An antibacterial agent with synergistic antibacterial effect by encapsulating iodide ions in a silver cage, and its preparation method and application
By encapsulating an antibacterial agent with iodide ions in a silver cage and utilizing the synergistic effect of multiple antibacterial mechanisms, the problems of bacterial resistance and multiple infections faced by existing antibacterial agents are solved, achieving a highly efficient antibacterial effect.
Patent Information
- Application Number
- CN202510080424.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-20
- Publication Date
- 2025-10-03
- Estimated Expiration
- 2045-01-20
AI Technical Summary
Existing antimicrobial agents face the challenges of bacterial resistance and multiple infections, and a single antimicrobial mechanism is difficult to effectively deal with complex bacterial infections.
An antibacterial agent that uses a 16-core silver cage to encapsulate iodide ions is assembled into a one-dimensional chain structure using thiol as a connector, and uses the synergistic effect of hydroxyl radicals with I- and Ag+ under light to kill bacteria.
It achieves the synergistic effect of multiple antibacterial mechanisms, improves the antibacterial efficacy, stably releases I- and Ag+, and has a significant synergistic antibacterial effect against bacteria such as Escherichia coli. The preparation process is simple and the raw materials are cheap and easily available.
Smart Images
Figure CN119874726B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of antibacterial materials, and in particular to an antibacterial agent with synergistic antibacterial effect, which encapsulates iodide ions in a silver cage, and a preparation method and application thereof. Background Art
[0002] Persistent infections caused by multidrug-resistant bacteria and the spread of foodborne pathogens pose significant challenges to human and animal health. The World Health Organization considers bacterial resistance one of the most pressing threats to global public health and development. Superbugs such as multidrug-resistant Gram-negative bacteria Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii, and Gram-positive methicillin-resistant Staphylococcus aureus, cause hundreds of thousands of deaths annually. Therefore, there is an urgent need to explore new antimicrobial agents with good safety profiles, strong antimicrobial activity, and the potential to induce bacterial resistance, for the treatment and prevention of bacterial infections.
[0003] Currently, a variety of organic, inorganic, and organic-inorganic hybrid antimicrobial materials have been extensively studied to improve their antimicrobial properties. Silver ions are widely known for their broad-spectrum bactericidal properties. They are not only highly effective against bacteria, fungi, and viruses, but also relatively low in toxicity to mammalian cells and have a low risk of introducing bacterial resistance. Consequently, metallic silver and its compounds have been widely used as antimicrobial agents in various biomedical fields. The activity of these antimicrobial agents is primarily attributed to several bactericidal mechanisms, including physical contact, silver ion release, oxidative stress, and photothermal effects. In recent years, bacterial resistance and various viral mutations have continued to emerge, making a single antimicrobial mechanism insufficient to fully combat complex bacterial infections. Therefore, the development of highly effective silver antimicrobial systems based on multiple antimicrobial mechanisms is crucial. Summary of the Invention
[0004] One of the objects of the present invention is to provide an antibacterial agent that encapsulates iodide ions in a silver cage and can act synergistically through multiple antibacterial mechanisms.
[0005] In order to achieve the above objectives, the present invention adopts the following technical solution: an antibacterial agent with synergistic antibacterial effect that encapsulates iodide ions in a silver cage. The antibacterial agent uses a 16-core silver cage as a basic structural unit, and encapsulates iodide ions in the silver cage, using thiol as a connector to assemble into a one-dimensional chain structure.
[0006] Wherein, the antibacterial agent can generate hydroxyl radicals under light conditions, and the hydroxyl radicals react with I - 、Ag + Synergistic effect for sterilization.
[0007] Wherein, the molecular formula of the antibacterial agent is [Ag 14 ( m -S t Bu) 12 I2]n .
[0008] Another object of the present invention is to provide a method for preparing the aforementioned antibacterial agent, the preparation method comprising the following steps:
[0009] Silver metal salt, iodine salt, organic ligand and sodium alcohol are dissolved in a solvent and placed in a reaction vessel. The mixture is reacted at 105-130° C. for 24-72 hours. After cooling, light yellow crystals are obtained, which are the antibacterial agent.
[0010] Among them, after cooling, filtering, washing, purification, drying and other operations (these operations can be performed in sequence) can be performed to improve the purity of the product.
[0011] The molar ratio of the silver metal salt, iodine salt, organic ligand and sodium alcoholate is 1:(1-2):(1-2):(1-2).
[0012] Wherein, the silver metal salt is a nitrate (such as silver nitrate).
[0013] Wherein, the iodine salt is selected from at least one (for example, one) of sodium iodide, potassium iodide, and tetraethylammonium iodide.
[0014] Wherein, the organic ligand is tert-butyl mercaptan.
[0015] Wherein, the sodium alkoxide is selected from at least one (for example, one) of sodium methoxide and sodium ethoxide.
[0016] Wherein, the solvent is selected from at least one of acetone, ethanol and water.
[0017] Wherein, the cooling rate is 10°C / h.
[0018] In addition, the aforementioned antibacterial agents can be used in the preparation of drugs with enhanced antibacterial activity.
[0019] The aforementioned antimicrobial agents can also be used to enhance synergistic antimicrobial efficacy against E. coli. Specifically, the antimicrobial agent crystals are ground into a fine powder, added to a culture dish containing a culture medium (e.g., nutrient agar), shaken well, and poured onto a plate. After the plate solidifies, the E. coli culture solution is evenly applied and incubated at a constant temperature under illumination (e.g., at 37°C for 18 hours).
[0020] Among them, every 2 to 8 mg of antibacterial agent corresponds to 10 mL of culture medium and 100 μL of Escherichia coli liquid.
[0021] Wherein, the concentration of the antibacterial agent is 0-0.8 mg / mL (preferably 0.8 mg / mL).
[0022] Wherein, the illumination is white light LED illumination.
[0023] The present invention constructs Ag 16 Silver nanocages are used to encapsulate iodide ions in the silver cages, and then thiol is used as a connector to assemble a one-dimensional chain-like antibacterial agent. The antibacterial agent has a simple synthesis step, is cheap and easy to obtain, and has suitable stability and can continuously and stably release iodine. - and Ag + , and produces hydroxyl radicals under light, which has good synergistic antibacterial activity. Moreover, the antibacterial agent can synergize through three antibacterial mechanisms to achieve the diversification of antibacterial material properties and structures. BRIEF DESCRIPTION OF THE DRAWINGS
[0024] Figure 1 A microscopic diagram of the antimicrobial agent encapsulating iodide ions in a silver cage.
[0025] Figure 2 The X-ray powder diffraction pattern of the antibacterial agent encapsulating iodide ions in a silver cage;
[0026] Figure 3 Thermogravimetric curve of the antimicrobial agent encapsulating iodide ions in silver cages;
[0027] Figure 4 This is a graph showing the antibacterial effect of an antibacterial agent encapsulating iodine ions in a silver cage at different concentrations;
[0028] Figure 5 Schematic diagram of the synergistic antibacterial effects of the three antibacterial mechanisms of the antibacterial agent encapsulating iodide ions in silver cages;
[0029] Figure 6 The EPR pattern of the antibacterial agent encapsulating iodide ions in a silver cage;
[0030] Figure 7 This is a SEM image of an antibacterial agent encapsulating iodide ions in silver cages killing Escherichia coli. DETAILED DESCRIPTION
[0031] To facilitate understanding by those skilled in the art, the present invention is further described below with reference to the examples, which are not intended to limit the present invention. It should be noted in advance that the following examples were performed in the laboratory, and those skilled in the art should understand that the amounts of the components given in the examples merely represent the ratios between the components, and are not intended to be specific limitations.
[0032] The present invention aims to develop a highly effective antibacterial agent with multiple antibacterial mechanisms to address the problem of persistent infections caused by complex bacterial infections and multidrug-resistant bacteria. Among them, metallic silver and its compounds are widely used in various biomedical fields due to their versatility and effectiveness, and are one of the commonly used antibacterial agents. Iodine, as an efficient and inexpensive topical fungicide, can cause irreversible, nonspecific damage to microbial cells, help overcome drug resistance problems, and is also widely used in the antibacterial field. Studies have shown that adding iodine to antibacterial agents can significantly improve the overall antibacterial efficacy.
[0033] Based on the above concept, the present invention provides an antibacterial agent that encapsulates iodide ions in silver cages and can act synergistically through multiple antibacterial mechanisms. The antibacterial agent uses a 16-core silver cage as the basic structural unit, and encapsulates iodide ions in the silver cage, using thiol as a connector to assemble into a one-dimensional chain structure. The molecular formula of the antibacterial agent is [Ag 14 ( m -S t Bu) 12 I2] n .
[0034] Among them, the above antibacterial agent can generate hydroxyl radicals under light conditions, and the hydroxyl radicals react with I - 、Ag + Synergistic effect for sterilization.
[0035] The above antibacterial agent can be prepared by the following preparation method, the steps are as follows:
[0036] (1) Dissolve silver metal salt, iodine salt, organic ligand and sodium alkoxide in a solvent for later use;
[0037] (2) transferring the mixed solution of step (1) into a reaction vessel (e.g., a reactor), reacting at a temperature of 105-130°C (e.g., 105°C, 120°C, or 130°C) for 24-72 hours (e.g., 24 hours, 33 hours, or 72 hours), and then cooling (e.g., programmed cooling) to room temperature;
[0038] (3) Filtration and washing;
[0039] (4) Purify and dry to obtain light yellow crystals, which are antibacterial crystal materials.
[0040] Furthermore, the above preparation method comprises the following steps:
[0041] First, add the sodium alkoxide and organic ligand to solvent A and stir for 30 minutes to fully dissolve them. Next, dissolve the silver metal salt in solvent B and add it dropwise to the previous solution. At this point, the mixture will turn milky white and begin to form a flocculent precipitate. Iodized salt and solvent C are then added sequentially to the reaction system. The resulting turbid mixture is transferred to an autoclave and reacted at 105-130°C for 24-72 hours. The temperature is then programmed to cool to room temperature. After the autoclave cools, it is filtered, washed, purified (to remove white impurities), and dried to obtain a pale yellow crystalline antimicrobial agent.
[0042] In step (1), the molar ratio of the silver metal salt, the iodine salt, the organic ligand and the sodium alkoxide is 1:(1-2):(1-2):(1-2). For example, the molar ratio is 1:1:1:1 or 1:1.5:1.5:1.5 or 1:2:2:2.
[0043] In step (1), the silver metal salt is a nitrate (such as silver nitrate), the iodine salt is selected from at least one (for example, one) of sodium iodide, potassium iodide, and tetraethylammonium iodide, the organic ligand is tert-butyl mercaptan, and the sodium alkoxide is selected from at least one (for example, one) of sodium methoxide and sodium ethoxide.
[0044] In step (1), the solvent is selected from at least one of acetone, ethanol, and water. The solvent includes solvents used in three stages: solvent A in the first stage is ethanol; solvent B in the second stage is a mixed solution of water and ethanol; and solvent C in the third stage includes acetone and ethanol. The solvents used in the three stages, i.e., solvent A, solvent B, and solvent C, are used in a ratio (volume ratio) of 2:1:1. In the second stage, the ratio (volume ratio) of water to ethanol is 1:2. In the third stage, the ratio (volume ratio) of acetone to ethanol is 2:1.
[0045] In step (2), the cooling rate is 10°C / h.
[0046] The present invention is to combine I with excellent antibacterial properties - and Ag + , self-assembled with organic ligands to obtain a molecular formula of [Ag 14 ( m -S t Bu) 12 I2] n An antibacterial agent comprising I - and Ag + , can realize the joint antibacterial, and also realize the diversification of the performance and structure of antibacterial materials. Moreover, the antibacterial agent constructs a Ag-based 16 The one-dimensional chain structure of silver nanocages encapsulates iodide ions in the silver cages, which has appropriate stability and can continuously and stably release I - and Ag +, and produces hydroxyl radicals under light, showing excellent synergistic antibacterial activity. This antibacterial agent also has a good synergistic antibacterial effect against Escherichia coli. Its preparation process is simple, and the raw materials have good biocompatibility. They are inexpensive and readily available, making them easy to translate into clinical applications, and have good application prospects.
[0047] The present invention will be further described below with reference to specific embodiments, but the protection scope of the present invention is not limited thereto. Example 1
[0048] In this example, antimicrobial crystals containing iodide ions encapsulated in silver cages were prepared according to the following method.
[0049] First, 0.014 g (0.2 mmol) of sodium ethoxide and 0.022 mL (0.2 mmol) of tert-butyl mercaptan were added to 6 mL of ethanol and stirred for 30 minutes to allow for complete dissolution. Next, 0.034 g (0.2 mmol) of silver nitrate was dissolved in a mixture of 1 mL of water and 2 mL of ethanol and slowly added dropwise to the previous solution. The mixture turned milky white and a flocculent precipitate began to form. Subsequently, 0.029 g (0.2 mmol) of sodium iodide, 2 mL of acetone, and 1 mL of ethanol were added sequentially to the reaction system. The resulting turbid mixture was transferred to an autoclave and heated at 105°C for 24 hours. The temperature was then programmed to cool to room temperature (10°C / min). After the autoclave cooled, it was filtered, washed three times with DMF, water, and ethanol to remove white impurities, and dried to obtain a pale yellow crystalline antimicrobial agent. Example 2
[0050] In this example, antimicrobial crystals containing iodide ions encapsulated in silver cages were prepared according to the following method.
[0051] First, 0.017 g (0.3 mmol) of sodium methoxide and 0.033 mL (0.3 mmol) of tert-butyl mercaptan were added to 6 mL of ethanol and stirred for 30 minutes to allow for complete dissolution. Next, 0.034 g (0.2 mmol) of silver nitrate was dissolved in a mixture of 1 mL of water and 2 mL of ethanol and slowly added dropwise to the previous solution. The mixture turned milky white and a flocculent precipitate began to form. Subsequently, 0.771 g (0.3 mmol) of tetraethylammonium iodide, 2 mL of acetone, and 1 mL of ethanol were added sequentially to the reaction system. The resulting turbid mixture was transferred to an autoclave and heated at 120°C for 72 hours. The temperature was then programmed to cool to room temperature (10°C / min). After the autoclave cooled, it was filtered, washed three times with DMF, water, and ethanol to remove white impurities, and dried to obtain a pale yellow crystalline antimicrobial agent. Example 3
[0052] In this example, antimicrobial crystals containing iodide ions encapsulated in silver cages were prepared according to the following method.
[0053] First, 0.028 g (0.4 mmol) of sodium ethoxide and 0.043 mL (0.4 mmol) of tert-butyl mercaptan were added to 6 mL of ethanol and stirred for 30 minutes to allow for complete dissolution. Next, 0.034 g (0.2 mmol) of silver nitrate was dissolved in a mixture of 1 mL of water and 2 mL of ethanol and slowly added dropwise to the previous solution. The mixture turned milky white and a flocculent precipitate began to form. Subsequently, 0.066 g (0.4 mmol) of potassium iodide, 2 mL of acetone, and 1 mL of ethanol were added sequentially to the reaction system. The resulting turbid mixture was transferred to an autoclave and heated at 130°C for 33 hours. The temperature was then programmed to cool to room temperature (10°C / min). After the autoclave cooled, it was filtered, washed three times with DMF, water, and ethanol to remove white impurities, and dried to obtain a pale yellow crystalline antimicrobial agent.
[0054] The antibacterial agent crystals encapsulating iodide ions in silver cages prepared in Example 1 were collected using a single crystal X-ray diffractometer and the structure was analyzed using Olex2 software. Figure 1 As shown in the figure, the antibacterial agent is composed of 16-nuclear silver cage basic units that encapsulate iodide ions and self-assemble into a stable one-dimensional chain structure through tert-butylthiol linkers. Figure 2 As shown in Figure 2, the simulated peaks of XRD are consistent with the test peaks, indicating that the obtained antibacterial agent is a pure phase and can be used for structural characterization and antibacterial performance testing. Figure 3 As shown, the antibacterial agent crystal material has good thermal stability and can exist stably before 285℃.
[0055] The subsequent antibacterial properties of the antibacterial materials prepared in Examples 1-3 are basically the same.
[0056] Antibacterial experiments
[0057] The antibacterial agent crystals prepared in Example 1 were selected to carry out the following experiments.
[0058] The strain selected for this experiment is Escherichia coli MG1655. First, grind the antimicrobial crystals into a very fine powder, add 10 mL of nutrient agar medium to each culture dish, and then add 2 mg, 4 mg, 6 mg, 7 mg, and 8 mg of antimicrobial powder respectively, shake well, pour the plate, and evenly apply 10 6 Escherichia coli liquid (100μL) was cultured at 37℃ under light conditions for 18h, and compared with the blank plate without antimicrobial agent. The growth of Escherichia coli colonies was observed and recorded by taking photos. The antibacterial effect of the antimicrobial agent was explored by colony counting, and the antibacterial effect of antimicrobial agent at different concentrations was obtained.
[0059] Result analysis: Figure 4 As shown in the figure, with the increase of the powder concentration of the antibacterial agent prepared in Example 1, it can be clearly seen that the colony count is significantly reduced, and the inhibitory effect on the growth of Escherichia coli is gradually enhanced. When the antibacterial agent concentration is 0.8 mg / mL, bacteria can be completely killed. In the antibacterial experiment determination, the relevant data analysis of the antibacterial performance of Escherichia coli was selected, but in fact, in other tests, it was drawn that the antibacterial agent has equally strong antibacterial performance to various strains such as Streptococcus mutans, Actinomyces viscosus, and Lactobacillus paracasei.
[0060] like Figure 5 As shown in the diagram of antibacterial mechanism, antibacterial agents kill bacteria through the synergistic action of three antibacterial mechanisms. Antibacterial agents can continuously and stably release silver ions and iodine ions, and generate hydroxyl free radicals (such as Figure 6 As shown), the three work synergistically to kill bacteria. Figure 7 As can be seen from the SEM image of E. coli shown, the E. coli cells are completely destroyed.
[0061] Since the above antibacterial agent has strong antibacterial properties against Escherichia coli and multiple bacterial species such as Streptococcus mutans, Actinomyces viscosus, and Lactobacillus paracasei, the antibacterial agent can be used in the preparation of drugs with enhanced antibacterial activity and has good application prospects.
[0062] The above embodiments are preferred implementation schemes of the present invention. In addition, the present invention can also be implemented in other ways. Any obvious replacement without departing from the concept of the present technical solution is within the scope of protection of the present invention.
[0063] Finally, it should be emphasized that in order to make it easier for those skilled in the art to understand the improvements of the present invention over the prior art, some descriptions of the present invention have been simplified, and for the sake of clarity, some other elements have been omitted in this application document. Those skilled in the art should realize that these omitted elements may also constitute the content of the present invention.
Claims
1. An antimicrobial agent having a synergistic antimicrobial effect by encapsulating iodide ions in a silver cage, characterized in that: The antibacterial agent uses a 16-nuclear silver cage as a basic structural unit, and encapsulates iodide ions in the silver cage, and uses tert-butyl mercaptan as a connector to assemble into a one-dimensional chain structure; the molecular formula of the antibacterial agent is [Ag 14 ( m -S t Bu) 12 I2] n .
2. The antibacterial agent according to claim 1, characterized in that: The antibacterial agent can generate hydroxyl radicals under light conditions, and the hydroxyl radicals react with I - 、Ag + Synergistic effect for sterilization.
3. The method for preparing the antibacterial agent according to claim 1 or 2, characterized in that: The following steps are involved: First, sodium alcohol and tert-butyl mercaptan are added to solvent A and stirred for 30 minutes to fully dissolve them; then, silver metal salt is dissolved in solvent B and then added dropwise to the previous solution; at this time, the mixture will turn milky white and begin to form flocculent precipitates; thereafter, iodine salt and solvent C are added to the reaction system in sequence; the resulting turbid mixture is transferred to a high-pressure reactor, reacted at a temperature of 105-130°C for 24-72 hours, and programmed to cool to room temperature. After the reactor is cooled, it is filtered, washed, purified, and dried to obtain a light yellow crystalline antibacterial agent.
4. The method for preparing the antibacterial agent according to claim 3, wherein: The molar ratio of the silver metal salt, iodine salt, tert-butyl mercaptan and sodium alkoxide is 1:(1-2):(1-2):(1-2).
5. The method for preparing the antibacterial agent according to claim 3, wherein: The silver metal salt is nitrate, the iodine salt is selected from at least one of sodium iodide, potassium iodide, and tetraethylammonium iodide, the sodium alkoxide is selected from at least one of sodium methoxide and sodium ethoxide, the solvent A is ethanol, the solvent B is a mixed solution of water and ethanol, and the solvent C includes acetone and ethanol.
6. Use of the antibacterial agent according to claim 1 or 2 in the preparation of drugs with enhanced antibacterial activity.
7. Use of the antibacterial agent according to claim 1 or 2 in improving the synergistic antibacterial efficiency against Escherichia coli.
8. The use of the antimicrobial agent according to claim 7 for improving the synergistic antimicrobial efficiency against Escherichia coli, characterized in that: The antimicrobial agent crystals are ground into fine powder, added to a culture dish containing a culture medium, shaken and poured onto a plate, and after the plate solidifies, the Escherichia coli liquid is evenly coated and cultured at a constant temperature under light conditions.
9. Use of the antimicrobial agent according to claim 8 in improving the synergistic antimicrobial efficiency against Escherichia coli, characterized in that: Every 2-8 mg of antimicrobial agent corresponds to 10 mL of culture medium and 100 μL of E. coli liquid.
10. Use of the antimicrobial agent according to claim 8 in improving the synergistic antimicrobial efficiency against Escherichia coli, characterized in that: The concentration of the antimicrobial agent was 0.8 mg / mL.