Preparation And Quality Evaluation Of Tilmicosin Intramammary Infusion

The cow mastitis caused by Staphylococcus aureus has brought huge economic losses to the cow industry,such as the decline of milk production and quality.Timicosin is a semi synthetic macrolide antibiotic,which has good antibacterial activity against Staphylococcus aureus.It is easy to accumulate in the milk area of cows,and has good advantages in the treatment of cow mastitis.However,the stimulation and cardiac toxicity of timicocin injection are relatively high,and its retention time in cow cells is short,which is easy to disappear rapidly with the decrease of extracellular concentration,leading to its treatment failure in Staphylococcus aureus cow mastitis.Focusing on the scientific problems of the stimulation of timicocin injection and the short intracellular retention time,this project plans to develop a new type of timicocin breast perfusion agent-solid lipid particles with a long intracellular retention time and an efficient antibacterial mechanism.Because of its high permeability and low toxicity,they can easily penetrate the cell membrane,accumulate and stay in the cell,and improve the concentration and time of timicocin in the cell,And then achieve the goal of highly effective treatment of cow mastitis caused by staphylococcus aureus.In this study,we screened and optimized the prescription of this new tilmicosin intramammary infusion,and evaluated its quality.Through pharmacodynamic tests,we proved its clinical therapeutic effect.Methods: The tilmicosin intramammary infusion was prepared by ultrasonic emulsification method.The formulation of the stabilizer(flocculant)was screened and the preparation process was optimized according to the single factor variable method with the appearance,particle size,zeta potential and encapsulation efficiency as indicators.The appearance of the preparation was observed with naked eyes,and the shape,size and distribution of particles in tilmicosin intramammary infusion were observed with transmission electron microscope.According to the relevant requirements of the Good Pharmacopoeia of the People’s Republic of China(2020),the pharmaceutical evaluation was carried out,the detection method for related substances was established,and the content and related substances under the relevant inspection items were determined by HPLC according to the provisions of the Pharmacopoeia.According to the Guiding Principles for the Stability Test of Drug Substance and Drug Preparations,the compatibility test and stability test of raw and auxiliary materials of the preparation were carried out in combination with the differential thermal display analysis technology.The clinical pharmacodynamics experiment of the optimal formula was carried out by using the field cases of cow mastitis caused by Staphylococcus aureus.Results: The influence of various factors? All inspection items for compatibility of raw and auxiliary materials and packaging materials meet the requirements.After screening and optimization,the best formula was 1.2% sodium carboxymethyl cellulose,3% polyvinyl alcohol,0.8 g timicocin and 2 g palm wax.The Tilmicosin suspension is a milky white viscous liquid with a content of 2.5%,and the specification is 300mg: 12 mL.The encapsulation efficiency,particle size and zeta potential of tilmicosin gel were 70%,1500 nm and-25 mv,respectively.The gel particles have good dispersion and uniform shape and size.The settling coefficient of the breast perfusion agent is 0.999,with good dispersibility.The stability test showed that the tilmicosin intramammary infusion was stable for 1 month and 2 months under accelerated test conditions.Its properties,zeta potential and encapsulation rate had no significant changes,and its content and related substances were in line with the regulations.The clinical pharmacodynamics test showed that the cure rate of this product against Staphylococcus aureus cow mastitis was 83.3%,and the effective rate was 100%.Therefore,Tilmicosin suspension has a good clinical therapeutic effect on cow mastitis caused by Staphylococcus aureus.Conclusion: Tilmicosin intramammary infusion has been successfully prepared in this project,and the corresponding small test technology and quality evaluation standards have been established.It is determined that tilmicosin intramammary infusion has good clinical therapeutic effect on Staphylococcus aureus cow mastitis,and has broad market application prospects.