The Synthesis And Quality Research Of Tilmicosin

Tilmicosin is a semi-synthetic macrolide antibiotic developed for veterinary use. As a newly developed preparation, it has broad antibacterial spectrum against Grampositive and Gramnegtive bacteria, as well as Mycoplasma and Leptospira. Tilmicosin is mainly indicated for the treatment of respiratory disease caused by Peripneumonitis Actinobacillus, Pasteurella haemolytica-multocida bacteria and Mycoplasma happened in poultry and livestockThe processing route for tilmicosin synthesis was formed by extensive file searches and iterative experiments, it took the following steps: firstly, hydrolyzed the tylosin phosphate in the acid to get the hydrolysate-Desmycosin, then put the Desmycosin in Amyl acetate, it will interact with 3,5-Dimethylpiperidine. Wash the semi-product with the solution of dilute hydrochloric acid, adjust the PII value to be 11 with 5N of NaOII solution, after being filtrated, the finished product tilmicosin was achieved.During the procedure of making Desmycosin from tylosin phosphate, lots of work had been done to validate the condition, ensure one hour of reacting time by maintaining temperature, PII value of 60% sulfuric acid controlled between 1.5-1.6, the reacting temperature between 35C and 40C. During the procedure of making tilmicosin with Desmycosin they have chosen Formic acid Between 70C to 75癈, to validate 2 hours of reacting and maintaining temperature, dissolve after using 10% dilute hydrochloric acid to adjust the PH value between 4-4. 5,then use 5N of NaOH to adjust the PH value between 10 and 11, finally to separate out tilmicosin.They conduct the structure corroboration about the tilmicosin material made by the above processing and make comparison with the standard sample suppl ied by Saigma, IR:VmaxKBr cm-1 :3453.99 is the stretching bibration of hydroxyl, 2931. 62-1836. 18 is the stretching vibration of alkyl, 1741. 95 is the stretching vibration of carboxyl bond in ester, 15922.62 is the stretching vibration of carboxyl bond conjugated with carbon-carbon double bond,1456. 56is C-H bending vibration of methyl. These IR Spectrum of the sarnie is consistent with reference. In the solution of 95% ethanol.,0. 1mol/HCl or 0. 1mol/NaOH, the UV spectrum of sample is consistent with the reference. NMR Spectrum is detected in CDCl3 and obtained the data of carbon hydrogen bonds. They determined every carbon atom and hydrogen atoms by HMBC, HSQC, HSQXTOXY, COSY. The obtained data accord to the molecular structure, and the data of reference is totally in accordance with that of sample.In this article, Tilmicosin' s quality standard is basically determined after careful research on the menstruum, relative material limit, and effective ingredient contents, with which to determine the water contents. During the determination of the quality standard, American Pharmacopoeia has been used for reference. The stability research has also been performed under acidic, alkaline and high temperature circumstances respectively. Conclusions have been drawn out that at acidic circumstances, the quality is stable, and at alkaline circumstances, the quality is unstable and when the storage temperature exceeds 60C, tilmicosin will be liquefied. All these achieved results construct the foundation for further stability research of tilmicosin and its preparation.