CN102641261B - Application of Vorinostat in preparation of soft-resistant Eimeria drugs - Google Patents
Application of Vorinostat in preparation of soft-resistant Eimeria drugs Download PDFInfo
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- CN102641261B CN102641261B CN 201210121663 CN201210121663A CN102641261B CN 102641261 B CN102641261 B CN 102641261B CN 201210121663 CN201210121663 CN 201210121663 CN 201210121663 A CN201210121663 A CN 201210121663A CN 102641261 B CN102641261 B CN 102641261B
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Abstract
The invention discloses application of Vorinostat in preparation of soft-resistant Eimeria drugs; powder is formed by the Vorinostat and an acceptable auxiliary material, and then is added into a feed to mix uniformly so as to feed chicken by a daily feed amount; or a Vorinostat water-soluble powder is prepared by the Vorinostat, and is dissolved in water to feed chicken by a daily feed amount. Animal infection experiments confirm an anticoccidia index (ACI) of the Vorinostat is more than 175, and the Vorinostat has function of resisting soft-resistant Eimeria.
Description
Technical field
The present invention relates to a kind of new purposes of Vorinostat, be specifically related to the application of Vorinostat in the preparation medicament for resisting Eimeria tenella.
Background technology
Chicken coccidiosis is the main epidemic disease that the intensive poultry husbandry of serious harm is produced, and the therefore annual and economic loss that causes is up to more than 2,500,000,000 pounds, its cause of disease be the former insects of the multiple door in top Eimeria (
Eimeriaspp), wherein harm is maximum be Eimeria tenella (
Eimeria tenella).Although so far without accurate statistics, its loss of the most conservative estimation should be not less than 2,500,000,000 yuan of RMB to this in China.Chemotherapy is to control one of important measures of chicken coccidiosis, but the chicken coccidiosis has extensive and serious Drug resistance at present, appears on the market in the urgent need to new coccidiostat.
(chemistry is by name: Vorinostat, Vorinostat), the molecular formula of this compound is C to Vorinostat
14H
20N
2O
3, molecular weight 264.32, CAS accession number: 149647-78-9, its chemical constitution is as shown in formula I.
Vorinostat is a kind of oral histone deacetylase inhibitors, can suppress to be in preclinical malignant mesothe.I clinical trial phase about Vorinostat shows, this safety of medicine, can tolerate, and can suppress mononuclear cell histone deacetylase in peripheral blood, has anti-tumor activity widely.Recently research finds except the anti-tumor activity of himself, Vorinostat with the use in conjunction of numerous traditional chemotherapeutics in also have potentiation.
Not yet there is so far Vorinostat to have the report of resisting Eimeria tenella effect, can't infers by the known character of Vorinostat whether it has the effect of resisting Eimeria tenella.
Summary of the invention
The object of the present invention is to provide Vorinostat in the application of preparation medicament for resisting Eimeria tenella.
The present invention makes powder by with Vorinostat and acceptable adjuvant, is added in feedstuff, and mixing, by daily forage volume feeding chicken, the addition of Vorinostat is to add the 5g Vorinostat in every 100kg feedstuff; Or Vorinostat is made the Vorinostat water solube powder, soluble in water, by daily amount of drinking water feeding chicken, the addition of Vorinostat is to be dissolved in the 2.5g Vorinostat in every 100kg water.Anticoccidial index (ACI) by zoogenetic infection experiment confirm Vorinostat can reach more than 175, has resisting Eimeria tenella effect preferably.
The specific embodiment
The present invention is further illustrated below in conjunction with specific embodiment, but do not limit to so.
Embodiment 1
The preparation of Vorinostat powder: get 5g Vorinostat (content is not less than 99%) and 95g starch mixing, get final product.
The usage and dosage of powder: above-mentioned 100g powder is admixed in 100 kg feedstuffs, by daily appetite feeding.
Embodiment 2
The preparation of Vorinostat water solube powder: get 2.5 g Vorinostats (content is not less than 99%) and 97.5g glucose mixing, get final product.
The usage and dosage of water solube powder: above-mentioned 100g powder is dissolved in 100 premium on currency.Cut off the water supply for before medication sick chicken 2 hours, then by normal amount of drinking water feeding.
Anti-chicken coccidiosis experiment below in conjunction with concrete description of test Vorinostat.
Experiment material:
Control drug: conventional coccidiostat three word coccidiosis powder (30% sulfaclozine sodium, lot number 001010), produced by Shanghai Novartis animal health company limited.
The Vorinostat powder of Vorinostat: embodiment 1, the Vorinostat water solube powder of embodiment 2.
Coccidian oocyst: Eimeria tenella (
Eimeria tenella) the Guangdong Strain Sporulated Oocysts, preserved rejuvenation in the non-ball worm Chickens before using by the Guangdong Provincial Academy Of Agricultural Sciences Veterinary Institute.
Chickling: the Lingnan Yellow chickling, provided by Animal Husbandry Inst., Guangdong Prov. Academy of Agricultural Sciences, raise in the special-purpose Animal House of having sterilized; Chicken coop and the equal strict sterilization of vessel used, free choice feeding and drinking pure water; Observe chickling before test and have or not clinical symptoms and continuous 2d to check that feces has or not coccidian oocyst, standby.
Feedstuff: by the Xin Nan of Guangdong Province feed corporation,Ltd customization material of brooding all, do not contain any coccidiostat.
Experimental technique:
Grouping: by testing grouping and processing with 150 Lingnan Yellow breeding chickling to 10 ages in days, by only weighing, a little less than eliminating, the young and excessive person of body weight, will remain chickling and be divided at random 5 groups, and 30 every group, and suitable the adjustment makes every group of chickling TBW about equally.
Process: except I (blank) group, all the other are respectively organized the equal per os of chickling and gavage Eimeria tenella Sporulated Oocysts l * 10
5Individual/plumage; Except I group and II (positive control) group, all the other are respectively organized chickling and all feed immediately or drink feedstuff or the water that contains coccidiostat after infecting, the III group is fed and is contained the feedstuff of three word coccidiosis powder, IV group feed the Vorinostat powder of embodiment 1 and the Vorinostat spice that feedstuff is made, the V group is drunk the Vorinostat water solube powder of embodiment 2 and is drunk water with the Vorinostat that drinking-water is made, and consumption of each group drinking-water and feedstuff is all identical.The grouping situation of test chickling sees Table 1.
Observe and record every day such as mental status, feed intake, feces situation of chicken group etc.; Dead chickling is weighed, cuts open inspection, if Eimeria Tenella Infection cause death lesion score be+4 minutes; All chickling are cutd open inspection in infecting rear the 7th day by only weighing, and carry out caecum lesion and score; Calculate at last weightening finish and the price of deed of respectively organizing chickling.
Drug effect decision method and standard anticoccidial index (ACI) are pressed the formula that Merck company recommends and are calculated: ACI=(the relative weight gain rate+survival rate) (egg capsule value+pathological changes value); The relative weight gain rate=(weightening finish of test group weightening finish ÷ blank group) * 100%; Survival rate=(each group survival chickling is counted ÷ and respectively organizes the chickling sum) * 100%.Pathological changes is scored by Pyatyi: 1. without egg capsule, caecum is normal, is 0 minute; 2. egg capsule is arranged, and the caecum mucosa slightly thickens, and has to be dispersed on a small quantity hemorrhage or a small amount of blood sample intestinal contents, is+1 minute; 3. egg capsule is arranged, and the caecum mucosa thickens, and obviously hemorrhage or obvious blood sample intestinal contents is arranged, and is+2 minutes; 4. egg capsule is arranged, and the caecum mucosa thickens, and a large amount of sludged bloods or blood sample intestinal core are arranged, and is+3 minutes; 5. chickling is dead or have a large amount of egg capsules, caecum outward appearance to be color of soy sauce (or small intestinal middle part the point-like necrosis region is arranged, the mucosa face is blush) because of coccidiosis, the obvious enlargement of intestinal tube, and content forms obvious blood sample intestinal core, is+4 minutes.Pathological changes value in group=every group of average lesion score * 20.Drug effect criterion is that ACI＜120 are invalid, and 120～160 is weak effect, and 160～180 is middle effect, is potent more than 180.The egg capsule value is converted by cecal content gram egg sac number (OPG).
Experimental result:
Clinicing symptom observation:
The matched group of inoculation Eimeria tenella Sporulated Oocysts the 2nd day, it is depressed that spirit appears in sick chicken, slow-witted vertical, loss of appetite; Occurred obvious hemafecia on the 5th day, and death occurs, hemafecia reduces gradually subsequently.
Calculate respectively the anticoccidial index of each group, the results are shown in Table shown in 2.As shown in Table 2, the anticoccidial index of III, IV, V group is all higher than the II group, the anticoccidial index of IV, V group is apparently higher than the III group, therefore the anticoccidial index (ACI) of experiment confirm Vorinostat can reach more than 175, have resisting Eimeria tenella effect preferably, and obviously be better than conventional coccidiostat three word coccidiosis powder.
Claims (1)
1. the application of Vorinostat in the preparation medicament for resisting Eimeria tenella.
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| CN 201210121663 CN102641261B (en) | 2012-04-24 | 2012-04-24 | Application of Vorinostat in preparation of soft-resistant Eimeria drugs |
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| CN102641261B true CN102641261B (en) | 2013-11-06 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106668038A (en) * | 2017-02-27 | 2017-05-17 | 河南牧业经济学院 | Application of rhodosin in preparing anti-eimeria tenella drug |
| CN108272811A (en) * | 2018-01-20 | 2018-07-13 | 广东省农业科学院动物卫生研究所 | Application of the scutelloside in preparing medicament for resisting Eimeria tenella |
| CN108392469A (en) * | 2018-04-08 | 2018-08-14 | 广州市汇鑫动物药业有限公司 | Application of the Tiopronin in preparing medicament for resisting Eimeria tenella |
| CN109364046A (en) * | 2018-11-27 | 2019-02-22 | 广东省农产品质量安全中心(广东省绿色食品发展中心) | Cedrol and its medicinal derivative are preparing the application in medicament for resisting Eimeria tenella |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101874793A (en) * | 2009-04-29 | 2010-11-03 | 北京本草天源药物研究院 | Vorinostat solid preparation |
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| CN101874793A (en) * | 2009-04-29 | 2010-11-03 | 北京本草天源药物研究院 | Vorinostat solid preparation |
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Inventor after: Sun Mingfei Inventor after: Xie Mingquan Inventor after: Qi Nanshan Inventor after: Wu Caiyan Inventor after: Lv Minna Inventor after: Liao Shenquan Inventor after: Wen Liena Inventor before: Sun Mingfei Inventor before: Xie Mingquan Inventor before: Qi Nanshan Inventor before: Wu Caiyan Inventor before: Lv Minna Inventor before: Liao Shenquan Inventor before: Wen Liena |
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Address after: 510640 Baishigang Street, Wushan District, Tianhe District, Guangzhou City, Guangdong Province Patentee after: Institute of Animal Health, Guangdong Academy of Agricultural Sciences Address before: 510640 Baishigang Street, Wushan District, Tianhe District, Guangzhou City, Guangdong Province Patentee before: Veterinary Research Inst., Guangdong Agricultural Science Academy |