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A kind of biodegradable core cross-linked gadolinium complex-containing polymer and its preparation method and use

A biodegradable and polymer technology, applied in the field of nuclear cross-linked gadolinium complex-containing polymers, can solve problems such as 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 the degree of aggregation

Active Publication Date: 2019-11-26
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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

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  • A kind of biodegradable core cross-linked gadolinium complex-containing polymer and its preparation method and use
  • A kind of biodegradable core cross-linked gadolinium complex-containing polymer and its preparation method and use
  • A kind of biodegradable core cross-linked gadolinium complex-containing polymer and its preparation method and use

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Embodiment 1

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

[0062] 1. Preparation method

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

[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 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 andcopolymerization. Eur Polym J.1973; 9:7-14 prepared by the HPMA preparation method disclosed.

[0067] MA-DOTA: its structural formula is According to the MA-DOTA method disclosed...

experiment example 1

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

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

[0096] 1.1 Biodegradability research

[0097] Dissolve the Core-crosslinked pHPMA-DOTA-Gd in McIlvaine's buffer containing glutathione (GSH) (4mg / mL, 50mM citrate / 0.1M phosphate, 2mM EDTA, 4mM 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 sample, Superose6HR10 / 30 prepacked column loaded with sodium acetate solution containing 30% methanol (pH 6.5) as the mobile phase (flow rate: 0.4mL / min).

[0098] 1.2 In vitro T 1 Aqueous Phase Relaxation Experiment

[0099] Dissolve the material in PBS at room temperature at pH 7.4, the material concentrat...

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Abstract

The invention discloses a biodegradable core-crosslinked gadolinium complex-containing polymer, a preparation method and application thereof. The invention also discloses a biodegradable linear HPMA copolymer, a preparation method and application thereof. The biodegradable gadolinium complex-containing polymer of the invention has a high relaxation rate, has excellent effect as a magnetic resonance imaging contrast agent, is degradable, nontoxic, has good biocompatibility, and has good clinical application prospects.

Description

technical field [0001] The invention relates to a biodegradable core-crosslinked gadolinium complex-containing polymer, a preparation method and application thereof. 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 which, contrast-enhanced magnetic resonance imaging can further enhance the contrast between normal tissue and diseased tissue Contrast for clear and accurate images. Currently, DTPA-Gd, DTPA-Gd, and other gadolinium chelate contrast agents are being widely used in enhanced magnetic resonance imaging, but these contrast agents have limitations in their effectiveness, sensitivity, and circulatory relaxation time. For example, these contrast agents Will be cleared quickl...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/12C08G83/00C08F220/58C08F220/60
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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