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Modified chitosan targeted medicament carrying nano microsphere and preparation method thereof

A nano-microsphere, drug-carrying nanotechnology, applied in pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., to achieve the effects of large drug loading, improved targeting, and high killing rate

Inactive Publication Date: 2011-08-31
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Aiming at the shortcomings of the existing chitosan-based nano-microspheres, the purpose of the present invention is to provide a nano-microsphere with small particle size, high drug encapsulation efficiency, large drug loading capacity, high coupling efficiency of targeted biomolecules, Preparation of Modified Chitosan Targeted Drug-loaded Nanospheres with Mild Conditions and Strong Targeting

Method used

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  • Modified chitosan targeted medicament carrying nano microsphere and preparation method thereof
  • Modified chitosan targeted medicament carrying nano microsphere and preparation method thereof
  • Modified chitosan targeted medicament carrying nano microsphere and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0037] Embodiment 1: the preparation method and application of Tf-ADR / CMCS nano microsphere

[0038](1) Preparation of carboxymethyl chitosan (CMCS): 5g chitosan (CS) is dissolved in 50ml isopropanol solution, and adding mass concentration is 50% NaOH solution 20ml under stirring condition, makes chitosan The sugar swells under alkaline conditions, and stored at 0°C for 6 hours to make it fully alkalized; at 30°C, add 2 g of solid chloroacetic acid to the above solution to prepare a crude CMCS product; use glacial acetic acid to adjust the pH of the solution to 7.0, Then wash with ethanol solution successively, dialyze the dialysis bag to remove small molecular impurities, and dry to obtain white powdery CMCS.

[0039] (2) Preparation of ADR / CMCS nano-microspheres: Under the acetic acid buffer solution medium of pH 4.0, according to the molar ratio of 1.0:0.5:0.2, CMCS, carbodiimide (EDAC) and ADR were stirred for 10 minutes, centrifuged Collect and dry to obtain ADR / CMCS nan...

Embodiment 2

[0043] Embodiment 2: the preparation method and application of Tf-ADR / CMCS nano microsphere

[0044] (1) Preparation of carboxymethyl chitosan (CMCS): 15g chitosan (CS) is dissolved in 150ml isopropanol solution, adding mass concentration under agitation is 100ml of 50% NaOH solution to make chitosan Swell under alkaline conditions, store at 10°C for 18 hours to make it alkalized completely; add 10 g of solid chloroacetic acid to the above solution at 50°C to prepare a crude CMCS product; use glacial acetic acid to adjust the pH of the solution to 7.0, and then Wash with ethanol solution in turn, dialyze the dialysis bag to remove small molecular impurities, and dry to obtain white powdery CMCS.

[0045] (2) Preparation of ADR / CMCS nano-microspheres: Under the acetic acid buffer solution medium of pH 7.0, according to the molar ratio of 5.0:1.5:0.8, CMCS, carbodiimide (EDAC) and ADR were stirred and reacted for 40min, centrifuged Collect and dry to obtain ADR / CMCS nano-micros...

Embodiment 3

[0049] Embodiment 3: the preparation method and application of Tf-5-Fu / CMCS nano microsphere

[0050] (1) Preparation of carboxymethyl chitosan (CMCS): 6g chitosan (CS) is dissolved in 60ml isopropanol solution, adding mass concentration is 50% NaOH solution 30ml under stirring condition, let chitosan The sugar swells under alkaline conditions, and stored at 2°C for 7 hours to make it fully alkalized; at 35°C, add 6 g of solid chloroacetic acid to the above solution to prepare a crude CMCS product; use glacial acetic acid to adjust the pH of the solution to 7.0, Then wash with ethanol solution successively, dialyze the dialysis bag to remove small molecular impurities, and dry to obtain white powdery CMCS.

[0051] (2) Preparation of 5-Fu / CMCS nano-microspheres: under the acetic acid buffer solution medium of pH 4.0, according to the molar ratio of 1.0:0.5:0.5, CMCS, carbodiimide (EDAC) and 5-Fu were stirred React for 10 minutes, collect by centrifugation, and dry to prepare ...

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Abstract

The invention provides a modified chitosan targeted medicament carrying nano microsphere and a preparation method thereof. The method comprises the following steps of: modifying chitosan into carboxymethyl chitosan; then crosslinking an active amino group on a medicament molecule with an active carboxyl on the carboxymethyl chitosan by using a biological cross-linking agent and preparing a medicament carrying nano microsphere; and finally, connecting the targeted biological molecule to the surface of the medicament carrying microsphere by a chemical modification method and obtaining the modified chitosan targeted medicament carrying nano microsphere. The medicament carrying nano microsphere has small particle diameter, high medicament encapsulating rate, large medicament carrying quantity, high coupling efficiency of targeted biological molecules, mild preparation condition, strong targeted performance and low medicament toxic and side effect and can improve the targeted function and the slow release function on tumor cells, thereby strengthening the killing rate for the tumor cells.

Description

technical field [0001] The invention relates to the application of biological nanomaterials in the field of biomedicine, and discloses a modified chitosan targeted drug-loaded nano-microsphere capable of actively targeting tumor cells and a preparation method thereof. Background technique [0002] The active targeting and low side effects of anti-tumor drugs are very important for the clinical treatment of diseases. As a carrier of drugs, how to maximize the efficacy of drugs, reduce the frequency and dosage of drugs, and improve the utilization rate and curative effect of drugs is a key issue. One of the very crucial questions. Studies have shown that an ideal anti-tumor drug delivery system can selectively accumulate anti-tumor drugs in cancerous parts of the body, reduce the toxic and side effects of drugs on normal tissues, improve the bioavailability of drugs, and thereby improve drug efficacy. This is the current anti-tumor drug hotspots in research and development. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/16A61K47/48A61K47/36A61K47/42A61K47/22A61K31/704A61K31/513A61P35/00A61K47/61A61K47/69
Inventor 杨培慧蔡怀鸿张文豪蔡继业
Owner JINAN UNIVERSITY
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