磷酸替米考星对人工感染鸡支原体病的药效学及其对鸡的安全性试验研究

发布时间：2018-05-01 06:22

本文选题：磷酸替米考星 + 最小抑菌浓度　；参考：《南京农业大学》2015年硕士论文

【摘要】：替米考星是一种半合成的畜禽专用大环内酯类抗生素,它对所有的革兰氏阳性菌、部分革兰氏阴性菌、支原体及螺旋体均具有良好的抗菌活性。由于它对畜禽肺炎支原体的高度敏感性而被广泛用于畜禽肺炎的治疗。然而,由于替米考星不溶于水的特性,所以在兽医临床上的应用受到较大限制和不便。磷酸替米考星是替米考星增加了磷酸基团后形成的化合物,其水溶性显著增强,且水溶后的有效成分仍然为替米考星。本研究针对新兽药10%磷酸替米考星可溶性粉进行了体内、外的药效学试验,及其对靶动物鸡的安全性试验,为磷酸替米考星在兽医临床上的使用提供理论和实验依据。本研究通过采用微量稀释法来测定磷酸替米考星等抗生素对9种病原微生物的最小抑菌浓度(MIC),来评价其抗菌活性。试验结果显示,磷酸替米考星对猪胸膜肺炎放线杆菌、猪链球菌、副猪嗜血杆菌等临床常见畜禽致病菌均有良好的抗菌活性,MIC均在0.0049-2.5 μg/mL之间;其对猪肺炎支原体与鸡毒支原体的MIC分别为0.0049 μg/mL和0.3125 μg/mL,表现出显著的抑菌活性。磷酸替米考星与其他抗生素相比抑菌活性更强或相当。磷酸替米考星与主要对照药物替米考星相比,具有更好的水溶性。不同剂量磷酸替米考星可溶性粉对人工感染鸡支原体肺炎受试鸡气囊损伤评分等指标的检测结果显示,以60-80 mg/L剂量投服磷酸替米考星可溶性粉,其对支原体肺炎感染鸡的治愈率和有效率分别可达70%与100%,与目前已经上市销售的10%替米考星可溶性粉(75 mg/L水,以替米考星计)的效果相当,但由于磷酸替米考星通过增加磷酸基团而显著增加了该药的水溶性,使得该药在兽医临床上的应用更加便捷。本研究给靶动物鸡投服不同剂量的磷酸替米考星可溶性粉,通过测定受试鸡的血液生化指标、凝血指标、血液常规指标、尿液常规指标、饲料报酬和病理学检查等来评价其兽医临床的应用安全性。研究结果显示,以10倍于推荐剂量(800 mg/L)饮水投服10%磷酸替米考星可溶性粉后,药物对靶动物鸡的血液、尿液指标均未产生不良影响,组织病理学检查结果也未见其对靶动物鸡的器官组织造成药物不良影响,说明低于800 mg/L剂量的10%磷酸替米考星可溶性粉对靶动物鸡的使用是安全的。
[Abstract]:Telmicoxacin is a semi-synthetic macrolide antibiotic for livestock and poultry. It has good antibacterial activity against all Gram-positive bacteria, some Gram-negative bacteria, Mycoplasma and Spirulina. Because of its high sensitivity to mycoplasma pneumoniae, it is widely used in the treatment of poultry pneumonia. However, the application of telmicosin in veterinary clinic is limited and inconvenient because of its insoluble water properties. Tenmicosin phosphate is a compound formed by the addition of temicosin to phosphoric acid group, and its water solubility is significantly enhanced, and the effective component after water dissolution is still telmicosin. In this study, in vivo and in vitro pharmacodynamics tests were carried out for the new veterinary drug 10% temicosin phosphate soluble powder, and the safety test for the target animal chicken was carried out, which provided the theoretical and experimental basis for the clinical use of telmicosine phosphate in veterinary clinic. In this study, microdilution method was used to determine the minimal inhibitory concentration (MIC) of tenmicosin phosphate and other antibiotics on 9 pathogenic microorganisms to evaluate its antibacterial activity. The results showed that the antimicrobial activity of telmicoxacin against Actinobacillus pleuropneumoniae, Streptococcus suis, Haemophilus parahaemophilus and so on was 0.0049-2.5 渭 g/mL. The MIC of Mycoplasma pneumoniae and Mycoplasma gallus were 0.0049 渭 g/mL and 0.3125 渭 g / mL, respectively, showing significant bacteriostatic activity. Telmicosine phosphate has more or more antimicrobial activity than other antibiotics. Telmicosine phosphate has better water solubility than that of the main control drug temicosin. The test results of different doses of timicosin phosphate soluble powder on the injury score of airbag of artificially infected chicken Mycoplasma pneumoniae showed that the dosage of 60 to 80 mg/L was used to take the soluble powder of telmicosin phosphate. The cure rate and effective rate for chickens infected with Mycoplasma pneumoniae can reach 70% and 100% respectively, which is comparable to that of 10% tenmicosin soluble powder 75 mg/L water, calculated in terms of telmicosin, which has been sold on the market at present. However, telmicosine phosphate can increase the water solubility of the drug by increasing the phosphate group, which makes its application in veterinary clinic more convenient. In this study, the target chickens were given different doses of timicosin phosphate soluble powder. The blood biochemical index, coagulation index, blood routine index and urine routine index were measured. Feed remuneration and pathological examination were used to evaluate the safety of veterinary clinical application. The results showed that after 10 times the recommended dose of 800 mg / L, the drug had no adverse effect on the blood and urine indexes of the target chickens after drinking 10% timicosin phosphate soluble powder. The results of histopathological examination showed no adverse effects on the organs and tissues of the target chickens, indicating that the use of 10% timicosin phosphate soluble powder of less than 800 mg/L was safe for the target chickens.
【学位授予单位】：南京农业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S859.796

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