【作者】 徐志勇；

【导师】 刘启德；

【作者基本信息】 广州中医药大学 ， 中西医结合基础， 2005， 硕士

【摘要】 穿心莲软胶囊（APN soft capsules）系广州中医药大学新近开发的中药提取物制剂,是用爵床科植物穿心莲（Andrographis Paniculata Nees,APN）地上部分提取的浸膏制成。穿心莲属清热药,功效清热解毒,凉血消肿,辩证用于“里热证”的治疗,《泉州本草》记:“清热解毒,消炎退肿。治咽喉炎症,痢疾,高热”。药理研究表明,穿心莲制剂在解热、抗炎、抗菌抗病毒方面药效作用较强,临床广泛应用于感冒发热,急慢性咽炎,痢疾,内毒素血症等。本研究对穿心莲软胶囊进行急性毒性和主要药效学研究,为临床安全合理用药提供药理和实验依据。在药效学研究基础上,对穿心莲软胶囊解热机制进行探讨。 研究内容分三个部分: 一.穿心莲软胶囊急性毒性试验 预试验未能求得穿心莲软胶囊灌服小鼠半数致死量(LD₅₀),用最大耐受量法求得穿心莲软胶囊灌服小鼠1日最大耐受量为110.25g（生药）/kg。 二.穿心莲软胶囊主要药效学试验 1.穿心莲软胶囊解热试验 穿心莲软胶囊高剂量组（23.52g/kg）、中剂量组（11.76g/kg）1次灌胃给药,可显著抑制细菌脂多糖（LPS）诱导的家兔发热反应（与模型对照组比较P<0.05或P<0.01）,与等剂量的药典制剂穿心莲片（11.76g/kg）比较,注射LPS后1h内解热作用明显优于穿心莲片组（P<0.05）;穿心莲软胶囊高剂量组（22.68 g/kg）、中剂量组（11.34g/kg）1次灌胃给药,可显著降低啤酒酵母致大鼠发热的体温（与模型对照组比较P<0.05或P<0.01）,与等剂量的穿心莲片（11.34g/kg）比较,无显著性差异（P>0.05）。 2.穿心莲软胶囊抗炎试验 穿心莲软胶囊每日灌胃给药1次,连续3天,高剂量组（11.34g/kg）、中剂量组（5.67g/kg）均有显著抑制角叉菜胶致大鼠足肿胀作用（P<0.05或P<0.01）,与等剂量的药典制剂穿心莲片（5.67g/kg）比,无显著性差异（P>0.05）;穿心莲软胶囊每日灌胃给药1次,连续3天,高、中、低剂量组16.38g/kg、8.19g/kg、4.10g/kg均有显著降低二甲苯致小鼠耳肿胀作用;8.19g/kg、4.10g/kg、2.05g/kg可显著抑制醋酸所致的小鼠腹腔毛细血管通透性增加,与模型对照组比较,有显著性差异（P<0.05或P<0.01）。 3.穿心莲软胶囊镇痛试验 穿心莲软胶囊高、中、低剂量组（16.38g/kg、8.19g/kg、4.10g/kg）灌胃给药更多还原

【Abstract】 Andrographis Paniculata Nees soft capsules (APN soft capsules) is a pure traditional Chinese drug preparation that developed in Guangzhou university of traditional Chinese medicine recently, was made up of extraction from the plant Andrographis Paniculata. Andrographis Paniculata Nees is one kind of herbal drug for relieving the internal heat of the body, it has the effect of antifebrile, detoxifies, cooling blood and detumescence, so it’s used to treat the heat-syndrome of the interior in the differential diagnosis. In the medicinal works "the herbalism of QuanZhou" , there was the record for this medicinal plant that it may lower febrile, detoxify, diminish inflammation and tumefaction, may be used to the throat inflammation, dysentery and high fever. Previous pharmacological research indicated that APN preparation have strong action in antipyretic, antiphlogistic, antibacterial and antiviral. Therefore it’ s applied to the fever of cold, acute and chronic pharyngitis, dysentery, endotoxemia in clinic. In this study, we designed the acute toxicity and Pharmacodynamics experiments of APN soft capsules and its antipyretic mechanisms in order to offer pharmacological and experimental basis for its safe and effective use in clinic.There are three parts in the thesis:Part Ⅰ The experiment on acute toxicity of APN soft capsulesWe observed that the maximum tolerance dose(MTD) of APN soft capsules on mice, administered orally, is 110.25(crude drug)/kg, and no acute toxicity reaction has been observed.Part Ⅱ The experimental on Pharmacodynamics of APN soft capsules1. The experiment on antipyretic effect of APN soft capsulesIn acute fever model, the dose of 23. 52g/kg and 11.76g/kg of APN soft capsules administered orally showed potent inhibitory effect(p<0.05 or p<0. 01) on LPS-induced rabbit fever, and when compared with same dose of APN tablets (the preparation in pharmacopoeia), there was a remarkable difference within one hour after setting up of fever model. 22. 68g/kg, 11.34g/kg APN soft capsules, administered orally, have a better antipyretic effect in rat baker’ s yeast-induced fever(p<0.05 or p<0.01), but there was no remarkable difference compared with same dose APN tablet.2. The experiment on anti-inflammatory effect of APN soft capsulesIn acute inflammatory model, the dose of 11. 34g/kg and5. 67g/kg of APN soft capsules administered orally(three days) could reduce the pedal swelling in rat induced by carrageenin(vs model group p<0. 05), but there was no remarkable difference compared with same dose APN tablet. Moreover, APN soft capsules (16. 38, 8. 19, 4.lOg/kg), administered orally(three days), showed potent inhibitory effect on dimethylbenzene-induced mice auricle edema, and APN soft capsules(8.19,4.10,2.05g/kg) all showed inhibitory effect on acetic acid-induced increased permeability of mice abdominal capillary(vs model group p<0. 05 or p<0. 01).3. The experiment on analgesic effect of APN soft capsules16. 38g/kg, 8.19g/kg, 4. lOg/kg APN soft capsules administered orally, showed no effect on increasing the mice pain threshold of hot-plate test(vs model group p>0.05). Again, APN soft capsules showed no effective antinociception in the acetic acid induced writhing test in mice(vs model group p>0.05). PartHJ The research on antipyretic mechanism of APN soft capsules17.64g/kg APN soft capsules, administered- orally, showed potent inhibitory effects on LPS-induced rabbit fever, and within one hour after setting up of fever model, the AT, thermal response index(TRI) are all less than the model group(p<0.05), but have no remarkable difference with the control group(p>0. 05).Concentration of 5-HT and cAMP in rabbit’ s hypothalamus and cerebrospinal fluid (CSF) were measured lh after the fever model. The results indicated that 5-HT content in hypothalamus in APN soft capsules group are更多还原