PREPARATION OF NANO SILVER/DUAL MODIFIED CHITOSAN ANTIBACTERIAL HYDROGEL DRESSING WITH DISCOLORATION EFFECT FOR WOUND INFECTION JUDGEMENT AND HYDROGEL DRESSING PREPARED BY THE SAME

Abstract

A preparation of nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for wound infection judgement and hydrogel dressing prepared by the same provided. The preparation includes the following: carrying out quaternization water-soluble modification on high molecular weight chitosan, and carrying out catecholamination water-soluble modification to prepare dual water-soluble modified chitosan; reducing silver nitrate by using the dual water-soluble modified chitosan to prepare a nano silver/dual water-soluble modified chitosan solution; adding the dual water-soluble modified chitosan, the nano silver/dual water-soluble modified chitosan, curcumin, zwitterion, acrylamide, a cross-linking agent and an initiator into deionized water in sequence, mixing and stirring uniformly, centrifugal de-foaming and casting, to prepare a nano silver/dual modified chitosan antibacterial color-changing hydrogel dressing by one-pot in-situ radical polymerization. The nano silver/dual modified chitosan antibacterial hydrogel dressing exhibits great potential for application in fields such as intelligent indicative wound repair hydrogel dressing and the like.

Claims

1. A method for preparing a nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for judging wound infection, comprising the following: carrying out quaternization water-soluble modification on high molecular weight chitosan, and carrying out catecholamination water-soluble modification to prepare dual water-soluble modified chitosan; reducing silver nitrate by using the dual water-soluble modified chitosan to prepare a nano silver/dual water-soluble modified chitosan solution; adding the dual water-soluble modified chitosan, the nano silver/dual water-soluble modified chitosan, curcumin, zwitterion, acrylamide, a cross-linking agent and an initiator into deionized water in sequence, mixing and stirring uniformly, centrifugal de-foaming and casting, to prepare a nano silver/dual modified chitosan antibacterial discoloration hydrogel dressing by one-pot in-situ radical polymerization.

2. The method for preparing a nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for judging wound infection according to claim 1, wherein, the method comprises the following: 1) dispersing a powder raw material of the high molecular weight chitosan in deionized water with stirring, and adding 0.1-5 wt % acetic acid to prepare a 0.1-1 wt % chitosan aqueous solution; adding glycidyl trimethylamine chloride to the chitosan aqueous solution, reacting for 8 h to prepare quaternized water-soluble modified chitosan, and obtaining a quaternized water-soluble modified chitosan material after dialysis and lyophilization; 2) dissolving the quaternized water-soluble modified chitosan obtained in step 1) in deionized water to prepare an aqueous solution with a mass concentration of 0.1-1 wt %, sequentially adding 3-(2,4-dihydroxy) phenylpropionic acid and 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride, and adjusting pH within 4-5.5 by using acetic acid throughout; further reacting for 12 h to obtain catecholamination-modified dual water-soluble modified chitosan, and obtaining the dual water-soluble modified chitosan after dialysis and lyophilization, wherein pH is adjusted within 4-5.5 by acetic acid during the dialysis; 3) dissolving the water-soluble modified chitosan obtained in step 2) in deionized water, adding silver nitrate, and reacting in the dark for 0.5 h to prepare a nano silver/dual water-soluble modified chitosan solution; and 4) dissolving the dual water-soluble modified chitosan prepared in step 2), the nano silver/dual water-soluble modified chitosan prepared in step 3), curcumin, zwitterion, acrylamide, the cross-linking agent and the initiator in deionized water in sequence, mixing and stirring uniformly, casting into a mold after centrifugal defoaming, and reacting at 60° C. for 4 h by a one-pot free radical polymerization method to prepare a hydrogel dressing with a nano-composite and semi-interpenetrating polymer network structure.

3. The method for preparing a nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for judging wound infection according to claim 2, wherein, the high molecular weight chitosan has a deacetylation degree of 70% to 90%, and a molecular weight of 0.5 million to 3 million; and the dual water-soluble modified chitosan has a quaternization degree of 10% to 60%, a catecholamination degree of 5% to 60%, and a solubility of 25 mg/mL or more.

4. The method for preparing a nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for judging wound infection according to claim 2, wherein, the concentration of the glycidyl trimethylamine chloride in step 1) is 0.025-0.10 g/ml; the concentrations of the 3-(2,4-dihydroxy) phenylpropionic acid and 1-ethyl-(3-dimethylamino propyl) carbodiimide hydrochloride in step 2) are 0.001-0.005 g/ml and 0.001-0.005 g/ml respectively; the concentrations of the dual water-soluble modified chitosan and silver nitrate in step 3) are 0.015-0.05 g/ml and 0.015-0.05 g/ml respectively; and the zwitterion in step 4) is phosphorylcholine (PC), sulfobetaine methacrylate (SBMA) or carboxybetaine methacrylate (CBMA); the cross-linking agent is N,N-methylene bisacrylamide (MBAA); the initiator is ammonium persulfate, sodium persulfate or potassium persulfate; wherein, the concentrations of each components are as follows: 0.05-0.1 g/ml of the water-soluble modified chitosan, 0.0002-0.0005 g/ml of the nano silver/dual water-soluble modified chitosan, 0.001-0.005 g/ml of the curcumin, 0.02-0.1 g/ml of the zwitterions, 0.1-0.5 g/ml of the acrylamide, 0.0002-0.0008 g/ml of the cross-linking agent and 0.001-0.004 g/ml of the initiator.

5. A nano silver/dual modified chitosan antibacterial hydrogel dressing with discoloration effect for judging wound infection prepared by the method according to claim 1.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0030] FIG. 1 illustrates the particle size test result and physical drawing of nano silver prepared according to the present application;

[0031] FIG. 2 illustrates the stability test result of the nano silver/dual modified chitosan solution prepared according to the present application;

[0032] FIG. 3 is a schematic diagram of the discoloration effect of the hydrogel material prepared according to the present application.

DESCRIPTION OF EMBODIMENTS

[0033] The present application will be further illustrated with reference to examples.

Example 1

[0034] 1) High molecular weight chitosan powder of raw material-grade (1 million molecular weight, a deacetylation degree 86%) was dispersed in deionized water with stirring, and 2.5 wt % acetic acid was added to prepare a 0.5 wt % chitosan aqueous solution; glycidyl trimethylamine chloride (0.10 g/ml) was added to the chitosan aqueous solution to react for 8 h to obtain a quaternized water-soluble modified chitosan aqueous solution, which, after dialysis and lyophilization, yielded quaternized water-soluble modified chitosan with a quaternization degree of 60%;

[0035] 2) the quaternized water-soluble modified chitosan obtained in step 1) was dissolved in deionized water to prepare an aqueous solution with a mass concentration of 0.5 wt %, and 3-(2,4-dihydroxy) phenylpropionic acid (0.0025 g/ml) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.003 g/ml) were added in sequence; the pH of the solution was adjusted to 4-5.5 by acetic acid throughout, and reaction was carried out for 12 h to obtain an aqueous solution of dual water-soluble modified chitosan that was further catecholamination; the dual water-soluble modified chitosan was obtained after dialysis and lyophilization; during dialysis, acetic acid was used to adjust the pH of dialysate to 4-5.5, and the degree of catecholamination of the product was 46%;

[0036] 3) the dual water-soluble modified chitosan obtained in step 2) was dissolving in deionized water (0.05 g/ml), silver nitrate (0.05 g/ml) was added to react in the dark for 0.5 h to prepare a nano silver/dual water-soluble modified chitosan solution;

[0037] 4) the dual water-soluble modified chitosan (0.05 g/ml) obtained in step 2), the nano silver/dual water-soluble modified chitosan (0.0005 g/ml), curcumin (0.005 g/ml), SBMA (0.1 g/ml), acrylamide (0.25 g/ml), MBAA (0.0005 g/ml), ammonium persulfate (0.0025 g/ml) and the like were added into deionized water in sequence, mixed and stirred uniformly; after centrifugal de-foaming and casting, and a gel was prepared by one-pot in-situ free radical copolymerization at 60° C. for 4 h;

[0038] 5) the prepared hydrogel dressing had a tensile strength of 324.6 kPa, an elongation at break of 531%, and an adhesive strength of 8.2 kPa; combined with an ICP-MS test, it was found that the release amount of silver in 7 days was 80%; combined with living dead bacteria staining and antibacterial experiments, it was found that the hydrogel dressing could inhibit the adhesion of bacteria and had good antibacterial effect on Staphylococcus aureus and Escherichia coli models.

Example 2

[0039] 1) High molecular weight chitosan powder of raw material-grade (1.8 million molecular weight, a deacetylation degree 74%) was dispersed in deionized water with stirring, and 5 wt % acetic acid was added to prepare a 1 wt % chitosan aqueous solution; glycidyl trimethylamine chloride (0.05 g/ml) was added to the chitosan aqueous solution to react for 8 h to obtain a quaternized water-soluble modified chitosan aqueous solution, which, after dialysis and lyophilization, yielded quaternized water-soluble modified chitosan with a quaternization degree of 34%;

[0040] 2) the quaternized water-soluble modified chitosan obtained in step 1) was dissolved in deionized water to prepare a quaternized water-soluble modified chitosan aqueous solution with a mass concentration of 0.75 wt %, and 3-(2,4-dihydroxy) phenylpropionic acid (0.005 g/ml) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.003 g/ml) were added in sequence; the pH of the solution was adjusted to 4-5.5 by acetic acid throughout, and reaction was carried out for 12 h to obtain an aqueous solution of dual water-soluble modified chitosan that was further catecholamination; the dual water-soluble modified chitosan was obtained after dialysis and lyophilization; during dialysis, acetic acid was used to adjust the pH of dialysate to 4-5.5, and the degree of catecholamination of the product was 21%;

[0041] 3) the dual water-soluble modified chitosan obtained in step 2) was dissolving in deionized water (0.03 g/ml), silver nitrate (0.025 g/ml) was added to react in the dark for 0.5 h to prepare a nano silver/dual water-soluble modified chitosan solution;

[0042] 4) the dual water-soluble modified chitosan (0.05 g/ml) obtained in step 2), the nano silver/dual water-soluble modified chitosan (0.0002 g/ml), curcumin (0.001 g/ml), SBMA (0.04 g/ml), acrylamide (0.5 g/ml), MBAA (0.0002 g/ml), potassium persulfate (0.0035 g/ml) and the like were added into deionized water in sequence, mixed and stirred uniformly; after centrifugal de-foaming and casting, and a gel was prepared by one-pot in-situ free radical copolymerization at 60° C. for 4 h;

[0043] 5) the prepared hydrogel dressing had a tensile strength of 167 kPa, an elongation at break of 608%, and an adhesive strength of 5.7 kPa; combined with an ICP-MS test, it was found that the release amount of silver in 7 days was 64%; combined with living dead bacteria staining and antibacterial experiments, it was found that the hydrogel dressing could inhibit the adhesion of bacteria and had good antibacterial effect on Staphylococcus aureus and Escherichia coli models.

Example 3

[0044] 1) High molecular weight chitosan powder of raw material-grade (2.5 million molecular weight, a deacetylation degree 72%) was dispersed in deionized water with stirring, and 0.1 wt % acetic acid was added to prepare a 0.1 wt % chitosan aqueous solution; glycidyl trimethylamine chloride (0.10 g/ml) was added to the chitosan aqueous solution to react for 8 h to obtain a quaternized water-soluble modified chitosan aqueous solution, which, after dialysis and lyophilization, yielded quaternized water-soluble modified chitosan with a quaternization degree of 56%;

[0045] 2) the quaternized water-soluble modified chitosan obtained in step 1) was dissolved in deionized water to prepare a quaternized water-soluble modified chitosan aqueous solution with a mass concentration of 0.1 wt %, and 3-(2,4-dihydroxy) phenylpropionic acid (0.001 g/ml) and 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.001 g/ml) were added in sequence; the pH of the solution was adjusted to 4-5.5 by acetic acid throughout, and reaction was carried out for 12 h to obtain an aqueous solution of dual water-soluble modified chitosan that was further catecholamination; the dual water-soluble modified chitosan was obtained after dialysis and lyophilization; during dialysis, acetic acid was used to adjust the pH of dialysate to 4-5.5, and the degree of catecholamination of the product was 7.8%;

[0046] 3) the dual water-soluble modified chitosan obtained in step 2) was dissolving in deionized water (0.015 g/ml), silver nitrate (0.015 g/ml) was added to react in the dark for 0.5 h to prepare a nano silver/dual water-soluble modified chitosan solution;

[0047] 4) the dual water-soluble modified chitosan (0.1 g/ml) obtained in step 2), the nano silver/dual water-soluble modified chitosan (0.0005 g/ml), curcumin (0.003 g/ml), SBMA (0.02 g/ml), acrylamide (0.25 g/ml), MBAA (0.0008 g/ml), sodium persulfate (0.0015 g/ml) and the like were added into deionized water in sequence, mixed and stirred uniformly; after centrifugal de-foaming and casting, and a gel was prepared by one-pot in-situ free radical copolymerization at 60° C. for 4 h;

[0048] 5) the prepared hydrogel dressing had a tensile strength of 138 kPa, an elongation at break of 431%, and an adhesive strength of 4.4 kPa; combined with an ICP-MS test, it was found that the release amount of silver in 7 days was 53%; combined with living dead bacteria staining and antibacterial experiments, it was found that the hydrogel dressing could inhibit the adhesion of bacteria and had good antibacterial effect on Staphylococcus aureus and Escherichia coli models.