【作者】 李书慧；

【导师】 吴立军； 折原裕；

【作者基本信息】 沈阳药科大学 ， 药物化学， 2005， 博士

【摘要】 祖师麻为瑞香科(Thymelaeaceae)瑞香属植物黄瑞香(Daphne giraldii Nitsche)的根皮和茎皮，具有“祛风除湿，止痛散瘀”之功效，主治“风湿痹痛、四肢麻木、头痛、胃痛及跌打损伤”等症，为民间治疗风湿和止痛的常用中药。黄瑞香多分布在我国陕西、甘肃、四川、宁夏、青海等地，为落叶灌木，多生于高山地的疏林中及阔叶树木下的阴湿处。 药理研究表明：祖师麻具有较强的镇痛、抗炎、抑菌等药理活性，在临床上多用于风湿病痛的治疗，疗效显著。鉴于祖师麻镇痛抗炎成分(祖师麻甲素)明确，临床疗效好，我们采用大孔吸附树脂柱色谱法，对镇痛抗炎活性成分进行富集，获得祖师麻活性部位，以此活性部位制成的药物制剂，药效实验显示有较强的镇痛抗炎活性，与临床作用一致；家兔长毒实验无明显肝、肾毒性，对体内主要脏器无毒性反应，对皮肤有一定的刺激作用，停药后可逐渐恢复；家兔急毒实验显示高剂量对皮肤有轻度刺激反应，黏膜、眼睛、中枢神经系统等未见有毒性反应。药理药效学研究结果表明祖师麻贴剂临床计量安全、有效。 本论文为了对祖师麻进行进一步开发，对祖师麻水提醇沉物的氯仿和正丁醇萃取层进行了深入的化学成分研究。利用各种色谱技术，共分离得到了32个化合物，根据理化性质和谱学数据鉴定了25个化合物的结构，其中新化合物2个，分别为黄瑞香苷A(giraldoid A，G-12)和黄瑞香苷B(giraldoid B，G-13)；一个新天然产物：1-(4-羟基-3,5-二甲氧基苯基)-1，2-丙二酮(1-(4-hydroxy-3,5-dimethoxyphenyl)-1，2-propanedione，G-21)。首次从瑞香属植物中分离得到了9个化合物，它们分别是：4-甲基-7-羟基香豆素(4-methy-7-hydroxycoumarin，G-6)，rutarensin(G-10)，edgeworoside C(G-11)，(+)-里立脂素-B-二甲酯((+)-liriorosinol-B-dimethyl ether，G-16)，(+)-丁香树脂酚双葡萄糖苷((+)-syringaresinol-di-O-β-D-glucoside，G-17)，罗汉松脂醇(matairesinol，G-18)，woonenoside Ⅺ (G-19)，4-羟基-3,5-二甲氧基苯甲醛(4-hydroxy-3,5-dimethoxybenzaldehyde，G-23)和α-D-吡喃果糖(α-D-fructopyrannose，G-25)。 由于大量砍伐，导致植物资源匮乏，祖师麻已被列为国家三级保护中药材。为解决祖师麻资源匮乏问题，本论文运用组织和细胞培养技术对祖师麻的原植物——黄瑞香进更多还原

【Abstract】 The bark of rhizoma and stems of Daphne giraldii Nitsche （Thymelaeaceae） , commonly called ’Zushima’ in China, is used as a folk medicine for the treatments of ache and rheumatism, especially for toothache, waist-ache, rheumatoid arthritis, quadriplegia, etc. D. giraldii Nitsche is a short shrub growing in alpine forest, and likes to shade site under broadleaf trees, and widely distributes in Shannxi, Gansu, Sichuan and Qinghai provinces of China.Pharmacological investigations showed that Zushima had strong analgesia, anti-inflammation, anti-thrombus, anti-tumor and anti-fertility activities and have been used as a analgesia and anti-inflammation agent in clinical treatments. In order to go further study on this plant, the effective part of Zushima had been obtained by macroporous resin chromatography （which is determined having most effective constituents by HPLC） from extract of it, and then made into the ZSM pastes, meanwhile, the pharmacodynamical investigations of ZSM pastes showed the analgesia and anti-inflammation activities, consisting with clinical applications. The ZSM pastes showed no toxic effect on liver, kidney and main viscera, and the stimulate effect was found in skin, but it can be recovered by drug-ending in chronic toxicological investigations. The results showed the high dose of ZSM paste had stimulate effect on rabbit’s skin, but no toxic effect was found in mucous membrane, eyes and nerve central system in acute toxicological investigations, which suggested that the paste is safe for the clinic usement.In order to go further research on the Zushima, the chemical investigations on the CHCl₃ and n-BuOH layer were carried out. By using silica gel C.C. and PHPLC chromatographies, 32 compounds were isolated and the structures of 25 compounds were identified by their physico-chemical characteristic and spectra data. Among them, two compounds were identified as novel compounds, which named as giraldoid A更多还原