Gadolinium-containing macromolecule magnetic resonance intravascular contrast medium and preparation method thereof

An angiography and magnetic resonance technology, applied in the field of magnetic resonance angiography contrast agent and its preparation, can solve the problems of incomplete clearance and accumulation toxicity, and achieve the effect of solving gadolinium accumulation and simple treatment

Inactive Publication Date: 2010-05-26
NANTONG GUANGTAI BIOCHEM PROD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] But so far, the biggest problem limiting the further clinical application of this kind of gadolinium macromolecule contrast agent is the accumulation toxicity caused by the incomplete clearance of gadolinium

Method used

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  • Gadolinium-containing macromolecule magnetic resonance intravascular contrast medium and preparation method thereof
  • Gadolinium-containing macromolecule magnetic resonance intravascular contrast medium and preparation method thereof
  • Gadolinium-containing macromolecule magnetic resonance intravascular contrast medium and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: The small-molecule gadolinium complex is gadolinium diethylenetriaminepentaacetate (Gd-DTPA), and the double metal hydroxide is Mg 2 Al(OH) 6 NO3 .

[0031] a. Add 15.42g Mg(NO 3 ) 2 ·6H 2 O and 7.48g Al(NO 3 ) 3 9H 2 O was dissolved in 50mL freshly boiled high-purity water to form solution A.

[0032] b. Add 5.25g NaNO 3 and 9.2mL NH 3 ·H 2 O was dissolved in 50mL freshly boiled high-purity water to form solution B;

[0033] c. Take 1.5 mL of solution A and add it to the organic phase containing nonylphenol polyoxyethylene ether, wherein the volume ratio of each substance in the organic phase is fixed as cyclohexane: nonylphenol polyoxyethylene ether: n-hexanol 20:3:3.

[0034] d. Take 1.5mL of solution B and 1.5mL of 2.0M ammonia water and add an equal volume of the above organic phase;

[0035] e. Add the microemulsion containing solution B dropwise into the microemulsion containing solution A, and heat to 80° C. for 8 hours after the additi...

Embodiment 2

[0039] Embodiment two: the present embodiment is basically the same as embodiment one, and the difference is that the total volume of the aqueous solution added in each step of steps c, d, and f is increased to 2 times that of embodiment one, that is, after adding Na 2 [Gd(dtpa)H 2 O] After the solution was added, the volume ratio of the substances in the reaction system, cyclohexane: nonylphenol polyoxyethylene ether: n-hexanol: aqueous solution increased from 20:3:3:3 to 20:3:3:6. figure 2 It can be seen from the TEM photo in (b) that the particle size of the product composite of Example 2 has increased to 48 nanometers, and the particle size is relatively large. Longitudinal relaxation efficiency 4.0mM -1 the s -1 , transverse relaxation efficiency 5.5mM -1 the s -1 .

Embodiment 3

[0040] Embodiment three: this embodiment is basically the same as embodiment one, the difference is that step f is adjusted to add Na with a molar ratio of gadolinium to aluminum of 1:1 2 [Gd(dtpa)H 2 O] solution, that is, the amount of gadolinium added is 2 times that of Example 1, and the loading amount of Gadolinium in the product complex is increased to Gd%=5.94% from Gd%=5.41% of Example 1, but the longitudinal relaxation efficiency is relatively Embodiment 1 decreased to 5.9mM -1 the s -1 , see image 3 curve b; Figure 4 Curve b is its transverse relaxation efficiency.

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Abstract

The invention relates to a gadolinium-containing macromolecule magnetic resonance intravascular contrast medium and a preparation method thereof. The easy degradable gadolinium (III) macromolecule magnetic resonance intravascular contrast medium is an intercalation compound of a gadolinium complex and inorganic layered double hydroxides (LDHs) and has the average grain diameter of 17-34nm. The contrast medium adopts the easily biodegradable LDHs as a main material and realizes the nano compounding of the gadolinium-containing complex and the LDHs by intercalation reaction, and the inorganic macromolecule product grain diameter is controlled in a required range of the intravascular contrast medium by a reverse-phase micro-emulsion system; the longitudinal relaxation rate r1 and the transverse relaxation rate r2 are respectively 7.5mM-1s-1 and 10mM-1s-1 and are respectively twice and three times higher than free gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA); and meanwhile, the macromolecule compound can be degraded into inorganic ions and a micromolecule gadolinium complex by simple processing due to the LDHs, thereby solving the problems of slow degradation and difficult gadolinium removal of the gadolinium (III) macromolecule magnetic resonance intravascular contrast medium.

Description

technical field [0001] The invention relates to a magnetic resonance angiography agent and a preparation method thereof, in particular to an easily degradable gadolinium-containing macromolecular magnetic resonance angiography agent and a preparation method thereof. technical background [0002] Magnetic resonance blood pool contrast agent (or magnetic resonance angiography contrast agent) is a kind of contrast agent that is not easy to pass through the inner wall of healthy blood vessels, and can stably shorten the longitudinal relaxation time (T 1 ), and is a macromolecular substance characterized by its ability to image blood vessels, which has great potential in assisting sensitive detection and obtaining information about tissue cancer and cardiovascular system diseases. In addition, since most macromolecular complexes have the characteristics of significantly enhanced relaxation efficiency, it means that when macromolecular complexes are used as contrast agents, less d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/06
Inventor 李佼徐甲强潘庆谊
Owner NANTONG GUANGTAI BIOCHEM PROD
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