Electrical stimulation and pH dual response antibacterial injectable hydrogel and preparation method and application thereof

A dual-response, electrical stimulation technology, applied in chemical instruments and methods, colloid chemistry, colloid chemistry, etc., can solve the problems of hydrogel structure damage, affecting drug delivery, reducing therapeutic effect, etc., to achieve stable cross-linking, bioresistance Good degradability and good water solubility

Inactive Publication Date: 2018-01-19
XI AN JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
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Problems solved by technology

However, in recent years, injectable hydrogels based on chitosan and its derivatives have the following deficiencies: First, some chronic diseases require long-term and multiple administration, and even need to accurately release a certain amount of Drugs, correspondingly, patients also hope to replenish sufficient amount of drugs in the most appropriate time period and reduce the number of administrations as much as possible, but these gels cannot meet these needs; The pH will fluctuate slightly, most of which are weakly alkaline, and a small part such as gastric juice is about 1-3, intestinal tissue is about 5-7, and the pH value of the occasional cancer tumor is about 6 or less. Any floating will cause structural damage and destruction to the hydrogel used for drug controlled release, which will greatly affect the delivery of the drug and reduce the therapeutic effect; third, the infection of common microorganisms, and even the emergence of some drug-resistant bacteria, are also inevitable. The clinical application of these hydrogels is limited to a certain extent

Method used

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  • Electrical stimulation and pH dual response antibacterial injectable hydrogel and preparation method and application thereof
  • Electrical stimulation and pH dual response antibacterial injectable hydrogel and preparation method and application thereof
  • Electrical stimulation and pH dual response antibacterial injectable hydrogel and preparation method and application thereof

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preparation example Construction

[0038] An antibacterial injectable hydrogel with dual responsiveness to electrical stimulation and pH and its preparation method and application, comprising the following steps:

[0039] 1) Preparation of CP (chitosan-graft-polyaniline, chitosan-polyaniline copolymer) polymer: add chitosan and aniline to HCl aqueous solution (0.08mol / L~0.12mol / L), the addition amount of HCl aqueous solution is as the criterion that can dissolve chitosan and polyaniline, and the ratio of chitosan and HCl aqueous solution is 100mg: (8~20) mL, add ammonium persulfate subsequently, The mass ratio of chitosan to ammonium persulfate is 100 mg: (2 ~ 12) mg, react at 15 ~ 40 ° C for 18 ~ 36 h, preferably 24 h; then add 1mol / L NaOH aqueous solution to adjust the pH to 9 ~ 10, so that The product is gradually precipitated in the solution and the polyaniline is dedoped; the reaction solution is precipitated with 5 to 8 times the volume of ethanol of the reaction solution to completely precipitate the bl...

Embodiment 1

[0045] 1) Preparation of CP (chitosan-graft-polyaniline, chitosan-polyaniline copolymer) polymer: 100mg chitosan and 4.16mg aniline were added to 10mL of 0.1mol / L HCl aqueous solution, followed by 10.2mg Ammonium persulfate, stirred and reacted at 25°C for 24 hours, then added 1mol / L NaOH aqueous solution to adjust the pH to 9, so that the product was gradually precipitated in the solution and polyaniline was de-doped; the reaction solution was precipitated with 5 times the volume of ethanol Solution, so that the black-purple solid is completely precipitated, after suction filtration, rinse with N-methyl-2-pyrrolidone 3 times to remove unreacted polyaniline, after precipitation again, dry at room temperature for later use;

[0046] 2) Preparation of OD (Oxidized Dextran, oxidized dextran) polymer: Dissolve 3.28mg of sodium periodate in 100mL deionized water to make a solution, and dissolve dextran in deionized water according to the mass volume ratio of 1.25mg: 80mL Make a sol...

Embodiment 2

[0049] The OD polymer solution in step 3) was replaced by 3wt%, 5wt%, 6wt% and 8wt%, respectively, and the crosslinking time was 180 seconds, 45 seconds, 35 seconds, 30 seconds, and other conditions were the same as in Example 1, respectively Named CP / OD3, CP / OD5, CP / OD6, CP / OD8.

[0050] After testing, when the OD polymer solution concentration is 1wt%, 3wt%, 5wt% and 6wt%, the hydrogel exhibits moderate storage modulus, indicating good stability; the gel strength is too high after exceeding 6wt% , brittle, difficult to practical application; where the concentration of OD polymer solution is 1wt%, 3wt% and 5wt% test results such as figure 2 shown. Therefore, the concentration of the OD polymer solution in the present invention is 1wt%-6wt%.

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Abstract

The invention relates to an electrical stimulation and pH dual response antibacterial injectable hydrogel and a preparation method and application thereof, first, a chitosan-polyaniline copolymer is prepared by grafting polyaniline onto chitosan; the chitosan-polyaniline copolymer is prepared into a solution, and the solution is mixed with an oxidized dextran solution for crosslinking at 25-40 DEGC for 30-800 seconds to get the electrical stimulation and pH dual response antibacterial injectable hydrogel; the mass ratio of chitosan-polyaniline copolymer and oxidized dextran is (1-5): (1-8). The CP / OD hydrogel has dual response to electrical stimulation and pH, meets the demand for specific time administration and has excellent antibacterial properties.

Description

technical field [0001] The invention belongs to the technical field of degradable biomedical materials, and in particular relates to an antibacterial injectable hydrogel with dual response properties to electrical stimulation and pH, and a preparation method and application thereof. Background technique [0002] In general chemotherapy, after administration of conventional preparations, the drug is freely distributed throughout the body of the human body, and only a small part can reach the lesion site. The drug dispersed in the non-lesion site not only causes certain side effects, but also greatly weakens the therapeutic effect. (Upadhyaya L, Singh J, Agarwal V, et al. Journal of Controlled Release, 2014, 186:54-87.) At the same time, some chronic diseases that require long-term and frequent drug administration also bring great suffering to patients. Therefore, It is of great clinical significance to prepare a material that can allow chemotherapy drugs to be injected in sit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/36A61K47/34B01J13/00C08G73/02
Inventor 郭保林屈锦赵鑫
Owner XI AN JIAOTONG UNIV
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