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Nano-drug carrier, reduction response nano-drug granules, nano-drug granular preparation and preparation method thereof

A nano-drug carrier and nano-drug technology, applied in the field of medicine, can solve the problems of limiting the wide application of nano-carriers, difficult drug release at the target site, and inability to simultaneously load multiple small molecule drugs.

Active Publication Date: 2013-05-22
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing nano-drug carriers still have many shortcomings, such as poor biocompatibility, serious leakage in the blood circulation, inability to escape lysosomes well, difficulty in drug release at the target site, and inability to simultaneously load multiple Small molecule drugs, genes and proteins, etc., the existence of these shortcomings largely limits the wide application of nanocarriers
The release of the drug at the target site is the key to the drug's efficacy. If the drug cannot be released well after reaching the target site, the drug will not be able to exert its efficacy
Therefore, covalent systems for stimulus-responsive release have received extensive attention, among which pH-responsive and enzyme-responsive studies are the most widely studied, while reduction-sensitive systems are rarely studied.

Method used

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  • Nano-drug carrier, reduction response nano-drug granules, nano-drug granular preparation and preparation method thereof
  • Nano-drug carrier, reduction response nano-drug granules, nano-drug granular preparation and preparation method thereof
  • Nano-drug carrier, reduction response nano-drug granules, nano-drug granular preparation and preparation method thereof

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Experimental program
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Effect test

preparation example Construction

[0061] see image 3 , the preparation method of the reduction-responsive nano drug particle preparation of one embodiment, comprising the following steps:

[0062] Step S110: dissolving the polysaccharide, phenyl p-nitrochloroformate and 4-dimethylaminopyridine in a mixture of dimethyl sulfoxide and pyridine, reacting in an ice bath for 4 hours, precipitating, collecting by centrifugation, and drying in vacuo to obtain p- Phenyl nitrochloroformate activates polysaccharides.

[0063] The polysaccharide is selected from one of dextran, pectin, pullulan, hydroxyethyl cellulose, modified chitosan and cyclodextrin.

[0064] In the mixture of dimethyl sulfoxide and pyridine, the volume ratio of dimethyl sulfoxide and pyridine is 1:1.

[0065] The solid-to-liquid ratio of the mixture of polysaccharide, phenyl p-nitrochloroformate, 4-dimethylaminopyridine, dimethyl sulfoxide and pyridine is 1g:0.7g:0.05g:40mL.

[0066] The polysaccharide is activated to generate phenyl p-nitrochlor...

Embodiment 1

[0087] (1) Dissolve 1g dextran, 0.7g phenyl p-nitrochloroformate and 0.05g 4-dimethylaminopyridine in a mixed solution of 40ml dimethyl sulfoxide and pyridine (the amount of dimethyl sulfoxide and pyridine The volume ratio is 1:1), reacted in ice bath for 4 hours, precipitated, collected by centrifugation, and dried in vacuum to obtain dextran activated by phenyl p-nitrochloroformate;

[0088] (2) Dissolve 0.5g of phenyl-p-nitrochloroformate-activated dextran in 40ml of water, drop into 5g of polyethyleneimine, react overnight, dialyze with ultrapure water, and freeze-dry to obtain the nano drug carrier—polyethyleneimine Grafted dextran, expressed as dextran-PEI;

[0089] (3) Dissolve 0.15g doxorubicin and 0.05g dithiodipropionic anhydride in 30mL N,N-dimethylformamide to obtain a mixture, react for 12 hours, add 0.12g N-hydroxysuccinimide (NHS) , 0.18g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was activated for 4 hours, added 0.6g dextran-PEI, reacted f...

Embodiment 2

[0095] (1) Dissolve 1g dextran, 0.7g phenyl p-nitrochloroformate and 0.05g 4-dimethylaminopyridine in a mixed solution of 40ml dimethyl sulfoxide and pyridine (the amount of dimethyl sulfoxide and pyridine The volume ratio is 1:1), reacted in ice bath for 4 hours, precipitated, collected by centrifugation, and dried in vacuum to obtain dextran activated by phenyl p-nitrochloroformate;

[0096] (2) Dissolve 0.5g of phenyl-p-nitrochloroformate-activated dextran in 40ml of water, drop into 5g of polyethyleneimine, react overnight, dialyze with ultrapure water, and freeze-dry to obtain the nano drug carrier—polyethyleneimine Grafted dextran, expressed as dextran-PEI;

[0097] (3) Dissolve 0.15g doxorubicin and 0.05g dithiodipropionic anhydride in 30mL N,N-dimethylformamide to obtain a mixture, react for 24 hours, add 0.12g N-hydroxysuccinimide (NHS) , 0.18g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was activated for 4 hours, added 0.6g dextran-PEI, reacted...

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Abstract

The invention relates to a nano-drug carrier, reduction response nano-drug granules, a nano-drug granular preparation and a preparation method thereof. The nano-drug carrier comprises a main chain which is formed by polysaccharide and a side chain which is formed by polyethylenimine on the main chain. Because of the characteristics of the nano-drug carrier, when the nano-drug carrier carries drug, the drug is connected with the nano-drug carrier through a disulfide bond (-SS-), and the disulfide bond is disconnected in a cell in the reduction environment so as to well release the drug to a target location.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a nano-medicine carrier, a reduction-responsive nano-medicine particle, a preparation of the nano-medicine particle and a preparation method thereof. Background technique [0002] Nano-drug carriers generally refer to systems with nanoscale dimensions that can load one or more drugs. Because of its quantum size effect, large specific surface area, and easy surface modification, it has many advantages in drug delivery and controlled release. Generally, nano-drug carriers have various forms such as liposomes, polymer micelles, dendrimers, carbon nanotubes, and quantum dots. [0003] The existing nano-drug carriers still have many shortcomings, such as poor biocompatibility, serious leakage in the blood circulation, inability to escape lysosomes well, difficulty in drug release at the target site, and inability to simultaneously load multiple Small molecule drugs, genes and prote...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K47/38A61K47/40A61K31/704A61K31/4745A61K31/337A61K33/24A61K48/00A61K9/14A61P35/00C08G81/00C08B37/02C08B37/06C08B37/00C08B15/06C08B37/08C08B37/16
Inventor 蔡林涛刘朋石碧华岳彩霞王碧易虎强刘斌魏伟
Owner SHENZHEN INST OF ADVANCED TECH
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