Separation method of chiral medicament by applying protein functionalized magnetic nano-particles

Abstract

The invention discloses a separation method of a chiral medicament by applying protein functionalized magnetic nano-particles. The method comprises the following steps: (1) modifying the surfaces of superparamagnetic particles by adopting a physical adsorption method; (2) loading protein with chiral identification effect; and (3) mixing protein-modified superparamagnetic nano-particle aqueous solution and a chiral medicament racemic aqueous solution at a volume ratio of 1:1, adsorbing, and performing magnetic separation, wherein the supernatant is liquid containing the separation product of one enantiomer, and the superparamagnetic particle adsorbate is the separation product of the other enantiomer. The method is simple to operate, and has mild condition, short reaction time, and large protein immobilization capacity; the medicament identification capability of the protein is maintained; and the optical purity of the product is remarkably increased.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for splitting chiral drugs by using protein functionalized magnetic nanoparticles. Background technique [0002] Enantiomers of chiral drugs often exhibit different physiological behaviors—often one stereoisomer is potent, while its mirror image is either toxic, has the opposite potency, or has no effect at all Pharmacodynamics [J.Chromat.A, 2001, 906, 3-33]. Therefore, the research and development of high-efficiency single-enantiomer chiral compound production technology has become the focus of scientific research and industry. The preparation of single-enantiomer chiral compounds relies on stereoselective synthesis and chiral resolution. Sub technology. At present, the methods for enantiomer resolution of chiral drugs mainly include crystallization, membrane resolution, chromatography, capillary electrophoresis, etc. Chromatography and capillary electro...

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Problems solved by technology

Chinese patent 200510110689.4 invented a method of carbon nanotube immobilized protein as a stationary phase filled in a PMMA chip separation channel, based on a microfluidic chip for chiral separation and analysis. This method has a fast separation and analysis speed and is suitable for drug detection and analysis, but Due to the small sample load, it is not suitable for preparative separations with large throughput

Chinese patent 200810113779.2 invented a tandem continuous multi-stage chiral separation device. Firstly, a macromolecular chiral selector (BSA, etc.) Membrane separation, this method overcomes the disadvantages of chiral membrane separation flux and low enantioselectivity, but the device is more complicated, and the separation time is 1-4h

At present, the separation of chiral drug enantiomers by loading functionalized proteins on the surface of superparamagnetic particles and magnetic separation has not been reported.