Preparation method and application of calcium alginate-based gel material with fluorescent reversible effect

Abstract

The application provides a preparation method and application of a calcium alginate-based gel material with a fluorescent reversible effect, and comprises the following steps: first, preparing a calcium alginate gel with a fluorescent effect, then immersing the calcium alginate gel in a solution containing copper ions to obtain a fluorescently quenched calcium alginate-based gel material; and then releasing the copper ions in the gel material to obtain a calcium alginate-based gel material with a fluorescent effect. The method utilizes the different responsiveness of sodium alginate to calcium ions and copper ions, so that the prepared gel material has a fluorescent reversible effect; when the fluorescently quenched calcium alginate-based gel material is applied to antibacterial dressings, the copper ions are released for antibacterial action, and at the same time, the gel material exhibits a fluorescent effect, so that the antibacterial effect of the dressing is intelligently monitored through fluorescent reversible response. The gel material has excellent antibacterial performance and mechanical properties, the preparation method is mild, the process is simple, the operation environment requirement is low, the gel material can be rapidly prepared in batches, and the gel material is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of gel materials, and particularly relates to a preparation method and application of a calcium alginate-based gel material with a fluorescent reversible effect. BACKGROUND

[0002] New medical dressings mainly include gel film, hydrogel, alginate, foam, hydrogel and medicinal materials, etc. Hydrogel materials have the advantages of high water content, strong water absorption, smooth surface, no adhesion to the wound, good biocompatibility, etc. and show unique advantages in promoting wound healing. It is widely used in the field of new medical dressings. For example, the high water content of hydrogel can continuously provide a moist environment for the wound and promote autolytic debridement of the wound; the special three-dimensional space structure of hydrogel can provide a microenvironment highly simulating the extracellular matrix; the regular pores can provide a larger effective area for cell proliferation, promote fibroblasts to adhere, diffuse and proliferate rapidly, and good stimulus responsiveness can realize drug loading and slow release.

[0003] Hydrogel is soft and can closely adhere to irregular wounds, but the poor mechanical properties and single chemical components greatly limit the function and application of hydrogel dressings, which often need to be assisted by blending with other materials and multi-layer dressings for treatment, so as to improve the mechanical strength and effectively combine the properties of multiple materials. However, this method may affect the performance of hydrogel materials, and the combination of multiple materials increases the production cost and process difficulty.

[0004] In addition, fluorescent hydrogel has stable fluorescent effect and can be applied in the fields of biological imaging, fluorescent detection, optical devices, photodynamic therapy and photocatalysis. The invention patent (application number CN201610060548.4) discloses a high-strength fluorescent hydrogel and a preparation method thereof. Carbon dots are used as fluorescent substances and are doped in polyacrylamide / sodium alginate composite hydrogel materials to obtain a covalent / ionic bond cross-linked double-interpenetrating high-strength fluorescent hydrogel material. However, the gel material needs to add substances such as crosslinking agent and initiator ammonium persulfate in the preparation process, which has strong oxidizing and corrosive properties and is not conducive to the application of fluorescent hydrogel in the field of biological medicine. Moreover, the preparation process is too complicated, it is difficult to control the forming process and structural uniformity of the gel, and it is not suitable for mass production. In the prior art, few studies have realized the reversible response of fluorescent hydrogel and applied it in the fields of medical dressings and antibacterial materials, and the effect of the gel plays a role in fluorescent monitoring.

[0005] Therefore, it is necessary to design an improved preparation method and application of a calcium alginate-based gel material with a fluorescent reversible effect to solve the above problems. SUMMARY

[0006] The application aims to provide a preparation method and application of a calcium alginate-based gel material with fluorescent reversible effect, utilize different responses of sodium alginate molecules to calcium ions and copper ions respectively, realize multiple regulation of mechanical properties and fluorescent properties of the gel dressing, and realize intelligent monitoring of the antibacterial effect of the dressing through the fluorescent reversible response when the prepared gel is applied as the dressing, and the mechanical properties of the gel material are controllable.

[0007] To achieve the above-mentioned application purposes, the application provides a preparation method and application of a calcium alginate-based gel material with fluorescent reversible effect, wherein the preparation method of the calcium alginate-based gel material with fluorescent reversible effect comprises the following steps:

[0008] S1, preparing a calcium alginate gel with fluorescent effect;

[0009] S2, immersing the calcium alginate gel obtained in step S1 in a solution containing copper ions to crosslink and obtain a calcium alginate-based gel material with fluorescent quenching; the concentration of copper ions in the solution containing copper ions is 0.05-4 mol / L;

[0010] S3, releasing the copper ions in the calcium alginate-based gel material in step S2 to obtain a calcium alginate-based gel material with fluorescent effect.

[0011] As a further improvement of the application, in step S1, the preparation process of the calcium alginate gel comprises: drying a solution containing sodium alginate by injection molding to obtain a gel film, and then immersing the gel film in a solution containing calcium ions to prepare the calcium alginate gel; the concentration of calcium ions in the solution containing calcium ions is 0.05-4 mol / L.

[0012] As a further improvement of the application, the solution containing sodium alginate further contains carboxymethyl chitosan, and the mass ratio of the carboxymethyl chitosan to the sodium alginate is 1:(0.3-3), preferably 1:1.

[0013] As a further improvement of the application, the mass percentage of solutes in the solution containing sodium alginate or the solution containing sodium alginate and carboxymethyl chitosan is 0.5%-2.5%, preferably 2%.

[0014] As a further improvement of the application, the soaking time of the gel film in the solution containing calcium ions is 2-48 h, and the soaking time of the calcium alginate gel in the solution containing copper ions is 2-24 h.

[0015] As a further improvement of the present application, in step S3, the releasing mode of the copper ions includes: releasing the copper ions by using the pH response of the calcium alginate-based gel material, or soaking treatment with an ethylenediaminetetraacetic acid solution.

[0016] As a further improvement of the present application, the solution containing copper ions is an aqueous solution containing one of copper sulfate pentahydrate, copper chloride, and copper nitrate; and the solution containing calcium ions is an aqueous solution containing one of calcium chloride, anhydrous calcium chloride, and calcium disodium ethylenediaminetetraacetate.

[0017] As a further improvement of the present application, when the solution containing calcium ions is the aqueous solution of calcium disodium ethylenediaminetetraacetate, the aqueous solution of calcium disodium ethylenediaminetetraacetate needs to be acid-treated to be acidic before the gel film is immersed.

[0018] An application of a calcium alginate-based gel material with a fluorescent reversible effect, the fluorescently quenched calcium alginate-based gel material prepared by any one of the preparation methods described above is applied to the field of antibacterial dressings for covering or bandaging wounds.

[0019] As a further improvement of the present application, after the fluorescently quenched calcium alginate-based gel material is applied as antibacterial dressing, the fluorescent effect appears, and the gel material exerts antibacterial effect.

[0020] The present application has the following beneficial effects:

[0021] 1. The preparation method of a calcium alginate-based gel material with a fluorescent reversible effect, first, a calcium alginate gel with a fluorescent effect is prepared, which is immersed in a solution containing copper ions, cross-linked to obtain a fluorescently quenched calcium alginate-based gel material; then the copper ions in the calcium alginate-based gel material are released, and a calcium alginate-based gel material with a fluorescent effect is obtained again. The present application realizes reversible regulation of the fluorescent properties of the gel material by using the different responses of sodium alginate to calcium ions and copper ions, so that the prepared antibacterial gel material has antibacterial effect due to the release of copper ions when applied in wound dressing or antibacterial material because of the acidic pH of the application environment, and the antibacterial gel material has fluorescent properties again, realizing the effect of intelligent monitoring dressing through the fluorescent reversible response; and the gel material has multiple antibacterial functions as a dressing, and has good mechanical properties.

[0022] 2. In the calcium alginate gel of the present invention, calcium ions selectively chelate and cross-link with the G units in the sodium alginate molecular chain, restricting the freely rotating luminescent groups in the sodium alginate, causing them to aggregate and exhibit a fluorescence effect, i.e., the gel material exhibits a significant fluorescence effect under specific conditions. However, the chelation between calcium ions and the M units of sodium alginate is relatively weak, leaving the M units in the sodium alginate molecular chain still in a free state. When the calcium ion-induced luminescence calcium alginate gel is further immersed in a solution containing copper ions, the copper ions undergo chelation coordination with the M units in the sodium alginate molecular chain. Due to the presence of copper ions, the energy on the luminescent groups is converted to Cu. 2+ The above process, characterized by fluorescence quenching of the gel material, yields a fluorescence-quenched calcium alginate-based gel material. When this fluorescence-quenched calcium alginate-based gel material is applied to antibacterial dressings, the surrounding wound environment is acidic, causing the Cu on the gel material surface to... 2+ While precipitating and producing an antibacterial effect, the antibacterial dressing also regains its fluorescent effect, enabling intelligent monitoring of the dressing's antibacterial efficacy.

[0023] 3. This invention uses a two-component polymer of sodium alginate and carboxymethyl chitosan to prepare a gel material, forming a double-network structure, which improves the mechanical properties of the gel material; moreover, carboxymethyl chitosan itself has antibacterial properties, enhancing the antibacterial effect of the gel material. Furthermore, when the gel of calcium alginate and carboxymethyl chitosan is immersed in a copper ion solution, Cu... 2+ Copper ions can simultaneously chelate with the M units of sodium alginate molecular chains and the molecular chains of carboxymethyl chitosan. As a crosslinking agent between the two molecules, copper ions increase the degree of crosslinking between sodium alginate and carboxymethyl chitosan, thereby further improving the mechanical properties of the gel material. When this gel material is applied, although copper ions precipitate out, causing the loss of crosslinking ionic bonds between sodium alginate and carboxymethyl chitosan molecules, the degree of physical crosslinking between the molecular chains does not change significantly. Therefore, the gel material still maintains good mechanical properties and has strong practicality.

[0024] 4. The calcium alginate-based gel material with reversible fluorescence effect prepared by this invention has good biocompatibility and degradability, and is non-toxic; moreover, the preparation method is mild, no extra raw materials are added, the process is simple, the requirements for the operating environment are low, it can be prepared in batches quickly, and it is suitable for industrial production. Attached Figure Description

[0025] Figure 1 This is a molecular structure diagram of sodium alginate and carboxymethyl chitosan used in this invention.

[0026] Figure 2 This is a schematic diagram illustrating the different responses of sodium alginate and carboxymethyl chitosan to calcium and copper ions in this invention.

[0027] Figure 3Process diagram for preparing calcium alginate-based gel material with fluorescent reversible effect for example 1 of the present application.

[0028] Figure 4 For Cu 2+ Effect diagram of quenching fluorescence of gel material and recovering fluorescence of gel material by EDTA solution.

[0029] Figure 5 Fluorescence response test result diagram of gel material prepared for example 1 at different pH values, wherein (a) is a flowchart of the test, (b) is a macroscopic picture of the gel material, and (c) is a fluorescence picture of the gel material under UV = 365 nm at different pH values.

[0030] Figure 6 Fluorescence effect test diagram of SA / CMC gel film crosslinked by calcium ions at different pH values; wherein (a) is an optical picture and a fluorescence picture under 365 nm excitation wavelength irradiation of the gel film, and (b) is the fluorescence spectrum test result thereof.

[0031] Figure 7 Test result diagram of strain of surface patterned gel material prepared by the scheme of example 1.

[0032] Figure 8 Test result diagram of stress-strain performance of materials prepared for examples 2-5 and comparative examples 1-11.

[0033] Figure 9 Antibacterial effect comparison diagram of gel materials prepared for examples 2-5 and comparative examples 1-11.

[0034] Figure 10 Optical diagram of gel film after soaking in different metal ion solutions.

[0035] Figure 11 Fluorescence performance test result diagram of gel film after soaking in different metal ion solutions. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be described in detail below in combination with the drawings and specific examples.

[0037] Here, it also needs to be explained that, in order to avoid obscuring the present application due to unnecessary details, only structures and / or processing steps closely related to the scheme of the present application are shown in the drawings, and other details not closely related to the present application are omitted.

[0038] It is also to be noted that the terms "comprising", "including", or any other variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but can also include other elements not expressly listed or inherent to such process, method, article, or apparatus.

[0039] A preparation method of a calcium alginate-based gel material with a fluorescent reversible effect, comprising the following steps:

[0040] S1, a solution containing sodium alginate is prepared and is subjected to injection molding drying to obtain a gel film; sodium alginate is used as a raw material for preparing the gel material, in order to utilize its different responses to calcium ions and copper ions, so as to realize intelligent regulation of the fluorescent performance of the gel material, and realize monitoring of the effect of the intelligent dressing through fluorescent response;

[0041] S2, the gel film obtained in step S1 is immersed in a solution containing calcium ions to obtain a calcium alginate gel with a fluorescent effect; after being washed with deionized water, it is immersed in a solution containing copper ions to obtain a calcium alginate-based gel material with fluorescence quenching;

[0042] The concentration of calcium ions in the solution containing calcium ions is 0.05-4 mol / L, and the concentration of calcium ions is limited to ensure the crosslinking effect of calcium ions and polymers, and to avoid too few calcium ions, which causes a large number of sodium alginate molecular chains to be free; the concentration of copper ions in the solution containing copper ions is 0.05-4 mol / L, and the concentration of copper ions is limited to avoid excessive copper ions from causing excessive fluorescence quenching effect of the gel material, and to realize the fluorescent reversible effect;

[0043] S3, the copper ions in the calcium alginate-based gel material of step S2 are released to obtain a calcium alginate-based gel material with a fluorescent effect again; the release mode of the copper ions includes: using the pH responsiveness of the calcium alginate-based gel material to release the copper ions, or using ethylenediaminetetraacetic acid solution for soaking treatment.

[0044] Please refer to Figures 1-2As shown, the gel material prepared from sodium alginate is first immersed in a solution containing calcium ions. The calcium ions selectively chelate and cross-link with the G units in the molecular chain of sodium alginate, limiting the free rotation of the luminophore groups in the sodium alginate, causing the luminophore groups to aggregate and have a fluorescence effect, and the photoluminescence efficiency is increased, that is, the gel material exhibits a significant fluorescence effect under certain conditions (for example, under UV = 365 nm conditions). However, the chelation of calcium ions with the M units of sodium alginate is weak, so that the M units in the molecular chain of sodium alginate are still in a free state. The calcium alginate gel with a fluorescence effect is immersed in a solution containing copper ions. The copper ions chelate with the M units in the molecular chain of sodium alginate. Because of the presence of copper ions, the energy on the luminophore groups is converted to Cu 2+ The above, the gel material exhibits fluorescence quenching, and a calcium alginate-based gel material with fluorescence quenching is obtained. When the calcium alginate-based gel material with fluorescence quenching is applied to an antibacterial dressing, the environment around the wound is acidic, causing the Cu 2+ ions on the surface of the gel material to precipitate, producing an antibacterial effect, while the gel material regains a fluorescence effect, functioning as a fluorescence intelligent monitoring dressing for antibacterial effect.

[0045] Specifically, the solution containing sodium alginate further contains carboxymethyl chitosan, and the mass ratio of carboxymethyl chitosan to sodium alginate is 1:(0.3-3), preferably 1:1. The gel film is prepared by using a two-component polymer of sodium alginate and carboxymethyl chitosan, forming a double network structure material, which improves the mechanical properties of the gel material; and when the gel film material is immersed in a copper ion solution, the Cu 2+ ions can simultaneously chelate with the M units of the molecular chain of sodium alginate and the molecular chain of carboxymethyl chitosan. The copper ions act as a cross-linking between the two molecules, increasing the cross-linking degree of sodium alginate and carboxymethyl chitosan, thereby further improving the mechanical properties of the gel material. In addition, because carboxymethyl chitosan itself has antibacterial function, the antibacterial effect of the gel material can be improved; and when the mass ratio of carboxymethyl chitosan to sodium alginate is 1:1, the antibacterial effect of the obtained antibacterial gel material is the best.

[0046] It should be noted that when the calcium alginate-based gel material is applied, although the copper ions precipitate, the fluorescence effect reappears at the same time, causing the intermolecular cross-linking ionic bonds between sodium alginate and carboxymethyl chitosan to be lost, but the degree of physical cross-linking between the molecular chains of sodium alginate and carboxymethyl chitosan changes little, so the gel material still maintains good mechanical properties and is highly practical.

[0047] Specifically, in step S2, the gel film is soaked in a solution containing calcium ions for 2 to 24 hours and in a solution containing copper ions for 2 to 48 hours. Controlling the treatment time of the gel material in the calcium ion solution and the copper ion solution is the same as controlling the concentration of calcium ions and copper ions in the solution, both of which are to better control the fluorescence performance of the calcium alginate-based gel material.

[0048] Specifically, in the solution containing sodium alginate or the solution containing sodium alginate and carboxymethyl chitosan, the mass percentage of the solute is 0.5% to 2.5%, preferably 2%; the solute includes single-component sodium alginate or two-component sodium alginate and carboxymethyl chitosan.

[0049] In some specific embodiments, in step S2, the solution containing calcium ions is an aqueous solution containing one of calcium chloride, anhydrous calcium chloride, and disodium calcium ethylenediaminetetraacetate; the solution containing copper ions is an aqueous solution containing one of copper sulfate pentahydrate, copper chloride, and copper nitrate. When the solution containing calcium ions is an aqueous solution of disodium calcium ethylenediaminetetraacetate, the aqueous solution of disodium calcium ethylenediaminetetraacetate needs to be acid-treated to make it acidic before the sodium alginate gel film is immersed. This is because the release of calcium ions from disodium calcium ethylenediaminetetraacetate requires certain conditions to induce, so acid treatment is necessary to make the solution acidic, thereby promoting the release of calcium ions from disodium calcium ethylenediaminetetraacetate and their chelation coordination with polymer molecules.

[0050] In some specific embodiments, in step S1, the template used for injection molding drying is a polymethyl methacrylate template, and the drying temperature is room temperature.

[0051] In some specific embodiments, after the solutions in step S1, solution A and solution B in step S2 are prepared, they are all magnetically stirred for 1 hour to ensure that the solute is completely dissolved.

[0052] An application of a calcium alginate-based gel material with reversible fluorescence effect is disclosed. This calcium alginate-based gel material, prepared by the aforementioned method, is used in antibacterial dressings after fluorescence quenching for wound covering or bandaging. When the fluorescence-quenched calcium alginate-based gel material is used as an antibacterial dressing, its fluorescence effect is observed, indicating that the gel material exhibits good antibacterial efficacy. This invention utilizes the different responsiveness of sodium alginate to calcium and copper ions to achieve intelligent control of the fluorescence properties of the gel material. When the prepared gel material is applied as an antibacterial dressing, the acidic pH environment causes copper ions to precipitate, generating an antibacterial effect, and the antibacterial gel dressing regains its fluorescence effect. The fluorescence response enables intelligent monitoring of the dressing's antibacterial effect. Furthermore, the gel material, as a dressing, possesses multiple antibacterial functions, and its mechanical properties are controllable.

[0053] Example 1

[0054] This embodiment provides a method for preparing a calcium alginate-based gel material with reversible fluorescence effect, including the following steps:

[0055] S1. Weigh out sodium alginate (SA) and carboxymethyl chitosan (CMC) separately, and dissolve them in deionized water. Stir magnetically for 1 hour until completely dissolved to prepare sodium alginate solution and carboxymethyl chitosan solution. Mix the two solutions and stir magnetically for 1 hour to obtain SA / CMC solution. The mass ratio of sodium alginate to carboxymethyl chitosan in SA / CMC solution is 1:1, and the concentration of total solute is 2%.

[0056] S2. Pour the CMC / SA mixed solution onto the constructed polymethyl methacrylate (PMMA) template and air dry at room temperature to obtain a CMC / SA gel film with a ratio of 1:1.

[0057] S3. Weigh out anhydrous calcium chloride (CaCl2) and copper sulfate pentahydrate (CuSO4·5H2O), dissolve them separately in deionized water, and stir magnetically until fully dissolved to obtain CaCl2 solutions with a concentration of 0.1 mol / L. 2+ and Cu 2+ Solution;

[0058] S4. Immerse the CMC / SA gel film obtained in step S2 into Ca 2+ A calcium alginate gel film with fluorescent effect was prepared by immersion in solution for 2 hours, and then washed with deionized water. The gel film was then subjected to Cu... 2+ Crosslinking in solution for 4 hours yields a calcium alginate-based gel material with reversible fluorescence effect.

[0059] S3. Release the copper ions from the calcium alginate-based gel material obtained in step S2 to obtain a new calcium alginate-based gel material with fluorescent effect.

[0060] Please refer to Figure 3, which shows the process of preparing the calcium alginate-based gel material with reversible fluorescence effect in Example 1. From the figure, it can be seen that the gel film and Ca... 2+ After cross-linking, the color changes to Ca 2+ Its characteristic color is white, and the gel film softens, exhibiting a certain degree of flexibility; further, it reacts with Cu... 2+ It turns blue after cross-linking, which is Cu. 2+ It has a characteristic color and improved mechanical properties of the gel film.

[0061] Please see Figure 4 As shown, the Ca-loaded material prepared using the method in Example 1 is shown. 2+ The gel film exhibits fluorescence under 365nm UV light; Cu2+ In the area of "porpoise", the area was found to have fluorescence quenching; by soaking in EDTA solution, Cu 2+ removed, the printed area returned to white, and the fluorescence effect reappeared. Again using another template to print Cu 2+ printed the letter "HAPPY", the area had fluorescence quenching, and by soaking in EDTA, Cu 2+ removed, the printed area returned to white, and the fluorescence reappeared. Under the condition of UV = 365 nm, the fluorescence properties of the film can be seen to be reversible with the printing and removal of Cu 2+ ions. The results show that the fluorescence properties of the gel film of the application have reversible regulation, and can be cross-linked and removed by Cu 2+ ions to achieve the effect of repeated quenching and appearance.

[0062] Please refer to Figure 5 , Figure 5 The fluorescence response test results of the gel material prepared in Example 1 under different pH conditions, (a) is a flowchart of the test, (b) is a macroscopic picture of the gel material, and (c) is a fluorescence picture of the gel material under different pH conditions under the condition of UV = 365 nm. As can be seen from figures (b) and (c), after the gel film cross-linked with calcium ions is bent, cross-linking with copper ions can fix the film shape and keep the bent state, and by soaking in EDTA solution under a specific pH condition, copper metal ions can be induced to release, accompanied by shape and fluorescence recovery. Under the condition of pH = 3.5 / EDTA soaking, the film finally changes from blue to transparent, indicating that most of the metal ions Cu / Ca are removed by competitive chelation, but the film does not dissolve and still maintains the bent state, indicating that the dual-metal ion cross-linking effect can endow the gel with shape memory properties. Under the condition of pH = 10 soaking, the film finally changes from blue to white, indicating that most of the Cu ions are removed, and the Ca ions still exist, indicating that the chelation between them and the polymer molecules is relatively stable, and the film shape returns to the initial flat state, and its fluorescence gradually recovers. Therefore, when preparing the dressing, the gel film is cross-linked with calcium ions first, then cross-linked with copper ions, and the cross-linking degree of copper ions is controlled, so that when applied to a wound, the surface cross-linked copper ions are released under acidic conditions, while the calcium ions are still stably chelated with the polymer, so that the dressing reappears the fluorescence effect, playing the role of fluorescence intelligent monitoring of the antibacterial effect of the dressing.

[0063] Please refer to Figure 6The fluorescence effect test diagram of SA / CMC gel film crosslinked by calcium ions under different pH values is shown. (a) is the optical photograph and fluorescence photograph under 365 nm excitation wavelength irradiation of the gel film, and (b) is the fluorescence spectrum test result thereof. As can be seen from the diagram, the acidic environment can stimulate the swelling change of the gel film structure to a certain extent, and cause the corresponding change of fluorescence. However, the fluorescence response of the gel film crosslinked by single ion (Ca 2+ ) under different pH conditions is less sensitive than that of Cu / Ca double ions. It can be seen that the fluorescence effect of the gel film crosslinked by single ion (Ca 2+ ) changes greatly only when pH = 1, and the change of fluorescence spectrum is not obvious under the condition of pH 2-6.

[0064] The surface patterned gel material is prepared by the scheme of Example 1, and the strain test thereof is carried out, and the result is shown in Figure 7 . As can be seen from the diagram, the Cu 2+ crosslinked region presents blue color, and the mechanical property of the film without soaking Cu 2+ is the worst. The copper ion crosslinking in the stretching direction obviously strengthens the mechanical strength of the gel film, which indicates that the crosslinking of Cu 2+ to the polymer can improve the mechanical property of the gel material.

[0065] Example 2

[0066] The embodiment provides a preparation method of calcium alginate-based gel material with fluorescence reversible effect. Compared with Example 1, the difference lies in that only SA solution is used to prepare the gel film, and the soaking time of the gel film in Ca 2+ solution and Cu 2+ solution is 4 h, and the rest is basically the same as Example 1, which will not be repeated here.

[0067] Examples 3-4

[0068] Examples 3-4 provide a preparation method of calcium alginate-based gel material with fluorescence reversible effect. Compared with Example 1, the difference lies in that the mass ratio of SA:CMC in the SA / CMC mixed solution of Examples 3-5 is 3:1 and 1:3 respectively, and the soaking time of the gel film in Ca 2+ solution and Cu 2+ solution is 4 h, and the rest is basically the same as Example 1, which will not be repeated here.

[0069] Example 5

[0070] Example 5 provides a preparation method of calcium alginate-based gel material with fluorescence reversible effect. Compared with Example 1, the difference lies in that the soaking time of the gel film in Ca 2+Solution and Cu 2+ The soaking time for the solution was 4 hours, and the rest was roughly the same as in Example 1, so it will not be repeated here.

[0071] Comparative Example 1

[0072] Comparative Example 1 provides a method for preparing a gel material. The difference from Example 1 is that only CMC solution is used to prepare the gel film. The rest is roughly the same as Example 1 and will not be repeated here.

[0073] Comparative Examples 2-6

[0074] Comparative Examples 2-6 provide a method for preparing a gel material. Comparative Examples 2-6 respectively employ the methods of Examples 2-5 and Comparative Example 1, the difference being that the gel films of Comparative Examples 2-6 are prepared only on Cu... 2+ Soak in the solution for 4 hours.

[0075] Comparative Examples 7-11

[0076] Comparative Examples 7-11 provide a method for preparing a gel material. Comparative Examples 2-6 adopt the schemes of Examples 2-5 and Comparative Example 1, respectively. The difference is that the gel films of Comparative Examples 7-11 are prepared only in Ca... 2+ Soak in the solution for 4 hours.

[0077] The gel materials prepared in Examples 2-5 and Comparative Examples 1-11 were subjected to stress-strain performance tests, and the results are as follows: Figure 8 As shown; it should be noted that the ratios marked in the figure are the mass ratios of SA:CMC in the SA / CMC mixed solution. From Figure 8 It can be seen that only Ca is used 2+ The gel film soaked in the solution is relatively soft, and then soaked in Cu 2+ Afterwards, the mechanical strength of the gel film was significantly increased. The gel film prepared using pure SA solution had poor mechanical properties, but the addition of carboxymethyl chitosan significantly improved the mechanical properties of the prepared gel material; however, there was no obvious correlation between the amount added and the change in mechanical properties.

[0078] Please see Figure 9 The figure shows a comparison of the antibacterial effects of the gel materials prepared in Examples 2-5 and Comparative Examples 1-11. It should be noted that the ratios indicated in the figures are the mass ratios of SA:CMC in the SA / CMC mixed solution. As can be seen from the figures, under the same component ratio, Cu... 2+ Cu 2+ / Ca 2+ The antibacterial zone of the cross-linked film is significantly larger than that of Ca. 2+Antibacterial properties of cross-linked films: Under the same cross-linking method, the CMC / SA ratio of 1:1 resulted in the most significant inhibition zone and the best antibacterial effect. This result indicates that the mixing ratio of metal ions and polymers affects the antibacterial properties of the composite film; among them, a CMC / SA ratio of 1:1 and Cu... 2+ Cross-linking significantly enhances the antibacterial effect.

[0079] Comparative Examples 12–16

[0080] Comparative Examples 12-16 provide a method for preparing an antibacterial gel material. The difference from Example 1 is that Comparative Examples 12-16 use only one type of metal ion solution for soaking, namely Ni... 2+ Co 2+ Fe 3+ Zn 2+ Ag + The solution was soaked for 4 hours, and the rest was roughly the same as in Example 1, so it will not be repeated here.

[0081] Please see Figure 10 As shown, Figure 10 Optical images of gel films treated with different metal ion solutions. The images show that the film changes color after cross-linking with the metal ions, exhibiting common characteristic colors of those metal ions; the gel film, through interaction with Ca... 2+ Zn 2+ Ionic crosslinking causes the gel to produce bright fluorescence under 365nm UV light, while other metal ions do not produce this effect.

[0082] Comparative Example 17

[0083] Comparative Example 17 provides a method for preparing an antibacterial gel material, which differs from Example 1 in that Comparative Example 17 uses Zn 2 Solution replacing Cu 2+ The solution was used for soaking, and the rest was roughly the same as in Example 1, so it will not be described again.

[0084] Please see Figure 11 As shown, Figure 11 The graph shows the fluorescence performance of the gel film after treatment with different metal ion solutions. As can be seen from the graph, the gel film exhibits fluorescence properties after treatment with Ca... 2+ Zn 2+ Ionic crosslinking can cause the gel to exhibit fluorescent properties, Cu 2+ It will not cause the gel film to exhibit fluorescent properties; however, after Ca... 2+ Crosslinking, then Cu 2+ The fluorescence effect of the cross-linked gel is weakened, while that of the Zn gel is reduced. 2+ Replace Cu 2+Solution treatment of calcium alginate gel film does not produce the effect of fluorescence quenching. 2+ Ca 2+ The treated gel fluorescence effect is weakened, and Cu 2+ can enhance the mechanical properties of the gel material, and Ca 2+ and Cu 2+ solutions are used to treat the gel film in sequence, and then the copper ions are released, so that the calcium alginate-based gel material with a reversible fluorescence effect is obtained.

[0085] In summary, the present application provides a preparation method of a calcium alginate-based gel material with a reversible fluorescence effect. First, a calcium alginate gel with a fluorescence effect is prepared, which is immersed in a solution containing copper ions to obtain a calcium alginate-based gel material with fluorescence quenching. Then, the copper ions in the calcium alginate-based gel material are released to obtain a calcium alginate-based gel material with a fluorescence effect again. In the calcium alginate gel material, calcium ions selectively chelate and cross-link with G units in the sodium alginate molecular chain, limiting the free rotation of the luminophore groups in sodium alginate, causing them to aggregate and exhibit a fluorescence effect. The calcium alginate gel with a fluorescence effect is immersed in a copper ion solution again, and copper ions chelate and coordinate with M units in the sodium alginate molecular chain. Because of the presence of copper ions, the energy on the luminophore groups is transferred to Cu 2+ , resulting in fluorescence quenching of the gel material, and a calcium alginate-based gel material with fluorescence quenching is obtained. When the calcium alginate-based gel material with fluorescence quenching is used as an antibacterial dressing, the environment around the wound is acidic, causing the Cu 2+ on the surface of the gel material to be released, producing an antibacterial effect while the material regains its fluorescence effect, thereby achieving the function of intelligent monitoring of the antibacterial effect through fluorescence. In addition, a double-network structure gel is prepared using sodium alginate and carboxymethyl chitosan as a bi-component polymer, which improves the mechanical properties. At the same time, Cu 2+ can chelate with both M units in the sodium alginate molecular chain and the molecular chain of carboxymethyl chitosan, increasing the cross-linking degree of the two and further improving the mechanical properties of the gel material. The gel material of the present application has multiple antibacterial functions and controllable mechanical properties, and realizes intelligent regulation of the fluorescence properties of the gel material and intelligent monitoring of the antibacterial effect of the dressing through fluorescence response.

[0086] The above examples are only used to illustrate the technical solutions of the present application and are not limiting. Although the present application has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application.

Claims

1. A method for preparing a calcium alginate-based gel material with reversible fluorescence effect, characterized in that, Includes the following steps: S1. Preparation of calcium alginate gel with fluorescent effect; The preparation process of the calcium alginate gel includes: casting and drying a solution containing sodium alginate and carboxymethyl chitosan to obtain a gel film; then immersing the gel film in a solution containing calcium ions to obtain the calcium alginate gel; the mass percentage of the solute in the solution containing sodium alginate and carboxymethyl chitosan is 0.5%~2.5%; S2. Immerse the calcium alginate gel obtained in step S1 in a solution containing copper ions to crosslink and obtain a fluorescence-quenched calcium alginate-based gel material; the concentration of copper ions in the solution containing copper ions is 0.05~4 mol / L; S3. Release the copper ions from the calcium alginate-based gel material described in step S2 to obtain a calcium alginate-based gel material with a fluorescent effect; the copper ion release method includes: releasing copper ions by utilizing the pH responsiveness of the calcium alginate-based gel material, and soaking the material in an ethylenediaminetetraacetic acid solution; wherein, the method of releasing copper ions by utilizing the pH responsiveness of the calcium alginate-based gel material includes: soaking the material under pH=10 conditions.

2. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 1, characterized in that, In step S1, the concentration of calcium ions in the solution containing calcium ions is 0.05~4 mol / L.

3. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 2, characterized in that, The mass ratio of the carboxymethyl chitosan to the sodium alginate is 1:(0.3~3).

4. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 3, characterized in that, The mass ratio of the carboxymethyl chitosan to the sodium alginate is 1:

1.

5. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 3, characterized in that, The solution containing sodium alginate and carboxymethyl chitosan has a solute mass percentage of 2% for each.

6. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 2, characterized in that, The gel film is immersed in the solution containing calcium ions for 2 to 48 hours; the calcium alginate gel is immersed in the solution containing copper ions for 2 to 24 hours.

7. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 2, characterized in that, The solution containing copper ions is an aqueous solution containing one of copper sulfate pentahydrate, copper chloride, and copper nitrate; the solution containing calcium ions is an aqueous solution containing one of calcium chloride, anhydrous calcium chloride, and calcium disodium ethylenediaminetetraacetate.

8. The method for preparing the calcium alginate-based gel material with reversible fluorescence effect according to claim 7, characterized in that, When the solution containing calcium ions is an aqueous solution of calcium disodium ethylenediaminetetraacetate, the aqueous solution of calcium disodium ethylenediaminetetraacetate needs to be acid-treated to make it acidic before the gel film is immersed.

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