PH-sensitive double-drug skeleton polymer prodrug and preparation method and application thereof

A polymer and dual-drug technology, applied in drug combinations, pharmaceutical formulations, active ingredients of heterocyclic compounds, etc., can solve problems such as difficult to achieve precise drug delivery, and achieve the effects of completely inhibiting tumor growth, enhancing retention, and accelerating drug release

Active Publication Date: 2021-03-26
ANHUI UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above-mentioned polymer prodrugs in the prior art achieve the purpose of synergis

Method used

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  • PH-sensitive double-drug skeleton polymer prodrug and preparation method and application thereof
  • PH-sensitive double-drug skeleton polymer prodrug and preparation method and application thereof
  • PH-sensitive double-drug skeleton polymer prodrug and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] A pH-sensitive double-drug backbone polymer prodrug, the structure of which is shown in formula VI:

[0073]

Embodiment 2

[0075] Preparation of pH-sensitive dual-drug backbone polymer prodrugs:

[0076] The synthetic route of the pH-sensitive dual-drug backbone polymer prodrug is as follows:

[0077]

[0078] The preparation steps of the pH-sensitive double-drug backbone polymer prodrug are as follows:

[0079] Formula I synthetic steps:

[0080] H 2 o 2 Dihydroxycisplatin (500mg, 1.493mmol), norcantharidin (1004mg, 5.972mmol) and triethylamine (catalytic amount) obtained by oxidation of the aqueous solution were dissolved in DMF, stirred at 65°C for 24 hours, and the solvent was distilled off under reduced pressure . Finally, the cisplatin-norcantharidin conjugate of formula I was obtained by precipitating twice with glacial ether. Formula I 1 H NMR picture as figure 1 shown.

[0081] Formula III synthesis steps:

[0082] Under the protection of nitrogen, polyethylene glycol monomethyl ether 550 (550mg, 1mmol) and CDI (648mg, 4mmol) were dissolved in anhydrous dichloromethane (10mL) ...

Embodiment 3

[0087] Preparation, particle size and electron microscope observation of pH-sensitive dual-drug backbone polymer prodrug nanoparticles:

[0088] Take 30 mg of the polymer prodrug in Example 2 and add it into 1 mL of DMSO to fully dissolve it, then add it dropwise into phosphate buffer (20 mL, pH 7.4, 0.01 M), and stir for 2 h. Then, the mixture was dialyzed against deionized water (MWCO 3500Da) for 24h, and the nano-prodrug particles were obtained after lyophilization.

[0089] Disperse the polymer prodrug nanoparticles in 0.01M pH 8.0 phosphate buffer, take 1mL of the nanoparticle solution, dilute it to an appropriate concentration, and measure its particle size with DLS (Malvern, Zeta-sizer Nano-ZS90) at room temperature and distribution, particle size and distribution such as image 3 As shown, it can be seen that the size of the prepared polymer prodrug nanoparticles is about 150nm, and the dispersion is good.

[0090] Take a drop of diluted polymer prodrug nanoparticle ...

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Abstract

The invention discloses a pH-sensitive double-drug skeleton polymer prodrug, and relates to the technical field of controllable polymer prodrug preparation. The structural formula of the polymer prodrug is shown as VI. The invention further provides a preparation method and application of the polymer prodrug. The pH-sensitive double-drug skeleton polymer prodrug has the beneficial effects that inthe structure of the polymer prodrug disclosed by the invention, the molar ratio of cis-platinum to norcantharidin is always kept at 1: 2; accurate administration is implemented; and the polymer prodrug can remarkably improve the targeted enrichment, cellular uptake and intracellular rapid drug release capabilities of a drug at a tumor site, so that the effect of completely inhibiting tumor growthis achieved.

Description

technical field [0001] The invention relates to the technical field of controllable polymer prodrug preparation, in particular to a pH-sensitive double-drug skeleton polymer prodrug and its preparation method and application. Background technique [0002] As a new type of treatment, nanomedicine has greatly improved the shortage of anticancer agents. In recent decades, drug delivery systems based on nanocarriers have made great progress in cancer treatment, and some of them have been clinically tested. . However, little progress has been made due to its limited tumor selectivity and imprecise control over the drug composition, carrier framework, and drug delivery from batch to batch. In recent years, with the continuous development and in-depth research of nano-drug delivery systems, polymer prodrugs with good biocompatibility have become a research hotspot for tumor treatment. [0003] Compared with the traditional physical embedding nano-delivery system, the chemically b...

Claims

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Application Information

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IPC IPC(8): A61K47/60A61K47/55A61K47/59A61K33/243A61K31/34A61P35/00A61K47/34
CPCA61K47/60A61K47/59A61K47/55A61K33/243A61K31/34A61P35/00A61K47/34A61K2300/00Y02P20/55
Inventor 唐汝培杨龙顺闫国卿王鑫
Owner ANHUI UNIVERSITY
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