【作者】 王选慧；

【导师】 王雯慧； 梁剑平；

【作者基本信息】 甘肃农业大学 ， 基础兽医学， 2006， 硕士

【摘要】 金丝桃素新制剂是中国农业科学院兰州畜牧与兽药研究所在国内外首次研制成功并用于防治畜禽疾病的高效兽用抗病毒药物。该新制剂的主要成分金丝桃素（hypericin,HY）是从贯叶连翘（hypericum perforatum L.）中提取的一种萘骈二蒽酮类化合物,具有显著的抗病毒作用。为了客观评价金丝桃素新制剂的安全性,以便在临床推广应用。本文对金丝桃素新制剂进行了急性和亚急性毒性实验。首先选用30只健康小白鼠,按1:0.6的等比级数设0.8g/kg、1.3g /kg、2.2g/kg、3.6g /kg、6.0g/kg和10.0g/kg体重6个给药剂量组,每只小白鼠均按各自所需药量灌服给药一次,进行急性毒性预实验研究。结果表明,6个给药剂量组小白鼠的临床表现正常,未出现中毒现象,说明该实验所设剂量范围偏小,需在正式实验时加大剂量范围,拉大剂量差值。在预实验基础上又选用50只健康小白鼠,按1:0.75的等比级数设7.5g/kg、10.0g/kg、13.3g/kg、17.7g/kg和23.6g/kg体重5个给药剂量组,每只小白鼠均按各自所需药量灌服给药一次进行急性毒性实验。结果显示:5个给药剂量组小白鼠临床表现正常,未出现中毒现象;大体剖检与组织学检查未见变化,说明金丝桃素新制剂毒性极低。因为小白鼠的胃容积较小,不能在急性毒性实验中测算出金丝桃素新制剂的半数致死量,故而改用50只健康雏鸡,按1:0.75的等比级数设13.3g/kg、17.7g/kg、23.6g/kg、31.5g/kg和42.0g/kg体重5个剂量组进行急性毒性实验。结果显示,金丝桃素新制剂的半数致死量LD₅₀为32.42±0.0312g/kg,95%置信区间为28.16g/kg～37.33g/kg,根据药物急性毒性分级,可确定金丝桃素新制剂属实际无毒药物。因为金丝桃素新制剂临床应用期为3d,根据评价程序需要进行为期14d的亚急性毒性实验。为此本文又分别进行了雏鸡和大白鼠的亚急性毒性实验。首先选用60只健康雏鸡进行亚急性毒性实验,3个给药组剂量分别为高剂量组3.24g/kg体重、中剂量组0.76 g/kg体重和低剂量组0.22g/kg体重,每只动物均按各自所需药量灌服,1次/d,连续14d。结果显示:在雏鸡亚急性毒性实验整个给药期间,各给药组实验动物无死亡现象;三个给药组动物的临床表现、体重增长情况、脏器系数、大体剖检、组织学检查情况和超微结构观察结果等与空白对照组动物相比无异常改变,上述结果表明金丝桃素新制剂无毒副作用,临床应用安全。然后又选用60只健康大白鼠进行亚急性毒性实验,3个给药组更多还原

【Abstract】 The new preparations of hypericin was developed successfully in LanZhou Institute of Animal and Veterinary Pharmaceutics Science of Chinese Academy of Agricultural Sciences for the first time. It was mainly used to inhibiting animal disease such as anti-virosis. The most important component of the new preparations was hypericin, which was extracted from hypericum perforatum Linn and had effect on anti-virosis of animals.Acute and subacute toxicity experiments of the new preparations of hypericin were proceeded to evaluate the security of the preparations objectively so that the new preparations was used in clinical widely. First,30 mice were divided into six pharmaceutical dose groups （0.8g/kg、1.3g /kg、2.2g/kg、3.6g /kg、6.0g/kg and 10.0g/kg）. According to these datas, preparing acute toxicity experiment was proceeded. It was concluded that the toxicological phenomenas won`t observed in six giving pharmaceutical dose groups. The results showed that the random of dose of this experiment was narrow and needed to improve dose random in formal acute experiment. Second,50 mice were divided into five pharmaceutical dose groups on the basis of preparing experiment（7.5g/kg、10.0g /kg、13.3g/kg、17.7g /kg and 23.6g/kg）. According to these datas, the formal acute toxicity experiment was proceeded. It was concluded that these mice of five giving pharmaceutical dose groups didn’t appear toxicological symptoms, and that the clinical representation and histology checking had no abnormal surroundings. The results showed that the toxicity of the new preparations of hypericin was very low. Because of the acute toxicity experiment in mice didn’t give the LD50 of the new preparations of hypericin,acute toxicity experiment in chicken was proceeded,50 chickens were divided into five dose groups（13.3g/kg、17.7g /kg、23.6g/kg、31.5g /kg and 42.0g/kg）. It can be drawn conclusion that the LD₅₀ of the new preparations of hypericin was 32.42±0.0312g/kg.The results showed that the new preparations of hypericin was a practical non-poisonous drug.According to standard, subacute toxicity experiment was proceeded necessarily to evaluate the security of the new preparations of hypericin. So subacute experiments of chicken and rat were proceeded. There were three giving pharmaceutical dose groups of subacute toxicity experiment in chikens, the high dose group was 3.24g/kg,medium dose group was 0.76g/kg and the low dose group was 0.22g/kg. The three giving pharmaceutical dose groups of rats were 2.95g/kg、0.76g/kg and 0.20g/kg. In these experiments, all the animals were given更多还原