liquid chromatography combined with thermospray and continuous flow fast atom bombardment mass spectrometry of
glycosides in crude plant extracts, J Mass Spectrom, 1995: 535
48 Sweetnam P M, Caldwell L, Lancaster J, Bauer C, The role of receptor binding in drug discovery, J Nat Prod ,1993, 56: 441
49 中药辞海，第三卷，25005雷公藤，中国医药科技出版社，1997，10：1151—1160
50 Lin S, Li YC, Sakurai N, Zheng YL, Isolation and structure of sesquiterpene alkaloids from Tripterygium wilfordii Hook, Acta pharmaceutica sinica, 1995, 30(7): 513-516
51 Crombie L, Crombie WM, Whiting DA, Alkaloids of catha edulis, structures of cathedulins k_1, k_2, k_6 and k_(15): new macrolide bridged polyesters of euongminol, J Chem Soc., 1979: 2976
52 Yamada K, Shizuri Y, Hirata Y, Isolation and structures of a new alkaloid alatamine and an insecticidal alkaloid wilfordine from Thumb., Tetrahedron, 1978, 34: 1915
53 Cheng ZZ, Xiao YS, Fang YJ, Wang WD, Research on extraction technology of Tripterygium wilfordii Hook, Chinese Journal of Pharmaceuticals, 1990, 21(10): 435-436
54 Kupchan SM, Willian AC, Richard GD, Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii Hook, J Am.Chem. Soc, 1972, 92: 7194
55 Lai CK, Total synthesis ofracemic triptolide and triptonide, J Org. Chem, 1982, 47: 235
56 Li CY, Li YC, The chemical constituents of Tripterygium wilfordii Hook, Acta Pharmaceutica Sinica, 1999,34(8): 605-607
57 Gang YY, Zhang ZX, Pharmacological action adxance of Tripterygium wilfordii Hook and its components, J Chin Pham Univ., 1995, 26: 252
58 Takaishi Y, Wariishi N, Tateishi H, Phenolic diterpenes from Tripterygium wilfordii Hook var. regelii., Phytochemistry, 1997, 45: 979
59 Yu DQ, Xie FZ, Ling XT, A new diterpene lectone from Tripterygium wilfordii Hook, Chinese Chem. Letters, 1992, 3: 435
60 Zhang DC, Hu CQ, Jin JQ, Anti-AIDS agents tripterifordin, a novel anti-HIV principle from Tripterygium wilfordii Hook, isolation and structural elucidation, J Nat. Prod., 1992, 55: 88
61 Zeng XJ, Zhang NZ, Effects of tripchlorolide of Tripterygium wilfordii Hook on the production of immunoglobulins by peripheral blood mononuclear cells and by synovial cells of rheumatoid arthritis patients in vitro, Acta Phar. Sinica, 1997, 32(3): 171-173
62 Arnett FC, Edworthy SM, Bloch DA, The american rheumatism association revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum, 1988, 31: 315
63 马鹏程，固克显，徐兰芳等，雷公藤抗免疫及抗生育活性成分的筛选，7个环氧二萜内酯化合物体内抗炎免疫活性的比较，中国医学科学院学报，1991，13(6)：391
64 Brennan FM, Chantry D, Jackson AM, Cytokine production in culture by cells isolated from the synovial membrane, J Autoimmun, 1989, 2(suppl): 177
65 Engvall E, Perlmann P, Enzyme linked immunosorbent assay, quantitation of specific antibodies by enzyme labelled anti-immunoglobulin in antigen coated tubes,J Immunol,1972, 109: 129
66 陈发奎，常用中草药有效成分含量测定，雷公藤，人民卫生出版社，1997，222：761—767
67 刘春安，彭明，抗癌中草药大辞典，雷公藤，湖北科学技术出版社，1994，382：1072—1076
68 郭晓庄，有毒中草药大辞典，雷公藤，天津科技翻译出版社，1992，429，580—587
69 袁珂，刘延泽，冀春茹，中草药化学成分研究中几种不同提取方法的比较研究，天然产物研究与开发，1997，9(4)：57—61
70 Kutney J P, Han Kang, Studies with plant cell culture of the Chinese herbal plant,Tripterygium wilfordii Hook F, Synthesis and biotransformation of diterpene analogs, Heterocycles, 1997, 44: 95-104
71 Musser J H, Synthesis of triptolide prodrogs having high aqueous solubility for
immunosuppressive and anti-inflammatory treatment, 美国专利: 0012483,2000-03-09
72 Jung M J, Wickramaratne M, Hepperle M, Preparation of triptolide derivatives useful in the treatment of autoimmune disease, 美国专利: 6004999, 1999-12-21
73 Yang D, Ye XY, Xu M, Enantioseletive total synthesis of(triptolide), (-)-(triptonide), (+)-(triptoquinonide), (+)-(triptophenolide), J Org Chem, 2000, 65(7): 2208-2217
74 Li Y, New alkaloids synthesis of frontalin analogs and isoprenoids, Diss Absir Int B, 1995, (8): 3291
75 Kutney J P, Han Kang, Studies with plant cell culture of the Chinese herbal plant,Tripterygium wilfordii Hook F, Recl Trav Chim Pays-Bas, 1996, 115(1): 77-93
76 Nakano K, A novel epoxy-triterpene and nortriterpene from callus of Tripterygium wilfordii Hook F, Phytochemistry, 1997, 46(7): 1179-1182
77 Nakano K, Tripenoids in transformed root culture of Tripterygium wilfordii Hook F, Phytochemistry, 1998, 49(6): 1820-1824
78 Nakano K, A diterpenoid and triterpenes from tissue culture of Tripterygium wilfordii Hook F, Phytochemistry, 1997, 45(2): 293-296
79 Milanove R, Moore M, Hirai Y, Hydroxylation of synthetic abietane diterpenes by aspergillus and cunninghamella species, novel routes to the family of diterpenes isolated from Tripterygium wilfordii Hook F, J Nat. Prod, 1994, 57(7): 882-889
80 Milanove R, Han K, Moore M, Oxidation and glucose conjugation of synthetic abietane diterpenes by cunninghamella sp. Ⅱ Novel routes to the family diterpenes from Tripterygium wilfordii Hook F, J Nat Prod, 1995, 58(1): 68-73
81 Kyowa HK Co, Ltd, Antitumor substance [P], 日本专利: 8202699, 1982-01-08
82 Wiedmann TW, Wang J, Plian NB, Immunotherapy composition and method[P],美国专利: 9513082, 1995-05-18
83 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis[P], 美国专利: 9515174, 1995-01-08
84 Ikegawa T, Ikegawa A, Extracts of leucotreiene antagonist phenanthrene
derivatives from Tripterygium wilfordii Hook[P], 日本专利: 95267895,1995-10-17
85 Tamaoki T, Nunome C, Komatsu Y, Extracts of demethylzey lastral from Tripterygium wilfordii Hook as immunosuppressive and anti-inflammatory agent[P],日本专利: 96113538, 1996-05-07
86 Lipsky PE, Tao XL, Cai J, Preparation of Tripterygium wilfordii Hook and use of it[P], 美国专利: 5580562, 1996-12-03
87 Lipsky PE, Tao XL, Cai J, Tripterygium wilfordii Hook extracts and components,use for treatment of inflammation or an immune disorders with concomitant lack of steroidal effect, and screening method for glocoticoid receptor ligands[P], 美国专利: 5616458, 1997-04-01
88 Morota T, Saito K, Komatsu Y, Extracts of new leukotriene antagonist for therapeatic use [P], 日本专利: 9752899, 1997-02-25
89 Ushiro M, Ono M, Kono K, Extracts of nortriterpenoids [P], 日本专利: 97100294,1997-04-15
90 Vigo-Pelfreg Cammen, The use of celastrol to treat aliheimer's disease[P],美国专利: 9825573, 1998-06-18
91 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
92 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection [P], 美国专利:5843452, 1998-11-09
93 Wu CA, Wang ZM, Li N, Natural plant in secticide [P], 中国专利: 1120890,1996-04-24
94 Zhang HC, Kong FR, Amino-acid compound fertilizer [P], 中国专利: 1137030,1996-12-04
95 Jung MJ, Wickramaratne M, Hepperle M, Synthesis and acticity of triptolide terivatives useful in the treatment of autoimmune disease [P], 美国专利: 9852933,1998-11-26
96 夏志林，徐榕青，郭舜民等，雷公藤和昆明山海棠的薄层层析检查，中草药，1994，25(9)：464—465
97 于留荣，李吉来，雷公藤生药中雷公藤内酯的薄层扫描测定，中草药，1988，19(2)：18—20
98 Cai J, Tao XL, Lipsky PE, High performance liquid chromatographic determanation of triptolide and tripdiolide in an ethyl acetate extract of Tripterygium wilfordii Hook, Journal of Liquid Chromatography, 1994, 17(20): 4479-4487
99 罗明珠，李进，薄层扫描法及高效液相色谱法测定雷公藤甲素含量的比较，中国医院药学杂志，1996，16(2)：76
100 夏志林，陈俊元，徐榕青，柱层析—紫外分光光度法测定雷公藤中总碱的含量，中草药，1992，23(11)：579—580
101 姚发兴，徐斌，童秀英等，雷公藤的化学成分及提取物的检验方法探讨，湖北师范学院学报，2000，20(4)：35—39
1 谢明勇，李磊，青钱柳化学成分和生物活性研究概况，中草药，2001，32(4)：365—366
2 钟瑞建，舒任庚，倪小兰等，青钱柳酸A的结构研究，药学学报，1996，31(5)：398
3 林绥，李援朝，樱井信子等，雷公藤倍半萜生物碱的分离与结构，药学学报，1995，30(7)：513—516
4 何直昇，洪山海，李亚等，雷公藤碱乙、碱庚和碱己的结构，化学学报，1987，45：510
5 夏志林，陈俊元，邓福孝等，雷公藤茎叶中的生物碱成分的研究，中国药学杂志，1990，25(6)：266—267
6 夏志林，陈俊元，徐榕青等，雷公藤综合利用的探讨，中国医药工业杂志，1990，21(2)：58—59
7 程自珍，肖银生，方义杰等，雷公藤提取工艺的探讨，中国医药工业杂志，1990，21(10)：435—436
8 王玉玺，李汉堡，雷公藤制剂的研究进展，中草药，1997，28(1)：52—55
9 陈俊元，夏志林，邓福孝等，雷公藤内酯醇提取工艺的改进，中国医药工业杂志，1989，20(5)：195
10 Kupchan SM, Willian AC, Richard GD et al, Triptolide and tripdiolide, novel antieukemic diterpenoid triepoxides from Tripterygium wilfordii. J An. Chem.Soc., 1972, 92: 7194
11 Lai CK, Lipsky PE, et al, Total synthesis ofracemic triptolide and triptonide, J Org.Chem., 1982, 47: 2354
12 刘春安，彭明，《抗癌中草药大辞典》，湖北科学技术出版社，1994，382：10712
13 郭晓庄，《有毒中草药大辞典》，天津科技翻译出版社，1992，429：580
14 陈发奎，《常用中草药有效成分含量测定》，人民卫生出版社，1997，222：761
1 Chunan Liu, Ming Peng. Anticancer Chinese Herb Dictionary, Tripterygium wilfordii hook f, Wuhan, Hubei Science and Technology Publishing co., 1994, 382: 1072-1076
2 Xiaozhuang Guo, Poisoned Traditional Chinese Herb Dictionary, Tripterygium wilfordii hook f, Tianjin Science and Technology Publishing co., 1994, 429(11): 580-588
3 Zhong Yao Dacidian, Tripterygium wilfordii hook f, Shanghai Science and Technology Publishing co., 1993, 5150: 2469-2470
4 Kupchan SM, Court WA, Dailay RG, Triptolide and tripdiolide, novel antieukemic diterpenoid triepoxides from Tripterygium wilfordii.Journal America Chemical Soc. 1972, 92: 7194-7195
5 Kan Nie, Weijian An and Guangcheng Xia, Comparison content of the effective components in Tripterygium wilfordii hook from different sources, Traditional Chinese Medicine, 1994, 25(10): 539-541
6 李乐真，陈芍芳，谭宫屏等，雷公藤醋酸乙酯提取物药理作用研究，中草药，1991，13(4)：21
7 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis[P], 美国专利: 9515174, 1995-01-08
8 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
9 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection [P], 美国专利: 5843452, 1998-11-09
10 Xiurong Song, Gengliang Yang, Hanwen Sun and Jie Li, Determination of effective components in folium mori by capillary electrophoresis method, Chinese Traditional Patent Medicine, 2000, 22(2): 158-160
11 Xiurong Song, Gengliang Yang, Hongyi Zhang and Dexian Wang, Identification and determination of effective components in YHKFY by micellar capillary electrophoresis, Traditional Chinese Medicine. Addition, 1999, 30: 85-87
12 Hongyi Zhang, Xiurong Song, Zhihong Shi and Gengliang Yang, Capillary zone electrophoresis for the determination of average hydrodynamic velocity and diffusion coefficient, Fresenius' Journal of Analytical Chemistry, 1999, 365(11): 499-503
13 Dexian Wang, Gengliang Yang, H. Engelhardt and Hingyi Zhang, Micellar electrokinetic capillary chromatography of psoralen and isopsoralen,Electrophoresis. 1999, 20: 1895-1899
14 Gengliang Yang, Xiurong Song, Hongyi Zhang and Dexian Wang, Identification and determination of paeonol and paeoniflorin by micellar capillary electrophoresis, Chinese Journal of Analytical Chemistry, 1999, 27(1): 1-4
15 Guanbin Li, Hongyi Zhang, Yuquan Fan and Zhide Hu, Journal of Chromatography A, 1999, 863: 105-114
1 Liu C, Peng M. Anticancer Chinese Herb Dictionary. Tripterygium wilfordii Hook,Science and Technology Publishing co., Hubei, 1994, 382: 1072-6
2 Kupchan SM, Court WA, Dailay RG. Triptolide and triptonide novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii Hook, J. Amer. Chem. Soc.,1972, 94(20): 7194-5
3 Gu WZ, Chen RD, Wein BR. Isolation purification and characterization of immunosuppressive compounds from Tripterygium wilfordii Hook, triptolide and triptonide, Int. J. Immunopharmacol, 1995,17(5): 351-6
4 Cai JJ, Tao XL, Lipsky PE. High performance liquid chromatographic determination of triptolide and triptonide in an ethyl acetate extract of Tripterygium wilfordii Hook,J. Liq. Chromatogr., 1994, 17(20): 4479-87
5 Tao XL, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract of Tripterygium wilfordii Hook, J. Pharmacology Exp. Ther, 1995, 272(3): 1305-12
6 Zhang L, Zhang ZH, Sheng LS. Determination oftriptolide in Tripterygium wilfordii Hook from different sources by capillary gas chromatography, Journal of Chinese Pharmaceutical University, 1992, 23 (3): 158-200
7 Xia ZL, Chen JY, Xu RQ. Alkaloids in tripterygium wilfordii Hook by column layer chromatography ultraviolet spectroscopy, Chinese Traditional and Herbal Drugs,1992, 23(11): 579
8 Zhang HY, Song XK, Shi ZH, Yang GL, Hu ZD. Capillary zone electrophoresis for the determination of average hydrodynamic velocity and diffusion coefficient,Fresenius' Journal of Analytical Chemistry, 1999, 365(6): 499-503.
9 Wang DX, Yang GL, Engelhardt H, Zhang HY. Micellar electrokinetic capillary chromatography of psoralen and isopsoralen. Electrophoresis, 1999, 20: 1895-99.
10 Yang GL, Song XR, Zhang HY, Wang DX, Sun HW. Identification and determination of paeonol and paeoniflorin by mieellar capillary electrophoresis,Chinese Journal of Analytical Chemistry, 1999, 27(1): 1-4.
11 陈俊元，夏志林，邓福孝等，雷公藤内酯醇提取工艺的改进，中国医药工业杂
志，1989，20(5)：195
1 熊建辉，张维冰，许国旺，张玉奎，非水毛细管电泳进展，色谱，2000，18(3)：218—223
2 Herrero-Martinez JM, Femandez-Marti M, Simo-Alfonso E, Rarnis-Ramos G, Determination of alkyphenol ethoxylates by micellar electrokinetic chromatography with bile salts, Electrophoresis, 2001, 22: 526-534
3 Walbrohel Y, Jorgenson J W, On-column UV absorption detector for open tubular capillary zone electrophoresis, J Chromatogr A, 1984, 315: 135-143
4 Hansen SH, Bjφrnsdottir I, Tjφrnrlund J, Separation of cationic cistrans isomers and diastereoisomers using non aqueous capillary electrophoresis, Electrophoresis,1998, 19: 2179-2186
5 Altria K D, Kelly MA, Clark BJ, Current applications in the analysis of pharmaceuticals by capillary electrophoresis, Trends Anal Chem., 1998, 17(14): 204-214
6 Salimi-Moosavi H, Capillary electrophoresis in pure nonaqueous solvents, Dss Abstr Int., B 1998, 58(12): 6543
7 徐木生，王小如，杨芃原，贾丽，非水介质毛细管电泳，色谱，1998，16(4)：309—313
8 Ji SG, Chai YF, Zhang GQ, Wu YT, Yin XP, Determination oftetrahydro- palmatine in Chinese traditional medicine by nonaqueous capillary electro- phoresis,Electrophoresis, 1999, 20: 1904-1906
9 Fillet M, Bechet I, Piette V, Crommen J, Separation of nonateroidal anti-inflammatory drug by capillary electrophoresis using nonaqueous electrolytes,Electrophoresis, 1999, 20: 1907-1915
10 Samir C, Serge R, Jean-Luc V, Nonaqueous capillary electrophoresis-mass spectrometry for separation of venlafaxine and its phase 1 metabolites, Electro-
phoresis, 2001, 22: 491-496
11 Lin S, Li YC, Sakurai N, Zheng YL, Isolation and structure of sesquiterpene alkaloids from Tripterygium wilfordii Hook, Acta pharmaceutica sinica, 1995, 30(7): 513-516
1 概述，佐米曲坦及片剂(Zoming)项目简介，http://www.Orientpharm.Com/b1/bxm2hr4.htm
2 Castaner J, Zomitriptan and synthetize, Drag of the future, 1997, 22(3): 260
3 Schoenen J, Sawyer J, Zolmitriptan [Zoming(TM, 311C90)], a novel dual central and peripheral 5-HTIB/ID agonist: an overview of efficacy, Cephalalgia, 1997,17(18): S28
4 Dixon R, Warrander A, The clinical pharrnacokinetics of zolmitriptan, Cephalalgia,1997, 17(18): S15
5 Seaber E, On N, Dixon RM, The absolute bioavailability and metabolic disposition of the novel antimigraine componed zolmitriptan(311C90), J Clin Pharmcol, 1997,43(6): 579
6 Gotti R, Pomponio R, Cavrini V, Linear, netural polysaccharides as chiral selectors in enantioresolution of basic drug racemates by capillary electrophoresis,Chromatographia, 2000, 52(5/6): 273-278
7 Crego AL, Gonzalez MJ, Marina ML, Chiral separation of polychlorinated biphenyls by micellar electrokinetic chromatography with sodium cholate,Electrophoresis, 1998, 19: 2113-2118
8 Akos V, Martin GS, Ferenc K, Gerald G, Chiral separation of α-amino acids by ligand-exchange capillary electrophoresis using N-(2-hydroxy-octyl)-L-4-hydroxyproline as a selector, Eleetrophoresis, 1998, 19: 2109-2112
9 Wang F, Khaledi MG, Capillary electrophoresis chiral separations of basic compounds using cationic cyclodextrin, Electrophoresis, 1998, 19: 2095-2100
10 Jin YK, Stalcup AM, Application of heparin to chiral separations of antihistamines by capillary electrophoresis, Electrophoresis, 1998, 19: 2119-2123
11 阮总琴，尤进茂，李菊白，欧庆瑜，磺化β—环糊精的合成及其在毛细管电泳手性拆分中的应用，色谱，2000，18(2)：183—186
1 Morota T, Saito K, Komatsu Y, Extracts of new leukotriene antagonist for therapeatic use [P], 日本专利: 9752899, 1997-02-25
2 李耐三，于东晖，中药雷公藤毒代动力学研究，中国药科大学学报，1992，23(1)：25
3 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis [P], 美国专利: 9515174, 1995-01-08
4 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
5 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection[P], 美国专利: 5843452, 1998-11-09
6 Vigo-Pelfreg Cammen, The use of celastrol to treat aliheimer's disease [P], 美国专利: 9825573, 1998-06-18
7 李秀才，雷公藤的研究与临床作用，中国中药杂志，1997，22(1)：53
8 程自珍，肖银生，方义杰等，雷公藤提取工艺的探讨，中国医药工业杂志，1990，21(10)：435—436
9 Cai JJ, Tao XL, Lipsky PE. High performance liquid chromatographic determination of triptolide and triptonide in an ethyl acetate extract of Tripterygium wilfordii Hook,J. Liq. Chromatogr., 1994, 17(20): 4479-87
10 Tao XL, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract of Tripterygium wilfordii Hook, J. Pharmacology Exp. Ther, 1995, 272 (3): 1305-12
11 Zhang L, Zhang ZH, Sheng LS. Determination of triptolide in Tripterygium wilfordii Hook from different sources by capillary gas chromatography, Journal of Chinese Pharmaceutical University, 1992, 23 (3): 158-200
2 Cheng X M, In annual reports of medicinal chemistry, American Chemistry Society,Washington D C., 2001, 29(34): 331
3 Lowis J A, In human medicinal agents from plants, ACS Symposium Series 534,American Chemical Society, Washington D C., 1993, 48
4 王德心，药物开发的新策略：并联有机合成及库筛选，药学学报，1995，30(8)：627—640
5 嵇汝运，庆祝中国药学会成立九十周年大会论文集。北京：中国药学会，1997，39
6 Cordell G A., Natural products as medicinal and biological agents, potentiating the resources of the rain forest, Phytochemistry, 1995, 50: 1585
7 Phillipson J D, Anderson L A, Plants as sources of new medicines, J Ethnopharmacol, 1989, 25: 61
8 Vance N C, Kelsey R G, Sabin, T. E, Seasonal and tissue variation in taxane concentrations of taxus brevifolia, Phytochemistry, 1994, 36: 1241
9 Elsohly H N, Croom E M, El-kashoury, Elsayeda, Taxol content of stored fresh and dried taxus clippings, J Nat Prod, 1994, 57: 1025
10 Hostettmann K, Hostettmann M, Marston A, Preparative chromatography techniques, applications in natural product isolation, Phytochemical Anal, 1990, 1: 3
11 Giddings J C, Molecular genetics and immunoanalysis in blood coagulation, J Chromatogr, 1989, 480: 21
12 罗国安，王义明，周国华，毛细管电泳的原理及应用—毛细管电泳在氨基酸、肽及蛋白分析中的应用，色谱，1997，15(4)：305—309
13 王义明，罗国安，魏伟，关燕华，毛细管电泳的原理及应用—毛细管电泳在医药领域中的应用，色谱，1997，15(6)：494—498
14 李方，顾峻岭，傅若农，毛细管电色谱法的研究进展，色谱，1997，15(5)：392—395
15 彭清涛，胡文祥，谭生建，药物对映体HPLC分离测定研究新进展，药学学报，1998，(10)：793—800
16 Zare R N, Gassman E, Kuo J E, Laser excitation fluorescence detection electrokinetic separation, Science, 1985, 230: 813
17 Gozel P, Gassman E, Michelsen H, Zare R N, Electrokinetic resolution of amino acid enantiomers with copper(Ⅱ) aspartame support electrolyte, Anal Chem., 1989,61: 413
18 Kuhn R, Hoffsttter-Kuhn S, Chiral separation by capillary electrophoresis,Chromatographia, 1992, 34: 505
19 Kuhn R, StoeeKlin F, Enri F, Chiral separation by host-guest complexation with cyclodextrin and crown ether in capillary zone electrophoresis, Chromatographia,1992, 33: 32
20 Kuhn R, Enri F, Bereuter T, Hansler J, Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis, Anal Chem., 1992, 64: 2815
21 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary electrophoresis, Ⅰ Initial evaluation of a model, J Chromatogra., 1992, 603: 235
22 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary, electrophoresis, Ⅱ The role of organic solvent, J Chromatogra., 1992, 609: 363
23 Quang C, Khaladi MG, Chiral separations of acidic compounds by dextrin mediated capillary zone electrophoresis, J High Resolut Chromatogra, 1994, 17(8): 609-612
24 Quang C, Khaladi MG, Extending the scope of chiral separation of basic compounds by cyclodextrin-mediated capillary zone electrophoresis, J Chromatogra. A, 1995, 692: 253-265
25 Peterson T E, Trowbridge D, Quantitation of L-epinephrine and determination of
D-/L-epinephrine enantiomer ratio in a pharmaceutical formulation by capillary electrophoresis, J Chromatogra., 1992, 603: 298
26 Peterson T E, Separation of drug stereoisomers by capillary electrophoresis with cyclodextrins, J Chromatogra., 1992, 630: 353
27 Fanali S, Bocek P, Resolution of racemic tryptophan and determination of the enantiomer composition of commercial pharmaceutical epinephrine,Electrophoresis, 1990, 11: 757
28 Quang C, Khaladi MG, Improved chiral separation of basic compounds in capillary electrophoresis using β-cyclodextrin and tetralkylammonium reagents, Anal Chem.,1993, 65: 3354
29 Quang C, Khaladi MG, Direct separation of the enantiomers of β-blockers by cyclodextrin-mediated capillary zone electrophoresis, HRC., 1994, 17: 99
30 Bernreuther A, Krammer G, Full G, Pabst A, Schreier P, Chiral analysis of natural flavor compounds, Riv. Ital. Eppos, 1993, 4: 18-32
31 Miyashita Y, Terabe S, Separation of dansyl DL-amino acid by micellar electrokinetic capillary chromatography with and without cyclodextrins using P/ACE system 2000, Chromatographia, 1990, 11(2): 6
32 Jiang Z Z, Boyer M T, Sen A, Chiral and steric recognition in optically active,isotactic, alternating α-olefin-carbon monoxide copolymers, effect on physical properties and chemical reactivity, J AM. Chem. Soc., 1995, 117(26): 7037-7038
33 Penn S G etal, Differential binding of tioconazole enantiomers to hydroxypropyl β-cyclodextrin studied capillary electrophoresis, J Chrornatogra., 1993, 636: 149
34 Wren S A C, Rowe R C, Theoretical aspects of chiral separation in capillary electrophoresis, Ⅲ Application to β-blockers, J Chromatogra. 1993, 635: 113
35 Nielen M W F, Chiral separation of basic drugs using cyclodextrin-mediated capillary zone electrophoresis, Anal Chem. 1993, 65: 885
36 Schutzner W, Fanali S, Enantiomers resolution in capillary zone electrophoresis by using cyclodextfins, Electrophoresis, 1992, 13: 687
37 Palmarsdottir S, Edholm L E, Capillary zone electrophoresis for separation of drug
enantiomers using cyclodextrins as chiral selectors, influence of experimental parameters on separation, J Chromatogr. 1994, 666: 337
38 Nardi A, Eliseev A, Bocek P, Fanali S, Use of charged and neutral cyclodextrins in capillary zone electrophoresis enantiomeric resolution of some 2-hydroxy acids,119: 151379
39 Nardi A, Ossicini L, Fanali S, Use of cyclodextrins in capillary zone electrophoresis for the separation of optical isomers, resolution of racemic tryptophan derivatives, 117: 19580
40 Gahm K H, Stalcup A M, Capillary zone electrophoresis study of naphthylethyl-carbarnoylated β-cyclodextrin, Anal Chem., 1995, 67: 19
41 Nishi H, Fukuyama T, Matsuo M, Terabe S, Separation and determination of the ingredients of a cold melicine by micellar electrokinetic chromatography with bile salts, J Microcol Sep., 1989, 1: 234
42 Nishi H, Fukuyama T, Matsuo M, Terabe S, Chiral separation of trimeto-quinol hydrochloride and related compounds by micellar electrokinetic chromatography using sodium taurodeoxycholate solutions and application to optical purity determination, Anal Chem Acta., 1990, 236: 281
43 Nishi H, Fukuyama T, Matsuo M, Terabe S, Chiral separation of diltiazem, trimeto-quinol and related compounds by micellar electrokinetic chromatography with bile salts, J Chromatogra., 1990, 515: 233
44 Cole R O, Sepaniak M J, Hinze W L, Gorse J, Bile salt surfactants in micellar electrokinetic capillary chromatography, application to hydrophobic molecule separations, J Chromatogra., 1991, 557(1-2): 113-123
45 Wolfender J L, Maillard M, Hostettmann K, Thermospray liquid chromatographymass spectrometry in phytochemical analysis, Phytochemical Anal, 1994, 5: 153
46 Breyn L T, Detection isolation and structure determinatio, Bioactive Natural Products, CRC, 1993, 75
47 Wolfender J L, Hostettmann K, Nagao T, Liquid chromatography combined with thermospray and continuous flow fast atom bombardment mass spectrometry of
glycosides in crude plant extracts, J Mass Spectrom, 1995: 535
48 Sweetnam P M, Caldwell L, Lancaster J, Bauer C, The role of receptor binding in drug discovery, J Nat Prod ,1993, 56: 441
49 中药辞海，第三卷，25005雷公藤，中国医药科技出版社，1997，10：1151—1160
50 Lin S, Li YC, Sakurai N, Zheng YL, Isolation and structure of sesquiterpene alkaloids from Tripterygium wilfordii Hook, Acta pharmaceutica sinica, 1995, 30(7): 513-516
51 Crombie L, Crombie WM, Whiting DA, Alkaloids of catha edulis, structures of cathedulins k_1, k_2, k_6 and k_(15): new macrolide bridged polyesters of euongminol, J Chem Soc., 1979: 2976
52 Yamada K, Shizuri Y, Hirata Y, Isolation and structures of a new alkaloid alatamine and an insecticidal alkaloid wilfordine from Thumb., Tetrahedron, 1978, 34: 1915
53 Cheng ZZ, Xiao YS, Fang YJ, Wang WD, Research on extraction technology of Tripterygium wilfordii Hook, Chinese Journal of Pharmaceuticals, 1990, 21(10): 435-436
54 Kupchan SM, Willian AC, Richard GD, Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii Hook, J Am.Chem. Soc, 1972, 92: 7194
55 Lai CK, Total synthesis ofracemic triptolide and triptonide, J Org. Chem, 1982, 47: 235
56 Li CY, Li YC, The chemical constituents of Tripterygium wilfordii Hook, Acta Pharmaceutica Sinica, 1999,34(8): 605-607
57 Gang YY, Zhang ZX, Pharmacological action adxance of Tripterygium wilfordii Hook and its components, J Chin Pham Univ., 1995, 26: 252
58 Takaishi Y, Wariishi N, Tateishi H, Phenolic diterpenes from Tripterygium wilfordii Hook var. regelii., Phytochemistry, 1997, 45: 979
59 Yu DQ, Xie FZ, Ling XT, A new diterpene lectone from Tripterygium wilfordii Hook, Chinese Chem. Letters, 1992, 3: 435
60 Zhang DC, Hu CQ, Jin JQ, Anti-AIDS agents tripterifordin, a novel anti-HIV principle from Tripterygium wilfordii Hook, isolation and structural elucidation, J Nat. Prod., 1992, 55: 88
61 Zeng XJ, Zhang NZ, Effects of tripchlorolide of Tripterygium wilfordii Hook on the production of immunoglobulins by peripheral blood mononuclear cells and by synovial cells of rheumatoid arthritis patients in vitro, Acta Phar. Sinica, 1997, 32(3): 171-173
62 Arnett FC, Edworthy SM, Bloch DA, The american rheumatism association revised criteria for the classification of rheumatoid arthritis, Arthritis Rheum, 1988, 31: 315
63 马鹏程，固克显，徐兰芳等，雷公藤抗免疫及抗生育活性成分的筛选，7个环氧二萜内酯化合物体内抗炎免疫活性的比较，中国医学科学院学报，1991，13(6)：391
64 Brennan FM, Chantry D, Jackson AM, Cytokine production in culture by cells isolated from the synovial membrane, J Autoimmun, 1989, 2(suppl): 177
65 Engvall E, Perlmann P, Enzyme linked immunosorbent assay, quantitation of specific antibodies by enzyme labelled anti-immunoglobulin in antigen coated tubes,J Immunol,1972, 109: 129
66 陈发奎，常用中草药有效成分含量测定，雷公藤，人民卫生出版社，1997，222：761—767
67 刘春安，彭明，抗癌中草药大辞典，雷公藤，湖北科学技术出版社，1994，382：1072—1076
68 郭晓庄，有毒中草药大辞典，雷公藤，天津科技翻译出版社，1992，429，580—587
69 袁珂，刘延泽，冀春茹，中草药化学成分研究中几种不同提取方法的比较研究，天然产物研究与开发，1997，9(4)：57—61
70 Kutney J P, Han Kang, Studies with plant cell culture of the Chinese herbal plant,Tripterygium wilfordii Hook F, Synthesis and biotransformation of diterpene analogs, Heterocycles, 1997, 44: 95-104
71 Musser J H, Synthesis of triptolide prodrogs having high aqueous solubility for
immunosuppressive and anti-inflammatory treatment, 美国专利: 0012483,2000-03-09
72 Jung M J, Wickramaratne M, Hepperle M, Preparation of triptolide derivatives useful in the treatment of autoimmune disease, 美国专利: 6004999, 1999-12-21
73 Yang D, Ye XY, Xu M, Enantioseletive total synthesis of(triptolide), (-)-(triptonide), (+)-(triptoquinonide), (+)-(triptophenolide), J Org Chem, 2000, 65(7): 2208-2217
74 Li Y, New alkaloids synthesis of frontalin analogs and isoprenoids, Diss Absir Int B, 1995, (8): 3291
75 Kutney J P, Han Kang, Studies with plant cell culture of the Chinese herbal plant,Tripterygium wilfordii Hook F, Recl Trav Chim Pays-Bas, 1996, 115(1): 77-93
76 Nakano K, A novel epoxy-triterpene and nortriterpene from callus of Tripterygium wilfordii Hook F, Phytochemistry, 1997, 46(7): 1179-1182
77 Nakano K, Tripenoids in transformed root culture of Tripterygium wilfordii Hook F, Phytochemistry, 1998, 49(6): 1820-1824
78 Nakano K, A diterpenoid and triterpenes from tissue culture of Tripterygium wilfordii Hook F, Phytochemistry, 1997, 45(2): 293-296
79 Milanove R, Moore M, Hirai Y, Hydroxylation of synthetic abietane diterpenes by aspergillus and cunninghamella species, novel routes to the family of diterpenes isolated from Tripterygium wilfordii Hook F, J Nat. Prod, 1994, 57(7): 882-889
80 Milanove R, Han K, Moore M, Oxidation and glucose conjugation of synthetic abietane diterpenes by cunninghamella sp. Ⅱ Novel routes to the family diterpenes from Tripterygium wilfordii Hook F, J Nat Prod, 1995, 58(1): 68-73
81 Kyowa HK Co, Ltd, Antitumor substance [P], 日本专利: 8202699, 1982-01-08
82 Wiedmann TW, Wang J, Plian NB, Immunotherapy composition and method[P],美国专利: 9513082, 1995-05-18
83 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis[P], 美国专利: 9515174, 1995-01-08
84 Ikegawa T, Ikegawa A, Extracts of leucotreiene antagonist phenanthrene
derivatives from Tripterygium wilfordii Hook[P], 日本专利: 95267895,1995-10-17
85 Tamaoki T, Nunome C, Komatsu Y, Extracts of demethylzey lastral from Tripterygium wilfordii Hook as immunosuppressive and anti-inflammatory agent[P],日本专利: 96113538, 1996-05-07
86 Lipsky PE, Tao XL, Cai J, Preparation of Tripterygium wilfordii Hook and use of it[P], 美国专利: 5580562, 1996-12-03
87 Lipsky PE, Tao XL, Cai J, Tripterygium wilfordii Hook extracts and components,use for treatment of inflammation or an immune disorders with concomitant lack of steroidal effect, and screening method for glocoticoid receptor ligands[P], 美国专利: 5616458, 1997-04-01
88 Morota T, Saito K, Komatsu Y, Extracts of new leukotriene antagonist for therapeatic use [P], 日本专利: 9752899, 1997-02-25
89 Ushiro M, Ono M, Kono K, Extracts of nortriterpenoids [P], 日本专利: 97100294,1997-04-15
90 Vigo-Pelfreg Cammen, The use of celastrol to treat aliheimer's disease[P],美国专利: 9825573, 1998-06-18
91 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
92 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection [P], 美国专利:5843452, 1998-11-09
93 Wu CA, Wang ZM, Li N, Natural plant in secticide [P], 中国专利: 1120890,1996-04-24
94 Zhang HC, Kong FR, Amino-acid compound fertilizer [P], 中国专利: 1137030,1996-12-04
95 Jung MJ, Wickramaratne M, Hepperle M, Synthesis and acticity of triptolide terivatives useful in the treatment of autoimmune disease [P], 美国专利: 9852933,1998-11-26
96 夏志林，徐榕青，郭舜民等，雷公藤和昆明山海棠的薄层层析检查，中草药，1994，25(9)：464—465
97 于留荣，李吉来，雷公藤生药中雷公藤内酯的薄层扫描测定，中草药，1988，19(2)：18—20
98 Cai J, Tao XL, Lipsky PE, High performance liquid chromatographic determanation of triptolide and tripdiolide in an ethyl acetate extract of Tripterygium wilfordii Hook, Journal of Liquid Chromatography, 1994, 17(20): 4479-4487
99 罗明珠，李进，薄层扫描法及高效液相色谱法测定雷公藤甲素含量的比较，中国医院药学杂志，1996，16(2)：76
100 夏志林，陈俊元，徐榕青，柱层析—紫外分光光度法测定雷公藤中总碱的含量，中草药，1992，23(11)：579—580
101 姚发兴，徐斌，童秀英等，雷公藤的化学成分及提取物的检验方法探讨，湖北师范学院学报，2000，20(4)：35—39
1 谢明勇，李磊，青钱柳化学成分和生物活性研究概况，中草药，2001，32(4)：365—366
2 钟瑞建，舒任庚，倪小兰等，青钱柳酸A的结构研究，药学学报，1996，31(5)：398
3 林绥，李援朝，樱井信子等，雷公藤倍半萜生物碱的分离与结构，药学学报，1995，30(7)：513—516
4 何直昇，洪山海，李亚等，雷公藤碱乙、碱庚和碱己的结构，化学学报，1987，45：510
5 夏志林，陈俊元，邓福孝等，雷公藤茎叶中的生物碱成分的研究，中国药学杂志，1990，25(6)：266—267
6 夏志林，陈俊元，徐榕青等，雷公藤综合利用的探讨，中国医药工业杂志，1990，21(2)：58—59
7 程自珍，肖银生，方义杰等，雷公藤提取工艺的探讨，中国医药工业杂志，1990，21(10)：435—436
8 王玉玺，李汉堡，雷公藤制剂的研究进展，中草药，1997，28(1)：52—55
9 陈俊元，夏志林，邓福孝等，雷公藤内酯醇提取工艺的改进，中国医药工业杂志，1989，20(5)：195
10 Kupchan SM, Willian AC, Richard GD et al, Triptolide and tripdiolide, novel antieukemic diterpenoid triepoxides from Tripterygium wilfordii. J An. Chem.Soc., 1972, 92: 7194
11 Lai CK, Lipsky PE, et al, Total synthesis ofracemic triptolide and triptonide, J Org.Chem., 1982, 47: 2354
12 刘春安，彭明，《抗癌中草药大辞典》，湖北科学技术出版社，1994，382：10712
13 郭晓庄，《有毒中草药大辞典》，天津科技翻译出版社，1992，429：580
14 陈发奎，《常用中草药有效成分含量测定》，人民卫生出版社，1997，222：761
1 Chunan Liu, Ming Peng. Anticancer Chinese Herb Dictionary, Tripterygium wilfordii hook f, Wuhan, Hubei Science and Technology Publishing co., 1994, 382: 1072-1076
2 Xiaozhuang Guo, Poisoned Traditional Chinese Herb Dictionary, Tripterygium wilfordii hook f, Tianjin Science and Technology Publishing co., 1994, 429(11): 580-588
3 Zhong Yao Dacidian, Tripterygium wilfordii hook f, Shanghai Science and Technology Publishing co., 1993, 5150: 2469-2470
4 Kupchan SM, Court WA, Dailay RG, Triptolide and tripdiolide, novel antieukemic diterpenoid triepoxides from Tripterygium wilfordii.Journal America Chemical Soc. 1972, 92: 7194-7195
5 Kan Nie, Weijian An and Guangcheng Xia, Comparison content of the effective components in Tripterygium wilfordii hook from different sources, Traditional Chinese Medicine, 1994, 25(10): 539-541
6 李乐真，陈芍芳，谭宫屏等，雷公藤醋酸乙酯提取物药理作用研究，中草药，1991，13(4)：21
7 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis[P], 美国专利: 9515174, 1995-01-08
8 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
9 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection [P], 美国专利: 5843452, 1998-11-09
10 Xiurong Song, Gengliang Yang, Hanwen Sun and Jie Li, Determination of effective components in folium mori by capillary electrophoresis method, Chinese Traditional Patent Medicine, 2000, 22(2): 158-160
11 Xiurong Song, Gengliang Yang, Hongyi Zhang and Dexian Wang, Identification and determination of effective components in YHKFY by micellar capillary electrophoresis, Traditional Chinese Medicine. Addition, 1999, 30: 85-87
12 Hongyi Zhang, Xiurong Song, Zhihong Shi and Gengliang Yang, Capillary zone electrophoresis for the determination of average hydrodynamic velocity and diffusion coefficient, Fresenius' Journal of Analytical Chemistry, 1999, 365(11): 499-503
13 Dexian Wang, Gengliang Yang, H. Engelhardt and Hingyi Zhang, Micellar electrokinetic capillary chromatography of psoralen and isopsoralen,Electrophoresis. 1999, 20: 1895-1899
14 Gengliang Yang, Xiurong Song, Hongyi Zhang and Dexian Wang, Identification and determination of paeonol and paeoniflorin by micellar capillary electrophoresis, Chinese Journal of Analytical Chemistry, 1999, 27(1): 1-4
15 Guanbin Li, Hongyi Zhang, Yuquan Fan and Zhide Hu, Journal of Chromatography A, 1999, 863: 105-114
1 Liu C, Peng M. Anticancer Chinese Herb Dictionary. Tripterygium wilfordii Hook,Science and Technology Publishing co., Hubei, 1994, 382: 1072-6
2 Kupchan SM, Court WA, Dailay RG. Triptolide and triptonide novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii Hook, J. Amer. Chem. Soc.,1972, 94(20): 7194-5
3 Gu WZ, Chen RD, Wein BR. Isolation purification and characterization of immunosuppressive compounds from Tripterygium wilfordii Hook, triptolide and triptonide, Int. J. Immunopharmacol, 1995,17(5): 351-6
4 Cai JJ, Tao XL, Lipsky PE. High performance liquid chromatographic determination of triptolide and triptonide in an ethyl acetate extract of Tripterygium wilfordii Hook,J. Liq. Chromatogr., 1994, 17(20): 4479-87
5 Tao XL, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract of Tripterygium wilfordii Hook, J. Pharmacology Exp. Ther, 1995, 272(3): 1305-12
6 Zhang L, Zhang ZH, Sheng LS. Determination oftriptolide in Tripterygium wilfordii Hook from different sources by capillary gas chromatography, Journal of Chinese Pharmaceutical University, 1992, 23 (3): 158-200
7 Xia ZL, Chen JY, Xu RQ. Alkaloids in tripterygium wilfordii Hook by column layer chromatography ultraviolet spectroscopy, Chinese Traditional and Herbal Drugs,1992, 23(11): 579
8 Zhang HY, Song XK, Shi ZH, Yang GL, Hu ZD. Capillary zone electrophoresis for the determination of average hydrodynamic velocity and diffusion coefficient,Fresenius' Journal of Analytical Chemistry, 1999, 365(6): 499-503.
9 Wang DX, Yang GL, Engelhardt H, Zhang HY. Micellar electrokinetic capillary chromatography of psoralen and isopsoralen. Electrophoresis, 1999, 20: 1895-99.
10 Yang GL, Song XR, Zhang HY, Wang DX, Sun HW. Identification and determination of paeonol and paeoniflorin by mieellar capillary electrophoresis,Chinese Journal of Analytical Chemistry, 1999, 27(1): 1-4.
11 陈俊元，夏志林，邓福孝等，雷公藤内酯醇提取工艺的改进，中国医药工业杂
志，1989，20(5)：195
1 熊建辉，张维冰，许国旺，张玉奎，非水毛细管电泳进展，色谱，2000，18(3)：218—223
2 Herrero-Martinez JM, Femandez-Marti M, Simo-Alfonso E, Rarnis-Ramos G, Determination of alkyphenol ethoxylates by micellar electrokinetic chromatography with bile salts, Electrophoresis, 2001, 22: 526-534
3 Walbrohel Y, Jorgenson J W, On-column UV absorption detector for open tubular capillary zone electrophoresis, J Chromatogr A, 1984, 315: 135-143
4 Hansen SH, Bjφrnsdottir I, Tjφrnrlund J, Separation of cationic cistrans isomers and diastereoisomers using non aqueous capillary electrophoresis, Electrophoresis,1998, 19: 2179-2186
5 Altria K D, Kelly MA, Clark BJ, Current applications in the analysis of pharmaceuticals by capillary electrophoresis, Trends Anal Chem., 1998, 17(14): 204-214
6 Salimi-Moosavi H, Capillary electrophoresis in pure nonaqueous solvents, Dss Abstr Int., B 1998, 58(12): 6543
7 徐木生，王小如，杨芃原，贾丽，非水介质毛细管电泳，色谱，1998，16(4)：309—313
8 Ji SG, Chai YF, Zhang GQ, Wu YT, Yin XP, Determination oftetrahydro- palmatine in Chinese traditional medicine by nonaqueous capillary electro- phoresis,Electrophoresis, 1999, 20: 1904-1906
9 Fillet M, Bechet I, Piette V, Crommen J, Separation of nonateroidal anti-inflammatory drug by capillary electrophoresis using nonaqueous electrolytes,Electrophoresis, 1999, 20: 1907-1915
10 Samir C, Serge R, Jean-Luc V, Nonaqueous capillary electrophoresis-mass spectrometry for separation of venlafaxine and its phase 1 metabolites, Electro-
phoresis, 2001, 22: 491-496
11 Lin S, Li YC, Sakurai N, Zheng YL, Isolation and structure of sesquiterpene alkaloids from Tripterygium wilfordii Hook, Acta pharmaceutica sinica, 1995, 30(7): 513-516
1 概述，佐米曲坦及片剂(Zoming)项目简介，http://www.Orientpharm.Com/b1/bxm2hr4.htm
2 Castaner J, Zomitriptan and synthetize, Drag of the future, 1997, 22(3): 260
3 Schoenen J, Sawyer J, Zolmitriptan [Zoming(TM, 311C90)], a novel dual central and peripheral 5-HTIB/ID agonist: an overview of efficacy, Cephalalgia, 1997,17(18): S28
4 Dixon R, Warrander A, The clinical pharrnacokinetics of zolmitriptan, Cephalalgia,1997, 17(18): S15
5 Seaber E, On N, Dixon RM, The absolute bioavailability and metabolic disposition of the novel antimigraine componed zolmitriptan(311C90), J Clin Pharmcol, 1997,43(6): 579
6 Gotti R, Pomponio R, Cavrini V, Linear, netural polysaccharides as chiral selectors in enantioresolution of basic drug racemates by capillary electrophoresis,Chromatographia, 2000, 52(5/6): 273-278
7 Crego AL, Gonzalez MJ, Marina ML, Chiral separation of polychlorinated biphenyls by micellar electrokinetic chromatography with sodium cholate,Electrophoresis, 1998, 19: 2113-2118
8 Akos V, Martin GS, Ferenc K, Gerald G, Chiral separation of α-amino acids by ligand-exchange capillary electrophoresis using N-(2-hydroxy-octyl)-L-4-hydroxyproline as a selector, Eleetrophoresis, 1998, 19: 2109-2112
9 Wang F, Khaledi MG, Capillary electrophoresis chiral separations of basic compounds using cationic cyclodextrin, Electrophoresis, 1998, 19: 2095-2100
10 Jin YK, Stalcup AM, Application of heparin to chiral separations of antihistamines by capillary electrophoresis, Electrophoresis, 1998, 19: 2119-2123
11 阮总琴，尤进茂，李菊白，欧庆瑜，磺化β—环糊精的合成及其在毛细管电泳手性拆分中的应用，色谱，2000，18(2)：183—186
1 Morota T, Saito K, Komatsu Y, Extracts of new leukotriene antagonist for therapeatic use [P], 日本专利: 9752899, 1997-02-25
2 李耐三，于东晖，中药雷公藤毒代动力学研究，中国药科大学学报，1992，23(1)：25
3 Wiedmann TW, Wang J, Use of extracts of Tripterygium wilfordii Hook for treatment coronary arterial restenosis [P], 美国专利: 9515174, 1995-01-08
4 Wiedman TW, Wang J, Method for suppressing xeograft rejection [P], 美国专利: 5759550, 1998-06-02
5 Wiedman TW, Wang J, Plian NB, Immunosuppressants and root extracts of Tripterygium wilfordii Hook for treatment of transplant rejection[P], 美国专利: 5843452, 1998-11-09
6 Vigo-Pelfreg Cammen, The use of celastrol to treat aliheimer's disease [P], 美国专利: 9825573, 1998-06-18
7 李秀才，雷公藤的研究与临床作用，中国中药杂志，1997，22(1)：53
8 程自珍，肖银生，方义杰等，雷公藤提取工艺的探讨，中国医药工业杂志，1990，21(10)：435—436
9 Cai JJ, Tao XL, Lipsky PE. High performance liquid chromatographic determination of triptolide and triptonide in an ethyl acetate extract of Tripterygium wilfordii Hook,J. Liq. Chromatogr., 1994, 17(20): 4479-87
10 Tao XL, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract of Tripterygium wilfordii Hook, J. Pharmacology Exp. Ther, 1995, 272 (3): 1305-12
11 Zhang L, Zhang ZH, Sheng LS. Determination of triptolide in Tripterygium wilfordii Hook from different sources by capillary gas chromatography, Journal of Chinese Pharmaceutical University, 1992, 23 (3): 158-200