A kind of nuclear magnetic contrast agent with oligomer specificity and its preparation method and application

A nuclear magnetic contrast agent and specific technology, which can be used in preparations, pharmaceutical formulations, drug delivery and other directions for in vivo tests, and can solve the problems of low diagnostic specificity, no relaxation properties, and poor diagnostic effects. The effect of good specificity, good application prospect and good relaxation properties

Active Publication Date: 2021-10-08
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] CN102430130A discloses a modified dextran-coated magnetic nanoparticle composite material for medicine and its preparation method. It uses solvothermal conditions to react ferric oxide nanoparticles, but its diagnostic effect is not good and its diagnostic specificity is not high. , does not have good relaxation properties

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  • A kind of nuclear magnetic contrast agent with oligomer specificity and its preparation method and application
  • A kind of nuclear magnetic contrast agent with oligomer specificity and its preparation method and application
  • A kind of nuclear magnetic contrast agent with oligomer specificity and its preparation method and application

Examples

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Effect test

Embodiment 1

[0083] In this example, an NMR contrast agent with oligomer specificity was prepared through the following steps, named W20-SPION:

[0084] (1) Fe coated with polyethylene glycol dicarboxylic acid 3 o 4 1.5 mg of ferromagnetic nanoparticles was replaced in 1.5 mL, 10 mM PBS solution, centrifuged at 10000 rpm for 10 min for the first time; then 2.5 μmol EDC and 6.25 μmol sulfo-NHS were added, left at room temperature for 15 min, and then centrifuged at 10000 rpm for 10 min for the second time.

[0085] (2) Take the single-chain variable region antibody (W20 antibody) that specifically recognizes amyloid oligomers, 9.5 mg / mL, and add 0.5 mg to 950 μL magnetic nanoparticle solution. Put it at 4 degrees and let it react for 12 hours. In the afternoon of the next day, take the reaction solution for ultracentrifugation, 25,000 rpm, and centrifuge 3 times, 1 hour each time, to remove excess W20 antibody and obtain an oligomer-specific nuclear magnetic contrast agent, Fe 3 o 4 The ...

Embodiment 2

[0088] In this example, an NMR contrast agent with oligomer specificity was prepared through the following steps, named W20-SPION:

[0089] (1) Fe coated with polyethylene glycol dicarboxylic acid 3 o 4 1.5mg of ferromagnetic nanoparticles was replaced in 3mL, 10mM PBS solution, centrifuged at 8000rpm for 12min for the first time; then 2.25μmol EDC and 4.5μmol sulfo-NHS were added, left at room temperature for 15min, then centrifuged for 12min at 8000rpm for the second time.

[0090] (2) Take the single-chain variable region antibody (W20 antibody) that specifically recognizes amyloid oligomers, 9.5 mg / mL, and add 0.5 mg to 750 μL magnetic nanoparticle solution. Put it at 6 degrees, and let it react for 18 hours. In the afternoon of the next day, take the reaction solution for ultracentrifugation, 22000rpm, and centrifuge 4 times, 1 hour each time, to remove excess W20 antibody and obtain an oligomer-specific NMR contrast agent, Fe 3 o 4 The final concentration was 1 mg / mL....

Embodiment 3

[0093] In this example, an NMR contrast agent with oligomer specificity was prepared through the following steps, named W20-SPION:

[0094] (1) Fe coated with polyethylene glycol dicarboxylic acid 3 o 4 1.5 mg of ferromagnetic nanoparticles was replaced in 1.5 mL, 10 mM PBS solution, centrifuged at 12000 rpm for 8 min for the first time; then 3.75 μmol EDC and 11.25 μmol sulfo-NHS were added, left at room temperature for 20 min, and centrifuged for the second time at 12000 rpm for 8 min.

[0095] (2) Take the single-chain variable region antibody (W20 antibody) that specifically recognizes amyloid oligomers, 9.5 mg / mL, and add 0.5 mg to 1000 μL magnetic nanoparticle solution. Put it at 2 degrees and let it react for 12 hours. In the afternoon of the next day, take the reaction solution for ultracentrifugation, 26,000 rpm, and centrifuge 5 times, 1 hour each time, to remove excess W20 antibody and obtain an oligomer-specific nuclear magnetic contrast agent, Fe 3 o 4 The fina...

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Abstract

The present invention provides a nuclear magnetic contrast agent with oligomer specificity and its preparation method and application. The nuclear magnetic contrast agent with oligomer specificity includes iron ferric oxide magnetic nanoparticles and single-chain antibodies. The four Ferric oxide magnetic nanoparticles are coated in polyethylene glycol dicarboxylic acid, the single-chain antibody is connected to the outer surface of polyethylene glycol dicarboxylic acid, and the preparation method of the present invention has oligomer-specific NMR contrast agent that can penetrate the blood-brain barrier, recognize and bind to a variety of brain oligomers, has good specificity, high stability, good biocompatibility, and has good relaxation properties, reducing oligomeric Polymer toxicity, it has a good application prospect and high application value in the preparation or diagnosis of amyloid disease preparations.

Description

technical field [0001] The invention belongs to the field of biological materials and relates to a nuclear magnetic contrast agent and its preparation method and application, in particular to an oligomer-specific nuclear magnetic contrast agent and its preparation method and application. Background technique [0002] Amyloid diseases (Amyloidoses) refer to a class of diseases caused by amyloid aggregation. At present, there are about 40 kinds of such diseases, mainly including Alzheimer's disease (Alzheimer's Disease, AD), Parkinson's disease (Parkinson's Disease, PD), Huntington's disease (Huntington's disease, HD), muscular atrophy Neurodegenerative diseases such as lateral sclerosis (Amyotrophic lateral sclerosis / Lou Gehrig's disease, ALS) and Prion protein-related diseases, as well as related diseases caused by type 2 diabetes, lysozyme and light chain deposition, these diseases have seriously endangered human health and quality of life. As society gradually ages, the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/16A61K49/12A61K49/18
CPCA61K49/126A61K49/16A61K49/186A61K49/1875
Inventor 刘瑞田刘小歌于晓琳卢帅
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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