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

PH-triggering-to-release multilevel targeting polymer micelle in tumor cells and preparation method of multilevel targeting polymer micelle

A technology of tumor cells and polymer glue, which is applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as chemotherapy failure, achieve saturated drug resistance mechanisms, improve anti-tumor efficacy, and overcome multi-drug resistance of tumors Effect

Active Publication Date: 2017-01-04
NINGXIA MEDICAL UNIV
View PDF1 Cites 26 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Chemotherapy is currently an effective method for treating tumors clinically, but the multidrug resistance of tumor cells to anticancer drugs is an important reason for the failure of chemotherapy

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
  • PH-triggering-to-release multilevel targeting polymer micelle in tumor cells and preparation method of multilevel targeting polymer micelle
  • PH-triggering-to-release multilevel targeting polymer micelle in tumor cells and preparation method of multilevel targeting polymer micelle
  • PH-triggering-to-release multilevel targeting polymer micelle in tumor cells and preparation method of multilevel targeting polymer micelle

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0046] Example 1: Synthesis of HA-DOCA-His polymer

[0047] 0.5 g DOCA was dissolved in 5 mL N,N-dimethylformamide, 0.29 g EDC and 0.18 g NHS were added, and stirred at room temperature for 2 h. 0.37 g of trityl histidine methyl ester hydrochloride (H-His (Trt)-OMe HCl) was dissolved in 20 mL of DMF, and 50 µL of triethylamine was added, and slowly added dropwise to the DOCA mixture, the mixture Stir in a water bath at 35 °C for 24 h. NaHCO was added to the reaction mixture 3 solution (pH 9-10), the precipitate was obtained by suction filtration, and dried under reduced pressure to obtain DOCA-His (Trt).

[0048] Dissolve 0.1 g HA in 5 mL anhydrous formamide, heat to dissolve at 50°C, and cool to room temperature. Add 96 mg EDC and 58 mg NHS, and stir in an ice bath for 2 h. 0.4 g DOCA-His(Trt) was dissolved in 5 mL of anhydrous DMF, slowly added dropwise to the HA mixture, stirred in a water bath at 50 °C for 6 h, and then stirred at room temperature for 24 h. The reacti...

example 2

[0050] Example 2: Synthesis of HA-DOCA-His polymer

[0051] 0.5 g DOCA was dissolved in 5 mL N,N-dimethylformamide, 0.29 g EDC and 0.18 g NHS were added, and stirred at room temperature for 24 h. 0.37 g of trityl histidine methyl ester hydrochloride (H-His (Trt)-OMe HCl) was dissolved in 20 mL of DMF, slowly added dropwise to the DOCA mixture, and the mixture was stirred in a water bath at 35 °C for 24 h. The reaction mixture was spun to remove the organic solvent, and separated by a column to obtain DOCA-His (Trt).

[0052] 0.1 g HA was dissolved in 5 mL of anhydrous formamide, heated to dissolve at 50 °C, and cooled to room temperature. Add 96 mg EDC and 58 mg NHS, and stir in an ice bath for 2 h. 0.4 g DOCA-His(Trt) was dissolved in 5 mL of anhydrous DMF, slowly added dropwise to the HA mixture, stirred in a water bath at 50 °C for 6 h, and then stirred at room temperature for 24 h. The reaction mixture was dialyzed in distilled water for 2-3 days (dialysis bag molecula...

example 3

[0054] Example 3: Synthesis of HA-DOCA-His polymer

[0055] 0.5 g DOCA was dissolved in 5 mL N,N-dimethylformamide, 0.29 g EDC and 0.18 g NHS were added, and stirred at room temperature for 24 h. 0.37 g of trityl histidine methyl ester (H-His(Trt)-OH) was dissolved in 20 mL of DMF, slowly added dropwise to the DOCA mixture, and the mixture was stirred in a water bath at 35 °C for 24 h. The reaction mixture was rotary evaporated to remove the organic solvent, and separated by column to obtain DOCA-His(Trt).

[0056] 0.1 g HA was dissolved in 5 mL anhydrous formamide, heated to dissolve at 60 °C, and cooled to room temperature. Add 192 mg EDC and 116 mg NHS, and magnetically stir in ice bath for 5 h. 0.8 g DOCA-His (Trt) was dissolved in 5 mL of anhydrous DMF, slowly added dropwise to the HA mixture, and stirred at room temperature for 48 h. Ethanol was added to the reaction mixture to precipitate and remove impurities to obtain HA-DOCA-His (Trt) white powder.

[0057] Disso...

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

The invention relates to pH-triggering-to-release multilevel targeting polymer micelle in tumor cells and a preparation method of the multilevel targeting polymer micelle. The micelle is formed by self assembly of hydrophobic modified polysaccharide polymer with an endosome pH sensitive characteristic in a water medium. A hyaluronic acid-deoxycholate-histidine polymer is used as a carrier, and caner initiatively-targeting endosome pH sensitive polymer micelle is prepared by virtue of an ultrasonic method or a dialysis method to wrap an antitumor drug difficult to dissolve. By using the synergistic mechanism of EPR-mediated passive targeting, CD44 receptor initiative targeting and pH sensitive targeting strategies, the 'whole-course targeting' guidance is performed at four medicine delivery key steps, i.e., blood long circulation, tumor tissue accumulation, cell digestion and intracellular drug release, so that multilevel targeting drug delivery is realized, the intracellular drug concentration is effectively increased, and a novel carrier and a preparation strategy are provided for improving the antitumor effect of the difficultly-soluble antitumor drug.

Description

technical field [0001] The invention belongs to the technical field of polymer materials and pharmaceutical preparations, and relates to a multi-level targeting polymer micelle for pH-triggered drug release in tumor cells and a preparation method thereof. [0002] technical background [0003] Chemotherapy is an effective method for clinical treatment of tumors, but the multidrug resistance of tumor cells to anticancer drugs is an important reason for the failure of chemotherapy. The classic tumor drug resistance mechanism is the highly expressed drug resistance protein, mainly P-glycoprotein, which "pumps" the anticancer drugs in the cell to the outside of the cell, resulting in a decrease in the level of intracellular drugs and drug resistance. Therefore, using the drug-loading system to deliver targeted drugs into tumor cells and avoid the efflux of P-glycoprotein is the key problem to be solved for reversing multidrug resistance and improving the efficacy of drugs for tum...

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): A61K9/107A61K47/36A61K31/337A61K31/704C08B37/08A61P35/00
CPCA61K9/1075A61K31/337A61K31/704A61K47/36C08B37/0072
Inventor 刘艳华周成铭王文苹杨建宏
Owner NINGXIA MEDICAL UNIV
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