Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of tyr/ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors

A technique of artesunate and double modification, which is applied in the field of medicine and achieves the effects of good targeting, safe use and strong targeting killing effect

Active Publication Date: 2022-05-31
中国人民解放军陆军特色医学中心
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there has been no report on the preparation of artesunate into brain-targeted nano-preparations with double-target modification and its use in the treatment of brain tumors such as glioma.

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
  • Preparation method of tyr/ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors
  • Preparation method of tyr/ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors
  • Preparation method of tyr/ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Polyethylene glycol-polycaprolactone (PEG 2000 -PCL 7500 , referred to as PEG-PCL) as the carrier material to prepare PCL-PEG-Tyr and PCL-PEG-Ang.

[0033] (1) Synthesis and characterization of PCL-PEG-Tyr

[0034] Take Boc-PEG 2000 -OH 0.5g, add 1.9g caprolactone and 0.3g stannous octoate catalyst, polymerize at 130°C for 24 hours, add 10mL dichloromethane to dissolve completely, then pour into a large amount of ether to precipitate to obtain Boc-PEG 2000 -PCL 7500 product. Take 1.5g Boc-PEG 2000 -PCL 7500 Dissolve in 6 mL of dichloromethane, add 5 mL of trifluoroacetic acid, stir at room temperature for 1 h, wash with pure water 3 times, dry over anhydrous sodium sulfate, and then pour into a large amount of ether to precipitate to obtain NH 2 -PEG 2000 -PCL 7500 product. Take 1g NH 2 -PEG 2000 -PCL 7500 Dissolve in 5mL chloroform, add Boc-L-Tyr (2eq.), EDC (2eq.) and 0.2g DMAP, react at room temperature for 10h, wash with pure water 3 times, and dry over...

Embodiment 2

[0039] Preparation of PCL-PEG Series Nanoparticles Loaded with Artesunate

[0040] Preparation of unmodified PCL-PEG nanoparticles loaded with artesunate: 20.0 mg of PCL-PEG and 1.0 mg of artesunate were dissolved in 1.0 mL of THF, then stirred at 400 rpm, and then 5 mL of purified In water, continue stirring for 6 hours to volatilize tetrahydrofuran to obtain drug-loaded PCL-PEG nanoparticles.

[0041] Single-target modified nanoparticles loaded with artesunate: 17.97mg unmodified PCL-PEG nanoparticles, 2.03mg Tyr-modified carrier material PCL-PEG-Tyr (or 17.51mg unmodified PCL-PEG nanoparticles, 2.49mg Ang-modified carrier material (PCL-PEG-Ang) was dissolved in 1.0 mL of tetrahydrofuran, 1.0 mg of artesunate drug was added, then stirred at a speed of 400 rpm, and 5.0 mL of purified water was added dropwise, and the stirring was continued for 6 hours After the tetrahydrofuran is volatilized, the drug-loaded PCL-PEG-Tyr or PCL-PEG-Ang nanoparticles are obtained.

[0042] Pr...

Embodiment 3

[0053] Study on drug properties of PCL-PEG series nanoparticles loaded with artesunate

[0054] (1) In vitro release study

[0055] 20.0 mg of lyophilized artesunate-loaded nanoparticles were redispersed in 5.0 mL of phosphate buffered saline (PBS, 0.1 M, pH 7.4), and then loaded into dialysis bags (molecular weight cut-off 3.5–5 kDa). Dialysis bags were soaked in 15.0 mL of release medium (PBS containing 0.5% w / v SDS) and incubated in a shaking air bath (37.0±0.5°C) at 80 rpm for 96 hours. At designated time points (2, 4, 6, 8, 10, 24, 48, 72, 96 h), 1.0 mL of release medium was taken out for HPLC analysis of drug content, and an equal volume of fresh release medium was added to meet the leak slot condition.

[0056] The results of the in vitro release behavior of artesunate were as follows: Figure 4 As shown, artesunate was entrapped in PCL-PEG nanoparticles, which met the sink condition during the release process. The in vitro release was measured for 96 hours. Overall,...

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 a preparation method of a Tyr / Ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors, belonging to the technical field of medicine. The nano-targeting preparation prepared by the present invention uses artesunate as a raw material, polyethylene glycol-polycaprolactone as a carrier material, and Tyr / Ang as a double target head modification carrier, and is prepared by a solvent evaporation method. The Tyr / Ang double-modified artesunate nano-preparation of the present invention can be enriched in the blood-brain barrier in a targeted manner, and after passing through the blood-brain barrier and entering the brain parenchyma, it can be targeted in the brain glioma cells so as to protect the brain glia. The tumor plays a targeted killing effect, has good targeting, and a good tumor growth inhibitory effect, low toxic and side effects, and is relatively safe to use. The preparation of the antimalarial drug artesunate into a targeted nano-preparation with double-target modification provides a new idea for the treatment of brain tumors such as new gliomas, and has important clinical significance.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a preparation method of a Tyr / Ang double-modified artesunate nano-targeted preparation and its application in the treatment of brain tumors. Background technique [0002] Glioma is the most common primary brain tumor, accounting for about 46% of intracranial tumors, and has a high mortality rate. The comprehensive treatment of surgery combined with radiotherapy and chemotherapy is a commonly used standard treatment for glioma. Due to the aggressive growth characteristics and the special anatomical location of malignant glioma, it is difficult to completely remove it by surgery. Although radiotherapy has a certain curative effect, it is easy to cause radiation necrosis, and the remission period usually does not exceed 8 months. General antitumor drugs have insufficient ability to penetrate the blood-brain barrier (BBB) ​​and the local tumor drug concentration is low, and drug res...

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 Patents(China)
IPC IPC(8): A61K47/60A61K47/62A61K47/69A61K31/357A61P35/00A61P25/00C08G63/664C08G63/91
CPCA61K47/60A61K47/62A61K47/6935A61K31/357A61P35/00A61P25/00C08G63/664C08G63/912A61K2300/00Y02P20/55
Inventor 陈剑鸿李斌倪睿王显凤蔡永青傅若秋明月段冬玉李紫薇李莉
Owner 中国人民解放军陆军特色医学中心