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Novel CT contrast medium and preparation method and application thereof

A technology of contrast agents and nanoparticles, which is applied in the preparation of X-ray contrast agents, pharmaceutical formulations, medical preparations of non-active ingredients, etc. It can solve the problems of low X-ray attenuation coefficient, heavy heart load, enhanced scanning, etc. Good compatibility and excellent contrast effect

Inactive Publication Date: 2015-12-09
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

The CT contrast agent currently used clinically is an iodine-based material. Due to the low X-ray attenuation coefficient of iodine, a large dose of contrast agent must be used in order to achieve a satisfactory enhancement effect clinically, and a large amount of contrast agent is necessary for heart disease patients. Undoubtedly, it will overload the heart; in addition, the circulation time of iodine is short and the metabolism is fast. A large amount of iodine is quickly metabolized by the kidneys, which may cause nephrotoxicity. For patients with kidney disease, iodine-enhanced scans cannot be performed

Method used

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  • Novel CT contrast medium and preparation method and application thereof
  • Novel CT contrast medium and preparation method and application thereof
  • Novel CT contrast medium and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Weigh 1mmolHoCl respectively 3 ·6H 2 O (379.38 mg) and BaCl 2 2H 2 O (244.26mg), dissolved in 5mL of deionized water for later use; add 20mL of absolute ethanol, 12mL of oleic acid and 12mL of oleylamine to the lining of the hydrothermal kettle, stir magnetically for 0.5 hours, and then add the pre-prepared The above-mentioned chloride aqueous solution containing rare earth ions was stirred at room temperature for 1 hour; then 5 mL of aqueous solution containing 210 mg of NaF was added dropwise, stirred at room temperature for 1 hour, and then the hydrothermal kettle was placed in a constant temperature box at 160 ° C for 12 hours of hydrothermal reaction. When it was a child, take it out and cool it down to room temperature naturally, and then carry out centrifugation; the collected solids are cleaned successively with cyclohexane and ethanol for 3 times; 5 particles);

[0060] Take 3 mL of the above chloroform solution, add 1 ml of phospholipid PEG chloroform solu...

Embodiment 2

[0069] Medical Imaging Application Effect Experiment

[0070] 1. CT imaging

[0071] 1.1 Experimental materials and instruments:

[0072] The nCAs hydrophilic particles prepared in Example 1;

[0073] CT imaging detection instrument model: PhilipsBrillianceiCT256; PhilipsMedicalSystems, Cleveland, OH

[0074] 1.2 Experimental animals: healthy male Sprague-Dawley rats, with an average age of 2 months and an average weight of 200 g, purchased from the animal room of Fudan University School of Medicine;

[0075] 1.3 Experimental method: After SD rats were intraperitoneally anesthetized with chloral hydrate, the nCAs aqueous solution and clinical iohexol solution (both 52 mg / mL, 260 mg / kg) prepared in Example 1 were catheterized through the rat femoral vein Inject boluses into normal rats, perform CTA imaging, and observe the changes in the CT values ​​of the heart, liver, spleen, kidney, and bladder at different time points; in addition, to prepare a stroke model in the left m...

Embodiment 3

[0081] Toxicity evaluation experiment

[0082] 1. In vitro cytotoxicity test

[0083] 1.1 Experimental materials:

[0084] The nCAs hydrophilic nanoparticles prepared in Example 1;

[0085] 1.2 Experimental method:

[0086]MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazoliumbromide) method was used to evaluate cell viability, and the specific experimental methods were: (1) inoculated cells: cultured with 10% fetal calf serum solution to make a single cell suspension, 10 per well 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 with cells for 24 and 48 hours, add MTT solution (5mg / ml, prepared with PBS, pH = 7.4) 50 microliters, 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. (3) Quantification: add 150 ...

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Abstract

The invention relates to a novel CT contrast medium and a preparation method and application thereof. The CT contrast medium is phospholipids PEG-modified BaHoF5 particles. The CT contrast medium disclosed by the invention contains elements Ba and Ho, and the advantages of the two elements are combined. Compared with the existing iodine-based contrast medium, the novel CT contrast medium has the advantages of excellent contrast effect, small use amount and low kidney toxicity; furthermore, by use of the hydrophilic modification of phospholipids PEG for the BaHoF5 particles, the biocompatibility of the contrast medium is improved, the toxic and side effect is reduced, and the blood circulating performance is promoted.

Description

technical field [0001] The invention belongs to the technical field of medical contrast agents, and in particular relates to a novel CT contrast agent and its preparation method and application. Background technique [0002] CT imaging, that is, X-ray computed tomography, has good density resolution and spatial resolution, and has been used on a large scale in clinical practice. However, the low soft tissue resolution of CT limits its further clinical application. In view of this, researchers have developed a variety of CT contrast agents to improve the contrast effect of imaging and obtain detailed information on the lesion site. The CT contrast agent currently used clinically is an iodine-based material. Due to the low X-ray attenuation coefficient of iodine, a large dose of contrast agent must be used in order to achieve a satisfactory enhancement effect clinically, and a large amount of contrast agent is necessary for heart disease patients. Undoubtedly, it will overlo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/04A61K9/14A61K47/48
Inventor 王静倪大龙步文博姚振威
Owner SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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