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Chlorin e6 chitosan-stearic acid graft micelle

A technology of chlorin and stearic acid, applied in the field of targeted preparations, can solve the problems of lack of specificity, toxic and side effects, skin phototoxicity, etc., and achieve the effects of increasing drug concentration and reducing toxic and side effects

Inactive Publication Date: 2009-09-09
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage is that dihydrophyllin e6 exhibits long-term skin phototoxicity and the effective dose is large
Since tumor tissue is relatively selective in absorbing photosensitizers without specificity, a small amount of photosensitizers are inevitably distributed in normal tissues, which may cause phototoxic side effects

Method used

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  • Chlorin e6 chitosan-stearic acid graft micelle
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 1) Preparation of low molecular weight chitosan

[0019] Take 90g of commercially available chitosan with a molecular weight of 450kDa (degree of deacetylation: 95%), add it to 3000mL 1.25% (v / v) hydrochloric acid aqueous solution, swell at 55-60°C for 2 hours, Add 5% cellulase (w / w) and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan. The resulting degradation reaction solution is classified by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and then the ultrafiltrate with a molecular weight of 10-50Kda is freeze-dried. The molecular weight of chitosan was determined by gel permeation chromatography using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH 6.0) as the mobile phase, and the molecular weight of 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda An elution curve was prepared from the glycan standard, and the molecular weight of chitosan ...

Embodiment 2

[0036] 1) Preparation of low molecular weight chitosan

[0037] Take 90g of commercially available chitosan with a molecular weight of 450kDa (degree of deacetylation 95%), add it to 3000mL 1.25% (v / v) hydrochloric acid aqueous solution, swell at 55-60℃ for 2 hours, Add 5% cellulase (w / w), and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan. The resulting degradation reaction solution is classified by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda is freeze-dried. The molecular weight of chitosan was determined by gel permeation chromatography, using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH 6.0) as the mobile phase, and the molecular weight of 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda An elution curve was prepared from the glycan standard, and the molecular weight of chitosan was c...

Embodiment 3

[0054] 1) Preparation of low molecular weight chitosan

[0055] Take 90g of commercially available chitosan with a molecular weight of 450kDa (degree of deacetylation 95%), add it to 3000mL 1.25% (v / v) hydrochloric acid aqueous solution, swell at 55-60℃ for 2 hours, Add 5% cellulase (w / w), and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan. The resulting degradation reaction solution is classified by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda is freeze-dried. The molecular weight of chitosan was determined by gel permeation chromatography, using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH6.0) as the mobile phase, and the molecular weight of 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda An elution curve was prepared from the glycan standard, and the molecular weight of chitosan was ca...

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Abstract

The invention provides a preparation of chlorin e6 chitosan-stearic acid graft micelle. The preparation comprises a chitosan-stearic acid graft and chlorin e6, wherein, the chlorin e6 accounts for 4.76-16.76% of the total weight; the chitosan-stearic acid graft is formed by chemically grafting low molecular weight chitosan with average molecular weight being 18.0 KDa and stearic acid; and the amino substituted ration of the chitosan-stearic acid graft accounts for 4.96%. The invention utilizes the chitosan-stearic acid graft micelle to effectively pack the photosencitizer of chlorin e6, so as to prepare the intracellular administration preparation of chlorin e6 chitosan-stearic acid graft micelle. Compared with the chlorin e6 solution, the preparation of the invention can significantly improve the drug concentration of chlorin e6 in tumour cells and provide probability for the follow-up realization of efficient and harmless photodynamic therapy of tumors.

Description

Technical field [0001] The invention belongs to a targeted preparation, and specifically relates to a chlorin e6 chitosan-stearic acid graft micelle preparation and its application. Background technique [0002] Photodynamic therapy (PDT), an antitumor photosensitizer, is a novel treatment method that emerged in the early 1980s and has developed rapidly in recent years. Photodynamic therapy has the characteristics of low toxicity and quick effect. Through biophotodynamic sensitization, that is, after a specific wavelength of laser irradiation, the photosensitizer is excited, from the ground state (S 0 ) The excited singlet state (S 1 ) Into an excited triplet state (T 1 ), then excited by the triplet state (T 1 ) To make the molecular oxygen in the surrounding medium singlet oxygen ( 1 O 2 ) And other active substances, which interact with the oxidation-sensitive groups in biomolecules, leading to their oxidative inactivation, and ultimately causing tumor cell death to show their...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/36A61K31/409A61K41/00A61P35/00
Inventor 胡富强杜永忠袁弘
Owner ZHEJIANG UNIV
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