妥曲珠利毒性及其残留的实验研究
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摘要
鸡球虫病是由艾美耳球虫引起的一种细胞内寄生虫病,本病主要发生于3月龄内的雏鸡,15～50日龄内最易感染,发病率高达70%,死亡率20～50%,全球每年因本病造成的经济损失达20亿美元。目前,药物防治仍是防止本病流行的主要措施,但是因鸡球虫耐药虫株的迅速产生而大大降低了药效。鉴于此,高效、低毒、不易产生耐药性的抗球虫新药的研制已迫在眉捷。
本研究拟评价对上海新亚药业有限公司生产的妥曲珠利对鸡球虫的临床疗效、药物毒性和药物残留等,进而为兽医临床的合理应用和食品卫生奠定理论和实验基础。
临床疗效实验,分别对给药后的各组试验鸡的临床症状、发病率、死亡率、相对增重率、粪便记分、病变记分、卵囊值等指标进行考察,并按默克公司的抗球虫指数方法进行计算。
急性毒性实验,分别以不同剂量的药物给大鼠灌胃给药,同时设立空白对照组。结果显示,妥曲珠利的半数致死量LD50为4645mg/kg,95%置信区间为4358mg/kg～4950mg/kg。根据药物急性毒性分级,妥曲珠利属毒性小药物。
药物残留实验,检测妥曲珠利在鸡肝、肾、肌肉3种组织中的残留。用乙腈一乙酸乙酯(3/2 v/v)提取组织中的药物,利用高效液相色谱法测定组织中妥曲珠利的浓度。结果表明,100mg/kg饲料添加妥曲珠利在鸡体内休药期为14d,50mg/kg时休药期为8d,与农业部制定的无公害兽药标准75～100 mg/kg一致。
上述实验结果证实,妥曲珠利具有高效、低毒、不易产生耐药性的特点,有望成为新一代抗球虫药物。
Fowl Globidiosis pertains to a kind of cytozoon disease caused by Eimeria tenella and mainly occurs in three months especially from 15 months to 45 months, leading to 70 percent disease incidence, death rate ranging from 20 percent to 50 percent and 2 billion dollor loss every year. Nowadays, fowl globidiosis was mainly treated by drugs, which pharmacodynamic action was cut down as the birth of new coccidian strain. It was urgent to develop the anti-coccidian drug possessing the characteristic of high performance, least toxicity and difficult to form drug resistance.
Experimental researchs including curative effect, toxicity and residual of toltrazuril produced by shanghai xinya Co.Ltd in order to provide certain theory and experiment foundation for veterinary practice and food sanitation.
Clinical curative effect was determined by clinical symptom, disease incidence,mortalit, relative growth rate, excrement and urine score, pathological change score, oosphere etc, and gained anti-coccidian index by Merck method.
Different group of rats were treated by intragastric administration and meanwhile control group was prepared.The results showed that median lethal dose(LD50) of toltrazuril was 4645mg/kg and 95% confidence interval ranged from 4358mg/kgto 4950mg/kg.Toltrazuril was a kind of least toxicity drug according to acute toxic ranking standard.
Toltrazuril residual was determined by high efficiency liquid chromatography after extracting from fowl liver, kidney and muscle (acetonitrile and acetoacetate, 3/2v/v).The results showed that drug holiday of 100 mg/kg and 50 mg/kg toltrazuril were respectively 14 days and 7 days, which conformed to safe animal medicine standard enacted by Ministry of Agriculture(from 75mg/kg to 100mg/kg).
These experimental results demonstrates that toltrazuril has the feature of high performance, least toxicity and difficult to form drug resistance and would be new anti-coccidian drug in future .
本研究拟评价对上海新亚药业有限公司生产的妥曲珠利对鸡球虫的临床疗效、药物毒性和药物残留等,进而为兽医临床的合理应用和食品卫生奠定理论和实验基础。
临床疗效实验,分别对给药后的各组试验鸡的临床症状、发病率、死亡率、相对增重率、粪便记分、病变记分、卵囊值等指标进行考察,并按默克公司的抗球虫指数方法进行计算。
急性毒性实验,分别以不同剂量的药物给大鼠灌胃给药,同时设立空白对照组。结果显示,妥曲珠利的半数致死量LD50为4645mg/kg,95%置信区间为4358mg/kg～4950mg/kg。根据药物急性毒性分级,妥曲珠利属毒性小药物。
药物残留实验,检测妥曲珠利在鸡肝、肾、肌肉3种组织中的残留。用乙腈一乙酸乙酯(3/2 v/v)提取组织中的药物,利用高效液相色谱法测定组织中妥曲珠利的浓度。结果表明,100mg/kg饲料添加妥曲珠利在鸡体内休药期为14d,50mg/kg时休药期为8d,与农业部制定的无公害兽药标准75～100 mg/kg一致。
上述实验结果证实,妥曲珠利具有高效、低毒、不易产生耐药性的特点,有望成为新一代抗球虫药物。
Fowl Globidiosis pertains to a kind of cytozoon disease caused by Eimeria tenella and mainly occurs in three months especially from 15 months to 45 months, leading to 70 percent disease incidence, death rate ranging from 20 percent to 50 percent and 2 billion dollor loss every year. Nowadays, fowl globidiosis was mainly treated by drugs, which pharmacodynamic action was cut down as the birth of new coccidian strain. It was urgent to develop the anti-coccidian drug possessing the characteristic of high performance, least toxicity and difficult to form drug resistance.
Experimental researchs including curative effect, toxicity and residual of toltrazuril produced by shanghai xinya Co.Ltd in order to provide certain theory and experiment foundation for veterinary practice and food sanitation.
Clinical curative effect was determined by clinical symptom, disease incidence,mortalit, relative growth rate, excrement and urine score, pathological change score, oosphere etc, and gained anti-coccidian index by Merck method.
Different group of rats were treated by intragastric administration and meanwhile control group was prepared.The results showed that median lethal dose(LD50) of toltrazuril was 4645mg/kg and 95% confidence interval ranged from 4358mg/kgto 4950mg/kg.Toltrazuril was a kind of least toxicity drug according to acute toxic ranking standard.
Toltrazuril residual was determined by high efficiency liquid chromatography after extracting from fowl liver, kidney and muscle (acetonitrile and acetoacetate, 3/2v/v).The results showed that drug holiday of 100 mg/kg and 50 mg/kg toltrazuril were respectively 14 days and 7 days, which conformed to safe animal medicine standard enacted by Ministry of Agriculture(from 75mg/kg to 100mg/kg).
These experimental results demonstrates that toltrazuril has the feature of high performance, least toxicity and difficult to form drug resistance and would be new anti-coccidian drug in future .
引文
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[3] Levine PP.The effect of sulfan ide on the course of experimental avian coccidiosis [J]. Cornell Vet. 1939,29: 309-320
[4]马立农.球痢灵对肉鸡抗球虫促生长效果的观察[J].北农学院学报,1997,7(1): 48-52
[5]张传津,丁新仁.莫能菌素预混剂防治鸡球虫病的试验[J].兽药与饲料添加剂,2002,7: 11-12
[6]甘德培.抗球虫药与球虫的抗药性研究进展[J] .中国兽医寄生虫病,1999,7(2): 53-56
[7] Peeters J E,Gerroms R. Efficacy of toltrazuril against intestinal and hepatic coccidiosis in rabbits[J] . Veterinary Parasitol,1986,22( 1 - 2): 21-35
[8] Horton-Smith C. Sulphaquinoxaline in the treatment of caecal coccidiosis in chick-ens caused by the E.tenella .Investigation of diseases and their control. Section III. Paris : 9th world Poultry congress,1951,3-8
[9] Waletzky E. A field strin of E.tenella resistant to sulfona mide[J]. Parasitol,1954,4@: 24
[10] Cuckler A C,Malanga C M. Studies on drug resistance in coccidian. Jparasitol, 1955, 41: 302-311
[11] Hodgson J N, Ball S J, Ryan K C, et al. The incidence of drug resistant strains of Eimeria in chicken in Great Britain. Br Vet J,1969,125: 31-35
[12] Jeffers T K. E.tenella incidence distribution and anticoccidial drug resistance of isolates in major broiler producing areas. Avian Disease,1974,18: 74-84
[13] Harnet N. Resistance to Anticoccidial drugs in poultry farms in France from 1975 to1984. Proc Georgia Coccidosis Conf Univ Georgia Athens,1986,415-424
[14] Oikawa H. Survev on drug resistance of coccidian in broilers.Jap J Vet Sci,1975, 37: 357-362
[15] Mc Dougald L R. A survey of sensitivity to anticoccidial drugs in 60 isolates of coccidian from broiler chickens in Brazil and Argertina. Avian Diseases, 1987, 31 (2): 287 - 292
[16] Chap man H D. Drug resistance in avisn coccidian(A review). Vet Parasitol, 1984, 15: 11-27
[17] Mc Dougald L R. Drug-sensitivity of 99 isolates of coccidian from broiler farms. Avian Diseases,1986,30(4): 690-694
[18] Rotibi A, Mc Dougald L R, Solis j. Response of 21 Canadian field isolates of chicken coccidian to commercial anticoccidial drugs. Avian Diseases,1989,33: 365-367
[19]孔繁瑶,宁申长.15株柔嫩艾美耳球虫对五种抗球虫药的抗药性的调查[J].北京:农业大学学报,1994,20 (3): 302-308
[20] Kawazon U, Fabio J D. Resistance to dic1azuril in field isolates of Eimeria species obtained from commercial bruiler flocks in Brazil. Avian pathology, 1994, 23: 305 - 311
[21] Jeffers T K. Genetics of coccidian and the host response. In: P L Long,K N Boor man and B M Free man. Avian coccidiosis. 50-125 Thirteenth Poultry Science Symposium. British Poultry Science, 1978
[22]马立农,陈杖榴.鸡球虫耐药性的产生及其延缓措施[J].湖北农学院学报,1999, 19 (2): 179~183
[23] Chapman H D. Bioche mical genetic and applied aspect of drug resistance in Eimeria parasites of the fowl. Avian pathology,1997,26: 221-244 56
[24] (美) P L朗编著.球虫生物学.蒋金书,刘中灵,陆信武译.广西科学技术出版社, 1990,208-210
[25]索勋,李国清,李安兴.鸡球虫病学[M].中国农业大学出版社,1998, 158-178
[26]安建,孔繁瑶,汪明.马杜霉素抗药性诱导的实验研究[J].畜牧兽医学报,1997, 28 (4): 349~356
[27] Chapman H D. E tenellαExperimental studies on the development of resistance to robenidine. J Parasitol, 1976, 73: 265-273
[28] (日)角田清主编.鸡球虫.陈谊,明如镜译.上海科学技术文献出版社, 1986,82-93
[29]甘德培,汪明,吴忘光.柔嫩艾美耳球虫地克珠利抗药株与克球粉抗药株的实验室诱导[J].中国农业大学学报, 1998 (增刊): 160
[30] Bedrnik P, Jurkovic P, Firmanova A, et al. The effect of ionophore anticoccidial agents on coccidia isolated in field conditions 1984-1985[J]. Vet Med(Praha), 1987, 32(12): 731-739
[31] Mathis G F, Mc Dougald L R, Mc Murray B. Drug sensitivity of coccidia from broiler breeder pullets and from broilers in the same integrated company[J]. Avian Dis, 1984,28(2): 453-459
[32]张健鳞,彭新字,魏文康.近年来广东省鸡球虫病防治的反思及今后的对策[J].饲养管理,1999,3: 38-39
[33]孔繁瑶,宁长申. 15株柔嫩艾美耳球虫对五种球虫药的抗药性调查[J] .北京农业大学学报,1994,20 (3): 302 -308
[34] Pressma BC. Biological applications of ionophores. Annu Rev Riochem 1976, 45:501-530
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