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Targeted nano magnetic resonance contrast agent for articular cartilage injury as well as preparation and application of targeted nano magnetic resonance contrast agent

A magnetic resonance contrast agent and articular cartilage technology, applied in the field of molecular imaging, can solve the problems of interfering with the imaging effect of the articular cartilage defect area, the delayed enhancement is not obvious, the relaxation rate of Gd agent is low, etc., so as to prevent joint effusion. The effect of preventing interference, ensuring MRI signal strength, improving efficiency and safety

Inactive Publication Date: 2021-09-28
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This type of contrast agent is easy to mix with the surrounding joint effusion through free diffusion into the joint cavity. The clinical Gd agent has a low relaxation rate and poor cartilage permeability, which not only interferes with the imaging effect of the articular cartilage defect area, but also delays the degree of enhancement. less obvious

Method used

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  • Targeted nano magnetic resonance contrast agent for articular cartilage injury as well as preparation and application of targeted nano magnetic resonance contrast agent
  • Targeted nano magnetic resonance contrast agent for articular cartilage injury as well as preparation and application of targeted nano magnetic resonance contrast agent
  • Targeted nano magnetic resonance contrast agent for articular cartilage injury as well as preparation and application of targeted nano magnetic resonance contrast agent

Examples

Experimental program
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Effect test

Embodiment 1

[0045] Example 1: Preparation and physical and chemical characterization of targeted nano-magnetic resonance contrast agent

[0046] a. Take 200mg of hyaluronic acid HA (0.5mM) with a molecular weight of 990,000Da and fully dissolve it in a 50ml test tube, add 20mL of double distilled water, stir at room temperature for 1h until clear and transparent, add 1% (2-3mg) 5 carboxyfluorescein ( 5-FAM SE) was stirred for 1-2h; 90mg of diethylenetriaminepentaacetic dianhydride (0.25mM) was added to 600μL dimethyl sulfoxide to dissolve, and stirred at room temperature for 2-3h; Gadolinium (0.25mM), stirred for 0.5h, put the reaction solution into a dialysis bag with a molecular weight cut-off of 30,000, dialyzed in double distilled water for 24h-48h, pay attention to protect it with tinfoil paper, and finally prepare a solution of 14.26mmol / L A: The mass ratios of diethylenetriaminepentaacetic dianhydride, hyaluronic acid, gadolinium chloride hexahydrate and 5-carboxyfluorescein are 1:...

Embodiment 2

[0050] Example 2: Study on in vitro relaxation rate of targeted nano-magnetic resonance contrast agent

[0051] Take an appropriate amount of nano-magnetic resonance contrast agent solution samples, prepare different concentrations of HA-DTPA-Gd NPs solutions with double-distilled water, Gd(III) concentration 0.0005–0.06mM, and place them in 2ml centrifuge tubes. Then prepare DTPA-Gd with corresponding gadolinium concentration as a control. The tubes are placed sequentially in plastic test tube racks and placed in boxes filled with water. The clinical 3.0T MRsystem (Discovery MR750, GE Medical System, USA) and supporting animal coils were used for T1 Map sequence scanning to evaluate the effect of negative reinforcement. The T1 Map was post-processed with GE Function Tool 4.6 special software.

[0052] Susceptibility such as image 3 As shown in a, compared with the control group, with the gradual increase of gadolinium ion concentration, T1 gradually increased. After meas...

Embodiment 3

[0053] Example 3: Research on the change of signal-to-noise ratio of targeted nano-magnetic resonance contrast agent in vivo.

[0054] Gd-HA-NPs, Gd-DTPA-HA and Gd-DTPA were injected into rabbit knee articular cartilage injury model respectively. After injection, the knee joint was imaged with a Siemens Verio 3T magnetic resonance imaging system equipped with a rabbit knee coil.

[0055] Such as Figure 4 Articular cartilage (red dotted line) and damaged area (blue dotted line) were not clearly visible in the two groups before contrast agent injection in a and b. One hour after the intra-articular injection of Gd-DTPA, the signal intensity of the entire joint cavity increased, but the image of the lesion was only slightly enhanced, and the outline of the cartilage was still unclear. At 2h and 3h after injection, the signal intensities of cartilage and lesion remained very close. One hour after injection, the signal intensity of cartilage and injury sites in Gd-DTPA-HA group...

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Abstract

The invention belongs to the technical field of molecular imaging, and relates to a targeted nano magnetic resonance contrast agent for articular cartilage injury as well as preparation and application of the targeted nano magnetic resonance contrast agent. The structure of the contrast agent is HA-DTPA-Gd, hyaluronic acid HA and gadolinium ions Gd (III) are linked through diethylenetriamine pentaacetic acid DTPA, and the molecular structural formula of the contrast agent is shown in the formula (I). The contrast agent can be injected through an articular cavity, the size of the contrast agent is nanoscale, nanoparticles are combined with an extracellular matrix of a cartilage defect area based on the surface effect of the nanoparticles, specific aggregation in the cartilage injury area is easier, the enhancement degree of a focus area after MRIT1 weighted delay enhancement is more obvious than that of a clinical gadolinium-containing contrast agent, and therefore the cartilage injury focus can be accurately and visually displayed; improvement of accuracy and safety of clinical treatment is facilitated, the curative effect of a knee joint cartilage injury treatment mode is evaluated, and prognosis of a patient is evaluated.

Description

technical field [0001] The invention belongs to the technical field of molecular imaging, and relates to a targeted nano magnetic resonance contrast agent for articular cartilage damage and its preparation and application, in particular to a hyaluronic acid (Hyaluronic Acid, HA)-based mucopolysaccharide-modified joint Cartilage damage-specific nano magnetic resonance contrast agent and its preparation method and application. Background technique [0002] Articular cartilage injury is a common clinical disease, frequently-occurring disease, affecting a wide range of people. The cartilage covers the joint surface and plays the role of reducing friction generated by joint movement, absorbing mechanical shock, and distributing joint load; the cartilage is composed of scattered chondrocytes and extracellular matrix, and lacks blood supply. The extracellular matrix mainly includes collagen (15-20%), proteoglycan (3-10%) and water (65-80%). There are many causes of cartilage dama...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/12A61K49/10B82Y40/00B82Y25/00
CPCA61K49/1818B82Y25/00B82Y40/00A61K49/105A61K49/12
Inventor 鹿蓉陈爽陶虹月张宇阳陆遥周璐李慧逖
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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