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Grapheme-oxide based contrast agent and preparation method thereof

A contrast agent, graphene technology, applied in the directions of graphite, NMR/MRI contrast agent, preparations for in vivo experiments, etc., can solve the problems of short retention time, slow metabolism in vivo, poor stability, etc.

Active Publication Date: 2015-03-25
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The contrast agent currently on the market is mainly DTPA-Gd, but it has problems such as low relaxation rate, fast metabolism in the body, short retention time, and poor stability.
Therefore, there is still a lack of a contrast agent with high relaxation rate, slow metabolism in vivo, long retention time and good stability in the art.

Method used

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  • Grapheme-oxide based contrast agent and preparation method thereof
  • Grapheme-oxide based contrast agent and preparation method thereof
  • Grapheme-oxide based contrast agent and preparation method thereof

Examples

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Effect test

preparation example Construction

[0128] Preparation of contrast agent

[0129] The contrast agent of the present invention can be prepared by the following method:

[0130] (i) Provide a graphene oxide A-(B) with bridging molecules attached to its surface m , wherein the bridging molecule B is chemically bonded to the surface of graphene oxide A;

[0131] (ii) Graphene oxide A-(B) with bridged molecules connected to the surface with the complex molecule Ra m Carry out reaction, form the graphene oxide that the surface is connected with complex molecules, shown in formula Ia;

[0132] A-(B-Ra) n (Ia)

[0133] (iii) complexing the graphene oxide with complex molecules attached to the surface shown in formula Ia and gadolinium salt and / or gadolinium salt solution to obtain the contrast agent shown in formula I as described in the first aspect of the present invention ;

[0134] Wherein, the definitions of A, B, R, and n are as described in the first aspect of the present invention;

[0135] Ra is a co...

Embodiment 1

[0148] Embodiment 1 Preparation of Magnetic Resonance Imaging Contrast Agent

[0149] In this example, the preparation of the magnetic resonance imaging contrast agent is divided into three steps, including the preparation of graphene oxide, polyethylene glycol molecular modification of graphene oxide, covalently linking diethylenetriaminepentaacetic acid to complex gadolinium ions, Specific steps are as follows:

[0150] The first step, the preparation of graphene oxide:

[0151] Dissolve 1g of flake graphite, 0.5g of potassium persulfate, and 0.5g of phosphorus pentoxide in 1.5mL of concentrated sulfuric acid, heat it to 80°C for 6 hours, cool to room temperature, wash it with water to make it neutral, and dry it naturally into powder. Add the above powder into 23mL of concentrated sulfuric acid pre-cooled to 0°C, add 3g of potassium permanganate while stirring, and keep the temperature below 20°C. The temperature of the mixture was raised to 35° C., and after stirring fo...

Embodiment 2

[0164] Embodiment 2 Preparation of Magnetic Resonance Imaging Contrast Agent

[0165] Step one, step two are the same as embodiment 1.

[0166] The third step, the preparation and application of graphene oxide-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-gadolinium system:

[0167]The polyethylene glycol-modified graphene oxide obtained in the second step reaction is dispersed in the organic phase, in the 5ml polyethylene glycol-modified graphene oxide dispersion, add 1ml concentration of 100mg / mL of 1,4, Add 1ml of EDAC to 7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid solution, stir overnight, and dialyze to remove unreacted molecules. Then add gadolinium chloride salt solution, stir for 4 hours, dialyze to remove unreacted Gd ions, and obtain the desired contrast agent.

[0168] The results show that the prepared contrast agent can significantly enhance the contrast effect compared with the commercially available Magnevist, which is 2-3 times higher at...

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Abstract

A contrast agent based on graphene oxide material and preparation method therefor. The contrast agent has a structure represented by formula I: A-(B-R)n, wherein A is graphene oxide, R is gadolinium metal complex, B is bridging molecule, and A, B and R are bonded to each other via chemical bond. The contrast agent has characteristics of high relaxation, good stability, non-specificity and the like.

Description

technical field [0001] The invention relates to the field of medical nanomaterials, in particular, the invention relates to a functionalized graphene oxide material with superior magnetic resonance contrast performance, and a preparation method thereof. Background technique [0002] Graphene consists of carbon atoms with sp 2 The monoatomic layer is composed of hybrid connections, and its basic structural unit is the most stable benzene six-membered ring in organic materials. In the past two years, the research on graphene in the field of biomedicine has developed rapidly. In particular, one of the most important derivatives of graphene, graphene oxide, can be widely used in biomedicine for targeted drug delivery due to its good biocompatibility, ultra-high specific surface area, and chemical functional modification. , cell imaging, biological detection, tumor therapy, etc. (Liu, Z.; Robinson, J.T.; Sun, X.; Dai, H.J. Am. Chem. Soc. 2008, 130, 10876. ;Zhao,Q.;Liu,L.;Zhang...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/14A61K49/12A61K49/10A61K49/08A61K49/00A61K47/42A61K47/36A61K47/34A61K47/04
CPCA61K49/08A61K49/06C01B31/04A61K49/1887A61K49/085A61K49/105C01B32/23
Inventor 张智军张萌欣
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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