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Nuclear magnetic contrast agent with oligomer specificity as well as preparation method and application of nuclear magnetic contrast agent

A nuclear magnetic contrast agent and specific technology, which can be used in preparations for in vivo experiments, pharmaceutical formulations, emulsion delivery, etc., and can solve the problems of lack of relaxation properties, low diagnostic specificity, and poor diagnostic effects. Achieve good relaxation properties, good specificity, and less side effects

Active Publication Date: 2019-02-22
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

Method used

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  • Nuclear magnetic contrast agent with oligomer specificity as well as preparation method and application of nuclear magnetic contrast agent
  • Nuclear magnetic contrast agent with oligomer specificity as well as preparation method and application of nuclear magnetic contrast agent
  • Nuclear magnetic contrast agent with oligomer specificity as well as preparation method and application of nuclear magnetic contrast agent

Examples

Experimental program
Comparison scheme
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 1.5mg of ferromagnetic nanoparticles was replaced in 1.5mL, 10mM PBS solution, centrifuged at 10000rpm for 10min for the first time; then 2.5μmol EDC and 6.25μmol sulfo-NHS were added, left at room temperature for 15min, and then centrifuged for 10min at 10000rpm 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 final conc...

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, and centrifuged for the second time at 8000rpm for 12min.

[0090] (2) Take the single-chain variable region antibody (W20 antibody) specifically recognizing 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, 22000 rpm, and centrifuge 4 times, 1 hour each time, to remove excess W20 antibody and obtain an oligomer-specific nuclear magnetic contrast agent, Fe 3 o 4 The final concentration was...

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) specifically recognizing 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, 26000rpm, 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 final conc...

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Abstract

The invention provides a nuclear magnetic contrast agent with oligomer specificity as well as a preparation method and application of the nuclear magnetic contrast agent. The nuclear magnetic contrastagent with oligomer specificity comprises ferroferric oxide ferromagnetic nanoparticles and a single-chain antibody; the ferroferric oxide ferromagnetic nanoparticles are coated in polyethylene glycol dicarboxylate; and the single-chain antibody is connected to the outer surface of polyethylene glycol dicarboxylate. The nuclear magnetic contrast agent with oligomer specificity, prepared by usingthe preparation method provided by the invention, is capable of penetrating through a blood brain barrier, identifying and bonding with various brain oligomers, good in specificity, high in stability,good in biocompatibility and relaxation property and capable of reducing the toxicity of the oligomers and has a good application prospect and a relatively high application value in a preparation fortreating or diagnosing amyloid protein diseases.

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 Applications(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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