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Nitric oxide donor based on sodium alginate as well as synthesis method and application of nitric oxide donor

A technology of sodium alginate and nitric oxide, which is applied to medical preparations containing active ingredients, prostheses, drug combinations, etc., and can solve the problems of prolonging the release time of nitric oxide, poor solubility of small molecule donors, and Over-fast release and other problems, to achieve the effect of increasing bioavailability, simple synthesis method, and long release time

Pending Publication Date: 2022-06-24
NANJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The sodium alginate-based nitric oxide donor synthesized by the present invention prolongs the release time of nitric oxide, and solves the problems of poor solubility of small molecule donors and excessive nitric oxide release

Method used

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  • Nitric oxide donor based on sodium alginate as well as synthesis method and application of nitric oxide donor
  • Nitric oxide donor based on sodium alginate as well as synthesis method and application of nitric oxide donor
  • Nitric oxide donor based on sodium alginate as well as synthesis method and application of nitric oxide donor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] (1) Dissolve 0.2 g of sodium alginate in 20 mL of ultrapure water, add a final concentration of 50 mMEDC·HCl, and react for 1 h at room temperature to obtain solution A.

[0041] (2) Advocating N 2 5min, weigh L-cysteine ​​hydrochloride with twice the molar amount of sodium alginate and add it to solution A in step (1), adjust the pH of the solution to 5 with 1M NaOH, and react at 25°C for 12h in the dark to obtain Reaction solution B.

[0042] (3) The reaction solution B of step (2) was placed in a dialysis bag with MWCO=3500Da, and the ultrapure water was changed every 12h, and the solution was dialyzed at room temperature for 48h, and the solution C was obtained after the dialysis.

[0043] The sulfhydryl grafting rate on sodium alginate in solution C was measured by Ellman method, and solution C was freeze-dried to obtain sulfhydrylated sodium alginate. Through infrared solid tableting operation experiments, such as image 3 As shown, infrared spectroscopy charact...

Embodiment 2

[0048] (1) Dissolve 0.2 g of sodium alginate in 20 mL of ultrapure water, add a final concentration of 50 mMEDC·HCl, and react for 1 h at room temperature to obtain solution A.

[0049] (2) Advocating N 2 5min, weigh L-cysteine ​​hydrochloride with twice the molar amount of sodium alginate and add it to solution A in step (1), adjust the pH of the solution to 6 with 1M NaOH, and react at 25°C for 12h in the dark to obtain Reaction solution B.

[0050] (3) The reaction solution B of step (2) is placed in the dialysis bag of MWCO=3500Da, and the ultrapure water is changed every 12h, and the dialysis is performed for 48h. Thiol grafting ratio.

[0051] (4) Directly adding tert-butyl nitrite with five times the molar amount of mercapto into solution C, adjusting the pH of the solution to 9, reacting at room temperature under nitrogen protection for 12h, using a dialysis bag with a molecular weight cut-off of 3500Da to dialyze with ultrapure water for 48h, Freeze drying to obta...

Embodiment 3

[0053] (1) Dissolve 0.2 g of sodium alginate in 20 mL of ultrapure water, add a final concentration of 50 mMEDC·HCl, and react for 1 h at room temperature to obtain solution A. (2) Advocating N 2 5min, weigh twice the molar amount of sodium alginate cystamine dihydrochloride and add it to solution A in step (1), adjust the pH of the solution to 6 with 1M NaOH, and react at 25°C for 12h in the dark to obtain reaction solution B .

[0054] (3) The reaction solution B of step (2) was placed in a dialysis bag with MWCO=3500Da, the water was changed every 12h, and the solution was dialyzed for 48h, and the solution C was obtained after the dialysis.

[0055] (4) DTT with a final concentration of 10 mM was added to solution C, the pH of the solution was adjusted to 7.5, and after 12 h of reaction, ultrapure water was used for dialysis for 48 h, the water was changed every 12 h, and solution D was obtained after dialysis.

[0056] (5) adopt the Ellman method to measure the sulfhyd...

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Abstract

The invention discloses a sodium alginate-based nitric oxide donor as well as a synthesis method and application thereof. The synthesis method comprises the following steps: dissolving sodium alginate in ultrapure water, adding an activating agent for reaction, adding L-cysteine hydrochloride or cystamine dihydrochloride for continuous reaction; and dialyzing the reaction solution, adding tert-butyl nitrite, continuously reacting, dialyzing the obtained solution, and freeze-drying to obtain the sodium alginate nitric oxide donor. The sodium alginate nitric oxide donor synthesized by the method is S-nitrosylated sodium alginate, sulfydryl is grafted on sodium alginate, SNO groups are formed through nitrosation, the synthesis method is simple and easy to implement, non-toxic and low in cost, and the prepared nitric oxide donor is long in release time, can exist stably, and can be used for preparing the sodium alginate nitric oxide donor. And the material and other polymer materials are expected to be applied to preparation of multifunctional nitric oxide release composite materials.

Description

technical field [0001] The invention belongs to a nitric oxide donor, in particular to a sodium alginate-based nitric oxide donor and a synthesis method and application thereof. Background technique [0002] Nitric oxide is an important small gas signal molecule in the human body, and it has always been the focus of many researchers in the scientific and medical circles. NO is involved in many physiological systems in the human body, such as: immune system, cardiovascular system, central nervous system and external circulation physiological system. In addition, nitric oxide has antibacterial, anti-platelet adhesion, promotes angiogenesis, promotes wound healing, inhibits the excessive proliferation of smooth muscle cells and anti-cancer. In the human body, nitric oxide is mainly synthesized by nitric oxide synthase (NOS), but the half-life of nitric oxide is short and unstable, only 1-5s, which limits the many applications of nitric oxide in biomedicine. Therefore, many re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/734A61K9/06C08B37/00A61P9/10A61L15/28A61L15/44A61L27/20A61L27/50A61L27/52A61L27/54
CPCA61K31/734A61K9/06A61P9/10C08B37/0084A61L27/20A61L27/54A61L27/507A61L15/28A61L15/44A61L27/52A61L2300/236A61L2300/422C08L5/04
Inventor 沈健袁江王丽娟
Owner NANJING NORMAL UNIVERSITY
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