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 precisel

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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Example Embodiment

[0059] Example 1: Oxidation of polysaccharide polymer

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

[0061] Dissolve 1g of sodium carboxymethylcellulose (Mw: 100kDa) in 70mL of deionized water, add 18mL of sodium periodate solution (0.5M, 107mg / mL) drop by drop, stir for 4h in the dark, add 2mL of ethylene glycol, The reaction was terminated by stirring for 1 hour, and then the reactant was removed by dialysis (molecular weight cut-off: 3500 Da). After 2 days of dialysis, the sample was lyop...

Example Embodiment

[0066] Example 2: Preparation of antibacterial hydrogel

[0067] The examples (1) to (9) mainly take oxidized dextran as the representative of polysaccharide polymer, and observe the cross-linking reaction of it with various aminoglycoside antibiotic drugs, such as image 3 Shown in A; (10)~(12) are the cross-linking reaction of oxidized carboxymethyl cellulose, oxidized sodium alginate, oxidized chondroitin sulfate and amikacin; image 3 Shown in B; combined image 3 A and image 3 B is available. Both oxidized natural polysaccharide polymer and aminoglycoside antibiotic drugs can form a transparent and uniform hydrogel. In contrast, the longer time for oxidized sodium alginate to form a hydrogel with the drug 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 gel in about 2 minutes at room temperature.

[0069] (2) Mix 150 μL of oxidized dextran solution (50 ...

Example Embodiment

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

[0084] Preparation of oxidized dextran-amikacin hydrogel with an amikacin content of 0.71%: mix 170 μL of oxidized dextran solution (50 mg / mL, 48% oxidation) with 30 μL of amikacin solution (50 mg / mL), Gel can be formed in about 90s.

[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: 850μL of oxidized dextran solution (50mg / mL, 48% oxidation degree) is mixed with 150μL of amikacin solution (50mg / mL), and then immediately transferred to the 37 ℃ rheometer plate for time-dependent simulation Quantity test (the rheometer model is ARES-G2, TA Instrument Company, strain rate is 1%, frequency is 1Hz). Such as Figure 5 As shown, the storage modulus of the obtained ge...

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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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