The Preventive Effect Of Ligustrazine Hydrochloride Microemulsion And Insitugel On The Abdominal Adhesion

This article made systemic literature retrieval on prevention and cure of peritoneal adhesion and the unique superiority of Chinese Medicine in this field. And also, it summarized on the new type of pharmaceutical dosage forms: microemulsion and situ-gel. Combining with the physiopathology characteristic of peritoneal adhesion formation, we brought in the traditional Chinese medicine and external treatment into abdominal cavity. We prepared microemulsion and situ-gel of Ligustrazine Hydrochloride, a traditional Chinese drug monomer effective constituent, developed Ligustrazine Hydrochloride microemulsion and situ-gel with delayed release, temperature sensitive and machinery barricade characteristics. For that, we did the preparation of microemulsion and situ-gel, the degradation and compatibility experiments of situ-gel, the efficacy experiment of microemulsion and situ-gel.Microemulsion preparation: Ligustrazine Hydrochloride microemulsion was prepared in titrimetric method with water. The formation was optimized in single-factor experiments, ternary phase diagram and stability investigation. The type of microemulsion was judged in several methods. HPLC method was employed in Ligustrazine Hydrochloride content determination. At the same time, the loaded-drug, stability and clarity of microemulsion were investigated. The optimized formation of Ligustrazine Hydrochloride microemulsion were OP as the emulsifier, glycerol as the co-emulsifier and ethyl oleate as oil, the concentration of Ligustrazine Hydrochloride was 50mg/mL.Situ-gel preparation: The solution of Poloxamer 407 in different concentrations was prepared. We determined the phase variation temperature, drew the viscosity-temperature curve and determined the drug release in 37℃in vitro. It showed that the P-407 situ-gel in 40% prolonged the drug release in vitro obviously, which was consistent with experiment request.The study of biological degradation and compatibility: We added lysozyme into phosphate buffer in pH 7.4 to determine the degradation of situ-gel in vitro. And also, the compatibility test was conducted in vivo with SD rats. It showed that: the preparation degradation was 45.1% in 60h and 74.2% in 120h. Greater omentum was not found in abdominal cavity. There was no part effusion and obvious edema. It suggested that situ-gel would not show up rejection obviously in abdominal cavity, had good histocompatibility and was consistent with the working condition in abdominal cavity.Pharmacodynamic action of microemulsion and situ-gel: Divide the SD rats into ten groups randomly after mode-make: sodium chloride group, Ligustrazine Hydrochloride group, blank microemulsion group, Ligustrazine Hydrochloride microemulsion in high doss group, and also in middle and low doss group, blank situ-gel group, Ligustrazine Hydrochloride situ-gel in high doss group, and also in middle and low dose group. The preparations were used in abdominal cavity. All the rats were killed 22 days after operation. Peritoneal adhesion score and immunity SABC statistical analysis were undertaken. It showed that Ligustrazine Hydrochloride situ-gel in low doss possessed the best effect.