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Ultrasonic micro-reactor preparation method of nano-drug

A micro-reactor and nano-drug technology, applied in chemical instruments and methods, chemical/physical processes, chemical/physical/physical-chemical processes, etc. Good monodispersity, preventing clogging of channels, and small average particle size

Pending Publication Date: 2021-04-23
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to overcome the technical problems of low mixing efficiency of the above-mentioned prior art, large average particle size of the product, poor monodispersity, easy blockage of the system, poor operating flexibility, and difficulty in realizing continuous scale-up production

Method used

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  • Ultrasonic micro-reactor preparation method of nano-drug
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Examples

Experimental program
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Embodiment 1-4

[0029] Embodiment 1-4, preparation of lipid nanoparticle nanomedicine (siRNA)

[0030] The experimental procedure follows figure 2 The process flow shown. Among them, the nano-drug precursors are selected from DOTAP ((2,3-dioleoyl-propyl)-trimethylamine, cationic lipid), DSPC (distearoylphosphatidylcholine, structural lipid), cholesterol, PEG2000-DMG (1,2-Dimyristoyl-rac-glycerol-3-methoxypolyethylene glycol 2000, modified with polyethylene glycol lipid) system as a lipid substance, wherein the content of each component DOTAP: DSPC: cholesterol : PEG2000-DMG=50:10:38.5:1.5 (molar ratio); wherein DOTAP, DSPC, and cholesterol are analytically pure and purchased from AVT, and PEG2000-DMG is purchased from Avanti. Lipids were dissolved in absolute ethanol as an organic phase solution, and the aqueous phase solution was double-stranded siRNA (19nt) (purchased from General Biology) dissolved in citrate buffer (10mM, pH=4.0); siRNA and lipid The molar ratio of the species is 1:8,...

Embodiment 5-6

[0031] Embodiment 5-6, polymer nanoparticle nano drug preparation

[0032] The experimental procedure follows figure 2 The process flow shown. Among them, the nano drug precursor is selected from mPEG5K-PLGA10K (methyl polyethylene glycol 10k polylactic acid-glycolic acid 5k-block copolymer, purchased from Shanghai Yayi Biotechnology Company), and the active ingredient of the drug is selected from curcumin (purchased from Shanghai Mike Lin Biochemical Technology Co., Ltd.), wherein mPEG5K-PLGA10K and curcumin are dissolved in dimethylformamide as an organic phase solution, the molar ratio of curcumin and mPEG5K-PLGA10K is 1:5, and the aqueous phase solution is a phosphate buffer solution (20mM , pH=7.4), the flow ratio of the organic phase solution to the aqueous phase solution is 1:3, and the residence time in the ultrasonic microreactor at room temperature is 0.5s. The buffer solution is a phosphate buffer solution (20mM, pH=7.4), the mixed product is diluted 10 times in ...

Embodiment 7-8

[0033] Embodiment 7-8, preparation of lipid nanoparticle nanomedicine (mRNA)

[0034] The experimental procedure follows figure 2 The process flow shown. Among them, the nano-drug precursors are selected from DOTAP ((2,3-dioleoyl-propyl)-trimethylamine, cationic lipid), DSPC (distearoylphosphatidylcholine, structural lipid), cholesterol, PEG2000-DMG (1,2-Dimyristoyl-rac-glycerol-3-methoxypolyethylene glycol 2000, modified with polyethylene glycol lipid) system as a lipid substance, wherein the content of each component DOTAP: DSPC: cholesterol : PEG2000-DMG=50:10:38.5:1.5 (molar ratio); wherein DOTAP, DSPC, and cholesterol are analytically pure and purchased from AVT, and PEG2000-DMG is purchased from Avanti. Lipids were dissolved in absolute ethanol as an organic phase solution, and the aqueous phase solution was ARCA EGFP mRNA (mRNA of enhanced green fluorescent protein modified with ARCA) (purchased from Blue Que Bio) dissolved in citrate buffer ( 10mM, pH=4.0); the mol...

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Abstract

The invention discloses an ultrasonic micro-reactor preparation method of a nano-drug, which adopts a preparation method of ultrasonic mixing, infiltration, solvent replacement, concentration and sterile filtration, and specifically comprises the steps of conveying two solutions into an ultrasonic micro-reactor to realize ultrasonic rapid mixing, feeding the obtained crude product into a tangential filtration system through a pump, continuously supplementing a fresh buffer solution to the tangential flow filtration system through a pump so as to realize solvent replacement, and removing the redundant organic solvent; stopping supplementing the fresh buffer solution to the tangential flow system, and circulating the crude product in the tangential flow system to concentrate the product; and finally, carrying out sterile filtration to obtain the product. According to the invention, ultra-fast mixing of reaction fluid is realized, the obtained product has smaller average particle size and better monodispersity, the PDI is as low as 0.044, the product is prevented from blocking a channel, and continuous long-time production of the product is realized.

Description

technical field [0001] The invention relates to the field of nano-medicine synthesis, in particular to a method for preparing lipid nanoparticles, liposomes and polymer nanoparticles loaded with pharmaceutical active ingredients. Background technique [0002] Nano-drugs refer to a new class of drugs that use nano-materials as delivery carriers and carry active ingredients such as nucleic acids and small molecules. They have the characteristics of high absorption and utilization and targeted delivery. They are important tools for tumor therapy and gene therapy. Considered to be the next generation of novel drugs. [0003] The commonly used preparation methods of nano-medicines include nano-precipitation method and emulsification-solvent evaporation method. Among them, nano-precipitation method is widely used because of its simple process and high product quality. The U.S. Patent (US9005654) discloses this method in detail: the nanoprecipitation method dissolves the pharmaceu...

Claims

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Application Information

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IPC IPC(8): B01J19/00B01J19/10
Inventor 陈光文刘志凯董正亚杨梅尧超群
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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