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Magnetic resonance contrast agent based on hyaluronic acid as well as preparation method and application of magnetic resonance contrast agent

A technology of hyaluronic acid and sodium hyaluronate, applied in the field of medical imaging, can solve the problems of further improvement of safety and use effect, achieve excellent fibrotic tissue targeting ability, and achieve the effect of accurate staging

Active Publication Date: 2022-07-29
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its safety and effectiveness still need to be further improved

Method used

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  • Magnetic resonance contrast agent based on hyaluronic acid as well as preparation method and application of magnetic resonance contrast agent
  • Magnetic resonance contrast agent based on hyaluronic acid as well as preparation method and application of magnetic resonance contrast agent
  • Magnetic resonance contrast agent based on hyaluronic acid as well as preparation method and application of magnetic resonance contrast agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0111] Embodiment 1, targeting molecule mal-ONH 2 Synthesis

[0112] Targeting molecule mal-ONH 2 The synthetic route is as follows:

[0113]

[0114] 1. Preparation of mal-ONHBoc

[0115] N-(2-Aminoethyl)maleimide trifluoroacetic acid (284 mg, 1.2 mmol), [(tert-butoxycarbonyl)aminooxy]acetic acid (191 mg, 1 mmol), HBTU (569 mg, 1.5 mmol) and HOBT (203 mg, 1.5 mmol) were placed in a reaction flask, and N 2 Protect. 2 mL of N,N-dimethylformamide (DMF) was then added under an ice bath, followed by 0.69 mL of DIEA. The reaction solution was stirred at room temperature for 2 hours, then 50 mL of CH 2 Cl 2 Diluted with water, then saturated NaHCO 3 solution, 1M HCl solution was washed. CH 2 Cl 2 solution with anhydrous Na 2 SO 4 dried and concentrated. The final product was purified by column chromatography (eluent was CH 2 Cl 2 / CH 3 OH, the volume ratio is 10 / 1) to obtain 170 mg of white solid with a yield of 54%. mal-ONHBoc in CDCl 3 middle 1 H NMR ( figu...

Embodiment 2

[0118] Example 2. Synthesis of magnetic resonance contrast agent HA-Target-Cy5.5-DOTA-Gd (HTCDGd) of the present invention

[0119] The synthetic route of HA-Target-Cy5.5-DOTA-Gd(HTCDGd) is as follows:

[0120]

[0121] in,

[0122] n is an integer from 0 to 50;

[0123] m is an integer from 0 to 18;

[0124] o is an integer from 0 to 3;

[0125] p is an integer from 0 to 10;

[0126] n≥m;

[0127] m≥o+p.

[0128] 1. Preparation of HA-SSPy

[0129] HA.Na 20K (2.4 g) was dissolved in 240 mL MES buffer (100 mM, pH 5.5) to give a 1% w / v solution, DMTMM (2.5 g, 1.5 equiv.) was added and stirred for 30 min to activate the carboxyl. 2-(Pyridin-2-yldisulfanyl)ethylamine hydrochloride (2.1 g, 1.5 equiv.) was then dissolved in MES buffer and added dropwise to the reaction solution. The reaction mixture was stirred at 25°C for 24 hours and then washed with reverse osmosis (RO)H 2 O was dialyzed (3.5 kDa MWCO) for 48 hours and lyophilized to obtain HA-SSPy as a white spongy ...

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Abstract

The invention provides a magnetic resonance contrast agent based on hyaluronic acid as well as a preparation method and application thereof, and belongs to the technical field of medical imaging. The magnetic resonance contrast agent is a hyaluronic acid-based polymer, and the structure of the polymer is shown as a formula (I). The relaxation rate of the liver fibrosis specific MRI imaging contrast agent HTCDGd is three times that of clinical small molecule DTPA-Gd. Pharmacokinetic analysis, MRI and fluorescence imaging confirm that HTCDGd circulates in vivo for a long time and accumulates effectively in the liver. For the diagnosis of hepatic fibrosis, HTCDGd shows excellent fibrosis tissue targeting ability, through MRI enhancement, not only are differences of different degrees of hepatic fibrosis tissue enhancement degrees and longer imaging window observation periods provided, but also morphological characteristics of different degrees of hepatic fibrosis can be directly displayed, and early diagnosis and accurate staging of hepatic fibrosis are realized. The results show that as a non-invasive detection method, HTCDGd has huge potential in the aspect of detecting and accurately monitoring hepatic fibrosis change.

Description

technical field [0001] The invention belongs to the technical field of medical imaging, and in particular relates to a hyaluronic acid-based magnetic resonance contrast agent and a preparation method and application thereof. Background technique [0002] Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are both chronic liver diseases (CLD). The incidence of CLD in developed and developing countries is increasing year by year, and the health problems of nearly 1 billion adults worldwide are affected by the disease. The vast majority of CLDs, including viruses, autoimmunity, alcohol, and metabolic abnormalities, can cause varying degrees of liver fibrosis and chronic liver damage. Long-term, persistent liver damage and untreated liver fibrosis lead to cirrhosis and a higher risk of developing liver failure or hepatocellular carcinoma. In previous studies, the early stage of liver fibrosis is reversible, and timely detection and treatment of early s...

Claims

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Application Information

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IPC IPC(8): C08B37/08A61K49/12
CPCC08B37/003A61K49/126
Inventor 罗奎王小铭张孝琴
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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