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Polyphosphoester polymer, preparation method thereof, modified porous silicon nanoparticles and preparation method and application of modified porous silicon nanoparticles

A polyphosphate and polymer technology, applied in the field of pharmaceutical preparations, can solve the problems of refractory degradation, reduced cell effective uptake, slow drug release, etc., and achieves increased affinity, good biocompatibility, degradability, and affinity. high effect

Active Publication Date: 2019-05-17
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

For example, the use of polyethylene glycol to modify the surface of nanoparticles can effectively avoid the electrostatic adsorption of mucin, but the hydrophilicity of polyethylene glycol limits the mutual contact between nanoparticles and epithelial cells, thereby reducing the effective uptake by cells.
At the same time, polyethylene glycol is difficult to degrade in the body, and the drug is released slowly after entering the cell

Method used

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  • Polyphosphoester polymer, preparation method thereof, modified porous silicon nanoparticles and preparation method and application of modified porous silicon nanoparticles
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  • Polyphosphoester polymer, preparation method thereof, modified porous silicon nanoparticles and preparation method and application of modified porous silicon nanoparticles

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preparation example Construction

[0035] The present invention provides the preparation method of polyphosphate polymer described in above-mentioned technical scheme, comprises the following steps:

[0036] mixing N-(tert-butoxycarbonyl)ethanolamine, hydroxyethyl dithiopyridinated phosphate and the first solvent, and performing ring-opening polymerization reaction under the action of an organometallic catalyst to obtain a ring-opening polymerization product;

[0037] Mixing the ring-opening polymerization product with a reducing agent and a second solvent to perform a depyridine reaction to obtain a depyridine product;

[0038] The depyridine product is mixed with the zwitterionic monomer and the third solvent, and click chemical reaction is carried out under the catalysis of 4-dimethylaminopyridine to obtain the polyphosphate polymer having the structure shown in formula I.

[0039] In the invention, N-(tert-butoxycarbonyl)ethanolamine, hydroxyethyl dithiopyridinated phosphate and the first solvent are mixed,...

Embodiment 1

[0079] A silicon wafer (n-type doped single crystal silicon, with a resistivity of 0.01 to 1 Ω·cm) is placed in a mixed reagent of hydrogen peroxide and concentrated sulfuric acid (the mass concentration of the hydrogen peroxide is 40.0%, and the mass concentration of the concentrated sulfuric acid is 98.0%, the volume ratio of the hydrogen peroxide and concentrated sulfuric acid is 3:1) in ultrasonic cleaning 5min, then successively adopt acetone, absolute ethanol and deionized water to clean to remove surface impurities; the silicon chip after cleaning is put into electrochemical In the etching device, add the mixed reagent of hydrofluoric acid and ethanol (the mass concentration of described hydrofluoric acid is 40.0%, the volume ratio of described hydrofluoric acid and ethanol is 2:1), at 100mA / cm 2 Continue to etch for 20min under the current intensity, add absolute ethanol to clean, continue to add the mixed reagent of hydrofluoric acid and ethanol (the mass concentration...

Embodiment 2

[0082] (1) Prepare the ethanol dispersion of porous silicon nanoparticles according to the method of Example 1, collect porous silicon nanoparticles after centrifugation at 12000rpm for 15min, disperse 100mg of porous silicon nanoparticles in 20mL of anhydrous methanol, add 1.5mL of 3-aminopropyl Trimethoxysilane, heated up until the system refluxed (40°C), carried out amination treatment for 10 h, cooled naturally to room temperature, and washed by anhydrous DMSO for several times, and the obtained aminated porous silicon nanoparticles were stored in anhydrous DMSO, 4 Store at ℃ until use.

[0083] (2) After centrifuging the anhydrous DMSO dispersion of aminated porous silicon nanoparticles in step (1), the aminated porous silicon nanoparticles were collected, and 100 mg of aminated porous silicon nanoparticles, 60 mg of insulin and hydrochloric acid (6 mL, a concentration of 0.02 mol / L), mixed with stirring, and incubated at 25°C for 1.2h; then centrifuged at 9000rpm for 5mi...

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Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to a polyphosphoester polymer, a preparation method thereof, modified porous silicon nanoparticles and a preparation method and application of modified the porous silicon nanoparticles. A main chain of the polyphosphoester polymer is a polyphosphoester chain segment, side chains of the polyphosphoester polymer are amphoteric ionic chain segments, good biocompatibility and degradability are achieved, the polyphosphoester polymer is introduced into the surfaces of the porous silicon nanoparticles, thus thestability of nanoparticle colloids can be improved significantly, the polyphosphoester polymer penetrates through mucus more rapidly, the retention volume of the nanoparticles on a mucous layer is decreased, better affinity to epithelial cells is achieved, the endocytosis amount of the cells is greatly increased, intracellular and extracellular drug release can be effectively conducted in a transcellular mode, and the bioavailability of drugs is improved advantageously; meanwhile, active sites of the polyphosphoester chain segments in the polyphosphoester polymer are easily coupled with targeted factors, the affinity of hydrophilic polyphosphoester chain segments and a cell membrane are high, and compared with existing nanoparticles for promoting mucus diffusion, the safety of the nanoparticles can be effectively improved.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a polyphosphate polymer, a preparation method thereof, a modified porous silicon nanoparticle, a preparation method and application thereof. Background technique [0002] Porous silicon nanoparticles have unique physical and chemical properties, and have a wide range of applications in drug delivery systems, catalysis and adsorption, and protein separation. It is a kind of nanomaterial with high specific surface area, uniform and controllable pore size and particle size, high drug loading capacity, easy surface modification and good biocompatibility. In the drug delivery system, its controllable pore, particle size and surface modification, It is conducive to loading various drugs, and realizes the controllable drug loading and release of drugs, and finally reaches the target tissue. [0003] The behavior of nanoparticles in living organisms is closely relate...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G79/04A61K47/34A61K47/04
Inventor 刘卫饶荣任园园谭熙
Owner HUAZHONG UNIV OF SCI & TECH
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