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Small-size gadolinium-polyphenol polymer nano-particles and preparation method and application thereof

A polyphenolic polymer and nanoparticle technology, which can be used in preparations, pharmaceutical formulations, drug delivery and other directions for in vivo experiments, can solve problems such as limited applications, and achieve low synthesis cost, strong process controllability, and easy functionalization. and targeted modification

Active Publication Date: 2019-06-28
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the lack of effective methods for regulating the assembly of gadolinium and polyphenols, the prepared gadolinium-tannic acid polymers usually have large particle sizes (micron scale), which limits their application in vivo

Method used

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  • Small-size gadolinium-polyphenol polymer nano-particles and preparation method and application thereof
  • Small-size gadolinium-polyphenol polymer nano-particles and preparation method and application thereof
  • Small-size gadolinium-polyphenol polymer nano-particles and preparation method and application thereof

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preparation example Construction

[0033] The preparation of small-sized gadolinium-polyphenol polymer nanoparticles proposed by the present invention is under weakly alkaline conditions, in a water / ethanol mixed solvent, with polyphenols as organic ligands and polymer monomers, and aldehydes as crosslinks agent to covalently crosslink polyphenols into polyphenol oligomers. Then add the metal precursor (containing Gd 3+ )Gd 3+ And polyphenol oligomers further coordinate cross-linking to form Gd-polyphenol polymer nanoparticles.

[0034] Concrete preparation method comprises the following steps:

[0035](1) Fully dissolve polyvinylpyrrolidone (PVP) in a certain proportion of water / ethanol mixed solvent, and adjust the pH value of the solution to 8-10. Add freshly prepared polyphenol solution and cross-linking agent solution in turn, and continue to stir at room temperature for 12-24h.

[0036] (2) Add Gd(NO 3 ) 3 solution, continue to stir for 12-24h, and then dialyze the prepared sample for 36-48h to remo...

Embodiment 1

[0043] (1) Accurately weigh 0.3g of polyvinylpyrrolidone (PVP-K30), add it to 35mL of ultrapure water and 10mL of absolute ethanol mixed solvent, add 0.3mL of ammonia water (25wt%) to adjust the pH to 8-10 after fully dissolving , a clear and transparent solution was obtained.

[0044] (2) Accurately weigh 0.20 g of tannic acid and dissolve it in 8 mL of ultrapure water, add it to the above solution, stir for a while, then add 3 mL of formaldehyde solution (3.7 wt %), and continue stirring for 12 h.

[0045] (3) Add 1 mL of freshly prepared Gd(NO 3 ) 3 Solution (2wt%) was stirred for 12 hours to obtain Gd-TA polymer nanoparticles.

[0046] (4) Dialysis through a dialysis membrane with a molecular cut-off of 14,000 for 48 hours to remove unreacted small molecules to purify the sample.

[0047] Such as figure 1 As shown, the Gd-TA polymer nanoparticles prepared in this example have an ultra-small particle size (average particle size is about 20.9 nm), and the particle size d...

Embodiment 2

[0051] (1) Accurately weigh 0.3g of polyvinylpyrrolidone (PVP-K30), add it to 35mL of ultrapure water and 10mL of absolute ethanol mixed solvent, add 0.3mL of ammonia water (25wt%) to adjust the pH to 8-10 after fully dissolving , a clear and transparent solution was obtained.

[0052] (2) Accurately weigh 0.20 g of gallic acid (GA) and dissolve it in 8 mL of ultrapure water, add it to the above solution, stir for a while, then add 3 mL of formaldehyde solution (3.7 wt %), and continue stirring for 12 h.

[0053] (3) Add 1 mL of freshly prepared Gd(NO 3 ) 3 Solution (2wt%) was stirred for 12 hours to obtain Gd-GA polymer nanoparticles.

[0054] (4) Dialysis through a dialysis membrane with a molecular cut-off of 14,000 for 48 hours to remove unreacted small molecules to purify the sample.

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Abstract

The invention discloses small-size gadolinium-polyphenol polymer nano-particles and a preparation method and application thereof. In a mixed solvent containing polyvinylpyrrolidone, under the alkalescent condition, polyphenol is covalently cross-linked into polyphenol oligomer with an aldehyde cross-linking agent, then metal gadolinium salt is added, and the metal gadolinium salt and the polyphenol oligomer are cross-linked through metal-organic ligand to form the small-size gadolinium-polyphenol polymer nano-particles. In the reaction process, the size of the gadolinium-polyphenol polymer nano-particles is controlled by adjusting the use level of the polyvinylpyrrolidone. The method is easy to operate, low in synthesis process and high in process controllability, and the size and composition of the small-size (10-100 nm) metal-polyphenol polymer nano-particles can be precisely regulated and controlled. Due to the fact that functional and targeted modification of the polymer nano material are easy, the small-size gadolinium-polyphenol polymer nano-particles have wide application prospects in the fields of medical imaging, drug delivery, photo-thermal treatment, biosensing and the like.

Description

technical field [0001] The invention belongs to the technical field of biomedical polymer materials, and relates to a small-sized gadolinium-polyphenol polymer nanoparticle and a preparation method and application thereof. Background technique [0002] Magnetic resonance imaging (MRI) technology has the characteristics of non-invasive, non-radiation and high spatial resolution, and has become one of the most effective diagnostic methods for cancer and cardiovascular diseases. Since normal and diseased tissues exhibit only minor signal differences, contrast agents are often required to improve the contrast of imaging. Gadolinium chelates (such as Magnevist, chemical name: gadolinium diethyltriaminepentaacetic acid, English abbreviation: Gd-DTPA) are usually used clinically as T 1 type contrast agent to improve resolution. However, gadolinium chelates can cause damage to the kidneys. Therefore, reducing the dosage of contrast agents and improving resolution and sensitivity ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/12
Inventor 魏晶秦婧王根冯冰溪冯尤优
Owner XI AN JIAOTONG UNIV
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