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Release-controllable antibiotic hydrogel and preparation method and application thereof

A technology of antibiotics and hydrogels, applied in the fields of polymer chemistry and biomaterials, can solve the problems of inability to precisely control drug release, and achieve the effects of avoiding drug burst release, good tissue adhesion performance, and good antibacterial effect

Active Publication Date: 2017-06-13
EAST CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention overcomes the deficiency that existing traditional gels cannot accurately control drug release, and proposes an innovative on-demand gel that can precisely control the release of aminoglycoside antibiotics, which consists of oxidized natural polysaccharides and aminoglycoside antibiotics through acid-sensitive Schiff base cross-linked

Method used

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  • Release-controllable antibiotic hydrogel and preparation method and application thereof
  • Release-controllable antibiotic hydrogel and preparation method and application thereof
  • Release-controllable antibiotic hydrogel and preparation method and application thereof

Examples

Experimental program
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Embodiment 1

[0059] Example 1: Oxidation of polysaccharide macromolecules

[0060] Dissolve 1 g of dextran (Mw: 45-60 kDa) in 12.5 mL of deionized water, add 8 mL of sodium periodate solution (0.5 M, 107 mg / mL) dropwise, and stir for 4 h in the dark, then add 1 mL of ethylene glycol and stir for 1 h After the reaction was terminated, impurities were removed from the reactant by dialysis (molecular weight cut-off: 3500Da). After 2 days of dialysis, the sample was freeze-dried and prepared into an aldylated dextran solution (80 mg / mL), which was refrigerated for use. , the synthetic route of oxidized dextran is as figure 1 shown.

[0061] Dissolve 1 g of sodium carboxymethylcellulose (Mw: 100 kDa) in 70 mL of deionized water, add 18 mL of sodium periodate solution (0.5 M, 107 mg / mL) dropwise, and stir for 4 h in the dark, then add 2 mL of ethylene glycol, Stir for 1 h to terminate the reaction, then remove impurities from the reactant by dialysis (molecular weight cut-off: 3500 Da), lyophi...

Embodiment 2

[0066] Embodiment 2: the preparation of antibacterial hydrogel

[0067] This embodiment (1)~(9) mainly uses oxidized dextran as the representative of polysaccharide macromolecule, and observes its cross-linking reaction with various aminoglycoside antibiotic drugs, such as image 3 Shown in A; (10)~(12) are respectively the cross-linking reaction of oxidized carboxymethyl cellulose, oxidized sodium alginate, oxidized chondroitin sulfate and amikacin; as image 3 Shown in B; Combined image 3 A and image 3 B can be obtained, oxidized natural polysaccharide macromolecule and aminoglycoside antibiotic drugs can form transparent and uniform hydrogel. In contrast, oxidized sodium alginate took longer to form hydrogels with drugs, which may be due to its lower water solubility and higher viscosity.

[0068] (1) Mix 150 μL of oxidized dextran solution (50 mg / mL) and 50 μL of netilmicin solution (50 mg / mL), and form a gel at room temperature for about 2 minutes.

[0069] (2) Mix ...

Embodiment 3

[0083] Embodiment 3: Determination of gel time and mechanical properties of 0.71% amikacin hydrogel (0.71% is the drug content of amikacin (accounting for the percentage of total hydrogel mass))

[0084] Preparation of oxidized dextran-amikacin hydrogel with amikacin content of 0.71%: Mix 170 μL of oxidized dextran solution (50 mg / mL, 48% degree of oxidation) with 30 μL of amikacin solution (50 mg / mL), About 90s to form a gel.

[0085] Test of mechanical properties: A multifunctional rheometer was used to test the mechanical properties of the hydrogel with an amikacin content of 0.71%. The specific method is: 850 μL oxidized dextran solution (50 mg / mL, 48% oxidation degree) was mixed with 150 μL amikacin solution (50 mg / mL), and then immediately transferred to a rheometer plate at 37 ° C for time-dependent simulation. Quantitative measurement (the rheometer model is ARES-G2, TA Instrument Company, the strain rate is 1%, and the frequency is 1 Hz). Such as Figure 5 As shown...

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Abstract

The invention relates to a release-controllable antibiotic hydrogel and a preparation method and application thereof. The release-controllable antibiotic hydrogel based on aminoglycoside antibiotics is formed by crosslinking the oxidized polysaccharide macromolecules and the aminoglycoside antibiotics through acid-sensitive schiff base groups; the schiff base bonds are broken under the acid environment produced by bacteria infection, so that the gel is degraded, and the antibiotics is released according to requirements. The invention also provides antibacterial application of the oxidized polysaccharide-aminoglycoside antibiotics hydrogel in vitro and in vivo. The release-controllable antibiotic hydrogel has the advantages that the preparation is simple, and the cost is low; the strength, shape and degrading of the gel, the medicine release rate and the like can be controlled according to the content of antibiotics, the broad-spectrum high-efficiency antibacterial property is realized, and the antibacterial effect is better than the antibacterial effect of multiple types of commercial antibacterial gels on market; the hydrogel may be prepared into creams, implants and medical apparatus coatings, so as to resist the infection by gram-negative bacterium, gram-positive bacterium and the like.

Description

technical field [0001] The invention relates to the technical fields of polymer chemistry and biomaterials. It specifically relates to a medical antibiotic hydrogel, in particular, its linker is an aminoglycoside antibiotic drug itself, and the linker is an acid-sensitive chemical bond. The hydrogel can be degraded in the acidic environment generated by bacterial proliferation, thereby releasing drugs for sterilization, realizing the on-demand release of aminoglycoside antibiotics, and the drug release rate can be self-regulated. Background technique [0002] Bacterial infection has always been a huge threat to human health. Aminoglycoside antibiotics have been listed by the World Health Organization as a class of drugs that are very effective in treating bacterial infections. They have a very broad antibacterial spectrum and are effective against tuberculosis, meningitis, and plague. However, such drugs still face the problems of drug resistance and side effects, making i...

Claims

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Application Information

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IPC IPC(8): A61K47/61A61K45/00A61K9/06A61P31/04
CPCA61K9/06A61K45/00Y02A50/30
Inventor 程义云胡婧婧
Owner EAST CHINA NORMAL UNIVERSITY
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