Study On Self-microemulsifying Nano Preparation And Pharmacodynamics Of Myricitrin

Myricitrin?MYT?is abundant in Myrica bark and Myrica leaves,and the extraction process is very simple.MYT has a variety of pharmacological activities such as antioxidant,anti-inflammatory,analgesic and neuroprotective.However,MYT has poor water solubility,which greatly limits the application of MYT.Therefore,improving the oral bioavailability of MYT can provide a theoretical basis for the wide application of MYT.At present,the research on the pharmacological activity of MYT mainly focuses on the aspects of antioxidant,anti-inflammatory analgesia and neuroprotection,and there is little research on reducing uric acid.The purpose of this study is to improve the oral bioavailability of MYT and to explore the activity of MYT in reducing uric acid.Chapter I:IntroductionThis chapter introduces the pharmacological activity and related research progress of Myrica rubra bark and MYT,related research progress of Self-microemulsifying drug delivery system?SMEDDS?,and related research progress of HUA.It mainly includes the main chemical constituents,pharmacological activities of Myrica rubra bark,the physical and chemical properties,pharmacological activity and the related nanoformulation research of MYT,the composition,preparation and related research of SMEDDS,the pathogenesis,hazards and treatment of HUA.Chapter II:Myricitrin's Extraction and Its Physicochemical PropertiesIn this chapter,the bark of Myrica rubra is extracted by 60%ethanol aqueous solution.Then the extract was further separated and purified by silica gel and C₁₈column material.The purity of the extracted MYT was identified by thin layer chromatography?TLC?and high performance liquid chromatography?HPLC?.The structure of the extracted MYT was identified by nuclear magnetic resonance spectroscopy?NMR?and liquid chromatography-mass spectrometry?LC-MS?.The constructed in vitro analysis method of MYT was verified,and the basic physical and chemical properties of MYT were investigated.The results showed that the purity of the extracted MYT was 95.41%,and the molecular weight was 464.38.The in vitro analysis method of MYT verified that the analysis method was feasible and reliable.The equilibrium solubility of MYT in different media does not exceed 40?g/mL,and the oil-water partition coefficient value?Log P?is more than 1.3,which proves that MYT is a water-insoluble compound.Chapter III:Preparation and Characterization of Myricitrin Self-Microemulsion Drug Delivery SystemIn this chapter,the solubility of MYT in different excipients was measured and the compatibility between different excipients was tested.The pseudo-ternary phase diagram was used to select the optimal formulation ratio of myricitrin self-microemulsifying drug delivery system?M-SMEDDS?,and the preparation process of M-SMEDDS was screened.Finally,transmission electron microscopy,particle size,Zeta potential,encapsulation rate and in vitro release of M-SMEDDS were evaluated.The results showed that the best prescription for M-SMEDDS was:18%ethyl oleate,51%Cremophor EL,22%isopropanol,and 9%MYT.The optimal process conditions for preparing M-SMEDDS are:the preparation temperature is 37°C,and the stirring speed is 300 r/min.The TEM results of M-SMEDDS show that M-SMEDDS is spherical with good dispersion and uniform shape.The particle size of M-SMEDDS is21.68 nm,the Zeta potential is-23.17 mV,and the encapsulation efficiency is 92.73%.The in vitro cumulative release rate of M-SMEDDS is more than 79%in different pH aqueous media,which is significantly higher than that of MYT API.Chapter IV:Pharmacokinetics of Myricitrin Self-Microemulsion Drug Delivery System in RatsIn this chapter,an in vivo analysis method of MYT was established to examine the differences in oral bioavailability of rats between M-SMEDDS and MYT API.Twelve male SD rats of standard weight?200±20?g were adapted to the laboratory environment and then grouped.Six rats were in the MYT API group and another six rats were in the M-SMEDDS group.The twelve SD rats were fasted for 12 hours before the experiment and had free access to water.Rats in the MYT API group were given a single intragastric administration of 300 mg/kg of MYT suspension,and rats in the M-SMEDDS group were given a single intragastric administration of the same dose of MYT.At different times after the end of administration,blood was collected from the posterior orbital venous plexus of rats,and the MYT content in serum was measured,and related parameters such as oral bioavailability of MYT were calculated by BAPP2.3 pharmacokinetic parameter calculation software.The results show that MYT in vivo analysis method has good specificity and high precision.The C_maxax of M-SMEDDS and MYT are?1.81±0.26??g/mL and?0.57±0.03??g/mL,t_1/2 are?5.00±1.22?h and?7.37±1.19?h,MRT are?10.54±1.01?h and?12.834±1.11?h,and the T_max of M-SMEDDS and MYT are both 8 h.C_max of M-SMEDDS is greater than that of MYT API,and the relative oral bioavailability?F?is247.86%,which shows that M-SMEDDS can significantly improve the oral bioavailability of MYT.Chapter V:Study on the Antihyperuricemia Activity of MyricitrinIn this chapter,an in vivo analysis method for uric acid?UA?was established and verified.Rats were intragastrically administered with a suspension of hypoxanthine?HX?and intraperitoneally injected with potassium oxazinate?PO?emulsion to construct a rat acute HUA model.Acute HUA models were divided into groups:blank control group?NC?,acute HUA model group?MC?,positive control group?PC,Allopurinol?,low-dose MYT group?L-M,100 mg/kg?,and medium-dose MYT group?M-M,200mg/kg?,high-dose MYT group?H-M,300 mg/kg?,low-dose M-SMEDDS group?L-M-S,100 mg/kg?,medium-dose M-SMEDDS group?M-M-S,200 mg/kg?),High-dose M-SMEDDS group?H-M-S,300 mg/kg?.Except for the NC and MC groups,the other groups were given therapeutic drugs 1 hour after modeling,and the UA value,XOD value in the serum and XOD value in the liver of each group were detected 3hours after the modeling.The research results show that the in vivo analysis method of UA has good specificity.Precision,method recovery and stability meet the analytical methodological requirements.MYT can significantly reduce UA and XOD levels in acute HUA rat models,and the dose is dose-dependent.M-SMEDDS has a better effect on reducing uric acid and inhibiting XOD activity than MYT API.