奶牛用头孢洛宁乳房注入剂(干乳期)的安全性评价
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摘要
【目的】确定自主研发新兽药——头孢洛宁乳房注入剂(干乳期)对靶动物的安全性。【方法】选择经产和初产健康泌乳期奶牛各6头,入选前30日内未接受过全身性或乳房内抗生素给药,产奶量在15-35 kg。给药前1日、给药当日(0日),记录各试验奶牛的日产奶量、直肠温度,并采集奶样进行体细胞检测。采样时先用清水冲洗乳房,用75%乙醇对乳头及周围进行消毒,待酒精挥发后,手工挤奶,弃去前三把奶后,采集奶样于灭菌试管中,贴好标签,低温(4℃)保存并于6 h内送实验室检测。给药当天,待奶牛挤完奶后,先用消毒毛巾清洁各乳区,再用消毒药液浸泡乳头约30 s,然后进行乳头内灌注给药。灌注时轻轻推压活塞,将药物缓缓注入乳池内,使药物均匀分布。按照推荐剂量,每头奶牛的4个乳区分别单次注入头孢洛宁乳房注入剂(干乳期)一支(含头孢洛宁250 mg)。给药后1日、3日、5日、7日和10日对4个乳区各采集奶样。记录奶牛标识、观察时间、试验日期和时间、每头奶牛日产奶量及体温等参数。检测乳样中体细胞数(SCC),对给药当日(0日)和给药后第10日各采集的乳样进行细菌学检查。将各奶样接种至选择性培养基分离各种病原菌。分离菌株经纯化培养后,依据菌落形态、染色特征、生化特点鉴定其种类。主要分离金黄色葡萄球菌、链球菌(无乳链球菌、乳房链球菌)、大肠杆菌。【结果】在整个试验期间,给药乳区未出现乳房红、肿、热、痛等临床症状。给药前1日、0日和给药后的1、3、5、7和10日,体细胞数大多在25-40万个/mL,平均体细胞数分别为33.26、32.74、32.70、31.63、31.24、30.62、30.04万个/mL,给药后各时间点奶样体细胞数与给药前体细胞检测结果相比,体细胞数有所降低,但经重复测量方差分析显示无显著性差异(P>0.05);日产奶量在23-33 kg,平均日产奶量分别为27.30、27.35、27.25、27.40、27.64、27.83、28.00 kg,经重复测量方差分析显示无显著性差异(P>0.05);所有试验奶牛在给药前和给药后不同时间点的直肠温度均在奶牛的正常温度范围内(38.4-39.2℃),直肠平均温度分别为38.79、38.82、38.83、38.77、38.71、38.71、38.69℃,经重复测量方差分析显示无显著性差异(P>0.05);故按推荐剂量单次给药对奶牛的体细胞数、日产奶量、体温无显著影响。病原菌鉴定结果表明:在给药当日(0日)采集的乳样中,分离到链球菌、葡萄球菌和大肠杆菌分别为2、3和4株;给药后第10日,仅检测到葡萄球菌和链球菌各1株,给药前后目标菌数量有显著降低。【结论】头孢洛宁乳房注入剂(干乳期)对奶牛体温、产奶量和奶中体细胞数等无不良影响,该制剂用于奶牛安全。
【Objective】 The purpose of this paper was to investigate the safety of cefalonium intramammary infusion(dry cow) for target animals. 【Method】 Six primiparous and six multiparous healthy dairy cows were selected, which have not been treated with any antibiotics by systemic or intramammary administration 30 days before. Their daily milk yield was 15-35 kg. At day 1 and day 0 prior to administration of the tested drug, the daily milk production and body temperature of the tested animals were recorded, and their milk samples were collected for somatic cell count analysis. For milk sampling,the udder was rinsed with clean water and the nipples and the close skin were disinfected with 75% ethanol. Milk samples were collected in sterilized test tubes(milking by hand and discarding the first three times of milking). The collected sample were stored at low temperature(4℃) and sent to laboratory for testing within 6 h. For drug infusion, each quarter of udder was cleaned with a disinfected towel and the teats were soaked for 30 seconds with disinfectant. The drug was slowly inject into the quarter so that it could be evenly distributed. Each quarter was injected with a single dose of cefalonium(Dry Cow)(250 mg). Samples of each quarter were collected at 1, 3, 5, 7, and 10 days after the drug administration. Individual milk production, quantitative somatic cell count(SCC) and body temperature were recorded. Day 0 and day 10 milk samples were cultivated with selective medium to isolate bacteria. The isolated strains were identified according to their colony morphology, staining and biochemical characteristics. The main pathogens analyzed were Staphylococcus aureus, Streptococcus(Streptococcus agalactiae, Streptococcus uberis), Escherichia coli. 【Result】 During the whole test period, there was no clinical symptoms such as swelling, erythema, pain, or heat. On day 1, 0 prior to and 1, 3, 5, 7 and 10 day after administration of the drug, somatic cell count was 250-400 thousand per milliliter. The mean somatic cells count for the seven time points were 332.6, 327.4, 327.0, 316.3, 312.4, 306.2, 300.4 thousand per milliliter respectively, but there is no significant difference(P>0.05) among them by analysis of repeated measures anova. Daily milk yield was 23-33 kg. The average daily milk yield for the seven time points was 27.30, 27.35, 27.25, 27.40, 27.64, 27.83, 28.00 kg, respectively. It had no significant difference(P>0.05) by repeated measures anova. The rectal temperature of all tested cows before and after administration was within the normal range. The mean values of rectal temperature were 38.79, 38.82, 38.83, 38.77, 38.71, 38.71 and 38.69 ℃ respectively, and there was no significant difference(P>0.05). Therefore, according to the recommended dose of a single administration, it had no significant effect on somatic cell count, daily milk yield and rectal temperature of the tested animals. The results for bacteria isolation showed that there were 2, 3 and 4 strains of Streptococcus, Staphylococcus and Escherichia coli, respectively on day 0 of the administration of the drug, and there were 1, 1 and 0 strains of Streptococcus, Staphylococcus and Escherichia coli on day 10 after administration, respectively. The number of pathogens was significantly decreased through the treatment of the drug. 【Conclusion】 The recommended dose of cofalonium had no adverse effect on rectal temperature, milk yield and somatic cell counts for dairy cows after mammary administration. It is safe for the drug to be used in dairy cows by intramammary infusion(Dry Cow).
【Objective】 The purpose of this paper was to investigate the safety of cefalonium intramammary infusion(dry cow) for target animals. 【Method】 Six primiparous and six multiparous healthy dairy cows were selected, which have not been treated with any antibiotics by systemic or intramammary administration 30 days before. Their daily milk yield was 15-35 kg. At day 1 and day 0 prior to administration of the tested drug, the daily milk production and body temperature of the tested animals were recorded, and their milk samples were collected for somatic cell count analysis. For milk sampling,the udder was rinsed with clean water and the nipples and the close skin were disinfected with 75% ethanol. Milk samples were collected in sterilized test tubes(milking by hand and discarding the first three times of milking). The collected sample were stored at low temperature(4℃) and sent to laboratory for testing within 6 h. For drug infusion, each quarter of udder was cleaned with a disinfected towel and the teats were soaked for 30 seconds with disinfectant. The drug was slowly inject into the quarter so that it could be evenly distributed. Each quarter was injected with a single dose of cefalonium(Dry Cow)(250 mg). Samples of each quarter were collected at 1, 3, 5, 7, and 10 days after the drug administration. Individual milk production, quantitative somatic cell count(SCC) and body temperature were recorded. Day 0 and day 10 milk samples were cultivated with selective medium to isolate bacteria. The isolated strains were identified according to their colony morphology, staining and biochemical characteristics. The main pathogens analyzed were Staphylococcus aureus, Streptococcus(Streptococcus agalactiae, Streptococcus uberis), Escherichia coli. 【Result】 During the whole test period, there was no clinical symptoms such as swelling, erythema, pain, or heat. On day 1, 0 prior to and 1, 3, 5, 7 and 10 day after administration of the drug, somatic cell count was 250-400 thousand per milliliter. The mean somatic cells count for the seven time points were 332.6, 327.4, 327.0, 316.3, 312.4, 306.2, 300.4 thousand per milliliter respectively, but there is no significant difference(P>0.05) among them by analysis of repeated measures anova. Daily milk yield was 23-33 kg. The average daily milk yield for the seven time points was 27.30, 27.35, 27.25, 27.40, 27.64, 27.83, 28.00 kg, respectively. It had no significant difference(P>0.05) by repeated measures anova. The rectal temperature of all tested cows before and after administration was within the normal range. The mean values of rectal temperature were 38.79, 38.82, 38.83, 38.77, 38.71, 38.71 and 38.69 ℃ respectively, and there was no significant difference(P>0.05). Therefore, according to the recommended dose of a single administration, it had no significant effect on somatic cell count, daily milk yield and rectal temperature of the tested animals. The results for bacteria isolation showed that there were 2, 3 and 4 strains of Streptococcus, Staphylococcus and Escherichia coli, respectively on day 0 of the administration of the drug, and there were 1, 1 and 0 strains of Streptococcus, Staphylococcus and Escherichia coli on day 10 after administration, respectively. The number of pathogens was significantly decreased through the treatment of the drug. 【Conclusion】 The recommended dose of cofalonium had no adverse effect on rectal temperature, milk yield and somatic cell counts for dairy cows after mammary administration. It is safe for the drug to be used in dairy cows by intramammary infusion(Dry Cow).
引文
[1]DE OLIVEIRA A P,WATTS J L,SALMON S A,AARESTRUP F M.Antimicrobial susceptibility of Staphylococcus aureus isolated from bovine mastitis in Europe and the United States.Journal of Dairy Science,2000,83(4):855-862.
[2]KIBEBEW K.Bovine Mastitis:A review of causes and epidemiological point of view.Journal of Biology,Agriculture and Healthcare,2017,7(2):1-14.
[3]GOMES F,HENRIQUES M.Control of bovine mastitis:old and recent therapeutic approaches.Current Microbiology,2016,72(4):377-382.
[4]KUMAR A,RAHAL A,DWIVEDI S K,GUPTA M K.Bacterial prevalence and antibiotic resistance profile from bovine mastitis in Mathura,India.Egyptian Journal of Dairy Science,2010,38(1):31-34.
[5]ZHANG L L,LI Y C,BAO H D,WEI R C,ZHOU Y,ZHANG H,WANG R.Population structure and antimicrobial profile of Staphylococcus aureus strains associated with bovine mastitis in China.Microbial Pathogenesis,2016,97:103-109.
[6]ZHAO F,GAO X,TANG Z X,LUO X,WU M M,XU J C,FU X T.Development of a simple multi-residue determination method of 80veterinary drugs in Oplegnathus punctatus by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.Journal of Chromatography B,2017,1065-1066:20-28.
[7]WOOLFORD M W,WILLIAMSON J H,DAY A M,COPEMAN P J.The prophylactic effect of a teat sealer on bovine mastitis during the dry period and the following lactation.New Zealand Veterinary Journal,1998,46(1):12-19.
[8]RABIEE A R,LEAN I J.The effect of internal teat sealant products(Teatseal and Orbeseal)on intramammary infection,clinical mastitis,and somatic cell counts in lactating dairy cows:a meta-analysis.Journal of Dairy Science,2013,96(11):6915-6931.
[9]GRUET P,MAINCENT P,BERTHELOT X,KALTSATOS V.Bovine mastitis and intramammary drug delivery:review and perspectives.Advanced Drug Delivery Reviews,2001,50(3):245-259.
[10]ROYSTER E,WAGNER S.Treatment of mastitis in cattle.Veterinary Clinics of North America Food Animal Practice,2015,31(1):17-46.
[11]NICKERSON S C.Control of heifer mastitis:antimicrobial treatment-an overview.Veterinary Microbiology,2009,134(1-2):128-135.
[12]KANG J H,JIN J H,KONDO F.False-positive outcome and drug residue in milk samples over withdrawal times.Journal of Dairy Science,2005,88(3):908-913.
[13]Committee for Veterinary Medicinal Products.CefaloniumSummary report(2)[R].2002.
[14]李帅鹏,郭春娜,孟蕾,黄显会.高效液相色谱-串联质谱法检测牛奶中头孢洛宁残留.色谱,2014,32(5):519-523.LI S P,GUO C N,MENG L,HUANG X H.Determination of cefalonium residue in milk by high performance liquid chromatographytandem mass spectrometry.Chinese Journal of Chromatography,2014,32(5):519-523.(in Chinese)
[15]华伟毅,刘义明,徐飞,李秀波.头孢洛宁的药理作用及其在奶牛乳房炎防治中应用的研究进展.中国畜牧兽医,2016,43(10):2742-2747.HUA W Y,LIU Y M,XU F,LI X B.Research progress on pharmacological action of cephalonium and its application in prevention and treatment of mastitis in dairy cow.Chinese Husbandry and Veterinary Medicine,2016,43(10):2742-2747.(in Chinese)
[16]MORONI P,VELLERE F,ANTONINI M,G PISONI,RUFFO G,CARLI S.Antibiotic susceptibility of coagulase-negative staphylococci isolated from goats'milk.International Journal of Antimicrobial Agents,2004,23(6):637-640.
[17]MORONI P,PISONI G,ANTONINI M,RUFFO G,CARLI S,VARISCO G,BOETTCHER P.Subclinical mastitis and antimicrobial susceptibility of Staphylococcus caprae and Staphylococcus epidermidis isolated from two Italian goat herds.Journal of Dairy Science,2005,88(5):1694-1704.
[18]MORONI P,PISONI G,ANTONINI M,VILLA R,BOETTCHER P,CARLI S.Short communication:antimicrobial drug susceptibility of Staphylococcus aureus from subclinical bovine mastitis in Italy.Journal of Dairy Science,2006,89(8):2973-2976.
[19]李维静.头孢洛宁乳房注入剂防治干乳期奶牛乳腺炎的药效学及残留消除研究[D].扬州:扬州大学,2014.LI W J.Studies on the efficacy and residue elimination of Cephalonium intramammary infusion for the treatment of bovine mastitis during the drying off period[D].Yangzhou:Yangzhou University 2014.(in Chinese)
[20]OWENS W E,NICKERSON S C,BODDIE R L,TOMITA G M,RAY C H.Prevalence of mastitis in dairy heifers and effectiveness of antibiotic therapy.Journal of Dairy Science,2001,84(4):814-817.
[21]BRADLEY A J,BREEN J E,PAYNE B,WILLIAMS P,GREEN M J.The use of a cephalonium containing dry cow therapy and an internal teat sealant,both alone and in combination.Journal of Dairy Science,2010,93(4):1566-1577.
[22]SHEPHARD R W,BURMAN S,MARCUN P.A comparative field trial of cephalonium and cloxacillin for dry cow therapy for mastitis in Australian dairy cows.Australian Veterinary Journal,2004,82(10):624-629.
[23]NEWTON H T,GREEN M J,BENCHAOUI H,CRACKNELL V,ROWAN T,BRADLEY A J.Comparison of the efficacy of cloxacillin alone and cloxacillin combined with an internal teat sealant for dry-cow therapy.Veterinary Record,2008,162(21):678-684.
[24]WENTE N,ZOCHE-GOLOB V,BEHR M,KROMKER V.Susceptibility to cephalosporins of bacteria causing intramammary infections in dairy cows with a high somatic cell count in Germany.Preventive Veterinary Medicine,2016,131:146-151.
[25]SCHOFIELD J S.Animal-health pharmaceuticals:research responsibilities and efforts in target animal safety and laboratory animal welfare.Future Medicinal Chemistry,2011,3(7):851-854.
[26]U.S.Food and drug administration CVM GFI#49.Target Animal Safety And Drug Effectiveness Studies for Anti-Microbial Bovine Mastitis Products(Lactating and Non-Lactating Cow Products)[S]Revised April 4,1996(Revises the February 1,1993 Guideline)
[27]萧惠来.VICH兽药靶动物安全性研究指导原则概述.中国兽药杂志,2009,43(12):33-37.XIAO H L.Overview of VICH guideline of target animal safety for veterinary pharmaceutical product.Chinese Journal of Veterinary,2009,43(12):33-37.(in Chinese)
[28]周绪正,张继瑜,李金善,李冰,李剑勇,魏小娟,牛建荣,杨亚军,刘希望.赛拉菌素溶液对靶动物犬的安全性研究.黑龙江畜牧兽医,2013(5):120-122.ZHOU X Z,ZHANG J Y,LI J S,LI B,LI J Y,WEI X J,NIU J R,YANG Y J,LIU X W.Target animal safety study of selamectin solution in dogs.Heilongjiang Animal Science and Veterinary Medicine,2013(5):120-122.(in Chinese)
[29]冯言言,郑莉,林红,孟芳,孔梅,吴连勇,曹兴元.盐酸头孢噻呋注射液对奶牛的安全性研究.中国兽药杂志,2016,50(12):34-39.FENG Y Y,ZHENG L,LIN H,MENG F,KONG M,WU L Y,CAO XY.Study on safety of ceftiofur hydrochloride sterile suspension in dairy cows.Chinese Journal of Veterinary,2016,50(12):34-39.(in Chinese)
[30]闫星,刘义明,路永强,张道康,刘茂林,张宁,王天坤,郭江鹏,李秀波.硫酸头孢喹肟乳房注入剂对泌乳期奶牛的安全性研究.中国畜牧兽医,2014,41(11):278-282.YAN X,LIU Y M,LU Y Q,ZHANG D K,LIU M L,ZHANG N,WANG T K,GUO J P,LI X B.Safety study on cefquinome sulfate intramammary infusion of lactating cows.Chinese Husbandry and Veterinary Medicine,2014,41(11):278-282.(in Chinese)
[31]瞿红颖,魏丽娟,刘欣,魏占勇,宋婷婷,贾兴,耿智霞,吴聪明,张越.硫酸头孢喹肟子宫注入剂对泌乳期奶牛的安全性研究.中国畜牧兽医,2016,43(1):227-234.QU H Y,WEI L J,LIU X,WEI Z Y,SONG T T,JIA X,GENG Z X,WU C M,ZHANG Y.Safety study on cequinome sulfate intrauterine infusion for lactating cows.Chinese Husbandry and Veterinary Medicine,2016,43(1):227-234.(in Chinese)
[2]KIBEBEW K.Bovine Mastitis:A review of causes and epidemiological point of view.Journal of Biology,Agriculture and Healthcare,2017,7(2):1-14.
[3]GOMES F,HENRIQUES M.Control of bovine mastitis:old and recent therapeutic approaches.Current Microbiology,2016,72(4):377-382.
[4]KUMAR A,RAHAL A,DWIVEDI S K,GUPTA M K.Bacterial prevalence and antibiotic resistance profile from bovine mastitis in Mathura,India.Egyptian Journal of Dairy Science,2010,38(1):31-34.
[5]ZHANG L L,LI Y C,BAO H D,WEI R C,ZHOU Y,ZHANG H,WANG R.Population structure and antimicrobial profile of Staphylococcus aureus strains associated with bovine mastitis in China.Microbial Pathogenesis,2016,97:103-109.
[6]ZHAO F,GAO X,TANG Z X,LUO X,WU M M,XU J C,FU X T.Development of a simple multi-residue determination method of 80veterinary drugs in Oplegnathus punctatus by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.Journal of Chromatography B,2017,1065-1066:20-28.
[7]WOOLFORD M W,WILLIAMSON J H,DAY A M,COPEMAN P J.The prophylactic effect of a teat sealer on bovine mastitis during the dry period and the following lactation.New Zealand Veterinary Journal,1998,46(1):12-19.
[8]RABIEE A R,LEAN I J.The effect of internal teat sealant products(Teatseal and Orbeseal)on intramammary infection,clinical mastitis,and somatic cell counts in lactating dairy cows:a meta-analysis.Journal of Dairy Science,2013,96(11):6915-6931.
[9]GRUET P,MAINCENT P,BERTHELOT X,KALTSATOS V.Bovine mastitis and intramammary drug delivery:review and perspectives.Advanced Drug Delivery Reviews,2001,50(3):245-259.
[10]ROYSTER E,WAGNER S.Treatment of mastitis in cattle.Veterinary Clinics of North America Food Animal Practice,2015,31(1):17-46.
[11]NICKERSON S C.Control of heifer mastitis:antimicrobial treatment-an overview.Veterinary Microbiology,2009,134(1-2):128-135.
[12]KANG J H,JIN J H,KONDO F.False-positive outcome and drug residue in milk samples over withdrawal times.Journal of Dairy Science,2005,88(3):908-913.
[13]Committee for Veterinary Medicinal Products.CefaloniumSummary report(2)[R].2002.
[14]李帅鹏,郭春娜,孟蕾,黄显会.高效液相色谱-串联质谱法检测牛奶中头孢洛宁残留.色谱,2014,32(5):519-523.LI S P,GUO C N,MENG L,HUANG X H.Determination of cefalonium residue in milk by high performance liquid chromatographytandem mass spectrometry.Chinese Journal of Chromatography,2014,32(5):519-523.(in Chinese)
[15]华伟毅,刘义明,徐飞,李秀波.头孢洛宁的药理作用及其在奶牛乳房炎防治中应用的研究进展.中国畜牧兽医,2016,43(10):2742-2747.HUA W Y,LIU Y M,XU F,LI X B.Research progress on pharmacological action of cephalonium and its application in prevention and treatment of mastitis in dairy cow.Chinese Husbandry and Veterinary Medicine,2016,43(10):2742-2747.(in Chinese)
[16]MORONI P,VELLERE F,ANTONINI M,G PISONI,RUFFO G,CARLI S.Antibiotic susceptibility of coagulase-negative staphylococci isolated from goats'milk.International Journal of Antimicrobial Agents,2004,23(6):637-640.
[17]MORONI P,PISONI G,ANTONINI M,RUFFO G,CARLI S,VARISCO G,BOETTCHER P.Subclinical mastitis and antimicrobial susceptibility of Staphylococcus caprae and Staphylococcus epidermidis isolated from two Italian goat herds.Journal of Dairy Science,2005,88(5):1694-1704.
[18]MORONI P,PISONI G,ANTONINI M,VILLA R,BOETTCHER P,CARLI S.Short communication:antimicrobial drug susceptibility of Staphylococcus aureus from subclinical bovine mastitis in Italy.Journal of Dairy Science,2006,89(8):2973-2976.
[19]李维静.头孢洛宁乳房注入剂防治干乳期奶牛乳腺炎的药效学及残留消除研究[D].扬州:扬州大学,2014.LI W J.Studies on the efficacy and residue elimination of Cephalonium intramammary infusion for the treatment of bovine mastitis during the drying off period[D].Yangzhou:Yangzhou University 2014.(in Chinese)
[20]OWENS W E,NICKERSON S C,BODDIE R L,TOMITA G M,RAY C H.Prevalence of mastitis in dairy heifers and effectiveness of antibiotic therapy.Journal of Dairy Science,2001,84(4):814-817.
[21]BRADLEY A J,BREEN J E,PAYNE B,WILLIAMS P,GREEN M J.The use of a cephalonium containing dry cow therapy and an internal teat sealant,both alone and in combination.Journal of Dairy Science,2010,93(4):1566-1577.
[22]SHEPHARD R W,BURMAN S,MARCUN P.A comparative field trial of cephalonium and cloxacillin for dry cow therapy for mastitis in Australian dairy cows.Australian Veterinary Journal,2004,82(10):624-629.
[23]NEWTON H T,GREEN M J,BENCHAOUI H,CRACKNELL V,ROWAN T,BRADLEY A J.Comparison of the efficacy of cloxacillin alone and cloxacillin combined with an internal teat sealant for dry-cow therapy.Veterinary Record,2008,162(21):678-684.
[24]WENTE N,ZOCHE-GOLOB V,BEHR M,KROMKER V.Susceptibility to cephalosporins of bacteria causing intramammary infections in dairy cows with a high somatic cell count in Germany.Preventive Veterinary Medicine,2016,131:146-151.
[25]SCHOFIELD J S.Animal-health pharmaceuticals:research responsibilities and efforts in target animal safety and laboratory animal welfare.Future Medicinal Chemistry,2011,3(7):851-854.
[26]U.S.Food and drug administration CVM GFI#49.Target Animal Safety And Drug Effectiveness Studies for Anti-Microbial Bovine Mastitis Products(Lactating and Non-Lactating Cow Products)[S]Revised April 4,1996(Revises the February 1,1993 Guideline)
[27]萧惠来.VICH兽药靶动物安全性研究指导原则概述.中国兽药杂志,2009,43(12):33-37.XIAO H L.Overview of VICH guideline of target animal safety for veterinary pharmaceutical product.Chinese Journal of Veterinary,2009,43(12):33-37.(in Chinese)
[28]周绪正,张继瑜,李金善,李冰,李剑勇,魏小娟,牛建荣,杨亚军,刘希望.赛拉菌素溶液对靶动物犬的安全性研究.黑龙江畜牧兽医,2013(5):120-122.ZHOU X Z,ZHANG J Y,LI J S,LI B,LI J Y,WEI X J,NIU J R,YANG Y J,LIU X W.Target animal safety study of selamectin solution in dogs.Heilongjiang Animal Science and Veterinary Medicine,2013(5):120-122.(in Chinese)
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