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Nanoparticle magnetic resonance imaging contrast agent containing gadolinium oxide as well as preparation method and application thereof

A nanoparticle, gadolinium oxide-containing technology, used in the field of magnetic resonance imaging contrast agents, can solve problems such as signal confusion, image blur, magnetic field distortion or background distortion, and achieve the effect of good water dispersion.

Active Publication Date: 2018-08-14
SUZHOU ZHECI PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these MIONs base T 2 Contrast agents also have many disadvantages: 1) T 2 Dark images of contrast agents may be confused with signals in certain conditions, such as hemorrhage, calcification, and metal deposition such as endogenous iron; 2)T 2 The high magnetic moment of the contrast agent may cause susceptibility-type artifacts (i.e. distortion of the magnetic field around the diseased area or distortion of the background), resulting in blurred images; 3)T 2 Imaging takes much longer than T 1 Imaging; 4) MIONs-based T 2 The larger size of the contrast agent (60-180nm) results in a longer clearance time from the body (typically weeks or months), which may lead to long-term chronic side effects
r 1 The value is 47.2mM -1 the s -1 GdON r 2 / r 1 The ratio is 1.7 (1.4T magnetic field), and its synthesis method is a thermal decomposition method (oil phase method), and the common problem of the oil phase method is that the aqueous phase dispersion of the obtained nanoparticles is not good

Method used

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  • Nanoparticle magnetic resonance imaging contrast agent containing gadolinium oxide as well as preparation method and application thereof
  • Nanoparticle magnetic resonance imaging contrast agent containing gadolinium oxide as well as preparation method and application thereof
  • Nanoparticle magnetic resonance imaging contrast agent containing gadolinium oxide as well as preparation method and application thereof

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Experimental program
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Effect test

Embodiment 1

[0054] Preparation of Gadolinium Oxide Nanoparticles (GdON)

[0055] Prepare 40 mL of polyacrylic acid solution (molecular weight: 1800) with a concentration of 4.0 mg / mL. After bubbling nitrogen gas for 50 minutes (to remove oxygen), the solution was heated to 100°C. 0.8 mL of gadolinium nitrate solution (62.5-1000 mM) was firstly added through a syringe, and then 6.0 mL of ammonia solution (28%) was added immediately, and reacted for 60 minutes under magnetic stirring. After cooling to room temperature, GdON can be obtained by purifying by dialysis (molecular weight cut-off 6-8 kDa), and then concentrating by ultrafiltration (molecular weight cut-off 3 kDa). The nanoparticles prepared from 1000, 750, 500, 250, 125, and 62.5 mM gadolinium nitrate solutions are GdON1-6, respectively. The relevant synthesis conditions and characterization results are shown in Table 1.

[0056] Table 1. Synthesis conditions and characterization results of GdON nanoparticles

[0057]

[005...

Embodiment 2

[0065] Preparation of Gadolinium Oxide-Iron Oxide Composite Nanoparticles (FeGd-HN)

[0066] Prepare 40 mL of polyacrylic acid solution (molecular weight: 1800) with a concentration of 4.0 mg / mL. After bubbling nitrogen gas for 50 minutes (to remove oxygen), the solution was heated to 100°C. First add 0.8mL iron ion solution (500mM ferric chloride, 250mM ferrous sulfate) through a syringe, then immediately add 12mL ammonia solution (28%), and react for 30 minutes under magnetic stirring. Then 0.8 mL of gadolinium nitrate solution (62.5-1000 mM) was added through a syringe, and then 6.0 mL of ammonia solution (28%) was added immediately, and reacted for 90 minutes under magnetic stirring. After cooling to room temperature, purification by dialysis (molecular weight cut-off 6-8 kDa), and concentration by ultrafiltration (molecular weight cut-off 3 kDa), FeGd-HN can be obtained. The nanoparticles prepared from 1000, 750, 500, 250, 125, and 62.5 mM gadolinium nitrate solutions w...

Embodiment 3

[0079] Preparation of Gadolinium Oxide-Manganese Oxide Composite Nanoparticles (GdMn-HN)

[0080] Prepare 40 mL of polyacrylic acid solution (molecular weight: 1800) with a concentration of 4.0 mg / mL. After bubbling nitrogen gas for 50 minutes (to remove oxygen), the solution was heated to 100°C. Add 0.8 mL manganese oxide nanoparticles solution (MnO, MnO 2 or Mn 3 o 4 , C Mn =500mM), after magnetic stirring for 30 minutes, add 0.8mL gadolinium nitrate solution (400mM), then immediately add 6.0mL ammonia solution (28%), and react under magnetic stirring for 90 minutes. After cooling to room temperature, purify by dialysis (molecular weight cut-off 6-8 kDa), and then concentrate by ultrafiltration (molecular weight cut-off 3 kDa), GdMn-HN can be obtained.

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Abstract

The invention relates to nanoparticles containing gadolinium oxide. The inner core of the nanoparticles is nano gadolinium oxide; the surface of the inner core is covered with a hydrophilic high molecular compound; the hydrophilic high molecular compound is a high molecular compound containing a plurality of carboxyl groups or a plurality of amino groups. The invention further provides composite nanoparticles containing the gadolinium oxide; the composite nanoparticles are formed by compounding the nanoparticles containing the gadolinium oxide and other nanoparticles; outer layers of the othernanoparticles are covered with the hydrophilic high molecular compound and the inner core is any one of an iron oxide nanoparticle, a manganese oxide nanoparticle, a gold nanoparticle, a mesoporous silicon nanoparticle and an albumin nanoparticle. The nanoparticles containing the gadolinium oxide and the composite nanoparticles, provided by the invention, have good water-phase dispersity, stability and biocompatibility and have ultrahigh r1 value and ultralow r2 / r1 specific value, and can be used for a T1 contrast agent for magnetic resonance imaging. The invention further provides a method for preparing the nanoparticles through a water-phase method.

Description

technical field [0001] The invention relates to a contrast agent for magnetic resonance imaging, in particular to a nanometer material for magnetic resonance imaging, in particular to a nanometer particle containing gadolinium oxide. technical background [0002] Malignant tumor (cancer) is a common disease that seriously endangers human life and health. It has become the first cause of death in some countries or regions, and has become the second cause of death after cardiovascular disease in developed countries. The rapid development of China's economy in recent years has inevitably brought about environmental pollution problems, especially the increase in the concentration of fine particulate matter (PM2.5) in the atmosphere may lead to an increase in the incidence of lung cancer. Therefore, early diagnosis of lung cancer and non-toxic chemotherapy are particularly important and urgent in today's Chinese society. [0003] Early diagnosis is recognized as the key to savin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K49/14A61K49/18
CPCA61K49/12A61K49/146A61K49/1854A61K49/1863A61K49/1872
Inventor 陈小元沈折玉
Owner SUZHOU ZHECI PHARM TECH CO LTD
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