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Compound covalent hydrogel capable of being released according to requirements as well as preparation method and application of compound covalent hydrogel

A hydrogel and covalent technology, applied in the fields of polymer chemistry and biomaterials, can solve problems such as poor stability and uncontrollable release kinetics, and achieve avoidance of toxic and side effects, good biological safety, and high biological safety Effect

Active Publication Date: 2018-03-09
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In view of the prior art nano-silver gels are all directly physically mixed nano-silver particles in the gel, the stability is not good enough, and the release kinetics cannot be controlled. It is necessary to develop a method that can stabilize the nano-silver particles in the gel. , and a gel capable of controlling the release of nanosilver on demand

Method used

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  • Compound covalent hydrogel capable of being released according to requirements as well as preparation method and application of compound covalent hydrogel
  • Compound covalent hydrogel capable of being released according to requirements as well as preparation method and application of compound covalent hydrogel
  • Compound covalent hydrogel capable of being released according to requirements as well as preparation method and application of compound covalent hydrogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1: Synthesis of G5-Ag nanoparticles

[0064] Synthesis of G5-Ag (molar ratio 1:20) nanoparticles: First, 10 mg of the fifth-generation polyamide-amine dendrimer (G5-NH 2 PAMAM) was dissolved in 10 mL deionized water. Use nitric acid (1.53M) to adjust the pH value of the solution to 2.5, and slowly add silver nitrate (AgNO 3 , 10mg / mL) 118μL, after stirring in the dark for 0.5h, slowly add a 5-fold excess of sodium borohydride (NaBH 4 , 10mg / mL) 131μL, avoid light and stir for 2h to fully react, the solution turns from colorless to brown. Impurities were removed from the reactant by dialysis (molecular weight cut-off: 3500Da). After 10 times of dialysis, the product was freeze-dried and formulated into a G5-Ag(20) solution (20mg / mL) for storage until use.

[0065] Synthesis of G5-Ag (molar ratio of G5 to Ag: 1:30) nanoparticles: First, 10 mg of G5-NH2PAMAM was dissolved in 10 mL of deionized water. Use nitric acid (1.53M) to adjust the pH value of the solutio...

Embodiment 2

[0068] Example 2: Characterization of G5-Ag nanoparticles

[0069] The morphology and size of G5-Ag nanoparticles were characterized by high-resolution transmission electron microscopy (HRTEM, instrument model JEM-2100F, Hitachi Corporation).

[0070] The size of silver nanoparticles can be measured according to the HRTEM image, wherein the average size of G5-Ag(20) is 3.15±1.30nm, the average size of G5-Ag(30) is 3.33±1.31nm, and the average size of G5-Ag(40) The average size is 3.87±1.52 nm. Take G5-Ag(30) as an example ( figure 2 ), it can be seen that the size of the silver nanoparticles is relatively uniform, and the silver nanoparticles are dispersed and not aggregated, the reason is that the G5-NH 2 The dendrimers are positively charged, and the polymers repel each other and disperse. From the side, it is reflected that the silver nanoparticles are contained in the dendrimers.

Embodiment 3

[0071] Embodiment 3: the synthesis of oxidized dextran (Dex-CHO)

[0072] Synthesis of Dex-CHO (degree of oxidation 15%): Dissolve 1 g of dextran (Mw: 450-650 kDa) in 10 mL of deionized water, add 2.4 mL of sodium periodate solution (0.5 M, 107 mg / mL) dropwise, and keep away from light Stir the reaction for 4h, add 1mL of ethylene glycol, stir for 2h to terminate the reaction, then remove impurities from the reactant by dialysis (cut-off molecular weight: 3500Da), after 10 times of dialysis, concentrate the sample, and prepare a Dex-CHO solution (100mg / mL ), and refrigerate until use.

[0073] Synthesis of Dex-CHO (oxidation degree 20%): Dissolve 1g dextran (Mw: 450-650kDa) in 10mL deionized water, add 3.2mL sodium periodate solution (0.5M, 107mg / mL) dropwise, avoid light Stir the reaction for 4h, add 1mL of ethylene glycol, stir for 2h to terminate the reaction, then remove impurities from the reactant by dialysis (cut-off molecular weight: 3500Da), after 10 times of dialysi...

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Abstract

The invention discloses compound covalent hydrogel capable of being released according to requirements as well as a preparation method and application of the compound covalent hydrogel. The hydrogel is used for sterilizing based on the cooperation of a cationic high polymer and silver nanoparticles. The cationic high polymer is used as a template to synthesize the silver nanoparticles and then thesilver nanoparticles are subjected to covalent crosslinking with an oxidized polysaccharide high polymer through an acid-sensitive Schiff base bond; and under an acidic environment generated by bacterium infection, the Schiff base bond is broken, so that the cationic high polymer is released through gel degradation, and silver ions are generated by oxidization and are used for common sterilization. The invention further discloses in-vitro and in-vivo antibacterial application of the compound covalent hydrogel. The compound covalent hydrogel is simple to prepare and low in cost, and the cationic high polymer and nano-silver are combined to prepare the compound hydrogel. The gel prepared by the preparation method can be used for improving the antibacterial effect of the single cationic highpolymer gel, and an antibacterial spectrum of nano-silver gel can be expanded; and the toxic or side effect of the nano-silver is reduced and the synergistic effect of the cationic high polymer gel and the nano-silver gel is realized. The antibacterial effect of the hydrogel disclosed by the invention is better than that of various commercial antibacterial hydrogel in the market.

Description

technical field [0001] The invention belongs to the technical field of polymer chemistry and biomaterials. The invention relates to an on-demand release composite covalent covalent hydrogel and its preparation method and application, in particular to a medical composite antibacterial hydrogel. Background technique [0002] Bacterial infection has always been a huge threat to human health, such as causing abscess inflammation of surgical wounds and failure of implanted devices. At present, the method of flushing with antibiotic solution and systemic intravenous infusion of antibiotics is usually used to prevent infection clinically immediately after surgery. Although antibiotics have quick onset and good bacteriostatic effect, the systemic administration of antibiotics has a short duration of action, which can cause toxic side effects, make bacteria develop drug resistance, and multiple administrations will also bring discomfort to patients. At present, the gel has become a...

Claims

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Application Information

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IPC IPC(8): C08J3/075C08J3/24C08B37/02A61K9/06A61K33/38A61K47/36A61P31/02A61L27/34A61L27/52A61L27/54C08L5/02C08L79/02
CPCA61K9/06A61K33/38A61K47/36A61L27/34A61L27/52A61L27/54A61L2300/104A61L2300/404A61L2300/606C08B37/0021C08J3/075C08J3/246C08J2305/02C08J2479/02
Inventor 程义云戴天娇胡婧婧
Owner EAST CHINA NORMAL UNIV
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