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

Triblock polymer, drug-loaded nano-micelle, nano-drug as well as preparation method and application of nano-drug

A drug-loading nanometer and nanomedicine technology, applied in the field of nanomedicine, can solve the problem of inability to accurately deliver multi-target drugs, achieve high drug loading rate and stability, and achieve the effect of precise regulation and control of the structure

Active Publication Date: 2019-11-22
SUN YAT SEN UNIV
View PDF12 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to overcome the problems and deficiencies in the prior art that the multi-target drug cannot be accurately delivered to the specific position of the corresponding tumor site, and to provide a tri-block polymer

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
  • Triblock polymer, drug-loaded nano-micelle, nano-drug as well as preparation method and application of nano-drug
  • Triblock polymer, drug-loaded nano-micelle, nano-drug as well as preparation method and application of nano-drug
  • Triblock polymer, drug-loaded nano-micelle, nano-drug as well as preparation method and application of nano-drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Synthesis of Example 1 Cyclodextrin Polypeptide Conjugate

[0054] Synthesis of cyclodextrin-peptide conjugates as figure 1 As shown, it is divided into the following three parts:

[0055] First, weigh 30g of β-cyclodextrin, dissolve it in 300mL of 1mol / L NaOH solution, add 6g of p-toluenesulfonyl chloride in an ice-water bath, and continue the magnetic stirring reaction at 0-5°C for 5h. After the reaction is complete, filter with suction , to remove solid insolubles. The filtrate was adjusted to pH=7 with 10% hydrochloric acid, and a large amount of white precipitate was produced at this time, and then it was put into a refrigerator at 4°C overnight to allow the precipitate to fully separate out. Then, the solid was obtained by suction filtration and washed three times with a small amount of cold deionized water, and the solid was recrystallized in hot water to obtain the product CD-OTs. like image 3 Shown in A, its proton nuclear magnetic resonance spectrum in de...

Embodiment 2

[0058] The synthesis of embodiment 2 related polymers

[0059] like figure 2 As shown, the synthesis of polymer (i.e. triblock polymer) is divided into the following steps:

[0060] First, 1g mPEG 5k -NH 2 (Amino conversion rate of 95%) was put into a 100 mL Schlenk tube, dried under vacuum at 70° C. for 2 h, and then cooled to room temperature. Ice water bath, filled with N 2 Under protection, add 20 mL of freshly distilled CHCl 3 , Weigh 0.5g of MA-Lysine-NCA and dissolve it in 5mL of ultra-dry DMF, and add it to the reaction bottle at one time. The reaction was sealed, and the magnetic stirring was carried out at 35° C. for 48 h (at this time, sampling was used for nuclear magnetic measurement to determine the number of PLLMA repeating units), and then in N 2 Under protection, dissolve 1g of BLA-NCA monomer in 5mL of ultra-dry DMF and add it to the above reaction flask, and add 10mL of freshly distilled CHCl 3 , sealed, and continued to react at 35°C for 48h. After...

Embodiment 3

[0066] Preparation of Example 3 Empty Carrier Nanoparticles

[0067] This example provides a method for preparing empty carrier nanoparticles (ie, drug-loaded nanomicelles responsive to the tumor microenvironment), as follows.

[0068] Dissolve a certain amount of polymer mPEG-PLLMA(CD-Peptide-SH)-PAsp(DBP) in an appropriate amount of good solvent DMF, and then add the polymer solution dropwise to a large amount of selective solvent H under stirring or ultrasonic dispersion conditions. 2 O middle. The specific operation is as follows, 20 mg of polymer is dissolved in 2 mL of DMF, 20 mL of deionized water is placed in a small beaker and placed in an ice-water bath, and the polymer solution is added dropwise to the deionized water under ultrasonic vibration. After all the addition was completed, the micellar solution was put into a dialysis bag and dialyzed with deionized water for 2 days to remove DMF. After the organic solvent is removed by dialysis, it is concentrated by ul...

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
Concentrationaaaaaaaaaa
Particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention relates to a triblock polymer, a drug-loaded nano-micelle, a nano-drug as well as a preparation method and application of the nano-drug. The triblock polymer comprises a hydrophilic segment polyethylene glycol, an intermediate segment poly (methacryloyl lysine-g-(cyclodextrin polypeptide)) and a hydrophobic segment poly (aspartyl-N, N-dibutyl propylamine). The triblock polymer comprises a pH-sensitive chain segment and an MMP-2 enzyme-sensitive middle segment, and can be self-assembled into a nano-micelle; the assembled nano-micelle takes a pH-sensitive chain segment as a core, takes an MMP-2 enzyme-sensitive chain segment as a middle layer and takes methoxy polyethylene glycol as an outermost layer, so that the nano-micelle has smaller particle size, higher drug loading rate, good pH and MMP enzyme sensitivity and low toxicity to cells. The triblock polymer has the advantages that chemotherapy drugs and anti-angiogenesis drugs can be loaded at the same time, microenvironment responsive release of the drugs can be achieved, targeted drug therapy of different cells of tumor sites is achieved, and the drug carrier has great innovativeness and application value.

Description

technical field [0001] The invention belongs to the field of nanomedicine, and more specifically relates to a triblock polymer, drug-loaded nano-micelle, nano-medicine, and a preparation method and application thereof. Background technique [0002] Solid tumors have a complex physiological microenvironment such as: low pH, high intracellular concentration of reduced glutathione (GSH), and anaerobic environment inside the tumor. At the same time, the cellular composition of solid tumor tissues is also very complex. Non-malignant cells in tumor tissue except cancer cells are closely related to tumor growth, proliferation, invasion, metastasis and angiogenesis. [0003] The complex composition and rapid proliferation behavior of tumor tissue result in heterogeneity of tumor tissue structure and complex tumor microenvironment. Chemotherapy strategies that only target cancer cells are often unable to completely eliminate tumors. In order to solve the problem of limited curativ...

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): C08G81/00A61K9/107A61K47/34A61K47/40A61K31/337A61K31/404A61P35/00
CPCA61K9/1075A61K31/337A61K31/404A61K47/34A61K47/40A61P35/00C08G81/00A61K2300/00
Inventor 帅心涛何进肖洪王勇
Owner SUN YAT SEN 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