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

Glycyrrhetinic acid-modified lipid, liver targeting liposome, micelle and compound, and their preparation method

A glycyrrhetic acid, liver targeting technology, applied in the field of medicine, can solve the problems of increasing the incorporation ratio, phagocytosis, and difficulty in ensuring biocompatibility, and achieves the effect of increasing the enrichment concentration and improving the targeting.

Active Publication Date: 2012-02-01
SICHUAN UNIV
View PDF1 Cites 16 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the introduction of stearyl alcohol in liposomes, its biocompatibility is difficult to guarantee
[0009] 2. Glycyrrhetinic acid-modified liposomes recorded in the literature are easily phagocytized by the mononuclear macrophage system, and it is difficult to reach hepatic parenchymal cells in large quantities, so they cannot be used as excellent carriers for drugs based on hepatic parenchymal cell diseases
[0010] 3. In the glycyrrhetinic acid-modified liposomes recorded in the literature, the molar content of directing molecules incorporated is up to 10%. If the proportion of incorporation is further increased, the obtained liposomes are white turbid liquid, and a large amount of flocculation will appear in a short time. Precipitate, unable to produce stable liposomes with high glycyrrhetinic acid targeting ligand content
[0011] 4. The average particle size of glycyrrhetinic acid surface-modified liposomes is between 65-79nm, and the particle size range is narrow, which is difficult to meet the particle size requirements of different liver diseases
[0012] 5. The glycyrrhetinic acid surface-modified liposomes recorded in the literature, the phospholipid used in the prescription is soybean phospholipid, which is prepared by injection method, which cannot meet the high-efficiency entrapment of drugs with different properties such as hydrophilic drugs, gene proteins and other macromolecular drugs
The main reason why macromolecular drugs such as gene proteins cannot be efficiently entrapped is that macromolecules such as gene proteins often have positive charges, and soybean phospholipids are neutral phospholipids, which cannot be efficiently entrapped by electrostatic adsorption; in addition, the preparation of injection method The encapsulation efficiency of macromolecular drugs such as hydrophilic drugs and gene proteins is relatively low.

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
  • Glycyrrhetinic acid-modified lipid, liver targeting liposome, micelle and compound, and their preparation method
  • Glycyrrhetinic acid-modified lipid, liver targeting liposome, micelle and compound, and their preparation method
  • Glycyrrhetinic acid-modified lipid, liver targeting liposome, micelle and compound, and their preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] The preparation of embodiment 1 glycyrrhetinic acid modified cholesterol:

[0055] Weigh 5g of glycyrrhetinic acid and place it in a 500mL round bottom flask, add 250mL of dichloromethane into the bottle, and magnetically stir to dissolve. Then add 2.5g of EDC into the bottle, stir magnetically until dissolved, then add 4g of cholesterol, continue to stir, and react at room temperature for 12 hours. The organic layer was washed with 1 mol / L HCl solution, saturated sodium bicarbonate solution and saturated NaCl solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent. The obtained solid was subjected to column chromatography (petroleum ether: acetone = 90:10-30:70 gradient elution) to obtain 7.4 g of a light yellow solid (yield 82.6%).

[0056] Above-mentioned solid also can adopt high performance liquid phase to purify, and its chromatographic condition is methanol / acetonitrile-water system, and detector is ul...

Embodiment 2

[0057] The preparation of embodiment 2 glycyrrhetinic acid modified phospholipids:

[0058] Weigh 1g of glycyrrhetinic acid and place it in a 250mL round bottom flask, add 100mL of dichloromethane into the bottle, and magnetically stir to dissolve. Then add 0.5g EDC to the bottle, stir magnetically until dissolved, cool in an ice-water bath, add 0.4g distearoylphosphatidylethanolamine (hereinafter referred to as DSPE), continue to stir until completely dissolved, keep ice-water bath cooling, avoid light for 24 hours . The organic layer was washed with 1 mol / L HCl solution, saturated sodium bicarbonate solution and saturated NaCl solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent. The resulting solid was subjected to column chromatography (n-hexane:acetone=95:5-25:75 gradient elution) to obtain 0.5 g of a white solid (yield 76.8%).

[0059] Above-mentioned solid also can adopt high performance liquid phase to p...

Embodiment 3

[0060] Example 3 Preparation of Glycyrrhetinic Acid Modified PEGylated Cholesterol:

[0061] Weigh 5g of glycyrrhetinic acid and place it in a 500mL round bottom flask, add 250mL of dichloromethane into the bottle, and magnetically stir to dissolve. Then add 2.5g of EDC and 0.9g of 4-dimethylaminopyridine (hereinafter referred to as DMAP) into the bottle, stir magnetically until dissolved, then add 18g of polyethylene glycol 2000, continue to stir, and react at room temperature for 12 hours. The organic layer was washed with 1 mol / L HCl solution, saturated sodium bicarbonate solution and saturated NaCl solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to remove the organic solvent. The resulting solid was subjected to column chromatography (dichloromethane:methanol=0:100-30:70 gradient elution) to obtain 7.8 g of a light yellow solid. The solid was placed in a 500 mL round bottom flask, 200 mL of dichloromethane was added into the bottle, ...

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
particle sizeaaaaaaaaaa
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
Login to View More

Abstract

The invention belongs to the medical field, and specifically, relates to a novel glycyrrhetinic acid-modified lipid, a liver targeting liposome, a micelle and a compound, and their preparation method. The novel glycyrrhetinic acid-modified lipid contains glycyrrhetinic acid as a liver targeting mediating material, and is utilized as a membrane material of a liposome or a micelle to enable the liposome or the micelle to have liver targeting activity. Specifically, the novel glycyrrhetinic acid-modified lipid is prepared from raw materials of glycyrrhetinic acid and a phosphatide or cholesterol by a reaction in a condensing agent-containing solvent. The invention also provides a liver targeting liposome carrier and a liver targeting micelle carrier mediated by glycyrrhetinic acid. The liver targeting liposome carrier is prepared from the novel glycyrrhetinic acid-modified lipid, cholesterol and a phosphatide. The liver targeting micelle carrier is prepared directly from the novel glycyrrhetinic acid-modified lipid. The invention also provides a liver targeting liposome compound or a liver targeting micelle compound comprising an encapsulation layer of the liver targeting liposome carrier and the liver targeting micelle carrier. Therefore, glycyrrhetinic acid mediation-related drugs can be targeted to hepatic cells; toxicity of the glycyrrhetinic acid mediation-related drugs on normal tissue is reduced; and drug effects of prevention and treatment of liver complaints are improved.

Description

technical field [0001] The invention belongs to the field of medicine, and specifically relates to glycyrrhetinic acid-modified lipids, liver-targeted liposomes, micelles and complexes and a preparation method. Background technique [0002] At present, liver diseases such as liver cancer and hepatitis are still one of the major diseases that endanger human health. A lot of work has been done in the vast scientific research work, but the prevention and treatment effect is still not satisfactory. Liver disease is still one of the powerful challenges facing the medical field. [0003] The treatment of hepatitis is mainly to use two or more antiviral drugs in combination. Since most patients with refractory hepatitis are in a state of immune tolerance, the curative effect of using only one drug is relatively poor. Different drugs are selected for different disease sites, so that the drugs can exert their efficacy at different sites at the same time. In addition, the body's own...

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): C07J63/00C08G65/48A61K9/127A61K47/28A61K47/34A61K9/00A61K48/00A61K38/00A61K47/48A61K31/56A61K31/352A61P1/16A61P35/00
Inventor 宋相容何谷吴晓华魏于全
Owner SICHUAN 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