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Methotrexate metal coordination polymer, and preparation method and application thereof

A technology of metal coordination and methotrexate, which can be used in pharmaceutical formulations, preparations for in vivo tests, and active ingredients of artificially synthesized polymeric materials, etc., can solve problems such as poor stability, reduce additive dosage, and efficiently treat tumors. and immune diseases, the effect of simple synthesis process

Active Publication Date: 2020-03-06
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to solve this thorny problem, the carrier-free amphiphilic nano-diagnosis and treatment system is currently attracting attention by constructing hydrophilic and hydrophobic diagnostic and therapeutic agents through chemical bonding, physical interaction, and metal coordination. The system is less stable than the traditional nano-diagnosis and treatment system with carriers

Method used

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  • Methotrexate metal coordination polymer, and preparation method and application thereof
  • Methotrexate metal coordination polymer, and preparation method and application thereof
  • Methotrexate metal coordination polymer, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] (MTX-Gd III Synthesis of coordination polymer): Dissolve 0.1mmol of MTX completely in 15mL of ammonium acetate solution, add 0.2mmol of GdCl 3 ·6H 2 After stirring vigorously for 0.5h, the pH of the reaction system was adjusted to 8.5 with 0.2M sodium hydroxide, and the reaction was terminated after 6h at room temperature, and the MTX-Gd III The crude product of the coordination polymer is transferred to a dialysis bag with a molecular weight cut-off of 1000Da for dialysis for 24 hours, and then freeze-dried to obtain high-purity MTX-Gd III Coordination polymer (40% yield). MTX-Gd synthesized by this method III The infrared spectrum of the coordination polymer ( figure 1 ) explains Gd III It can be connected with MTX through a coordination chemical bond, transmission electron microscope image ( figure 2 ) Description MTX-Gd III Coordination polymers can self-assemble into nanoparticles with a diameter of about 100 nm.

Embodiment 2

[0044] (MTX-Fe III Synthesis of coordination polymer): Dissolve 0.1mmol of MTX completely in 15mL of ammonium acetate solution, add 0.2mmol of GdCl 3 ·6H 2 After stirring vigorously for 0.5h, the pH of the reaction system was adjusted to 8.5 with 0.2M sodium hydroxide, and the reaction was terminated after 12h at room temperature, and the MTX-Fe III The crude product of the coordination polymer is transferred to a dialysis bag with a molecular weight cut-off of 1000Da for dialysis for 24 hours, and then freeze-dried to obtain high-purity MTX-Fe III Coordination polymer (50% yield). MTX-Fe synthesized by this method III The infrared spectrum of the coordination polymer ( image 3 ) shows that Fe III It can be connected with MTX through a coordination chemical bond, transmission electron microscope image ( Figure 4 ) Description MTX-Fe III Coordination polymers can self-assemble into nanoparticles with a diameter of about 100 nm.

Embodiment 3

[0046] (MTX-Zn II Synthesis of coordination polymer): Dissolve 0.1mmol of MTX completely in 15mL of ammonium acetate solution, add 0.2mmol of ZnCl 2 ·6H 2 After stirring vigorously for 0.5h, the pH of the reaction system was adjusted to 8.5 with 0.2M sodium hydroxide, and the reaction was terminated after 6h at room temperature, and the MTX-Zn II The crude product of the coordination polymer is transferred to a dialysis bag with a molecular weight cut-off of 1000Da for dialysis for 24 hours, and then freeze-dried to obtain high-purity MTX-Zn II Coordination polymer (44% yield). Utilize the MTX-Zn synthesized by this method II The infrared spectrum of the coordination polymer ( Figure 5 )Description-Zn II It can be connected with MTX through a coordination chemical bond, transmission electron microscope image ( Image 6 ) Description MTX-Zn II Coordination polymers can self-assemble into nanoparticles with a diameter of about 100 nm.

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Abstract

The invention discloses a methotrexate metal coordination polymer, and a preparation method and application thereof. The structural formula of the methotrexate metal coordination polymer is as described in the description, wherein R is a functional metal ion. According to the invention, GdIII and FeIII capable of being imaged by magnetic resonance imaging (MRI) are introduced into a structure of MTX to obtain a coordination polymer of MTX-GdIII and MTX-FeIII, and the polymer can be efficiently delivered to tumor cells with overexpressed folate receptors under active targeting mediation (the MTX and the folate receptor have extremely strong affinity), so that the administration dosage is reduced, and accurate and efficient diagnosis and treatment of tumor focus are realized. An MTX-ZnII coordination polymer is obtained by introducing ZnII with an immune promotion effect into the structure of the MTX, and the polymer is expected to be used for efficiently treating tumors and immune diseases.

Description

technical field [0001] The invention belongs to the technical field of coordination chemistry, and in particular relates to a methotrexate metal coordination polymer and its preparation method and application. Background technique [0002] Coordination chemistry is the interaction of metal atoms or ions with organic and inorganic ions and the formation of coordination compounds through coordination bonds. With the deepening of life science and disease research, many life phenomena have been found to involve the interaction between metal ions. In addition, the design of new diagnostic and therapeutic agents based on coordination chemistry is also the main strategy to overcome major diseases. Therefore, coordination chemistry has been widely used in the field of biomedicine in recent years. Some organic molecules and metals with diagnostic and therapeutic effects cannot be directly used in clinical practice due to their shortcomings such as poor curative effect, high toxicit...

Claims

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Application Information

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IPC IPC(8): C08G83/00A61K31/80A61K49/12A61P35/00A61P37/04
CPCA61K31/80A61K49/122A61P35/00A61P37/04C08G83/008
Inventor 侯振清范仲雄王衍戈朱富凯
Owner XIAMEN UNIV
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