Preparation And Pharmacodynamics Study On Compound Hydrochloride Ceftiofur Injection

The purpose of this study is to develop a kind of compound ceftiofur hydrochlorideinjection to treat cow mastitis, and then to study its quality control, stability, safety testing,and efficacy, so that an efficient treatment of cow mastitis, with stable medicinal properties,convenience to use and short period of wasting milk, can be developed, providing a scientificbasis for its application in veterinary clinic.1. The preparation of hydrochloride ceftiofur injection and quality control:Hydrochloric acid of ceftiofur as raw materials, injection of propylene glycol and ethanol asthe solvent, by adding an appropriate amount of synergist and cosolvent, a series ofhydrochloric ceftiofur injections are prepared, among which a screening hydrochlorideceftiofur injection is successfully developed. Quality inspection shows that the preparingprocess has better adaptability, simplicity, and operability. Finished product is a yellowtransparent liquid, with pH8.7.Its sterility test meets the requirement of injection.2. Establish the method for determining hydrochloride CEF in hydrochloride CEF injection: Byultraviolet spectrophotometer, and using diethyl formamide-butanol （1:1, V: V） to dissolve the sample,ethanol to dilute, the content of the hydrochloric acid of ceftiofur was determined at the wavelength of288nm. The average recovery was100.07%, and RSD was0.11%（n=9）.The ceftiofur detection concentrationand the absorbance values showed a good linear relationship （r2=0.9950） in the concentration range of2.50¹5.00μg/ml.It also showed high recovery, good stability, rapidness and accuracy. Therefore,ultraviolet spectrophotometry can be applied to the fast measurement of hydrochloride ceftiofur injection’scontent and quality control.3. Stability experiment of hydrochloride ceftiofur injection: Light stability testing,accelerated testing were carried out respectively with the injection of the compoundhydrochloric cephalosporin ceftiofur. The compound hydrochloric acid cephalosporinceftiofur injections were irradiated by fluorescent lamps,and natural light, and measured atdifferent time. It decreased2.50%after15days and4.14%after30days, its appearance andcolor showed insignificant change. Place compound hydrochloride ceftiofur injection at40±2℃,75%relative humidity （RH） for6months, there is no significant change in itsappearance and color. 4. The security of hydrochloride ceftiofur injection: Irritation test showed that theinjection has non-irritating to the muscles and blood vessels, indicating that the drug is suitable forintramuscular and intravenous administration.The heat source trials have shown that this medicine meetsthe provisions of the national pharmacopoeia about pyrogen. Acute toxicity test show the result of LD₅₀was2088.33mg/kg, far more than clinical recommended dose, indicating that the drug is very safe inclinical application.5. Pharmacodynamics experiment of hydrochloride ceftiofur injection: The antibacterialtest and the risk of mastitis in cows’ clinical trial of compound hydrochloride ceftiofurinjection in vitro were conducted. The results showed that MIC of compound hydrochlorideceftiofur injection against Streptococcus glaciate, E.coli, Staphylococcus aurous were0.025μg/mL,0.25μg/mL,1.00μg/mL.The cured proportion of hydrochloride ceftiofur injection is20%higher than that of hydrochloride ceftiofur suspension, but also the same as effective。...