Zwitter-ion hydrogel capable of visually monitoring pH of wound in real time as well as preparation method and application of zwitter-ion hydrogel

Abstract

The invention relates to zwitterionic hydrogel capable of visually monitoring the pH of a wound in real time, a preparation method and application. A zwitterionic monomer, sodium chloride, a cross-linking agent, an initiator, a pH indicator and a solvent are uniformly mixed according to a certain component content. The super-hydrophilicity and antifouling property of the hydrogel can promote wound healing and avoid secondary damage caused by adhesion during wound nursing, and the hydrogel shows different color changes in different pH environments and is visible to naked eyes, so that visual monitoring is realized. After the hydrogel is integrated on the wound nursing material, a cotton swab, gauze and a band-aid with an indication function can be obtained, so that the wound healing condition can be more conveniently, practically and visually monitored.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedical materials, and more particularly to a zwitterionic hydrogel capable of visually monitoring wound pH in real time, a preparation method and an application thereof. Background Art

[0002] Skin damage can lead to impaired sensory and physical barrier functions, resulting in sensory loss or wound infection caused by microbial communities. During the complex healing process, dynamic changes in wound exudates such as metabolites and pH can reflect the status of the wound. pH is an important parameter. The pH of intact and non-infected skin is slightly acidic, usually between 4-6, and the pH of chronic wounds is usually between 7-9. Compared with wounds with a pH close to neutral, chronic wounds with an alkaline pH are more conducive to bacterial infection, which often manifests before other clinical symptoms appear. Therefore, monitoring wound pH can be used to assess wound status and detect early infection, so that appropriate treatment can be carried out in a timely manner.

[0003] Currently, wound pH monitoring methods include indicator dyes, electrochemical methods, and fluorescence methods. Fluorescent materials require an excitation light source (usually a UV lamp), while electrochemical methods require complex circuits and external instrumentation. Determining wound pH by color change with an indicator dye is the simplest and most effective method, offering ease of use, low cost, and the absence of instrumentation, making it more readily accepted. Fluctuations in the acidity and alkalinity of the wound environment can cause reversible changes in the dye's molecular structure (protonation / deprotonation). This shift in electronic conformation within the dye molecule leads to a color change.

[0004] Compared to wounds exposed to air, wounds treated with occlusive dressings in a moist environment have a stronger ability to heal. A moist environment reduces the number of cells in the inflammatory phase and increases the number of cells in the proliferative phase, leading to faster healing of full-thickness defects. Wound growth factors, such as fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), can only be effective in a sufficiently moist environment.

[0005] Betaine-based zwitterionic hydrogels are highly charged, yet their charge balance maintains macroscopic neutrality. They strongly bind to water molecules through ion dissolution. Their super-hydrophilic and anti-fouling properties resist protein adsorption and cell and bacterial adhesion, promoting wound healing. They offer unique advantages as anti-fouling skin sensors capable of comprehensively monitoring human parameters. Therefore, the development of hydrophilic hydrogels with wound pH monitoring capabilities is of great significance for biomedical applications. Summary of the Invention

[0006] The present invention addresses the shortcomings of existing technologies and provides a zwitterionic hydrogel dressing for real-time visual monitoring of wound pH. The dressing exhibits excellent hydrophilicity and antifouling properties, providing a moist environment for wounds and preventing bacterial invasion, thereby avoiding wound contamination and accelerating wound healing. Furthermore, the dressing can rapidly and accurately monitor wound pH in real time for wound management and treatment. The preparation method is relatively simple, easy to operate, and suitable for widespread application.

[0007] The technical solutions of the present invention are as follows:

[0008] On one hand, the present invention provides a zwitterionic hydrogel capable of real-time visual monitoring of wound pH, which comprises the following components, by mass percentage: 10% zwitterionic monomer, 0.9% to 2% sodium chloride (NaCl), 0.05% to 0.1% cross-linking agent, 0.05% to 0.1% initiator, 0.01% pH indicator, and the balance being solvent.

[0009] The zwitterionic monomer is any one of carboxybetaine methacrylate (CBMA), carboxybetaine acrylamide (CBAA), sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethylphosphorylcholine (MPC).

[0010] The indicator dye is any one of synthetic dyes such as phenol red, bromothymol blue, bromocresol purple, methyl red, naphthalimide-rhodamine, etc., or natural dyes such as curcumin, anthocyanin, alizarin, hematoxylin, etc.

[0011] The cross-linking agent is any one of N,N-methylenebisacrylamide (MBAA) and N,N′-dimethylacryloylcystine (NDMCC).

[0012] The initiator is one of ammonium persulfate (APS) and N, N, N', N'-tetramethylethylenediamine (TEMED), or a combination of the two.

[0013] The solvent is ultrapure water or phosphate buffer solution.

[0014] Another aspect of the present invention provides a method for preparing a zwitterionic hydrogel capable of real-time visual monitoring of wound pH, comprising the following steps:

[0015] S1. Add the zwitterionic monomer methacrylate carboxybetaine to a brown bottle, add NaCl solution and sonicate in an ice-water bath for 30 minutes until completely dissolved.

[0016] S2. Add N, N'-dimethylacryloylcystine and sonicate until dissolved.

[0017] S3. Add ammonium persulfate and bromothymol blue and gently stir to mix to form a homogeneous solution;

[0018] S4. Place the mixture between two glass slides separated by a 1 mm thick polytetrafluoroethylene spacer and polymerize at 37°C for 3 hours to ensure complete reaction.

[0019] S5. After polymerization, remove the hydrogel from the slide and soak in PBS; change the PBS every day for five consecutive days to remove unreacted chemicals and reagents until no dye is detected in the supernatant by spectrophotometer. Store in PBS before use.

[0020] As described above, when the pH value of the wound is 5.5-8.0, the color of the hydrogel changes from yellow to green.

[0021] Another aspect of the present invention provides an application of a zwitterionic hydrogel capable of real-time visual monitoring of wound pH. The zwitterionic hydrogel is used in wound care related materials to prepare zwitterionic hydrogel cotton swabs, wound dressings, and gauze.

[0022] The specific method is as follows:

[0023] After uniformly mixing the components according to the above proportions, completely immerse the cotton swab tip in the reaction solution, dry it with a heat gun to evenly distribute the solution, and then wash it multiple times with PBS. A bandage and gauze are spread flat on a glass slide, and a certain amount of the mixed solution is pipetted onto the slide. After a cross-linking reaction, a zwitterionic hydrogel-modified wound care material is obtained.

[0024] Technical effects and advantages of the present invention:

[0025] (1) The zwitterionic hydrogel of the present invention is highly hydrophilic and can maintain a moist environment in the wound. It has excellent anti-fouling properties against the adsorption of proteins, cells, and bacteria, is easy to remove, and avoids secondary damage caused by adhesion during wound care. It can be widely used in the biomedical field.

[0026] (2) The zwitterionic hydrogel of the present invention incorporates an indicator dye, which displays different colors depending on the pH of the wound environment, allowing for real-time visual monitoring of the wound pH value. This eliminates the need for complex information transmission equipment, making it more convenient and practical.

[0027] (3) The zwitterionic hydrogel of the present invention is integrated into traditional dressings used for wound care, such as cotton swabs, gauze, and bandages, so that the hydrogel adheres firmly to the wound and has an indicator function. It can monitor the pH of the wound in a more portable manner and manage the wound in a timely manner according to the changes in the wound. Its control and regulation have therapeutic significance for guiding clinical treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a preparation and application flow chart of the present invention. DETAILED DESCRIPTION

[0029] The following is a clear and complete description of the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0030] Example 1:

[0031] A method for preparing a zwitterionic polycarboxylate betaine hydrogel for real-time visual monitoring of wound pH:

[0032] S1. Add 10% zwitterionic monomer carboxybetaine methacrylate to a brown bottle, add 2% NaCl solution and sonicate in an ice-water bath for 30 minutes until completely dissolved.

[0033] S2. Add 0.05% N, N'-dimethylacryloylcystine and sonicate until dissolved.

[0034] S3. Add 0.05% ammonium persulfate and 0.01% bromothymol blue and gently stir to mix to form a homogeneous solution.

[0035] S4. Place the mixture between two glass slides separated by a 1 mm thick polytetrafluoroethylene spacer and polymerize at 37°C for 3 hours to ensure the reaction is complete.

[0036] S5. After polymerization, remove the hydrogel from the slide and soak in PBS. Change the PBS daily for five consecutive days to remove unreacted chemicals and reagents until no dye is detected in the supernatant by spectrophotometer. Store in PBS until use.

[0037] As described above, when the pH value of the wound is 5.5-8.0, the color of the hydrogel changes from yellow to green.

[0038] Example 2:

[0039] A preparation method for a zwitterionic polysulfobetaine hydrogel for real-time visual monitoring of wound pH:

[0040] S1. Add 10% zwitterionic monomer methacrylic acid sulfobetaine to a brown bottle, add 0.9% NaCl solution and sonicate in an ice water bath for 30 minutes until completely dissolved.

[0041] S2. Add 0.05% N,N-methylenebisacrylamide and sonicate until dissolved.

[0042] S3. Add 0.05% ammonium persulfate, 0.05% N, N, N', N'-tetramethylethylenediamine, and 0.01% bromothymol blue, and gently stir to mix to form a uniform solution.

[0043] S4. Place the mixture between two glass slides separated by a 1 mm thick polytetrafluoroethylene spacer and polymerize at 37°C for 3 hours to ensure the reaction is complete.

[0044] S5. After polymerization, remove the hydrogel from the slide and soak in PBS. Change the PBS daily for five consecutive days to remove unreacted chemicals and reagents until no dye is detected in the supernatant by spectrophotometer. Store in PBS until use.

[0045] As described above, when the pH value of the wound is 5.0-8.5, the color of the hydrogel changes from yellow to purple.

[0046] Example 3:

[0047] A method for preparing an indicator cotton swab for real-time visual monitoring of wound pH:

[0048] S1. Add 10% zwitterionic monomer acrylamide carboxybetaine to a brown bottle, add 1% NaCl solution and sonicate in an ice water bath for 30 minutes until completely dissolved.

[0049] S2. Add 0.05% N,N-methylenebisacrylamide and sonicate until dissolved.

[0050] S3. Add 0.05% ammonium persulfate, 0.05% N, N, N', N'-tetramethylethylenediamine, and 0.01% curcumin, and gently stir to mix to form a uniform solution.

[0051] S4. Place the mixture between two glass slides separated by a 1 mm thick polytetrafluoroethylene spacer, completely immerse the cotton swab tip in the mixed solution, and polymerize at 37°C for 3 hours to ensure complete reaction.

[0052] S5. Dry with a heat gun to evenly distribute the surface, and wash with plenty of PBS several times until no dye is detected in the supernatant by spectrophotometer, and store in PBS before use.

[0053] As described above, when the pH value of the wound is 5.5-8.5, the color of the indicator cotton swab will change from yellow to orange.

[0054] Example 4:

[0055] A method for preparing an indicator bandage for real-time visual monitoring of wound pH:

[0056] S1. Add 10% zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine to a brown bottle, add 0.9% NaCl solution and sonicate in an ice-water bath for 30 minutes until completely dissolved.

[0057] S2. Add 0.05% N,N-methylenebisacrylamide and sonicate until dissolved.

[0058] S3. Add 0.05% ammonium persulfate, 0.05% N, N, N', N'-tetramethylethylenediamine, and 0.01% phenol red, and gently stir to mix to form a uniform solution.

[0059] S4. Place the bandage flat on the table, use a pipette to absorb a certain amount of solution, gradually add it dropwise to the cotton pad, and place it at 37°C to polymerize for 3 hours to ensure complete reaction.

[0060] S5. After polymerization, wash the supernatant several times with plenty of PBS until no dye is detected by spectrophotometer. Store in PBS until use.

[0061] As described above, when the pH value of the wound is 5.0-8.0, the color of the indicator wound dressing will change from yellow to red.

[0062] Obviously, the above preferred embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. However, any obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A zwitterionic hydrogel capable of real-time visual monitoring of wound pH, characterized in that: The invention comprises the following components by mass percentage: 10% zwitterionic monomer, 0.9%-2% sodium chloride (NaCl), 0.05%-0.1% crosslinking agent, 0.05%-0.1% initiator, 0.01% pH indicator, and the balance is solvent.

2. The zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that: The zwitterionic monomer is any one of carboxybetaine methacrylate (CBMA), carboxybetaine acrylamide (CBAA), sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethylphosphorylcholine (MPC).

3. The zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that: The indicator dye is any one of synthetic dyes such as phenol red, bromothymol blue, bromocresol purple, methyl red, naphthylimide-rhodamine, etc., or natural dyes such as curcumin, anthocyanin, alizarin, hematoxylin, etc.

4. The zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that: The cross-linking agent is any one of N,N-methylenebisacrylamide (MBAA) and N,N′-dimethylacryloylcystine (NDMCC).

5. The zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that: The initiator is one or a combination of ammonium persulfate (APS) or N, N, N', N'-tetramethylethylenediamine (TEMED).

6. The zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that: The solvent is ultrapure water or phosphate buffer solution.

7. A method for preparing a zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to claim 1, characterized in that , including the following steps: S1. Add the zwitterionic monomer methacrylate carboxybetaine to a brown bottle, add NaCl solution and sonicate in an ice water bath for 30 minutes until it is completely dissolved. S2. Add N, N'-dimethylacryloylcystine and sonicate until dissolved. S3. Add ammonium persulfate and bromothymol blue and gently stir to mix to form a uniform solution; S4. The mixture was placed between two glass slides separated by a 1 mm thick polytetrafluoroethylene spacer and then polymerized at 37 °C for 3 hours to ensure complete reaction; S5. After polymerization, remove the hydrogel from the slide and soak in PBS; change PBS every day for five consecutive days to remove unreacted chemicals and reagents until no dye is detected in the supernatant by spectrophotometer, and store in PBS before use.

8. The preparation method according to claim 7, characterized in that ,When the wound pH is 5.5-8.0, the color of the hydrogel changes from yellow to green.

9. The use of the zwitterionic hydrogel capable of real-time visual monitoring of wound pH according to any one of claims 1 to 6, characterized in that: The zwitterion hydrogel is used in relevant materials for wound care to prepare zwitterion hydrogel cotton swabs, band-aids and gauze.

10. The use according to claim 9, characterized in that: The specific method is as follows: After mixing evenly according to a certain component content, the cotton swab head is completely immersed in the reaction solution, dried with a heat gun, evenly distributed on the surface, and washed with PBS multiple times; the band-aid and gauze are spread flat on a glass slide, and a certain amount of the mixed solution is taken with a pipette and dropped on it. After a cross-linking reaction, a zwitterionic hydrogel-modified wound care material can be obtained.

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