| Schisandra(Schisandra chinensis)is Magnoliaceae Schisandra dry fruit.Modern pharmacological studies have shown that Schisandra lignans.volatile oil,et al.components have a variety of pharmacological activities,and lignans are the main components of the active substance of Schisandra in lowing(SPGT)activityliver,and it is also has a good effect in anti-inflammatory,anti-aging,anti-oxidation,enhanced myocardial function.However,lignans such as Deoxyschizandrin,schisandrin,schizandrol,et al are fat-soluble,difficult soluble compounds in vitro dissolution,low bioavailability,taking large doses,that seriously affect its efficacy.In this research,Use of macroporous resin purification and solid dispersion technology intends to develop a new formulations that can significantly improve lignans dissolution in vitro and improve its bioavailability and reduce dose and improve efficacy.Firstly,Schisandra extract is purified by macroporous resin to refined and remove impurities,in order to reduce the dose of the drug.Established Schizandrin,Deoxyschizandrin,schisandrin HPLC analysis method as index components to filter macroporous resin and investigate purification process.Finalized the process of resin AB-8,the sample concentration 0.128g/ml,flow rate 3ml/min,diameter and height ratio of 1:3 or more,95%ethanol at a flow rate 3ml/min.And by measuring changes in HPLC chromatograms and total lignans before and after purification to evaluate the reasonableness of purification,the results show lignans transfer rate above 70%,UV spectroscopy determination of total lignan content of total lignans factors accounted for 64%solids content.Scientific and rational purification process can be used for industrial promotion.Above-mentioned Purified drug is preparated into solid dispersion by using solid dispersion technology,in order to improve lignans dissolution in vitro and improve its bioavailability and efficacy.Given the nature of the solid Schisandra,we selected volatiling solvent to prepare the solid dispersion.the alternative carrier is PVPK30,KVA64,HPMC,Soluplus,each of the four kinds of materials according 1:1,1:3,1:6,1:9 ratio of the solid dispersion prepared by dispersing in vitro-dissolving out of the filter materials and proportions of materials finalized KVA64,solid ratio:1:3 excipients.By measuring of the equilibrium solubility of schisandrin of the solid content and the solid dispersion,and IR,DSC Characterization to evaluative the solid dispersions prepared in the dissolution of the active ingredient can be improved.Furthermore we select from six lignans,respectively Schizandrin,deoxyschizandrin schizandrol B,schisanhenol,schisandrin,Schizandrin C,to compare the total Schisandra lignans solid dispersion and solids bioavailability,establish analysis method in vivo and plasma processing method of the six components,Through pharmacokinetic analysis,we conclude that:the six components bioavailability from solid dispersion composition can be significantly improved.And increased the amount of female rats was lower than male rats,indicating that oral absorption of lignans exist gender differences in vivo.Finally,we compared the total Schisandra lignans solid dispersion and solid protective effect on the liver of mice with acute liver injury,and established mouse model of CCL4 acute liver injury,by measuring serum levels and pathological ALT,AST liver to evaluative prepared lignans solid dispersion can significantly enhance its protective effect on the liver,the drug significantly improved performance. |
PDF Full Text Request