伊维菌素微乳制剂的过敏性研究

本试验旨在观察伊维菌素微乳制剂对动物的过敏性反应。以《化学药物刺激性、过敏性和溶血性研究技术指导原则》为指导,选用豚鼠及Wistar大鼠为试验动物,采用全身主动过敏试验和被动皮肤过敏试验观察伊维菌素微乳制剂对动物的致敏作用。结果显示伊维菌素微乳制剂对豚鼠和Wistar大鼠的过敏性反应均为阴性。本试验为伊维菌素微乳制剂的安全性评价提供了试验依据。     

伊维菌素微乳制剂的溶血性试验

为了观察新型兽药制剂伊维菌素微乳是否具有溶血和红细胞凝聚等反应,试验以《化学药物刺激性、过敏性和溶血性研究技术指导原则》为指导,取兔血,采用常规体外试管法,观察伊维菌素微乳制剂是否出现溶血现象。结果表明:伊维菌素微乳制剂未出现溶血和红细胞凝聚现象,可供注射使用。说明伊维菌素微乳制剂无溶血性,安全可靠。     

1%莫西菌素微乳制剂的绵羊安全性试验

试验旨在研究1%莫西菌素微乳制剂对于靶向动物绵羊的安全性。选择60只绵羊,随机分为5组,每组4个重复,每个重复3只绵羊。分别为对照组、推荐剂量组、3倍剂量组、5倍剂量组、10倍剂量组,按0、0.2、0.6、1.0、2.0 mg/kg颈部皮下注射1%莫西菌素微乳制剂,给药两次后采集全血及肝素抗凝血测定血液生理指标、血清生化指标,采集尿液测定尿液理化指标。试验期7 d。结果显示,各组绵羊生长性能和血液生理指标、血清生化指标以及尿液理化指标差异均不显著（P>0.05）。研究表明,1%莫西菌素微乳制剂对绵羊安全。     

伊维菌素微乳中伊维菌素的含量测定方法研究

为建立伊维菌素微乳中伊维菌素含量的高效液相色谱（HPLC）测定方法,选用Hypersil ODS2 （5 μm,4.6 mm×250 mm）色谱柱,流动相为甲醇∶乙腈∶水为35∶60∶5（V/V/V）,检测波长为244 nm,柱温为30 ℃,流速为1 mL/min进行测定。结果显示,伊维菌素在该色谱条件下,系统适应性良好,在80~320 μg/mL浓度范围内线性关系良好,回归方程为：Y=22 700X+2 510,R²=0.9998,总平均回收率为101.90%±2.94%,RSD为2.88%,对中试生产的3批伊维菌素微乳进行含量测定,RSD为1.86%。表明该含量测定方法准确可靠,重现性好,可用于伊维菌素微乳中伊维菌素含量的测定,并为该新型制剂的质量标准的制定和质量评价提供依据,也为后期的临床安全应用提供可靠的参考。     

伊维菌素干混悬剂驱除猪蛔虫效果与安全性试验

应用伊维菌素干混悬剂进行了驱除猪蛔虫的效力及安全性试验。结果：0．3mg/kg b.w剂量对猪蛔虫的虫卵转阴率、虫卵减少率和驱虫率均达100％，猪可耐受1．5mg/kg剂量。试验证明伊维菌素干混悬剂驱除猪蛔虫安全高效，投药方便，成本较低，具有推广前景。     

HPLC法测定微乳中伊维菌素的含量

建立了HPLC测定伊维菌素微乳中伊维菌素含量的方法。色谱柱为ZirchromC18(4.6mm×250 mm,5μm),流动相为甲醇∶水(85∶15),测定波长为245 nm,流速为1.0 mL/min,柱温为40℃。伊维菌素与辅料及溶剂峰分离良好,在2.22~111.0μg/mL时线性关系良好(R2=0.999 9)。HPLC测定伊维菌素方法便捷、准确、重复性好,可用于伊维菌素微乳含量的测定。     

伊维菌素脂质体的急性毒性试验

为了解伊维菌素脂质体的毒性，将伊维菌素脂质体给试验小鼠按一定浓度一次腹腔注射，连续观察7-14d，用改良寇氏法计算半数致死量（LD50）及95％的可信限，并在同一方法和条件下与伊维菌素注射剂相比较。结果表明，伊维菌素脂质体（脂质体组）的LD50（92．1516mg／kg．BW）显著高于伊维菌素注射剂（原药组）的LD50（24．2493mg／kg．BW），是原药组的3．80倍。证明伊维菌素脂质体的毒性更低，刺激性更小，安全范围更广。     

伊维菌素浇泼剂对牦牛皮蝇蛆病的防治效果及安全性试验

应用0.5％伊维菌素浇泼剂，10月中下旬每头牛100kg体重分别按1ml、2ml用量，沿背中线皮肤一次浇泼给药，翌年3月、5月份检查防治效果。结果：感染率、感染强度由对照组牛的86．2％和5．24(0—24)个虫体(瘤疱)，均下降为0，有效率达100％；按0．1ml/kg bw、0．15ml/kg bw、0．2ml/kg bw剂量给药牦牛均可耐受。试验证明：伊维菌素浇泼剂防治牦牛皮蝇蛆病效果好，用量小，给药方便，毒副作用小，安全范围大，适宜各地推广。     

伊维菌素浇泼剂对绵羊线虫的驱虫效力与安全性试验

应用0.5%伊维菌素浇泼剂按0.3,0.4,0.5mg/kg.b w剂量对绵羊沿背中线皮肤一次浇泼给药,并以伊维菌素注射剂0.2mg/kg.b w剂量做对照。结果:伊维菌素浇泼剂0.3mg/kg,0.4mg/kg.b w剂量对消化道线虫虫卵转阴率分别为85%和90%,减少率分别为89.1%和95.9%;对原圆科线虫幼虫转阴率分别为60%和75%,减少率分别为77.2%和86.7%;0.5mg/kg.b w剂量对消化道线虫虫卵转阴率和减少率均为100%,对原圆科线虫幼虫转阴率为85%,减少率为95.4%。解剖检查结果:伊维菌素浇泼剂三种剂量对绵羊消化道、呼吸道多属线虫均有效,总计驱虫率分别为90.8%,95.6%和99.7%,伊维菌素浇泼剂0.5mg/kg.b w剂量与伊维菌素注射剂0.2mg/kg.b w剂量驱虫效果基本一致;绵羊经皮给药可耐受1.0mg/kg.b w剂量。试验证明:伊维菌素浇泼剂经皮给药驱除绵羊线虫高效安全,临床推荐剂量以0.5mg/kg.b w为宜。     

伊维菌素 酸微球的研制及其体外释药试验

以生物可降解材料聚乳酸为载体,用乳化溶剂挥发法制备含伊维菌素的聚乳酸微球,采用Ｌ１８（３＾７）正交设计,以微球粒径分布为主要优选指标,筛选出最佳制备条件。     

伊维菌素微乳无菌检查方法学的研究

本试验旨在对伊维菌素微乳制剂进行无菌检查方法学验证和无菌检查试验,确认本试验所用的方法适用于该制剂的无菌检查。按《中国兽药典》2005版一部(附录118)所载"无菌检查法"项下进行试验,通过对阳性对照菌、不同量冲洗液等条件的选择,采用薄膜过滤法对10瓶供试品(每种试验菌的样品量)进行检测,建立了无菌检查方法。经方法验证,用400mL 0.1%蛋白胨水溶液冲洗后,含供试品容器中的7个阳性菌试验组与阳性菌对照组相比均生长良好,说明供试品的该检验量在该检验条件下无抑菌作用或其抑菌作用可以忽略不计,可以用该方法进行供试品的无菌检查。对3批供试品进行无菌检查,阳性对照菌均在24h内生长良好,阴性对照均澄清,无菌生长,3批供试品均澄清,无菌生长,无菌检查试验结果符合规定。     

Study on Sterility Test Method of Ivermectin Microemulsion

The assay was aimed to study the sterility test and validation test of ivermectin microemulsion preparation and establish a sterility test method for ivermectin microemulsion preparation.The test method was carried out according to the method in volumeⅠ, Chinese Veterinary Pharmacopoeia Edition 2005.By choosing positive control bacteria and defining washing volumes in sterility test, the membrane-filter method was used to test the quantity of 10 bottles of test samples, and the sterility test was established.The result of method validation test showed that the test and all of positive control bacteria and microorganism growth after each filter being washed with 400 mL 0.1% peptone solution.It illustrated that the samples had no antimicrobial activity under the sample quantity and test condition.This method was available for sterility test of ivermectin microemulsion preparation.Using this method to test three lots test samples, the results showed that the positive control bacteria grew well within 24 h.The negative control bacteria and three lots test samples were sterile.It indicated that sterility test results met the requirements.     

Content Determination of Ivermectin in the Ivermectin Microemulsion Injection

In order to establish the determination method of ivermectin (IVM) in the ivermectin microemulsion injection by high performance liquid chromatography (HPLC), Hypersil ODS2 colunm (5 μm,4.6 mm×250 mm) was used in this study. The mobile phase composed of methanol, acetonitrile and water (35:60:5,V/V/V) at a flow rate of 1 mL/min. The detection wave length was set at 244 nm and the column temperature was 30 ℃. The results showed that the HPLC system suitability of IVM was good. A good linear correlation of IVM was observed within the concentration range 80 to 320 μg/mL, and the average recovery rate was 101.90%±2.94% with RSD was 2.88%, the regression equation was Y=22 700X+2 510 (R²=0.9998). The RSD of IVM content in ivermectin microemulsion injection was 1.86%. The method was accurate and reliable,reproducible,easy to operate, which could be used in new type of ivermectin microemulsion injection. The method could be used as the basis of quality control and establishing a quality standard, and to provide basis for quality evaluation, also can provide reliable reference for safe veterinary clinical application in the future.     

伊维菌素原粉急性吸入毒性试验研究

对伊维菌素原粉急性吸入毒性进行研究,采用限量试验,设定2000 mg/m3一个剂量组,动式口鼻式染毒,有效染毒时间2 h。结果显示,伊维菌素原粉对雌雄大鼠的急性吸入半数致死浓度(LC50)均大于2089 mg/m3。伊维菌素原粉急性吸入毒性属低毒,该结论为安全使用提供了依据。     

伊维菌素长效注射液对小鼠的急性毒性试验

为考察伊维菌素长效注射液的急性毒性,用简化寇氏法对小鼠的LD50进行了测定。将伊维菌素长效注射液以1：0．7的组间剂量给试验小鼠一次皮下注射,连续观察7d。结果表明,伊维茵素长效注射液的LD50为257．04mg／kg,9500可信限范围为192．84mg／kg-342．61mg／kg,符合低毒标准,说明该药临床皮下注射使用安全。