【摘要】：伊維菌素微乳制劑是一種新型高效、廣譜、低毒和對多種動物體內外寄生蟲有高效驅殺作用的新制劑,是以納米乳為載體,以80%以上水為溶劑制成。本論文對該制劑的安全性評價、制劑含量測定方法的建立、穩(wěn)定性試驗、制劑的無菌檢查進行了研究。1.對新型伊維菌素微乳制劑進行了過敏性試驗、溶血試驗、肌肉刺激性試驗、熱原檢查、注射途徑的急性毒性試驗、亞慢性毒性試驗等安全性評價試驗。結果顯示:制劑對豚鼠和大鼠的過敏性反應均為陰性,無致敏性;制劑未出現(xiàn)溶血和紅細胞凝聚現(xiàn)象;制劑對家兔股四頭肌未見明顯刺激作用;熱原限度符合規(guī)定,無致熱原;制劑對大鼠腹腔注射的LD50為3.8256g/kg,95%可信限為3.4639 g/kg~4.2251 g/kg,對小鼠腹腔注射的LD50為3.2200 g/kg,95%可信限為1.8197 g/kg~5.6979 g/kg,高于伊維菌素原料藥對小鼠腹腔注射的的LD50(24.2493 mg/kg);亞慢性毒性試驗,各給藥劑量組大鼠的體重、血液學指標、生化指標與對照組比較均無顯著性差異,顯示伊維菌素微乳制劑對大鼠長期給藥無明顯毒副作用,臨床用藥安全。以上結果證明:新型伊維菌素微乳制劑安全可靠,可應用于獸醫(yī)臨床。2.建立了新型伊維菌素微乳制劑中伊維菌素的高效液相色譜法的含量測定方法。伊維菌素的色譜條件為Hypersil ODS2(5um,4.6mm x 250mm)色譜柱,流動相為甲醇:乙腈:水=35:60:5(v/v),柱溫30℃,進樣量10μl,檢測波長244 nm,流速1mL·min-1。用該方法檢測3批制劑中伊維菌素的含量為標示量的94%~100%,方法準確可靠、選擇性好、重現(xiàn)性好、操作簡便、快速,可用于伊維菌素微乳制劑中伊維菌素的含量測定。3.對新型伊維菌素微乳制劑的中試產(chǎn)品進行了高溫、高濕、強光照射和加速試驗。結果表明,在以上條件下伊維菌素的含量沒有明顯變化,樣品正立、倒立、平放放置對含量無明顯影響,即橡膠塞可用于該制劑的封裝。試驗結果證明該制劑易于存儲和運輸。4.對新型伊維菌素微乳制劑進行無菌檢查,進行了無菌檢查的方法驗證試驗,確立了該制劑無菌檢查的方法,并對3批伊維菌素微乳制劑進行了無菌檢查,結果顯示,陽性對照菌均在24h內生長良好,陰性對照均澄清,無菌生長,3批供試品均澄清,無菌生長,無菌檢查試驗結果符合規(guī)定。
[Abstract]:Ivermectin microemulsion is a novel preparation with high efficiency, broad spectrum, low toxicity and high efficiency in killing parasites in vivo and in vitro. It is prepared with nanometer emulsion as carrier and more than 80% water as solvent. In this paper, the safety evaluation, determination method, stability test and aseptic examination of the preparation were studied. The safety evaluation tests such as hypersensitivity test hemolysis test muscle irritation test pyrogen test acute toxicity test of injection route subchronic toxicity test and so on were carried out on the new Ivermectin microemulsion. The results showed that the allergic reaction of the preparation to both guinea pigs and rats was negative without sensitization, no hemolysis and erythrocyte condensation, no obvious stimulation to the quadriceps femoris muscle of rabbits, no pyrogen limit and no pyrogen. The LD50 of intraperitoneal injection was 3.8256g / kg 95% confidence limit was 3.4639 g/kg~4.2251 / kg, the LD50 confidence limit of mice was 3.2200 g / kg 95% confidence limit was 1.8197 g/kg~5.6979 / kg, which was higher than that of Ivermectin API LD50 (24.2493 mg/kg). There was no significant difference in body weight, hematological index and biochemical index between each dosage group and control group, which showed that Ivermectin microemulsion had no obvious side effect on long-term administration of Ivermectin in rats, and was safe in clinical use. The results show that the new Ivermectin microemulsion is safe and reliable and can be used in veterinary clinic. A HPLC method for the determination of ivermectin in new Ivermectin microemulsion was established. The chromatographic conditions of ivermectin were as follows: Hypersil ODS2 (5umn 4.6mm x 250mm) column, mobile phase: methanol: acetonitrile: water 35: 60: 5 (v / v), column temperature 30 鈩，

本文編號：2207579