The Study Of Multiplex Propofol Submicron Emulsion

Propofol, a new total intravenous anesthetic, is commonly used in clinically. However, local injection pain is a well-known side effect of propofol, the incidence of pain is very high, which can't be neglected and distresses the patient, the injection pain restrict the use of propfol clinically in some degree.Based on the preparation of propofol(Diprivan) the studies were carried out, the multiplex propofol sub-micron emulsion was obtained through added lidocaine hydrochloride into the propofol emulsion, the incidence and extent of propofol injection pain reduced when administered the new preparation of proporol.Propofol and lidocaine hydrochloride was assayed on the same time and in the same HPLC system in first time, and the assay method had High Sensitivity and Specibility. The stability of propofol and lidocaine hydrochloride was investigated when they stored under high temperature, huminity and strong light. The consequence of the study indicated that the preparation degraded in some degree, it needed to store under common temperature, drying and protection from light.The effects and dosages of F68, SPC, glycerol, propylene glycol, antioxidant were studied by single factor test, and based on these we found the final formulation by orthogonal design. At the same time used single factor and orthogonal test investigate the agitate velocity, emulsifying temperature, emulsifying time. The technology of ultrasonic and microfluidic were considerated when they were used to prepare multiplex sub-micron propofol emulsion, and the autoclaving stability of the preparation was determined. The feasible preparation technology was obtained.The physico-chemical property of multiplex propofol sub-micron emulsion was studied, the particle size distribution was 130.0±20.5nm, Zeta potential was -25.72mV, pH value was 6.20, osmotic pressure was 473.2osm(osmotic pressure was 290.3osm when it was diluted by 5ï¼… lactose at the ratio of one to five), acid value was 0.40, peroxide value was 0.030, The stability of the preparation was studied by strong light tests, accelerating and long-term stability tests, compatibility test, freeze thawing test and cold-hot circuit test. The self made multiplex propofol submicron emulsion was stable.In order to evaluate the administration security of multiplex propofol sub-micron emulsion the common pharmacology experiments were performed which containing haemolyticus, anaphylaxis, stimulus and acute toxicity tests, it demonstrated that the preparation had good pharmacology. It was no obvious difference in LD₅₀ and ED₅₀ between multiplex propofol submicron emulsion and common propofol emulsion. The anaesthetic action of multiplex propofol sub-micron emulsion was elucidated by the studies of propofol pharmacodynamics, and it was compared with Diprivan. The pharmacokinetics studies demonstrated that the was no obvious difference between the three preparations. The pharmacokinetics of propofol in rats fitted for open three compartment model.