Preparation method of kidney-removing ultra-small double-targeted bimodal magnetic resonance contrast agent

A magnetic resonance contrast agent and ultra-small pair technology, applied in the fields of biomedicine, nanomaterials and bioengineering, can solve problems such as difficult to distinguish internal bleeding and inaccurate patient diagnosis

Inactive Publication Date: 2019-03-08
NANJING UNIV
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Problems solved by technology

But radiologists strongly prefer T 1 contrast agent, because T 2 Imaging of contrast agents appears as dark areas, which makes it difficult to distinguish internal hemorrhages, air-tissue boundaries, or other artifacts, resulting in less accurate diagno

Method used

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Embodiment 1

[0023] (1) Preparation of succinyl ultra-low-molecular-weight heparin: 5.0 g of low-molecular-weight heparin sodium was dissolved in 75 mL of acetic acid solution, and 15 mL of sodium nitrite solution was added to the solution, and the reaction was carried out at room temperature for 3 hours. The pH value of the solution was adjusted to 7.0, and the solution was freeze-dried to obtain 3.0 g of ultra-low molecular weight heparin sodium. Dissolve 3.0 g of ultra-low molecular weight heparin sodium in 10 mL of water, and permeate the solution through a 200 mL acidified gel column, then adjust the pH of the solution to 7.0 with tri-n-butylamine solution, and freeze-dry the solution to obtain 4.0 gUltra-low molecular weight heparin tributylammonium salt. Dissolve 4.0g of ultra-low molecular weight heparin tributylammonium salt in 400mL of dry solvent DMF, under the protection of nitrogen, add 30.8g of succinic anhydride and 5.0g of DMAP to the reaction solution in sequence, and the ...

Embodiment 2

[0028] (1) with embodiment 1;

[0029] (2) Preparation of ultra-small water-soluble superparamagnetic iron ferric oxide nanoparticles: 300.0 mg of the ultra-low molecular weight succinoheparan tributylammonium salt prepared in step (1) was dissolved in 5.0 mL of deionized water and waited until it was completely Dissolve, add 0.05mg FeCl to the solution at one time 3 ·6H 2 O and 0.01 mg FeCl 2 4H 2 O, and NH under the protection of nitrogen 3 ·H 2 O was added to the solution until the pH of the solution was 11.0, the temperature of the solution was raised to 80°C, and after stirring at this temperature for 40 min, the solution was dialyzed in an aqueous solution of pH=4.0 for 4 days with a dialysis bag with a molecular weight of 2000. Finally, the ultra-small water-soluble superparamagnetic ferric oxide nanoparticles are kept in deionized water for use.

[0030] (3) with embodiment 1;

[0031] (4) Preparation of dual-targeted ultra-small water-soluble superparamagnetic ...

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Abstract

The invention discloses a preparation method of a kidney-removing ultra-small double-targeted bimodal magnetic resonance contrast agent and belongs to the technical field of nano materials and bioengineering. The method comprises the following step: by adopting an improved co-precipitating method, preparing succinyl ultralow molecular weight heparin coated water soluble ultra-small ferroferric oxide nanoparticles under the nitrogen protection, wherein the average grain size of the obtained nanoparticle nucleus is 2 nm, and the thickness of a polymer coating is 1.0-2 nm. A lot of carboxyl on succinyl ultralow molecular weight heparin not only can enable ferric oxide nanoparticles to be dispersed in deionized water stably, but also can be combined with targeted molecules, so that the material is endowed with magnetic property and folic acid double targeted function. The synthesized magnetic and folic acid double targeted compound magnetic nanoparticles are uniform in shape, high in dispersibility, high in biocompatibility, high in T1 relaxation rate and short in half life in blood of a mouse body, and is substantially and fully removed out of the body within 48 hours. Precise targeted tumor T1 and T2 magnetic resonance imaging is achieved without affecting the normal physiological activity of the mouse. As the magnetic resonance contrast agent, the ultra-small double-targeted bimodal magnetic nanoparticles prepared by the method have a wide application prospect in the biomedical fields of magnetic resonance imaging, early diagnosis of cancers, image tracking therapeutic effect evaluation and the like.

Description

technical field [0001] The invention belongs to the technical field of nanomaterials and bioengineering, in particular to a preparation method of an ultra-small dual-target dual-mode magnetic resonance contrast agent, and belongs to the field of biomedicine. Background technique [0002] Magnetic resonance imaging (MRI) has been intensively studied as an effective imaging tool in medical research and clinical diagnosis. MRI can effectively detect tissue necrosis, ischemia, and various malignant lesions (such as tumors), and can perform early diagnosis and monitor organ transplantation. However, there is only a small difference in relaxation time between normal tissue and diseased tissue, which will reduce the specificity and sensitivity of diagnosis. Diagnosis based solely on images may not be able to obtain accurate results. Therefore, about 30% of clinical scanning imaging uses contrast imaging. agent to enhance the contrast of the image. MRI contrast agents are mainly d...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/12A61K9/51A61K47/36
CPCA61K49/126A61K49/1863
Inventor 王毅庆谢曼曼卢乾张旭东王子阳
Owner NANJING UNIV
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