两种给药方式下伊维菌素在虹鳟体内的药物代谢动力学研究

研究旨在通过口灌和腹腔注射两种给药方式,研究伊维菌素在虹鳟体内的药动学特征。采用高效液相色谱-紫外检测法（HPLC-UV）研究了以0.3 mg/kg剂量分别单次口灌和腹腔注射伊维菌素后,药物在虹鳟体内的药代动力学特征。结果表明：口灌给药方式下,伊维菌素在虹鳟血浆、肌肉中的药物浓度和时间关系符合一级吸收二室开放模型,而在肝脏、肾脏中符合一级吸收一室开放模型;腹腔注射给药方式下,伊维菌素在虹鳟血浆、肌肉、肝脏和肾脏中的药时关系均符合一级吸收一室开放模型。口灌给药后,伊维菌素在血浆中主要的药动学参数：AUC为123.709 mg/(L?h)、Ka为3.749 h^-1、t_1/2ke为 466.569 h、T_max为0.454 h、C_max为0.319 mg/L。腹腔注射给药后,伊维菌素在血浆中主要的药动学参数：AUC为52.560 mg/(L?h)、Ka为5.033 h^-1、t_1/2ke为103.236 h、T_max为1.317 h、C_max为0.350 mg/L。说明在两种给药方式下,伊维菌素在虹鳟体内的药动学特征存在明显的差异,伊维菌素在腹腔注射给药方式下吸收和消除速率均较口灌给要快。     

伊维菌素人工抗原的制备及鉴定

为制备伊维菌素人工完全抗原,通过对伊维菌素进行化学修饰,引入活性基团羧基,合成具有半抗原结构特征的伊维菌素半琥珀酸酯。然后采用NHS法将半抗原与牛血清白蛋白(BSA)和鸡卵清蛋白(OVA)偶联,制备人工免疫原IVM-BSA和检测原IVM-OVA,经SDS-PAGE和紫外光谱扫描鉴定。用人工免疫原IVM-BSA免疫Balb/c小鼠,间接竞争ELISA法测定抗血清效价。结果发现：偶联物IVM-BSA和IVM-OVA的偶联比分别为14.1:1和14.7:1,免疫小鼠抗血清效价达到1:12800,结果说明成功制备出人工完全抗原并且具有良好的免疫原性。     

伊维菌素微胶囊的制备及其体外释放的研究

市售伊维菌素制剂存在生物利用度低,释药峰谷浓度差异大等问题,本文以明胶为囊材,采用单凝聚法制备伊维菌素长效注射微胶囊油混悬剂。以微胶囊的粒径、载药量和包封率为制备工艺的优化指标,采用分光光度法测定微胶囊内药物含量及包封率。结果显示：最佳工艺制备的微胶囊的平均包封率为63.2%,载药量为18.3%,微胶囊的正圆度高、表面平滑,粒径分布在20~50 μm,药物呈缓慢持续释放,体外累计释放率18 h为30.0%,44 h后仅为51.0%。伊维菌素微胶囊制剂可大大增加体内留存时间,提高生物利用度,缓释效果显著。     

中药犬螨灵对犬蠕形螨的疗效试验

为筛选具有显著治疗犬蠕形螨的中药制剂,试验将中药小茴香、蛇床子、羊蹄根采用水煮醇沉及蒸馏等提取方法制备成中药制剂犬螨灵,并观察其对犬蠕形螨的疗效。将犬螨灵设为高、中、低3个浓度,其生药含量分别为2.0、1.0和0.5 g/mL,采用点滴法进行体外抑杀蠕形螨试验,在此基础上对12只接种蠕形螨的试验犬进行治疗试验,为验证治疗效果,对临床上已确诊的45只患有蠕形螨的病犬分3组进行临床治疗试验。结果显示,中药犬螨灵3种剂量均有较强的体外抑杀螨虫作用,高剂量组作用后4 h即可完全抑杀蠕形螨,1%伊维菌素对照组则为作用后8 h;高剂量组在治疗3周后,患处有大量新毛生长,红疹结节和皮屑消失,患处皮肤已痊愈,1%伊维菌素治疗组患犬皮肤好转,仅有少量新毛生长,不能达到痊愈标准;高、中剂量组皮肤刮取物螨虫数量平均比例及停药1个月后复发率均为0,1%伊维菌素治疗组皮肤刮取物螨虫数量平均比例及停药1月后的复发率分别为10.63%和9.17%。高剂量中药犬螨灵与1%伊维菌素两种药物联合治疗组,对临床上患病犬进行3周治疗,其虫卵平均转阴率、治愈率与平均治愈天数分别为100.00%、93.33%和19.56 d,其效果均优于中药犬螨灵与1%伊维菌素单独治疗组。结果表明,高剂量自制中药制剂犬螨灵对犬蠕形螨体外抑杀作用、接种蠕形螨试验犬与临床自然感染病例均有显著的治疗效果,优于1%伊维菌素对照组,犬螨灵作为中药杀螨虫制剂具有较好的市场开发前景。     

高效液相色谱法测定乳品与饲料中阿维菌素类药物残留

建立乳品与饲料中阿维菌素类药物(埃普利诺菌素、阿维菌素、多拉菌素和伊维菌素)残留液相色谱的测定方法。乙腈为提取剂,tC18固相萃取小柱净化,三氟乙酸酐和N-甲基咪唑柱前衍生,C18柱分离,甲醇-乙腈的混合溶剂与水梯度洗脱,液相色谱仪荧光检测器检测,外标法定量。每1 000 g乳粉(或每1 000 mL液态乳)中阿维菌素添加量为1.5 μg时,回收率大于95％。本方法液态乳、酸乳、乳粉的定量限为2μg/kg,饲料的定量限为10 μg/kg。该方法具有结果准确、操作简便、重复性好等优点,可用于乳品和饲料中阿维菌素类药物残留的检测。     

伊维菌素脂质体的制备及质量控制研究

为研究伊维菌素脂质体 ,以卵磷脂和胆固醇为载体 ,采用注入法制备了伊维菌素脂质体 ,并应用紫外倍率系数法测定脂质体中伊维菌素的含量 ,采用高速离心法测定其包封率。结果表明 ,采用注入法制备的伊维菌素脂质体稳定性好 ,大小均匀 ,包封率效果良好 (77.42 %以上 ) ,紫外倍率系数法能消除辅料干扰 ,可作为伊维菌素脂质体质量控制的有效方法     

Resistance to Ivermectin and the Effect of Topical Eprinomectin on Faecal Egg Counts in St Croix White Hair Sheep

Veterinary Research Communications -     

Sarcoptic mange in captive maras: the first known outbreak and complete recovery with colony-wide acaricide treatment

Among 16 maras housed as a colony at a zoo, 2 initially showed generalized dermal lesions on the legs, head and abdomen. Approximately 1 month later, following completion of therapy with amitraz, 6 maras in the same colony, including the 2 previously diseased animals, showed dermal lesions with severe alopecia and crusting. Sarcoptic mange was diagnosed on skin scrapings on the basis of morphological criteria. The mites were highly mobile and abundant in all cases, and no other causative agents were detected. Colony-wide treatment with ivermectin and prednisolone was administered weekly for a total of 4 treatments. After therapy was completed in all cohabitants, follow-up scrapings were negative for Sarcoptes scabiei. This report describes the first known outbreak of sarcoptic mange in captive maras and successful treatment with acaricides.     

高效液相色谱法测定伊维菌素缔合胶体溶液的含量

建立了0.3%伊维菌素缔合胶体溶液中伊维菌素含量的HPLC测定方法。采用的流动相为乙腈-甲醇-水（60∶32∶8）,检测波长为254 nm。结果表明,伊维菌素H2B1a在6.795-217.4μg/mL浓度范围内线性关系良好（r=0.999 8）,平均回收率为99.7%。该方法准确可行,伊维菌素H2B1a与相邻峰分离完全,能排除溶剂和表面活性剂的干扰。     

Electroretinographic changes after intravenous lipid emulsion therapy in a dog and a foal with ivermectin toxicosis

This case report describes ivermectin‐induced blindness in a dog and a foal with normal ophthalmic fundic examinations and attenuated electroretinography (ERG). Subsequent recovery in ERG was noted following intravenous lipid emulsion (ILE) therapy. A dog and a foal were evaluated for ivermectin‐induced blindness. Clinical signs included dull mentation, absent pupillary light reflexes (PLRs), and absent menace on presentation. The animals had normal fundoscopic examinations; however, in both cases ERG was consistent with neurosensory retinal dysfunction. Following ILE therapy for ivermectin toxicosis, return of menace, PLRs, and normal mentation were noted, as was improvement in ERG and serum ivermectin levels. These are the first documented cases of ivermectin‐induced blindness in a dog and a foal with normal fundic examinations and attenuated ERG. ERG improved in both animals after ILE therapy. ERG may assist in the diagnosis of ivermectin toxicosis in dogs and horses. ILE therapy may hasten recovery in treatment of ivermectin‐induced blindness.