| Background In recent years, as people living standard rise ceaselessly, the people's diet structure is changing ; the proportion of fatty, sweets, alcohol in the human diet is more and more rising. Fatty liver which is increasing year by year seriously threat to people's health. Therefore, looking for safe and effective drugs to control alcoholic liver injury becomes very important.The experiment results show that the emodin(EMO) has many pharmacological activity, such as anti-inflammatory, antibacterial, antiviral and anti-oxidation, inhibit trypsin, protect liver and kidney, antitumor, etc. Emodin is one effective components of rheum and has similar pharmacological functions with rheum. Rheum as a traditional Chinese medicine has been applied to clinical using , mainly used in the treatment of jaundice, acute pancreatitis, etc. Along with studing on the pharmacological effects of emodin, its application in clinical prospects will be more broad.But, emodin itself almost insoluble in water, easily absorbed in the intestine and the bioavailability is low. So we need to exploitation efficient, strong effect new dosage form of emodin in order to make solubility increasing and get better dispersancy. It can improve the bioavailability and lay the foundation for better clinical applications.Objectives Take emodin make into emodin solid dispersion to improve the solubility of emodin and in vitro dissloution degrees. On the basis of establishing experimental alcohol liver injury model in rats, emodin and emodin solid dispersion were used in the rat model. And then we research and compares emodin and its solid dispersion to the influence of alcoholic liver injury in rat and discusse emodin solid dispersion whether can more effectively play a role on resisting oxidation, scavenging free radicals, reducing the liver injury effect of alcohol , to lay experimental basis for new dosage form clinical medicine .Methods Screening the best preparation method for emodin solid dispersion: With PVPK30 and PEG 6000 as carrier, prepare emodin solid dispersion of three different ratio (1:2, 1:4, 1:6). Through the determination of content, solubility and dissolution in-vitro, screen the best carrier and best ratio to determine the best solid dispersion prescription .And then Emodin solid dispersion were tested by DSC and Ir scan and its stability in different pH environment .Pharmacodynamics:Make healthy SPF male SD rats be experimental animals.These animals were divided into five groups at random after being raised adaptability for a week, 5 per group, including: alcoholic liver injury model group, emodin in treatment group (EMO), lower-dose emodin solid dispersion lower dose treatment group (E - SDL), high-dose emodin solid dispersion treatment group (E - SDH), while establishing a control group. Morning: control group: feeding ordinary food; Alcoholic liver injury model group, EMO group, E - SDL group and E - SDH groups: were given 10 ml/kg /d alcohol lipid emulsion; Afternoon: blank control, alcoholic liver damage model group stomach give 1.5 % respectively; EMO group were given 40 mg/kg/d; E - SDL group were given emodin solid dispersion 40 mg/kg/d; E - SDH group were given emodin solid dispersion 80 mg/kg/d. Above 5 groups of dosing once daily for eight weeks. Weekly weigh rat once, according to the weight adjusted to dosage, until end of experiment.After the last time giving drugs, all animals are fasting 12h. Five group rats, weigh, take blood serum from heart, take animals' liver, preparation organization homogenate; Calculation liver index, determination total cholesterol (TC), triglycerides (TG), alanine amino transferase, aspartic acid amine transferase, MDA and reduced glutathione, gamma - GT, superoxide dismutase (SOD). Observe liver form of rats, liver tissue pathology after HE colouration.The database was established with Excel, the obtained data were expressed as mean±SD, and the analysis was carried on with SPSS17.0, significance was tested with one-way ANOVA.Results Emodin solid dispersion in vitro dissloution experiments show that: after emodin preparation into solid dispersion, solubility and dissloution degrees were increased significantly. DSC and infrared spectrometer scanning appraisal solid dispersion existence; According to the mensuration, confirmed emodin solid dispersion were stability in different pH environment .Emodin solid dispersion to rat alcoholic liver injury experimental research shows that: emodin solid dispersion can significantly reduce alcoholic liver injury in rats triglycerides (TG) and total cholesterol (TC) content in serum and liver homogenate and reduce serum aspartic acid amine transferase(AST) , alanine amino transferase (ALT) activity , and reduced MDA content and improve liver tissue SOD in activity. Compared with the control group, TG and TC content in the model rats increases obviously (P < 0.05), indicating that the model of alcoholic liver injury in rats builded successfully . Compared with the model group, E - SDL and E - SDH group could significantly reduce rat blood lipid levels (P < 0.05).Compared with the control group, AST, ALT activity the model rats and liver index rise significantly (P < 0.05), indicating that alcoholic liver injury rat liver injury. Compared with the model group, EMO group and E - SDL and E - SDH group can significantly reduce the AST and ALT activity and liver index (P < 0.05), and as the dosage increased protect liver degree increase.Compared with the control group, GSH, gamma - GT content in the model rats is low (P < 0.05), indicating that liver injury. Compared with model group, EMO group and E - SDL and E - SDH group can make GSH conten eleations, gamma - GT active heighten (P < 0.05). Pathological can be observed in model group liver cells appear sizes of fat drops; Give medicine group of liver disease change in different degree improvement.Conclusions Using the water soluble materials PVPk30 as the carrier, emodin and PVPk30 in ratio of 1:2 , will be prepared to solid dispersion, successful improved the drug emodin of dispersion , overcome the problem of low emodin water-soluble.Emodin solid dispersion play obviously a role of liver protecting and antioxidant effecton experimental alcoholic liver injury in rats , and better than pure emodin; Emodin solid dispersion in play when pharmacological appears a certain extent concentration-response relations; in addition side effects of emodin , has certain protective effect to liver. |
PDF Full Text Request