A method for immobilizing metal-organic framework material Zn-BDC on the surface of a substrate material with the assistance of polytannic acid.

Abstract

This invention discloses a method for immobilizing a metal-organic framework material Zn-BDC on the surface of a substrate material with the assistance of polytannic acid, comprising the following steps: Step 1, at room temperature, first immerse the clean substrate material in a weakly alkaline aqueous solution of tannic acid, then wash and dry it sequentially to obtain a substrate material with a polytannic acid coating on its surface; Step 2, first immerse the substrate material with the polytannic acid coating in a zinc acetate solution, then wash and dry it sequentially, and then immerse it in a sodium 1,4-terephthalate solution, then wash and dry it sequentially; Step 3, repeat step 2 multiple times to obtain a substrate material modified with the metal-organic framework material Zn-BDC. This invention is not only simple to operate and environmentally friendly, but also can stably immobilize Zn-BDC on the surface of the substrate material, giving the substrate material good antibacterial and hemostatic properties.

Description

Technical Field

[0001] This invention belongs to the field of medical material surface modification technology, specifically a method for fixing metal-organic framework material Zn-BDC on the surface of a substrate material with the assistance of polytannic acid. Background Technology

[0002] Metal-organic frameworks (MOFs) are a class of crystalline porous materials with periodic network structures formed by the self-assembly of inorganic metal centers (metal ions or metal clusters) and bridging organic ligands. Due to their excellent properties such as large specific surface area, high porosity, easily modifiable structure, good biodegradability and biocompatibility, MOFs have been widely used in fields such as bioimaging, diagnostics, drug delivery, biosensing, and photothermal therapy.

[0003] Zn-BDC, a metal-organic framework material, is a crystalline material formed by the reaction of sodium 1,4-terephthalate and anhydrous zinc acetate. Compared with other Zn-MOF materials with the same metal center and ligands, Zn-BDC has good stability, moisture resistance, and stable physicochemical properties, making it suitable for storage in different environments. It is expected to be fixed on the surface of medical matrix materials. The zinc ions released by Zn-BDC will participate in activating the coagulation cascade and promote the adsorption, aggregation, and activation of blood cells and platelets, thereby accelerating the hemostasis process. At the same time, zinc ions can endow the matrix material with good antibacterial effects. Therefore, it is necessary to fix Zn-BDC on the surface of medical matrix materials in a long-term and effective manner.

[0004] However, current methods for immobilizing metal-organic framework materials onto matrix surfaces using solvothermal techniques mostly involve the use of toxic organic reagents such as methanol and DMF, and the reaction conditions are extremely harsh, which greatly limits the application of Zn-BDC metal-organic framework materials in the surface modification of medical materials. Therefore, it is imperative to explore a simple, efficient, energy-saving, and environmentally friendly method for immobilizing Zn-BDC on the surface of medical substrate materials. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the present invention aims to provide a method for fixing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid. This method is not only simple to operate and environmentally friendly, but also can stably fix Zn-BDC on the surface of the substrate material, giving the substrate material good antibacterial and hemostatic properties.

[0006] To achieve the above objectives, the present invention employs the following technical solution:

[0007] A method for immobilizing a metal-organic framework material Zn-BDC on the surface of a substrate material with the assistance of polytannic acid includes the following steps:

[0008] Step 1: At room temperature, first soak the clean substrate material in a weakly alkaline tannic acid aqueous solution, then wash and dry it in sequence to obtain a substrate material with a polytannic acid coating on the surface.

[0009] Step 2: First, immerse the substrate material with the polytannic acid coating on its surface in zinc acetate solution, then wash and dry it in sequence. Next, immerse it in sodium 1,4-terephthalate solution, then wash and dry it in sequence.

[0010] Step 3: Repeat step 2 multiple times to obtain the substrate material modified with Zn-BDC metal-organic framework material.

[0011] Furthermore, in step 1, the base material is the inner layer patch of a medical passive pressure hemostatic patch, medical gauze, medical cotton ball, or medical suture.

[0012] Furthermore, the concentration of the tannic acid aqueous solution in step 1 is greater than 5 mg / mL.

[0013] Furthermore, the pH value of the tannic acid aqueous solution in step 1 is 7.5~9.

[0014] Furthermore, the soaking time in step 1 is 3 to 24 hours.

[0015] Furthermore, the concentration of the zinc acetate solution in step 2 is 0.2~0.8 mol / L.

[0016] Furthermore, in step 2, the sodium 1,4-terephthalate solution is prepared by mixing sodium hydroxide solution and 1,4-terephthalic acid solution at a molar ratio of 2.2:1, and the concentration of the sodium 1,4-terephthalate solution is 0.1~0.4 mol / L.

[0017] Furthermore, in step 2, the molar ratio of zinc acetate solution to sodium 1,4-terephthalate solution is 2:1.

[0018] Furthermore, the soaking time in step 2 is 15-30 minutes.

[0019] Furthermore, step 3 involves repeating step 2 3 to 7 times.

[0020] Compared with the prior art, the present invention has the following technical effects:

[0021] This invention first immerses the substrate material in an aqueous tannic acid solution, forming a polytannic acid coating on the substrate material surface through tannic acid self-polymerization. Utilizing polytannic acid as a polyphenol, which exhibits excellent adhesion to substrate materials of different materials, the in-situ synthesized metal-organic framework material Zn-BDC is persistently and stably fixed on the substrate material surface. Since the zinc ions released by Zn-BDC can participate in activating the coagulation cascade pathway and promote the adsorption, aggregation, and activation of blood cells and platelets, thereby accelerating hemostasis, and zinc ions have excellent inhibitory effects on both Gram-negative and Gram-positive bacteria, and zinc promotes collagen synthesis in the human body, it can promote wound healing and benefit skin recovery. Therefore, it endows the substrate material with good antibacterial and hemostatic properties. Furthermore, tannic acid and polytannic acid are green and non-toxic, possessing excellent biocompatibility and cell affinity, as well as good anti-inflammatory, hemostatic, and antioxidant properties. Combining them with Zn-BDC can further improve the hemostatic and anti-inflammatory properties of the substrate material. It is evident that this invention not only has a simple, efficient, and environmentally friendly preparation method, but also provides a biomimetic platform for the design of functional materials, broadening the application of Zn-BDC in the surface modification of medical materials.

[0022] This invention utilizes biomimetic polytannic acid to synthesize Zn-BDC in situ. The empty orbitals of zinc ions chelate with the carboxyl groups in the organic ligand sodium 1,4-terephthalate, participating in the formation of the Zn-BDC metal framework. This achieves the in-situ synthesis and fixation of Zn-BDC crystals on the substrate surface. Simultaneously, the polyphenolic hydroxyl groups provided by the polytannic acid coating form coordination bonds with the inorganic metal center zinc ions, permanently and stably fixing the Zn-BDC material on the substrate surface. Furthermore, Zn-BDC is permanently and stably fixed on the substrate surface through layer-by-layer self-assembly technology. The thickness of the Zn-BDC coating on the substrate surface can be controlled by adjusting the number of repetitions of step 2, according to actual needs.

[0023] This invention is applicable to fixing Zn-BDC on the surface of various existing substrate materials, that is, it is applicable to the surface functionalization modification of various substrate materials. Not only are the raw materials readily available and inexpensive, and easy to convert into products, which is conducive to industrial-scale production; moreover, there is no application or emission of toxic or harmful substances in the preparation process, which is a green and pollution-free process. Attached Figure Description

[0024] Figure 1 : A schematic diagram of the process of this invention;

[0025] Figure 2 Antibacterial effect of cotton gauze before and after Zn-BDC modification;

[0026] Figure 3 Statistical chart of the antibacterial rate of cotton gauze against Escherichia coli before and after Zn-BDC modification;

[0027] Figure 4 Statistical chart of the antibacterial rate of cotton gauze against Staphylococcus aureus before and after Zn-BDC modification;

[0028] Figure 5 Coagulation index (BCI) of cotton gauze before and after Zn-BDC modification;

[0029] Figure 6 : Statistical graph of wound area at different time points before and after Zn-BDC modification with cotton gauze dressing. Detailed Implementation

[0030] The specific content of the present invention will be further explained in detail below with reference to the embodiments.

[0031] Sodium hydroxide solution and 1,4-terephthalic acid solution were mixed at a molar ratio of 2.2:1 to obtain a sodium 1,4-terephthalate solution with a concentration of 0.1~0.4 mol / L. This solution was used in Examples 1 to 9 to functionalize the inner layer of the medical passive pressure hemostatic patch, medical gauze, medical cotton balls, or medical sutures. Taking medical gauze as an example, the functionalization process is described in [link to example]. Figure 1 .

[0032] Example 1

[0033] Step 1: Cut the medical cotton gauze into pieces, wash with deionized water for 1 hour, and dry in an oven to obtain clean medical cotton gauze.

[0034] Step 2: Soak clean medical cotton gauze in a tannic acid aqueous solution with a pH of 8.5 and a concentration of 40 mg / mL for 12 hours, then rinse with pure water and dry to obtain medical cotton gauze with a polytannic acid coating on the surface, which is called tannic acid modified gauze.

[0035] Step 3: Soak the medical cotton gauze with polytannic acid coating in a 0.2 mol / L zinc acetate solution for 30 min, then wash it with pure water and dry it in an oven; then soak it in a 0.1 mol / L sodium 1,4-terephthalate solution for 30 min, wash it with pure water, and then dry it in an oven.

[0036] Step 4: Repeat step 3 5 times to obtain medical cotton gauze modified with metal-organic framework material Zn-BDC, denoted as five-layer zinc-based MOF modified gauze.

[0037] Example 2

[0038] The only difference from Example 1 is that step 2 is repeated 3 times, and the resulting medical cotton gauze modified with the metal-organic framework material Zn-BDC is denoted as three-layer zinc-based MOF modified gauze.

[0039] Example 3

[0040] The only difference from Example 1 is that step 2 is repeated 7 times, and the resulting Zn-BDC-modified medical cotton gauze is referred to as seven-layer zinc-based MOF-modified gauze.

[0041] 1) In vitro antibacterial experiment: The antibacterial properties of the prepared medical gauze were evaluated using the plate coating counting method. The specific process is as follows: First, weigh out the original medical gauze before modification, the medical gauze with polytannic acid coating obtained in step 2 of Example 1, and the medical gauze modified with metal-organic framework material Zn-BDC obtained in Examples 1-3, and arrange them in test tubes. Then, add 10 mL of 1.1×10⁻⁶ mL of each of these materials. 7 CFU / mL Staphylococcus aureus suspension and 10 mL of 5.2×10⁻⁶ CFU / mL Staphylococcus aureus suspension 7 A CFU / mL E. coli bacterial suspension was co-incubated at 37°C for 12 h using a cell culture incubator. The bacterial suspension was then serially diluted four times with physiological saline at a ratio of 1:10 to a final concentration of 1×10⁻⁶. -4 The solution was then diluted 1 mL and spread onto a solid agar plate of TSA medium. It was incubated at 37°C for 48 h. Microscopic observations were performed as follows: Figure 2 As shown, the medical cotton gauze modified with Zn-BDC metal-organic framework material obtained in Examples 1 to 3 has a good inhibitory effect on both Gram-negative representative bacteria Escherichia coli and Gram-positive representative bacteria Staphylococcus aureus.

[0042] By recording the number of colony-forming units on solid agar plates, the inhibition rates (i.e., bacterial killing efficiency) of the medical cotton gauze with a polytannic acid coating obtained in step 2 of Example 1 and the medical cotton gauze modified with the metal-organic framework material Zn-BDC obtained in Examples 1-3 against Escherichia coli and Staphylococcus aureus were calculated. The results are shown in [reference needed]. Figure 3 and Figure 4 The formula for calculating the antibacterial rate is as follows:

[0043] Antibacterial rate (%) = Nt / Nc × 100%

[0044] In the formula, Nt represents the number of colonies on the solid agar plate corresponding to the medical cotton gauze with polytannic acid coating obtained in step 2 of Example 1 and the medical cotton gauze modified with metal-organic framework material Zn-BDC obtained in Examples 1 to 3, and Nc represents the number of colonies on the solid agar plate corresponding to the original medical cotton gauze before modification.

[0045] from Figure 3 and Figure 4 It can be seen that the medical cotton gauze with polytannic acid coating and the medical cotton gauze modified with Zn-BDC metal-organic framework material obtained in Examples 1 to 3 have the highest antibacterial rate against Escherichia coli and Staphylococcus aureus, which is significantly better than the antibacterial rate of the original medical cotton gauze before modification.

[0046] 2) In vitro hemostasis experiment: The original medical gauze before modification, the medical gauze with a polytannic acid coating obtained in step 2 of Example 1, and the medical gauze modified with Zn-BDC metal-organic framework material obtained in Examples 1-3 were cut into 10 mm × 10 mm square samples and placed in 50 mL centrifuge tubes. The samples were preheated at 37°C for 20 min. Then, 200 μL of fresh rabbit blood (V / V = 1:9) anticoagulated with citrate was dropped onto the gauze surface in the centrifuge tube. The tubes were then incubated at 37°C for 10 min. Next, 15 mL of deionized water was slowly added to the centrifuge tube, and the mixture was shaken at 30 rpm for 10 min. The liquid in the centrifuge tube was collected and centrifuged at 1000 rpm for 3 min. Finally, the molecular weight of the corresponding liquid from the original medical gauze and the modified medical gauze from Examples 1-3 was measured at 540 nm. The absorbance values ​​at the specified locations were used to calculate the coagulation index (BCI) of the tannic acid-modified gauze and the Zn-BDC-modified medical cotton gauze obtained in Examples 1-3, respectively, using the following formula:

[0047] BCI = As / Ab × 100%

[0048] In the formula, Ab represents the absorbance value of the original medical cotton gauze corresponding to the liquid, and As represents the absorbance value of the tannic acid modified gauze and the medical cotton gauze modified in Examples 1 to 3 corresponding to the liquid.

[0049] The results of the in vitro hemostasis experiment are as follows Figure 5As shown, the coagulation index (BCI) of tannic acid-modified gauze, three-layer zinc-based MOF-modified gauze, five-layer zinc-based MOF-modified gauze, and seven-layer zinc-based MOF-modified gauze are all lower than that of the original medical cotton gauze. Moreover, the coagulation index (BCI) of the seven-layer zinc-based MOF-modified gauze is the lowest. This indicates that Zn-BDC-modified medical cotton gauze has excellent hemostatic properties, and the thicker the coating, the better the hemostatic properties.

[0050] 3) In vitro wound healing experiment: A full-thickness skin defect model was established using C57 male mice. The specific modeling process was as follows: After anesthetizing the mice, the hair on their backs was shaved, the skin was disinfected with iodine, and an 8 mm circular wound was made on the mouse's back using ophthalmic scissors. The original medical gauze (before modification), the medical gauze with a polytannic acid coating obtained in step 2 of Example 1, and the modified medical gauze from Example 1 were respectively placed over the wound on the mouse's back and secured with medical tape. The wound healing status was recorded on the third, seventh, and fourteenth days, and the change in wound area was calculated to assess the wound healing status. The results are as follows: Figure 6 As shown, at different time points, the wound area covered by the medical gauze modified in Example 1 was the smallest, indicating that the Zn-BDC modified medical gauze has excellent wound healing promotion ability.

[0051] Example 4

[0052] Step 1: Wash the medical cotton balls with deionized water for 3 hours, then dry them in an oven to obtain clean medical cotton balls;

[0053] Step 2: Soak clean medical cotton balls in a tannic acid aqueous solution with a pH of 8 and a concentration of 40 mg / mL for 6 hours, then rinse with pure water and dry to obtain medical cotton balls with a polytannic acid coating on the surface.

[0054] Step 3: Soak the medical cotton balls with polytannic acid coating in a 0.2 mol / L zinc acetate solution for 15 min, then wash with pure water and dry in an oven; then soak them in a 0.1 mol / L sodium 1,4-terephthalate solution for 15 min, wash with pure water, and then dry in an oven.

[0055] Step 4: Repeat step 3 three times to obtain medical cotton balls modified with metal-organic framework material Zn-BDC.

[0056] Example 5

[0057] Step 1: Wash the medical sutures with deionized water for 1 hour, then dry them in an oven to obtain clean medical sutures;

[0058] Step 2: Soak clean medical cotton balls in a tannic acid aqueous solution with a pH of 8.5 and a concentration of 40 mg / mL for 6 hours, then rinse with pure water and dry to obtain medical sutures with a polytannic acid coating on the surface.

[0059] Step 3: Soak the medical sutures with polytannic acid coating in a 0.2 mol / L zinc acetate solution for 30 min, then wash with pure water and dry in an oven; then soak them in a 0.1 mol / L sodium 1,4-terephthalate solution for 30 min, wash with pure water, and then dry in an oven.

[0060] Step 4: Repeat step 3 7 times to obtain medical sutures modified with metal-organic framework material Zn-BDC.

[0061] Example 6

[0062] Step 2: Soak the inner layer of the medical passive pressure hemostatic patch in a tannic acid aqueous solution with a pH of 8 and a concentration of 40 mg / mL for 4 hours, then rinse with pure water and dry to obtain the inner layer of the medical passive pressure hemostatic patch with a polytannic acid coating on the surface.

[0063] Step 3: Soak the inner layer of the medical passive pressure hemostatic patch with a polytannic acid coating in a 0.2 mol / L zinc acetate solution for 30 min, then wash with pure water and dry in an oven; then soak it in a 0.1 mol / L sodium 1,4-terephthalate solution for 30 min, wash with pure water, and then dry in an oven.

[0064] Step 4: Repeat step 3 5 times to obtain the inner layer patch of the medical passive pressure hemostatic patch modified with metal-organic framework material Zn-BDC.

[0065] Example 7

[0066] Step 1: Cut the medical cotton gauze into pieces, wash with deionized water for 1 hour, and dry in an oven to obtain clean medical cotton gauze.

[0067] Step 2: Soak clean medical cotton gauze in a tannic acid aqueous solution with a pH of 7.5 and a concentration of 40 mg / mL for 18 hours, then rinse with pure water and dry to obtain medical cotton gauze with a polytannic acid coating on the surface, which is called tannic acid modified gauze.

[0068] Step 3: Soak the medical cotton gauze coated with polytannic acid in a 0.5 mol / L zinc acetate solution for 15 min, then wash it with pure water and dry it in an oven; then soak it in a 0.25 mol / L sodium 1,4-terephthalate solution for 15 min, wash it with pure water, and then dry it in an oven.

[0069] Step 4: Repeat step 3 7 times to obtain medical cotton gauze modified with metal-organic framework material Zn-BDC, denoted as five-layer zinc-based MOF modified gauze.

[0070] Example 8

[0071] Step 1: Wash the medical cotton balls with deionized water for 3 hours, then dry them in an oven to obtain clean medical cotton balls;

[0072] Step 2: Soak clean medical cotton balls in a tannic acid aqueous solution with a pH of 9 and a concentration of 40 mg / mL for 24 hours, then rinse with pure water and dry to obtain medical cotton balls with a polytannic acid coating on the surface.

[0073] Step 3: Soak the medical cotton balls with polytannic acid coating in a 0.8 mol / L zinc acetate solution for 20 min, then wash with pure water and dry in an oven; then soak them in a 0.4 mol / L sodium 1,4-terephthalate solution for 20 min, wash with pure water, and then dry in an oven.

[0074] Step 4: Repeat step 3 5 times to obtain medical cotton balls modified with metal-organic framework material Zn-BDC.

Claims

1. A method for immobilizing a metal-organic framework material Zn-BDC on the surface of a substrate material with the assistance of polytannic acid, characterized in that, Includes the following steps: Step 1: At room temperature, first soak the clean substrate material in a weakly alkaline tannic acid aqueous solution, then wash and dry it in sequence to obtain a substrate material with a polytannic acid coating on the surface. The base material is the inner layer patch of a medical passive pressure hemostatic patch, medical gauze, medical cotton ball, or medical suture. Step 2: First, immerse the substrate material with the polytannic acid coating on its surface in zinc acetate solution, then wash and dry it in sequence. Next, immerse it in sodium 1,4-terephthalate solution, then wash and dry it in sequence. Step 3: Repeat step 2 multiple times to obtain the substrate material modified with Zn-BDC metal-organic framework material.

2. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, In step 1, the concentration of the tannic acid aqueous solution is greater than 5 mg / mL.

3. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, The pH value of the tannic acid aqueous solution in step 1 is 7.5~9.

4. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, The soaking time in step 1 is 3 to 24 hours.

5. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, In step 2, the concentration of the zinc acetate solution is 0.2~0.8 mol / L.

6. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 5, characterized in that, In step 2, the sodium 1,4-terephthalate solution is prepared by mixing sodium hydroxide solution and 1,4-terephthalic acid solution at a molar ratio of 2.2:1, and the concentration of the sodium 1,4-terephthalate solution is 0.1~0.4 mol / L.

7. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 6, characterized in that, In step 2, the molar ratio of zinc acetate solution to sodium 1,4-terephthalate solution is 2:

1.

8. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, The soaking time in step 2 is 15-30 minutes.

9. The method for immobilizing Zn-BDC metal-organic framework material on the surface of a substrate material with the assistance of polytannic acid according to claim 1, characterized in that, Step 3 is to repeat step 2 3 to 7 times.

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