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Novel anti-tumor nano-drug carrier and preparation method and application thereof

A nano-drug carrier and anti-tumor technology, which is applied in the direction of anti-tumor drugs, drug combinations, powder delivery, etc., can solve the problem of inability to effectively reduce the toxic and side effects of anti-cancer drugs, the cycle time is not long enough, and there are few delivery carriers and other problems to achieve the effects of avoiding rapid phagocytosis, promoting the formation of micelles, and strong three-dimensional protection

Active Publication Date: 2014-12-31
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although the micelles formed by simple hydrophobically modified chitosan have the advantages of degradability, non-toxicity, and high drug loading, as anti-tumor drug carriers, such nanoparticles are easily absorbed by phagocytes in the body after intravenous injection. It is swallowed for foreign body recognition, and the circulation time in the human body is not long enough, which reduces the bioavailability
In addition, simple hydrophobically modified chitosan micelles do not have strong targeting, and cannot specifically bind to tumor cells, so they cannot effectively reduce the toxic and side effects of anticancer drugs on normal cells.
Before this study, although some researchers prepared hydrophobic chitosan micelles with targeting and long circulation in vivo, there were few delivery vehicles that met the above requirements at the same time.

Method used

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  • Novel anti-tumor nano-drug carrier and preparation method and application thereof
  • Novel anti-tumor nano-drug carrier and preparation method and application thereof
  • Novel anti-tumor nano-drug carrier and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] (1) Hydrophobic modification of chitosan:

[0060] Take by weighing 1.0g chitosan in reaction bottle, add 1% (v / v) acetic acid aqueous solution of 100ml and dissolve it, obtain chitosan acetic acid solution; 0.3180g DA (chitosan (CS) and deoxycholic acid (DA) molar ratio is 1:40), 0.6211g EDC, 0.1243g NHS join in another beaker, add 200ml methanol activation for half an hour, obtain mixed solution; Then mixed solution is added dropwise in chitosan acetic acid solution, Magnetic stirring, react at 25°C for 48 hours, when the reaction is over, add 60ml of ammonia water to the reaction bottle, transfer the reactant to a centrifuge tube and centrifuge for 10 minutes (speed 5000r / min), discard the supernatant, wash the precipitate with 40ml of methanol 3 Then the precipitate was transferred to a dialysis bag (the molecular weight cut-off of the dialysis bag is 10000, the same below.) Dialyzed for 7 days, freeze-dried (after being frozen overnight at -10°C, placed in a lyophi...

Embodiment 2

[0074] (1) Hydrophobic modification of chitosan:

[0075] Take by weighing 1.0g chitosan in reaction flask, add 1% (v / v) acetic acid aqueous solution of 100ml and dissolve it, obtain chitosan acetic acid solution; 1.2720g DA (chitosan (CS) and deoxycholic acid (DA) molar ratio is 1:162), 2.4844g EDC, 0.4971g NHS join in another beaker, add 200ml methanol activation for half an hour, obtain mixed solution; Then mixed solution is added dropwise in chitosan acetic acid solution, Magnetic stirring, react at 25°C for 60h, when the reaction is over, add 60ml of ammonia water to the reaction bottle, transfer the reactant to a centrifuge tube and centrifuge for 10 minutes (speed 5000r / min), discard the supernatant, wash the precipitate with 40ml of methanol 4 Then, the precipitate was transferred to a dialysis bag for dialysis for 7 days, freeze-dried (after being frozen overnight at -10°C and placed in a lyophilizer for 24 hours), to obtain a chitosan-deoxycholic acid polymer;

[00...

Embodiment 3

[0086] (1) Hydrophobic modification of chitosan:

[0087] Take by weighing 1.0g chitosan in reaction bottle, add 1% (v / v) acetic acid aqueous solution of 100ml and dissolve it, obtain chitosan acetic acid solution; 0.8480g DA (chitosan (CS) and deoxycholic acid (DA) molar ratio is 1:108), 1.6563g EDC, 0.3315g NHS join in another beaker, add 200ml methanol activation for half an hour, obtain mixed solution; Then mixed solution is added dropwise in chitosan acetic acid solution, Magnetic stirring, react at 25°C for 72h, when the reaction is over, add 60ml of ammonia water to the reaction bottle, transfer the reactant to a centrifuge tube and centrifuge for 10 minutes (speed 5000r / min), discard the supernatant, wash the precipitate with 40ml of methanol 5 Then, the precipitate was transferred to a dialysis bag for dialysis for 7 days, freeze-dried (after being frozen overnight at -10°C and placed in a lyophilizer for 24 hours), to obtain a chitosan-deoxycholic acid polymer;

[0...

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Abstract

The invention discloses a novel anti-tumor nano-drug carrier and a preparation method and application thereof. The method comprises the following steps: carrying out an amidation reaction on chitosan and deoxycholic acid to form a copolymer chitosan-deoxycholic acid, forming an intermediate of the chitosan-deoxycholic acid and formaldehyde, carrying out a reaction on the intermediate and polyethylene glycol, carrying out an amidation reaction on the obtained chitosan-deoxycholic acid-polyethylene glycol so as to prepare the novel anti-tumor nano-drug carrier. The characteristics that a folate receptor on the surface of the tumor cells has high expression and the folate receptor hardly has excessive expression in normal tissues are utilized, the novel anti-tumor nano-drug carrier connected with folate and the tumor cells have high affinity, and the defect that the common nanoparticle function is single is overcome. The prepared novel anti-tumor nano-drug carrier can well avoid cytophagy of phagocyte, the carrier circulates in vivo for a long time and is not eliminated, the active targeting modification can be better combined with tumor cell specificity, and the harm of the drug to normal human cells is reduced.

Description

technical field [0001] The invention belongs to the technical field of nano drug carriers, in particular to an anti-tumor nano drug carrier and its preparation method and application. Background technique [0002] Cancer is the biggest killer of human life and health. Chemotherapy is the most important means of cancer treatment. However, most chemotherapeutic drugs lack the ability to specifically reach tumor tissue, lack selective killing effect on tumor cells, and harm normal cells while killing tumor cells. Cells, especially cancer cells, develop drug resistance due to drug treatment. In order to overcome the drug resistance of cancer cells, higher doses of anticancer drugs need to be given, which will cause greater side effects on normal cells and even interrupt treatment; on the other hand However, the efficacy of most antitumor drugs also limits the effect of tumor treatment due to their own properties, such as poor water solubility and narrow therapeutic window. [0...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61K9/19A61P35/00C08B37/08
Inventor 郭瑞张渊明师忠根唐渝
Owner JINAN UNIVERSITY
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