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A high-sensitivity dual-mode magnetic resonance contrast agent and its preparation method

A magnetic resonance contrast agent, dual-mode technology, applied in general/multifunctional contrast agents, pharmaceutical formulations, preparations for in vivo tests, etc., can solve the problem of dual-mode imaging nanoprobe research reports, unable to synthesize manganese oxide Embedded iron oxide nanoparticles and other issues

Active Publication Date: 2020-06-19
BEIJING TECHNOLOGY AND BUSINESS UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since the radii of manganese ions and iron ions are not much different, and Mn(II) tends to occupy the position of Fe(II), therefore, existing conventional methods cannot synthesize manganese oxide-embedded iron oxide nanoparticles, and based on manganese oxide inner Embedded Iron Oxide Nanoparticles T 1 -T 2 The technology of dual-modal imaging nanoprobes has not been reported so far

Method used

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  • A high-sensitivity dual-mode magnetic resonance contrast agent and its preparation method
  • A high-sensitivity dual-mode magnetic resonance contrast agent and its preparation method
  • A high-sensitivity dual-mode magnetic resonance contrast agent and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Preparation of 22nm Spherical MnO Embedded Iron Oxide Nanoparticles

[0062] First, weigh 1.8g (2mmol) of ferric oleate and add it to a three-necked flask, then add 2mL of octadecene, 79mg (0.4mmol) of manganese chloride tetrahydrate, 1.4mL (4.38mmol) of oleic acid and 10mL of deca octane solvent;

[0063] Then, until the raw material is completely dissolved in the solvent octadecene, the entire reaction system is placed in a magnetically stirred reflux device and protected with nitrogen;

[0064] Next, first raise the temperature of the reaction solution to 120°C, keep at 120°C for 60 minutes, then raise the temperature to 200°C, keep at 200°C for 30 minutes, then raise the temperature to 320°C within 30 minutes, and keep at 320°C for 1 hour;

[0065] Afterwards, the heat source was removed and the system was allowed to cool down. Wait until the reaction system is cooled to room temperature, wash with 20mL ethanol 2-3 times;

[0066] Finally, oleic acid-modified 22n...

Embodiment 2

[0068] Preparation of 20nm Spherical MnO Embedded Iron Oxide Nanoparticles

[0069] First, weigh 1.8g (2mmol) iron oleate, add it to a 50mL three-necked flask, add 2mL octadecene, 0.16g (0.8mmol) manganese chloride tetrahydrate, 2mL oleic acid and 20mL octadecene solvent;

[0070] Then, until the raw material is completely dissolved in the solvent octadecene, the entire reaction system is placed in a magnetically stirred reflux device and protected with nitrogen;

[0071] Next, first raise the temperature of the reaction solution to 120°C, keep at 120°C for 60 minutes, then raise the temperature to 200°C, keep at 200°C for 30 minutes, then raise the temperature to 320°C within 30 minutes, and keep at 320°C for 30 minutes;

[0072] Afterwards, the heat source was removed and the system was allowed to cool down. Wait until the reaction system is cooled to room temperature, wash with 20mL ethanol 2-3 times;

[0073] Finally, oleic acid-modified 20nm spherical MnO embedded iron ...

Embodiment 3

[0075] Preparation of 16nm Spherical MnO Embedded Iron Oxide Nanoparticles

[0076] First, weigh 1.8g (2mmol) iron oleate, add it into a 50mL three-necked flask, add 2mL octadecene, 39.6mg (0.2mmol) manganese chloride tetrahydrate, 4mL oleic acid, 1mL oleylamine and 15mL benzyl ether;

[0077] Then, until the raw material is completely dissolved in the solvent octadecene, the entire reaction system is placed in a magnetically stirred reflux device and protected with nitrogen;

[0078] Next, first raise the temperature of the reaction solution to 120°C, keep at 120°C for 60 minutes, then raise the temperature to 200°C, keep at 200°C for 30 minutes, then raise the temperature to 298°C within 30 minutes, and keep at 298°C for 30 minutes;

[0079] Afterwards, the heat source was removed and the system was allowed to cool down. Wait until the reaction system cools down to room temperature, wash with 20mL isopropanol 2-3 times;

[0080] Finally, oleic acid-modified 20nm spherical...

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Abstract

The invention discloses a preparation method for a high-sensitivity bimodal magnetic resonance contrast agent. According to the preparation method, by means of a method for preparing ferric oleate andmanganese chloride through thermal decomposition, a high-boiling-point solvent is adopted as a reaction medium, oleic acid and oleylamine are used as stabilizers, and therefore manganese oxide embedded iron oxide nanoparticles with narrow particle size distribution and high degree of crystallinity are obtained. The invention particularly relates to a preparation method for modifying the manganeseoxide embedded iron oxide nanoparticles by utilizing the oleic acid / the oleamine, or a preparation method for the biocompatible and water-soluble manganese oxide embedded iron oxide nanoparticles. The preparation method for the high-sensitivity dual-mode magnetic resonance contrast agent has the advantages that the requirements of magnetic resonance imaging for the contrast agent and the characteristics of the Nanotechnology are combined, by means of regulation and control over chemical synthesis, manganese oxide with the T1 contrast capability and superparamagnetic iron oxide nanoparticles with the T2 contrast capability are combined so as to form the manganese oxide embedded iron oxide nanoparticles, and therefore the cooperatively-enhancing dual-mode magnetic resonance contrast effectcan be achieved between the two imaging modes, namely, the T1 imaging mode and the T2 imaging mode.

Description

technical field [0001] The present invention relates to contrast agents for magnetic resonance imaging, the invention also relates to methods for the preparation of said contrast agents. Background technique [0002] Magnetic resonance imaging (MRI) is considered to be one of the most effective means of disease diagnosis due to its inherent advantages of non-invasiveness, biological safety and high spatial resolution. In MRI, differences in proton density and turnover time affect relaxation rates, leading to MRI contrasts in which different biological tissues and organs exhibit characteristics. However, when the contrast effect between the target organ and the surrounding parts is not obvious, it is difficult to accurately detect the target area. MRI contrast agents can accelerate T at the target site 1 or T 2 Relaxation rate, thereby enhancing the contrast between the lesion and normal tissue, in clinical applications, by enhancing the contrast to increase the sensitivit...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/00B82Y5/00B82Y15/00
CPCA61K49/0002A61K49/1839B82Y5/00B82Y15/00
Inventor 录驰冲
Owner BEIJING TECHNOLOGY AND BUSINESS UNIVERSITY
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