Gadolinium-containing macromolecular contrast agent and preparation method thereof

A technology of contrast agents and macromolecules, applied in the field of nuclear magnetic resonance targeted contrast agents and their preparation, can solve the problems of inability to target and locate contrast imaging, and achieve the effect of improving sensitivity and specificity

Inactive Publication Date: 2013-03-13
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] One of the objectives of the present invention is to provide a gadolinium-containing macromolecular contrast agent for targeted imaging of lymphatic system and tumor cells in view of the deficiency that existing gadolinium-containing magnetic resonance contrast agents cannot perform targeted positioning imaging. The contrast agent is chelated with gadolinium through the diethylenetriaminepentaacetic acid-hyaluronic acid complex to form a gadolinium-diethylenetriaminepentaacetic acid-hyaluronic acid macromolecular complex with targeting properties, so that it can actively orientate into the lymph system and tumor cells

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  • Gadolinium-containing macromolecular contrast agent and preparation method thereof
  • Gadolinium-containing macromolecular contrast agent and preparation method thereof
  • Gadolinium-containing macromolecular contrast agent and preparation method thereof

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Embodiment 1

[0027] A. Fully dissolve hyaluronic acid HA with a molecular weight of 6,800 in MES buffer solution to prepare 50 mL of a solution with a hyaluronic acid concentration of 0.5 g / L. Slowly add the condensing agent under stirring condition: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 200mg, N-hydroxysuccinimide (NHS) 300mg, react 15min, adjust the pH to 7 with PBS, add ethylenediamine, react for 24h, put the reaction solution into the dialysis bag, dialyze in deionized water for 8 days, then freeze-dry to obtain product A, and then dissolve the obtained product in 50mL MES buffer solution to obtain solution A,

[0028] B. Dissolve diethylenetriaminepentaacetic acid in MES buffer solution, prepare 50mL of a solution with a concentration of 0.5g / L, slowly add the condensing agent 1-(3-dimethylaminopropyl)-3-ethyl under stirring condition Carbodiimide hydrochloride 200mg, N-hydroxysuccinimide 300mg, react for 15min, adjust pH7 with PBS, add A solution, react...

Embodiment 2

[0031] A. Fully dissolve hyaluronic acid HA with a molecular weight of 10,000 in MES buffer solution to prepare 50 mL of a solution with a hyaluronic acid concentration of 0.5 g / L. Slowly add the condensing agent under stirring condition: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 200mg, N-hydroxysuccinimide (NHS) 300mg, react 15min, adjust the pH to 7 with PBS, add ethylenediamine, react for 24h, put the reaction solution into the dialysis bag, dialyze in deionized water for 8 days, then freeze-dry to obtain product A, and then dissolve the obtained product in 50mL MES buffer solution to obtain solution A,

[0032] B. Dissolve diethylenetriaminepentaacetic acid in MES buffer solution, prepare 50mL of a solution with a concentration of 0.5g / L, slowly add the condensing agent 1-(3-dimethylaminopropyl)-3-ethyl under stirring condition Carbodiimide hydrochloride 200mg, N-hydroxysuccinimide 300mg, react for 15min, adjust pH7 with PBS, add A solution, reac...

Embodiment 3

[0035]A. Fully dissolve hyaluronic acid HA with a molecular weight of 50,000 in MES buffer solution to prepare 50 mL of a solution with a hyaluronic acid concentration of 0.5 g / L. Slowly add the condensing agent under stirring condition: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) 200mg, N-hydroxysuccinimide (NHS) 300mg, react 15min, adjust the pH to 7 with PBS, add ethylenediamine, react for 24h, put the reaction solution into the dialysis bag, dialyze in deionized water for 8 days, then freeze-dry to obtain product A, and then dissolve the obtained product in 50mL MES buffer solution to obtain solution A,

[0036] B. Dissolve diethylenetriaminepentaacetic acid in MES buffer solution, prepare 50mL of a solution with a concentration of 0.5g / L, slowly add the condensing agent 1-(3-dimethylaminopropyl)-3-ethyl under stirring condition Carbodiimide hydrochloride 200mg, N-hydroxysuccinimide 300mg, react for 15min, adjust pH7 with PBS, add A solution, react...

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Abstract

The invention relates to a gadolinium-containing macromolecular contrast agent and a preparation method thereof. The structural formula of the contrast agent is shown as the specification and n is 16-185. The contrast agent can initiatively enter a lymph system and a tumor cell; and the contrast agent is initiatively absorbed by the lymph system and the tumor cell so that the sensitivity and the specificity of qualitative diagnosis of the lymph system and the tumor cell are improved.

Description

technical field [0001] The invention relates to a nuclear magnetic resonance targeting contrast agent and a preparation method thereof, in particular to a gadolinium-containing macromolecule contrast agent with high nuclear magnetic resonance signal intensity and a preparation method thereof. Background technique [0002] In recent years, the incidence of cancer has shown an obvious upward trend, and the main biological characteristics of cancer are invasion and metastasis. Tumor metastasis is mainly achieved through blood vessels and lymphatic vessels, and lymphatic vessels are the main channels for its metastasis. Once the tumor metastasizes, it will bring great difficulties to the treatment, so it is of great significance to the diagnosis of lymphatic diseases and tumors. [0003] Magnetic resonance imaging (MRI) is a non-invasive imaging diagnostic method. The MRI contrast agents currently studied mainly include two categories, one is superparamagnetic iron oxide and it...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12C08B37/08
Inventor 张华娟路青朱君姚远闫志强金彩虹何丹农许建荣
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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