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Antitumor drug PEGylation and applications of antitumor drug PEGylation in reversal of tumor multidrug resistance

An anti-tumor drug and tumor technology, applied in the direction of anti-tumor drugs, drug combinations, medical preparations of non-active ingredients, etc., can solve the problems of chemotherapy failure, cumulative cardiotoxicity, strong side effects, etc., and achieve immunogenicity and Decreased antigenicity, improved pharmacokinetic properties, and prolonged half-life

Inactive Publication Date: 2015-06-10
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Paclitaxel (PTX) has a good effect on a variety of tumors, but its low water solubility and strong side effects have greatly limited its clinical application, and long-term use is prone to drug resistance
[0007] Doxorubicin (DOX) is the most clinically used anti-tumor drug so far, but it has obvious cumulative cardiotoxicity, sometimes the treatment has to be terminated, and it is also easy to develop drug resistance, leading to the failure of chemotherapy

Method used

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  • Antitumor drug PEGylation and applications of antitumor drug PEGylation in reversal of tumor multidrug resistance
  • Antitumor drug PEGylation and applications of antitumor drug PEGylation in reversal of tumor multidrug resistance
  • Antitumor drug PEGylation and applications of antitumor drug PEGylation in reversal of tumor multidrug resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Taking PEG-RAPA as an example to illustrate its synthesis process, determination of physical and chemical properties and its reversal effect on MCF-7 / ADR cells:

[0043] Synthesis of PEG-RAPA: Dissolve 88 mg of mPEG-COOH in 10 mL of ice-free dichloromethane, then add 107 mg of rapamycin, 30 mg of DCC and 15 mg of DMAP. The temperature was naturally raised to room temperature, and the reaction was stirred for 3 d. After the reaction was completed, it was filtered, anhydrous ether precipitated twice, and then the precipitate was vacuum-dried to obtain the obtained product. PEG-RAPA (PEGylated Rapamycin) 1 H NMR spectrum as figure 1 shown.

[0044] Preparation of PEG-RAPA micelles and determination of particle size: PEG-RAPA micelles were prepared by solid dispersion method. Dissolve 1 mg PEG-RAPA in 100 μL of acetonitrile, evaporate to dryness naturally, dissolve in 2 ml of ultrapure water, vortex for 3 min, sonicate for 5 min, centrifuge at 12000 r / min for 10 min, ta...

Embodiment 2

[0064] Taking PEG-PTX as an example to illustrate its synthesis process, determination of physical and chemical properties and its reversal effect on MCF-7 / ADR cells:

[0065] Synthesis of PEG-PTX: Dissolve 88 mg of mPEG-COOH in 10 mL of anhydrous dichloromethane, cool to 0°C on ice, then add 100 mg of paclitaxel, 30 mg of DCC, and 15 mg of DMAP, stir and react, naturally warm to room temperature, and react for 3 days . After the reaction was completed, it was filtered and precipitated with glacial ether, and then the precipitate was vacuum-dried. PEG-PTX (PEGylated Paclitaxel) 1 H NMR spectrum as Image 6 shown.

[0066] Preparation of PEG-PTX micelles and determination of particle size: PEG-PTX micelles were prepared by solid dispersion method. Dissolve 1 mg PEG-PTX in 100 μL of acetonitrile, evaporate to dryness naturally, dissolve in 2 ml of ultrapure water, vortex for 3 min, sonicate for 5 min, centrifuge at 12000 r / min for 10 min, take the supernatant and filter it w...

Embodiment 3

[0082] Taking PEG-DOX as an example to illustrate its synthesis process, determination of physical and chemical properties and its reversal effect on MCF-7 / ADR cells:

[0083] Synthesis of PEG-DOX: Take 210mg mPEG-COOH, 58mg doxorubicin hydrochloride, 23mg NHS, 20mgDCC, 12mgTEA in 10ml of anhydrous dichloromethane, react at room temperature for 3 days under dark nitrogen, filter, dialyze, and freeze-dry. PEG-DOX (PEG Adriamycin) 1 H NMR spectrum as Figure 11 shown.

[0084] Preparation of PEG-DOX micelles and determination of particle size: PEG-DOX micelles were prepared by solid dispersion method. Dissolve 1 mg PEG-DOX in 100 μL of acetonitrile, evaporate to dryness naturally, dissolve in 2 ml of ultrapure water, vortex for 3 minutes, sonicate for 5 minutes, centrifuge at 12000 r / min for 10 minutes, take the supernatant and filter it with a 0.45 μm microporous membrane. have to.

[0085] The particle size of PEG-DOX micelles is measured by dynamic light scattering (DLS):...

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Abstract

The present invention discloses antitumor drug PEGylation and applications of the antitumor drug PEGylation in reversal of tumor multidrug resistance. The PEGylated antitumor drug is prepared by conjugating activated PEG onto an antitumor drug, and can be used for preparing the drug for reversal of tumor multidrug resistance. According to the present invention, the antitumor drugs (particularly water insoluble drugs) containing amino, carboxyl, hydroxyl and other modifiable groups are PEGylated so as to increase the water solubility, such that excellent characteristics of micelle self-assembly forming, production of invisible nanoparticles or active targeting tumor nanoparticles, drug release behavior regulation, system toxicity reducing, biological half-life improving, EPR effect production, tumor passive / active targeting production, tumor multidrug resistance reversal and the like are provided, and good clinical application prospects are provided.

Description

technical field [0001] The invention belongs to the technical field of drugs for treating tumors, and in particular relates to PEGylation of anti-tumor drugs and its application in reversing multi-drug resistance of tumors. Background technique [0002] Malignant tumor is one of the diseases that seriously endanger human health. According to the International Anti-Cancer Alliance, the number of people who die from cancer each year far exceeds the total number of deaths caused by malaria, AIDS and tuberculosis. By 2020, there may be 15 million new cancer patients worldwide each year. At present, the incidence of cancer in my country is about 200 per 100,000. There are more than 2.2 million new cancer cases in my country every year, more than 6 million patients are being treated every year, medical expenses are more than 150 billion, and more than 1.6 million people die of cancer every year. Cancer control has become one of the priorities of the global health strategy. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K45/00A61P35/00
Inventor 郭圣荣田伟吕立沈园园
Owner SHANGHAI JIAO TONG UNIV
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