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

Temozolomide nanoprodrug micelle and preparation method and application thereof

A technology of temozolomide and prodrugs, which is applied in the field of amphiphilic block polymers, can solve the problems of increasing drug carrier accumulation, reducing drug efficacy, and inability to release drugs, and achieve the effects of slow release, extended half-life, and difficult dissociation

Active Publication Date: 2021-11-02
XUZHOU NORMAL UNIVERSITY
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although drug carriers such as nanoparticles, nanomicelles, and polymer vesicles formed by self-assembly of amphiphilic copolymers can prolong the circulation time of drugs in the body and increase the accumulation of drug carriers in tumor sites, they are often ineffective. to release the drug, thereby reducing the efficacy of the drug

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
  • Temozolomide nanoprodrug micelle and preparation method and application thereof
  • Temozolomide nanoprodrug micelle and preparation method and application thereof
  • Temozolomide nanoprodrug micelle and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The synthesis method of polyoxazoline-polytemozolomide is similar except that the hydrophilic segment is different. Therefore, this embodiment only takes the synthesis of poly(2-methyl-2-oxazoline)-polytemozolomide as an example.

[0038] (1) Synthesis of temozolomide-methacrylate

[0039]

[0040]Dissolve 4.58g, 0.024mmol temozolomide (TMZ) in concentrated sulfuric acid, add 47.2mL of sodium nitrite aqueous solution dropwise under ice bath, keep stirring at room temperature for 17h and then drop to 0°C, add 122.0g of ice water to the system , to quench the reaction, filter, wash with ice water and dry to give temozolomide-8-carboxylic acid (TMZ-COOH).

[0041] Add 1.185g, 6.10mmol TMZ-COOH to the dichloromethane solution, then add 0.706mL of hydroxyethyl methacrylate (5.82mmol, HEMA), 1.348g of 1-(3-dimethylaminopropyl)- 3-Ethylcarbodiimide hydrochloride (7.02mmol, EDC) and 0.072g of 4-dimethylaminopyridine (0.58mmol, DMAP), continued to stir at room temperature fo...

Embodiment 2

[0062]

[0063] This embodiment is another preparation method of temozolomide nano-prodrug micelles (amphiphilic polyethylene glycol-polytemozolomide block polymer), and its preparation method is basically similar to that of Example 1, mainly comprising: anhydrous and oxygen-free Under the condition of environment, react polyethylene glycol (PEG) with 4-cyano-4-(thiobenzoyl)valeric acid (CTA) through esterification reaction, and then use PEG-CTA as macromolecular RAFT reagent, in Under the catalysis of azobisisobutyronitrile (AIBN), react with temozolomide-methyl methacrylate to obtain polyethylene glycol-polytemozolomide block polymer. The molecular weight of polyethylene glycol is 3000-10000Da, the molecular weight of polytemozolomide is 3000-10000Da, the degree of polymerization of polyethylene glycol is 39-131, and the degree of polymerization of polytemozolomide is 10-32.

Embodiment 3

[0065] Dissolve the hydrophobic drug in the organic solution first, then stir together with the organic solution of the amphiphilic block polymer, then add dropwise secondary water twice the volume of the organic solution, and stir the obtained solution for 1 hour Dialysis to obtain nanomicelles encapsulating the drug; the hydrophobic drug is selected from but not limited to: one of adriamycin, paclitaxel, methotrexate, curcumin or camptothecin.

[0066] The encapsulation of anticancer drugs in polyoxazolin-polytemozolomide micelles and polyethylene glycol-polytemozolomide micelles is all realized by dialysis. Taking PMeOx-PTMZ as an example, 2.4 mg of the polymer was dissolved in 1.0 mL of dimethyl sulfoxide, and the designed doxorubicin (DOX) required for a drug loading of 15% was added therein, and after ultrasonication for 0.5 h, Under the condition of stirring at room temperature, 1.8 mL of secondary water was slowly added dropwise to the dimethyl sulfoxide solution, and ...

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 diameteraaaaaaaaaa
molecular weightaaaaaaaaaa
particle diameteraaaaaaaaaa
Login to View More

Abstract

Temozolomide nano-prodrug micelles comprise a hydrophilic shell and a hydrophobic core, the hydrophilic shell is polyoxazoline or polyethylene glycol, and the hydrophobic core is polytemozolomide. Its preparation method is: react polyoxazoline or polyethylene glycol with 4-cyano-4-pentanoic acid through esterification, and use the obtained product as a macromolecular RAFT reagent under the catalysis of azobisisobutyronitrile to react with Temozolomide-methyl methacrylate reacts to obtain an amphiphilic block polymer. The amphiphilic block polymer of the present invention can prolong the half-life of temozolomide. The two kinds of amphiphilic block polymer nanomicelles belong to the drug prodrug of temozolomide. At the same time, the micelle core can carry other anticancer drugs to achieve different Combination therapy of drugs. After the polyoxazoline-polytemozolomide micelles enter the tumor cells, they are cleaved in the acidic environment of the cancer cells, and the encapsulated drugs are quickly released, thereby producing a highly effective therapeutic effect, which solves the problem of slow release of the drug carrier drug and easy to produce anti-inflammatory effects. Medicinal issues.

Description

technical field [0001] The invention relates to an amphiphilic block polymer, and relates to a temozolomide nano-prodrug micelle and a preparation method and application thereof. Background technique [0002] In recent decades, various nanocarriers have been widely developed to improve the efficacy of cancer chemotherapy, and these nanocarriers have the ability to target and control the release of anticancer drugs due to their enhanced permeability and retention (EPR) effect. Among them, micelles formed by amphiphilic block polymers have attracted great interest in the field of drug release. Polymer micelles of amphiphilic block polymers are a kind of nanocarriers for anticancer drugs, which are widely used in drug delivery, and they have several excellent salient features, including long circulation time, good drug solubility, and tumor site localization. Passive targeting ability. Amphiphilic polymers can self-assemble in water to form polymer nanomicelles (Micelles) thr...

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): A61K9/107A61K31/4188A61K47/60A61K47/59A61K31/704A61K31/337A61K31/519A61K31/12A61K31/4745A61P35/00
CPCA61K9/1075A61K31/12A61K31/337A61K31/4188A61K31/4745A61K31/519A61K31/704A61K47/59A61K47/60A61P35/00A61K2300/00
Inventor 李玉玲张诃娜许康杜百祥
Owner XUZHOU NORMAL UNIVERSITY
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