Study on the Preparation and Pharmacodynamics of Toltrazuril Oral Solution
|School||Henan Agricultural University|
|Keywords||Toltrazuril oral solution Develop Pharmacodynamic Toxicity ACI High Performance Liquid Chromatography|
Toltrazuril is a relatively new triazine anticoccidial drugs ketones, capable of efficient anticoccidial, the prevention and treatment of chicken coccidiosis. Toltrazuril clinically proven chicken ball echinococcosis good therapeutic effect, effects, anti-drug-resistant, high security, broad-spectrum characteristics of the study to the development of oral solution for the treatment of coccidiosis new formulations and pharmacodynamic clear. Coccidiosis research, epidemiological studies laid the foundation for China to lay the foundation for the diagnosis, prevention and control, and also provides a theoretical basis for the disease's clinical drug; serious areas of resistance, provide a new treatment, and reduce the economic losses of the people. 1 In this study, domestic toltrazuril raw materials reference to the commercially available sample quality standard study of of toltrazuril oral solution preparation process, in order to determine its formulation and preparation process, the quality of the oral solution and toltrazuril control traits, clarity, pH, moisture, and microbial limit and provide the basis for its quality standards according to the results of the quality control. Toltrazuril oral solution quality control results, determine the of toltrazuril oral solution quality standards: colorless or pale yellow viscous clear solution. The relative density 1.120 to 1.140, and the pH value should be 9.0 to 5.0, containing water shall not exceed 0.5%, microbial limit test membrane filtration method to check the microbial limit test (Chinese Veterinary Pharmacopoeia 2005 a, Appendix 125), are in line with requirements. 2, High Performance Liquid Chromatography toltrazuril oral solution formulations toltrazuril the content. A C18 reversed-phase column, acetonitrile phosphate buffer (53:476) as the mobile phase at a flow rate of 1.0mL · min -1 sup>, the detection wavelength was 240nm chromatographic conditions such determination properly Qu beads Lee content, the results show that the intraday and interday RSD were less than 10%. HPLC method can be fully used in the preparation of Determination and quality control, the method is simple, sensitive, accurate and reliable experimental content of 2.5% toltrazuril oral solution formulation is to identify the amount of 99.98%, in line with the requirements of the quality standards of veterinary drugs. 3, in order to assess the security of toltrazuril oral solution were toltrazuril on the mice oral acute toxicity test, the test results come toltrazuril solution of the the mouse oral median lethal dose (LD < sub> 50 ) 5032 mg · kg -1 sup> · bw, LD 50 95% confidence limit for the 3785 ~ 6863 mg · kg -1 sup> · bw. Reported the test results with the EMEA toltrazuril oral median lethal dose (LD 50 ) mice to 5000 mg · kg -1 sup> · bw agreement. Acute toxicity grading standards of exogenous compounds, toltrazuril oral LD ?? 50 greater than 5000 mg · kg -1 sup> · bw, an actual non-toxic. That toltrazuril low toxicity to mice, the results provide for the safety of the drug in clinical use reference. Toltrazuril oral solution, this test developed 12.5mg · L -1 sup>, 25mg · L -1 sup>, 50 mg · L -1 < / sup> 3 dose clinical anticoccidial efficacy trials. Artificially infected with coccidia 12h after drug treatment. The results showed that 25mg · L -1 sup> and 50 mg L -1 sup> ACI index dose group were 192.4 and 199.3 are efficient anticoccidial drugs test chickens relative weight gain rate of 93.5% and 99.3%, respectively, survival rates are up 100%; 12.5mg / L group ACI Index 178.0 effectiveness of moderate anticoccidial. From the the anticoccidial effects and drugs costs aspects into account, it is recommended that the clinical dose of 25 mg · L -1 sup>, drinking water administration, two days of continuous use. 5, this test developed properly Qu beads oral solution 25mg · L -1 sup> water, 100 ball clear drinking water to 25mg · L -1 sup>, Diclazuril 1mg Amprolium · L -1 sup> drinking, sulfa chloropyrazine sodium 300 mg · L -1 sup> drinking water, 125 mg · L -1 sup > drinking water, artificial chicken infect E.tenella efficacy comparison test, as a comprehensive evaluation of the efficacy of anticoccidial index (ACI). The results show that, the drugs were 192.0,191.5,175.0,155.0 and 147.0. This coccidia strains, this study developed toltrazuril oral solution and 100 ball clear the anticoccidial effect quite Diclazuril followed, the sulfa Chloropyrazine sodium and Amprolium less effective.