【作者】 黄玲利；

【导师】 袁宗辉；

【作者基本信息】 华中农业大学 ， 农产品加工与贮藏工程， 2006， 博士

【摘要】 喹噁啉类是具有广谱抗菌和促生长双重作用的动物专用药，20世纪70年代以来曾被广泛应用于畜禽养殖业。本类早期品种喹乙醇与卡巴氧被证明有较强的毒副作用，已被不同程度地限制或禁止使用。开发降低或消除本类毒副作用并能发挥其抗菌促生长优势的替代产品具有重大意义。喹赛多是喹噁啉类品种之一。临床研究表明，喹赛多毒性小，对猪、羊和鱼等靶动物具有良好的抗菌促生长、提高饲料利用率和改善胴体品质等作用。残留研究证实，喹赛多在猪体内消除迅速，残留量低，食品安全性高。因此，喹赛多具有较大的开发应用前景。喹噁啉类现有品种(喹烯酮除外)在家禽生产中存在安全性问题。喹赛多具有优于同类产品的安全性，早期研究表明其对家禽具有促生长作用，提示喹赛多存在应用于家禽生产的潜能。作为食品生产动物用药，食品安全性是考核其开发应用前景的一个重要指标，已成为食品科技领域的研究热点。兽药残留是影响食品安全性的主要因素之一，药物代谢与残留消除规律研究则是避免残留的科技基础。因此，代谢与残留是食品生产动物用药研发的有机组成部分。本课题以商品肉鸡为研究对象，按新药临床试验要求系统开展了喹赛多在鸡的安全性、药效学、药动学及残留消除研究，阐明了喹赛多在鸡的有效性与安全性，揭示了喹赛多在养鸡生产中的应用前景。 1．喹赛多对肉鸡的安全性。30同龄艾维茵肉鸡单次灌服1、2、4、8和16g／kgb．w．喹赛多后，14天内未观察到中毒反应，增重与饲料消耗均无明显变化(P＞0.05)，确定肉鸡对喹赛多的经口最大耐受量(MTD)＞16g／kg b．w．。根据新兽药一般毒性试验技术要求，喹赛多属实际无毒药物。 5日龄艾维茵肉鸡分别连续饲喂含喹赛多25、50、100、200和500mg／kg的基础日粮40天，观察鸡的生长性能、胴体品质、生理生化指标和脏器系数等的变化规律。结果表明，日粮中添加50～500mg／kg喹赛多，鸡日增重提高9％～18％，饲料利用率改善5％～12％。50、100和200mg／kg组效果更佳，全期日增重可分别提高9.2％、14.2％和18.1％，饲料利用率分别改善7.3％、10.5％和11.8％。25天前应用效果更明显。喹赛多各剂量组对鸡胴体品质、脏器系数及生理生化指标均无明显影响(P＞0.05)。结果表明，鸡日粮中喹赛多添加量低于500mg／kg可有效改善生长性能，且长期饲喂无明显不良反应，提示喹赛多对鸡安全性较高。综合考虑生产与经济效益，推荐喹赛多在鸡日粮中的适宜添加量为50～100mg／kg。更多还原

【Abstract】 Quinoxalines are synthetic antimicrobial agents with growth-promoting activity, and have been used extensively in food animals since 1970s. Olaquindox and carbadox are the well-known members, but they have been banned or strictly limited to use in food animals in some countries for their genetic or potential toxicities. It is necessary to develop a new drug of quinoxalines which can retain the good advantages of quinoxalines with less toxicity and more safety. Cyadox is a developing candidate. Some studies show that cyadox can promote the growth and improve the feed conversion in swine, sheep and fish with much lower toxicity than olaquindox. Hence, it is hopeful that cyadox would be developed as a replacer of olaquindox and carbadox with more safety and excellent effectiveness in growth promotion and antibacterial activity. Old quinoxalines are seldom used in poultry for their toxicities. Since cyadox is much more safer than the old drugs of quinoxalines, and early research had reported its growth promotion effect in poultry, it is possible for cyadox to be used safely and effectively in poultry. As a new drug for food producing animals, food safety is a key parameter to evaluate the application foreground, and has become a hotspot problem in the field of food science. Drug residue is one of the main factors to endanger food safety, while drug metabolism and residue depletion are the scientific groundwork to avoid drug residue. Therefore, metabolism and residue research is the organic composition in the exploitation of new drug for food animals. In this research, systemic studies have been carried out following the requirments of clinical evaluation in new drug research, which focuse on the safety, pharmacodynamics, pharmacokinetics and residue depletion of cyadox in broilers. The results clarified the effectiveness and safety of cyadox in broilers, and indicated that cyadox had a good application foreground in chicken production.1. The safety of cyadox in broilers. Cyadox at 1, 2, 4, 8 and 16g/kg b.w. levels were administrated orally to 30day old broilers to investigate the maximum tolerance dose(MTD) of chicken to cyadox. During 14 days after the administration, no obvious toxic effects were observed with no significant changes of daily weight gain and feed consumption(P>0.05). Hence, the MTD of chicken to cyadox was over 16g/kg b.w., which indicated that cyadox was a drug with no toxicity for chicken as the general toxicity guidline declares.Cyadox at 25, 50, 100, 200 and 500mg/kg levels were administrated in-feed to更多还原