Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Targeted tumor microenvironment amphiphilic micromolecule nano-drug and preparation method thereof

A nano-drug delivery system and compound technology, applied in the field of amphiphilic small molecule nano-drugs and their preparation, can solve problems such as poor solubility, low bioavailability, and lack of selectivity of drugs

Pending Publication Date: 2022-05-17
BEIJING HOSPITAL
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Using the strategy of prodrugs, small molecule anti-tumor drugs can be used to improve the shortcomings of drugs such as lack of selectivity, poor solubility, and low bioavailability through ingenious structural modification.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Targeted tumor microenvironment amphiphilic micromolecule nano-drug and preparation method thereof
  • Targeted tumor microenvironment amphiphilic micromolecule nano-drug and preparation method thereof
  • Targeted tumor microenvironment amphiphilic micromolecule nano-drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] Embodiment 1, the synthesis of metronidazole-fluridine

[0099] according to figure 2 The flowchart shown in the synthesis

[0100] Weigh metronidazole (MTI, 684mg, 4mmol) into a 250mL round bottom flask, measure 80mL of anhydrous dichloromethane (DCM) into the reaction flask, turn on magnetic stirring, add 3,3' -Dithiodipropionic acid (DTPA, 1260mg, 6mmol), 4-dimethylaminopyridine (DMAP, 171mg, 1.4mmol), after 5min in ice bath, weigh dicyclohexylcarbodiimide (DCC, 989mg, 4.8 mmol) was added into dichloromethane, and reacted at room temperature for 24h. After the reaction, the white precipitate 1,3-dicyclohexylurea (DCU) precipitated in the solvent was removed by filtration through a Buchner funnel, and the solvent DCM was evaporated to dryness using a rotary evaporator at 30°C. Using methanol: dichloromethane (volume ratio 1:30) as the developing solvent, separated and purified by silica gel column chromatography, and evaporated the solvent to obtain 494 mg of the ...

Embodiment 2

[0120] Embodiment 2, preparation of metronidazole-fluridine nanoparticles

[0121] Metronidazole-fluridine was made into nanoparticles by film hydration method. Weigh 5 mg of MTI-FDU into a flask, and dissolve the MTI-FDU compound with 5 mL of dichloromethane (DCM). Then weigh 20mg of DSPE-PEG2000 into a 15mL centrifuge tube, dissolve DSPE-PEG2000 with 6mL of dichloromethane, slowly drop into the flask, and stir magnetically to make it evenly mixed. DCM was evaporated to dryness by rotary evaporation at 30°C, and a light white film was covered on the bottle wall. A total of 5ml of deionized water was added dropwise, and the flask was placed in a constant temperature water bath at 30°C to incubate for 10min.

[0122] Characterization of Metronidazole-Foxuridine Nanoparticles

[0123] (1) Transmission electron microscope (TEM) observation

[0124] Dilute the prepared MTI-FDU nano-preparation to an appropriate multiple, drop it on a 200-mesh copper grid, wait for the water to...

Embodiment 3

[0131] Example 3, Preparation of MTI-FDU@Cy5.5 NPs

[0132] Accurately weigh 5mg of MTI-FDU into a round bottom flask, and dissolve the compound with 5mL of dichloromethane. Weigh 20mg of DSPE-PEG2000-Cy5.5 in a 15mL centrifuge tube under dark conditions, dissolve DSPE-PEG2000-Cy5.5 with 6mL of dichloromethane, slowly drop into the flask, and stir magnetically to make it evenly mixed. DCM was evaporated to dryness under reduced pressure at 30°C, and a layer of turquoise film was covered on the bottle wall. A total of 5ml of deionized water was added dropwise, and the flask was placed in a constant temperature water bath at 30°C to incubate for 10min.

[0133] The characterization results of MTI-FDU@Cy5.5 NPs are shown in Example 5.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Ld50aaaaaaaaaa
The average particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention discloses an amphiphilic drug-drug connector and a nano drug delivery system containing the amphiphilic drug-drug connector. The structural formula of the medicine is as shown in formula I in the specification. According to the amphiphilic drug-drug connector, a drug is connected by taking a chemical bond sensitive to a tumor microenvironment as a medium, so that a nano drug delivery system capable of intelligently responding to a tumor site is constructed. According to the research, two small molecule drugs are connected to form connection of a hydrophilic end and a hydrophobic end, self-assembly is performed in water, the drugs are conveyed to a tumor site, release of the anti-tumor drugs is triggered under stimulation of a tumor microenvironment under the condition of a high glutathione level (GSH), and a method is provided for targeted therapy of the drugs. Meanwhile, a new thought is further provided for clinical application of the anti-tumor small molecule medicine.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to an amphiphilic small-molecule nano-medicine targeting the tumor microenvironment and a preparation method thereof. Background technique [0002] The statistics of global cancer epidemiology show that the number of newly diagnosed cancers and death cases worldwide are increasing year by year. Cancer has become the second leading cause of death for all human beings. Due to its high mortality rate, cancer treatment has long been the focus of scientists all over the world. [0003] With the rapid progress of biotechnology, in-depth research has been conducted on the occurrence and development of malignant tumors, and chemotherapy drugs with different mechanisms of action have been developed one after another. After half a century of research, hundreds of small-molecule anti-tumor drugs have been clinically used in the treatment of malignant tumors. Small-molecule anti-tumor drug...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07H19/073C07H1/00A61P35/00A61K9/14A61K47/55
CPCC07H19/073C07H1/00A61P35/00A61K47/55A61K9/146
Inventor 马洁黄卫袁伟尹春香高春晓
Owner BEIJING HOSPITAL
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com