Hyaluronic acid-stabilized high relaxivity gadolinium oxide magnetic resonance nanoprobes

A technology of hyaluronic acid and nanoprobes, which can be applied in preparations for in vivo experiments and pharmaceutical formulations, can solve the problems that gadolinium-based contrast agents cannot meet special imaging requirements, reduce immune reactions in vivo, and make preparation conditions simple , reducing the effect of the immune response

Inactive Publication Date: 2018-02-09
TIANJIN MEDICAL UNIV
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Problems solved by technology

[0005] The purpose of the invention is in order to solve the clinically widely used low T 1 The gadolinium-based contrast agent with relaxation efficiency cannot meet the special imaging requirements at high magnetic field strength 3T, and the development of gadolinium-based T 1 Magnetic resonance molecular probe, providing a preparation method of gadolinium oxide magnetic resonance imaging nanoprobe with high relaxation rate and good biocompatibility

Method used

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  • Hyaluronic acid-stabilized high relaxivity gadolinium oxide magnetic resonance nanoprobes
  • Hyaluronic acid-stabilized high relaxivity gadolinium oxide magnetic resonance nanoprobes
  • Hyaluronic acid-stabilized high relaxivity gadolinium oxide magnetic resonance nanoprobes

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Effect test

Embodiment 1

[0020] 1) In a beaker, dissolve 0.2g of enzymatically cleaved hyaluronic acid sodium salt with a molecular weight of 5000 in 10ml of water, and stir until completely dissolved. Add 1mL of 0.1M Gd(NO 3 ) 3 ·6H 2 O aqueous solution, in which hyaluronic acid sodium salt and Gd(NO 3 ) 3 ·6H 2 The mass ratio of O was 40:9. After 5 min, NaOH aqueous solution was added to adjust the pH to 10. After continuing to stir at room temperature for 1 h, a colorless liquid was obtained;

[0021] 2) Put the obtained hyaluronic acid gadolinium oxide nanomaterial into a dialysis bag (molecular weight cut-off is 8000-14000Da), and purify. The dialysis time is 24 hours, and the water is changed every 4 hours. After dialysis, a total volume of 50 mL of purified nanoprobe solution was obtained;

[0022] 3) Obtain a flocculent white solid product by freeze-drying, which is a gadolinium oxide magnetic resonance nanoprobe;

[0023] Get 20mg of the magnetic resonance imaging probe solid prepared...

Embodiment 2

[0025] A method for preparing a gadolinium oxide magnetic resonance imaging nanoprobe with good biocompatibility, the steps and methods are basically the same as in Example 1, except that the sodium hyaluronic acid and Gd(NO 3 ) 3 ·6H 2 O mass ratio is 200:9.

[0026] Get 20mg of the magnetic resonance imaging probe solid prepared by this embodiment and carry out high power transmission electron microscope characterization, T 1 Relaxation rate and T 1 Weighted imaging and in vitro cytotoxicity test MTT, the test results are similar to Example 1.

Embodiment 3

[0028] A method for preparing a gadolinium oxide magnetic resonance imaging nanoprobe with good biocompatibility, the steps and methods are basically the same as in Example 1, except that the sodium hyaluronic acid and Gd(NO 3 ) 3 ·6H 2 The O mass ratio is 80:9.

[0029]Get 20mg of the magnetic resonance imaging probe solid prepared by this embodiment and carry out high power transmission electron microscope characterization, T 1 Relaxation rate and T 1 Weighted imaging and in vitro cytotoxicity test MTT, the test results are similar to Example 1.

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Abstract

The preparation method of hyaluronic acid-stabilized high-relaxation gadolinium oxide magnetic resonance nanoprobes, the steps are as follows: 1) in a beaker, dissolve hyaluronic acid in water and stir until completely dissolved; add Gd(NO3) to the above solution 3.6H2O aqueous solution, after stirring evenly, after adding NaOH aqueous solution, adjust to pH = 10, and continue to stir at room temperature for 1 hour to obtain a colorless liquid; 2) Purify the obtained impurity-containing gadolinium oxide nanoprobe, and the dialysis time is 24 hours, The water was changed every 4 hours; the purified nanoprobe was obtained after dialysis; 3) the flocculent white solid product was obtained by freeze-drying. The probe has a simple preparation method, simple preparation conditions, green raw materials, good water solubility, high T1 relaxation rate and low potential biological toxicity, and is convenient for large-scale production. It has great development potential and application value in the field of medical imaging.

Description

technical field [0001] The invention relates to the field of preparation of magnetic resonance imaging probes, in particular to a preparation method of high-relaxation gadolinium oxide magnetic resonance imaging nano-probes with good biocompatibility. Background technique [0002] Compared with other imaging methods such as optical imaging, X-ray imaging, computed tomography (CT) and positron emission computed tomography (PET-CT), magnetic resonance imaging (MRI) has no radiation damage and high spatial Features such as resolution play an extremely important role in the clinical diagnosis of various diseases. When imaging some lesions with low tissue resolution, in order to improve the sensitivity and accuracy of diagnosis, it is necessary to use contrast agent to assist imaging. Magnetic resonance contrast agents can be divided into positive contrast agents (such as gadolinium and manganese complexes or nanomaterials) and negative contrast agents (such as superparamagnetic...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/14A61K49/12
Inventor 于春水王浩宇孙少凯
Owner TIANJIN MEDICAL UNIV
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