Pharmacodynamic Study On The Preparation Of Silybin Microparticles And Acute CCl <4> /

Objective:Stainless steel quick membrane emulsification to insoluble drugs silibinin as a model drug, the preparation of silibinin particle dispersion, study the silibinin particle dispersion stability、acute toxicity tests.and treatment and prevention in mice with acute liver injury induced by carbon tetrachloride, for preparing medicine or natural medicine more effective ingredients to provide methodological support.Methods:With silybin powder as a model drug, stainless steel quick membrane emulsification equipment prepare silybin particle. Particle diameter (DO.5), span as an indicator single factor membrane type, stainless steel membrane pore size, oil and water volume ratio, the concentration of the aqueous phase, emulsions and PVA solution volume ratio, PVA solution concentration drug concentration, emulsion mixing method, emulsion solvent evaporation time and the membrane pressure. According to the results, filter out larger three factors in impact the preparation of particles:pressure through the membrane, the oil phase volume ratio of aqueous phase and an aqueous phase concentration of PVA. Though uniform design, optimize the preparation process. Study silibinin particle dispersion stability, acute toxicity test particle. Using CCl4-induced liver fibrosis to make liver injury model established, compare the original powder and silibinin particles treatment and preventive effects of the liver of mice, low, Medium high and ultra high-dose group were intravenously administered and powder group were oral administration, detect the serum of alanine aminotransferase and aspartate aminotransferase, the liver tissue of hydroxyproline, glutathione peroxidase. SOD by using kits.Results Single factor experiment include1 Single factor experiment include, Stainless steel membrane material, stainless steel membrane pore size of 1μm, the oil phase water phase volume ratio of 1:4, the aqueous phase concentration of 6%, and the concentration of PVA emulsion solution of 1:1, the drug concentration of 0.5%, the emulsion was stirred way by magnetic stirring, volatilization time 2h, through the membrane pressure 0.8MPa conditions. By uniform design experiments to determine the concentration of 5% aqueous phase, the oil phase water phase volume ratio of 1:4, through the membrane pressure of 0.2 MPa to optimize the preparation process.2 In the high-temperature experiment, three batches of silibinin particles placed at 60℃ in 10d, 10d content increased three batches of samples was 6.88%,5.90%,5.81%; (75±5)% humidity environment placed under 10d, 10d three batches of samples decreased rate of 9.33%, 8.78%,9.25%; (90±5)% humidity environment placed 10 d,10 d three batches of samples in a decreased rate of 10.03%,12.56%,9.90%. Classic temperature testing,65℃ silibinin particulate 24 h, the decreased rate of 3.12%; 75℃, the decreased rate of 4.78%; while 85℃ in 24h, the decreased rate of 7.58%; after 95℃ and 24h, the decreased rate of 13.44%.3 In the acute toxicity test, the pharmaceutical tail vein 245mg/kg, the mice no mortality, good adaptability. CCl4 liver fibrosis model, treatment trials, silibinin particles intravenously administered low dose (4mg/kg) in Mice for ALT,113.36±11.77, AST,165.00±22.56, SOD, 114.36±11.8, HYP,140.22±39.04, GSH-PX,120.05±30.82; dose group (8mg/Kg) for ALT, 94.84±9.18, AST,121.16 ±27.37, SOD,139.96±15.09, HYP,128.78±16.47, GSH-PX 266.49±21.97; high-dose group (16mg/kg) for ALT,69.86±8.72, AST,128.16±18.07, SOD, 140.94±14.86, HYP,137.36±12.57, GSH-PX,249.76±24.43; ultra-high-dose group (40mg/kg) for ALT,32.52±3.26, AST,78.57±25.29, SOD,172.89±10.46, HYP,109.32± 16.31, GSH-PX, 372.41±60.81; original oral powder group (40mg/kg) ALT,99.29±12.90, AST,155.49±20.74, SOD,137.94±13.34, HYP,153.96±29.35, GSH-PX,102.58±15.51; prevention trials, silibinin particles intravenously administered low-dose group (2mg/kg) in Mice for ALT,113.36±11.77, AST,97.50±6.33, SOD,106.98±10.6, HYP,213.48±11.83, GSH-PX,142.82±20.03; dose group (4mg/Kg) for ALT,94.84±9.18, AST,84.04±8.01, SOD,125.38±7.04, HYP,181.47±9.71, GSH-PX,181.32±14.38; high-dose group (8mg/kg) for ALT,69.86±8.72, AST,65.41±11.60, SOD,146.02±13.98, HYP,159.21±10.54, GSH-PX,225.79±14.98; ultra-high dose group (40mg/kg) ALT,32.52±3.26, AST,34.11±4.32, SOD,197.22±11.64, HYP,113.97±8.06, GSH-PX,367.68±13.15; original oral powder group (40mg/kg) ALT,99.29±12.90, AST, 80.67±6.53, SOD,122.37±11.47, HYP,182.04±20.07, GSH-PX,212.75±40.03.Conclusions:Take particle size and particle diameter as the index to optimize preparation of silibinin particle dispersion by uniform design. And analyze the particle dispersion particle size, span, appearance, stability, found silibinin particle dispersion particle size uniformity, stabilty and testimony of stainless steel quick membrane emulsification method suitable preparation of insoluble particulate component silibinin dispersion. In the acute toxicity test, after intravenous administration in mice, does not appear the phenomenon of death, indicating that silibinin particle dispersion less toxic, drug safety. CCL4 liver injury, treatment trials, the middle dose group (8mg/Kg) with the original powder group (40mg/Kg) is basically the same therapeutic effect; liver injury prevention trials, the middle dose group (4mg/Kg) with the original powder group (40mg/kg) is basically the same therapeutic effect, by the preparation of silibinin into particles dispersion can reduce the dose, and improve efficacy.