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

An antitumor prodrug with p-glycoprotein inhibitory function

An anti-tumor drug and anti-tumor technology, applied in the direction of anti-tumor drugs, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of slow drug release, no special effect, and enhance the therapeutic effect and other issues, to achieve small steric hindrance, improve solubility and stability, and achieve long cycle effects

Inactive Publication Date: 2015-08-26
WUHAN PINGHUA BIOMEDICAL TECH
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in clinical studies, such prodrugs did not show enhanced therapeutic effects, which may be related to the fact that the drug is surrounded by polymer chains, which is not easily reduced to the original structure by enzymes and can only rely on the slow hydrolysis of the linkage to lead to drug release. slow speed
For drug-resistant tumors, this type of prodrug has no special effect

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
  • An antitumor prodrug with p-glycoprotein inhibitory function
  • An antitumor prodrug with p-glycoprotein inhibitory function
  • An antitumor prodrug with p-glycoprotein inhibitory function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] This embodiment provides a paclitaxel prodrug with P-glycoprotein inhibitory function, which is synthesized through the following steps:

[0046] (1) Synthesis of 3,3'-dithiodipropionic anhydride: Weigh 2g of 3,3'-dithiodipropionic acid into a 50ml round bottom flask, add 20ml of acetyl chloride, and reflux at 65°C for 3 hours, distilled under reduced pressure to remove impurities such as acetic acid and acetyl chloride; washed three times in diethyl ether, and evaporated diethyl ether under reduced pressure to obtain 3,3'-dithiodipropionic anhydride.

[0047] (2) Synthesis of TPGS-S-S-COOH: Weigh 1.5g TPGS into a 100mL round-bottomed flask, dry in a vacuum oven at 60°C for 3-5 hours, and then add 0.276g 3,3'-COOH Thiodipropionic anhydride, 0.183g 4-dimethylaminopyridine, 0.15mL triethylamine, dissolved in 5-10mL dimethyl sulfoxide; in an anhydrous environment, stirred at room temperature for 24 hours.

[0048] (3) Activation of TPGS-S-S-COOH: Dialyze the above product i...

Embodiment 2

[0053] This embodiment provides a doxorubicin prodrug with P-glycoprotein inhibitory function, which is synthesized through the following steps:

[0054] (1) Obtain activated TPGS-S-S-COOH in the same manner as in the first three steps of Example 1.

[0055] (2), connect doxorubicin: add 0.6g doxorubicin in a 100mL round bottom flask, add 5-10mL DMSO and 0.12ml triethylamine to dissolve, and do light-proof treatment; the product of step (1) Filtrate, add the filtrate to the doxorubicin solution; stir at room temperature for 48 hours in an anhydrous environment; use a dialysis bag with a molecular weight of 2000 to dialyze in a mixed solvent of absolute ethanol and DMSO for 24-48 hours, and evaporate the ethanol to dryness after the dialysis That is doxorubicin prodrug (TPGS-S-S-DOX), its structure is as follows:

[0056]

Embodiment 3

[0058] This embodiment provides a paclitaxel prodrug with P-glycoprotein inhibitory function, which is synthesized by the following steps:

[0059] (1) Synthesis of diselenomalonic acid: Weigh 1.5g of sodium borohydride in a 100mL round bottom flask, add 20ml of deionized water, and then add 3.2g of selenium powder; after stirring for 10 minutes, heat the solution to 70°C React until the selenium powder disappears completely; add 3-chloropropionic acid tetrahydrofuran solution (4.36g / 50ml) under the protection of nitrogen, react at 50°C for 12h, remove tetrahydrofuran by rotary evaporation, freeze-dry and wash with ether to obtain diselenide On behalf of malonic acid.

[0060] (2) Synthesis of TPGS-Se-Se-COOH: Weigh 1.5g of TPGS into a 100mL round bottom flask, dry in a vacuum oven at 60°C for 3 to 5 hours, and then add 0.306g of diselenide Acetic acid, 0.183g 4-dimethylaminopyridine, 0.15mL triethylamine, dissolved in 5-10mL DMSO; in anhydrous environment, stirred at room te...

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

No PUM Login to View More

Abstract

Antitumor prodrugs with function of P-glycoprotein inhibition are disclosed. The prodrugs are amphiphilic substances composing of antitumor drug covalently linked with polyethylene glycol succinate with function of P-glycoprotein inhibition via a linker. The linker has a sensitive bond and two reactive groups separately covalently linked with antitumor drug and polyethylene glycol succinate. The sensitive bond is a scissile chemical bond in the intracelluar reducing environment or acidic environment of tumor cells.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and in particular relates to an antitumor prodrug capable of treating tumors, especially drug-resistant tumors. Background technique [0002] Cancer is one of the leading causes of death in modern society. The national cause of death survey released by the Ministry of Health in 2008 shows that cancer has become the first cause of death in my country's cities and the second in rural areas. An important means of treating cancer is chemotherapy. However, during the course of treatment, tumor patients often develop drug resistance to chemotherapeutic drugs, and also develop cross-resistance to other drugs with different chemical structures and different mechanisms of action. The emergence of multidrug resistance (MDR) greatly reduces the efficacy of drugs and leads to the failure of chemotherapy. In addition, most antitumor drugs have low water solubility, and the modification of hydrop...

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
Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/48A61K31/337A61K31/704A61K31/475A61K31/55A61K31/4745A61P35/00
CPCA61K31/475A61K31/704A61K31/337A61K47/48215A61K31/4745A61K31/55A61K47/60A61P35/00
Inventor 谭松巍张志平
Owner WUHAN PINGHUA BIOMEDICAL TECH
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