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

Preparation method and application of a pH-sensitive hyaluronic acid-doxorubicin nano-prodrug

A technology of hyaluronic acid and doxorubicin, which can be used in pharmaceutical formulations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. problems, to achieve the effect of easy storage, easy directional drug delivery, and improved solubility

Inactive Publication Date: 2020-01-14
WUHAN UNIV OF TECH
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although doxorubicin has a broad anti-tumor spectrum and good curative effect, the side effects of doxorubicin after intravenous injection, mainly including nausea, vomiting, bone marrow suppression, gastrointestinal adverse reactions and cardiotoxicity, etc., severely limit the efficacy of doxorubicin. Clinical application

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 and application of a pH-sensitive hyaluronic acid-doxorubicin nano-prodrug
  • Preparation method and application of a pH-sensitive hyaluronic acid-doxorubicin nano-prodrug
  • Preparation method and application of a pH-sensitive hyaluronic acid-doxorubicin nano-prodrug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Dissolve 400mg of hyaluronic acid (HA, molecular weight 5300Da) in 30mL of formamide, and add 256mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) while magnetic stirring HCl), after reacting at room temperature for 30 min, 146 mg of N-hydroxysuccinimide (NHS) was added, and the reaction was continued for 2 h. At the same time, 255 mg of methyl 4-aminomethylbenzoate was dissolved in 15 mL of formamide, and after dissolution, it was added dropwise into the hyaluronic acid activation system, and reacted with magnetic stirring for 24 hours. After the reaction, the reaction mixture was dialyzed with distilled water (MWCO, 3500) for 3 days, and freeze-dried to obtain the product HA-Ester.

[0035] Weigh 300 mg of lyophilized HA-Ester and dissolve it in 15 mL of formamide, then add 1.5 mL of hydrazine hydrate (NH 2 -NH 2 ·H 2 O, mass fraction 85%), reflux reaction at 60° C. for 16 h under nitrogen protection condition. After removing most of the solv...

Embodiment 2

[0039] Dissolve 400mg of hyaluronic acid (HA, molecular weight: 9800Da) in 30mL of formamide, and add 256mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) while magnetically stirring HCl), after reacting at room temperature for 30 min, 146 mg of N-hydroxysuccinimide (NHS) was added, and the reaction was continued for 2 h. At the same time, 255 mg of methyl 4-aminomethylbenzoate was dissolved in 15 mL of formamide, and after dissolution, it was added dropwise into the hyaluronic acid activation system, and reacted with magnetic stirring for 24 hours. After the reaction, the reaction mixture was dialyzed with distilled water (MWCO, 3500) for 3 days, and freeze-dried to obtain the product HA-Ester.

[0040] Weigh 300 mg of lyophilized HA-Ester and dissolve it in 15 mL of formamide, then add 1.5 mL of hydrazine hydrate (NH 2 -NH 2 ·H 2 O, mass fraction 85%), reflux reaction at 60° C. for 16 h under nitrogen protection condition. After removing most of the...

Embodiment 3

[0044] Dissolve 400mg of hyaluronic acid (HA, molecular weight 37000Da) in 30mL of formamide, and add 256mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) while magnetically stirring HCl), after reacting at room temperature for 30 min, 146 mg of N-hydroxysuccinimide (NHS) was added, and the reaction was continued for 2 h. At the same time, 255 mg of methyl 4-aminomethylbenzoate was dissolved in 15 mL of formamide, and after dissolution, it was added dropwise into the hyaluronic acid activation system, and reacted with magnetic stirring for 24 hours. After the reaction, the reaction mixture was dialyzed with distilled water (MWCO, 3500) for 3 days, and freeze-dried to obtain the product HA-Ester.

[0045] Weigh 300 mg of lyophilized HA-Ester and dissolve it in 15 mL of formamide, then add 1.5 mL of hydrazine hydrate (NH 2 -NH 2 ·H 2 O, mass fraction 85%), reflux reaction at 60° C. for 16 h under nitrogen protection condition. After removing most of the...

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
particle sizeaaaaaaaaaa
particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention discloses a preparation method and application of a pH-sensitive hyaluronic acid-doxorubicin nanometer prodrug. The nanometer prodrug is prepared through the following preparation steps of firstly reacting amino in 4-aminomethyl methyl benzoate with carboxyl of hyaluronic acid to form an amido bond; forming hydrazine by using methoxy in a reactant in the previous step and hydrazine hydrate, and further forming a hydrazone bond by using a product and carbonyl of doxorubicin; and finally preparing nanometer prodrug particles through an ultrasonic assisted self-assembly method. The microstructure and the in vitro release property of the nanometer particles are researched, cellular uptake and a cytotoxicity test can be further carried out to prove that the macromolecular prodrug nanometer particles have obvious pH sensitivity and ideal in vitro anti-tumor activity, the problem of large toxic and side effects of the micromolecular drug doxorubicin can be solved and a basis can be provided for clinical application.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a preparation method and application of a pH-sensitive hyaluronic acid-doxorubicin nanometer prodrug. Background technique [0002] Malignant tumor is a major disease that seriously threatens human life, and liver cancer is one of the common digestive system tumors. Doxorubicin, also commonly known as doxorubicin and daunorubicin, is an anthracycline broad-spectrum antitumor antibiotic, cycle non-specific drug, and has killing effects on tumor cells of various growth cycles. Doxorubicin can successfully inhibit a variety of malignancies, including acute leukemia, lymphoma, soft tissue and osteosarcoma, childhood malignancies, and adult solid tumors. Although doxorubicin has a broad anti-tumor spectrum and good curative effect, the side effects of doxorubicin after intravenous injection, mainly including nausea, vomiting, bone marrow suppression, gastrointestinal adverse reac...

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): A61K47/61A61K31/704A61P35/00A61K9/51
CPCA61K9/5161A61K31/704
Inventor 郑化费增明廖健洪曹俊王宝龙危培魏璇
Owner WUHAN UNIV OF TECH
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