Nanoscale chitosan derivative ultrasonic contrast medium capable of converting surface charges and preparation method of contrast medium

A chitosan derivative and ultrasonic contrast agent technology, applied in the field of chitosan derivative nano-scale ultrasonic contrast agent and its preparation, can solve the problem of poor targeting of nano-scale ultrasonic contrast agent, no drug-carrying characteristics treatment effect research and Evaluation, physical stability and poor blood circulation stability, etc., to achieve good blood compatibility and stability, good physical stability, and improve the effect of high efficiency

Active Publication Date: 2019-08-23
SHANDONG UNIV QILU HOSPITAL
View PDF2 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Chinese patent literature (CN106139174A) discloses a preparation method based on chitosan derivatives nano-scale ultrasonic contrast agent. The invention is to modify hydroxymethyl chitosan through acylation reaction, and synthesize amphiphilic On the basis of n-caproyl hydroxymethyl chitosan, liquid fluorocarbon is added, and a nano-scale ultrasonic contrast agent composed of a liquid fluorocarbon core and a chitosan derivative shell is prepa...

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
  • Nanoscale chitosan derivative ultrasonic contrast medium capable of converting surface charges and preparation method of contrast medium
  • Nanoscale chitosan derivative ultrasonic contrast medium capable of converting surface charges and preparation method of contrast medium
  • Nanoscale chitosan derivative ultrasonic contrast medium capable of converting surface charges and preparation method of contrast medium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0068] Example 1: Preparation of chitosan derivative nanoscale ultrasound contrast agent with switchable surface charge

[0069] A method for preparing a chitosan derivative nanoscale ultrasonic contrast agent capable of switching surface charges, the steps are as follows:

[0070] (1) Disperse 150 μL of perfluorohexane liquid, 6 μL of Tween 20, and 0.004 g of lecithin in 2.7 mL of deionized water, and homogenize at a high speed of 19,000 rpm for 1 min to prepare a suspension;

[0071] (2) Under the condition of 14000rpm high-speed mechanical stirring for 2min, add 0.225mL of O-carboxymethyl chitosan solution of 0.02g / mL dropwise to the suspension prepared in step (1), to obtain a suspoemulsion;

[0072] (3) Leave the suspoemulsion prepared in step (2) at room temperature for 5-10 minutes, centrifuge at 500 rpm for 3 minutes, take the upper layer liquid, and filter it through a 0.45 μm filter to obtain a nanoscale ultrasonic wave of chitosan derivatives that can switch surface...

Embodiment 2

[0075] Example 2: Analysis of Surface Charge Conversion of Chitosan Derivative Nanoscale Ultrasonic Contrast Agents

[0076]The chitosan derivative nano-scale ultrasound contrast agent (O-CS NDs) prepared in Example 1 and the chitosan nano-scale ultrasound contrast agent (CS NDs) were respectively dispersed in phosphate buffered saline (PBS) with a pH of 7.4 and 6.3. buffer), pH 7.4 simulates the normal blood environment, and pH 6.3 simulates the tumor microenvironment. After co-incubating for different times (0, 0.5, 1, 3h), use nano-laser particle size and Zeta potential analyzer to detect its particle size and surface charge. The result is as Figure 4 As shown, when the pH of O-CS NDs changes from 7.4 to 6.3, the surface charge changes from negative to positive, while the surface charge of CS NDs remains positive when the pH changes, without significant change. Moreover, O-CS NDs did not show obvious changes in particle size during the surface charge conversion process, ...

Embodiment 3

[0078] Embodiment 3: In vitro stability analysis of chitosan derivative nanoscale ultrasound contrast agent

[0079] The chitosan derivative nano-scale ultrasonic contrast agent (O-CS NDs) prepared in Example 1 was stored at 4°C, and after a certain period of time (0.5, 1, 3, 5, 24, 48h), it was detected by a nano-laser particle size analyzer Particle size variation of ultrasound contrast agents. Such as Image 6 As shown, the particle size of the ultrasound contrast agent is relatively stable within 48 hours of storage at 4°C, without significant changes.

[0080] The chitosan derivative nano-scale ultrasound contrast agent (O-CS NDs) prepared in Example 1 and the chitosan nano-scale ultrasound contrast agent (CS NDs) prepared in Example 2 were mixed with 10% fetal bovine serum (FBS) After incubation with phosphate buffered saline (PBS buffer) for a certain period of time (0, 1, 2, 4, 24 h), the particle size change of the ultrasound contrast agent was detected using a nano...

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 sizeaaaaaaaaaa
The average particle sizeaaaaaaaaaa
Login to view more

Abstract

The invention relates to a nanoscale chitosan derivative ultrasonic contrast medium capable of converting surface charges and a preparation method of the contrast medium. According to the nanoscale chitosan derivative ultrasonic contrast medium, tween 20, lecithin and perfluorohexane are adopted for preparing a mixed suspension solution through a nano emulsion method, O-carboxymethyl chitosan is stirred and dispersed in the mixed suspension solution through a high-speed machine, and after low-speed centrifugation and filtering, the nanoscale chitosan derivative ultrasonic contrast medium, witha small and even particle size, capable of converting the surface charges is obtained. According to the prepared nanoscale chitosan derivative ultrasonic contrast medium capable of converting the surface charges, with the O-carboxymethyl chitosan as a shell membrane, a perfluorohexane solution is wrapped by the interior of the shell membrane, the particle size is 150-200 nanometers, the ultrasonic contrast medium can penetrate through the blood vessel endothelium and enter the tumor microenvironment and has targeting performance and high efficiency on tumor treatment, the ultrasonic contrastmedium and protein substances in the serum are not easily subjected to protein agglutination in the blood environment, and the ultrasonic contrast medium has good blood compatibility and stability andfurther has a good drug(doxorubicin)-loaded capacity.

Description

technical field [0001] The invention relates to a chitosan derivative nanoscale ultrasonic contrast agent capable of converting surface charges and a preparation method thereof, belonging to the technical field of ultrasonic molecular imaging. Background technique [0002] Nanoparticle-based drug delivery systems can overcome the shortcomings of systemic toxicity, acquired drug resistance, and severe drug side effects of cancer chemotherapy, and have become an alternative to current cancer chemotherapy. In recent years, many studies have successfully synthesized multifunctional nanoscale drug delivery systems. These nanoparticles (such as liposomes, polymer micelles, nanoemulsions, nanobubbles, and nanodroplets, etc.) have the functions of targeting, imaging, and treatment. A variety of functions. Among them, chitosan (CS) has become an ideal nanoparticle shell material because of its safety, non-toxicity, good biocompatibility and biodegradability. Chitosan itself is inso...

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
IPC IPC(8): A61K49/22A61K9/107A61K47/36A61K31/704A61P35/00
CPCA61K9/107A61K31/704A61K47/36A61K49/22A61K49/226A61P35/00
Inventor 李杰孟冬郭鲁孙霄商蒙蒙时丹丹
Owner SHANDONG UNIV QILU HOSPITAL
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