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Cholesterol derivatives, chelates, recombinant high-density lipoproteins and uses thereof

A technology of high-density lipoprotein and cholesterol derivatives, applied in steroids, organic chemistry, nuclear magnetic resonance/magnetic resonance imaging contrast agents, etc., to reduce the dosage and enhance the effect of magnetic resonance imaging

Active Publication Date: 2016-01-13
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

And there are no literature and patent reports on the use of cholesterol linked to paramagnetic ion chelates and then assembled into high-density lipoprotein for magnetic resonance imaging, especially for magnetic resonance imaging of the liver, gallbladder and duodenum

Method used

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  • Cholesterol derivatives, chelates, recombinant high-density lipoproteins and uses thereof
  • Cholesterol derivatives, chelates, recombinant high-density lipoproteins and uses thereof
  • Cholesterol derivatives, chelates, recombinant high-density lipoproteins and uses thereof

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Embodiment 1

[0050] Embodiment 1, the preparation of cholesterol derivative and chelate thereof

[0051] 1.1. Preparation of Cholesterol Derivatives

[0052] 1.1.1. Preparation of Cholesterol Derivatives I

[0053] Such as figure 1 As indicated, dissolve 500mmol of ethylenediamine in 100ml of anhydrous dichloromethane and add it to a dried 100ml three-necked flask, and at the same time add 10mmol of N,N-diisopropylethylamine, and stir to mix. Dissolve 5 mmol of cholesterol chloroformate in 20 ml of anhydrous dichloromethane, and slowly add it dropwise to the solution of ethylenediamine under an ice-water bath for half an hour, and the temperature of the reaction system rises to room temperature. Nitrogen was passed into the three-necked flask, and the reaction system was sealed and stirred at room temperature for 2 days. After the reaction, the reaction solvent was added to a 250ml eggplant-shaped flask, and the methylene chloride was removed using a vacuum pump to a minimum volume. I...

Embodiment 2

[0081] Embodiment 2, preparation of contrast agent

[0082] The gadolinium chelate Gd-DTPA-chol of the monocholesterol derivative in cholesterol derivatives Ⅰ was assembled into high-density lipoprotein using sodium cholate surfactant method to obtain recombinant high-density lipoprotein Gd-chol-HDL (used as contrast agent). The molar ratio of each component of high-density lipoprotein is: Gd-DTPA-chol: DMPC: sodium cholate=1:1:2 (mol / mol); Described high-density lipoprotein and chelate are mixed, at room temperature After incubation, sodium cholate was removed by dialysis to obtain recombinant high-density lipoprotein. Specifically: weigh Gd-DTPA-chol (5 mg, 5 μmol), DMPC (3.4 mg, 5 μmol), dissolve them in a mixed solvent of chloroform / methanol (3 / 1, v / v), dry the chloroform with nitrogen, and vacuum Remove the residual solvent in a drying oven, add 4.30 mg of sodium cholate, dissolve it with 1 ml of TBS buffer, and sonicate for 30 minutes to dissolve it. According to ap...

Embodiment 3

[0092] Embodiment 3, particle size and longitudinal relaxation efficiency measurement

[0093] The formulation of recombinant HDL can affect its properties. According to the method in Example 2, the gadolinium chelate Gd-DTPA-(chol) of the double cholesterol derivative in the cholesterol derivative II 2 To produce recombinant high-density lipoprotein, different lipid formulations were used to measure the particle size and longitudinal relaxation efficiency of recombinant high-density lipoprotein after production. Particle size was determined using dynamic light scattering and results are shown as particle size under intensity results. Table 2 below shows that when the molar ratio of DMPC: chelate increases, the particle size of the recombinant HDL increases proportionally, but the longitudinal relaxation efficiency decreases inversely.

[0094] Table 2

[0095]

[0096] In summary, the present invention connects cholesterol to the nitrogen-containing multi-carboxylate ...

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Abstract

The invention discloses a cholesterol derivative, chelate, recombinant high density lipoprotein and application thereof. According to the invention, a derivative ligand containing one or two cholesterol is obtained by connecting cholesterol to a nitrogen-containing polycarboxylic ligand; the cholesterol derivative chelates with metal ion to obtain the corresponding chelate; recombinant high density lipoprotein is prepared by assembling the chelate in high density lipoprotein; and the recombinant high density lipoprotein can be used as a contrast agent. The particle size, morphology and biological activity of the contrast agent is similar to those of the high density lipoprotein in the human body and the relaxation efficiency is higher than that of commercial contrast agent magnevist (Gd-DTPA). The liver specific contrast can be achieved by the active targeting of the high density lipoprotein, and magnetic resonance imaging of bile duct and duodenum can be realized in the metabolic process of the cholesterol in liver.

Description

technical field [0001] The invention relates to a paramagnetic magnetic resonance contrast agent for liver functional diagnosis, in particular to a cholesterol derivative, a chelate, a recombinant high-density lipoprotein and the use thereof as a contrast agent. Background technique [0002] As a non-destructive and non-invasive method with flexible imaging orientation and high spatial resolution, magnetic resonance imaging is widely used in clinical diagnosis. With the application of new contrast agents, magnetic resonance imaging technology has been widely used in liver imaging and cholangiopancreatic imaging. Liver magnetic resonance imaging can be used to diagnose hemangiomas, focal nodular hyperplasia, and cysts without the need for biopsy, surgery, or follow-up examinations. In addition, liver magnetic resonance imaging can be used to check liver cirrhosis, sebaceous gland disease, or hepatic hemochromatosis, etc. It can check liver cancer or hepatic duct cancer in pa...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J41/00C08G65/48A61K49/06A61K49/14
Inventor 徐宇虹芮蒙杰
Owner SHANGHAI JIAO TONG UNIV
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