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A kind of osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and preparation method thereof

A magnetic resonance imaging, osteoarthritis technology, applied in pharmaceutical formulations, preparations for in vivo experiments, drug delivery, etc., to achieve cartilage-specific targeting and MRI imaging, good in vitro chondrocyte targeting ability, improve biological Compatibility effect

Inactive Publication Date: 2020-03-31
THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The main purpose of the present invention is to provide a gadolinium-based magnetic resonance imaging contrast agent targeting osteoarthritis cartilage and its preparation method, to at least solve the problem that the existing gadolinium-based magnetic resonance imaging contrast agent cannot perform specific and efficient MRI on osteoarthritis cartilage imaging problem

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  • A kind of osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and preparation method thereof
  • A kind of osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and preparation method thereof
  • A kind of osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and preparation method thereof

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preparation example Construction

[0041] In another typical embodiment of the present invention, a method for preparing the aforementioned cartilage-targeted gadolinium-based magnetic resonance imaging contrast agent for osteoarthritis is provided, the preparation method comprising the following steps:

[0042] (1) Gd 2 (CO 3 ) 3 Nanoparticles were dispersed in Tris-HCl buffer solution, dropped into dopamine solution, stirred, and then centrifuged to obtain Gd coated with dopamine shell on the surface 2 (CO 3 ) 3 Nanoparticles, i.e. Gd 2 (CO 3 ) 3 @PDA nanoparticles;

[0043] (2) with step (1) gained Gd 2 (CO 3 ) 3 @PDA nanoparticles dispersed in deionized water, adding NH 2 -mPEG-SH, stirred, and then centrifuged to obtain Gd modified with polyethylene glycol on the surface of the dopamine shell 2 (CO 3 ) 3 Nanoparticles, i.e. Gd 2 (CO 3 ) 3 @PDA-PEG nanoparticles;

[0044] (3) The cartilage-targeting polypeptide whose amino acid sequence is DWRVIIPPRPSA is connected to the Gd obtained in st...

Embodiment 1

[0051] A method for preparing a cartilage-targeted gadolinium-based magnetic resonance imaging contrast agent for osteoarthritis according to an embodiment of the present invention, comprising the following steps:

[0052] (1) Synthesis of Gd 2 (CO 3 ) 3 nanoparticles

[0053] 0.5mM GdCl 3 ·6H 2 O and 2.7g of urea were dissolved in 35mL of deionized water, stirred and reacted at 80°C; during the reaction, the color of the system changed from colorless to milk-like color; min, separated to get Gd 2 (CO 3 ) 3 nanoparticles;

[0054] (2) Synthesis of Gd 2 (CO 3 ) 3 @PDA nanoparticles

[0055] The 2mg / mL Gd obtained by synthesis of the above step (1) 2 (CO 3 ) 3Nanoparticles were dispersed in 30mL of 10mM Tris-HCl (pH=8.5), and 5mL of dopamine solution (2mg / mL) was dripped clockwise, and the system was stirred overnight to obtain a black solution; Gd was separated by high-speed centrifugation (10000rpm) for 10 minutes. 2 (CO 3 ) 3 @PDA nanoparticles;

[0056] (3...

Embodiment 2

[0074] A method for preparing a cartilage-targeted gadolinium-based magnetic resonance imaging contrast agent for osteoarthritis according to an embodiment of the present invention, comprising the following steps:

[0075] (1) Synthesis of Gd 2 (CO 3 ) 3 nanoparticles

[0076] 0.5mM GdCl 3 ·6H 2 O and 2.7g of urea were dissolved in 35mL of deionized water, stirred and reacted at 80°C; during the reaction, the color of the system changed from colorless to milk-like color; after 2 hours of reaction, the milk-like nanoparticles were centrifuged at a high speed (12000rpm) for 10 min, separated to get Gd 2 (CO 3 ) 3 nanoparticles;

[0077] (2) Synthesis of Gd 2 (CO 3 ) 3 @PDA nanoparticles

[0078] The 2mg / mL Gd obtained by synthesis of the above step (1) 2 (CO 3 ) 3 Nanoparticles were dispersed in 30mL of 10mM Tris-HCl (pH=8.5), and 5mL of dopamine solution (2mg / mL) was dripped clockwise, and the system was stirred overnight to obtain a black solution; Gd was separa...

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Abstract

The invention discloses an osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and a preparation method thereof. The contrast agent comprises Gd2CO3 nanoparticles. The surface of the Gd2CO3 nanoparticles is coated with a dopamine shell, and the surface of the dopamine shell is loaded with cartilage targeting polypeptide through end-modified polyethylene glycol, and the amino acid sequence of the cartilage targeting polypeptide is DWRVIIPPRPSA. The osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent achieves osteoarthritis cartilage specific targeting and MRI imaging. According to test verification, the agent shows good T1-MRI imaging capability, good in vitro chondrocyte targeting capability and effective cartilage targeting capability in mice.

Description

technical field [0001] The invention relates to the technical field of contrast agents, in particular to an osteoarthritis cartilage targeting gadolinium-based magnetic resonance imaging contrast agent and a preparation method thereof. Background technique [0002] Osteoarthritis is a common chronic joint degenerative disease, mainly characterized by irreversible degeneration of cartilage, which seriously affects the quality of life and survival of patients. Therefore, how to effectively delay or even block cartilage degeneration is a major issue that needs to be solved urgently in the fields of contemporary medicine, chemistry and medicine. With the deepening of people's understanding of cartilage changes in osteoarthritis, the treatment effect of many osteoarthritis has been significantly improved, but limited by the existence of natural barrier tissues such as joint synovium, the local treatment effect of cartilage is not good. At the same time, since cartilage itself is...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/14A61K49/12
CPCA61K49/126A61K49/14A61K49/186A61K49/1866
Inventor 欧阳正晓张庆郭晓柠
Owner THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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