Sulfated PEG lipid derivative and its preparing process and application

A technology of lipid derivatives and sulfate esterification, applied in the field of medicine, can solve the problems of inability to cells, fusion, inability to combine, etc., and achieve the effects of reducing degradation, protecting drugs, and improving activity

Inactive Publication Date: 2007-08-08
SHENYANG PHARMA UNIVERSITY
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mutagenesis and antibody competition experiments proved that gp120 lacking the V3 loop can bind to CD4 normally, but cannot bind to CCR5 / CXCR4 and cannot fuse with cells

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
  • Sulfated PEG lipid derivative and its preparing process and application
  • Sulfated PEG lipid derivative and its preparing process and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Embodiment 1: Preparation of Cholesterol Polyethylene Glycol Sulfate

[0019] The methods for preparing the compound of formula I include concentrated sulfuric acid method, sulfur trioxide-pyridine method, chlorosulfonic acid-pyridine method, sulfur trioxide-dimethylformamide method and the like.

[0020] Chlorosulfonic acid method:

[0021] Add 2 mL of pyridine into a 25 mL three-necked flask, add 0.2 mL of chlorosulfonic acid dropwise under ice-cooling, stir and react at 5°C for 30 minutes, then add 0.2 g of cholesterol polyethylene glycol 2000 (with hydroxyl at the end of PEG), 60 ℃ and stirred for 1 hour, poured into ice water, stirred for 30 minutes to precipitate a precipitate, filtered, washed with water until the pH value was neutral, and dried to obtain 0.23 g of a white solid. IR(KBr)(cm -1 ): 1287, 1172, 851 (ROSO 3 h).

[0022] The same method can prepare PEG sulfate cholesterol derivatives and salts thereof with molecular weights of 300 or 30,000, respe...

Embodiment 2

[0023] Embodiment 2: Increase the degradation stability of AZTP in rat plasma

[0024] According to the conventional method, with AZTP / SPC 4 / V E (1:10:0.1) ratio to prepare liposomes; with AZTP / SPC 4 / V E / compound I (1:10:0.1:0.1) ratio to prepare coated liposomes. Likewise, submicroemulsions and coated submicroemulsions are prepared according to conventional methods.

[0025] Zidovudine (AZT) solution and lipid prodrug zidovudine palmitate (AZTP) different liposome groups (common liposomes, polyethylene glycol sulfate cholesterol-coated liposomes) 1. Different submicron emulsion groups (ordinary submicron emulsion, polyethylene glycol sulfate cholesterol-coated submicron emulsion) were respectively placed in 10% rat plasma, incubated at 37°C, samples were taken at different time points, and zidoxin in plasma was determined. The concentration of vudine, the t of solution group, common liposome group, coated liposome group 1 / 2 Respectively 18 times and 171 times of the solu...

Embodiment 3

[0028] Example 3: Prepare liposomes for injection coated with polyethylene glycol sulfate cholesterol derivatives, and investigate its distribution in various tissues of mice.

[0029]The parent drug zidovudine (AZT) solution and lipid prodrug zidovudine palmitate (AZTP) liposome group (polyethylene glycol sulfate cholesterol-coated liposome (PEG-CH-S group) ) mouse tail vein administration to investigate the distribution of zidovudine in different tissues of mice. Compared with the AZT solution, the distribution of the drug in the liposome in the heart, liver, spleen, lung, and brain increased, and the relative uptake rate (re) was greater than 1. See attached table 2 for specific values, indicating that the liposome can increase The targeting of drugs in these tissues, among which the increase of drug concentration in the brain is the most significant. Compared with the solution group, the distribution in the kidney of the liposome group was significantly reduced, which was...

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
wavelengthaaaaaaaaaa
Login to view more

Abstract

The invention relates to a method for preparing sulfuric (sulfonic acid) esterification PEG liposome derivate, and relative application in drug transmitter, especially the application of novel polyethylene glycol dimethyl ether cholesterol sulfate derivate in medical aera. The inventive sulfuric (sulfonic acid) esterification PEG liposome derivate is sulfuric (sulfonic acid) esterification PEG cholesterol, sulfuric (sulfonic acid) esterification PEG sterol, sulfuric (sulfonic acid) esterification PEG tocofecol, sulfuric (sulfonic acid) esterification PEG vitamin D, sulfuric (sulfonic acid) esterification PEG phosphatide, or sulfuric (sulfonic acid) esterification PEG-DSPE. And the drug transmitter comprises a gel beam, a nanometer gel beam, an emulsifier, a micro emulsifier, a nanometer emulsion, a liposome, and nanometer particles. The invention esterificates and connects the PEG sulfuric (sulfonic acid) with cholesterol to prepare derivate, to protect drug, reduce degradation, and prolong the circulation time in body, and realize the combination with gp120 specificity at the surface of HIV, to transmit drug targeted.

Description

Technical field: [0001] The invention belongs to the technical field of medicine, relates to a sulfated PEG lipid derivative and its preparation method and its application in a drug delivery system, and more specifically relates to a novel auxiliary material polyethylene glycol monomethyl ether cholesterol sulfate derivative Applications in the field of medical technology. Background technique: [0002] Generally speaking, drug delivery systems, such as emulsions, microemulsions, nanoemulsions, liposomes, nanoparticles, etc., will be damaged by various factors in the blood, mainly opsonin, and most of them will be transported to the liver In areas where mononuclear phagocyte system (MPS) is abundant, such as spleen and spleen, in order to reduce the uptake of MPS and prolong the circulation time, PEGylated carriers have appeared. At present, the more common PEG lipid derivative is PEG-DSPE, among which PEG2000-DSPE (PEG2000-phosphatidylethanolamine) has become a pharmaceuti...

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): A61K47/48A61K47/28A61K47/34C07J9/00A61K47/60A61K47/69
Inventor 邓意辉陈国良王绍宁徐晖金圣煊李杰周欣羽毕殿洲
Owner SHENYANG PHARMA UNIVERSITY
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