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A kind of doxorubicin and glycyrrhetinic acid double drug nano-delivery system and preparation method thereof

A technology of glycyrrhetic acid and delivery system, which is applied in pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve the problems of affecting clinical efficacy, low bioavailability, poor water solubility, etc., achieve effective tumor cell proliferation, and improve delivery efficiency. , the effect of high encapsulation rate

Active Publication Date: 2020-12-22
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Glycyrrhetinic acid has strong anti-inflammatory, anti-cancer, and immunomodulatory effects, but its poor water solubility and low bioavailability seriously affect its clinical efficacy.

Method used

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  • A kind of doxorubicin and glycyrrhetinic acid double drug nano-delivery system and preparation method thereof
  • A kind of doxorubicin and glycyrrhetinic acid double drug nano-delivery system and preparation method thereof
  • A kind of doxorubicin and glycyrrhetinic acid double drug nano-delivery system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The processing steps of the present embodiment are as follows:

[0033] Weigh 1.5 g of monomethoxypolyethylene glycol polycaprolactone with a molecular weight of 7000 kDa, 87.3 mg of dithiodipropionic acid, 165 mg of dicyclohexylcarbodiimide, and 98 mg of dimethylaminopyridine, and dissolve them in 5 mL of dimethyl In the sulfoxide solution, stir at room temperature for 24 hours, put the completed dispersion liquid into a dialysis bag with a molecular weight cut-off of 3.5 kDa, use pure water as the external fluid, and the dialysis time is 24 hours, during which the external fluid is replaced 6 times. The complete solution was lyophilized for 24 hours to obtain product A. Weigh 380 mg of product A, 20 mg of dicyclohexylcarbodiimide, and 18 mg of dimethylaminopyridine, dissolve in 2 mL of dimethyl sulfoxide solution, stir at room temperature for 2 hours, add 107 mg of doxorubicin, and react in the dark for 24 hours. The dispersion was put into a dialysis bag with a mole...

Embodiment 2

[0036] The processing steps of the present embodiment are as follows:

[0037]Weigh 0.5 g of monomethoxypolyethylene glycol polycaprolactone with a molecular weight of 8000 kDa, 27.1 mg of dithiodipropionic acid, 55 mg of dicyclohexylcarbodiimide, and 38 mg of dimethylaminopyridine, and dissolve them in 3 mL of dimethyl In the sulfoxide solution, stir at room temperature for 24 hours, put the completed dispersion liquid into a dialysis bag with a molecular weight cut-off of 3.5 kDa, use pure water as the external fluid, and the dialysis time is 12 hours, during which the external fluid is replaced 4 times. The complete solution was lyophilized for 24 hours to obtain product A. Weigh 200 mg of product A, 10 mg of dicyclohexylcarbodiimide, and 9 mg of dimethylaminopyridine, dissolve in 1 mL of dimethyl sulfoxide solution, stir at room temperature for 2 hours, add 50 mg of doxorubicin, and react in the dark for 24 hours. The dispersion was put into a dialysis bag with a molecula...

Embodiment 3

[0040] The processing steps of the present embodiment are as follows:

[0041] Weigh 0.3 g of monomethoxypolyethylene glycol polycaprolactone with a molecular weight of 7000 kDa, 30 mg of dithiodipropionic acid, 35 mg of dicyclohexylcarbodiimide, and 16 mg of dimethylaminopyridine, and dissolve them in 3 mL of dimethylaminopyridine In the sulfone solution, stir at room temperature for 24 hours, put the completed dispersion into a dialysis bag with a molecular weight cut-off of 3.5 kDa, use pure water as the external fluid, and perform dialysis for 12 hours, during which the external fluid is replaced 4 times. The product A was obtained by freeze-drying for 24 hours. Weigh 100 mg of product A, 10 mg of dicyclohexylcarbodiimide, and 8 mg of dimethylaminopyridine, dissolve in 2 mL of dimethyl sulfoxide solution, stir at room temperature for 2 hours, add 25 mg of doxorubicin, and react in the dark for 24 hours. The dispersion was put into a dialysis bag with a molecular weight cu...

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Abstract

The invention discloses an adriamycin and glycyrrhetinic acid double-drug nanometer transfer system and a method for preparing the same. The method includes catalyzing methoxy-polyethylene glycol polycaprolactone and di-thiodipropionic acid by dicyclohexylcarbodiimide and dimethylaminopyridine, connecting adriamycin onto catalysis products and carrying out dialysis impurity removal and drying to obtain macromolecular pro-drugs with oxidation-reduction properties; proportionally mixing the macromolecular pro-drugs and glycyrrhetinic acid with one another, dissolving the macromolecular pro-drugsand the glycyrrhetinic acid in organic solvents to obtain liquid, slowly dropwise adding the liquid into water phase, continuously stirring the liquid and the water phase, volatilizing the organic solvents and carrying out freeze drying to obtain nanometer particles. The methoxy-polyethylene glycol polycaprolactone and the di-thiodipropionic acid are used as raw materials. The adriamycin and glycyrrhetinic acid double-drug nanometer transfer system and the method have the advantages that the nanometer particles prepared by the aid of the method have small particle sizes, are uniformly distributed and are good in stability, accordingly, the water insolubility of the adriamycin and the glycyrrhetinic acid can be improved, the bioavailability of the adriamycin and the glycyrrhetinic acid canbe enhanced, curative effects can be synergistically realized by two drugs, and the antitumor activity can be enhanced.

Description

technical field [0001] The invention relates to a doxorubicin-glycyrrhetinic acid double-drug nano delivery system and a preparation method thereof. Background technique [0002] Cancer is a common public health problem, and tens of millions of people die from this deadly disease. Nanomedicine can achieve targeted delivery and slow release of chemotherapy drugs, thus becoming a research hotspot. Tumor cells have unique environmental characteristics, and the content of glutathione in tumor cytoplasm is significantly higher than that in normal tissues, making tumor cytoplasm highly reductive. As a first-line drug for tumor chemotherapy, doxorubicin can easily pass through the cell membrane and act on multiple targets. In addition, drug resistance is another unavoidable problem in chemotherapy, so simultaneous tumor chemotherapy with multiple drugs has been widely used in clinical practice. The synergy between different drugs can make them show obvious advantages in terms of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/60A61K31/704A61K31/56A61P35/00
Inventor 张雪琼汤明秀
Owner WUHAN UNIV OF TECH