| In this study, the tilmicosin phosphate and baicalin combined, using the traditional manual wet granulation method, to prepare the compound tilmicosin granules, and examined its quality control, acute toxicity, and antibacterial activity in vitro, provided for the scientific reference in the clinical application of the compound granular formulation.1. Antibacterial activity in vitro and combined drug sensitivity test of tilmicosin phosphate and baicalinUsing the classical double tube dilution method determination the MIC and MBC of tilmicosin phosphate and baicalin against Pasteurella multocida, Streptococcus agalactiae, Salmonella enteritidis and Escherichia coli, Staphylococcus aureus; the inhibitory concentration of the combined using of tilmicosin phosphate and baicalin was determined by the method of chess board,and calculate the FIC index.The results showed that,The MIC of tilmicosin phosphate on five kinds of bacteria were:15.2, 1.9, 15.2, 7.6, 3.8 μg/ml, MBC were 30.5, 3.8, 61.0, 30.5, 7.6 μg/ml; the MIC of Baicalin on five kinds of bacteria were: 0.95, 0.24, 3.8, 1.9, 0.12 mg/ml, MBC were: 1.9, 0.48, 7.6, 3.8, 0.12 mg/ml. The FIC of the combined using of tilmicosin phosphate and baicalin on five kinds of bacteria were less than or equal to 1,the Staphylococcus aureus was synergistic effect, on the other four kinds of bacteria showed additive effect, indicating that combined using of tilmicosin phosphate and baicalin has certain practical value.2.Preparation and quality control test of compound tilmicosin granuleAccording to the drug sensitivity test to determine the best ratio of tilmicosin phosphate and baicalin,the formula was determined as follows: 10% of tilmicosin phosphate, 2.5% of baicalin, 87.5% of β-cyclodextrin. According to the requirements of the prescription by wet granulation,to prepare the compound tilmicosin granules, so as to investigate the compound tilmicosin granules of size, loss on drying, melt index, and determined the content of the tilmicosin phosphate and baicalin by UV. The results showed that the compound tilmicosin granules of size, loss on drying, melt index and other indicators were in line with the Veterinary Pharmacopoeia; average content of tilmicosin phosphate was 98.2 mg/g, average content of baicalin was 24.2 mg/g, respectively marked amount of 98.2% and 96.8%, meet the requirements of pharmaceutical preparation.3.Acute toxicity test of the compound tilmicosin granuleUsing the simplified Karber method to determine the compound tilmicosin granules(the calculation is based on the content of the tilmicosin phosphate) toxicity on chicks. The results showed that the LD50 on the chicken was 919.80mg/kg, and the 95% confidence limit of LD50 was 736.17 ~ 1149.25 mg/kg,the preparation is a low toxic drug.4. In vitro antibacterial test of the compound tilmicosin granuleUsing the classical double tube dilution method determination the MIC and MBC of compound tilmicosin granule against Pasteurella multocida, Streptococcus agalactiae, Salmonella enteritidis and Escherichia coli, Staphylococcus aureus.Results show that bacteria inhibitory and bactericidal effect of the compound tilmicosin granule on five kinds ofbacteria were better than the single drugs,especially on Staphylococcus aureus improve more. |
