Inorganic bacteriostatic agents

Abstract

To provide an inorganic bacteriostatic agent that has a long lasting effect.SOLUTION: An inorganic bacteriostatic agent has porous silica doped with a bacteriostatic metal. For example, the bacteriostatic metal is copper, zirconium, cobalt.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an inorganic bacteriostatic agent having excellent durability of effect. [Background technology]

[0002] It has long been known that metals such as copper, silver, and zinc exhibit bacteriostatic effects in the form of ions, and inorganic bacteriostatic agents obtained by adsorbing these metal ions onto carriers such as silica gel and zeolite are used as materials for imparting bacteriostatic properties to everyday items such as textiles, leather products, building materials, wood, paints, adhesives, plastics, films, ceramics, paper, pulp, metal processing oils, water treatment agents, cosmetics, stationery, toys, containers, caps, dispensers, and spouts (e.g., Non-Patent Document 1). However, these inorganic bacteriostatic agents exhibit their bacteriostatic effects by desorbing the bacteriostatic metal ions adsorbed onto the carrier, and therefore, as the amount of bacteriostatic metal ions adsorbed onto the carrier gradually decreases, the bacteriostatic effect also gradually decreases. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Yoshinobu Matsumura, Antibacterial properties of silver ions and copper ions, Chemistry and Education, Vol. 53, No. 5 (2005), pp. 288-291 Summary of the Invention [Problem to be solved by the invention]

[0004] Therefore, an object of the present invention is to provide an inorganic bacteriostatic agent having excellent durability of effect. [Means for solving the problem]

[0005] The present inventors have been actively engaged in the research and development of porous silica doped with various metals, and as one of their results, they reported in JP 2020-15640 A that porous silica doped with manganese, copper, and iron exhibits excellent deodorizing effects against sulfur-containing odors. Here, "metal-doped porous silica" refers to porous silica in which a metal is chemically bonded and incorporated into the inorganic network consisting of siloxane bonds that constitutes the porous silica. As a result of further research and development of metal-doped porous silica, the present inventors discovered that porous silica doped with a bacteriostatic metal has excellent durability of the bacteriostatic effect.

[0006] The inorganic bacteriostatic agent of the present invention, which has been developed based on the above findings, is as described in claim 1, At least one selected from copper, zirconium, cobalt, silver, and zinc Consists of porous silica doped with bacteriostatic metals and aluminum 。 Ma and claims 2 The inorganic bacteriostatic agent described in claim 1 The inorganic bacteriostatic agent is further doped with at least one metal selected from manganese and iron. 。 Ma The present invention also provides the following claims: 3 As stated, At least one selected from copper, zirconium, cobalt, silver, and zinc Bacteriostatic metal and aluminum doped porous silica as a material for imparting bacteriostatic properties to articles use is. [Effects of the Invention]

[0007] According to the present invention, an inorganic bacteriostatic agent having excellent durability of effect can be provided. DETAILED DESCRIPTION OF THE INVENTION

[0008] The inorganic bacteriostatic agent of the present invention comprises porous silica doped with a bacteriostatic metal.

[0009] Examples of bacteriostatic metals that can be used in the present invention include copper, zirconium, and cobalt, which are metals that exhibit bacteriostatic effects in the form of ions and are known to be capable of being doped into porous silica. The bacteriostatic metals may be used alone or in combination of two or more.

[0010] The content of the bacteriostatic metal in the bacteriostatic metal-doped porous silica is, for example, 0.01 to 10 wt%, preferably 0.1 to 5 wt%. If the content of the bacteriostatic metal in the bacteriostatic metal-doped porous silica is less than 0.01 wt%, a sufficient bacteriostatic effect may not be obtained, while porous silica doped with a bacteriostatic metal in an amount exceeding 10 wt% may be difficult to produce.

[0011] An example of porous silica is mesoporous silica in which pores (mesopores) having a diameter of 2 to 50 nm are regularly arranged.

[0012] The specific surface area of porous silica is, for example, 500 to 2000 m 2 / g is preferable in terms of maintaining durability.

[0013] The mesoporous silica doped with a bacteriostatic metal can be produced according to the following method, which is known per se and described by the present inventors in JP-A-2020-15640, for example.

[0014] (Process 1) First, a surfactant and raw materials for doping mesoporous silica with a bacteriostatic metal are dissolved in a solvent and stirred, for example, at 30 to 200°C for 0.5 to 10 hours to form micelles in the surfactant.

[0015] The amount of surfactant dissolved in the solvent is, for example, 10 to 400 mmol / L, preferably 50 to 150 mmol / L, or, for example, 0.01 to 5.0 mol, preferably 0.05 to 1.0 mol, relative to 1 mol of the silica raw material added in Step 2 described below.

[0016] The surfactant may be a cationic surfactant, an anionic surfactant, or a nonionic surfactant, but is preferably a cationic surfactant such as an alkylammonium salt. The alkylammonium salt preferably has an alkyl group containing 8 or more carbon atoms, and from the perspective of industrial availability, an alkyl group containing 12 to 18 carbon atoms is more preferred. Specific examples of alkylammonium salts include hexadecyltrimethylammonium chloride, cetyltrimethylammonium bromide, stearyltrimethylammonium bromide, cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, dodecyltrimethylammonium bromide, octadecyltrimethylammonium bromide, dodecyltrimethylammonium chloride, octadecyltrimethylammonium chloride, didodecyldimethylammonium bromide, ditetradecyldimethylammonium bromide, didodecyldimethylammonium chloride, and ditetradecyldimethylammonium chloride. The surfactant may be used alone or in combination of two or more.

[0017] The amount of raw material dissolved in the solvent for doping the mesoporous silica with the bacteriostatic metal is, for example, 0.001 to 0.5 mol, preferably 0.01 to 0.1 mol, per 1 mol of the silica raw material added in step 2 described below.

[0018] As raw materials for doping mesoporous silica with a bacteriostatic metal, for example, nitrates, sulfates, chlorides, and oxychlorides of the bacteriostatic metal can be used. When the bacteriostatic metal is copper, it is preferable to use copper nitrate or copper chloride. When the bacteriostatic metal is zirconium, it is preferable to use zirconium oxychloride. When the bacteriostatic metal is cobalt, it is preferable to use cobalt nitrate. The raw materials for doping with the bacteriostatic metal may be used alone or in combination of two or more.

[0019] The solvent may be, for example, water, or a mixed solvent of water and a water-soluble organic solvent such as methanol, ethanol, diethylene glycol, or glycerin.

[0020] (Process 2) Next, the silica raw material is dissolved in the surfactant-forming micelle solution obtained in step 1, for example, at room temperature, and stirred until homogenous, allowing the silica raw material to accumulate on the surface of the surfactant micelles. The amount of silica raw material dissolved in the solution is, for example, 0.2 to 1.8 mol / L. Alternatively, when water or a mixed solvent of water and a water-soluble organic solvent is used as the solvent, the amount is, for example, 0.001 to 0.05 mol per 1 mol of water.

[0021] The silica raw material is not particularly limited as long as it forms an inorganic network consisting of siloxane bonds that constitute mesoporous silica by dehydration condensation. Specific examples of silica raw materials include tetraalkoxysilanes such as tetraethoxysilane, tetramethoxysilane, and tetra-n-butoxysilane, and sodium silicate. Tetraalkoxysilane is preferred, and tetraethoxysilane is more preferred. The silica raw materials may be used alone or in combination of two or more.

[0022] (Step 3) Next, the silica raw material accumulated on the surface of the surfactant micelles is dehydration-condensed to form an inorganic network consisting of siloxane bonds that constitute mesoporous silica, and a bacteriostatic metal is incorporated into the inorganic network by chemical bonding. The dehydration-condensation of the silica raw material can be carried out, for example, by adding a basic aqueous solution to the system to raise the pH, followed by stirring at room temperature for at least one hour. The basic aqueous solution is preferably added so that the pH is 8 to 14 immediately after addition, more preferably 9 to 11. Specific examples of basic aqueous solutions include aqueous sodium hydroxide, aqueous sodium carbonate, and aqueous ammonia, with aqueous sodium hydroxide being preferred. The basic aqueous solutions may be used alone or in combination of two or more. The dehydration-condensation of the silica raw material can also be carried out by adding an acidic aqueous solution such as an aqueous hydrochloric acid solution to the system to lower the pH, followed by stirring.

[0023] (Step 4) Finally, the surfactant micelles obtained in step 3, which form an inorganic network on the surface composed of siloxane bonds constituting the mesoporous silica and to which the bacteriostatic metal is chemically bonded, are collected as a precipitate by filtration, dried at 30 to 70°C for 10 to 48 hours, for example, and then calcined at 400 to 600°C for 1 to 10 hours to obtain the desired bacteriostatic metal-doped mesoporous silica. The bacteriostatic metal-doped mesoporous silica thus obtained may be pulverized in a mixer or mill as needed to obtain a desired particle size (e.g., a median diameter of 0.01 to 100 μm).

[0024] The addition of the raw material to the system for doping the bacteriostatic metal into the mesoporous silica is not limited to the above-mentioned step 1 in which the raw material is dissolved in a solvent together with a surfactant, but may be dissolved in a solution in step 2 or 3, as long as the formation of the inorganic network consisting of siloxane bonds that constitutes the mesoporous silica by dehydration condensation of the silica raw material in step 3 is completed.

[0025] For example, the inorganic bacteriostatic agent of the present invention produced by the above method has excellent durability of bacteriostatic effect. The reason for this is not entirely clear, but as will be shown in the Examples below, the present inventors believe that the inorganic bacteriostatic agent of the present invention exerts its bacteriostatic effect by retaining the bacteriostatic effect while chemically bonded and incorporated into the inorganic network consisting of siloxane bonds that constitute porous silica, rather than exerting its bacteriostatic effect by desorbing from the inorganic network, as conventionally known inorganic bacteriostatic agents exert their bacteriostatic effect by adsorbing bacteriostatic metal ions on a carrier and desorbing from the carrier.

[0026] In the inorganic bacteriostatic agent of the present invention, when the bacteriostatic metal doped into the porous silica is copper, the copper-doped porous silica exhibits an excellent deodorizing effect against sulfur-containing odors, as reported by the inventors in JP 2020-15640 A, and therefore has both a deodorizing effect and a bacteriostatic effect. Furthermore, when the bacteriostatic metal doped into the porous silica is zirconium, as reported by the inventors in JP 2020-15640 A, zirconium has the effect of increasing the durability of the porous silica, and therefore the zirconium-doped porous silica has excellent durability.

[0027] In addition, in the inorganic bacteriostatic agent of the present invention, porous silica may be doped with a metal other than a bacteriostatic metal. A specific example of the metal other than a bacteriostatic metal is aluminum, which, like zirconium, has the effect of increasing the durability of porous silica. The aluminum content in porous silica doped with aluminum together with a bacteriostatic metal is, for example, 0.01 to 10 wt%, preferably 0.1 to 5 wt%, and more preferably the total amount including the bacteriostatic metal is up to 10 wt%.

[0028] A method for doping porous silica with aluminum together with a bacteriostatic metal includes, for example, dissolving the raw material (e.g., aluminum chloride) in a solvent or solution together with the raw material for doping mesoporous silica with a bacteriostatic metal in the above-mentioned method for producing mesoporous silica doped with a bacteriostatic metal. The amount of raw material for doping mesoporous silica with aluminum dissolved in the solvent or solution is, for example, 0.001 to 0.5 mol, preferably 0.01 to 0.1 mol, per mol of silica raw material added in step 2. However, it is more preferable that the total amount of the raw material for doping mesoporous silica with a bacteriostatic metal dissolved in the solvent or solution is a maximum of 0.5 mol per mol of silica raw material.

[0029] In addition, manganese or iron may be doped into porous silica as a metal other than the bacteriostatic metal. As reported by the present inventors in JP 2020-15640 A, doping porous silica with manganese or iron together with a bacteriostatic metal exhibits an excellent deodorizing effect against sulfur-containing odors. The manganese or iron content in porous silica doped with manganese or iron together with a bacteriostatic metal is, for example, 0.01 to 10 wt%, preferably 0.1 to 5 wt%, and more preferably the total amount including the bacteriostatic metal content (when aluminum is doped into porous silica, the total amount including the content of aluminum) is a maximum of 10 wt%.

[0030] A method for doping porous silica with manganese or iron together with a bacteriostatic metal includes dissolving the raw material (e.g., manganese chloride or iron chloride) in a solvent or solution together with the raw material for doping mesoporous silica with a bacteriostatic metal in the above-described method for producing mesoporous silica doped with a bacteriostatic metal. The amount of the raw material for doping mesoporous silica with manganese or iron dissolved in the solvent or solution is, for example, 0.001 to 0.5 mol, preferably 0.01 to 0.1 mol, per mol of silica raw material added in step 2. However, the total amount, including the amount of the raw material for doping mesoporous silica with a bacteriostatic metal dissolved in the solvent or solution (when aluminum is dissolved in the solvent or solution, the total amount includes the amount of aluminum dissolved) is preferably up to 0.5 mol per mol of silica raw material.

[0031] The inorganic bacteriostatic agent of the present invention can be used as a material for imparting bacteriostatic properties to everyday items such as textiles, leather products, building materials, wood, paints, adhesives, plastics, films, ceramics, paper, pulp, metal processing oils, water treatment agents, cosmetics, stationery, toys, containers, caps, spouts, and the like. Its use may be the same as that of conventionally known inorganic bacteriostatic agents in which bacteriostatic metal ions are adsorbed onto a carrier. For example, by incorporating the agent into a paint or the like and applying it to the surface of an item, or by incorporating the agent into a material for manufacturing an item, bacteriostatic properties can be imparted to the item. In addition, when the item is a container or the like, the agent can be expected to exert a bacteriostatic effect on the contents enclosed or filled in the item. Furthermore, the inorganic bacteriostatic agent of the present invention can be formed into pellets or the like and mixed with an item, or used alone. Alternatively, it can be suspended in a dispersion medium such as water and used in the form of a slurry in various liquid items. [Example]

[0032] The present invention will be described in detail below with reference to examples, but the present invention should not be construed as being limited to the following description.

[0033] Example 1: Preparation of mesoporous silica doped with copper and aluminum as bacteriostatic metals and its bacteriostatic effect Hexadecyltrimethylammonium chloride (surfactant), copper chloride (copper chloride), and aluminum chloride (aluminum chloride) were dissolved in water and stirred at 100°C for 1 hour. The mixture was then cooled to room temperature and tetraethoxysilane (silica precursor) was further dissolved and stirred until homogeneous. A basic aqueous solution of sodium hydroxide was then added to the reaction mixture, adjusting the pH to 9 immediately after addition, and the mixture was stirred at room temperature for 20 hours. The resulting precipitate was collected by filtration, dried at 50°C for 24 hours, and then calcined at 570°C for 5 hours to obtain the desired copper- and aluminum-doped mesoporous silica as a slightly bluish white powder.

[0034] The amounts of hexadecyltrimethylammonium chloride as a surfactant, copper chloride as a raw material for doping copper into mesoporous silica, aluminum chloride as a raw material for doping aluminum into mesoporous silica, and water as a solvent were as follows, relative to 1 mol of tetraethoxysilane as a silica raw material: Hexadecyltrimethylammonium chloride: 0.225 mol Copper chloride: 0.0204 mol Aluminum chloride: 0.0482 mol Water: 125mol To prepare a sodium hydroxide aqueous solution as a basic aqueous solution, 0.195 mol of sodium hydroxide was used per 1 mol of tetraethoxysilane as a silica raw material.

[0035] The copper and aluminum doped mesoporous silica obtained by the above method has a specific surface area of 1100 m 2 / g, pore volume 0.72 cm 3The pore diameter was 2.6 nm (calculated using the BJH calculation based on nitrogen gas adsorption isotherm measurements at liquid nitrogen temperature using a Microtrackbell BELSORP MAX II multipoint method). Approximately 50 mg of copper- and aluminum-doped mesoporous silica was accurately weighed and dissolved in 4 mL of hydrochloric acid. The copper and aluminum concentrations in the hydrochloric acid solution were measured using an inductively coupled plasma optical emission spectrometer (Thermo Scientific ICP-OES). Based on the measurement results, the copper and aluminum contents in the copper- and aluminum-doped mesoporous silica were calculated to be 2.09 wt% and 2.00 wt%, respectively. The copper and aluminum doping of the mesoporous silica was confirmed using an X-ray photoelectron spectrometer (Thermo Scientific K-Alpha Surface Analysis) and a transmission electron microscope (JEOL JEM2010).

[0036] The bacteriostatic effect of the copper- and aluminum-doped mesoporous silica obtained by the above method was evaluated according to the preservative effectiveness test method described in the Japanese Pharmacopoeia. Specifically, this copper- and aluminum-doped mesoporous silica was pulverized in a mixer to a median diameter of approximately 25 to 31 μm (measured by a laser diffraction particle size distribution analyzer (SALD-3100, manufactured by Shimadzu Corporation; the same applies below). Five grams of the pulverized silica was then placed in a 250 mL polypropylene pot (Eye-Boy PP wide-mouth bottle, manufactured by AS ONE Corporation) with 95 g of water as a dispersion medium and 2 mm diameter alumina balls (manufactured by Nikkato Corporation, alumina purity: 93%, bulk density: 3.6 g / cm) as a medium. 3The mixture was placed in a pot mill along with 210 g (approximately 14,000 balls) of copper and aluminum doped mesoporous silica, and wet-milled for 8 hours. The alumina balls were then filtered off to obtain a slurry of copper and aluminum doped mesoporous silica suspended in water (containing 5 wt% copper and aluminum doped mesoporous silica with a median diameter of 0.50 μm). 10 mL of the resulting slurry of copper and aluminum doped mesoporous silica suspended in water was inoculated with 0.1 mL of each test bacterial solution, stirred, and then allowed to stand at 25°C for 28 days. The viable bacterial counts were measured before and after the start of the test. The results are shown in Table 1.

[0037] [Table 1]

[0038] As is clear from Table 1, it was found that copper- and aluminum-doped mesoporous silica exhibits a bacteriostatic effect against various types of fungi. Furthermore, the above-mentioned slurry containing 5 wt% copper- and aluminum-doped mesoporous silica showed almost no elution of copper ions into the liquid, and even after being left to stand for 55 days, the amount of elution was 10 ppm (measured using an inductively coupled plasma optical emission spectrometer (same as above)), demonstrating a sustained bacteriostatic effect.

[0039] The minimum inhibitory concentrations (MICs) of copper ions against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are known to be 400 ppm, 400 ppm, and 200 ppm, respectively. However, considering these MICs, the bacteriostatic effect of the copper- and aluminum-doped mesoporous silica described above is not due to copper ions dissolved in the slurry. In other words, the bacteriostatic effect of the copper- and aluminum-doped mesoporous silica is believed to be due to copper being chemically bonded and incorporated into the inorganic network of siloxane bonds that constitutes the mesoporous silica. This result was unexpected by those skilled in the art, including the present inventors. The bacteriostatic effect is not exerted by the copper ions eluted in the slurry, because blending this slurry with a liquid product does not increase the copper ion concentration in the liquid product, making it convenient for imparting a bacteriostatic effect to liquid products in which copper ions should not be added (for example, liquid hair care cosmetics and hair deodorants in which hair damage due to copper ions is a concern). From this perspective, assuming a slurry in which porous silica doped with a bacteriostatic metal is suspended in a dispersion medium to a bacteriostatic metal content of, for example, 0.1 to 10 wt%, the amount of bacteriostatic metal ions eluted into the slurry when the slurry is allowed to stand at 25°C for 55 days is preferably 400 ppm or less, more preferably 200 ppm or less, even more preferably 100 ppm or less, and most preferably 50 ppm or less.

[0040] Example 2: Preparation of mesoporous silica doped with zirconium as a bacteriostatic metal and aluminum and its bacteriostatic effect Except for using zirconium oxychloride instead of copper chloride, mesoporous silica doped with zirconium as a bacteriostatic metal and aluminum was obtained in the same manner as in Example 1. The bacteriostatic effect was similar to that of the mesoporous silica doped with copper as a bacteriostatic metal and aluminum obtained in Example 1, although to a different degree.

[0041] Example 3: Preparation of mesoporous silica doped with cobalt as a bacteriostatic metal and aluminum and its bacteriostatic effect Except for using cobalt nitrate instead of copper chloride, mesoporous silica doped with cobalt as a bacteriostatic metal and aluminum was obtained in the same manner as in Example 1. The bacteriostatic effect was similar to that of the mesoporous silica doped with copper as a bacteriostatic metal and aluminum obtained in Example 1, although to a different degree.

[0042] Example 4: Preparation of mesoporous silica doped with copper as a bacteriostatic metal, as well as aluminum and manganese, and its bacteriostatic effect Mesoporous silica doped with copper as a bacteriostatic metal, as well as aluminum and manganese, was obtained in the same manner as in Example 1, except that 0.0204 mol of manganese chloride, a raw material for doping mesoporous silica with manganese, was further dissolved in water as a solvent. The bacteriostatic effect was similar to that of the mesoporous silica doped with copper as a bacteriostatic metal, as well as aluminum, obtained in Example 1, although to a different extent. In addition, a deodorizing effect due to the doping with manganese was observed.

[0043] Application example 1: Production of water-based paints containing copper and aluminum doped mesoporous silica By blending the copper and aluminum doped mesoporous silica obtained in Example 1 into an aqueous paint so that its content was 0.5 wt%, an aqueous paint exhibiting bacteriostatic effects could be produced. [Industrial Applicability]

[0044] INDUSTRIAL APPLICABILITY The present invention has industrial applicability in that it can provide an inorganic bacteriostatic agent having excellent durability of effect.

Claims

1. An inorganic bacteriostatic agent comprising porous silica doped with aluminum and at least one bacteriostatic metal selected from copper, zirconium, cobalt, silver, and zinc.

2. 2. The inorganic bacteriostatic agent according to claim 1, which is further doped with at least one metal selected from the group consisting of manganese and iron.

3. Use of porous silica doped with aluminum and at least one bacteriostatic metal selected from copper, zirconium, cobalt, silver, and zinc as a material for imparting bacteriostatic properties to an article.

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