Unlock instant, AI-driven research and patent intelligence for your innovation.

Method of using oligonucleotide for chiral drug resolution

A technology of oligonucleotides and chiral drugs, applied in the field of medicine, can solve the problems of unreported separation of chiral drugs, and achieve the effect of safe separation

Active Publication Date: 2014-04-02
TIANJIN UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, the resolution of chiral drug enantiomers has not been reported using specific double-stranded oligonucleotide sequences through the induction and regulation of metal ions

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] A method utilizing oligonucleotides to split chiral drugs, comprising the steps of:

[0022] (1) At pH=7.2, add [(dG-dC) to 1000 μL molar concentration of 0.05 mmol / L 20 ] 2 Add 1 μL of an aqueous solution of copper chloride with a molar concentration of 0.1 mol / L to the solution, and mix well at 20°C to obtain [(dG-dC) 20 ] 2 - copper ion complex solution; [(dG-dC) 20 ] 2 The solvent of the solution is sodium phosphate buffer;

[0023] (2) At pH=7.2, 400 μL of [(dG-dC) prepared in step (1) 20 ] 2 -The copper ion complex solution is mixed with 100 μ L molar concentration of racemic ofloxacin solution of 0.5mmol / L, adsorbed for 20 minutes, the solvent of the racemic ofloxacin solution is sodium phosphate buffer; then the mixed solution Pack into the ultrafiltration centrifuge tube that molecular weight cut off is 3000, centrifugal 20 minutes under 8000rpm, filtrate is a kind of enantiomer solution of the enriched ofloxacin, [(dG-dC) 20 ] 2 - The adsorbate on the...

Embodiment 2

[0026] A method utilizing oligonucleotides to split chiral drugs, comprising the steps of:

[0027] (1) At pH=8.5, add [(dG-dC) to 1000 μL molar concentration of 0.05 mmol / L 10 ] 2 Add 10 μL of zinc sulfate aqueous solution with a molar concentration of 0.5 mol / L to the solution, and mix well at 20°C to obtain [(dG-dC) 10 ] 2 -Zinc ion complex solution; [(dG-dC) 10 ] 2 The solvent of the solution is Tris-hydrochloric acid buffer.

[0028] (2) At pH=8.5, 400 μL of [(dG-dC) prepared in step (1) 10 ] 2 -Zinc ion complex solution mixed with 10 μ L molar concentration of racemic ofloxacin solution of 2mmol / L, adsorbed for 40 minutes, the solvent of ofloxacin solution was Tris-hydrochloric acid buffer solution; then the mixed solution was loaded into In the ultrafiltration centrifuge tube that molecular weight cut-off is 1000, centrifugal 20 minutes under 8000rpm, filtrate is a kind of enantiomer solution of the enriched ofloxacin, [(dG-dC) 10 ] 2 - The adsorbate on the zin...

Embodiment 3

[0031] A method utilizing oligonucleotides to split chiral drugs, comprising the steps of:

[0032] (1) At pH=8.5, add [(dA-dT) to 1000 μL molar concentration of 0.025 mmol / L 400 ] 2 Add 20 μL of magnesium nitrate aqueous solution with a molar concentration of 0.05 mol / L to the solution, mix well at 30°C to obtain [(dA-dT) 400 ] 2 -magnesium ion complex solution; [(dA-dT) 400 ] 2 The solvent of the solution is Tris-hydrochloric acid buffer.

[0033] (2) At pH=8.5, 400 μL of [(dA-dT) prepared in step (1) 400 ] 2 -The magnesium ion complex solution is mixed with 400 μ L molar concentration of racemic ibuprofen solution of 0.15mmol / L, adsorbed for 15 minutes, the solvent of the ibuprofen solution is Tris-hydrochloric acid buffer; The ultrafiltration membrane of 10000, filtrate is a kind of enantiomer solution of the ibuprofen of enrichment, [(dA-dT) 400 ] 2 - The adsorbate on the magnesium ion complex is the other enantiomer of the enriched ibuprofen. The enantiomeric exc...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method of using oligonucleotide for chiral drug resolution, which includes the steps: firstly, adding divalent metal ion inorganic salt aqueous solution into double-strand oligonucleotide solution under the condition of pH (potential of hydrogen) ranging from 5 to 9, and well mixing to obtain oligonucleotide-metal ion compounded solution; and secondly, mixing the oligonucleotide-metal ion compounded solution with chiral drug solution under the same pH condition as the step one, adsorbing, and using an ultrafiltration membrane with the molecular weight cutoff ranging from 1000 to 10000 for ultrafiltration, wherein the filtrate is enantiomer solution of enriched chiral drug, and adsorbate on the oligonucleotide-metal ion compound is another enantiomer of the enriched chiral drug. Chiral drug resolution is simply and safely realized by means of the double-strand oligonucleotide which is high in biocompatibility, and the method is a novel, green and clean method for chiral drug enantiomer resolution.

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 oligonucleotides. Background technique [0002] With the development of modern analysis and testing technology, it is found that more and more pharmaceutical compounds have chiral structural characteristics, that is, enantiomers that are mirror images of each other but cannot be superimposed on each other; enantiomers of chiral drugs usually Show different physiological behaviors and have different or even opposite drug effects [J.Chromat.A, 2001, 906, 3-33]. Therefore, the research and development of chiral drugs with optical purity has become one of the key points and difficulties in the field of medical technology research. The preparation of chiral drugs with optical purity needs to rely on asymmetric synthesis and chiral resolution technology, and the key lies in the design and development of chiral resolution agents...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07B57/00C07D498/06C07C57/30C07C51/42C07D311/56C07C59/64C07C59/84C07C57/58C07D307/87C07C217/30C07C213/10
Inventor 李韡陈雄飞付雁段小丽张金利
Owner TIANJIN UNIV