Gluconic acid modified chitosan nucleophilic NO donator and synthesizing method thereof

A technology of gluconic acid and chitosan, which is applied in the field of medical engineering, can solve the problems of small load and poor targeting, and achieve the effect of large load, prevention of restenosis, and promotion of wound healing

Inactive Publication Date: 2008-06-11
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the present invention, by modifying chitosan or O-carboxymethyl chitosan with gluconic acid, a secondary amine (NH) nucleophilic site is produced, and after reacting with NO, a series of chitosan or chitosan modified with gluconic acid are obtained. O-carboxymethyl chitosan as carrier containing [N(O)NO] - A new type of NO donor with functional groups, which solves the problems existing in the clinical application of this type of nucleophilic NO donor (small loading, poor targeting)

Method used

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  • Gluconic acid modified chitosan nucleophilic NO donator and synthesizing method thereof
  • Gluconic acid modified chitosan nucleophilic NO donator and synthesizing method thereof
  • Gluconic acid modified chitosan nucleophilic NO donator and synthesizing method thereof

Examples

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Embodiment 1

[0026] Embodiment 1: the synthesis of gluconic acid modified 400,000 molecular weight chitosan / NO

[0027]400,000 molecular weight chitosan (1 g) and gluconic acid (0.1 or 0.2 equal parts / [-NH2]) were dissolved in 0.1N HCl hydrochloric acid solution (100 ml), then EDC (1.5 equal parts / gluconic acid) was added to the solution and NHS (0.25 equal parts / EDC), then adjust the pH of the solution to 5 with a solution of 1N NaOH / 1N HCl, and continue to stir the reaction solution at room temperature for 24 hours. After the reaction, adjust the pH to 9 with 1N NaOH solution, and the reaction solution The product was dialyzed with distilled water for 5 days in a dialysis bag and dried to obtain a colorless transparent film-like substance SBC (1.44 g).

[0028] Add 0.23g (0.001mol) of the above reaction product into 100ml of anhydrous methanol solution containing 0.22g (0.002mol) sodium methoxide, react with NO in an autoclave, maintain the pressure at 5atm, and react for 3 days. Wash w...

Embodiment 2

[0030] Embodiment 2: the synthesis of gluconic acid modified 1.24 million molecular weight 0-carboxymethyl chitosan / NO

[0031] O-carboxymethyl chitosan (1 g) with a molecular weight of 1.24 million and gluconic acid (0.1 or 0.2 equal parts / [-NH2]) were dissolved in 0.1N HCl hydrochloric acid solution (100 ml), and EDC (1.5 Equal parts / gluconic acid) and NHS (0.25 equal parts / EDC), then use 1N NaOH / 1N HCl solution to adjust the pH of the solution to 5, and the reaction solution continues to stir and react at room temperature for 24h. After the reaction is completed, use 1N NaOH solution to prepare pH=9, the reaction solution was dialyzed with distilled water for 5 days in a dialysis bag, and the product was obtained after drying, which was N-gluconic acid-O-carboxymethyl chitosan SBCS (1.33g) in the form of pink fine powder.

[0032] Add 0.32g (0.001mol) of the above reaction product SBCS into 100ml of anhydrous methanol solution containing 0.22g (0.002mol) sodium methoxide, r...

Embodiment 3

[0034] The synthesis of embodiment 3 gluconic acid modified 1.88 million molecular weight chitosan / NO

[0035] Chitosan (1 g) with a molecular weight of 1.88 million and gluconic acid (0.1 or 0.2 equal parts / [-NH2]) were dissolved in 0.1N HCl hydrochloric acid solution (100 ml), then EDC (1.5 equal parts / gluconic acid ) and NHS (0.25 equal parts / EDC), then use 1N NaOH / 1N HCl solution to adjust the pH of the solution to 5, and the reaction solution is stirred at room temperature for 24 hours. After the reaction is completed, adjust the pH to 9 with 1N NaOH solution. The liquid was dialyzed with distilled water for 5 days in a dialysis bag, and the product was obtained after drying, and a white opaque film-like substance SBC (1.20 g) was obtained.

[0036] Add 0.20 g (0.001 mol) of the above reaction product into 100 ml of anhydrous methanol solution containing 0.22 g (0.002 mol) of sodium methylate, react with NO in an autoclave, maintain a pressure of 10 atm, and react for 7 d...

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Abstract

A gluconic acid modified chitosan nucleophilic NO donor and synthesizing method belongs to the medicine engineering technical field. The invention modifies the carboxylation reaction to NH2 group on chitosan or O-carboxymethyl chitosan for leading the NH2 group to produce nucleophilic NH group which can react with NO. Secondary amine NH group on gluconic acid modified chitosan or O-carboxymethyl chitosan molecules carries out reaction in a methanol solution of sodium methoxide with NO gas molecules, wherein, Na+/NH=2, the [N(O)NO]- group is produced, and the molecular structural formula of the achieved gluconic acid modified chitosan or O-carboxymethyl chitosan nucleophilic NO donor is as follows.s The nucleophilic NO donor of the invention has different NO release speeds and larger load capacity, can simultaneously overcome cytotoxicity of nucleophilic reagent (polyamines) and avoid from producing oncogenicity coproduct of nitrosamine, and has a certain targeting capacity. R=H, CH2COONa.

Description

technical field [0001] The invention relates to a medicine in the technical field of medical engineering and a synthesis method thereof, in particular to a gluconic acid modified chitosan nucleophilic NO donor and a synthesis method thereof. Background technique [0002] Cardiovascular disease is the primary disease that threatens human health, and restenosis after percutaneous coronary angioplasty is still an unsolved worldwide medical problem. NO-releasing materials are considered to be an effective anti-restenosis drug. Materials capable of generating and releasing NO are currently considered to be the most promising solutions to clinical medical problems such as antithrombotic coagulation and inhibition of postoperative restenosis. Contains [N(O)NO] - Compounds with functional groups are one of the most important NO donor drugs developed in recent years. It can release NO molecules spontaneously under physiological conditions, and can be detached by specific enzymes i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/36A61P9/00A61P9/10C08B37/08A61K47/61
Inventor 万锕俊孙燕李慧丽张隐西
Owner SHANGHAI JIAO TONG UNIV
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