Cobalt-doped manganese dioxide nanosphere modified antibacterial gauze and preparation method thereof

Abstract

The invention discloses a cobalt-doped manganese dioxide nanosphere modified antibacterial gauze and a preparation method thereof. The antibacterial gauze comprises the following components by weight: 0.2-1 g of potassium permanganate, 0.2-1 g of cobalt dichloride, 10-50 g of deionized water and a proper amount of common gauze. The preparation method comprises the steps of pretreatment, mixing, hydrothermal reaction and washing. The antibacterial gauze tool shows excellent multi-mode multifunctional antibacterial performance, and can be applied to antibacterial dressings of common wounds, burn infection wounds, pressure sores, diabetes mellitus and other acute and chronic disease wounds.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical dressings, in particular to a cobalt-doped manganese dioxide nanosphere (Co@MnO2 NPs) modified antibacterial gauze and a preparation method thereof, and belongs to the technical field of functional medical materials.

[0002] Material research background

[0003] As an important part of wound care, medical dressings have undergone a transformation from simple protection to functional therapy. Traditional medical gauze is woven from natural cotton fibers and has good air permeability, liquid absorption and biocompatibility, making it one of the most widely used dressing materials in clinical applications. According to statistics, the global medical gauze market has exceeded 3 billion US dollars and is growing at an annual rate of 5-7%.

[0004] However, as a passive dressing, traditional gauze can only provide a physical barrier for protection and lacks active biological functions. In clinical use, gauze can easily become a breeding ground for bacteria, leading to a high wound infection rate of 15-25%, which seriously affects the quality of wound healing and the patient's recovery process. According to the World Health Organization (WHO), wound infection is one of the main reasons for prolonged hospital stays and increased medical costs. Manganese dioxide (MnO2) is an important transition metal oxide widely used in catalysis, energy storage, environmental governance and other fields. In recent years, MnO2 nanomaterials have gradually attracted attention in the field of biomedicine. Manganese is an essential trace element for the human body and is involved in the composition of various enzyme systems. Compared to metals such as silver and copper, manganese has better biocompatibility and lower cytotoxicity. In vivo studies have shown that appropriate amounts of MnO2 nanomaterials do not cause significant tissue toxicity. Metal ion doping is an effective strategy to improve the performance of MnO2. By introducing other metal ions, the electronic structure, surface properties and catalytic activity of MnO2 can be adjusted. Commonly used doping ions include Co2+, Ni2+, Cu2+, Fe3+, etc. The Co-doped MnO2 nanosphere modified antibacterial gauze prepared in the present application combines multiple sterilization mechanisms, significantly improving the antibacterial effect. Therefore, gauze with a lower Co@MnO2 NPs density can be used, reducing the toxicity of Co-doped MnO2 nanospheres and improving the biological safety of the gauze. SUMMARY

[0005] The technical problem to be solved by the present application is to provide a nanosphere material with multiple enzyme activities and photothermal properties, i.e. a preparation method for Co-doped MnO2 nanosphere (Co@MnO2 NPs) modified antibacterial gauze (Co@MnO2 Gauze) and its application in the preparation of antibacterial gauze, providing a simple and effective strategy for the functional modification of medical dressings.

[0006] The purpose of the present application can be achieved by the following technical solutions:

[0007] The first aspect of the present application provides a cobalt-doped manganese dioxide nanosphere modified antibacterial gauze and a preparation method thereof. The raw materials used include potassium permanganate, cobalt dichloride and deionized water. In some embodiments of the present application, the gram weight of potassium permanganate is 0.2-1g, the gram weight of cobalt dichloride is 0.2-1g, and the gram weight of deionized water is 10-50g. A simple hydrothermal method is used for preparation.

[0008] The second aspect of the present application provides a cobalt-doped manganese dioxide nanosphere modified antibacterial gauze and a preparation method thereof, comprising the following steps:

[0009] (1) 0.2-1g of potassium permanganate, 0.2-1g of cobalt dichloride and 10-50g of deionized water are weighed and loaded into a reaction kettle;

[0010] (2) An appropriate amount of gauze is rinsed and added to the reaction kettle, and all the above substances are mixed and sealed in a Teflon-lined hydrothermal reaction kettle;

[0011] (3) The above hydrothermal reaction kettle is placed in an oven for heating;

[0012] (4) After the reaction is completed, the gauze is taken out and washed with deionized water and anhydrous ethanol;

[0013] (5) The washed gauze is dried.

[0014] Further, in step (3), the heating temperature is 60-80℃, and the heating time is 2-4 hours.

[0015] Further, in step (5), the gauze drying temperature is 50℃, and the drying time is 12 hours. BRIEF DESCRIPTION OF DRAWINGS

[0016] Figure 1 is a transmission electron microscope image of Co@MnO2 nanoparticles of Example 1;

[0017] Figure 2 is a scanning electron microscope image of Co@MnO2 gauze of Example 1;

[0018] Figure 3 is an X-ray diffraction experiment of Co@MnO2 nanoparticles of Example 1;

[0019] Figure 4 is an X-ray diffraction spectrum of Co@MnO2 nanoparticles of Example 1;

[0020] Figure 5OXD enzyme activity verification experiment of Co@MnO2 nanoparticles of Example 1;

[0021] Figure 6 CAT enzyme activity verification experiment of Co@MnO2 nanoparticles of Example 1;

[0022] Figure 7 Temperature recording picture and temperature curve of Co@MnO2 gauze of Example 1;

[0023] Figure 8 Antibacterial experiment recording picture of Co@MnO2 gauze of Example 1;

[0024] Figure 9 Transmission electron microscope comparison picture of MRSA bacteria experiment of Co@MnO2 gauze of Example 1;

[0025] Figure 10 Action recording picture of Co@MnO2 gauze of Example 1 on mice;

[0026] Figure 11 Hemolysis experiment picture of Co@MnO2 gauze of Example 1. DETAILED DESCRIPTION

[0027] The following detailed description of the embodiments of the present application is based on the premise of the technical solutions of the present application, and detailed implementation modes and specific operation processes are given, but the protection scope of the present application is not limited to the following embodiments.

[0028] In the following embodiments, if no special raw materials or processing techniques are mentioned, it means that they are all conventional commercially available raw materials or conventional processing techniques in the art.

[0029] The sources of raw materials of each component are shown in Table 1.

[0030] Table 1 Machine purity of raw materials of each component and corresponding manufacturers

[0031]

[0032] Example 1:

[0033] (1) 0.4 g of potassium permanganate and 0.4 g of cobalt dichloride and 30 g of deionized water were weighed into a reaction kettle;

[0034] (2) An appropriate amount of gauze was rinsed and added to the reaction kettle;

[0035] (3) The above mixture was placed in an oven for heating;

[0036] (4) After the reaction was completed, the gauze was taken out and washed with deionized water and anhydrous ethanol;

[0037] (5) drying the washed gauze.

[0038] Further, in the step (3), the temperature of heating is 70°C, and the heating time is 3 hours.

[0039] Further, in the step (5), the drying temperature of gauze is 50°C, and the drying time is 12 hours.

[0040] Example 2:

[0041] (1) taking 0.8g of potassium permanganate and 0.4g of cobalt dichloride and 30g of deionized water into a reaction kettle;

[0042] (2) taking an appropriate amount of gauze for wet washing and adding into the reaction kettle;

[0043] (3) placing the above mixture in an oven for heating;

[0044] (4) taking out the gauze after the reaction, and washing with deionized water and anhydrous ethanol;

[0045] (5) drying the washed gauze.

[0046] Further, in the step (3), the temperature of heating is 70°C, and the heating time is 3 hours.

[0047] Further, in the step (5), the drying temperature of gauze is 50°C, and the drying time is 12 hours.

[0048] Example 3:

[0049] (1) taking 0.4g of potassium permanganate and 0.8g of cobalt dichloride and 30g of deionized water into a reaction kettle;

[0050] (2) taking an appropriate amount of gauze for wet washing and adding into the reaction kettle;

[0051] (3) placing the above mixture in an oven for heating;

[0052] (4) taking out the gauze after the reaction, and washing with deionized water and anhydrous ethanol;

[0053] (5) drying the washed gauze.

[0054] Further, in the step (3), the temperature of heating is 70°C, and the heating time is 3 hours.

[0055] Further, in the step (5), the drying temperature of gauze is 50°C, and the drying time is 12 hours.

[0056] Example 4:

[0057] (1) 0.4g of potassium permanganate and 0.4g of cobalt dichloride and 50g of deionized water are weighed into a reaction kettle;

[0058] (2) An appropriate amount of gauze is washed and added to the reaction kettle;

[0059] (3) The mixture is placed in an oven for heating;

[0060] (4) After the reaction is completed, the gauze is taken out and washed with deionized water and anhydrous ethanol;

[0061] (5) The washed gauze is dried.

[0062] Further, in the step (3), the heating temperature is 70 DEG C, and the heating time is 3 hours

[0063] Further, in the step (5), the gauze drying temperature is 50 DEG C, and the drying time is 12 hours.

[0064] The Co@MnO2 nanoparticles (NPs) prepared by the application have regular and stable urchin-like morphology, the Co@MnO2 NPs have OXD and CAT enzyme activities, and exhibit excellent photothermal performance, the gauze modified by the Co@MnO2 NPs is endowed with good antibacterial performance, and the Co@MnO2 gauze can be used as antibacterial dressing for ordinary wounds, burn infection wounds, pressure sores, diabetes and other acute and chronic wound surfaces.

[0065] The application further discloses application of the Co@MnO2 gauze in preparation of antibacterial dressing.

[0066] Compared with the prior art, the application has the beneficial effects as follows:

[0067] The application prepares the antibacterial gauze modified by Co-doped MnO2 nanospheres, and the product has simple preparation method and uniform morphology.

[0068] The potassium permanganate in the application will oxidize ordinary gauze, and a stable coating of manganese compound is formed on the surface of the gauze. On this basis, urchin-like nanoparticles are formed in situ on the surface of the gauze. The nanoparticles endow the gauze with good OXD and CAT enzyme activity. In the early stage of wound healing, the gauze can kill bacteria in a slightly acidic environment through OXD enzyme activity to produce ROS. In the inflammation recovery process, the CAT enzyme activity can convert excess ROS in the wound into oxygen, achieving the purpose of anti-inflammatory and solving the problem of local hypoxia in the wound, and promoting the healing of the wound in the later stage. At the same time, the gauze modified by the nanoparticles has excellent photothermal performance, and can kill bacteria through photothermal physical sterilization, further enhancing the antibacterial effect. In addition, the Co-doped MnO2 nanospheres on the surface of the gauze have urchin-like morphology, and can kill bacteria through the special urchin-like structure, showing excellent multi-mode and multi-functional antibacterial effect. Therefore, the Co@MnO2 NPs modified antibacterial gauze has a wide application prospect in the preparation of antibacterial dressings.

[0069] The Co-doped MnO2 nanospheres modified antibacterial gauze prepared in the application combines multiple sterilization mechanisms, significantly improves the antibacterial effect, and therefore can use gauze with a lower Co@MnO2 NPs density, reduces the toxicity of Co-doped MnO2 nanospheres, and improves the biological safety of the gauze.

[0070] Experimental Example 1

[0071] Transmission electron microscope

[0072] Taking Example 1 as a typical representative, the transmission electron image data of Example 1 was collected on a Thermo Fisher transmission electron microscope in the United States. As can be seen from the figure, the Co@MnO2 NPs are urchin-shaped, and the particle size is about 150-200 nm.

[0073] Experimental Example 2

[0074] Gauze scanning electron microscope

[0075] Taking Example 1 as a typical representative, the scanning electron microscope image data of Example 1 was collected by JSM-7900F of Japan Electron (JEOL). A, B and C are SEM pictures with magnifications of 2000, 20000 and 50000, respectively, and the scale is 5 μm, 500 nm and 200 nm. As can be seen from the figure, the Co@MnO2 NPs are uniformly covered on the surface of the gauze, and are urchin-shaped.

[0076] Experimental Example 3

[0077] X-ray diffraction experiment (XRD)

[0078] Example 1 is a typical example. The XRD data of Co@MnO2 NPs in Example 1 were collected by Bruker-D8Advance in Germany.

[0079] Experiment Example 4

[0080] X-ray photoelectron spectroscopy (XPS)

[0081] Example 1 is a typical example; the XPS data for Example 1 was collected by Thermo Fisher Scientific's K-Alpha XPS. Figure 4 As shown in the figure, the full spectrum of Co@MnO2 NPs, the fine spectrum of O 1s elements, the fine spectrum of Mn 2p elements, and the fine spectrum of Co 2p elements are respectively.

[0082] Experimental Example 5

[0083] OXD enzyme activity verification experiment

[0084] Taking Example 1 as a typical example, the OXD enzyme activity experiment in Example 1 was conducted using an Agilent Cary-7000 from the United States. Figure 5 As shown, the left panel displays the UV-Vis absorption spectra of Co@MnO2 NPs + o-phenylenediamine (OPD) solutions in phosphate-buffered saline (PBS) at different pH values, while the right panel displays the UV-Vis absorption spectra of Co@MnO2 NPs + 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) solutions in PBS at different pH values. UV-Vis spectroscopy demonstrates that Co@MnO2 NPs possesses good OXD enzyme activity.

[0085] Experimental Example 6

[0086] CAT enzyme activity verification experiment

[0087] Taking Example 1 as a typical example, the CAT enzyme activity verification experiment in Example 1 was tested using a Thermo Fisher portable dissolved oxygen meter from the United States. Figure 6 As shown in the figure, the dissolved oxygen curves for Co@MnO2 NPs at concentrations of 0 μg / ml and 100 μg / ml are displayed. The dissolved oxygen test demonstrates that Co@MnO2 NPs possesses good CAT-like enzyme activity.

[0088] Experimental Example 7

[0089] Temperature rise curve and thermal imaging

[0090] Taking Example 1 as a typical example, the thermal imaging of Example 1 was recorded by Guide Infrared's T120 portable handheld thermal imager. The recorded images and temperature rise curves are as follows: Figure 7As shown. By the temperature curve and thermal imaging shooting can prove that Co@MnO2 Gauze has excellent photothermal performance.

[0091] Experimental Example 8

[0092] Antibacterial experiment

[0093] As a typical representative of Example 1, MRSA bacteria and Pseudomonas aeruginosa were cultured to prepare the control group of the experiment, ordinary gauze, Co@MnO2 Gauze, and Co@MnO2 Gauze treated with near-infrared light irradiation, and then the four comparison groups were subjected to MRSA bacteria and Pseudomonas aeruginosa experiments. The experimental results are shown in Figure 8 From the figure, we can see that the ordinary gauze has weak resistance to the two bacteria, and the MRSA bacteria and Pseudomonas aeruginosa are basically not reduced, while the group of Co@MnO2 Gauze can clearly see that the two bacteria are significantly reduced, and the group of Co@MnO2 Gauze treated with near-infrared light irradiation cannot see the two bacteria, indicating that the antibacterial effect of the present application has been significantly improved compared with ordinary gauze.

[0094] Experimental Example 9

[0095] Transmission electron microscope comparison experiment

[0096] As a typical representative of Example 1, the data of Experimental Example 9 was collected by the American Thermo Fisher transmission electron microscope. As shown in Figure 9 , the left is the transmission electron microscope image of MRSA bacteria, and the right is the transmission electron microscope image of MRSA bacteria treated with Co@MnO2 Gauze treated with near-infrared light irradiation. From the figure, we can see that the MRSA bacteria treated with Co@MnO2 Gauze treated with near-infrared light irradiation has died, and the cell has been decomposed.

[0097] Experimental Example 10

[0098] Animal experiment

[0099] To further verify the antibacterial ability of Co@MnO2 Gauze in vivo, BALB / c mice were randomly divided into 2 groups (n = 5): (I) Control, (II) Co@MnO2 Gauze + NIR. After the back hair was shaved, the mice were anesthetized with sodium pentobarbital. A sterile scalpel was used to draw a circular wound about 9 mm in diameter on the skin. The MRSA suspension (40 μL, 109 CFU mL-1) was applied to the wound and allowed to dry naturally. Six hours later, Co@MnO2 Gauze was covered on the wound of the mice and irradiated using NIR. Two treatments were performed immediately after modeling and two days later. At different time periods, especially on days 0, 1, 3, 5, and 7, the wound was photographed using a digital camera. As shown in FIG. 8, the healing rate of the infected wound treated with Co@MnO2 Gauze irradiated with near-infrared light was significantly improved compared with the control group. Figure 10

[0100] Experimental Example 11

[0101] To further verify the biosafety of Co@MnO2 Gauze, a related hemolysis experiment was performed. 0.5 mL of freshly drawn mouse blood was poured into a test tube preloaded with heparin sodium as an anticoagulant. 10 mL of normal saline was added to the test tube, and the test tube was shaken to mix evenly. The mixed test tube was centrifuged at 1200 r / min for 15 min. After centrifugation, the supernatant was discarded, and the red blood cells were washed three times with normal saline. The red blood cells were dispersed in normal saline to prepare a 2% mass concentration of red blood cell suspension. Co@MnO2 NPs were dissolved in normal saline, and 800 μL of the above nanomaterial solution of different concentrations, 800 μL of normal saline, and 800 μL of deionized water were taken as the experimental group, the negative control group, and the positive control group, respectively. 200 μL of red blood cell suspension was added to each preheated test tube. The test tube containing red blood cells was placed back in a 37°C constant temperature water bath for further incubation for 4 hours. After incubation, all test tubes were centrifuged at 1200 r / min for 15 min. After centrifugation, the supernatant in each test tube was carefully taken out. The absorbance value of the supernatant was measured at a wavelength of 577 nm to evaluate the degree of hemolysis. As shown in FIG. 9, when the concentration of Co@MnO2 NPs reached 10 μg / mL, no significant hemolysis of red blood cells was observed. Figure 11

[0102] The above-described examples are for the convenience of those skilled in the art to understand and use the invention, and do not limit the application in any form. Any person skilled in the art can make changes or modifications to the above disclosed technical content without departing from the scope of the application, and such changes or modifications are equivalent to equivalent embodiments, and are within the scope of the technical solution.​​

Claims

1. Cobalt-doped manganese dioxide nanosphere modified antibacterial gauze and a preparation method thereof, characterized in that, It comprises the following steps: (1) Put 0.2-1g potassium permanganate and 0.2-1g cobalt dichloride and 10-50g deionized water into a reaction kettle; (2) Take an appropriate amount of gauze and rinse it, then add it into the reaction kettle, and mix all the above substances with polytetrafluoroethylene; (3) Put the gauze into the inner lining of the hydrothermal reaction kettle; (4) Place the hydrothermal reaction kettle in an oven for heating; (5) After the reaction is completed, take out the gauze and wash it with deionized water and anhydrous ethanol; (6) Dry the washed gauze.

2. The cobalt-doped manganese dioxide nanosphere modified antibacterial gauze according to claim 1, and a preparation method thereof, characterized in that: In step (3), the heating temperature is 60-80℃, and the heating time is 2-4 hours.

3. The cobalt-doped manganese dioxide nanosphere modified antibacterial gauze according to claim 1, and a preparation method thereof, characterized in that: In step (5), the gauze drying temperature is 50℃, and the drying time is 12 hours.

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