| Indomethacin which was from Merck of Germany was gone on the market in 1860. It was widely used in human clinical, often as standard treatment in non-steroidal anti-inflammatory drugs. Clinical applications of Indomethacin were rarely reported in veterinary, but expected to be used on common cold, influenza, other causes of febrile diseases, rheumatism and so on. That were currently listed Indomethacin enteric tablets, capsules, suppositories, patch etc, no its injection. The Indomethacin injection this article developed was a national three new veterinary drug. According to the Ministry of Agriculture of the "veterinary up approach" (Ministry of Agriculture Order No.44) requirements, the injection formulation and process, quality standards, stability, safety and efficacy of some other part of the pre-clinical studies were studied, next to provide the data for new veterinary drug registration and clinical trials. The main contents were as follows:Part 1:Formula and preparation technique study of Indomethacin injection. The amount of dimethylformamide, dimethylacetamide, propylene glycol, polyethylene glycol-400 and other organic solvents were screened through single factor experiments and orthogonal test. The initial period of injection was predicted by initial average rate method. The results were as follow:30% dimethylformamide,30% propylene glycol and 40% water were as mixed solvent, anhydrous sodium sulfite was as antioxidants, EDTANa2 was as a metal chelator, ethanolamine and lactic acid were as a pH regulator. The Indomethacin injection was prepared 20mg/mL Indomethacin, the initial period was up to 2 years.Part 2:The quality standard study of veterinary Indomethicon injection. Identifying, examining, assay of Iindomethicon injection were determined. Results: the identifications, content uniformity, pyrogen, clarity, pH, met the relevant requirements of injection. The content of Indomethicon injection was determined using HPLC method. The chromatographic condition was as follow:The separation was performed on the Ultimate XB C18 column. The mobile phase consisted of 0.1mol·L-glacial acetic acid-methanol (20:80) and the flow rate was 1.0mL·min-1. The detection wavelength was 228nm and the column temperature was room temperature. Results: the linear range of determination was 20μg·mL-1～1000μg·mL-1 with the correlation coefficient was 0.9993. The average recoveries (n=9) was 102.3%, the RSD was 1.03% and the LOQ was 3ng, LOD was 0.9ng.The content of veterinary Indometjacin injection was 18.648±0.295mg·mLPrat 3:The thermal stability research of Indomethicon injection. The period of validity of Indomethicon injection was predicted through the initial equal-speed method. Accelerated test conditions:temperature was 40℃±2℃, relative humidity was 75%±5%; long-term test conditions:temperature was 25℃±2℃, relative humidity was 60%±10%.The results showed that the Indomethicon injection can be stored 2.11 years at room temperature; accelerated test and long-term trial were respectively for 6 months and 12 months, the results of character, clarity, pH, etc. changed little, the content of Indomethicon declined a little, but that had no significant difference compared with the initial process (p>0.05).Part 4:The part safety test of Indomethacin injection. The LD50 of Indomethacin injection was determined by improved karber method. The accumulation and tolerance were determined by increased dose gradually in mouse, conventional method was used for the determination of its hemolytic and muscle irritation. The results showed that indomethacin injection LD50=50.2mg·kg-1; the injection was no accumulation and tolerance in mouse, was also no significant hemolysis and muscle irritation to rabbits.Part 5:Pharmacodynamic part trials of Indomethacin injection. Peptone was induced fever in rabbits using for antipyretic test, thermal sting apparatus and acetic acid writhing test using for analgesia, rats paw swell test using for anti-inflammatory. Result:Indomethacin injection showed better antipyretic effect, which was same as isochoric metamizole sodium injection, in febrile rabbits tat peptone was as the fever. The Indomethacin injection had better analgesic effect in hot and chemistry raw mouse, better anti-inflammatory effect in swell rats.
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