The Preparation Of Tilmicosin Long-acting Injection

Tilmicosin produced from Tylosin by semisynthesis is a macrolide antibiotic used for fowl and livestock specially.It have very strong antibacterial activity, antibacterial spectrum,no cross resistance. people often use its phosphate in clinical use, because of its physical and chemical properties. In this study, we prepared the tilmicosin long-acting injection by screening suitable organic composite solvents, sustained-release excipients, antioxidants, etc. and studied its stability, safety and effectiveness. Specific studies include:1.Literature reviewThis chapter provides an overview of research survey about Tilmicosin, including its physical and chemical properties, mechanism of action, antimicrobial activity, adverse reactions and clinical application, etc.and have a preliminary understanding about Tilmicosin and its formulations. Then introduced the research progress of the beast used sustained-release preparations, mainly introduced the types of long-acting injection and its advantages, as well as the long-acting injection present situation, problems and development, etc. Against the background of the study provides a comprehensive ouerview.2.The analysis methods of Tilmicosin in vitroThe results showed that the good linearity of Tilmicosin were obtained in the range of0.16～0.8μ g,and the average recovery,relative were99.32%, RSD were0.22%, RSD of the with-in-day precision and the day to day precision were all less than2%;The result show the method of HPLC which established were meet the requirements, It could offer a sensitive, accurate and reliable detection method of long-acting Tilmicosin injection for the design prescription and stability.3.The preparation and the prescription optimization of Tilmicosin long-acting injectionThis chapter we studied the physical and chemical properties of Tilmicosin through the pre-prescription studies, and preliminary studied its pH, solubility, stability, etc.Then determined the specifications of injection, the non-aqueous solvent for injection, antioxidants,metal ion complexing agent and sustained-release excipients by the prescription screening, then determined the best prescription of Tilmicosin long-acting injection by the orthogonal test.And verified the release effect through the release tests in vitro, the results showed that the Tilmicosin long-acting injection had a good sustained-release.4.The stability evaluation of Tilmicosin long-acting injectionThis chapter we did the influence factors experiment (high temperature experiment, high humidity experiment, light experiment), accelerated experiment and long-term experiment according to the standard of the2010edition of People’s Republic of China Veterinary Pharmacopoeia. And preliminary investigated the stability of Tilmicosin long-acting injection. The results showed that the Tilmicosin long-acting injection had good stability, and comply with the requirements. And avoid the light and high temperature when saving, because its sensitive to the light and high temperature.5.The safty evaluation of Tilmicosin long-acting injectionThe use method of Tilmicosin long-acting injection was subcutaneous injection or intramuscular injection, and should prohibited intravenously. We did the skin irritation experiment, local irritation experiment and acute toxicity experiment according to relevant regulations. The results showed:the Tilmicosin long-acting injection had small skin irritation for rabbit, and had no significant stimulation for the muscle and ears of rabbit. the Tilmicosin long-acting injection can be used in subcutaneous injection and intramuscular injection; the acute toxicity measured the LD50was595.36mg/kg,the95%confidence limits of LD50was:528-689mg/kg,belongs to low toxicity drugs.6.The study on antibacterial effect in vitro of Tilmicosin long-acting injectionThis chapter we studied the antibacterial activity in vitro of Tilmicosin long-acting injection, the phosphate Tilmicosin solution, the phosphate Tylosin solution against E.coli, Staphylococcus aureus, Pasteurella and Streptococcus, were studied by the double tube dilution method. The results showed: Tilmicosin long-acting injection had better antibacterial activity, the sensitivity for common bacteria was better than phosphate Tilmicosin and phosphate Tylosin, the MIC was less than phosphate Tilmicosin and phosphate Tylosin, it showed that the Tilmicosin long-acting injection has better antimicrobial effect.