JP6749747B2 - Inorganic antibacterial composition and use thereof - Google Patents

Description

The present invention relates to an inorganic antibacterial composition, and a cosmetic, clothing, resin material, ceramic material or metal material containing the inorganic antibacterial composition, which is its use.

Compared with organic antibacterial agents, inorganic antibacterial agents are currently expanding the market because they are superior in heat resistance and durability, non-volatile, and persistent in effect. However, silver, which is a typical inorganic antibacterial agent, has problems such as discoloration and cost. Therefore, a metal oxide is mentioned as an inorganic antibacterial agent which is safe and inexpensive for the human body. Among them, zinc oxide is expected to have various applications because it exhibits an antibacterial effect even in a dark place and exhibits neutrality in water.

Patent Document 1 is said to be an antibacterial material characterized by comprising a zinc oxide thin film, and is said to be able to dope a donor element. However, since it is a film shape formed by a sputtering method, its range of use is limited, and it is unsuitable for, for example, compounding into cosmetics or fixing to fibers or the like.

Patent Document 2 describes an antibacterial/antifungal agent comprising zinc oxide fine particles to which electroconductivity is added, containing a metal element selected from Group IIIB metal elements and Group IVB metal elements. As a method for producing the same, a method of adding and permeating a second component metal into zinc oxide particles is provided ([0022]). However, according to the knowledge of the applicant of the present application, it is difficult for this manufacturing method to replace the donor element with zinc to form a solid solution. Further, in order to make the substitutional solid solution of the second component in zinc oxide, a high temperature of 800° C. or higher is required, and even if the starting zinc oxide is nano-sized particles, the growth of the particles reduces the surface area. It will be noticeable.

In Patent Document 3, zinc ion produced by reacting zinc ion, carbonate ion, and hydroxide ion in a pH maintaining environment with water as a reaction solvent and calcining the basic zinc carbonate produced is used as an active ingredient. , Antibacterial and antifungal agents are described. No metal other than zinc is used in this manufacturing method. Further, it is proposed that the firing temperature in this production method is 150°C to 450°C ([0013]). At this firing temperature, the crystal growth of zinc oxide is insufficient, and even if a metal other than zinc is added and fired, solid solution is not promoted in the precipitate.

JP 2009-143841 JP JP 2002-104823 Patent 3938447

In the present invention, as an inexpensive inorganic antibacterial agent having excellent heat resistance, durability, and safety, and exhibiting an effect even in a dark place, zinc oxide having solved the above problems and remarkably improved antibacterial effect. A powder and a manufacturing method thereof are provided.

That is, the present invention provides the following.
(1) Aluminum salt aqueous solution or gallium salt aqueous solution, zinc salt aqueous solution, carbonate aqueous solution, and alkaline aqueous solution having a molar ratio of Zn/Al = more than 1 to 10,000 or a molar ratio of Zn/Ga = more than 1 to 10000 An inorganic antibacterial composition obtained by heat-treating a carbonate hydrate produced in the precipitation producing reaction of 1. at a temperature of 700° C. or higher.
(2) The inorganic antibacterial composition according to (1), wherein the precipitate obtained by the precipitate formation reaction contains basic zinc carbonate and a precipitate of zinc, aluminum and/or gallium.
(3) The inorganic antibacterial composition according to (1) or (2), wherein the carbonate hydrate contains a hydrozincite represented by the following formula (1) or a hydrate thereof.
M _4-6 (CO ₃ ) _1-3 (OH) _6-7 (1)
M: At least one metal selected from the group consisting of zinc element, aluminum, and gallium.
(4) A cosmetic containing the inorganic antibacterial composition according to any one of (1) to (3) and a carrier for cosmetics.
(5) An antibacterial fiber for fixing the inorganic antibacterial composition according to any one of (1) to (3) to a fiber, or an antibacterial clothing using the antibacterial fiber.
(6) A resin material, a ceramic material, or a metal material containing the inorganic antibacterial composition according to any one of the above (1) to (3) or having a coating containing the inorganic antibacterial composition.
(7) A drug containing the inorganic antibacterial composition according to any one of (1) to (3) above, or a coating containing the inorganic antibacterial composition or containing the inorganic antibacterial composition. Medical article.

The inorganic antibacterial composition of the present invention is an antibacterial agent that prevents the growth of fungi such as Escherichia coli and is excellent in killing ability as compared with conventional zinc oxide obtained by dehydration and decarboxylation from basic zinc carbonate. is there.

It is a schematic diagram explaining the experimental conditions used for antibacterial property evaluation.

1. Inorganic antibacterial composition of the present invention The present invention relates to an aluminum salt aqueous solution or a gallium salt aqueous solution having a molar ratio of Zn/Al = more than 1 to 10,000, or a molar ratio of Zn/Ga = more than 1 to 10,000, and a zinc salt. An inorganic antibacterial composition obtained by heat-treating a carbonate hydrate produced by a precipitation producing reaction of an aqueous solution, an aqueous carbonate solution, and an alkaline aqueous solution at a temperature of 700° C. or higher (hereinafter, referred to as the composition of the present invention. Yes).
As described below, the composition of the present invention is a composition in which zinc oxide is doped with aluminum or gallium. Its characteristic is the form of the precursor before firing, and its manufacturing conditions are as follows: zinc salt aqueous solution, carbonate aqueous solution, aluminum or gallium salt aqueous solution, and an alkaline agent are mixed, and the pH of the aqueous solution is kept constant. Precursors of different crystallinity are produced by different pH values which are kept constant during the reaction of stirring to produce a precipitate, and different zinc oxides are obtained by firing different precursors.

The specific manufacturing conditions for determining the morphology of the precipitate are as follows:
I composition 1. The molar ratio is Zn/Al=5 or more, Zn/Ga=10 or more. In terms of molar ratio, Zn/Al = more than 1 and less than 5, Zn/Ga = more than 1 and less than 10
II pH during precipitation reaction
a. Low pH, less than pH 7.5,
b. Suitable pH, pH 7.5-9.5,
c. High pH, pH over 9.5,
Can be expressed as
1) When the pH during the precipitation reaction is a and the composition is 1: a-1 or
When the pH during the precipitation reaction is a and the composition is 2: a-2
Under this condition, the mixture has low crystallinity as a carbonate hydrate.
2) When the pH during the precipitation reaction is b and the composition is 1: b-1
Under this condition, the precursor is a hydrozincite single phase (90 mass% or more),
M _4-6 (CO ₃ ) _1-3 (OH) _6-7 (1), and M is a zinc element and an aluminum element, or a zinc element and a gallium element. Here, M: at least one metal selected from the group consisting of elemental zinc, aluminum, and gallium. The molar ratio is Zn/Al=5 or more, or the molar ratio is Zn/Ga=10 or more. As the upper limit of the molar ratio is increased, a zinc carbonate-based hydrozincite containing less precursor as the precursor is obtained, and the doped metal is obtained. The effect of can not be seen. Since it is difficult to manufacture the dope metal in the hydrozincite phase in the precursor when the amount of the dope metal is small (certain doping becomes difficult and the antibacterial activity varies), Zn/Al or Zn/Ga The upper limit of the molar ratio is preferably 10000 or less, more preferably 1000 or less.
3) When the pH during the precipitation reaction is b and the composition is 2: b-2
Under this condition, a heterogeneous phase of zinc aluminum carbonate hydroxide and zinc gallium carbonate hydroxide exists, and ZnAl ₂ O ₄ , ZnGa ₂ O ₄ , and Al ₂ O ₃ , Ga ₂ O ₃ which are spinel phases by firing are present. The existence of such as. From this, it was confirmed that the precipitation of these different phases at the grain boundaries deteriorates the conductivity and reduces the antibacterial activity.
4) When the pH during the precipitation reaction is c and the composition is 1: c-1 or
When the pH during the precipitation reaction is c and the composition is 2: c-2
Under this condition, a hydroxide and a different phase of the oxide were observed in the precursor.

There are various theories about the antibacterial mechanism of zinc oxide, and the mechanism by which zinc ion destroys the cell membrane, the mechanism by which hydrogen peroxide generated from the surface of zinc oxide kills DNA or enzymes of bacteria and kills them are considered. The inventor of the present invention has considered that the effect of exhibiting antibacterial properties due to generation of hydrogen peroxide is large, and has reached the present invention. This hydrogen peroxide is generated when the carrier of zinc oxide comes into contact with oxygen or water on the particle surface. Therefore, it can be considered that by increasing the carrier concentration, which is the number of electrons in the composition, and promoting the carrier mobility, the hydrogen peroxide generation amount is increased and the antibacterial activity is improved.

In order to realize the increase in carrier concentration and the improvement in mobility, doping of zinc oxide with Al and Ga at the molecular level, promotion of solid solution, and improvement of crystallinity were invented. It was

2. Method for producing inorganic antibacterial composition of the present invention (production of precipitate)
The inorganic antibacterial composition of the present invention calcinates a carbonate hydrate of a precursor produced by a precipitation-forming reaction of a zinc salt aqueous solution, a carbonate aqueous solution, and an alkaline aqueous solution in the presence of aluminum and/or gallium. Obtained. Carbonate hydrate of the precursor is a mixture of a reaction product obtained by a precipitation generation reaction of an aqueous zinc salt solution, an aqueous carbonate solution, and an aqueous alkali solution, and raw materials as unreacted substances, by-products, and impurities mixed from the raw materials. is there.
Preferably, the metal salt aqueous solution of aluminum and/or gallium and the zinc salt aqueous solution are mixed such that the molar ratio of Zn and Al is Zn/Al=1 to 10000 or the molar ratio of Zn and Ga is Zn/Al. Ga=more than 1 and mixed in the range of 10,000. However, it is possible to use an excessive amount of Al or Ga in anticipation of unreacted substances. At the time of mixing, sodium carbonate, sodium hydrogencarbonate or sodium hydroxide aqueous solution as a mineralizer or pH adjuster is used, and the pH of the sodium hydrogencarbonate aqueous solution is 6.5 to 10.5, preferably 7.5 to 9 An aqueous sodium hydroxide solution is added dropwise to a mixed solution of an aqueous metal salt solution and an aqueous carbonate solution with stirring at a constant value within a range of 0.5 to obtain a precipitate produced by an alkaline precipitation method.
The precipitate is a precipitate containing a carbonate hydrate, preferably a basic zinc carbonate and a precipitate of zinc, aluminum and/or gallium. More preferably, it is preferable to obtain a precipitate containing hydrogenzincite as a main component as a precursor for the firing step.
After dropping the aqueous metal salt solution, it is preferable to stir for 10 to 30 hours, then perform solid-liquid separation by suction filtration and vacuum dry. The raw material carbonic acid source, zinc source, and mineralizing material are not limited to those described below. The carbonate source _{(NH 4) CO 3, Na} 2 CO 3, preferably, NaH (CO ₃₎ solution and the like, zinc source is selected zinc sulfate, zinc chloride, zinc acetate, among zinc nitrate, mineral The use of NH ₃ or NaOH as the chemical agent may be mentioned. The Al source and Ga source are selected from sulfates, chlorides, acetates, and nitrates.
A more preferable precipitate as a precursor in the firing step contains a hydrozincite represented by the following formula (1) or a hydrate thereof.
M _4-6 (CO ₃ ) _1-3 (OH) _6-7 (1)
M: At least one metal selected from the group consisting of zinc element, aluminum, and gallium.
The presence of hydrogenzite can be confirmed by XRD (X-ray diffractometry) peaks by X-ray analysis of the precipitate.
(Baking treatment)
The precipitate (precursor) obtained by the above-mentioned alkaline precipitation method is oxidized at 700° C. or higher, preferably at a temperature of more than 1000° C. to 1300° C. or less, more preferably 1100° C. to 1250° C. Inorganic antibacterial composition obtained by heat treatment in an atmosphere, the ratio of Zn and Al being Zn/Al=1 to more than 10000 in molar ratio, or the ratio of Zn and Ga being Zn/Ga=1 to more than 10000 in molar ratio. To get
The firing treatment may be performed by molding the precursor into pellets, or the powder may be fired without forming pellets.

3. Use of the inorganic antibacterial composition of the present invention The use of the composition of the present invention is not limited. The following can be given as specific examples.
(1) When the inorganic antibacterial composition of the present invention is used together with a wound healing agent, it can be made into an antibacterial drug having high safety and shelf life. It can also be used as a useful medical product by mixing it in a wound dressing or applying it on the surface.
(2) By using the inorganic antibacterial composition of the present invention together with a carrier for cosmetics, it is possible to obtain a cosmetic product having antibacterial properties and high safety and storability.
Examples of carrier products for cosmetics include cleaning cosmetics, hair cosmetics, basic cosmetics, makeup cosmetics, fragrance cosmetics, tanning cosmetics, sunscreen cosmetics, nail cosmetics, eyeliner cosmetics, lip cosmetics, oral cosmetics, bath cosmetics. Can be illustrated. In particular, for UVA-cut cosmetics, it is a more preferable use method because it is expected that zinc oxide absorbs ultraviolet rays.

Specifically, cleansing, soap, liquid body wash, hair wash cosmetics, shampoo, conditioner, hair lotion, hair essence, hair cream, hair treatment, hair coloring agent, hair finishing cosmetic, hair restorer, lotion, Serums, makeup creams, emulsions, packs, gels, masks, essences, body lotions, body creams, shaving cosmetics, hand care agents, foundations, cheek makeup, perfumes, colognes, sunscreens, sun care products, manicures. It is possible to add the inorganic antibacterial composition of the present invention to a nail enamel, eye make-up base, eye make-up, lip make-up, lipstick, toothpaste, mouthwash, bath agent, eye drops, suppositories, etc. it can.

(3) The inorganic antibacterial composition of the present invention is highly useful when fixed to a fiber and used for an antibacterial fiber or an antibacterial clothing article using the antibacterial fiber.
As the fibers, inorganic fibers such as natural fibers, synthetic fibers, glass fibers and metal fibers can be used, and among them, synthetic fibers of thermoplastic resin capable of melt spinning are preferably used. Examples of the thermoplastic resin forming the synthetic fiber include polyester, polyamide, polyolefin, acrylic, vinylon, polystyrene, polyvinyl chloride, polyvinylidene chloride, polylactic acid, silk, cellulose, etc. Can be selected and used. Also, a plurality of types may be used in combination. Specifically, for example, a method of impregnating fibers with a dispersion liquid of an inorganic antibacterial composition and a binder resin and drying it can be exemplified.

The binder resin may contain one or more components selected from the group consisting of hot-melt powder, latex, and water-dispersion type emulsion, and an appropriate one of commercially available materials should be used. You can Specific examples of the hot melt powder include polyethylene, ethylene vinyl acetate copolymer resin (EVA), polyester and polyamide. Examples of the latex include rubber-based latex such as SBR, NBR and polyurethane, resin-based latex such as polyacrylate, polyvinyl acetate and ethylene vinyl acetate copolymer resin (EVA). Examples of the water-dispersed emulsion include acrylic type, acrylic styrene type, acrylic silicone type, polyurethane type, polyester type, polyamide type and the like. In order to impregnate and apply the inorganic antibacterial composition as an aqueous dispersion to the fiber substrate among these binder resins, an aqueous dispersion type emulsion can be particularly preferably used.

The antibacterial fiber for fixing the inorganic antibacterial composition of the present invention to the fiber or the antibacterial clothing using the antibacterial fiber, in addition to general clothing, building fiber products, non-woven fabric products, floor Materials having an inorganic antibacterial composition are useful as materials and wall materials. Further, it can be suitably used for construction and air filter applications as automobile parts. In particular, in building materials and automobile cabins, the antibacterial fiber containing the inorganic antibacterial composition of the present invention can be preferably used.

(4) Furthermore, the inorganic antibacterial composition of the present invention is useful for applications of resin materials, ceramic materials, or metal materials containing an inorganic antibacterial composition or having a coating containing the inorganic antibacterial composition. is there. Specifically, the inorganic antibacterial composition of the present invention can be used as an antibacterial material by being contained in a resin material, a ceramic material, or a metal material. Further, it is useful if it is mixed with a resin binder and used by being coated on a resin panel, a ceramic panel, a metal panel or the like, since the structural member can be made antibacterial.

(5) Further, the pharmaceutical composition containing the inorganic antibacterial composition of the present invention can be used as an external medicine such as a wound healing agent, or contains the inorganic antibacterial composition of the present invention, or the inorganic antibacterial composition Examples of medical articles having a coating containing the composition include wound dressings used for wound healing agents.

The present invention will be specifically described below with reference to examples, but the present invention is not limited to the examples.

<Production of the inorganic antibacterial composition of the present invention>
In a reaction vessel, 500 mL of 0.04 M sodium hydrogen carbonate aqueous solution was prepared, and separately, 1000 mL of a metal salt aqueous solution having a total molar concentration of 0.1 M was prepared by mixing zinc nitrate and aluminum nitrate as a dropping reaction solution. A 30 mass% sodium hydroxide aqueous solution was prepared as a pH adjusting solution.
Using a pH controller connected to a pump, while maintaining the pH of the above sodium hydrogen carbonate solution at 9.0 and stirring the mixture, an aqueous solution of metal salt and an aqueous solution of sodium hydroxide were added dropwise. After all the metal salt aqueous solution was dropped, the reaction solution was stirred for 20 hours.
After stirring for 20 hours, the reaction solution was subjected to solid-liquid separation by centrifugation, and the obtained solid was washed with water and centrifuged three times. The precipitate washed in this way was vacuum dried to obtain basic zinc carbonate.
The basic zinc carbonate was molded into a pellet having a diameter of 20 mm and a weight of 2 g by a press machine, and the pellet was fired at 1200° C. for 4 hours.

<Production of antibacterial evaluation sample>
(Example 1)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and aluminum of 199/1 (99.5:0.5), and the firing temperature was 1200°C. Manufactured.
(Example 2)
Under the above manufacturing conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution was manufactured with the molar ratio of zinc and gallium being 99/1 (99:1.0) and the firing temperature being 1200°C. ..
(Example 3)
Under the above production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and aluminum of 199/1 (99.5:0.5), and the firing temperature was 1000°C. Manufactured.

(Example 4)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and aluminum of 199/1 (99.5:0.5), and the firing temperature was 1300°C. Manufactured.
(Example 5)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1M metal salt aqueous solution had a zinc/aluminum molar ratio of 9/1 (90:10), and the composition of the precursor before firing was hydrozincite. A precursor containing zinc aluminum carbonate hydroxide, which is not a single phase, was produced at a firing temperature of 1200°C.
(Example 6)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and gallium of 4/1 (80:20), and the composition of the precursor before firing was hydrozincite. A precursor containing zinc gallium carbonate hydroxide, which is not a single phase, was manufactured at a firing temperature of 1200°C.

(Comparative example 1)
It was manufactured under the same conditions as in Example 3, except that the firing temperature was 400°C.
(Comparative example 2)
It was manufactured under the same conditions as in Example 3, except that the firing temperature was 600°C.
(Comparative example 3)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and aluminum of 1/1 (50:50), and the composition of the precursor before firing was hydrozincite. It was prepared at a firing temperature of 1200° C. for a precursor in which a heterogeneous phase of zinc aluminum carbonate hydroxide, which is not a single phase, is dominant.
(Comparative example 4)
Under the above-mentioned production conditions, the pH was maintained at 9.0, the 0.1 M metal salt aqueous solution had a molar ratio of zinc and gallium of 1/1 (50:50), and the composition of the precursor before firing was hydrozincite. The precursor was predominantly a heterogeneous phase of zinc gallium carbonate, which was not a single phase, and was prepared at a firing temperature of 1200°C.

<Specific surface area>
All the above samples were heat-treated and then crushed in an agate mortar. The BET specific surface area of each sample is shown in Table 1.

<Antibacterial evaluation test method>
The above sample was subjected to dry heat sterilization at 180° C. for 2 hours to prepare 10 g/L to prepare a test solution. As shown in FIG. 1, the antibacterial effect of the above sample against E. coli (E. coli NBRC 3972) was evaluated. A bacterial suspension (10 ⁷ CFUml ⁻¹ ) was added to this test solution and shaken at 37° C. for 20 minutes in the dark. As a control, a bacterial suspension without a sample was used as a control. After shaking, 50 μL of the mixed solution was seeded on a regular agar medium and cultured at 37° C. for 24 hours. After culturing, the number of colonies formed on the agar medium was measured as N'CFU/mL. Similarly, the number of colonies was measured as N ₀ CFU/mL from the control agar medium and counted.
<Results>
From the measured number of bacteria, the killing rate constant k used as the efficacy of the antibacterial agent was calculated using the following formula. The death rate constant is the following value obtained from the treatment time of zinc oxide and bacterial suspension and the survival rate of bacteria, when the concentration of zinc oxide powder is constant.

t: treatment time (seconds), N: number of bacteria after shaking for t seconds, N ₀ : number of bacteria at 0 seconds.

When expressing the index of antibacterial activity, it was measured as N ₀ /N=N ₀ CFU/mL/N′CFU/mL, and k′ was determined as a kill rate constant per surface area obtained by dividing k by the BET specific surface area of each sample. And is shown in Table 2.

Evaluation of Examples and Comparative Examples The antibacterial compositions of Examples markedly improved antibacterial activity against E. coli. The killing rate constant k'per surface area, which is a performance index of antibacterial activity, was significantly improved to 2.7 to 163 times that of the composition of Comparative Example. Therefore, the inorganic antibacterial composition which is the zinc oxide powder of the present invention is useful as an antibacterial agent.

The inorganic antibacterial agent composition of the present invention is an antibacterial agent which prevents the growth of fungi such as Escherichia coli and has an excellent killing ability. By using the inorganic antibacterial composition of the present invention in cosmetics, clothing, furniture, building materials, etc., added as a powder into a material or a coating material, heat resistance, durability, and safety can be obtained. It is used as an inexpensive inorganic antibacterial agent that has excellent characteristics and exhibits effects even in the dark. Further, it is highly industrially useful as an inexpensive inorganic antibacterial agent exhibiting an effect even in the dark by using it in a food product or in a packaging material for a food product.

Claims (2)

Precipitation of aluminum salt aqueous solution or gallium salt aqueous solution, zinc salt aqueous solution, carbonate aqueous solution, and alkaline aqueous solution having a molar ratio of Zn/Al = more than 1 to 10,000 or a molar ratio of Zn/Ga = more than 1 to 10000 A method for obtaining an inorganic antibacterial composition by heat-treating a carbonate hydrate produced in a production reaction at a temperature of 700° C. or higher,
The method wherein the carbonate hydrate contains a hydrozincite represented by the following formula (1) or a hydrate thereof.
M _4-6 (CO ₃ ) _1-3 (OH) _6-7 (1)
M: At least one metal selected from the group consisting of zinc element, aluminum, and gallium. The method according to claim 1, wherein the precipitate obtained by the precipitation-forming reaction contains basic zinc carbonate and a precipitate of zinc, aluminum and/or gallium.