Crystallization And Structural Analysis Of Glycerophosphocholine And Process Design Of Annual Output Of100t Raw Materials

Glycerophosphorylcholine (GPC) is the product of two fattyacylphosphatidylcholine (PC) molecules are completely hydrolyzed out. It ispresented in the human body by water-soluble small molecules.Simultaneously it is also an important biosynthesis precursors ofneurotransmitter acetylcholine. GPC has been verified that it can help thebrain for learning，memory and other activities，it even can repair partiallydamaged cognitive abilities of early Alzheimer.This research exploits two methods to prepare GPC crystal， and thenchooses the best method: After Al2O3decolorization，the crude GPC oil wascrystallized by ethanol cooling method. The crystal was recrystallized byethanol. Optimal crystallization conditions:Valc：MGPC=2.5:1，70℃water-bathdissolution，0.22um organic membrane filtration， ice-water bath droptemperature from70℃to15℃in30min， crystal28h，filter the crystal andadd ethanol and water，then We can get GPC recrystallization. With suchmethod，we can get glycerophosphorylcholine with purity for drug. We make amain technological process for preparing GPC and the amplified experimentalresult is basically the same as the small.We prepare crystal by pure GPC oil，then define GPC structure by HPLC-ELSD， elementary analysis,DSC analysis, nuclear magnetic resonance(1H-NMR,1H-1H COSY,13C-NMR,13C-DEPT,13C-1H HSQC,13C-1HHMBC,31P-NMR),mass spectrum （MS）,single-crystal X-ray diffractionmethod and laboratory study. XRD shows the crystal belonged to theorthorhombic，space group P212121，with four molecules in the unit cell，andthe cell parameters were a=7.08030(10)10-10m, b=11.4303(2)10-10m, c=14.8078(2)10-10m, α=β=γ=90.00°. A feasible method was provided by theprocess for the preparation of GPC crystal and monocrystalline. It definedGPC structure and supplied a new polymorph. It provided a reference forpharmaceutic preparation of GPC in the future.We research the impurities of crystal and recrystallization. We found thereis not phospholipase in GPC recrystallization by coomassie brilliant blue（Bradford）and UV wavelength scanning. The GPC crystal has an impurities，which is verified CH3COONa by HPLC-ELSD and atomic absorption spectrometer.Base on all above，we design a progress of annual output of100t GPC rawmaterials. This design is based on mature technology of the lipase catalyzedhydrolysis of phosphatidylcholine to produce GPC. Through exploring theprocess of the Experiment，we determined the industrial production processparameters. finally，We complete the industrial production process design ofannual output of100t GPC raw materials. The design process is designedaccording to the2010version of GMP standard, so the design and processoperation requirments in the design process is fully standards compliant. Thisdesign is to lay the foundation for future large-scale GPC production processdesign.