| Leaf as fresh or dried leaves of persimmon Diospyros kaki L.F.plants,with clearing heat and detoxification,moistening lungs and strong heart,antitussive and hemostasis anti-cancer and cancer prevention and other effects.Modern pharmacological experiments show that the total flavonoids of persimmon leaves are the main pharmacological components of persimmon leaves extract.Mainly used for treatment of venous obstruction,chest pain,coronary heart disease,cerebral arteriosclerosis embolism.But persimmon leaf total flavonoids low in water solution,oral effect is poor,low bioavailability?The current use of preparations for the tablet,to the elderly patients,dysphagia and other special patients bring inconvenience.Purposes 1.The total flavonoids of persimmon leaves were prepared into solid dispersions to improve their solubility2.The total flavonoids of persimmon leaves are prepared into dosage forms to suit swallowing difficulties and special populations.3.To predict the mechanism of total flavonoids from persimmon leaves anti-coronary heart disease.Methods 1.The total flavonoids of persimmon leaves are prepared as solid dispersions.The cumulative release was used as the evaluation index,The formulation and preparation process of the solid dispersion were optimized by orthogonal test and Weibull model fitting,The solid dispersions of total flavonoids of persimmon leaves were detected by SEM,DSC and IR to analysis solubilizing mechanism,And study on its stability.2.The preparation of oral disintegrating tablet with persimmon leaves total flavonoid solid dispersion as intermediates,The disintegration time was used as the evaluation index,The types and amounts of disintegrating agents,fillers,lubricants and flavoring agents were examined by single factor,In order to select out the main factors affecting the disintegration time were optimized by central composite design and response surface methodology.3.According to the Rule of Five,The active chemical constituents of total flavonoids were screened,Using the pharmacophore to predict the target through the Pharm Mapper database.Compared with the target of small molecule anti coronary heart disease drugs that are approved by FDA in Drug Bank database to obtain the effective target,The selected target was imported into MAS 3.0,The obtained pathway was analyzed by GO enrichment and KEGG pathway annotation.Finally,the active chemical constituents,predicted targets and pathways were imported into Cytoscape3.4.0 software for mapping.Results 1.The solid dispersion was prepared by solvent method using methanol as solvent,PVP-K30 as carrier.Drugs and carriers were dissolved in methanol,sonicated for 5 min,50 ° C water bath,and dried for 48 h.The method greatly improved the solubility of total flavonoids in persimmon leaves.2.The tablets were prepared by direct powder compression,The final formulation was as follows: SD 60 mg /table,PVPP238 mg / table,MCC28 mg / table,mannitol 45 mg /table,aspartame 7.5mg / table ?,citric acid 7.5mg / table,magnesium stearate was added to tablets up to 390 mg / table.The disintegration time is about 30 s,the dissolution rate is high,the stability of the product is good,but it has some moisture absorption,should be closed dry preservation.3.Eight compounds,40 targets,and 60 pathways were directly or indirectly associated with the treatment of coronary heart disease.Conclusions 1.The solid dispersion significantly improved the solubility,which laid the foundation for the development of the new dosage forms of persimmon leaves.2.To determine the prescription of oral disintegration tablet,developed a quality control standards for oral disintegration tablets,for dysphagia and other special groups to provide a new selection.3.The network pharmacological map of "compound-target-pathway" was established,predicting the potential pathways for the treatment of coronary heart disease.Which provide a basis for further research. |
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