The Development Of Cefquinome Sulphate Ointment

Nowadays, bovine mastitis has become one of the most important diseases which is profoundly harmful to the safety of cows'milking and can lower the quality of dairy products. However, it can not be treated effectively by most of antibiotics always used today for its severe drug resistance. Thus, the development and application of new generations of antibiotics is a big conundrum or challenge for the prevention and treatment of bovine mastitis. Cefquinome, developed by a German corporation Hoechst AG in the 1980s, which concentrated on its products for animal health, is the first cephalosporin of the fourth generation specially used for animals. Comparing with other three generations of cephalosporins, cefquinome has many outstanding features such as a strong bactericidal activity, a high stability, a lower resistance and the like. Just because of those advantages presented above, cefquinome has extensively used to treat swine and bovine respiratory tract infections and bovine mastitis abroad. Nevertheless, studies on cefquinome sulphate and its relevant preparations in china had been conducted only recently. Until now, the bulk pharmaceutical chemical and injection of cefquinome sulphate were few products which had been ratified by the Ministry of Agriculture of China to manufacture and sell and there is still no information or report upon its ointment. Thus, the study and invention on cefquinome sulphate ointment can not only increase the types of cefquinome preparations, but also have a broad market prospect and application space. Based on those positive aspects, studies on the prescription design, preparation technology and quality control of cefquinome sulphate ointment have been performed and the content and results are reported as follows.The study of ointment prescription. Three groups of prescriptions, originated from trial test, were evaluated and compared by different indexes such as external appearance, stability and HLB value in order to screen the best one. The second group turned out to be the best one, which composed of emulsifierⅡ, surfactantⅤandⅥ, liquid paraffin, albolene, ethylparaben and glycerine and the acquired prescription was called the primitive one. Then based on the primitive prescription, organic concept chart theory was used to adjust the types of components in it and the optimized prescription was obtained. Results of contrast test upon external appearance, stability and HLB value between primitive and optimized prescription showed that the latter one was significantly superior to the former one. Finally, the orthogonal experiment was performed to adjust the proportion of components in the optimized prescription and the final one was gained, which contained 7% liquid paraffin, 5% emulsifierⅠ, 12% emulsifierⅡ, 0.4% surfactantⅣ, 1% surfactantⅤ, 0.4% surfactantⅥ, 0.4% surfactantⅦ, 10% glycerine and 0.1% ethylparaben.The preparation technology of ointment. The cefquinome sulphate ointment was made up by emulsification process. First, oleic phase were prepared according to the final prescription and fused in the temperature of 80℃and the aqueous phase was prepared and dissolved at the same temperature. Then the oleic phase solution was added slowly into the aqueous phase by continuous stirring. When the mixture was nearly emulsified adequately, the solution of main drug at the temperature of 75℃was added into it and stirred by the colloid mill for 10 min. After the mix solution cooled down, cefquinome sulphate ointment was obtained. In addition, some other factors which could probably cause drug denaturation, such as craft temperature and radiation disinfection, was inspected and evaluated. The results displayed that cefquinome sulphate had no obvious denaturation at the temperature of 75℃and the ointment had no distinct change by evaluation of external appearance and bacteriostatic effect after radiation disinfection.The quality control of ointment. According to the relevant method referred to the items of ointment in Chinese Veterinary Pharmacopoeia, different indexes, such as external appearance, drug content, stability, stimulation and the like was appraised. The external appearance of ointment turned out to be excellent with properties such as the gloss white color, good refinement, eminent uniformity and facile spread and so on. The PH value of ointment was 5.2. The maximum peak of absorbance was appeared in the wavelength of 265nm by UV scanning. The components of matrix in prescription had no palpable interferential peak in the wavelength of 265nm and the regression equation of standard curve was Y=0.0562X–0.2856,R2=0.9981. The average recovery and sample content were 98.72% and 99.40%, respectively. The ointment had less or no oily water separation or delamination after centrifugation and heat, cold, acceleration tests. The result of animal stimulation test showed that prepared ointment has less or no irritation to bovine teats and mammary areas. The microbial limit determination was up to the standard and specification in chinese veterinary pharmacopoeia. Therefore, the ointment can be tried out clinically for bovine mastitis.