【作者】 霍炎；

【导师】 郭澄； 秦路平；

【作者基本信息】 第二军医大学 ， 生药学， 2006， 硕士

【摘要】 根据国际疼痛研究会(IASP)对疼痛的定义:“一种不愉快的感觉和实际的或潜在的组织损伤所引发的情感经历;或者就这一损伤所做的描述”,疼痛属于一种不愉快的生理体验,它广泛出现于各种疾病的病程中,是临床上最常见的症状。由于外来的伤害或自身的病变,任何人的一生都难免疼痛,其中疼痛较重又不能自行缓解而需要就医者约占全人群的1/10。疼痛,特别是剧烈的或持久性疼痛,常使患者遭受种种痛苦,如惊慌、害怕、焦虑、悲伤、愤怒、烦躁、失眠,进而影响机体局部甚至整体的功能,严重者还可以导致生理功能紊乱,引发疼痛性休克。因此合理应用镇痛药,有效地控制疼痛十分重要,这不仅能解除患者痛苦,改善患者的生活质量,同时给他们心理极大的安慰,加强同疾病作斗争的信心。 目前用于疼痛治疗的药物主要有四类:一类是阿片类镇痛药,具有成瘾性;一类是作用于中枢的非阿片类镇痛药,但无抗炎抗风湿作用,并具有肝毒性;一类是作用于外周的抗炎镇痛药,但长期服用容易引起胃肠损害。一类是复方抗炎镇痛药,但由于联合用药机制的复杂性,该类药物还很少,而且安全性也需要进一步长期观察。 因此目前临床上仍缺乏理想的镇痛药物。近年来国内外对从天然药物中寻找新的镇痛成分研究十分活跃,从天然药物中寻找高效、低毒、无依赖性的镇痛新药将成为主流的发展趋势,已有用于临床的报道,如延胡索乙素、辣椒素等。 柠条籽是豆科锦鸡儿属植物小叶锦鸡儿(Caragana microphylla Lam.)的成熟种子,同时在不同地区也将中间锦鸡儿和树锦鸡儿的成熟种子作为柠条籽入药。其原植物生长于欧亚大陆干旱半干旱地区,主产于我国东北、华北、西北和西南各省区,我国产62种,大多数作为绿化及防风固沙植物,仅有少数应用于药用。柠条籽味苦,性寒。清热利咽,主治咽喉肿痛等症。 国内学者研究表明,锦鸡儿属植物中含有黄酮、二苯乙烯低聚体、三萜、生物碱等化学成分,但反映柠条籽临床功效与药理作用的有效成分有待阐明。目前柠条籽药材尚未被药典收载,且对于其原植物的植物分类学尚存在较大的争议。我们在内蒙古呼和浩特市采集柠条籽,将柠条籽75%乙醇浸膏用水混悬,依次用石油醚、氯仿、乙酸乙酯、正丁醇萃取,分成石油醚、氯仿、乙酸乙酯、正丁醇、水共5个极性部位,并对各部位进行了初步药效学试验,结果表明,柠条籽的总提物、石油醚及氯仿部位(1g更多还原

【Abstract】 In accordance with the International Association for the Study of Pain, pain has been defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. The pain appears widely in various kinds of diseases in clinic. Thousands of patients with intense and unrelenting pain need effective and potent analgesic agents. So it is very important to use analgesic exactly to control pain effectively, cause it can make the patient release their pain, improve their life quality, at the same moment give them a comfort and extra confidence to fight with diseases.According to the mechanism of pharmacological effect, analgesic agents are generally divided into opioid analgesics, such as alkaloid morphine, and non-steroidal anti-inflammatory drugs (NSAID), like aspirin. The opioid analgesics have some side effects such as addiction or respiratory depression and the NSAID has side effects to damage gastrointestinal tract. So it is necessary to search for new effective and nontoxic analgesics in plant-derived secondary metabolites. The antinociceptive substances obtained includealkaloids, terpenoids and flavonoids recently.Caragana microphylla Lam., a plant of Caragana genus (Leguminosae family), is widely distributed in the North and West parts of China. Its roots and seeds have been used to heal swollen and painful throat in folk medicine. And it is also used by the native farmers to prevent sand erosion thus making it stationary.The main compounds in Caragana microphylla Lam. were reported as flavonoids, oligomeric stilbenes, triterpene and alkaloids, but the active components reflecting clinical effectiveness were still unknown. 75% ethanol extraction of the seeds, collected from Huhehaote City of Inner-Mongolia Autonomous Region, People’s Republic of China, in July, 2004, was partitioned into five fractions as petroleum spirit, chloroform, acetic ether, n-butanol and water portion. Guided with initial pharmacological activities test on mice stretching model, petroleum and chloroform fractions were showed to have obvious analgesic action on reducing the times of mice writhing reaction caused by acetic acid.Twenty components were obtained from the chloroform fraction using column chromatography of silica gel, Sephadex LH-20, ODS and HPLC. Sixteen of them were identified on the basis of spectral analysis (UV, IR, EI-MS, FAB-MS, ^-NMR, 13C-NMR, 2D-NMR) and phytochemical properties, and we identified eighteen of them. Among them main components were flavonoids, triterpene and alkaloids. A new compound was elucidated and eleven compounds were isolated from Caragana microphylla Lam. for the first time. And we also identified twenty five compound of the petroleum fraction by GC-MS for the first time. The main compound of it is the linoleic acid (50.64%), oleic acid (17.43%) and palmitic acid (11.67%).The total alkaloids and the five alkaloids were essayed by the mice stretching model. We found that the total alkaloids and some alkaloids showed strong analgesia activity. And according to the traditional use, we also essayed the cytotoxicity activity of all the fractions and compounds in vitro and some compounds showed significant cytotoxicity activity. The results of the essay notified us that the seeds of Caragana microphylla Lam. may become the resource of antinociceptive and anticancer drugs.更多还原