Study On Bicyclol Liposome Preparation And Pharmacokinetics

Bicyclol is a structural analogue of schisandrin C which is Chinese herbal medicine Fructus Schisandra’s active constituent, was effective in improvement of the abnormal liver function of CHB patients. Academician Gengtao Liu by China Academy of Medical Sciences and Professor Chunzhen Zhang respectively in pharmacological research and chemical synthesis developed.It is the first international independent intellectual property rights of the treatment of hepatitis a class of synthetic chemical drug in China. Bicyclol have exact curative effect on chronic hepatitis B and chronic hepatitis C. The mechanism of anti hepatitis is to reduce alanine amino transferase(ALT) and Tianmen East acid aminotransferase(AST). Bicyclol can also Maintain Hepatocyte Membrane Stability Through Scavenging Free Radicals and protection Against Mitochondria Injury of Hepatocytes. At present, the form of bicyclol listed is the tablet. But the bicyclol’s weakness is poor solubility, low oral bioavailability.To increase drug solubility and improve the oral bioavailability,this preject is prepared to prepare Bicyclol-loaded liposomes.Liposomes have many advantages among new drug carrier systems. They are nontoxic for their composition and unique structure similar to cells. Meanwhile, bicyclol encapsulation by liposomes can improve the water solubility, modulate the distribution and improve the oral bioavailability. Liposomes loading bicyclol were prepared by film dispersion method with soybean phospholipids and cholesterol. The main methods and results were as follows:1. this preject established a method for the determination of bicyclol’s content with HPLC. Dialysis method were used to separate the free drug and liposomes. HPLC method be also applied to determine the entrapment efficieney of bicyclol-loaded liposomes.2. bicyclol-loaded liposomes were prepared by thin-film dispersion method.To evaluate the effects of the weight ratio of soya lecithin to cholesterol,the weight ratio of soya lecithin to drug,volume ratio of organic phase to water phase,bath temperature and the ultrasonic time on the entrapment efficiency of bicyclol-loaded liposomes.On this basis,the effects of the weight ratio of soya lecithin to cholesterol,the weight ratio of soya lecithin to drug and bath temperature on the entrapment efficiency,drug loading and average particle size were studied by composite design. The use of composite design has been optimized for the prescription and processes and indicated the optimized Parameters. the weight ratio of soya lecithin to cholesterol,the weight ratio of soya lecithin to drug was 10.65:1,40.27:1,respectively. The bath temperature was 47.91℃. The bicyclol-loaded liposomes encapsulation was 33.79%,drug loading was 0.53%, the average particle size was 81 nm.The composition of prescription was reasonable and preparation process was stable.3. this project studied the pharmaceutical properties, quality evaluation in vitro and preliminary stability of bicyclol-loaded liposomes.The results showed that the appearance of uniform spherical. the average particle size was 81 nm,Zeta potential was-22.1mv. The amount of accumulated release over 24 h was 91.20%.In vitro release results showed that in line with Weibull release model. No significant differences were detected in Physiochemieal charaeteristics during the storage of 30 days under4±2 ℃,which indicated that bicyclol-loaded liposomes was stable during the storage after freeze-drying.4. the pharmacokinectics on the bicyclol-loaded liposomes,bicyclol solutions and bicyclol Listed tablet with rats.The HPLC-MS technology was applied to determine the plasma level of bicyclol content and DAS2.0 pharmacokinectic processing software was used to analyze the results. The results showed that:bicyclol-loaded liposomes, bicyclol solutions and bicyclol Listed tablet are in line with the two-compartment model, bicyclol-loaded liposomes can significantly improve its pharmacokinetic behavior compared with other two. T1/2βextended to the 1~2h,MRT extended to the 1h,AUC increased nearly1000μg/L*h,CL of 1.792 L/h/Kg reduced to 1.115 L/h/Kg. Therefore,bicyclol-loaded liposomes could maintain a high blood concentration of the drug in the body,increase the bioavailability of the drug and increase the efficacy of the bicyclol.