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蒙藥復(fù)方“特潤舒都樂”有效成分臨床前的初步安全性評價(jià)

發(fā)布時間:2018-04-06 20:12

  本文選題:蒙藥復(fù)方 切入點(diǎn):有效成分 出處:《內(nèi)蒙古農(nóng)業(yè)大學(xué)》2015年碩士論文


【摘要】:在課題組前期研究了治療奶牛乳房炎蒙藥“特潤舒都樂”有效成分復(fù)方的體內(nèi)外抑菌抗炎免疫作用及其機(jī)理基礎(chǔ)上,為保證其對奶牛無毒害作用,對其進(jìn)行了體內(nèi)外急性、亞急性和其他毒理學(xué)實(shí)驗(yàn),進(jìn)行藥物的安全性評價(jià),為臨床應(yīng)用提供理論依據(jù)。試驗(yàn)結(jié)果如下:1.急性毒性試驗(yàn):采用最大耐受量法,設(shè)4個劑量組,一次性給藥,觀察7d。確定了蒙藥復(fù)方“特潤舒都樂”有效成分的最大耐受劑量5000mg/kg·b·w。2.亞慢性毒理試驗(yàn):為評價(jià)長期給藥在動物體內(nèi)的蓄積性毒性、耐受性及主要毒性靶器官,分高、低劑量組和陰性對照組,進(jìn)行30d喂養(yǎng)試驗(yàn)。給藥末期大鼠的精神狀態(tài)正常,攝食量和體重整體呈增長趨勢,與陰性對照組無顯著差異(P0.05)。臟器指數(shù)也無異常。血常規(guī)和血液生化指標(biāo)測定雖有統(tǒng)計(jì)學(xué)差異(P0.05),但波動在正常范圍內(nèi)。給藥末期,大鼠經(jīng)剖檢無肉眼可見病變,病理學(xué)檢查未發(fā)現(xiàn)明顯變性壞死和出血。所以沒有對臟器造成藥物性的損害。說明長期給藥無蓄積毒性,對臟器無影響。3.小鼠精子畸形試驗(yàn):設(shè)高、低劑量組、陰性和陽性對照組。連續(xù)5d給藥,第35d處死取睪丸。顯微鏡下觀察。結(jié)果顯示,陰性對照組和陽性對照組差異顯著(P0.05)。各劑量組和陰性對照組無顯著差異(P0.05),和陽性對照組相比差異顯著(P0.05)。說明蒙藥有效成分復(fù)方對小鼠精子畸形未造成影響,對生殖細(xì)胞沒有影響。4.小鼠骨髓細(xì)胞微核試驗(yàn):設(shè)高、低劑量組、陰性和陽性對照組。連續(xù)5d給藥,末次給藥6h后處死小鼠,取骨髓制片,顯微鏡下觀察,各劑量組和陰性對照組相比,差異不顯著(P0.05),和陽性對照組相比差異顯著(P0.01),陰性和陽性對照組相比差異顯著(P0.01)。說明蒙藥成分復(fù)方,不造成小鼠的染色體斷裂和紡錘體病變。5.小鼠睪丸染色體畸變試驗(yàn):設(shè)高、低劑量組,陰性和陽性對照組。在給藥12d后,取睪丸制冰凍切片,顯微鏡下觀察。各劑量組與陰性對照組相比,差異不顯著(P0.05)。各劑量組和陽性對照組相比差異顯著(P0.01)。陰性和陽性對照組差異極顯著(P0.01)。所以,蒙藥有效成分復(fù)方未造成小鼠染色體異常等遺傳病變。6.體外溶血試驗(yàn):采用兔血制備紅細(xì)胞懸液,分別加受試物。陰性對照組為生理鹽水,陽性對照組為蒸餾水,其余各管加不同劑量的蒙藥成分復(fù)方。肉眼觀察,蒙藥成分復(fù)方無溶血作用,對于臨床上用于注射類藥物可作參考。7.過敏試驗(yàn):蒙藥成分復(fù)方對家兔皮膚未造成紅斑和紅腫等過敏現(xiàn)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.
【學(xué)位授予單位】:內(nèi)蒙古農(nóng)業(yè)大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2015
【分類號】:S853.7

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