紫外分光光度法测定地克珠利溶液的含量

采用紫外分光光度法测定地克珠利溶液的含量，实验表明在5－25μg/ml的浓度范围内，吸收度与浓度呈良好线性关系，平均回收率：99.57%;RSD=0.22%。并用HPLC进行对照，结果基本一致。本法具有简便、快速、准确、重现性好等优点，可用于地克珠利溶液含量的快速测定。     

地克珠利混悬液对鸡球虫病的疗效观察

对20 g/L地克珠利混悬液,以4、2、1 mg/kg 3种浓度饮水预防鸡艾美耳球虫人工感染,并用地克珠利溶液以2 mg/kg浓度饮水作对照.结果表明,20 g/L地克珠利混悬液以4、2、1 mg/kg 3种浓度饮水预防鸡球虫病,具有良好的效果,抗球虫指数均在180以上,效果优于地克珠利溶液以2 mg/kg饮水.田间试验有效率81.8%,治愈率71%,证实20 g/L地克珠利混悬液是地克珠利又一种高效预防鸡球虫病新剂型.     

马杜霉素铵-地克珠利溶液对防治禽球虫病效果的试验

1试验动物及分组30日龄AA快大型肉仔鸡,购自天津市畜牧兽医研究所实验动物房,平均体重1.50kg。将鸡群随机分为A、B、C、、D、E、F组,每组110只。A组为健康对照组,B组为感染对照组,C组为马杜霉素铵-地克珠利溶液高剂量组,D组为马杜霉素铵-地克珠利溶液中剂量组,E组为马杜霉素铵-地克珠利溶液低剂量组,F组为磺胺喹恶啉钠可溶性粉对照组。分组情况见表1。     

紫外分光光度法测定地克珠利溶液的含量

地克珠利是一种新型的抗球虫药，在鸡的日粮中添加1mg/kg能明显提高抗球虫指数（ACI），但由于地克珠利使用浓度低，难合均匀，且地克珠利难溶于水，在一定程度上影响了该药在临床上的使用和推广。为此，公司开发了1％的溶液剂。为了快捷简便地控制日常生产过程中地克珠利溶液的含量，我们采用紫外分光光度法测定地克珠利的含量。方法与高效液相色谱法比较，结果基本一致。     

复方地克珠利可溶性粉剂抗鸡球虫病效果试验

分别以0.5、1.0和1.5mg/L复方地克珠利可溶性粉(以地克珠利有效成分计)饮水,预防鸡柔嫩艾美耳球虫人工感染。并用地克珠利可溶性粉(1.0mg/L)饮水、地克珠利(1.0mg/kg)混饲和硫酸新霉素(50.0mg/L,以效价计)饮水为对照。结果发现,复方地克珠利可溶性粉3种浓度饮水均能有效预防鸡柔嫩艾美耳球虫人工感染,抗球虫指数均在176.46以上,优于地克珠利混饲给药组。     

地克珠利安全性评价及临床药效

对地克珠利原料地小鼠急性毒性，微核试验和Ａｍｅｓ试验。采用１０日龄公雏进行了地克珠利预混剂驱除艾美耳氏球虫效力试验。结果表明小鼠口服地克珠利ＬＤ５０〉１００００ｍｇ／ｋｇ，属实际无毒；微核及Ａｍｅｓ检测结果无致突变作用。     

消毒药剂过氧乙酸的安全配制与使用

<正>过氧乙酸又叫过醋酸,为强氧化剂,不稳定,高浓度(25%以上)加热(70℃以上)能引起爆炸。所以,应密闭避光贮放在低温(3～4℃)处。过氧乙酸对病原微生物有强而快速的杀灭作用,不但能杀灭细菌、真菌和病毒,而且能杀死芽孢。常用0.5%溶液喷雾消毒畜舍、地面、墙壁、食具及周围环境等;用1%溶液作呕吐物和排     

肉用绵羊球虫的驱除实验

阿左旗动物疫病预防控制中心使用地克珠利,按0.15g/kg分组拌料饲喂60只绵羊,检测用药前后虫卵的数量和羊的体重。实验证明地克珠利驱除球虫有明显的效果,对羊的增重呈有利影响。     

肉用绵羊球虫的驱除实验

阿左旗动物疫病预防控制中心使用地克珠利,按0.15g/kg分组拌料饲喂60只绵羊,检测用药前后虫卵的数量和羊的体重。实验证明地克珠利驱除球虫有明显的效果,对羊的增重呈有利影响。     

0.5%地克珠利可溶性粉的制备及检测

采用适当的助溶剂，通过喷雾干燥法制成地克珠利可溶性粉。经检测，地克珠利可溶性粉性质稳定，溶解性好。按0.5-1mg/L饮水给药，能有效防治鸡球虫病。     

New therapeutic approaches for equine protozoal myeloencephalitis: pharmacokinetics of diclazuril sodium salts in horses

Diclazuril is a triazine-based antiprotozoal agent which may have clinical application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In this study, the use of the sodium salt diclazuril to increase the apparent bioavailability of diclazuril for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases is described. In this study, diclazuril sodium salt was synthesized and administered to horses as diclazuril sodium salt formulations. The absorption, distribution, and clearance of diclazuril sodium salt in the horse are described. Diclazuril was rapidly absorbed, with peak plasma concentrations occurring at 8-24 hours following an oral mucosal administration of diclazuril sodium salt. The mean oral bioavailability of diclazuril as Clinacox was 9.5% relative to oral mucosal administration of diclazuril sodium salt. Additionally, diclazuril in DMSO administered orally was 50% less bioavailable than diclazuril sodium salt following an oral mucosal administration. It was also shown that diclazuril sodium salt has the potential to be used as a feed additive for the treatment and prophylaxis of EPM and various other Apicomplexan mediated diseases.     

上海地区鸡球虫对6种抗球虫药的抗药程度研究

为了解上海地区的鸡球虫抗药性状况,作者采集了上海市9个区县10个鸡场的球虫,进行了对地克珠利（Diclazuril)、氯苯胍（Robenidine)、氯羟吡啶（Clopidol)、氨丙啉（Amprolium)、马杜拉霉素（Maduramicin)、莫能霉素（Monensin)的抗药性研究。试验设6个药物组和感染不用药、不感染不用药2个对照组,以抗球虫指数（ACI）、病变记分减少率（RLS）、相对卵囊产量（ROP）、最适抗球虫活性百分率（POAA）为试验指标,进行综合评定,其抗药程度分为无抗药性、轻度抗药性、中度抗药性、完全抗药性4个等级。结果显示来自10个鸡场的球虫中,对地克珠利有90％未产生抗药性,对氯苯胍有90％为无抗药性和轻度抗药,对驻杜拉霉素有50％为无抗药性和轻度抗药,对氯羟吡啶有80％达到完全抗药,对氨丙啉有90％达到中度和完全抗药,对莫能霉素则全部达到中度以上的抗药程度,作者认为目前在上海地区以放心地理合理使用地克珠利和氯苯胍,对马杜拉霉素要慎使用,对氯羟吡啶、氨丙啉、莫能霉素须减少或暂停使用。     

Increased level of Eimeria sensitivity to diclazuril after using a live coccidial vaccine

Anticoccidial vaccine and an anticoccidial drug rotation program were compared to determine which program was more effective in producing coccidia populations sensitive of 1 ppm diclazuril. The study used an anticoccidial drug-sensitivity battery test (AST) to determine the baseline level of diclazuril sensitivity to field isolates of Eimeria spp. from seven broiler complexes that had used diclazuril. Based on percentage reduction in weight gain and lesion scores, 25% or fewer of the isolates were effectively controlled by diclazuril. Following the baseline sampling, four of the complexes switched to a nondiclazuril in-feed anticoccidial drug program and three of the complexes switched to a vaccination program for two broiler grow-out cycles as the sole coccidiosis-control program. This study demonstrated that the vaccine used (Coccivac-B) contained anticoccidial drug-sensitive strains. Eimeria isolates were subsequently collected from the identical houses and diclazuril AST results were compared with the baseline AST results. Following the two grow-out cycles, sensitivity of the isolates to diclazuril from the four complexes that continued to use in-feed anticoccidial drugs remained essentially unchanged. The isolates from the three complexes that switched to the vaccination program demonstrated a marked increase in diclazuril sensitivity, with 60%-100% of the isolates from each complex effectively controlled by diclazuril. Vaccination with the anticoccidial drug-sensitive strains produced a measurable increase in the level of sensitivity to diclazuril.     

柔嫩艾美耳球虫对四种抗球虫药的交叉抗药性试验

为了测试柔嫩艾美耳球虫的４种抗药虫株（抗地克珠利、抗拉沙里菌素、抗盐霉素和抗克球粉虫株）对４种抗球虫药（地克珠利、拉沙里菌素、盐霉素和克球粉）的敏感性进行了本试验。结果表明：柔嫩艾美耳球虫地克珠利抗药虫株对拉沙里菌素、盐霉素和克球粉均表现敏感,拉沙里菌素抗药虫株、盐霉素抗药虫株和克球粉抗药虫株对地克珠利也表现为高度敏感,因此,柔嫩艾美耳球虫对地克珠利与拉沙里菌素、地克珠利与盐霉素、地克珠利与克球粉３组药物不存在交叉抗药性。     

柔嫩艾美耳球虫地克珠利抗药株的实验室诱导

采用药物浓度递增法,以0．07mg／L地克珠利为起始诱导浓度连续传代,以最适抗球虫指数（POAA）、病变记分减少率（RLS）和相对卵囊产量（ROP）3项指标综合判定抗药性。经12次传代,该诱导虫株对1．5mg／L地克珠利具有完全抵抗力。试验结果表明,用实验室方法诱导柔嫩艾美耳球虫抗药株完全可行。     

Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics

Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral data consistent with the presence of diclazuril. After a single oral dose of diclazuril at 2.5 g/450 kg (as 500 g Clinacox), plasma samples from four horses showed good plasma concentrations of diclazuril which peaked at 1.077 +/- 0.174 microg/mL (mean +/- SEM) with an apparent plasma half-life of about 43 h. When this dose of Clinacox was administered daily for 21 days to two horses, mean steady state plasma concentrations of 7-9 microg/mL were attained. Steady-state levels in the CSF ranged between 100 and 250 ng/mL. There was no detectable parent diclazuril in the urine samples of dosed horses by HPLC or by routine postrace thin layer chromatography (TLC). These results show that diclazuril is absorbed after oral administration and attains steady-state concentrations in plasma and CSF. The steady state concentrations attained in CSF are more than sufficient to interfere with Sarcocystis neurona, whose proliferation is reportedly 95% inhibited by concentrations of diclazuril as low as 1 ng/mL. These results are therefore entirely consistent with and support the reported clinical efficacy of diclazuril in the treatment of clinical cases of EPM.     

Higher incidence of Eimeria spp. field isolates sensitive for diclazuril and monensin associated with the use of live coccidiosis vaccination with paracox-5 in broiler farms

Twenty European Eimeria spp. field isolates were subjected to an anticoccidial sensitivity test (AST). The anticoccidial drugs tested were diclazuril (Clinacox) and monensin (Elancoban). The assay was performed in a battery cage trial. Infected medicated birds were compared with an unmedicated control group. Coccidial lesion scores and oocyst shedding were used as parameters. The results of the AST show that resistance is common amongst coccidiosis field isolates, especially Eimeria acervulina (68% and 53% resistance for diclazuril and monensin, respectively). Resistance is less frequent amongst Eimeria maxima (38% and 50% resistance for diclazuril and monensin, respectively) and Eimeria tenella isolates (23% and 38% resistance for diclazuril and monensin, respectively). A highly significant influence of the coccidiosis prevention program (live coccidiosis vaccination with Paracox-5 vs. anticoccidial drugs in feed) on the sensitivity patterns of Eimeria spp. field isolates for both diclazuril (P= 0.000) and monensin (P= 0.001) was found. Further, when looking at the single species and each anticoccidial drug level, significantly more sensitivity of E. acervulina for monensin (P= 0.018), E. maxima for diclazuril (P = 0.009), and E. tenella for diclazuril (P = 0.007) was found in isolates originating from vaccinated flocks. Moreover, for E. acervulina and diclazuril, E. maxima and monensin, and E. tenella and monensin a trend toward higher sensitivity of isolates for these products was found when live coccidiosis vaccination was applied. The present study shows that sensitivity for the anticoccidial drugs diclazuril and monensin is more frequent in Eimeria spp. field isolates originating from broiler farms where a coccidiosis vaccination policy is followed.     

2株柔嫩艾美耳球虫对5种抗球虫药的抗药性

选择130只21日龄雏鸡，研究了柔嫩艾美耳球虫（E.tenella)南京株和凤阳株对地克珠利（Diclazuril)、马杜霉毒（Maduramicin)、氯羟吡啶（Clopidol)、氯苯胍（Robenidine)和氨丙啉（Amprolium)的抗药性。试验鸡随机分成13组，其中每株球虫均设5个感染用药组，1个感染不用药组，另设1个不感染不用药组，每组10只鸡。以POAA，RLS，ROP，ACI作为指标。结果表明，2株柔嫩艾美耳球虫均对氨丙啉轻度抗药，对地克珠利敏感或轻度抗药，对氯羟吡啶中度抗药。对马杜霉和氯苯胍中度抗药或安全抗药。提示：目前在凤阳地区可合理地使用地克珠利和氨丙啉，对氯羟哟啶应慎用，对马杜霉素和氯苯胍须减少或暂停使用。     

液相色谱-串联质谱法研究地克珠利在家兔组织中残留及消除规律

[目的]建立一种检测家兔组织中地克珠利含量的液相色谱-串联质谱法（LC—MS／MS）,研究地克珠利在家兔组织中的残留及消除规律。[方法]选择48只家兔（雌雄各半）,在饲料中加入10g／1000kg地克珠利混饲,连续饲喂30d。分别于休药后的第0、1、2、3、4、5、6天,每个时间点随机处死6只家兔（雌雄各半）,取肌肉、肝脏、肾脏组织,DMF,乙腈沉淀法提取并用LC—MS,MS法检测地克珠利残留量。[结果]地克珠利在肾脏中的残留量最高（休药0d为912．6μg／kg）,肝脏次之（休药0d为156．μg／kg）,肌肉最低（休药0d为43．1μg／kg）,在肾脏中的消除速度最快。[结论]该方法适于检测家免组织中的地克珠利含量。休药0d即可满足欧盟要求