Preparation Of Microemulsion Of Tinidazole-Co-Nanosilver And Pharmacodynamic Study For Endometritis

AIMS: To prepare the high pharmacodynamic and safe microemulsion of tinidazole-co- nanosilver.While systematically investigate the stability,safety,cytotoxicity, the in vitro,in vivo and clinical pharmacodynamics of the microemulsion.METHODS:(1)The preparation and quality evaluation of the microemulsion of tinidazole-co-nanosilver The microemulsion of tinidazole-co-nanosilver was prepared by emulsification and characterized with TEM.The recipe ,which has the lowest releasing velocity,is the optimal of the microemulsion.Its quality evaluation was investigated through the tests of centrifugation accelaration, lucigen irridation, substience observing and constant temperature accelaration.(2)The safety research of the microemulsion of tinidazole-co-nano silver The safety research was done through the test of cutaneous stimulation,acute eye irritation of rabbits,uterus mucosa stimulation and the uterus accumulation toxicity of mice. (3)The cytotoxicity study of the microemulsion of tinidazole-co-nanosilver The effects of microemulsion on the RGR(relative growth rate) of the endometrium epithelial cell ,endometrium stroma cell and fibroblast was investigated with MTT method.(4)The pharmacodynamics in vitro and vivo of the microemulsion of tinidazole-co-nanosilver The minimum inhibition concentration (MIC)of the microemulsion to S.aureus, E.coli, S.agalactiae and Clostridieum welchii was determined by the bacteriostasis test in vitro.The therapeutical effect of the high,middle and low dose microemulsion on the polyinfection endometritis of mice was also investigated.(5)The clinical pharmacodymic study of the microemulsion of tinidazole-co-nanosilver The therapeutical effect on the clinical endometritis was studied and compared to the general drug- the Qing-gong solution.RESULTS:(1)The results of preparation and quality evaluation of the microemulsion of tinidazole-co-nanosilver The microemulsion was yellow, clarification and transparent and its average size was 70 nm. The optimal recipe was as the surfactant was RH40,the oil phase was isopropyl myristate(IPM).The physico-chemical property of the microemulsion was stable.(2) The result of safety research of the microemulsion of tinidazole-co-nanosilver The microemulsion had no stimulation to the skin and eye of the rabbit and the uterus mucosa of mice.There was no transparent accumulation toxicity to the uterus of mice.(3)The result of cytotoxicity study of the microemulsion of tinidazole-co-nanosilver It showed that the cytotoxicity grade of the microemulsion belonged to the first-order reaction,when its concentration was 2~16μg/mL.(4)The pharmacodynamics in vitro and vivo of the microemulsion of tinidazole-co-nanosilver The MIC of the microemulsion to S.aureus, E.coli,S.agalactiae were 20μg/mL,30μg/mL,20μg/mL,respectively.Its MIC to Clostridieum welchii was as follows:the concentration of nanosilver was 0.0138 mg/mL,when the concentration of tinidazole was 0.04 mg/L;And the concentration of nanosilver was 0.004 mg/mL,when the concentration of tinidazole was 0.1 mg/L.Tinidazole and nanosilver had the synergetic antisepticize effect.The healing well percent of the high and middle doser were both 93.3%,and the low dose of 20%.(5)The result of clinical pharmacodymic study of the microemulsion of tinidazole-co-nanosilver The healing well percent of the drug to clinical endometritis was 70%,the total conceiving percent was 100%. It had the similar therapeutical effect with the Qing-gong solution.CONCLUSION AND SENSE:The microemulsion of tinidazole-co-nanosilver was clarification,transparent and yellow solution with the average size of 70 nm.It had stable physico-chemical property and high safety.There was no transparent cytotoxicity to the endometrium epithelial cell,endometrium stroma cell and fibroblast at a range of concentration.The microemulsion had good antibacterial activity to S.aureus,E.coli, S.agalactiae,Clostridieum welchii and fine therapeutical effect on polyinfection endometritis of mice and clinical cow endometritis.The rsearch provides clinic with a novel nano-pharmaceutic preparation,which could cure the endometritis timely and effectively.The research outcome has been applied for Nation invention patent, apply order is 200810017373.4.