氯硝柳胺原位固化长效注射剂对感染日本血吸虫小鼠和水牛的预防效果
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摘要
目的观察氯硝柳胺原位固化长效注射剂对感染日本血吸虫(Schistosoma japonicum)的小鼠和水牛的疗效。方法 50只昆明小鼠随机均分为2组,给药组小鼠皮下注射低浓度氯硝柳胺原位固化长效注射剂(71 mg/ml)450 mg/kg 1次,对照组小鼠不作任何处理。给药后第1、15、43、57和71天,各组分别取5只小鼠采用腹部贴片法感染日本血吸虫尾蚴(80±4)条/鼠。35 d后,处死小鼠,检获成虫,计算减虫率。10头水牛分成2组,给药组4头、对照组6头。给药组水牛皮下注射高浓度氯硝柳胺原位固化长效注射剂(222 mg/ml)30 mg/kg1次,对照组水牛不作任何处理。于给药后第1和3个月粪检,计算粪检阳性率,并观察水牛的不良反应。采用SPSS19.0软件进行统计学分析,组间比较采用t检验。结果给药后第1、15、43、57和71天感染日本血吸虫尾蚴,35 d后给药组小鼠的虫荷分别为(3.6±1.4)条、(17.5±8.6)条、(10.0±6.8)条、0条、(11.3±8.4)条,均少于对照组小鼠的虫荷(P<0.05),且减虫率均超过50.0%。第1和3个月对水牛进行粪检,给药组均为阴性,对照组分别有2和3头阳性,其中1头牛给药后8 h出现精神沉郁。结论氯硝柳胺原位固化长效注射剂预防小鼠感染日本血吸虫尾蚴的作用达2个月,预防水牛感染日本血吸虫尾蚴的作用达3个月,具有现场应用预防血吸虫感染的潜力。
Objective To observe the protective effect of niclosamide in situ sustained-release injection against Schistosoma japonicum infection in mice and buffaloes. Methods Fifty female mice were randomly divided into 2 groups. One group received a subcutaneous low-concentration niclosamide in situ sustained-release injection(71 mg/ml) at a single dose of 450 mg/kg(drug group, n = 25), while the other group did not receive any treatment(control group, n = 25). Each group was further divided into 5 subgroups, in which five mice were infected with 80 ± 4Schistosoma japonicum cercariae on days 1, 15, 43, 57 and 71 after the treatment, and were sacrificed after 35 days to obtain adult worms and calculate the worm reduction rate. In the field trial, 10 buffaloes uninfected with Schistosoma japonicum were also divided into the drug group( n = 4) and the control group( n = 6). Buffaloes in the drug group were each given with a high concentration of niclosamide in situ sustained-release injection(222 mg/ml)at a single dose of 30 mg/kg, while those in the control did not receive any treatment. After 1 and 3 months, fecal examination was performed to detect Schistosoma japonicum infection in buffaloes. The positive rate was calculated and adverse reactions were observed. Between-group comparisons were made with t test by using the SPSS19.0 software. Results In mice infected with cercariae on days 1, 15, 43, 57 and 71 after drug treatment, the mean worm burden at 35 days after the infection was(3.6 ± 1.4),(17.5 ± 8.6),(10.0 ± 6.8), 0, and(11.3 ± 8.4) worms,respectively. All were significantly lower than that of the control( P < 0.05), and the worm reduction rates in drug group were all over 50.0%. Two and 3 infected buffaloes showed positive fecal examination at 1 and 3 months,respectively, while none in the drug group showed positive at both time points. One buffalo showed signs of depression at 8 h after treatment. Conclusion The niclosamide in situ sustained-release injection can protect mice against Schistosoma japonicum infection for 2 months and protect buffaloes for 3 months in the field, revealing a promising formulation to prevent schistosome infection.
Objective To observe the protective effect of niclosamide in situ sustained-release injection against Schistosoma japonicum infection in mice and buffaloes. Methods Fifty female mice were randomly divided into 2 groups. One group received a subcutaneous low-concentration niclosamide in situ sustained-release injection(71 mg/ml) at a single dose of 450 mg/kg(drug group, n = 25), while the other group did not receive any treatment(control group, n = 25). Each group was further divided into 5 subgroups, in which five mice were infected with 80 ± 4Schistosoma japonicum cercariae on days 1, 15, 43, 57 and 71 after the treatment, and were sacrificed after 35 days to obtain adult worms and calculate the worm reduction rate. In the field trial, 10 buffaloes uninfected with Schistosoma japonicum were also divided into the drug group( n = 4) and the control group( n = 6). Buffaloes in the drug group were each given with a high concentration of niclosamide in situ sustained-release injection(222 mg/ml)at a single dose of 30 mg/kg, while those in the control did not receive any treatment. After 1 and 3 months, fecal examination was performed to detect Schistosoma japonicum infection in buffaloes. The positive rate was calculated and adverse reactions were observed. Between-group comparisons were made with t test by using the SPSS19.0 software. Results In mice infected with cercariae on days 1, 15, 43, 57 and 71 after drug treatment, the mean worm burden at 35 days after the infection was(3.6 ± 1.4),(17.5 ± 8.6),(10.0 ± 6.8), 0, and(11.3 ± 8.4) worms,respectively. All were significantly lower than that of the control( P < 0.05), and the worm reduction rates in drug group were all over 50.0%. Two and 3 infected buffaloes showed positive fecal examination at 1 and 3 months,respectively, while none in the drug group showed positive at both time points. One buffalo showed signs of depression at 8 h after treatment. Conclusion The niclosamide in situ sustained-release injection can protect mice against Schistosoma japonicum infection for 2 months and protect buffaloes for 3 months in the field, revealing a promising formulation to prevent schistosome infection.
引文
[1]卫生部血吸虫病专家咨询委员会.人畜共患血吸虫病研究与防治策略重点[J].中国血吸虫病防治杂志,2006,18(2):81-82.
[2]Chitsulo L,Engels D,Montresor A,et al.The global status of schistosomiasis and its control[J].Acta Trop,2000,77(1):41-51.
[3]World Health Organization.Prevention and control of schistosomiasis and soil-transmitted helminthiasis:Report of a WHO Expert Committee[M].Geneva:World Health Organization,2004:912.
[4]雷正龙,周晓农.血吸虫病“十二五”防治规划实施进展及面临的挑战[J].中国寄生虫学与寄生虫病杂志,2014,32(2):81-85.
[5]李浩,刘金明,宋俊霞,等.2012年全国家畜血吸虫病疫情状况[J].中国动物传染病学报,2014,22(5):68-71.
[6]柳伟,曹淳力,陈朝,等.“以机代牛”等传染源综合治理措施防治血吸虫病的效果评价[J].中国寄生虫学与寄生虫病杂志,2013,31(3):206-211.
[7]肖树华.近年来发展抗血吸虫新药的进展[J].中国寄生虫学与寄生虫病杂志,2010,28(3):218-225.
[8]Andrews P,Thyssen J,Lorke D.The biology and toxicology of molluscicides,bayluscide[J].Pharmacol Ther,1982,19(2):245-295.
[9]陈淑玉,林辉环,陈炳德.氯硝柳胺(mansonil)对家禽消化道寄生驱虫试验[J].畜牧兽医科技,1980(2):14-18.
[10]Tchounwou PB,Englande AJ Jr,Malek EA,et al.The effects of bayluscide and malathion on the survival of Schistosoma mansoni miracidia[J].J Environ Sci Health B,1991,26(1):69-82.
[11]严晓岚,吴玲娟,杨明瑾,等.氯硝柳胺控释贴膜防御日本血吸虫尾蚴感染的初步试验[J].浙江省医学科学院学报,2004,15(1):23-25.
[12]吴莉菊.用氯硝柳胺治疗人体长膜壳绦虫和犬复孔绦虫感染[J].国外医学寄生虫病分册,1980,8(1):39-40.
[13]氯硝柳胺合并氨基阿的平和卡马拉治疗裂头绦虫病[J].国外医学参考资料(寄生虫病分册),1974(4):184-185.
[14]国家质量监督检验检疫总局.澳大利亚修订氯硝柳胺等物质残留限量[EB/OL].http://www.scnjzj.gov.cn/Article Show.asp?Article ID=7321.
[15]涂珍,姜斌,薛剑,等.氯硝柳胺在小鼠血浆中的代谢及抗日本血吸虫尾蚴侵袭作用[J].中国寄生虫学与寄生虫病杂志,2015,33(2):101-104.
[16]洪志勇,寇用义,黄铭西.灭绦灵预防小鼠血吸虫病研究[J].中国人兽共患病杂志,1990,6(3):43.
[17]徐明,许永良,沈林南.氯硝柳胺等涂肤剂防御血吸虫尾蚴感染实验观察[J].寄生虫病与感染性疾病,2004,2(4):181-182.
[18]蔡德全,卢永嵩,左世会,等.氯硝柳胺控释剂药物动力学的研究[J].中国血吸虫病防治杂志,1993,5(3):145-149.
[19]神学慧,戴建荣,李叶芳,等.氯硝柳胺悬浮剂灭蚴和预防血吸虫感染的研究[J].中国病原生物学杂志,2011,6(8):600-602.
[20]李洪军,梁幼生,戴建荣,等.氯硝柳胺悬浮剂杀灭日本血吸虫尾蚴的实验研究[J].中国血吸虫病防治杂志,2005,17(6):424-426.
[21]严晓岚,杨明瑾,漏磊君,等.长效涂肤剂“防蚴灵”预防血吸虫尾蚴感染的研究[J].中国血吸虫病防治杂志,2003,15(2):135-138.
[22]黄胜炎.抗肿瘤药新制剂[J].上海医药,2005,26(5):211-214.
[23]Singh K,Harikumar SL.Injectable in-situ gelling controlled release drug delivery system[J].Int J Drug Dev Res,2012,4(2):56-69.
[24]苏丹,涂家生.替硝唑原位固化缓释凝胶的处方研究[J].药学与临床研究,2009,17(2):100-104.
[25]王丽娟,朱照静,吴青,等.均匀设计法优选布洛芬缓释原位凝胶剂处方及释药性质的研究[J].重庆医科大学学报,2009,34(12):1704-1708.
[26]王飞,戴建荣.氯硝柳胺的毒理学安全性评价研究概况[J].中国人兽共患病学报,2013,29(1):86-90.
[27]徐颖,戴建荣.氯硝柳胺的细胞毒性机制研究[J].中国血吸虫病防治杂志,2015,27(1):104-107.
[28]Ofori-Adjei D,Dodoo ANO,Appiah-Danquah A,et al.A review of the safety of niclosamide,pyrantel,triclabendazole and oxamniquine[J].Int J Risk Safety Med,2008,20(3):113-122.
[29]陶奕,涂珍,张皓冰,等.氯硝柳胺在小鼠血浆、肌肉及皮肤中的药代动力学研究[J].国际医学寄生虫病杂志,2015,42(3):142-145,155.
[2]Chitsulo L,Engels D,Montresor A,et al.The global status of schistosomiasis and its control[J].Acta Trop,2000,77(1):41-51.
[3]World Health Organization.Prevention and control of schistosomiasis and soil-transmitted helminthiasis:Report of a WHO Expert Committee[M].Geneva:World Health Organization,2004:912.
[4]雷正龙,周晓农.血吸虫病“十二五”防治规划实施进展及面临的挑战[J].中国寄生虫学与寄生虫病杂志,2014,32(2):81-85.
[5]李浩,刘金明,宋俊霞,等.2012年全国家畜血吸虫病疫情状况[J].中国动物传染病学报,2014,22(5):68-71.
[6]柳伟,曹淳力,陈朝,等.“以机代牛”等传染源综合治理措施防治血吸虫病的效果评价[J].中国寄生虫学与寄生虫病杂志,2013,31(3):206-211.
[7]肖树华.近年来发展抗血吸虫新药的进展[J].中国寄生虫学与寄生虫病杂志,2010,28(3):218-225.
[8]Andrews P,Thyssen J,Lorke D.The biology and toxicology of molluscicides,bayluscide[J].Pharmacol Ther,1982,19(2):245-295.
[9]陈淑玉,林辉环,陈炳德.氯硝柳胺(mansonil)对家禽消化道寄生驱虫试验[J].畜牧兽医科技,1980(2):14-18.
[10]Tchounwou PB,Englande AJ Jr,Malek EA,et al.The effects of bayluscide and malathion on the survival of Schistosoma mansoni miracidia[J].J Environ Sci Health B,1991,26(1):69-82.
[11]严晓岚,吴玲娟,杨明瑾,等.氯硝柳胺控释贴膜防御日本血吸虫尾蚴感染的初步试验[J].浙江省医学科学院学报,2004,15(1):23-25.
[12]吴莉菊.用氯硝柳胺治疗人体长膜壳绦虫和犬复孔绦虫感染[J].国外医学寄生虫病分册,1980,8(1):39-40.
[13]氯硝柳胺合并氨基阿的平和卡马拉治疗裂头绦虫病[J].国外医学参考资料(寄生虫病分册),1974(4):184-185.
[14]国家质量监督检验检疫总局.澳大利亚修订氯硝柳胺等物质残留限量[EB/OL].http://www.scnjzj.gov.cn/Article Show.asp?Article ID=7321.
[15]涂珍,姜斌,薛剑,等.氯硝柳胺在小鼠血浆中的代谢及抗日本血吸虫尾蚴侵袭作用[J].中国寄生虫学与寄生虫病杂志,2015,33(2):101-104.
[16]洪志勇,寇用义,黄铭西.灭绦灵预防小鼠血吸虫病研究[J].中国人兽共患病杂志,1990,6(3):43.
[17]徐明,许永良,沈林南.氯硝柳胺等涂肤剂防御血吸虫尾蚴感染实验观察[J].寄生虫病与感染性疾病,2004,2(4):181-182.
[18]蔡德全,卢永嵩,左世会,等.氯硝柳胺控释剂药物动力学的研究[J].中国血吸虫病防治杂志,1993,5(3):145-149.
[19]神学慧,戴建荣,李叶芳,等.氯硝柳胺悬浮剂灭蚴和预防血吸虫感染的研究[J].中国病原生物学杂志,2011,6(8):600-602.
[20]李洪军,梁幼生,戴建荣,等.氯硝柳胺悬浮剂杀灭日本血吸虫尾蚴的实验研究[J].中国血吸虫病防治杂志,2005,17(6):424-426.
[21]严晓岚,杨明瑾,漏磊君,等.长效涂肤剂“防蚴灵”预防血吸虫尾蚴感染的研究[J].中国血吸虫病防治杂志,2003,15(2):135-138.
[22]黄胜炎.抗肿瘤药新制剂[J].上海医药,2005,26(5):211-214.
[23]Singh K,Harikumar SL.Injectable in-situ gelling controlled release drug delivery system[J].Int J Drug Dev Res,2012,4(2):56-69.
[24]苏丹,涂家生.替硝唑原位固化缓释凝胶的处方研究[J].药学与临床研究,2009,17(2):100-104.
[25]王丽娟,朱照静,吴青,等.均匀设计法优选布洛芬缓释原位凝胶剂处方及释药性质的研究[J].重庆医科大学学报,2009,34(12):1704-1708.
[26]王飞,戴建荣.氯硝柳胺的毒理学安全性评价研究概况[J].中国人兽共患病学报,2013,29(1):86-90.
[27]徐颖,戴建荣.氯硝柳胺的细胞毒性机制研究[J].中国血吸虫病防治杂志,2015,27(1):104-107.
[28]Ofori-Adjei D,Dodoo ANO,Appiah-Danquah A,et al.A review of the safety of niclosamide,pyrantel,triclabendazole and oxamniquine[J].Int J Risk Safety Med,2008,20(3):113-122.
[29]陶奕,涂珍,张皓冰,等.氯硝柳胺在小鼠血浆、肌肉及皮肤中的药代动力学研究[J].国际医学寄生虫病杂志,2015,42(3):142-145,155.
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