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Manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid and application in preparation of magnetic resonance imaging contrast material thereof

A paramagnetic nano, bimetallic technology, applied in the field of medicine, can solve problems such as acute complement activation, and achieve the effects of reducing side effects, improving biological safety, and reducing load

Active Publication Date: 2014-11-05
HARBIN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the structural stability of cyclic gadolinium chelates significantly reduces the risk of NSF, such cyclic chelates still have the potential to cause acute complement activation

Method used

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  • Manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid and application in preparation of magnetic resonance imaging contrast material thereof
  • Manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid and application in preparation of magnetic resonance imaging contrast material thereof
  • Manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid and application in preparation of magnetic resonance imaging contrast material thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0039] Example 1 Preparation of manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloid (MnOL-(1.25mol%)Gd-DOTA-PE NC).

[0040] Manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloids (MnOL-Gd NC) were synthesized by a two-step method.

[0041] 1. Add 360ml of ethanol-water-n-hexane mixture into a 500ml round bottom flask, add 10g of manganese chloride tetrahydrate (MnCl 2 .4H 2 O) and 40g sodium oleate (TCI chemical), reacted at 80°C for 14 hours, then reacted at 25°C for 4 hours, washed with water, salt, Na 2 SO 4 After drying and rotary evaporating to dryness to remove the solvent, divalent MnOL is prepared, wherein, in the mixture of ethanol-water-n-hexane, the volume ratio of ethanol, water and n-hexane is 4:5:9;

[0042] 2. Under a nitrogen atmosphere, suspend 10 g of divalent MnOL in 20 mL of sorbitan sesquioleate as an internal matrix, add a phospholipid surfactant at 141 MPa and 4 °C, Fully mixed, the final concentration of the ...

Embodiment 2

[0044] Example 2 Preparation of manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloid (MnOL-(1.25mol%)Gd-DTPA-BOA NC)

[0045] Manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloids (MnOL-Gd NC) were synthesized by a two-step method.

[0046] 1. Add 360ml of ethanol-water-n-hexane mixture into a 500ml round bottom flask, add 10g of manganese chloride tetrahydrate (MnCl 2 .4H 2 O) and 40g sodium oleate (TCI chemical), reacted at 80°C for 14 hours, then reacted at 25°C for 4 hours, and after the solvent was removed by rotary evaporation, divalent MnOL was prepared, wherein, in the mixture of ethanol-water-n-hexane, The volume ratio of ethanol, water and n-hexane is 4:5:9;

[0047] 2. In a nitrogen atmosphere, suspend 10g of divalent MnOL in 20mL of polysorbate 80 as the internal matrix, add phospholipid surfactant at 141 MPa and 4°C, and mix thoroughly, the added phospholipid surface The final concentration of the active agent is 0.02g / ml...

Embodiment 3

[0049]Example 3 Preparation of manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloid (MnOL-(2.5mol%)Gd-DOTA-PE NC)

[0050] Manganese-gadolinium hybrid bimetallic paramagnetic nanoparticle colloidal MnOL-Gd NCs were synthesized by a two-step method.

[0051] 1. Add 360ml of ethanol-water-n-hexane mixture into a 500ml round bottom flask, add 10g of manganese chloride tetrahydrate (MnCl 2 .4H 2 O) and 40g sodium oleate (TCI chemical), reacted at 75°C for 16 hours, then reacted at 24°C for 5 hours, and after the solvent was removed by rotary evaporation, divalent MnOL was prepared, wherein, in the mixture of ethanol-water-n-hexane, The volume ratio of ethanol, water and n-hexane is 5:5:8;

[0052] 2. In a nitrogen atmosphere, suspend 10 g of divalent MnOL in 25 mL of polysorbate 80 as an internal matrix, add a phospholipid surfactant at 150 MPa and 20 ° C, and mix thoroughly. The added phospholipid surface The final concentration of the active agent is 0.025...

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Abstract

The invention discloses a manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid and application in preparation of a magnetic resonance imaging contrast material thereof. The invention designs, synthesizes and evaluates a hybrid ''bimetallic'' magnetic resonance imaging nanocolloid composed of manganese element and trace gadolinium. Research shows that: the high relaxation rate of the nanocolloid provided by the invention derives from high concentration manganese oleate molecules suspending at the core of nanoparticles, and the small molecules can penetrate a phospholipid film layer to come into contact with a critical surface of water and nanoparticles. Integration of trace gadolinium chelates on the surfaces of the nanoparticles can provide an additional relaxation rate, thereby affecting the relaxation effect of surrounding protons. The manganese gadolinium heterozygous bimetallic paramagnetic nanocolloid provided by the invention can maximumly reduce gadolinium agent load, lower the side effects of gadolinium chelates and improve the biological safety, thus reaching the purpose of improving the nanoparticle r1 paramagnetic magnetic resonance contrast effect.

Description

technical field [0001] The present invention relates to the preparation of a paramagnetic nanoparticle colloid (Nanocolloid, NC) and its application as a magnetic resonance imaging contrast agent, in particular to the preparation of a manganese-gadolinium hybrid bimetallic paramagnetic NC and its use as a magnetic resonance imaging contrast material Applications. The invention belongs to the technical field of medicine. Background technique [0002] Paramagnetic and superparamagnetic metals have long been used as contrast materials in magnetic resonance imaging (MRI). Among them, the lanthanide metal gadolinium (Gd) is the most widely studied, and the gadolinium chelator has been used as the most important paramagnetic blood pool contrast agent in clinical and scientific research fields. Recently, the metal ion replacement and gadolinium ion dissociation of gadolinium chelating agents in the body have been proved to be the main cause of nephrogenic systemic fibrosis (NSF),...

Claims

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Application Information

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IPC IPC(8): A61K49/06A61K49/18
Inventor 申宝忠王可铮吴丽娜
Owner HARBIN MEDICAL UNIVERSITY
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