Study On Preparation And Drug Release Behavior Of Huperzine A Molecularly Imprinted Hydrogel Microspheres

Huperzine A(HupA)as an efficient and high selective acetylcholinesterase(AchE) inhibitor,is currently the most promising drug for Alzheimer’s disease(AD)treatment.secondly,HupA also has a certain effect on vasculardementia(VD)and mental retardation,Cerebral is chemic stroke and other diseases.The dosage form of HupA has maketed is mainly a commom preparation for oral or injection currently.The overall clinical safety of HupA is good,but 20%～30% of patients will have mild or moderate gastrointestinal reactions after taking HupA.In order to reduce the impact of side effects on patients,dosage form improvement has become a hot research direction.Molecular imprinting technology is developing rapidly currently,molecularly imprited polymers have the characteristics of specific recognition and specific selection,and have been greatly developed in many fields,it also provide a new research idea for the improvement of dosage forms.a molecularly imprinted hydrogel microsphere drug carrier can be preparedthat suitable for oral administration,it can increase the drug load and enhance the sustained release of the drug.The following research of paper arebased on the above theory.Chapter 1:Preparation and properties of hydrogel microspheres.The hydrogel microspheres were prepared by reversed phase suspension polymerization using hydroxypropyl methylcellulose(HPMC)as raw material and vinyl sulfone(DVS)as cross-linking agent.The particle size and morphology of the microspheres were measured by TEM and nanoparticle size analyzer.The drug-loaded microspheres were collected by ultrafiltration and the dialysis method was used to evaluate the degree of in vitro release.The hydrogel microspheres were prepared with particle size distribution and good dispersibility,the drug loading is 3.66 %.HupA can be released byhydrogel microspheres for 6h.Therefore,the prepared HupA hydrogel microspheres havecertain release effect.Chapter 2:Preparation and properties of HupA molecularly imprinted hydrogel microspheres.The HupA molecularly imprinted hydrogel microspheres were prepared by reversed phase suspension polymerzation using HupA as template molecule,HPMC as functional monomer,N,N,N’,N’-Tetramethylethylenediamine(TEMED)as catalystand DVS as cross-linker.The characterization of the HupA imprinted polymers were measured by TE M and nanoparticle size analyzer.The recognition mechanism of HupA imprinte dpolymers were studied by UV Spectrophotometer and infraredspectrometer.The type of catalyst and the ratio of template molecules to functional monomers were investigated.The adsorptionperformance and the drug loading were investigated,The in vitro release be havior was evaluated.Results indicated that such were prepared with particle sizedistribution and good dispersibility,The formation of MIPMs is mainly through the hydrogen bonding of template molecule and functional monomer.The selective adsorptionof MI PMs to HupA was significantly higher than that of Atractylodes.the drug loadingof MI PMs is 7.95%.HupA can be released by MIPs for 8h.Compared with hydrogelmicrospheres,MIPMs have higher drug loading and better sustained release effect on HupA.Chapter 3:Pharmacokinetics of molecularly imprinted hydrogel microspheres.To develop an LC-MS method for the quantification of hupA in plasma concentration of rat.Sample was analyzed on an ACQUITY UPLC BEH C18(100 mm×2.1mm,1.7μm)column,The mobile phase is methanol-1mmol/L ammonium acetate(65:35).The method using HupB as internal standard substances.Quantitative analysis of ions were m/z243.20(HupA)and m/z257.50(HupB).The separation of HupA from HupB was good and endogenous substances do not interfere with the determination when thesample was measured.The assay range of the methods was 5～500 μg/L.The limit of quantification is 0.37μg/L.The recovery range was 93.82%～94.48%.The intra and inter-day precisions were below 1.96%.The matrix effect range was 93.60%～96.77%.The sample was stable within 24 h.The method can be applied to deteminate the concentration of HupA in plasma of rat.Theresults of sample measurement showed that both MIPMs and NIP Ms had a sustained release effect on HupA,and the sustained releaseeffect of MIPMs was better.