滇鸡血藤的化学成分及复方鸡血藤制剂的制备工艺与质量标准研究
摘要
复方鸡血藤膏为传统中药，收载于《中国药典》(2005版一部)，由滇鸡血藤膏粉、川牛膝、续断、红花、黑豆等加工而成，功能补血、活血、调经，用于血虚、手足麻木、关节酸痛和月经不调。该制剂疗效确切、历史悠久，但由于基础研究薄弱，剂型落后，缺乏特征性的定性定量指标。本课题关键目的是研究制定可控性强的复方鸡血藤制剂的质量标准，为此首先需要对滇鸡血藤进行化学成分研究，阐明主要药效物质基础，并改革复方鸡血藤膏传统工艺，制备量小、方便的新制剂。
滇鸡血藤膏粉为滇鸡血藤的水提干浸膏粉，为方中君药，功效明显、剂量大，是复方鸡血藤制剂质量控制研究的重点。滇鸡血藤主要来源于五味子科南五味子属内南五味子(Kadsura interior A．C．Smith)和异型南五味子(K．heteroclita(Roxb．)Craib．)的藤茎。我们对滇鸡血藤化学成分进行研究，采用硅胶柱色谱、HPLC制备色谱以及红外、紫外、旋光谱、质谱、核磁共振(氢谱、碳谱、HMQC、HMBC和NOESY)等波谱技术从滇鸡血藤乙酸乙酯部位分离鉴定了17个木脂素、2个三萜(甘五酸、马五味子酸)和β—谷甾醇。木脂素类化合物包括联苯环辛烯类木脂素10个：南五味子酯甲、南五味子酯乙、滇南五味子酮、南五味子素、异型南五味子丙素、内南五味子酯丙、五脂酮A、binankadsurin A、angeloylbinankadsurin A、戈米辛U；螺苯骈呋喃型联苯环辛烯类木脂素6个：南五味子酯丙、滇南五味子酯、异型南五味子丁素、内南五味子素、schiarisanrin C、异型南五味子庚素；2，3-二甲基-1，4二芳基丁烷类木脂素1个：内消旋二氢愈创木脂酸。其中南五味子酯甲、乙、丙和滇南五味子酯为新化合物，滇南五味子酮为首次从自然界中分离得到；南五味子酯丙为首个C-2位无氧取代的联苯环辛烯类木脂素；异型南五味子丁素含量高，具有抗氧化、抗病毒活性，且能明显抑制KCl、CaCl_2和NA产生的血管收缩以及ADP和PAF诱导的兔血小板聚集，可作为复方鸡血藤膏质量控制的指标成分。
复方鸡血藤膏工艺改革同时以有效成分含量和药效为考察指标。建立了变色酸钠-浓硫酸比色法测定总木脂素的含量，以小鼠肠系膜微循环实验进行药效学研究。比较发现，滇鸡血藤醇提浸膏粉的总木脂素含量和促微循环作用都明显高于水提滇鸡血藤膏粉，说明总木脂素含量的高低可反映药效强弱，因而滇鸡血藤采用乙醇提取较为合理。采用正交设计优选出滇鸡血藤的最佳提取方案为：80％乙醇冷浸24小时，以每3小时1倍体积的流速渗漉，共收集渗漉液40倍体积。滇鸡血藤膏粉(醇提)新的处方剂量通过滇鸡血藤醇、水提取物的量效关系考察确定为原水提滇鸡血藤膏粉的1／4。新处方制备成复方鸡血藤胶囊后，每次服药剂量由10g降至1.2g(4粒)。另外，单纯改变传统剂型，制备了复方鸡血藤颗粒剂。新制剂克服了复方鸡血藤膏剂量大、服用不方便的缺点。
质量标准研究重点建立指标成分的含量测定方法。通过优化色谱条件，建立了滇鸡血藤药材、滇鸡血藤膏粉、复方鸡血藤颗粒、复方鸡血藤胶囊及其中间体中异型南五味子庚素、戈米辛A、内南五味子素、内南五味子乙素、异型南五味子丁素、南五味子素、五味子甲素和五味子丙素8个木脂素的HPLC-DAD含量测定方法，并进行了方法学考察。结果表明采用HPLC方法测定以上五个样品中的木脂素含量可行，滇鸡血藤醇提浸膏粉、复方鸡血藤胶囊及其中间体中8个木脂素成分均可准确定量；复方鸡血藤颗粒和滇鸡血藤药材中除五味子甲素外7个木脂素可准确定量。三批样品测定结果表明，异型南五味子丁素、南五味子素、内南五味子素3个木脂素在滇鸡血藤及其复方制剂中含量普遍较高，批次间无明显差异；其中异型南五味子丁素含量最高，活性较强，其抑制血管收缩和血小板聚集的作用体现了复方制剂的活血功效，被确定为复方鸡血藤制剂含量测定的指标成分。根据三批样品的测定结果建议复方鸡血藤胶囊每粒含丁素含量不得少于0.35mg；复方鸡血藤颗粒丁素含量不得少于8.2μg／g。另外，建立了复方鸡血藤制剂中滇鸡血藤、川牛膝和续断的TLC定性鉴别方法，特征明显。
本文明确了滇鸡血藤主要药效物质基础和指标成分，为复方鸡血藤制剂质量控制提供了对照品；同时以有效成分含量和药理活性为依据，改革了复方鸡血藤膏的制备工艺，克服了传统中药制剂剂量大、服用不便的缺点；首次建立起复方鸡血藤制剂较为系统、完善的质量标准，含量测定方法稳定，TLC鉴别特征性强，弥补了复方鸡血藤膏难以准确鉴别、定量的不足，提高了制剂质量的可控性。
Fufang Jixueteng Gao, a traditional Chinese patent medicine, is made up of the powder of Dian Jixueteng Gao, Radix Cyathulae, Radix Dipsaci, Flos Carthami and Semen Glycine. It's mainly used for the treatment of blood deficiency, numb hands and feet, painful aching of the joints and irregular menstruation. As the foundational research of Fufang Jixueteng Gao is very limited, there was no characteristic method to estimate and control its quality effectively. In order to establish the quality standards of Fufang Jixueteng preparations, the chemical constituents of Caulis Kadsurae was investigated first of all. The procedure of the traditional preparation was also improved.
Dian Jixueteng Gao is the water extract of Caulis Kadsurae, the stems Kadsura interior A. C. Smith and K. heteroclita (Roxb.) Craib. Previous studies indicated that the dibenzocyclooctene-type lignans were principal bioactive constituents of K. interior and K. heteroclita, which showed various biological activities, such as anti-lipid peroxidation, antitumor-promoting effect and calcium antagonism. No chemical study of Caulis Kadsurae has been reported yet. Our current investigation on the chemical constituents of the EtOAc soluble extract of Caulis Kadsurae led to the isolation and identification of 17 lignans, kadsutherins A~C, diankadsutherin, diankadsurinone, kadsurin, interiotherin C, heteroclitin C, schisanlignone A, binankadsurin A, gomisin U, heterocltin D, interiorin, schiarisanrin C, heteroclitein G, meso-dihydroguaiaretic acid, together with ganwuweizic acid, mawuweizic acid and P-sitosterol. Kadsutherins A~C and diankadsutherin were new compounds. Kadsutherin C is the first dibenzocyclooctene lignan without oxygen-containing substitute at C (2). Diankadsurinone was a new natural compound. Heteroclitin D was isolated from Caulis Kadsurae with a high yield, which showed significant anti-lipid peroxidative effect and inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation and on platelets aggregation induced by ADP and PAR Heteroclitin D can be used as the chemical marker for quality control of Fufang Jixueteng preparations.
The procedure of Fufang Jixueteng Gao was improved on the basis of the contents of bioactive lignans and the main activities of the preparations. Caulis Kadsurae was extracted with water and ethanol, respectively. The content of total lignans in the ethanolic extract was much higher than that of the water extract, as well as the activity to promote tiny blood circulation of mesentery. It suggested that the bioactive lignans couldn't be extracted completely by water. It's more reasonable to extract Caulis Kadsurae with ethanol to prepare Fufang Jixueteng Gao. The procedure was optimized by orthogonal designs. 54.69g of the ethanolic extracted Fufang Jixueteng Gao was equivalent to 218.75g of the water extract on the activity. Fufang Jixueteng Gao was transformed to capsules and granules. The two new preparations were more convenient for taking than the original Fufang Jixueteng Gao.
HPLC-DAD was used for quantitative determination of eight lignans, heteroclitin G, gomisin A, interiorin, interiorin B, heteroclitin D, kadsurin, deoxyschisandrin and schisandrin C, in Caulis Kadsurae and its preparations. The method was stable and feasible. All of the eight lignans could be determined exactly in the ethanolic extract of Caulis Kadsurae, Fufang Jixueteng capsules and its intermediate products. Seven of the lignans could be determined exactly in Caulis Kadsurae and Fufang Jixueteng granules. The content of heteroclitin D was higer than that of any other lignans in Fufang Jixueteng capsules and granules. And there was no significant difference among three batchs of capsules or granules on the content of Heterocltin D. Thus, heteroclitin D was taken as the chemical marker of the Fufang Jixueteng preparations. Additionally, TLC methods were established to identify Caulis Kadsurae, Radix Cyathulae and Radix Dipsaci in Fufang Jixueteng preparations.
Based on the above conclusions, the quality standards of Fufang Jixueteng capsules and granules were established. The quality of the traditional Fufang Jixueteng preparations can be controlled effectively by the above characteristic TLC identification and quantitative determination.
滇鸡血藤膏粉为滇鸡血藤的水提干浸膏粉，为方中君药，功效明显、剂量大，是复方鸡血藤制剂质量控制研究的重点。滇鸡血藤主要来源于五味子科南五味子属内南五味子(Kadsura interior A．C．Smith)和异型南五味子(K．heteroclita(Roxb．)Craib．)的藤茎。我们对滇鸡血藤化学成分进行研究，采用硅胶柱色谱、HPLC制备色谱以及红外、紫外、旋光谱、质谱、核磁共振(氢谱、碳谱、HMQC、HMBC和NOESY)等波谱技术从滇鸡血藤乙酸乙酯部位分离鉴定了17个木脂素、2个三萜(甘五酸、马五味子酸)和β—谷甾醇。木脂素类化合物包括联苯环辛烯类木脂素10个：南五味子酯甲、南五味子酯乙、滇南五味子酮、南五味子素、异型南五味子丙素、内南五味子酯丙、五脂酮A、binankadsurin A、angeloylbinankadsurin A、戈米辛U；螺苯骈呋喃型联苯环辛烯类木脂素6个：南五味子酯丙、滇南五味子酯、异型南五味子丁素、内南五味子素、schiarisanrin C、异型南五味子庚素；2，3-二甲基-1，4二芳基丁烷类木脂素1个：内消旋二氢愈创木脂酸。其中南五味子酯甲、乙、丙和滇南五味子酯为新化合物，滇南五味子酮为首次从自然界中分离得到；南五味子酯丙为首个C-2位无氧取代的联苯环辛烯类木脂素；异型南五味子丁素含量高，具有抗氧化、抗病毒活性，且能明显抑制KCl、CaCl_2和NA产生的血管收缩以及ADP和PAF诱导的兔血小板聚集，可作为复方鸡血藤膏质量控制的指标成分。
复方鸡血藤膏工艺改革同时以有效成分含量和药效为考察指标。建立了变色酸钠-浓硫酸比色法测定总木脂素的含量，以小鼠肠系膜微循环实验进行药效学研究。比较发现，滇鸡血藤醇提浸膏粉的总木脂素含量和促微循环作用都明显高于水提滇鸡血藤膏粉，说明总木脂素含量的高低可反映药效强弱，因而滇鸡血藤采用乙醇提取较为合理。采用正交设计优选出滇鸡血藤的最佳提取方案为：80％乙醇冷浸24小时，以每3小时1倍体积的流速渗漉，共收集渗漉液40倍体积。滇鸡血藤膏粉(醇提)新的处方剂量通过滇鸡血藤醇、水提取物的量效关系考察确定为原水提滇鸡血藤膏粉的1／4。新处方制备成复方鸡血藤胶囊后，每次服药剂量由10g降至1.2g(4粒)。另外，单纯改变传统剂型，制备了复方鸡血藤颗粒剂。新制剂克服了复方鸡血藤膏剂量大、服用不方便的缺点。
质量标准研究重点建立指标成分的含量测定方法。通过优化色谱条件，建立了滇鸡血藤药材、滇鸡血藤膏粉、复方鸡血藤颗粒、复方鸡血藤胶囊及其中间体中异型南五味子庚素、戈米辛A、内南五味子素、内南五味子乙素、异型南五味子丁素、南五味子素、五味子甲素和五味子丙素8个木脂素的HPLC-DAD含量测定方法，并进行了方法学考察。结果表明采用HPLC方法测定以上五个样品中的木脂素含量可行，滇鸡血藤醇提浸膏粉、复方鸡血藤胶囊及其中间体中8个木脂素成分均可准确定量；复方鸡血藤颗粒和滇鸡血藤药材中除五味子甲素外7个木脂素可准确定量。三批样品测定结果表明，异型南五味子丁素、南五味子素、内南五味子素3个木脂素在滇鸡血藤及其复方制剂中含量普遍较高，批次间无明显差异；其中异型南五味子丁素含量最高，活性较强，其抑制血管收缩和血小板聚集的作用体现了复方制剂的活血功效，被确定为复方鸡血藤制剂含量测定的指标成分。根据三批样品的测定结果建议复方鸡血藤胶囊每粒含丁素含量不得少于0.35mg；复方鸡血藤颗粒丁素含量不得少于8.2μg／g。另外，建立了复方鸡血藤制剂中滇鸡血藤、川牛膝和续断的TLC定性鉴别方法，特征明显。
本文明确了滇鸡血藤主要药效物质基础和指标成分，为复方鸡血藤制剂质量控制提供了对照品；同时以有效成分含量和药理活性为依据，改革了复方鸡血藤膏的制备工艺，克服了传统中药制剂剂量大、服用不便的缺点；首次建立起复方鸡血藤制剂较为系统、完善的质量标准，含量测定方法稳定，TLC鉴别特征性强，弥补了复方鸡血藤膏难以准确鉴别、定量的不足，提高了制剂质量的可控性。
Fufang Jixueteng Gao, a traditional Chinese patent medicine, is made up of the powder of Dian Jixueteng Gao, Radix Cyathulae, Radix Dipsaci, Flos Carthami and Semen Glycine. It's mainly used for the treatment of blood deficiency, numb hands and feet, painful aching of the joints and irregular menstruation. As the foundational research of Fufang Jixueteng Gao is very limited, there was no characteristic method to estimate and control its quality effectively. In order to establish the quality standards of Fufang Jixueteng preparations, the chemical constituents of Caulis Kadsurae was investigated first of all. The procedure of the traditional preparation was also improved.
Dian Jixueteng Gao is the water extract of Caulis Kadsurae, the stems Kadsura interior A. C. Smith and K. heteroclita (Roxb.) Craib. Previous studies indicated that the dibenzocyclooctene-type lignans were principal bioactive constituents of K. interior and K. heteroclita, which showed various biological activities, such as anti-lipid peroxidation, antitumor-promoting effect and calcium antagonism. No chemical study of Caulis Kadsurae has been reported yet. Our current investigation on the chemical constituents of the EtOAc soluble extract of Caulis Kadsurae led to the isolation and identification of 17 lignans, kadsutherins A~C, diankadsutherin, diankadsurinone, kadsurin, interiotherin C, heteroclitin C, schisanlignone A, binankadsurin A, gomisin U, heterocltin D, interiorin, schiarisanrin C, heteroclitein G, meso-dihydroguaiaretic acid, together with ganwuweizic acid, mawuweizic acid and P-sitosterol. Kadsutherins A~C and diankadsutherin were new compounds. Kadsutherin C is the first dibenzocyclooctene lignan without oxygen-containing substitute at C (2). Diankadsurinone was a new natural compound. Heteroclitin D was isolated from Caulis Kadsurae with a high yield, which showed significant anti-lipid peroxidative effect and inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation and on platelets aggregation induced by ADP and PAR Heteroclitin D can be used as the chemical marker for quality control of Fufang Jixueteng preparations.
The procedure of Fufang Jixueteng Gao was improved on the basis of the contents of bioactive lignans and the main activities of the preparations. Caulis Kadsurae was extracted with water and ethanol, respectively. The content of total lignans in the ethanolic extract was much higher than that of the water extract, as well as the activity to promote tiny blood circulation of mesentery. It suggested that the bioactive lignans couldn't be extracted completely by water. It's more reasonable to extract Caulis Kadsurae with ethanol to prepare Fufang Jixueteng Gao. The procedure was optimized by orthogonal designs. 54.69g of the ethanolic extracted Fufang Jixueteng Gao was equivalent to 218.75g of the water extract on the activity. Fufang Jixueteng Gao was transformed to capsules and granules. The two new preparations were more convenient for taking than the original Fufang Jixueteng Gao.
HPLC-DAD was used for quantitative determination of eight lignans, heteroclitin G, gomisin A, interiorin, interiorin B, heteroclitin D, kadsurin, deoxyschisandrin and schisandrin C, in Caulis Kadsurae and its preparations. The method was stable and feasible. All of the eight lignans could be determined exactly in the ethanolic extract of Caulis Kadsurae, Fufang Jixueteng capsules and its intermediate products. Seven of the lignans could be determined exactly in Caulis Kadsurae and Fufang Jixueteng granules. The content of heteroclitin D was higer than that of any other lignans in Fufang Jixueteng capsules and granules. And there was no significant difference among three batchs of capsules or granules on the content of Heterocltin D. Thus, heteroclitin D was taken as the chemical marker of the Fufang Jixueteng preparations. Additionally, TLC methods were established to identify Caulis Kadsurae, Radix Cyathulae and Radix Dipsaci in Fufang Jixueteng preparations.
Based on the above conclusions, the quality standards of Fufang Jixueteng capsules and granules were established. The quality of the traditional Fufang Jixueteng preparations can be controlled effectively by the above characteristic TLC identification and quantitative determination.
引文
[1] 丁智慧，罗士德．化学学报，1990，48：1075．
[2] D. F. Chen, S. X. Zhang, K. Chen, B. N. Zhou, P. Wang, L.M. Cosentino, K. H. Lee, J. Nat. Prod. 1996, 59, 1066.
[3] D. F. Chen, G. J. Xu, X. W. Yang, M. Hattori, Y. Tezuka, T. Kikuchi, T. Namba, Phytochemistry 1992, 31, 629.
[4] D. F. Chen, S. X. Zhang, M. Kozuka, Q. Z. Sun, J. Feng, Q. Wang, T. Mukainaka, Y. Nobukuni, H. Tokuda, H. Nishino, H. K. Wang, S. L. Morris-Natschke, K. H. Lee, J. Nat. Prod. 2002, 65, 1242.
[5] D. F. Chen, S. X. Zhang, L. Xie, J. X. Xie, K. Chen, Y. Kashiwada, B. N. Zhou, P. Wang, L. M. Cosentino, K. H. Lee, Bioorg. Med. Chem. 1997, 5, 1715.
[6] X.M. Zhang, D. F. Chen, X. J. He, S. Yang, P. Zheng, M. H. Jiang, Acta Pharmacol. Sin. 2000, 21,373.
[7] H.L. Peng, D. F. Chert, H. X. Lan, X. M. Zhang, Z. Gu, M. H. Jiang, Acta Pharmacol. Sin. 1996, 17, 538.
[8] X.W. Yang, H. Miyashiro, M. Hattori, T. Namba, Y. Tezuka, T. Kikuchi, D, F. Chen, G. J. Xu, T. Hori, M. Extine, H. Mizuno, Chem. Pharm. Bull. 1992, 40, 1510.
[9] L.N. Li, H. Xue, D. L. Ge, et al. Planta Medica, 1989, 55: 300.
[10] Z. W. Jia, Z. X. Liao, D. F. Chen. Helvetica Chimica Acta, 2005, 88: 2288.
[11] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull. 1979, 27, 1383.
[12] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull. 1980, 28, 3357.
[13] Li, L.; Xue, H. Phytochemistry 1990, 29, 2730.
[14] Y. H. Kuo, L. M. Yang, C. F. Chen. J. Org. Chem. 1997, 62, 3242.
[15] 秦国伟，陈业高．中药开发与研究综述．香港科技大学生物技术研究所编．科学出版社．2000，280．
[16] Y. Ikeya, N. Ookawa, H. Taguchi, et al. Chem. Pharm. Bull. 1982, 30, 3202.
[17] H. E. Gottlieb, M. Mervic, E. Ghera. Chem. Soc. Perkin Trans. I, 1982: 2353.
[18] 刘嘉森，周洪星．化学学报，1991，49：412．
[19] N. Ookawa, Y. Ikeya, H. Taguchi, et al. Chem. Pharm. Bull., 1981, 29 (1): 123.
[20] Y. Ikeya, H. Kanatani, M. Hakozaki, et al. Chem. Pharm. Bull., 1988, 36, 3974.
[21] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull., 1979, 27 (7):1583.
[22] 陈耀祖．高等学校化学学报，1987，8(5)：447．
[23] X. M. Zhang, D. F. Chen, X. J. He, et al. Acta Pharmacol. Sin. 2000, 21,373.
[24] 蒋仕丽，张蕴毅，陈道峰．复旦学报(医学版)，2005，32(4)：467．
[1] 陈道峰，翁强，施大文．南五味子属药用植物的木脂素含量．中草药，1994，25(5)：239．
[2] 徐莲英，侯世祥．中药制药工艺技术解析．北京：人民卫生出版社，2004：132．
[1] 司徒冰，陈道峰，郁韵秋．异型南五味子木脂素的HPLC法测定．中草药，1996，27(8)：465．
[2] 郁韵秋，陈道峰，司徒冰．高效液相色谱法测定内南五味子的木脂素含量．药物分析杂志，1996，16(5)：313．
[3] 陈道峰，翁强，施大文．南五味子属药用植物的木脂素含量．中草药，1994，25(5)：238．
[4] 蒋仕丽，张蕴毅，陈道峰．异型南五味子丁素、五味子酚和(+)-安五脂素对血小板聚集的影响．复旦学报(医学版)，2005，32(4)：467．
[5] X. M. Zhang, D. F. Chen, X. J. He, et al. Blocking effects of heteroclitin D and gomisin J on L-type calcium channels in ventricular cells of guinea pig. Acta Pharmacol. Sin. 2000, 21, 373.
[6] L. N. Li, X. J. Qi, D. L. Ge and M. Kung. Neokadsuranin, a terahydrofuranoid dibenzocyclootadiene lignan from stems of Kadsura coccinea. Planta med. 1988, 51 (4):45.
[2] D. F. Chen, S. X. Zhang, K. Chen, B. N. Zhou, P. Wang, L.M. Cosentino, K. H. Lee, J. Nat. Prod. 1996, 59, 1066.
[3] D. F. Chen, G. J. Xu, X. W. Yang, M. Hattori, Y. Tezuka, T. Kikuchi, T. Namba, Phytochemistry 1992, 31, 629.
[4] D. F. Chen, S. X. Zhang, M. Kozuka, Q. Z. Sun, J. Feng, Q. Wang, T. Mukainaka, Y. Nobukuni, H. Tokuda, H. Nishino, H. K. Wang, S. L. Morris-Natschke, K. H. Lee, J. Nat. Prod. 2002, 65, 1242.
[5] D. F. Chen, S. X. Zhang, L. Xie, J. X. Xie, K. Chen, Y. Kashiwada, B. N. Zhou, P. Wang, L. M. Cosentino, K. H. Lee, Bioorg. Med. Chem. 1997, 5, 1715.
[6] X.M. Zhang, D. F. Chen, X. J. He, S. Yang, P. Zheng, M. H. Jiang, Acta Pharmacol. Sin. 2000, 21,373.
[7] H.L. Peng, D. F. Chert, H. X. Lan, X. M. Zhang, Z. Gu, M. H. Jiang, Acta Pharmacol. Sin. 1996, 17, 538.
[8] X.W. Yang, H. Miyashiro, M. Hattori, T. Namba, Y. Tezuka, T. Kikuchi, D, F. Chen, G. J. Xu, T. Hori, M. Extine, H. Mizuno, Chem. Pharm. Bull. 1992, 40, 1510.
[9] L.N. Li, H. Xue, D. L. Ge, et al. Planta Medica, 1989, 55: 300.
[10] Z. W. Jia, Z. X. Liao, D. F. Chen. Helvetica Chimica Acta, 2005, 88: 2288.
[11] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull. 1979, 27, 1383.
[12] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull. 1980, 28, 3357.
[13] Li, L.; Xue, H. Phytochemistry 1990, 29, 2730.
[14] Y. H. Kuo, L. M. Yang, C. F. Chen. J. Org. Chem. 1997, 62, 3242.
[15] 秦国伟，陈业高．中药开发与研究综述．香港科技大学生物技术研究所编．科学出版社．2000，280．
[16] Y. Ikeya, N. Ookawa, H. Taguchi, et al. Chem. Pharm. Bull. 1982, 30, 3202.
[17] H. E. Gottlieb, M. Mervic, E. Ghera. Chem. Soc. Perkin Trans. I, 1982: 2353.
[18] 刘嘉森，周洪星．化学学报，1991，49：412．
[19] N. Ookawa, Y. Ikeya, H. Taguchi, et al. Chem. Pharm. Bull., 1981, 29 (1): 123.
[20] Y. Ikeya, H. Kanatani, M. Hakozaki, et al. Chem. Pharm. Bull., 1988, 36, 3974.
[21] Y. Ikeya, H. Taguchi, I. Yosioka, et al. Chem. Pharm. Bull., 1979, 27 (7):1583.
[22] 陈耀祖．高等学校化学学报，1987，8(5)：447．
[23] X. M. Zhang, D. F. Chen, X. J. He, et al. Acta Pharmacol. Sin. 2000, 21,373.
[24] 蒋仕丽，张蕴毅，陈道峰．复旦学报(医学版)，2005，32(4)：467．
[1] 陈道峰，翁强，施大文．南五味子属药用植物的木脂素含量．中草药，1994，25(5)：239．
[2] 徐莲英，侯世祥．中药制药工艺技术解析．北京：人民卫生出版社，2004：132．
[1] 司徒冰，陈道峰，郁韵秋．异型南五味子木脂素的HPLC法测定．中草药，1996，27(8)：465．
[2] 郁韵秋，陈道峰，司徒冰．高效液相色谱法测定内南五味子的木脂素含量．药物分析杂志，1996，16(5)：313．
[3] 陈道峰，翁强，施大文．南五味子属药用植物的木脂素含量．中草药，1994，25(5)：238．
[4] 蒋仕丽，张蕴毅，陈道峰．异型南五味子丁素、五味子酚和(+)-安五脂素对血小板聚集的影响．复旦学报(医学版)，2005，32(4)：467．
[5] X. M. Zhang, D. F. Chen, X. J. He, et al. Blocking effects of heteroclitin D and gomisin J on L-type calcium channels in ventricular cells of guinea pig. Acta Pharmacol. Sin. 2000, 21, 373.
[6] L. N. Li, X. J. Qi, D. L. Ge and M. Kung. Neokadsuranin, a terahydrofuranoid dibenzocyclootadiene lignan from stems of Kadsura coccinea. Planta med. 1988, 51 (4):45.