| Hepatic fibrosis developed due to a variety of chronic hepatic injury, characterized by excessive deposition of extracellular matrix, which was the inevitable stage of the formation of cirrhosis. And it heavily threated global human health. Fortunately, traditional Chinese medicine had an advantage of clinical treatment of liver fibrosis because of the rich cognitions for etiology and pathogenesis and holistic therapeutic principle based on integration concept and syndrome differentiation.Liuwei Wuling Tablets (LWWLT) were composed of schisandrae sphenantherae, curcumae rhizoma, forsythiae fructus, ganodermae lucidi, ligustri lucidi fructus, sonchi btachyoyi herba, widely used to treat chronic hepatitis B in clinic benefiting from its fine therapeutic efficiency of nourishing liver and kidney, activating blood circulation and detoxicating. Modern researches demonstrated that LWWLT could down-regulate the expression of monoamine oxidase and transforming growth factor-β1, and decrease the level of hyaluronic acid, laminin and hydroxyproline, and inhibit synthesis and deposition of collagen fibers.However, the preparation was lack of specific quality standards and accurately active components for hepatic fibrosis. Although the formulation was a representative prescription in clinical liver disease department, there still exsited blank fields in both dissolution area and pharmacokinetics area. Thus, the thesis intended to explore pharmacodynamic material basis of LWWLT for anti-liver fibrosis and carry out the relevant pharmaceutical preliminary study. The main research details were as follows: 1. Latin super vertical method was applied to randomly sample six raw materials to recombinate into twenty new prescriptions. The corresponding chemical fingerprints were obtained from the HPLC method. Combined with the in vitro inhibitory rate on LX-2 cells by extracts, the study used SPSS software to analyze spectrum-effect. And the results demonstrated that specnuezhenide、schisandrol A、schisantherin A、 deoxyschizandrin and schisandrin B were the part of the pharmacodynamic materials.2. By scanning a mass of literatures, seven active constituents from LWWLT for anti-liver fibrosis were chosen out, namely schisandrol A、schisantherin A deoxyschizandrin schisandrin B、forsythoside A、phillyrin and specnuezhenide. The study firstly established an HPLC simultaneous determination method for above seven ingredients. And the method was applied to measure the contents of ten batches of LWWLT. The results showed that the specificity, precision, stability, repeatability and recovery were fine, and there were little differences among ten batches.3. The in vitro dissolution study was carryed out based on the idea of "relating to therapeutic efficiency". The study regarded the inhibition effect on LX-2 cells by LWWLT dissolving solutions as pharmacodynamic index, and firstly created a novel approach of self-defined weighting coefficient with the effect intensity to calculate the chemical integrated dissolution. The result presented that the chemical integrated dissolution was similar with biological dissolution at the f2 value of 71.17.4. Pharmacokinetics study was conducted by oral administration ten times adult equivalent dose of LWWLT suspensions for rats. Results indicated that the drug-time curve of deoxyschizandrin had a bimodal peak, speculating that the phenomenon of enterohepatic circulation may exist in the body. The curve of schisantherin A was accorded with one-compartment model with the half-life of 1.8 h. The plasma concentration of forsythoside A reached the highest at 2h, and its area under the curve was the largest.The study provided a reference for overall quality control and in vivo and in vitro evaluation of LWWLT, and provided a new research model for quality appraisal of the modern Chinese medicine preparation. |
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