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Targeting chitosan carrier guided by folic acid receptor and the preparing method and the application

A technology of folic acid receptor and chitosan, applied in medical preparations with non-active ingredients, medical preparations containing active ingredients, pharmaceutical formulas, etc., can solve myocardial cell damage, doxorubicin limitation, strong cardiotoxicity and other issues, to achieve the effect of high bioavailability, obvious targeting, and low cost

Inactive Publication Date: 2007-09-12
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has been found clinically that doxorubicin is more likely to cause multidrug resistance in tumor cells. The reason for the drug resistance is that the membrane of cancer cells changes after administration of doxorubicin, which will resist doxorubicin from entering the cell. In order to reduce the uptake of doxorubicin by cells and reduce its toxicity
In addition, doxorubicin has strong cardiotoxicity to patients, causing damage to cardiomyocytes, and this damage is irreversible
All of these make doxorubicin greatly limited in clinical application.

Method used

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  • Targeting chitosan carrier guided by folic acid receptor and the preparing method and the application
  • Targeting chitosan carrier guided by folic acid receptor and the preparing method and the application
  • Targeting chitosan carrier guided by folic acid receptor and the preparing method and the application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] 0.2g of chitosan with a molecular weight of 200kDa and a degree of deacetylation of 92% was dissolved in 20ml of HAC-NaAC buffer at pH=4.7;

[0058] Dissolve 0.0044g of folic acid in 3ml of anhydrous DMSO (dimethyl sulfoxide), add 0.0019g of EDC·HCl, and stir at 25°C for 1 hour to activate the carboxyl group of folic acid;

[0059] The above-mentioned chitosan solution was mixed with folic acid solution, and stirred and reacted in the dark for 15 hours, and the pH value of the mixed solution after the reaction was adjusted to 9.0 with 5mol / L aqueous sodium hydroxide solution, and the mixture was placed in the phosphate buffer solution of pH=7.4 Dialyzed against medium for 3 days, then dialyzed in deionized water for 3 days, freeze-dried in vacuum to obtain chitosan-folate complex.

[0060] The general structural formula of the obtained chitosan-folate complex is as formula 1, wherein: n=1150;

[0061] The infrared spectrum of chitosan is shown in Figure 1; the infrared...

Embodiment 2

[0067] 0.2g of chitosan with a molecular weight of 200kDa and a degree of deacetylation of 92% was dissolved in 20ml of HAC-NaAC buffer at pH=4.7;

[0068] Dissolve 0.0044g of folic acid in 3ml of anhydrous DMSO, add 0.0019g of EDC·HCl, and stir at 25°C for 1 hour to activate the carboxyl group of folic acid;

[0069] The above-mentioned chitosan solution was mixed with folic acid solution, and stirred and reacted in the dark for 15 hours, and the pH value of the mixed solution after the reaction was adjusted to 9.0 with 5mol / L aqueous sodium hydroxide solution, and the mixture was placed in the phosphate buffer solution of pH=7.4 Dialyzed against medium for 3 days, then dialyzed in deionized water for 3 days, freeze-dried in vacuum to obtain chitosan-folate complex.

[0070] The general structural formula of the obtained chitosan-folate complex is as formula 1, wherein: n=1150;

[0071] The identification of chitosan-folate complex is the same as in Example 1.

[0072]Disso...

Embodiment 3

[0076] 0.2g of chitosan with a molecular weight of 200kDa and a degree of deacetylation of 92% was dissolved in 20ml of HAC-NaAC buffer at pH=5.5;

[0077] Dissolve 0.0044g of folic acid in 3ml of anhydrous DMSO, add 0.0019g of EDC·HCl, and stir at 25°C for 1 hour to activate the carboxyl group of folic acid;

[0078] The above-mentioned chitosan solution was mixed with folic acid solution, and stirred and reacted in the dark for 20 hours, and the pH value of the mixed solution after the reaction was adjusted to 9.0 with 5mol / L sodium hydroxide aqueous solution, and the mixture was placed in the phosphate buffer solution of pH=7.4 Dialyzed against medium for 3 days, then dialyzed in deionized water for 3 days, freeze-dried in vacuum to obtain chitosan-folate complex.

[0079] The general structural formula of the obtained chitosan-folate complex is as formula 1, wherein: n=1150;

[0080] The identification of chitosan-folate complex is the same as in Example 1.

[0081] 0.00...

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Abstract

The present invention discloses one kind of folic acid receptor mediated targeting chitosan carrier and its preparation process and application. The present invention has folic acid and its derivative as targeting agent, chitosan and its derivative as carrier and chemotherapeutic medicine adriamycin and other synergistic antisense nucleic acid as acting medicine to raise the stability and targeting property of the administration system. Therefore, the nanometer carrier has wide application foreground in treating tumor.

Description

technical field [0001] The invention belongs to the field of medicine, and the content is related to targeting chitosan nano-carriers mediated by folic acid receptors. Specifically, it relates to targeting tumor cells by cross-linking folic acid on chitosan and its derivatives Method, especially relate to the preparation method of this kind of chitosan (or chitosan derivative)-folic acid carrier and the anticancer drugs such as antisense nucleic acid and doxorubicin to form pharmaceutical composition, property and its antitumor treatment application. technical background [0002] With the development of biomaterial science, clinical medicine and pharmacy, drug carrier has become a new form of drug delivery. The key to this technology is how to choose the carrier material. [0003] At present, the vector systems commonly used in gene therapy are mainly divided into two categories: viral vector systems and non-viral vector systems. [0004] Said virus vector system includes...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K47/22A61K47/48A61K48/00A61K31/704A61K38/13A61P35/00A61K47/61
Inventor 任宇红张宇飞魏东芝王佳琪
Owner EAST CHINA UNIV OF SCI & TECH
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