11-deoxyglycyrrhetinic acid stearyl alcohol ester, derivative, cantharidin lipidosome, preparation method and application

A technology of deoxyglycyrrhizae and cantharidin lipids, which is applied in the field of preparation of stearyl 11-deoxyglycyrrhetinate, cantharidin liposomes, derivatives, and can solve the problems of restricting wide application and pseudoaldosteronism, etc.

Active Publication Date: 2019-07-19
HUNAN UNIV OF CHINESE MEDICINE
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, Wu Chao and others disclosed the use of glycyrrhetinic acid stearyl ester-3-O-galactoside to modify the cantharidin liposome Cantharidin liposomes, but stearyl glycyrrhetinate-3-O-galactoside is often accompanied by pseudoaldosteronism (manifested as edema, eczema, hypokalemia, etc. after long-term medication), limiting Its wide application in clinical

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
  • 11-deoxyglycyrrhetinic acid stearyl alcohol ester, derivative, cantharidin lipidosome, preparation method and application
  • 11-deoxyglycyrrhetinic acid stearyl alcohol ester, derivative, cantharidin lipidosome, preparation method and application
  • 11-deoxyglycyrrhetinic acid stearyl alcohol ester, derivative, cantharidin lipidosome, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Synthesis of stearyl 11-deoxyglycyrrhetinate: take 0.45g HgCl 2 , add 15mL of hydrochloric acid solution with a concentration of 1.2mol / L, fully shake to dissolve, then add 4.5g of uniformly ground zinc powder, shake fully for 5min, remove the water phase, and wash twice with 5mL of dioxane to obtain , set aside; take 0.45g of the prepared zinc amalgam in a 50mL round bottom flask, add 0.72g of stearyl glycyrrhetinate and 13.5mL of dioxane to fully dissolve it, and use an ice-water bath to control the temperature at about 10°C. Add 1.5mL of hydrochloric acid with a concentration of 12mol / L within 30min, keep stirring at 10°C to continue the reaction for 5h after the addition is complete, TLC indicates the end point, pour the reaction solution into about 100mL of distilled water to precipitate a white precipitate, filter it with suction, dry it, and purify it. have to.

Embodiment 2

[0059] Synthesis of 11-stearyl deoxyglycyrrhetinate: take by weighing 0.70 g of stearyl deoxyglycyrrhetinate obtained in Example 1, 2.1 g of succinic anhydride and 0.01 g of DMAP (4-dimethylaminopyridine) in a circle Add 20mL of anhydrous double-distilled pyridine to the bottom flask, heat to reflux at 106°C, and check the reaction process by TLC. After the reaction, pour the reaction solution into 200mL of distilled water to form a brown precipitate, filter it, dry and purify it.

Embodiment 3

[0061] Synthesis of 11-stearyl deoxyglycyrrhetinate-3-O-galactoside: Weigh 4 g of stearyl deoxyglycyrrhetinate obtained in Example 1, 3.3 g of bromoacetyl galactoside, and 3.8 g of silver oxide , 8.7g of dried gypsum, 0.4g of iodine, and 20ml of chloroform were placed in a 50ml round-bottomed flask, mixed thoroughly, and magnetically stirred at 15°C for 5h. During the reaction period, the reaction process was detected by TLC every 1 h (developing agent: ethyl acetate-petroleum ether=1:5; thin-layer plate: silica gel G plate; chromogenic agent: iodine) until the end of the reaction. Filter the reaction solution, rinse the filter residue twice with 20ml of chloroform, collect the filtrate and evaporate to dryness on a water bath at 60°C, and purify to obtain 11-deoxyglycyrrhetinic acid stearyl-3-O-bromoacetylgalactoside ; Take 0.5 g of pure stearyl 11-deoxyglycyrrhetinate-3-O-galactoside, add 60 ml of 5 mg / ml methanol-sodium methoxide solution, and stir magnetically at 30°C for ...

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 discloses 11-deoxyglycyrrhetinic acid stearyl alcohol ester, a derivative, cantharidin lipidosome, a preparation method and the application thereof. The 11-sodium deoxyglycyrrhetinic acid stearyl alcohol ester is prepared by directly putting glycyrrhetinic acid stearyl alcohol ester into amalgam zinc for deoxidation treatment, that is, an esterification reaction is firstly carried out, deoxidation treatment is carried out later, and the 11-deoxyglycyrrhetinic acid stearyl alcohol ester and succinic anhydride are further subjected to an acylation reaction to obtain 11-deoxycarbenoxolone stearyl alcohol ester which is reacted with acetyl bromide galactoside and the like to obtain the 11-deoxyglycyrrhetinic acid stearyl alcohol ester-3-O-galactoside. The cantharidin lipidosome modified by the 11-deoxycarbenoxolone stearyl alcohol ester and the 11-deoxyglycyrrhetinic acid stearyl alcohol ester-3-O-galactoside has good liver targeting and is capable of alleviating adverse reactions of livers, inhibiting tumor cell proliferation, inducing apoptosis of tumor cells and improving medicine treatment effects, and the lipidosome is high in encapsulation efficiency.

Description

technical field [0001] The invention belongs to the technical field of drug carriers, and in particular relates to stearyl 11-deoxyglycyrrhetinate, derivatives, cantharidin liposomes, preparation methods and applications. Background technique [0002] Liposome, as a main carrier for drug passive targeting, is mainly phagocytized and further eliminated by non-parenchymal cells of the liver after intravenous administration, and rarely reaches hepatic parenchymal cells. In fact, most diseases related to the liver, such as liver cancer, hepatitis, and cirrhosis, mostly occur in parenchymal cells, which are important cells of the liver and most of the metabolic sites of the liver. Therefore, only by improving the targeting of liposomes in hepatic parenchymal cells can anticancer drugs play a better role. [0003] Cantharidin is an anti-cancer active ingredient contained in the insect Cantharidin of the Coleoptera Turnipaceae. It is an anti-tumor drug developed in my country. It ...

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 Applications(China)
IPC IPC(8): C07J63/00A61K31/56A61K47/54A61K47/69A61P35/00
CPCC07J63/008A61K31/56A61K47/554A61K47/6911A61P35/00
Inventor 夏新华杜可杨晶颜红周莉莉周容钟思雨袁礼彭颖唐颖楠邹蔓姝朱坤乔勇
Owner HUNAN UNIV OF CHINESE MEDICINE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap