| Natural flavonoids are often used to reduce the risk of various cancers and prevent various chronic diseases because of their various pharmacological effects.However,the extremely low water solubility of some hydrophobic active substances will seriously affect their biological activity in the body and reduce the utilization rate.In recent years,many studies have shown that embedding these hydrophobic substances in amphiphilic polymers is conducive to the increase of their solubility,and then they can play a more effective role.Natural polysaccharides are widely concerned because of their special structure,excellent functional characteristics and easy to be effectively degraded by enzymes in vivo.Therefore,if the soluble natural polysaccharide can be.hydrophobically modified to form amphiphilic polysaccharide polymer to wrap some lipopholic drugs or bioactive substances,it is particularly important to achieve the effect of solubilizing drugs,targeted transport and protecting drugs from destruction.In order to obtain a kind of polysaccharide carrier which can successfully load these hydrophobic drugs,oat ?-glucan which is easy to be extracted is selected as the research raw material in this paper.Stearic acid is used to hydrophobically modify oat?-glucan to obtain oat ?-glucan,which has both hydrophilic and hydrophobic amphoteric characteristics,namely oat ?-glucan stearate ester.Myricetin is a kind of lipophilic flavonoid compound,which is favored by the public because of its wide existence and various pharmacological effects.However,myricetin has extremely poor water solubility,and is very sensitive to changes in the external environment,prone to oxidation.Therefore,the oat ?-glucan stearate ester was used to support myricetin to obtain a complex of the them.Based on the structural characterization,stability study,drug release,gastrointestinal stability in vitro and in vivo,the functional characteristics of the obtained complex were preliminarily studied.The main content and related results of this paper are as follows:1?The oat ?-glucan was used as raw material,hydrophobic fatty acid stearic acid was used to modify it by hydrophobic esterification to obtain amphiphilic oat ?-glucan ester.By investigating the effects of the added volume of the stearic acid imidazole activation solution,the temperature and time of the esterification reaction on the degree of substitution of the resulting reaction product.It was concluded that when the volume added was 6.50 mL,the temperature and time of the esterification reaction were 90?and 5.0 h,the substitution degree of the obtained product was the largest,which was 0.133.Subsequently,FT-IR and 1H NMR were used to characterize the resulting product,and the relevant characteristic peaks appeared,thus proving the successful preparation of oat ?-glucan stearate ester.After preliminary investigation of its related physical properties,further in vitro cytotoxicity test found that the oat ?-glucan stearate ester prepared in this experiment was not cytotoxic.2?Based on the basic characteristics of oat ?-glucan stearate esters,which can form self aggregation micelles with shell core structure at a lower concentration,the extremely unstable and poorly water-soluble myricetin was selected,by using the properties of oat ?-glucan stearate ester to load myricetin to achieve the effect of solubilizing myricetin and improving bioavailability.By optimizing the results of single factor orthogonal test,the best preparation conditions of the complex were explored.When the concentration of oat ?-glucan stearate ester was 1.5 mg/mL,the ratio of oat ?-glucan stearate ester to myricetin is 1:1,the homogenization speed is 12 Kr/min,and the homogenization time is 3 min,the loading capacity of myricetin in the obtained complex sample can reach 55.86 ?g/mg.The TEM,TGA and XRD characterization results all proved the successful encapsulation of myricetin by oat ?-glucan stearate ester,the particle size is about 200 nm.Through the study on the stability of the complex samples,it is found that the products can significantly improve the stability of myricetin in the higher storage temperature(50?-70?),as well as in the alkaline conditions,and have a longer shelf life.3?By comparing the antioxidative effect of myricetin and the prepared complex sample in vitro,it was concluded that the complex can significantly increase the myelination capacity of DPPH and·OH and the total antioxidant capacity(T-AOC).The results showed that the cumulative release rate of myricetin reached 88.74%at 180 min,while the cumulative release rate of myricetin in the oat ?-glucan stearate ester was 43.23%,only half of the total release rate of exposed myricetin,which proves that the prepared compound has a certain sustained-release effect on myricetin through the dialysis bag method.After storing the prepared complex in the simulated stomach and small intestine digestive solution for 120 min and 180 min respectively,it was found that the complex prepared in the experiment significantly improved the stability in the simulated small intestine digestive solution compared with the control substance of myricetin itself.So that the target substance could play its pharmacological role better.4?Using activated carbon powder to mark the gastric lavage working fluid,and measured the advancement length of activated carbon powder in the small intestine at different time periods,it was found that the compound of oat ?-glucan stearate ester and myricetin prepared in this experiment could significantly relieves the intestinal motility hindered by the addition of activated carbon powder.By measuring the content of free myricetin in the contents of the duodenum,it was found that the peak time of the myricetin content appeared differently.When the myricetin and sodium carboxymethylcellulose were mixed for intragastric administration,the peak time of myricetin content was 1 h,while the peak of myricetin in the compound prepared in this experiment was 2 h.This is consistent with the in vitro drug release of the compound,and all prove that the compound prepared in this experiment can slowly release the drug. |
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