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Surface-modified hydrophobically modified drug-carried chitosan polymer micelle and method for preparing same

A hydrophobic modification and surface modification technology, applied in the field of surface modification of polymer micelles, to achieve the effects of improving instability, improving curative effect and reducing drug burst release

Inactive Publication Date: 2008-09-10
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the clinical application of polymer drug-loaded micelles is still blank.

Method used

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  • Surface-modified hydrophobically modified drug-carried chitosan polymer micelle and method for preparing same
  • Surface-modified hydrophobically modified drug-carried chitosan polymer micelle and method for preparing same
  • Surface-modified hydrophobically modified drug-carried chitosan polymer micelle and method for preparing same

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] 1. Preparation of chitosan oligosaccharide

[0037] Add 6g of chitosan (average molecular weight 450kDa) to 200mL of 1.25% (v / v) hydrochloric acid aqueous solution, stir and dissolve at 55-60°C, adjust the pH to 5.0 with dilute ammonia water or dilute hydrochloric acid, press cellulase and shell The ratio of polysaccharides is 0.5:100 (w / w) to add cellulase, and after controlling the reaction time for 8 hours, the reaction product is 4000r×min -1 After centrifugation for 10 minutes, the supernatant was pretreated with a 0.45 μm microporous membrane, graded by ultrafiltration with ultrafiltration membranes of different molecular weights, and the ultrafiltrate was freeze-dried to obtain chitosan oligosaccharides with a certain molecular weight. And the average molecular weight was determined to be 50.6 kDa by gel permeation chromatography.

[0038]2. Preparation of hydrophobically modified chitosan oligosaccharides

[0039] Get above-mentioned chitosan oligosaccharide 5...

Embodiment 2

[0050] 1. Preparation of chitosan oligosaccharide

[0051] Add 6g of chitosan (average molecular weight 450kDa) to 200mL of 1.25% (v / v) hydrochloric acid aqueous solution, stir and dissolve at 55-60°C, adjust the pH to 5.0 with dilute ammonia water or dilute hydrochloric acid, press cellulase and shell The ratio of polysaccharides is 0.5:100 (w / w) to add cellulase, and after controlling the reaction time for 8 hours, the reaction product is 4000r×min -1 After centrifugation for 10 minutes, the supernatant was pretreated with a 0.45 μm microporous membrane, graded by ultrafiltration with ultrafiltration membranes of different molecular weights, and the ultrafiltrate was freeze-dried to obtain chitosan oligosaccharides with a certain molecular weight. And the average molecular weight was determined to be 50.6 kDa by gel permeation chromatography.

[0052] 2. Preparation of hydrophobically modified chitosan oligosaccharides

[0053] Get above-mentioned chitosan oligosaccharide ...

Embodiment 3

[0064] 1. Preparation of chitosan oligosaccharide

[0065] Add 6g of chitosan (average molecular weight 450kDa) to 200mL of 1.25% (v / v) hydrochloric acid aqueous solution, stir and dissolve at 55-60°C, adjust the pH to 5.0 with dilute ammonia water or dilute hydrochloric acid, and mix with cellulase Chitosan ratio 0.5:100 (w / w) was added to cellulase, and after controlling the reaction time for 8 hours, the reaction product was 4000r×min -1 After centrifugation for 10 minutes, the supernatant was pretreated with a 0.45 μm microporous membrane, graded by ultrafiltration with ultrafiltration membranes of different molecular weights, and the ultrafiltrate was freeze-dried to obtain chitosan oligosaccharides with a certain molecular weight. And the average molecular weight was determined to be 50.6 kDa by gel permeation chromatography.

[0066] 2. Preparation of hydrophobically modified chitosan oligosaccharides

[0067] Get above-mentioned chitosan oligosaccharide 5.0g, accurat...

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Abstract

Disclosed is a surfacely modified hydrophobic Chitosan oligosaccharide polymer drug-loaded colloidal cluster, obtained by grafting chitosan with a average molecular weight of 1.5kD-51kD and aliphatic acid of C10-C22, comprising based on hydrophobic modified Chitosan oligosaccharide polimer colloidal clusters, modifying amidogens or hydroxy groups of Chitosan oligosaccharide molecules on polimer surface with bi-functional small organic moleculers, forming chemical bond bridges between molecules on the surfaces of polymer colloidal clusters,to improve the instability of polymer colloidal cluster diluted, and to imorove the original loose structure of polimer colloidal cluster surfece to form a fine and close net-shaped structure, to decrease a sudden release of drugs, and to control drugs with slow release. The drug-loaded colloidal cluster provided is a nano-carrier with excellent organelle targeting, is applicated in life science field and pharmacy field.

Description

technical field [0001] The invention belongs to the surface modification of polymer micelles, and relates to the surface modification of hydrophobically modified chitosan oligosaccharide polymer micelles by bifunctional organic small molecules, and the control of the surface modification degree of polymer micelles to achieve polymer Sustained and controlled release properties of drug-loaded micelles. Background technique [0002] Polymeric micelles (PMs) are a new class of nanocarriers that are being developed in recent years, which have the advantages of solubilization, targeting, low toxicity and long circulation. It is formed spontaneously from amphiphilic polymers in an aqueous environment and has a unique core-membrane (shell) structure. Its internal core can provide storage for insoluble drugs, peptide and protein drugs and genes, and the hydrophilic outer membrane can be modified in physical and chemical properties to achieve targeted distribution in vivo, avoid phag...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/36A61K9/00A61K9/14
Inventor 胡富强杜永忠袁弘游剑任国飞
Owner ZHEJIANG UNIV
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