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Medicinal ultrahigh-field nuclear-magnetism contrast agent and preparation method thereof

A nuclear magnetic contrast agent and ultra-high field technology, which can be used in pharmaceutical formulations, preparations for in vivo testing, emulsion delivery, etc., and can solve problems such as unfavorable ultra-high-field nuclear magnetic resonance imaging and unsuitability for ultra-high-field nuclear magnetic contrast agents, etc. Achieve the effect of promoting blood circulation performance, excellent imaging effect, and improving efficiency

Inactive Publication Date: 2015-04-29
SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the clinically commonly used T 1 Gadolinium agent, the optimal value of the contrast effect is below 1.0T, and its contrast effect is only one-third of the optimal value at 3.0T, which is not suitable for ultra-high-field MRI contrast agents; another type of T 2 Iron oxide, a contrast agent, reaches magnetization saturation at about 1.5T, which is also not conducive to ultra-high field MRI

Method used

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  • Medicinal ultrahigh-field nuclear-magnetism contrast agent and preparation method thereof
  • Medicinal ultrahigh-field nuclear-magnetism contrast agent and preparation method thereof
  • Medicinal ultrahigh-field nuclear-magnetism contrast agent and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Weigh 2mmol (758.74mg) HoCl respectively 3 ·6H 2 O, dissolved in 2 mL of deionized water for later use; respectively add 15 mL of oleic acid and 30 mL of octadecene into a three-neck flask, then add the pre-prepared aqueous solution of chloride containing rare earth ions, and stir at room temperature for 2 hours; Argon to remove the air in the reaction flask; under the protection of argon atmosphere, heat slowly (the temperature rise rate is controlled at 30°C / hour), raise the temperature to 160°C, and keep it warm for 1 hour to remove the water in the system; stop heating, and naturally cool down to Room temperature; then dropwise add 200mg NaOH and 296.3mg NH 4 10 mL of methanol solution of F, stirred at room temperature for 3 hours to obtain a yellow-white solution; continue to pass in argon, and stirred at 120°C for 2 hours to remove methanol in the reaction system; after removing methanol, connect the condenser tube and raise the temperature To about 275°C, keep ...

Embodiment 2

[0073] Medical Imaging Application Effect Experiment

[0074] 1. MR imaging

[0075] 1.1 Experimental materials and instruments:

[0076] The UFCAs hydrophilic particle that embodiment 1 makes;

[0077] MR imaging detection instrument model: GE Signa 1.5T, GE Signa 3.0T and Agilent, 7T / 160

[0078] 1.2 Experimental animals: Kunming rats, with an average weight of 20g, purchased from the animal room of Fudan University School of Medicine;

[0079] 1.3 Experimental method: the influence of the UFCAs aqueous solution prepared in Example 1 with different concentrations on the transverse relaxation time of hydrogen protons at 1.5T / 3.0T / 7.0T; after the mice were intraperitoneally anesthetized with chloral hydrate, the thigh Contrast agent (2.5Ho mg / mL, ~30μL) imaging contrast effect at 3.0T / 7.0T; tail vein injection of contrast agent (dose 12mg Ho / kg), observe the MR contrast effect of the liver;

[0080] 1.4 Experimental results:

[0081] Figure 8 UFCAs hydrophilic particle ...

Embodiment 3

[0086] Toxicity evaluation experiment

[0087] 1. In vitro cytotoxicity test

[0088] 1.1 Experimental materials:

[0089] The UFCAs hydrophilic nano-particles that embodiment 1 makes;

[0090] 1.2 Experimental method:

[0091] MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide) method was used to evaluate the cell survival rate, and the specific experimental methods were: (1) inoculating cells: obtained with 10% fetal calf serum The culture medium was made into a single cell suspension, and 10 5 -10 6 Cells were inoculated into a 96-well plate, with a volume of 100 microliters per well. (2) Cell culture: After adding nanoparticles and co-cultivating the cells for 1 day, add MTT solution (5 mg / ml, prepared with PBS, pH=7.4) 50 to each well. Microliter, continue to co-cultivate for 4 hours, carefully aspirate and discard the culture supernatant in the well, for suspension cells, centrifuge and then aspirate and discard the culture supernatant in the well. (...

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Abstract

The invention relates to a medicinal ultrahigh-field nuclear-magnetism contrast agent and a preparation method thereof. The medicinal ultrahigh-field nuclear-magnetism contrast agent is NaHoF4 nano-particles modified by phospholipid PEG (polyethylene glycol). A paramagnetic element Ho in NaHoF4 has the maximal effective electron magnetic moment and can be used for effectively changing transverse relaxation time of water protons to produce a T2-weighted imaging effect which is sharply increased with the increase of filed strength and can be used for clinical ultrahigh-field nuclear-magnetism contrast imaging in the future. Moreover, the phospholipid PEG is utilized to perform hydrophilic modification on NaHoF4 particles, so that the biocompatibility is increased, the toxic or side effects are lowered and the blood circulation is promoted. The preparation method is convenient to modify, efficient and beneficial to further grafting biological ligand subsequently.

Description

technical field [0001] The invention belongs to the technical field of medical contrast agents, and in particular relates to an ultra-high-field nuclear magnetic contrast agent and its preparation method and application. Background technique [0002] Magnetic resonance imaging (MRI) is an imaging method that uses computer technology and image reconstruction methods for imaging. It has high resolution for soft tissues and has been used on a large scale in clinical practice. However, MRI has low sensitivity and cannot effectively diagnose tiny lesions, which limits its further clinical application. In view of this, researchers have developed a variety of MRI contrast agents to improve the contrast effect of imaging and obtain detailed information on the lesion site. At present, 1.5T / 3.0T clinical nuclear magnetic instruments are mainly used. In the past ten years, 3.0T has replaced 1.5T on a large scale, which has greatly improved the imaging quality and signal-to-noise ratio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K49/18
Inventor 倪大龙步文博施剑林
Owner SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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