蒙药复方“特润舒都乐”有效成分临床前的初步安全性评价

发布时间：2018-04-06 20:12

本文选题：蒙药复方　切入点：有效成分　出处：《内蒙古农业大学》2015年硕士论文

【摘要】：在课题组前期研究了治疗奶牛乳房炎蒙药“特润舒都乐”有效成分复方的体内外抑菌抗炎免疫作用及其机理基础上,为保证其对奶牛无毒害作用,对其进行了体内外急性、亚急性和其他毒理学实验,进行药物的安全性评价,为临床应用提供理论依据。试验结果如下：1.急性毒性试验：采用最大耐受量法,设4个剂量组,一次性给药,观察7d。确定了蒙药复方“特润舒都乐”有效成分的最大耐受剂量5000mg/kg·b·w。2.亚慢性毒理试验：为评价长期给药在动物体内的蓄积性毒性、耐受性及主要毒性靶器官,分高、低剂量组和阴性对照组,进行30d喂养试验。给药末期大鼠的精神状态正常,摄食量和体重整体呈增长趋势,与阴性对照组无显著差异(P0.05)。脏器指数也无异常。血常规和血液生化指标测定虽有统计学差异(P0.05),但波动在正常范围内。给药末期,大鼠经剖检无肉眼可见病变,病理学检查未发现明显变性坏死和出血。所以没有对脏器造成药物性的损害。说明长期给药无蓄积毒性,对脏器无影响。3.小鼠精子畸形试验：设高、低剂量组、阴性和阳性对照组。连续5d给药,第35d处死取睾丸。显微镜下观察。结果显示,阴性对照组和阳性对照组差异显著(P0.05)。各剂量组和阴性对照组无显著差异(P0.05),和阳性对照组相比差异显著(P0.05)。说明蒙药有效成分复方对小鼠精子畸形未造成影响,对生殖细胞没有影响。4.小鼠骨髓细胞微核试验：设高、低剂量组、阴性和阳性对照组。连续5d给药,末次给药6h后处死小鼠,取骨髓制片,显微镜下观察,各剂量组和阴性对照组相比,差异不显著(P0.05),和阳性对照组相比差异显著(P0.01),阴性和阳性对照组相比差异显著(P0.01)。说明蒙药成分复方,不造成小鼠的染色体断裂和纺锤体病变。5.小鼠睾丸染色体畸变试验：设高、低剂量组,阴性和阳性对照组。在给药12d后,取睾丸制冰冻切片,显微镜下观察。各剂量组与阴性对照组相比,差异不显著(P0.05)。各剂量组和阳性对照组相比差异显著(P0.01)。阴性和阳性对照组差异极显著(P0.01)。所以,蒙药有效成分复方未造成小鼠染色体异常等遗传病变。6.体外溶血试验：采用兔血制备红细胞悬液,分别加受试物。阴性对照组为生理盐水,阳性对照组为蒸馏水,其余各管加不同剂量的蒙药成分复方。肉眼观察,蒙药成分复方无溶血作用,对于临床上用于注射类药物可作参考。7.过敏试验：蒙药成分复方对家兔皮肤未造成红斑和红肿等过敏现象。因此不致敏。
[Abstract]:On the basis of the study on the anti-inflammatory and anti-inflammatory effect and its mechanism of the active component compound of "Terensudola", a Mongolian medicine for the treatment of dairy cow mastitis, in vivo and in vitro, in order to ensure that it has no toxic effect on dairy cattle, acute in vivo and in vitro was carried out.Subacute and other toxicological experiments were carried out to evaluate the safety of drugs and provide theoretical basis for clinical application.The test results are as follows: 1.Acute toxicity test: the method of maximum tolerance dose was used, four dose groups were divided into one dose group and observed 7 days.The maximum tolerated dose of the active component of the Mongolian medicine compound "Terensudule" was determined by 5000mg/kg b W. 2.Subchronic toxicology test: in order to evaluate the accumulative toxicity, tolerance and main toxic target organs of long-term administration in animals, a 30-day feeding test was carried out in high, low dose and negative control groups.The mental state of the rats at the end of the administration was normal, the intake and body weight of the rats were increasing, and there was no significant difference between the rats and the negative control group (P 0.05).There was also no abnormality in the viscera index.Although there were statistical differences in blood routine and blood biochemical indexes (P 0.05), they fluctuated within normal range.At the end of administration, no pathological changes were observed in the naked eyes, and no obvious degeneration, necrosis and bleeding were found in pathological examination.So there is no drug damage to the viscera.The results showed that long-term administration had no accumulative toxicity and had no effect on viscera.Sperm malformation test in mice: high and low dose groups, negative and positive control groups.After 5 days of administration, the testis were killed on the 35th day.Look under the microscope.The results showed that the difference between the negative control group and the positive control group was significant (P 0.05).There was no significant difference between each dose group and the negative control group (P 0.05), and the difference was significant compared with the positive control group (P 0.05).The results showed that the compound of active component of Mongolian medicine had no effect on sperm malformation in mice, but had no effect on germ cells.Mouse bone marrow micronucleus test: high, low dose, negative and positive control group.The mice were killed 6 hours after the last administration for 5 days. The bone marrow films were taken and observed under microscope. There was no significant difference between each dose group and the negative control group, but there was significant difference between the positive group and the positive control group (P 0.01), and the difference between the negative group and the positive control group was significant (P 0.01).The results showed that the compound of Mongolian medicine did not cause chromosomal breakage and spindle lesion in mice.Mouse testicular chromosome aberration test: high, low dose groups, negative and positive control group.After 12 days of administration, frozen sections of testis were taken and observed under microscope.There was no significant difference between each dose group and the negative control group (P 0.05).The difference between each dose group and the positive control group was significant (P 0.01).The difference between negative control group and positive control group was very significant (P 0.01).Therefore, the Mongolian medicine active ingredient compound did not cause mouse chromosome abnormality and other genetic diseases. 6. 6.In vitro hemolysis test: rabbit blood was used to prepare red blood cell suspension.The negative control group was normal saline and the positive control group was distilled water.Naked eye observation, Mongolian medicine compound has no hemolytic effect, for clinical use of injectable drugs can be used as a reference. 7.Allergic test: the compound of Mongolian medicine did not cause erythema and erythema in rabbit skin.So it is not sensitive.
【学位授予单位】：内蒙古农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S853.7

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