ZIF-8-based composite antibacterial material as well as preparation method and application thereof

Abstract

The invention provides a ZIF-8-based composite antibacterial material and a preparation method and application thereof.Ce6 is efficiently packaged into ZIF-8 through a simple one-pot method, Ce6 at-ZIF-8 is synthesized, Ce6 at-ZIF-8 is endowed with excellent photodynamic bacterium killing efficiency, then MnO2 is doped into Ce6 at-ZIF-8, the antibacterial efficiency is greatly improved under photodynamic and chemical kinetics synergistic antibacterial effects, and meanwhile, the composite antibacterial material can be used for preparing a composite antibacterial material. Due to the addition of berberine, the antibacterial effect is improved, the healing rate of a wound is increased, the berberine has good dispersity, can be uniformly dispersed in water, has large specific surface area, can well inhibit growth and adhesion of bacteria, can be used as a dressing for promoting wound healing or resisting bacteria, not only can effectively kill bacteria except the wound, but also can be used as a dressing for promoting wound healing or resisting bacteria. In particular, wound healing of diabetic patients can be promoted, and the antibacterial material can be used as a novel antibacterial material for antibiosis and wound healing.

Description

Technical Field

[0001] The present invention belongs to the technical field of antibacterial materials, and in particular relates to a ZIF-8-based composite antibacterial material and a preparation method and application thereof. Background Art

[0002] In recent years, wound healing has become one of the fundamental problems facing the medical community due to the susceptibility of skin wounds to bacterial infection. Due to the complexity of this process, many factors can interfere with wound healing, increase the morbidity and mortality of patients, and cause significant discomfort and pain. Other factors, such as nutritional and immune status, stress, smoking, diabetes, obesity and hypertension, can also affect wound healing. In addition, the general extension of life expectancy in the elderly has increased the prevalence of non-healing ulcers. The incidence of chronic wounds in the elderly has increased, which has a great impact on the quality of life. The reasons why diabetic patients have difficulty in wound healing are complex and diverse, mainly growth factor degradation, delayed wound healing, and persistent infection. Regardless of the cause, chronic wounds have a significant physical, mental, social and economic impact on patients and healthcare systems. In recent years, the use of wound dressings with antimicrobial drugs has been considered as one of the feasible ways to control the wound healing process.

[0003] Zeolitic imidazolate frameworks (ZIFs), as a subclass of metal organic frameworks (MOFs), have excellent properties such as large specific area, adjustable pore size, simple synthesis, pH responsiveness and nanoscale pore size, and have become potential candidates for drug carriers. The photosensitizer dihydrochlorin e6 (Ce6) converts oxygen into singlet oxygen ( 1 O2), which in turn damages bacterial proteins and DNA, but its application is often severely limited by insufficient oxygen. Unlike traditional antibiotics, PDT rarely causes bacterial resistance. MnO2 NPs are effective catalysts for decomposing H2O2 into H2O and O2, and can undergo a Fenton-like reaction in a weakly acidic environment. While compensating for the lack of oxygen in PDT, they can also produce highly toxic ·OH, which damages bacterial DNA and proteins, ultimately leading to bacterial death. Berberine (BBR) is an isoquinoline alkaloid with multiple pharmacological effects such as antibacterial, hypoglycemic, and anti-inflammatory. However, due to its low lipophilicity, berberine is difficult to penetrate the bacterial cell membrane and is not easily absorbed orally.

[0004] Therefore, developing a composite material with high antibacterial efficiency and almost no side effects has great potential for promoting diabetic wound healing. Summary of the invention

[0005] The purpose of the present invention is to provide a composite antibacterial material based on ZIF-8 on the basis of the prior art. Due to the porous structure of ZIF-8, Ce6 is efficiently encapsulated into ZIF-8 by a simple "one-pot method" to synthesize Ce6@ZIF-8, which gives it excellent photodynamic killing efficiency of bacteria. MnO2 is then doped into Ce6@ZIF-8. Under the synergistic antibacterial effect of photodynamic and chemical dynamics, the antibacterial efficiency is greatly enhanced. At the same time, due to the addition of berberine, the antibacterial effect is improved while the wound healing rate is increased. It has good dispersibility and can be evenly It is dispersed in water, has a large specific surface area, can effectively inhibit bacterial growth and adhesion, and can be used as a dressing to promote wound healing or antibacterial. However, diabetic wound infection is more serious. The composite antibacterial material of the present invention can not only effectively kill bacteria outside the wound, but also effectively promote wound healing, protect the wound from external damage and bacterial infection, enhance epidermal migration, promote angiogenesis and connective tissue generation, and has the effect of reducing inflammatory factors. It has almost no side effects on internal organs and can be used as a new type of antibacterial material for antibacterial and wound healing, especially for wound healing of diabetic patients, and has good application prospects.

[0006] The second object of the present invention is to provide a method for preparing the above-mentioned ZIF-8-based composite antibacterial material.

[0007] The third object of the present invention is to provide the use of the above-mentioned ZIF-8-based composite antibacterial material as a drug for antibacterial and / or promoting diabetic wound healing, especially as a drug for promoting wound healing in diabetic patients.

[0008] The technical solution of the present invention is as follows:

[0009] A composite antibacterial material based on ZIF-8 includes a zeolite imidazole skeleton material made of 2-methylimidazole and zinc ions, which is a regular dodecahedron porous structure, in which dihydrochlorin e6 and MnO2 are filled in the internal pores, and berberine is adsorbed on the surface of the regular dodecahedron porous structure.

[0010] In the present invention, the particle size of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 is 100-200 nm, preferably 150 nm. The encapsulation rate of the photosensitizer dihydrochlorin e6 in the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 is 80%-90%, preferably 85.6%.

[0011] The present invention also provides a method for preparing the above-mentioned ZIF-8-based composite antibacterial material, comprising the following steps:

[0012] (1) Preparation of Ce6@ZIF-8: Dissolve dihydrochlorin e6 in a solvent, add a zinc acetate aqueous solution, stir evenly, add a 2-methylimidazole solution prepared from 2-methylimidazole and a solvent to the resulting mixed solution, and stir to react. The resulting reaction solution is aged overnight, centrifuged, and dried to obtain Ce6@ZIF-8;

[0013] (2) Preparation of BSA-MnO2 nanoparticles: The potassium permanganate aqueous solution and the bovine serum albumin aqueous solution were mixed evenly, stirred for reaction, centrifuged, and dried to obtain BSA-MnO2 nanoparticles;

[0014] (3) Preparation of MnO2 / Ce6@ZIF-8: Ce6@ZIF-8 obtained in step (1) and BSA-MnO2 nanoparticles obtained in step (2) are dispersed in water respectively, mixed evenly and stirred to react, thereby obtaining MnO2 / Ce6@ZIF-8;

[0015] (4) Preparation of composite antibacterial material BBR-MnO2 / Ce6@ZIF-8: The MnO2 / Ce6@ZIF-8 obtained in step (3) is dispersed in water, a berberine solution prepared from berberine and a solvent is added, the mixture is stirred for reaction, centrifuged, and dried to obtain a composite antibacterial material BBR-MnO2 / Ce6@ZIF-8.

[0016] In the present invention, in step (1), the molar ratio of dihydrochlorin e6 to zinc acetate is 1:1900-2100, preferably 1:2000. The molar ratio of 2-methylimidazole to zinc acetate is 1:0.1-0.5; preferably 1:0.2.

[0017] In step (1), the solvent is methanol or dimethyl sulfoxide, preferably dimethyl sulfoxide.

[0018] In the present invention, in step (2), the mass ratio of potassium permanganate to bovine serum albumin is 1:7-9; preferably 1:8.

[0019] In the present invention, in step (3), the mass ratio of BSA-MnO2 nanoparticles to Ce6@ZIF-8 is 3-5:1; preferably 4:1.

[0020] In the present invention, in step (4), the mass ratio of berberine to MnO2 / Ce6@ZIF-8 is 1:0.0005-0.0015; preferably 1:0.0012.

[0021] In step (4), the solvent is methanol or dimethyl sulfoxide, preferably methanol.

[0022] The composite antibacterial material based on ZIF-8 provided by the present invention adopts a simple "one-pot method" to efficiently encapsulate Ce6 into ZIF-8 due to the porous structure of ZIF-8, and synthesizes Ce6@ZIF-8, which is endowed with excellent photodynamic killing efficiency of bacteria. Then, MnO2 is doped into Ce6@ZIF-8, and the antibacterial efficiency is greatly enhanced under the synergistic antibacterial effect of photodynamic and chemical dynamics. At the same time, due to the addition of berberine, the antibacterial effect is improved while the wound healing rate is increased. The material has good dispersibility and can be evenly dispersed in water. The specific surface area is 2.34×10-1. It has a large area and can effectively inhibit bacterial growth and adhesion. It can be used as a dressing to promote wound healing or antibacterial. It can effectively kill bacteria outside the wound and promote wound healing. It can protect the wound from external damage and bacterial infection, enhance epidermal migration, promote angiogenesis and connective tissue generation, and has the effect of reducing inflammatory factors. It has almost no side effects on internal organs. It can be used in drugs for antibacterial and / or wound healing. It can be used as a new antibacterial material for antibacterial and diabetic wound healing, especially for wound healing in diabetic patients, and has good application prospects.

[0023] Adopt the technical scheme of the present invention, the advantages are as follows:

[0024] (1) The composite antibacterial material for promoting wound healing by photodynamic chemical kinetics synergistic antibacterial effect based on ZIF-8 provided by the present invention has all raw materials that are easily obtained in nature, has good biocompatibility, is safe and reliable, is simple to synthesize, and is green and environmentally friendly.

[0025] (2) The composite antibacterial material based on ZIF-8 provided by the present invention can be decomposed and fully dispersed in a weak acid environment of bacteria, and can effectively exert photodynamic effects under 660nm laser irradiation, and cooperate with chemical kinetics for antibacterial. In addition, the addition of berberine to the zeolite imidazole framework material prepared from 2-methylimidazole and zinc acetate can improve solubility and dispersibility, providing a solid foundation for antibacterial and wound healing.

[0026] (3) The photosensitizer dihydrochlorin e6 in the present invention has low solubility and low bioavailability, so it is encapsulated in ZIF-8 by a "one-pot method", which has high encapsulation efficiency and can improve the stability and bioavailability of berberine.

[0027] (4) The present invention uses "photodynamic therapy" and "chemodynamic therapy" to synergistically fight bacteria, which can effectively kill bacteria, prevent the emergence of drug-resistant bacteria, and hinder the formation of bacterial biofilms, thereby solving the problem that existing antibacterial treatment methods may cause drug resistance to bacteria and cannot effectively eliminate bacteria.

[0028] (5) The present invention adopts a simple "one-pot method" to efficiently encapsulate Ce6 into ZIF-8 to synthesize Ce6@ZIF-8, giving it excellent photodynamic bacterial killing efficiency, and then doping MnO2 into Ce6@ZIF-8. Under the synergistic antibacterial effect of photodynamic and chemical dynamics, the antibacterial efficiency is greatly enhanced. At the same time, due to the addition of berberine, the antibacterial effect is improved while the wound healing rate is increased. The entire preparation method is simple, efficient, fast, and saves resources and costs.

[0029] (6) The composite antibacterial material based on ZIF-8 provided by the present invention for promoting wound healing by photodynamic chemical kinetic synergistic antibacterial has good antibacterial properties, excellent dispersibility and solubility, can reduce the occurrence of drug resistance, and has almost no side effects.

[0030] In summary, the composite antibacterial material based on ZIF-8 provided by the present invention has good dispersibility, can be evenly dispersed in water, has a large specific surface area, can effectively inhibit bacterial growth and adhesion, can be used as a dressing to promote diabetic wound healing or antibacterial, can effectively kill bacteria outside the wound, and can effectively promote wound healing, and can be used as a new antibacterial material for antibacterial and wound healing, especially for wound healing of diabetic patients. In addition, the composite material of the present invention is green and environmentally friendly, conforms to the current green development, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the standard curve for the determination of Ce6 by spectrophotometry;

[0032] Figure 2 This is a schematic diagram of the appearance of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention; wherein, Figure 2 a is a transmission electron microscopy image of ZIF-8; Figure 2 (b) is a transmission electron microscopy image of Ce6@ZIF-8; Figure 2 (c) is a transmission electron microscopy image of MnO2 / Ce6@ZIF-8; Figure 2 (d) is the transmission electron microscopy image of BBR-MnO2 / Ce6@ZIF-8; Figure 2 e is a scanning electron microscope image of ZIF-8; Figure 2 f is the scanning electron microscopy image of BBR-MnO2 / Ce6@ZIF-8;

[0033] Figure 3 The particle size distribution diagram of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention; wherein, Figure 3 a in the middle is ZIF-8; Figure 3 b in the middle is BBR-MnO2 / Ce6@ZIF-8;

[0034] Figure 4 Zeta potential diagram of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention;

[0035] Figure 5 This is the ultraviolet absorption spectrum of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention.

[0036] Figure 6 The growth curve of bacteria inhibited by the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention;

[0037] Figure 7 This is a plate antibacterial experiment of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention;

[0038] Figure 8 This is a scanning electron microscope image of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention after treating bacteria;

[0039] Fig. 9 The composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has an effect on the healing of wounds of mice after bacterial infection;

[0040] Fig.10 The wound healing trajectory diagram and wound healing rate of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention on the healing process of mice;

[0041] Fig.11 HE staining of mouse wound tissue after treatment with the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention;

[0042] Fig.12 HE staining of the heart, liver, spleen, lungs and kidneys of mice after treatment with the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention;

[0043] Fig.13 The composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has an effect on the healing of wounds of diabetic mice after bacterial infection;

[0044] Fig.14 The wound healing trajectory diagram and wound healing rate of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention on the healing process of diabetic mice. DETAILED DESCRIPTION

[0045] The present invention can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the contents described in the examples are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0046] Example 1 Preparation of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0047] 1. Preparation of Ce6@ZIF-8

[0048] Zinc acetate (0.95 g, 0.005 mol) was dissolved in 5 mL of aqueous solution to prepare a zinc acetate aqueous solution; 2-methylimidazole (2.052 g, 0.025 mol) was dissolved in 0.5 mL of dimethyl sulfoxide solution to prepare a 2-methylimidazole solution; dihydrochlorin e6 (1.5 mg, 0.0025 mmol) was dissolved in 0.5 mL of dimethyl sulfoxide solution to prepare a dihydrochlorin e6 solution; the dihydrochlorin e6 solution was added to the zinc acetate solution, stirred for 20 minutes, and then the 2-methylimidazole solution was added and stirred for 2 hours. The resulting reaction solution was aged overnight, centrifuged at 8000 rpm for 5 minutes, and then washed 3 times with a methanol solution. The washed product was freeze-dried to obtain the product Ce6@ZIF-8 nanoparticles.

[0049] In the preparation process of the product Ce6@ZIF-8 nanoparticles, the obtained reaction solution was aged overnight, centrifuged and the supernatant was taken, and the OD340 value was measured (340nm is the characteristic absorption peak of Ce6), and the amount of residual dihydrochlorin e6 was calculated according to the standard curve. The calculation formula is: encapsulation rate (%) = residual (amount of Ce6 in the supernatant / total amount of Ce6 input) * 100%. According to the calculation, the encapsulation rate of photosensitizer dihydrochlorin e6 is 85.6%.

[0050] 2. Preparation of BSA-MnO2 nanoparticles

[0051] Dissolve (31.6 mg, 0.2 mmol) potassium permanganate in 3 mL of water to prepare a potassium permanganate aqueous solution; add 250 mg of bovine serum albumin (BSA) to 7 mL of water to prepare a bovine serum albumin (BSA) aqueous solution; add the potassium permanganate aqueous solution to the bovine serum albumin (BSA) aqueous solution, stir overnight, centrifuge, and dry to obtain BSA-MnO2 nanoparticles.

[0052] 3. Preparation of MnO2 / Ce6@ZIF-8

[0053] 8 mg of BSA-MnO2 nanoparticles were dissolved in 5 mL of deionized water, and 2 g of Ce6@ZIF-8 nanoparticles were dissolved in 10 mL of deionized water. The two were mixed, stirred overnight, centrifuged, and dried to obtain MnO2 / Ce6@ZIF-8.

[0054] 4. Preparation of composite antibacterial material BBR-MnO2 / Ce6@ZIF-8

[0055] Berberine (3 mg, 0.09 mmol) was dissolved in 2 mL of methanol to prepare a berberine (BBR) solution. 2.5 g of MnO2 / Ce6@ZIF-8 was added to 10 ml of water to prepare an aqueous solution containing MnO2 / Ce6@ZIF-8. While stirring, berberine (BBR) solution was added to the above mixed solution. The mixture was stirred overnight, centrifuged, and dried to obtain the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8.

[0056] Example 2, effect verification:

[0057] 1. Appearance of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0058] The Ce6@ZIF-8, MnO2 / Ce6@ZIF-8 and the composite material BBR-MnO2 / Ce6@ZIF-8 prepared in Example 1 were observed and photographed using a transmission electron microscope and a scanning electron microscope. The results are as follows: Figure 2 As shown. Figure 2 Middle: The composite material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention is a regular dodecahedron with a relatively uniform particle size. Figure 2 It can be seen that the particle sizes of ZIF-8, Ce6@ZIF-8, and MnO2 / Ce6@ZIF-8 are about 100nm, and the particle sizes have not increased significantly, proving that Ce6 and MnO2 are included in the pore size of ZIF-8. The particle size of BBR-MnO2 / Ce6@ZIF-8 is about 150nm, and the particle size has increased slightly, proving that berberine is adsorbed on its surface. In summary, BBR-MnO2 / Ce6@ZIF-8 was successfully synthesized.

[0059] 2. Particle size distribution of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0060] The particle size distribution of ZIF-8 and the composite material BBR-MnO2 / Ce6@ZIF-8 was measured by a particle size analyzer. Figure 3 It can be seen that the composite material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has a particle size that gradually increases due to encapsulation.

[0061] 3. Zeta potential diagram of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0062] The Zeta potential was measured by Figure 4It can be seen that the potential of ZIF-8 is 23mV, the potential of Ce6@ZIF-8 is -6mV, the potential of BSA-MnO2 is -22mV, the potential of MnO2 / Ce6@ZIF-8 is -36mV, and the potential of BBR-MnO2 / Ce6@ZIF-8 is -23mV. It can be seen that the composite material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has stable properties, is not easy to precipitate, and has good dispersibility.

[0063] 4. Ultraviolet absorption spectrum of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention.

[0064] Depend on Figure 5 It can be seen that the ultraviolet absorption spectrum of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention shows that the characteristic absorption peak of Ce6 is around 340nm, and the characteristic absorption peak of berberine is around 420nm, which is consistent with the characteristic peaks in Ce6@ZIF-8 and MnO2 / Ce6@ZIF-8, further proving the successful synthesis of BBR-MnO2 / Ce6@ZIF-8.

[0065] 5. Effect of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention on bacterial growth

[0066] Depend on Figure 6 It can be seen that the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has different concentrations and at 660nm (112mW / cm 2 ) laser irradiation for 5 minutes, and the growth curves of Staphylococcus aureus and MRSA for 24 hours. Compared with the control group, the bacteria in the Ce6@ZIF-8 group and the MnO2 / Ce6@ZIF-8 group were inhibited, and BBR-MnO2 / Ce6@ZIF-8 had the most obvious inhibition on the growth of Staphylococcus aureus and MRSA.

[0067] 6. Plate antibacterial test of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0068] Depend on Figure 7It can be seen that in the absence of laser irradiation, Ce6@ZIF-8 decomposes zinc ions in the weak acid environment of bacteria, which can be adsorbed to the surface of bacterial cell walls, causing damage to the bacterial cell walls. In addition, zinc ions can replace the position of cations on the cell membrane surface, destroying the metabolism and structure of the membrane. After decomposition, while MnO2 / Ce6@ZIF-8 exerts the antibacterial effect of zinc ions, MnO2 uses H2O2 in the bacterial microenvironment to produce a large amount of ·OH through a Fenton-like reaction, causing damage to bacterial proteins and DNA, thereby killing bacteria. While BBR-MnO2 / Ce6@ZIF-8 exerts the antibacterial effect of zinc ions and MnO2, berberine can inhibit the efflux system of bacteria and enhance the antibacterial effect. The results show that as the antibacterial effect increases, the inhibitory effect on bacteria also gradually increases, and there is a significant difference. At 660nm (112mW / cm 2 ) laser irradiation, the dissociated Ce6 will convert oxygen into singlet oxygen, exerting a photodynamic antibacterial effect and damaging the bacterial cell membrane and protein. At the same time, H2O2 will also produce oxygen in a weak acid environment, thereby increasing the photodynamic antibacterial effect and exerting a synergistic antibacterial effect of photodynamics and chemical dynamics. The results showed that it had a significant inhibitory effect on Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

[0069] 7. Antibacterial mechanism of the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0070] Depend on Figure 8 It can be seen that under the observation of scanning electron microscopy, the surface of Staphylococcus aureus and MRSA treated with BBR-MnO2 / Ce6@ZIF-8 shrank.

[0071] 8. Experimental study on the healing of mouse wounds using the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0072] A wound with a diameter of 8 mm was taken from the back of the mice. Except for the Control group, the other groups were given 10 μL of MRSA. When abscesses appeared in the wound, the Control group and MRSA were treated with PBS. Fig. 9 As shown in the results, the wounds of mice in the MRSA group healed the slowest, while the wounds of mice in the BBR-MnO2 / Ce6@ZIF-8 group healed the fastest. This is due to the fact that berberine can promote wound healing while playing an antibacterial role. Fig.10 As shown, the wound healing trajectory diagram and wound healing rate statistical diagram can more intuitively evaluate the changes in mouse wound healing.

[0073] 9. HE staining of the heart, liver, spleen, lung and kidney of mice treated with the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0074] Depend on Fig.11 It can be seen that there is no obvious damage to the heart, liver, spleen, lungs and kidneys, indicating that the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has no obvious side effects.

[0075] 11. HE staining and Masson staining of wound tissue of mice treated with the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0076] Depend on Fig.12 It can be seen that the HE staining results show that the epidermal thickness of the Control and MRSA groups that were not treated with the material was thinner and the degree of tissue healing was relatively poor. After the material treatment, the epidermal thickness of the mouse wound was larger and the tissue healing was complete. The Masson staining results showed that after the material treatment, the number of collagen fibers near the mouse wound tissue was larger. It can be seen that the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention has a significant healing effect on mouse wounds.

[0077] 12. Experimental study on wound healing of diabetic mice using the composite antibacterial material BBR-MnO2 / Ce6@ZIF-8 prepared by the present invention

[0078] Dissolve streptozotocin (STZ) in 0.01M precooled citric acid buffer (pH = 4.5), and inject 0.1mL STZ for every 10g of mouse body weight. STZ should be prepared and used immediately. Inject continuously for 5 days to construct a diabetic mouse model. Take a wound with a diameter of 8mm on the back of the mouse. Except for the Control group, other groups are given 10μL of methicillin-resistant Staphylococcus aureus. When abscesses appear in the wound, the Control group and MRSA are treated with PBS. Fig.13 As shown in the results, the wounds of mice in the MRSA group healed the slowest, while the wounds of mice in the BBR-MnO2 / Ce6@ZIF-8 group healed the fastest. This is due to the fact that berberine can promote wound healing while playing an antibacterial role. Fig.14 As shown, the wound healing trajectory diagram and wound healing rate statistical diagram can more intuitively evaluate the changes in mouse wound healing.

[0079] The present invention efficiently encapsulates Ce6 into ZIF-8 through a simple "one-pot method" to synthesize Ce6@ZIF-8, giving it excellent photodynamic bacterial killing efficiency. In addition, MnO2 is doped into Ce6@ZIF-8, and the antibacterial efficiency is greatly enhanced under the synergistic antibacterial effect of photodynamic and chemical dynamics. At the same time, due to the addition of berberine, while improving the antibacterial effect, the wound healing rate is increased, especially the wound healing of diabetic patients. In short, BBR-MnO2 / Ce6@ZIF-8 composite antibacterial material can be used as a new antibacterial material for antibacterial and wound healing.

[0080] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that it is still possible to modify the technical solutions described in the aforementioned embodiments, or to perform equivalent replacements on some of the technical features therein. However, these modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composite antibacterial material based on ZIF-8, characterized in that: The invention comprises a zeolite imidazole framework material made of 2-methylimidazole and zinc ions, which is a regular dodecahedron porous structure, wherein the internal pores are filled with dihydrochlorin e6 and MnO2, and berberine is adsorbed on the surface of the regular dodecahedron porous structure.

2. The composite antibacterial material based on ZIF-8 according to claim 1, characterized in that: The particle size of the composite antibacterial material is 100-200 nm, preferably 150 nm; the encapsulation rate of the dihydrochlorin e6 is 80%-90%, preferably 85.6%.

3. The preparation method of the composite antibacterial material for promoting wound healing based on photodynamic chemical dynamics of ZIF-8 according to claim 1, characterized in that: The steps include: (1) Preparation of Ce6@ZIF-8: Dissolve dihydrochlorin e6 in a solvent, add a zinc acetate aqueous solution, stir evenly, add a 2-methylimidazole solution prepared from 2-methylimidazole and a solvent to the resulting mixed solution, and stir to react. The resulting reaction solution is aged overnight, centrifuged, and dried to obtain Ce6@ZIF-8; (2) Preparation of BSA-MnO2 nanoparticles: The potassium permanganate aqueous solution and the bovine serum albumin aqueous solution were mixed evenly, stirred for reaction, centrifuged, and dried to obtain BSA-MnO2 nanoparticles; (3) Preparation of MnO2 / Ce6@ZIF-8: Ce6@ZIF-8 obtained in step (1) and BSA-MnO2 nanoparticles obtained in step (2) are dispersed in water respectively, mixed evenly and stirred to react, thereby obtaining MnO2 / Ce6@ZIF-8; (4) Preparation of composite antibacterial material BBR-MnO2 / Ce6@ZIF-8: The MnO2 / Ce6@ZIF-8 obtained in step (3) is dispersed in water, a berberine solution prepared from berberine and a solvent is added, the mixture is stirred for reaction, centrifuged, and dried to obtain a composite antibacterial material BBR-MnO2 / Ce6@ZIF-8.

4. The preparation method according to claim 3, characterized in that: In step (1), the molar ratio of the dihydrochlorin e6 to zinc acetate is 1:1900-2100, preferably 1:2000; the molar ratio of the 2-methylimidazole to zinc acetate is 1:0.1-0.5, preferably 1:0.

2.

5. The preparation method according to claim 3, characterized in that: In step (1), the solvent is methanol or dimethyl sulfoxide, preferably dimethyl sulfoxide.

6. The preparation method according to claim 3, characterized in that: In step (2), the mass ratio of potassium permanganate to bovine serum albumin is 1:7-9, preferably 1:

8.

7. The preparation method according to claim 3, characterized in that: In step (3), the mass ratio of the BSA-MnO2 nanoparticles to Ce6@ZIF-8 is 3-5:1, preferably 4:

1.

8. The preparation method according to claim 3, characterized in that: In step (4), the mass ratio of berberine to MnO2 / Ce6@ZIF-8 is 1:0.0005-0.0015; preferably 1:0.0012.

9. The preparation method according to claim 3, characterized in that: In step (4), the solvent is methanol or dimethyl sulfoxide, preferably methanol.

10. Use of the composite antibacterial material based on ZIF-8 for photodynamic chemical dynamics synergistic antibacterial and wound healing promotion as claimed in claim 1 as a drug for antibacterial and / or wound healing promotion, especially as a drug for promoting wound healing in diabetic patients.

Images