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Biodegradable core-crosslinked gadolinium complex-containing polymer and preparation method and purpose thereof

A biodegradable polymer technology, applied in the field of nuclear cross-linked gadolinium-containing polymers, can solve the problems of large side effects, ineffective degradation, renal systemic fibrosis, etc., to increase the ability of passive targeting, increase Imaging effect and treatment effect, effect of increasing aggregation degree

Active Publication Date: 2017-07-04
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The existing reported HPMA copolymer has good biocompatibility, non-immunity, neutral charge and good water solubility, and is usually used as a tumor carrier, but it has the problem that it cannot be effectively degraded. If it carries substances such as gadolinium, The side effects on the human body are relatively large, and may cause diseases such as renal systemic fibrosis

Method used

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  • Biodegradable core-crosslinked gadolinium complex-containing polymer and preparation method and purpose thereof
  • Biodegradable core-crosslinked gadolinium complex-containing polymer and preparation method and purpose thereof
  • Biodegradable core-crosslinked gadolinium complex-containing polymer and preparation method and purpose thereof

Examples

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Embodiment 1

[0061] Example 1 Preparation of biodegradable core cross-linked branched macromolecular gadolinium polymer of the present invention

[0062] 1. Preparation method

[0063] Azobisisobutylimidazoline hydrochloride (VA044), cyclic azoamidine initiator V501, 4-cyanovaleric acid dithiobenzoic acid (4-CTA) and trimethylolpropane tris(3-mercapto) propionate) was purchased from sigma-Adrich.

[0064] Monomer HPMA (Eur.Polym.J., 1973, 9, 7-14), MA-DOTA (ACS Appl. Mater. Interfaces, 2016, 8, 10499-10512), PTEMA (Bioconjug. Chem., 1998, 9, 749 -757) were prepared according to the existing literature.

[0065] The preparation methods of HPMA, PTEMA and MA-DOTA are as follows:

[0066] HPMA: Its structural formula is according to J, H.Poly[N-(2-hydroxypropyl)methacrylamide]—I. Radical polymerization and copolymerization. Eur Polym J. 1973; 9:7-14 published by the HPMA preparation method.

[0067] MA-DOTA: Its structural formula is MA-DOTA method disclosed in the appendix secti...

experiment example 1

[0094] Experimental Example 1 Properties and applications of the biodegradable core-crosslinked gadolinium complex-containing polymer of the present invention

[0095] Take the core-crosslinked gadolinium complex-containing polymer pHPMA-DOTA-Gd prepared in Example 1, and carry out the following experiments to detect its properties:

[0096] 1.1 Biodegradability study

[0097] Core-crosslinked pHPMA-DOTA-Gd was dissolved in McIlvaine's buffer containing glutathione (GSH) (4 mg / mL, 50 mM citrate / 0.1 M phosphate, 2 mM EDTA, 4 mM glutathione, pH= 5.4), incubated at 37°C for 12 hours, and then passed through SEC ( System, GE Healthcare) to detect the degradability of the samples, Superose6HR10 / 30 prepacked column was loaded with 30% methanol (pH 6.5) sodium acetate solution as mobile phase (flow rate: 0.4mL / min).

[0098] 1.2 In vitro T 1 Aqueous relaxation experiments

[0099] The material was dissolved in PBS at pH 7.4 at room temperature, and the material concentration was...

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Abstract

The invention discloses a biodegradable core-crosslinked gadolinium complex-containing polymer and a preparation method and a purpose thereof. The invention also discloses a biodegradable linear HPMA copolymer and a preparation method and a purpose thereof. The biodegradable core-crosslinked gadolinium complex-containing polymer has high relaxation rate, has excellent effect as a magnetic resonance imaging contrast medium, has the advantages of degradable performance, no toxicity, good biological compatibility, and has good clinic application prospect.

Description

technical field [0001] The present invention relates to a biodegradable core cross-linked gadolinium complex-containing polymer and its preparation method and application. Background technique [0002] In clinical practice, imaging examinations play a very important role in the qualitative and localized diagnosis of most diseases. Among these imaging methods, magnetic resonance imaging as a non-invasive diagnostic tool has the advantages of high-resolution imaging and three-dimensional soft tissue imaging. Among them, contrast-enhanced magnetic resonance imaging can further enhance the relationship between normal tissue and diseased tissue through contrast agents. Contrast for clear and accurate images. Currently, DTPA-Gd, DTPA-Gd, and other gadolinium chelate contrast agents are widely used in magnetic resonance enhanced imaging, but these contrast agents have many limitations in their efficacy, sensitivity, and circulatory relaxation time. For example, these contrast agen...

Claims

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Application Information

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IPC IPC(8): C08G83/00C08F220/58C08F220/60A61K49/12
CPCA61K49/124A61K49/126C08F220/58C08G83/008C08F2438/03C08G2230/00C08F220/603C08F220/606
Inventor 龚启勇罗奎罗强段振宇
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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