Mechanism Study Of Solubilizing Five Flavonoid Compounds By Substituted Cyclodextrins

Cyclodextrin is a kind of natural cyclo-oligosaccharide,which is nontoxic and easy to be metabolized.Cyclodextrin is widely used as a solubilizer for insoluble drug molecules because of its structure characteristic of " hydrophobic inner cavity and hydrophilic outer part".Flavonoids are a kind of known natural compounds.Flavonoids are the main active ingredients in various drugs and health food due to their universal functions of anti-oxidation,anti-aging,preventing thrombosis,sterilization and antiviral.However,because flavonoids are generally insoluble in water,poorly dispersed in aqueous solutions,and bioavailability of direct oral administration is very low,people generally need to adopt appropriate solubilization methods to increase their solubility,so as to facilitate oral absorption.Compared with other methods,cyclodextrin encapsulation solubilization is the most suitable method for industrial production.In this thesis,two kinds of natural cyclodextrins: ?-cyclodextrin(?-CD)and?-cyclodextrin(?-CD)and three instead of cyclodextrin: 2,6-dimethyl-?-cyclodextrin(DM-?-CD),2-hydroxypropyl-?-cyclodextrin(2HP-?-CD)and6-glucose-?-cyclodextrin(6glu-?-CD)are used as solubilizer,where five kinds of flavonoids including daidzein,biochanin A,sophoricoside,hesperidin and genistein are adopted as insoluble drugs.The solubilization effect of cyclodetrins to durgs were invesgated and solubilization mechanism was speculated by molecular simulation method,either.In this thesis,UV-VIS spectroscopy was used to confirm that all the five cyclodextrins had certain solubilizing effect on the above five flavonoids,especially DM-?-CD had the best solubilizing effect on daidzein,biochanin A,hesperidin and genistein,and 6glu-?-CD has the most significant solubilizing effect on sophoricoside.Based on the Higuchi and Connors' theory,it can be inferred that cyclodextrin contributes to solubility by forming a 1:1 host-guest complex with these flavonoids.Infrared spectroscopy,X-ray powder diffraction and other methods were used to verify the formation of compounds between cyclodextrin and flavonoids.In this paper,molecular docking technology was used to simulate the complexation process between the host and the guest.MOPAC software was used to calculate andanalyze the results of molecular docking on a semi-empirical level.The results showed that the formation of the above compounds was a spontaneous process with the free energy less than zero.After the best docking result was imported into a box full of water molecules,the system was started to a 30 ns molecular dynamics simulation.Molecular dynamic simulation results show that the initial structure in the simulation process did not appear separation of the host and the guest.Root-mean-square deviation(RMSD)of the host and the guest is ranging between 1 ~3 ?,showing no obvious change,which indicated that molecular structure of the host and the gust in the process of simulation were not significant change.Thus,the host-guest combination in the complex is believed to be firm and the host and the guest in the compound has strong affinity.Since the results of molecular dynamics simulation are consistent with the results of molecular docking simulation,it can be determined that the stable 1:1 type complex can be formed during the solubilization process of cyclodextrins to daidzein,biochanin A,sophoricoside,hesperidin and genistein.