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Oxaliplatin chitosan-stearic acid grafting micelle and application

A technology of oxaliplatin and stearic acid, which is applied in the field of preparation of oxaliplatin chitosan-stearic acid graft micelles, can solve the problems of not many, difficult polymer micelles, etc., and achieve the improvement of cell Toxicity, improve clinical anti-tumor efficacy, increase the effect of intracellular drug concentration

Inactive Publication Date: 2010-08-11
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the water solubility of oxaliplatin to a certain extent, there are still some difficulties in encapsulating with polymer micelles, and there are not many reports on this aspect

Method used

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  • Oxaliplatin chitosan-stearic acid grafting micelle and application
  • Oxaliplatin chitosan-stearic acid grafting micelle and application
  • Oxaliplatin chitosan-stearic acid grafting micelle and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] 1) Preparation of low molecular weight chitosan

[0020] Get 90g of chitosan (95% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling 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 was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to measure chitosan molecular weight, using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH6.0) as mobile phase, with molecular weight 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda glucose The elution curve of the polysaccharide ...

Embodiment 2

[0029] 1) Preparation of low molecular weight chitosan

[0030] Get 90g of chitosan (95% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling 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 was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to measure chitosan molecular weight, using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH6.0) as mobile phase, with molecular weight 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda glucose The elution curve of the polysaccharide ...

Embodiment 3

[0039] 1) Preparation of low molecular weight chitosan

[0040] Get 90g of chitosan (95% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling 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 was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to measure chitosan molecular weight, using TSK-gel G3000SW chromatographic column, 0.1mol / L sodium acetate (pH6.0) as mobile phase, with molecular weight 0.73, 5.9, 11.8, 47.3, 212.0, 788.0Kda glucose The elution curve of the polysaccharide ...

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Abstract

The invention provides an oxaliplatin chitosan-stearic acid grafting micelle which comprises 0.5 percent of chitosan-stearic acid grafting, 0.009-0.02 percent of oxaliplatin, 0-0.2 percent of lecithin and the balance of water. The oxaliplatin chitosan-stearic acid grafting micelle is respectively prepared by using a probe ultrasonic method, a film dispersion method and a lecithin mediated film dispersion method. The oxaliplatin chitosan-stearic acid grafting micelle has rapid ingestion function of passive targeting and cancer cells in a polymer micelle, can greatly improve the intracellular medicine concentration of a molecular target in the oxaliplatin in the cancer cells by encapsulating the oxaliplatin chitosan-stearic acid grafting micelle on the oxaliplatin, improves the cytotoxicity and shifts the multidrug resistance, and enhances the clinical anti-tumor efficacy of the oxaliplatin. The oxaliplatin chitosan-stearic acid grafting micelle can be applied to preparing an anti-tumor medicine.

Description

technical field [0001] The invention belongs to the preparation and application of oxaliplatin targeting preparations, in particular to the preparation and application of oxaliplatin chitosan-stearic acid graft micelles. Background technique [0002] Chemotherapy is an important means of treating cancer at present. However, most chemotherapeutic drugs lack specific biodistribution in vivo, resulting in toxic side effects on normal cells and organs, thus limiting their clinical application. In addition, drug resistance and multidrug resistance of tumor cells have also become a very important factor leading to the failure of tumor chemotherapy. [0003] Platinum-based drugs are chemotherapy drugs with spectrum anticancer activity, also known as DNA alkylating agents. Oxaliplatin is the third-generation platinum-based antineoplastic drug, which kills cancer cells by cross-linking DNA and inhibiting DNA synthesis. However, oxaliplatin itself lacks the targeting of tumor tissu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/48A61K47/36A61K31/282A61P35/00A61K47/61
Inventor 胡富强杜永忠袁弘
Owner ZHEJIANG UNIV
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