JP6941871B2 - Antibacterial agent and its manufacturing method - Google Patents

Description

The present invention relates to a hybrid antibacterial agent containing an inorganic antibacterial material and an organic antibacterial compound, and more particularly to a hybrid antibacterial agent containing silver ions as an inorganic antibacterial material.

As antibacterial agents, inorganic antibacterial agents such as silver and organic antibacterial agents such as quaternary ammonium compounds and benzalkonium chloride are known (for example, Patent Documents 1 and 2). Inorganic antibacterial agents have the advantages that there are many types of effective bacteria, high heat resistance, and antibacterial properties can be exhibited over a long period of time. On the other hand, organic antibacterial agents have an immediate effect and have an advantage of exhibiting antibacterial properties in a small amount.
Further, as an antibacterial agent having immediate-acting and slow-acting antibacterial properties, a hybrid antibacterial agent containing a silver cluster which is an inorganic antibacterial agent and an aliphatic amine which is an organic antibacterial agent is known (for example). Patent Document 3).

Antibacterial resin products (antibacterial resin products) are widely used in medical products and daily necessities. These antibacterial resin products are manufactured by molding a resin material to which an antibacterial agent is added, or by applying an antibacterial agent-containing coating agent to the surface of the molded resin product. Antibacterial agents for antibacterial resin products are dissolved in organic solvents and added to resin materials or coating agents.

Japanese Unexamined Patent Publication No. 10-245305 Japanese Unexamined Patent Publication No. 2001-55452 JP-A-2017-197442

As a method of imparting antibacterial performance to a resin product, a method of molding a resin material to which an antibacterial agent is added into a predetermined shape (this is referred to as a "direct addition method") and an antibacterial agent on the surface of the molded resin product. There is a method of applying (this is referred to as an "antibacterial coating method").
Since the direct addition method has antibacterial activity even inside the resin product, it has a feature that the antibacterial performance does not deteriorate even if the surface is worn. On the other hand, since it is necessary to knead the antibacterial agent over the entire resin material, the amount of the antibacterial agent used is large, and high heat resistance is required so as to withstand heating during molding.
Since the antibacterial coating method only applies the antibacterial coat to the resin surface, the amount of antibacterial agent used is small, and the heat resistance is high enough to withstand the high temperature environment (usually about 50 ° C) that can be placed during use. It is good if there is sex. On the other hand, since the antibacterial ability is imparted only to the surface of the resin product, the antibacterial ability is lost when the antibacterial coat is removed due to surface wear.

The hybrid antibacterial agent disclosed in Patent Document 3 has a relatively high heat resistance of about 160 ° C. However, since many thermoplastic resins are molded at a high temperature of 200 ° C. or higher, the hybrid antibacterial agent of Patent Document 3 may not be used in the direct addition method.

Therefore, an object of the present invention is to provide an antibacterial agent having immediate-acting and slow-acting antibacterial performance and high heat resistance, and a method for producing the same.

Aspect 1 of the present invention comprises a silver ion, a ligand bound to the silver ion, and an organic compound bonded to the ligand.
The ligand has a thiol group and an acidic functional group.
The organic compound is an antibacterial agent that is a quaternary phosphonium ion.

Aspect 2 of the present invention is the antibacterial agent according to Aspect 1, wherein the acidic functional group of the ligand is a sulfonic acid group.

Aspect 3 of the present invention is the antibacterial agent according to Aspect 1 or 2, wherein the ligand is an aliphatic thiolsulfonate ion.

In aspect 4 of the present invention, the ligand is at least one selected from 2-mercaptoethanesulfonate ion, 2-mercapto-5-benzimidazole sulfonate ion, and 3-mercapto-1-propanesulfonate ion. The antibacterial agent according to any one of aspects 1 to 3 including the above.

In aspect 5 of the present invention, the organic compound is an _{aliphatic quaternary phosphonium in containing an alkyl group having C 4 to} C ₁₈ carbon atoms, or an aromatic quaternary phosphonium ion containing at least one aromatic ring. The antibacterial agent according to any one of aspects 1 to 4.

In aspect 6 of the present invention, the quaternary phosphonium ion is tetraethylphosphonium ion, tetrabutylphosphonium ion, tetraoctylphosphonium ion, tributyldodecylphosphonium ion, tributylhexadecylphosphonium ion, tributyl-n-octylphosphonium ion, tetraphenyl. The antibacterial agent according to any one of aspects 1 to 5, selected from the group consisting of phosphonium ion, benzyltriphenylphosphonium ion, methyltriphenylphosphonium ion, amyltriphenylphosphonium ion, and hexyltriphenylphosphonium ion. be.

Aspect 7 of the present invention comprises a step of synthesizing a silver ion complex containing a silver ion and a ligand bound to the silver ion.
Including a step of reacting the silver ion complex with the organic compound in order to bond the ligand and the organic compound.
The ligand has a thiol group and an acidic functional group.
The organic compound is a method for producing an antibacterial agent, which is a quaternary phosphonium ion.

In aspect 8 of the present invention, the organic compound is an aliphatic quaternary phosphonium ion.
The alkyl group contained in the aliphatic quaternary phosphonium salt has C _{4 to} C ₆ carbon atoms.
The production method according to aspect 7, further comprising a step of solidifying the reactant from the aqueous solution layer after the step of reacting.

In aspect 9 of the present invention, the organic compound is an _{aliphatic quaternary phosphonium ion containing at least one alkyl group having C 7 to} C ₁₈ carbon atoms, or an aromatic quaternary phosphonium containing at least one aromatic ring. Ion,
The production method according to aspect 7, further comprising a step of extracting the reaction product into an organic solvent layer after the step of reacting.

The antibacterial agent of the present invention can exhibit immediate and slow-acting antibacterial performance by combining (hybridizing) a silver ion and an organic antibacterial compound. Further, the antibacterial agent of the present invention has high heat resistance because the ligand has a thiol group and the organic compound is a quaternary phosphonium ion. According to the production method of the present invention, the above-mentioned antibacterial agent can be efficiently produced.

FIG. 1 shows a structural formula of a hybrid antibacterial agent according to an embodiment of the present invention. FIG. 2 (a) shows the particle size distribution of the aggregate by the TOP-Ag (MPS) complex, and FIG. 2 (b) shows the particle size distribution of the aggregate by the TBP-Ag (MPS) complex. FIG. 3 (a) shows the structural formula of 2-mercapto-5-benzimidazole sulfonate (MBISA), and FIG. 3 (b) shows the structural formula of 3-mercapto-1-propanesulfonate sodium (MPS). show. FIG. 4A shows the structural formula of tetrabutylphosphonium bromide (TBPB), and FIG. 4B shows the structural formula of tetraoctylphosphonium bromide (TOPB). FIG. 5 shows the IR spectra of MPS, TOPB, Ag (MPS) complex and TOP-Ag (MPS). FIG. 6 shows the structural formula of TOP-Ag (MPS). FIG. 7 shows the IR spectra of MPS, TBPB, Ag (MPS) complex and TBP-Ag (MPS). FIG. 8 shows the structural formula of TBP-Ag (MPS). FIG. 9 shows the TG curves of MPS and Ag (MPS) complexes. FIG. 10 shows the DTA curves of MPS and Ag (MPS) complexes. FIG. 11 shows the TOPB TG curve and DTA curve. FIG. 12 shows the TG and DTA curves of TBPB. FIG. 13 shows the TOP-Ag (MPS) TG curve and DTA curve. FIG. 14 shows the TG and DTA curves of TBP-Ag (MPS). FIG. 15 shows the transmission spectrum of a glass plate whose surface is coated with a resin film containing an antibacterial agent (TOP-Ag (MBISA), TOP-Ag (MPS) or TBP-Ag (MPS)). FIG. 16 shows the results of a TOP-Ag (MBISA) antibacterial test against Staphylococcus aureus. FIG. 17 shows the results of a TOP-Ag (MBISA) antibacterial test against Klebsiella pneumoniae. FIG. 18 shows the results of an antibacterial test (antibacterial agent concentration: 0.05 wt%) of TOP-Ag (MPS) and TBP-Ag (MPS) against Staphylococcus aureus. FIG. 19 shows the results of an antibacterial test (antibacterial agent concentration: 0.2 wt%) of TOP-Ag (MPS) and TBP-Ag (MPS) against Staphylococcus aureus.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. In the following description, terms indicating a specific direction or position (for example, "top", "bottom", "right", "left", and other terms including those terms) are used as necessary. .. The use of these terms is for facilitating the understanding of the invention with reference to the drawings, and the meaning of these terms does not limit the technical scope of the invention. Further, the parts having the same reference numerals appearing in a plurality of drawings indicate the same parts or members.

<Embodiment 1>
1. 1. Hybrid antibacterial agent The antibacterial agent of the present invention is an inorganic organic hybrid antibacterial agent containing a silver ion, a ligand bonded (coordinated bond) to the silver ion, and an organic compound bonded to the ligand. (Hereinafter, the antibacterial agent of the present invention may be referred to as a "hybrid antibacterial agent"). FIG. 1 shows an example of a hybrid antibacterial agent according to the present invention.
The quaternary phosphonium ion used as an organic compound in the present invention exhibits antibacterial properties because the phosphonium ion is a cation. That is, the organic compound used in the present invention is an organic antibacterial compound and functions as a quick-acting antibacterial agent. The hybrid antibacterial agent exhibits both immediate and slow-acting antibacterial properties because silver ions function as a slow-acting antibacterial agent and organic compounds function as a fast-acting antibacterial agent.

The present inventors have diligently studied that the hybrid antibacterial agent disclosed in Patent Document 3 does not have sufficient heat resistance, and as a result, formed a silver ion complex using a ligand containing a thiol group and a sulfonate. However, they have found that the heat resistance of the hybrid antibacterial agent can be remarkably improved by using the quaternary phosphonium ion as the organic compound, and have completed the present invention.
As a result of the studies by the inventors, the quaternary phosphonium ion used in the present invention is inferior in antibacterial performance as compared with the aliphatic quaternary ammonium salt used as the organic antibacterial compound in Patent Document 3. However, it is excellent in terms of heat resistance. It is considered that the quaternary phosphonium ion is electrostatically bonded to the sulfonate of the silver ion complex, so that the heat resistance is remarkably improved. Therefore, it is considered that the use of quaternary phosphonium ions is one of the factors that can improve the heat resistance of the hybrid antibacterial agent.

The hybrid antibacterial agent of the present invention has, for example, a high heat resistance temperature of 200 ° C. or higher, and more preferably 250 ° C. or higher. Therefore, even if a treatment step of, for example, 200 ° C. or higher is included in the manufacturing process of the resin product, it is possible to suppress the thermal decomposition of the hybrid antibacterial agent. Therefore, a resin product containing a hybrid antibacterial agent in the bulk can be easily manufactured.

In addition, the hybrid antibacterial agent of the present invention can exhibit sufficient antibacterial activity even at a relatively low concentration. This is considered to be due to the synergistic effect of the antibacterial property of the silver ion and the antibacterial property of the organic compound cation.
Further, the hybrid antibacterial agent of the present invention includes ones that absorb less in the visible light region. Therefore, even if the hybrid antibacterial agent is kneaded into the resin product, the color development property of the resin product is not easily hindered.

Hereinafter, the hybrid antibacterial agent of the present invention will be described in detail.

(Silver ion)
Silver ion (Ag ⁺ ) is an inorganic antibacterial agent, and its antibacterial property is slow-acting. Silver clusters show antibacterial properties against many bacteria such as bacteria and yeast. Silver ions easily turn black by reacting with oxygen (O), sulfur (S), etc. in the air. Therefore, antibacterial products using silver ions may discolor over time.
In the hybrid antibacterial agent of the present invention, a ligand binds to silver ions to form a complex, which forms a complex.
Since the complex associates to form micelles and stabilizes (Fig. 2), blackening of silver ions is suppressed. Therefore, although it is an antibacterial agent using silver ions, it does not easily discolor over time and is suitable for application to highly aesthetic products.

式中、Aは、適宜置換されていてもよいアルキレン、適宜置換されていてもよいヘテロアルキレン、適宜置換されていてもよいアリーレン、および適宜置換されていてもよいヘテロアリーレンからなる群から選択される。 (Ligand)
As the ligand that coordinates with the silver ion, a compound having a thiol group and an acidic functional group is used. The thiol group binds to the silver ion when forming the silver ion complex. The acidic functional group can be bonded to an organic compound (quaternary phosphonium ion).
The acidic functional group is preferably a sulfonic acid, which can improve the heat resistance of the silver ion complex and, by extension, the heat resistance of the hybrid antibacterial agent.
The organic compound containing a thiol group and a sulfonic acid is a so-called organic thiol sulfonic acid. The organic thiol sulfonic acid can be represented by the following general formula.

In the formula, A is selected from the group consisting of optionally substituted alkylene, optionally substituted heteroalkylene, optionally substituted arylene, and optionally substituted heteroarylene. NS.

When A in the above general formula is alkylene, it becomes an aliphatic thiolsulfonic acid.
In addition, the organic thiol sulfonic acid may be provided as an organic thiol sulfonate by reacting with sodium hydroxide or the like. The "organic thiol sulfonic acid" in the present application also includes an organic thiol sulfonic acid and a salt thereof.
Specific examples of the organic thiol sulfonic acid suitable for the present invention include sodium 2-mercapto-5-benzimidazole sulfonic acid (MBISA), sodium 3-mercapto-1-propane sulfonic acid (MPS), and 2-mercaptoethanesulfonic acid. Examples include sodium. FIG. 3A shows the structural formula of MBISA, and FIG. 3B shows the structural formula of MPS.

When added as a ligand to the reaction system, the ligand exists as a compound, but when incorporated into a hybrid antibacterial agent, it can be considered to exist as an ion. Therefore, when described as a ligand that constitutes a part of the hybrid antibacterial agent, "organic thiol sulfonate ion", "aliphatic thiol sulfonate ion", "2-mercaptoethane sulfonate ion", " It may also be described as an ion, such as "2-mercapto-5-benzoimidazole sulfonate ion" and "3-mercapto-1-propane sulfonate ion".

式中、R¹、R²、R³およびR⁴は炭素数４〜１８の炭化水素基(C₄〜C₁₈)、Ｘはアニオン性基である。 (Organic compound)
A quaternary phosphonium ion is used as the organic compound bonded to the silver ion complex. The quaternary phosphonium ion (cation) has a feature that the heat resistant temperature is higher than that of a general organic antibacterial compound.
The quaternary phosphonium ion can be expressed by the following general formula.

In the formula, R ¹ , R ² , R ³ and R ⁴ are hydrocarbon groups having 4 to 18 carbon atoms (C _{4 to} C ₁₈ ), and X is an anionic group.

^{R 1} , R ² , R ³ and R ⁴ of the above general formula may be a hydrocarbon group such as an alkyl group (for example, a butyl group or an octyl group) or an aromatic ring. Further, R ¹ , R ² , R ³ and R ⁴ may all be the same functional group, or some or all of them may be different functional groups.

If all of R ¹ , R ² , R ³ and R ⁴ are alkyl groups, they are aliphatic quaternary phosphoniums. The aliphatic quaternary phosphonium includes tetraethylphosphonium salt, tetrabutylphosphonium salt, tetraoctylphosphonium salt, tributyldodecylphosphonium salt, tributylhexadecylphosphonium salt, and tributyl-n-octylphosphonium salt. FIG. 4A shows the structural formula of tetrabutylphosphonium bromide (TBPB), and FIG. 4B shows the structural formula of tetraoctylphosphonium bromide (TOPB).

If ^{one or more of R 1} , R ² , R ³ and R ⁴ contains a benzene ring, it is an aromatic quaternary phosphonium. Aromatic quaternary phosphoniums include tetraphenylphosphonium salts, benzyltriphenylphosphonium salts, methyltriphenylphosphonium salts, amyltriphenylphosphonium salts, and hexyltriphenylphosphonium salts.

X in the above general formula may be an anionic group such as bromine, chlorine or iodine.
When added to the reaction system, the organic compound exists as a "salt" of bromide, chloride, iodide, etc., but when incorporated into a hybrid antibacterial agent, it exists as an ion. Can be regarded as. Therefore, when described as an organic compound constituting a part of a hybrid antibacterial agent, "quaternary phosphonium ion", "aliphatic thiolsulfonic acid ion", "aromatic quaternary phosphonium ion", "tetra" It may also be described as an ion, such as "butylphosphonium (TBP) ion" and "tetraoctylphosphonium (TOP) ion".

(Specific example of hybrid antibacterial agent)
Specific examples of the hybrid antibacterial agent suitable for the present invention include
・ TOP-Ag (MBISA) generated by the reaction of MBISA-coordinated Ag (MBISA) complex with Ag ion with TOPB ・ Ag (MPS) complex with MPS coordinated with Ag ion reacts with TOPB Generated TOP-Ag (MPS)
-TBP-Ag (MPS) produced by the reaction of the Ag (MPS) complex in which MPS is coordinated to the Ag ion with TBPB.
And so on.
The hybrid antibacterial agent of the present invention is not limited to these.

2. Method for producing antibacterial agent Next, a method for producing a hybrid antibacterial agent will be described.
The manufacturing process differs depending on the degree of hydrophilicity of the organic compound (quaternary phosphonium salt) used. For example, examples of the highly hydrophilic organic compound include those in which the functional group bonded to the quaternary phosphonium salt is an alkyl group _{having 4 to 6 carbon atoms (C 4 to} C _6). Organic compounds with low hydrophilicity (that is, hydrophobic) include those in which the functional group bonded to the quaternary phosphonium salt contains an aromatic substance, and an alkyl group having 7 to _{18 carbon atoms (C 7 to C 18).} Examples include those containing.
The production method will be described separately for the case where a hydrophilic organic compound is used and the case where a hydrophobic organic compound is used.

Production method (1): When a hydrophilic organic compound is used (step (1) -1. Synthesis of silver ion complex)
A silver compound aqueous solution containing silver ions is added to the aqueous solution containing a ligand, and the mixture is stirred for 1 to 10 hours. The ligand in the aqueous solution coordinates with the silver ion to give a silver ion complex.

(Step (1) -2. Reaction of silver ion complex with organic compound (quaternary phosphonium salt))
A quaternary phosphonium salt showing hydrophilicity is dissolved in distilled water to prepare an aqueous solution of an organic compound. Process (1) -1. To the silver ion complex aqueous solution obtained in the above, add the organic compound aqueous solution and stir for 3 to 10 minutes. As a result, the silver ion complex reacts with the quaternary phosphonium salt (more accurately, the ligand of the silver ion complex reacts with the quaternary phosphonium salt) to produce a hybrid antibacterial agent. Stirring can be performed by shaking firmly by hand, stirring with a vortex mixer, etc. in a state of being sealed in a closed container. At this point, the antibacterial agent is in the state of an aqueous solution.

(Step (1) -3. Removal of water)
Process (1) -2. Water is removed from the aqueous solution obtained in (1) to obtain a hybrid antibacterial agent. A freeze-drying method may be used to remove the water.

Production method (2): When a hydrophobic organic compound is used (step (2) -1. Synthesis of silver ion complex)
The above steps (1) -1. Is similar to. That is, a silver compound aqueous solution containing silver ions is added to the aqueous solution containing a ligand, and the mixture is stirred for 1 to 10 hours. The ligand in the aqueous solution coordinates with the silver ion to give a silver ion complex.

(Step (2) -2. Reaction of silver ion complex with organic compound (quaternary phosphonium salt))
A hydrophilic quaternary phosphonium salt is dissolved in an organic solvent (for example, toluene) to prepare an organic solution. Process (2) -1. Add an organic solution to the silver cluster complex aqueous solution obtained in (1) and stir for 5 to 10 minutes. As a result, the silver ion complex reacts with the quaternary phosphonium salt (more accurately, the ligand of the silver ion complex reacts with the quaternary phosphonium salt) to produce a hybrid antibacterial agent. Stirring can be performed by shaking firmly by hand, stirring with a vortex mixer, etc. in a state of being sealed in a closed container.

If the stirring is not sufficient here, the silver ion complex and the quaternary phosphonium salt do not react sufficiently, and a hybrid antibacterial agent cannot be obtained. Therefore, when stirring, it is important to stir vigorously for a sufficient period of time. Even if the silver ion complex and the hydrophobic quaternary phosphonium salt coexist, it is not easy for the hydrophilic silver cluster complex and the hydrophobic quaternary phosphonium salt to approach each other, and the reaction proceeds naturally. There is little to do.

The stirred solution is allowed to stand to separate it into an aqueous layer (lower layer) and an organic layer (upper layer). The hybrid antibacterial agent containing the hydrophobic organic compound is present in the organic layer because it dissolves in the organic solvent. Therefore, the organic layer (upper layer) is separated to obtain an organic solution containing a hybrid antibacterial agent.

(Step (2) -3. Removal of organic solvent)
Process (2) -2. The organic solvent is removed from the organic layer obtained in (1) to obtain a hybrid antibacterial agent. A vacuum dryer (evaporator) may be used to remove the organic solvent.

The hybrid antibacterial agent obtained by the above-mentioned production method (1) or (2) has high antibacterial properties, and further has an immediate effect peculiar to an organic antibacterial agent and a slow-acting antibacterial agent peculiar to an inorganic antibacterial agent. Demonstrate sex.

(Synthesis of hybrid antibacterial agent)
(1) TOP-Ag (MBISA), (2) TOP-Ag (MPS) and (3) TBP-Ag (MPS), three types of hybrid antibacterial agents) were synthesized. The procedure for synthesizing each antibacterial agent will be described in detail.

The types, purity, and acquisition routes of the reagents used in the synthesis of antibacterial agents are as follows.
-Purchased 2-Mercapto-5-benzimidazolesulfoni acid sodium salt dehydrate (99%) from Sigma Aldrich.
-Toluene (99.5%), acetonitrile, tetraoctylammonium Bromide (TOAB), N, N-dimethylformamide (DMF), tetrahydrofuran (THF), 0.1 mol / L silver nitrate solution (99.9%) are Wako Pure Chemical Industries, Ltd. Purchased from Kogyo Co., Ltd.
-Tetra-n-octylphosphonium Bromide (TOPB), Tetrabutylphosphonium Bromide (TBPB), 3-mercapto-1-propanesulfonic Acid Sodium Salt (MPS) ) Was purchased from Tokyo Kasei Kogyo Co., Ltd.
-Distilled water is purified by a water distillation apparatus (aquarius RFD250, ADVANTEC).

(1) Synthesis of TOP-Ag (MBISA)
(1-i) Synthesis of Ag (MBISA) complex
5 mL (1 × 10 ^-4 _{mol) of 0.02 M aqueous AgNO 3} solution was added to a 30 mL screw tube (Sample A). ^{Furthermore, a solution of 86.5 mg (3 × 10 -4} mol) of 2-mercapto-5-benzimidazole sulfonate sodium (MBISA) in 5 mL of pure water was added to sample A. A stir bar was placed in a screw tube wrapped with aluminum foil to block light. The solution was then stirred at 400 rpm for 30 minutes using a magnetic stirrer JEIO THEC Multi-Channel Stirrer. The solution became cloudy and an Ag (MBISA) complex was formed (Sample A').

(1-ii) Synthesis of TOP-Ag (MBISA)
112.7 mg of tetraoctylphosphonium bromide (TOPB) (amount corresponding to molar ratio TOPB / Ag = 2) was dissolved in 5 mL of toluene in a 30 mL screw tube (Sample C). Sample C and 10 mL (Sample A') of Ag (MBISA) complex generated in (1-i) above are mixed in a 30 mL screw tube, and mixed using a vortex mixer VYX-3000L for about 3 minutes. bottom. In addition, in order to separate the dispersed water droplets as an emulsion, 1 mL each of the separated upper toluene layer was placed in a 1.5 mL microtube, and the rotation speed was 14800 rpm, 5 using a SIGMA micromini centrifuge. Centrifuge for minutes. Then, the upper toluene layer was separated and transferred to an eggplant flask. When toluene was distilled off from the separated toluene layer using an evaporator EYELA CCA-1110, a colorless, transparent and highly viscous sample was produced. The appearance of the TOP-Ag (MBISA) complex and the sample did not change visually. To completely dissolve the sample attached to the eggplant flask, 10 mL of acetonitrile was added in 3 portions to dissolve the sample and transferred to a 30 mL transparent screw tube. Aluminum foil was wrapped around a screw tube to block light, and then solidified with a vacuum dryer EYELA VOM-1000. TOP-Ag (MBISA) yielded 80 mg.

(2) Synthesis of TOP-Ag (MPS) and TBP-Ag (MPS)
(2-i) Synthesis of Ag (MPS) complex 5 mL (1 × 10 ^-4 _{mol) of 0.02 M aqueous AgNO 3} solution was added to the screw tube (Sample D). ^{Further, a solution prepared by dissolving 53.5 mg (3 × 10 -4} mol) of sodium 3-mercapto-1-propanesulfonate (MPS) in 5 mL of pure water was added to Sample D. A stir bar was placed in a screw tube wrapped with aluminum foil to block light. The solution was then stirred at 400 rpm for 30 minutes using a magnetic stirrer JEIO THEC Multi-Channel Stirrer. The solution was clear and colorless, and an Ag (MPS) complex was formed (Sample D').

(2-ii) Synthesis of TOP-Ag (MPS)
169.1 mg of tetraoctylphosphonium bromide (TOPB) (amount corresponding to molar ratio TOPB / Ag = 3) was dissolved in 5 mL of toluene in a 30 mL screw tube (Sample E). Sample E and 10 mL of the Ag (MPS) complex (Sample D') produced in (2-i) above were mixed in a 30 mL screw tube, and mixed with a vortex mixer VYX-3000 L for about 3 minutes. After allowing to stand and separating into an upper layer (toluene layer) and a lower layer (aqueous layer), the upper toluene layer was separated. When toluene was distilled off from the separated toluene layer with an evaporator EYELA CCA-1110, a colorless, transparent and highly viscous sample was produced. TOP-Ag (MPS) had a lower viscosity than TOP-Ag (MBISA). To completely dissolve the sample attached to the eggplant flask, 10 mL of acetonitrile was added in small portions in 3 portions to dissolve the sample and transferred to a 30 mL transparent screw tube. Aluminum foil was wrapped around a screw tube to block light, and then solidified with a vacuum dryer EYELA VOM-1000. TOP-Ag (MPS) yielded 90 mg.

(3) Synthesis of TBP-Ag (MPS)
In a 30 mL screw tube, 101.8 mg of tetrabutylphosphonium bromide (TBPB) (amount corresponding to the molar ratio TOPB / Ag = 3) was dissolved in 5 mL of pure water (Sample F). In a 30 mL screw tube, mix sample F and 10 mL (sample D') of the Ag (MPS) complex produced by the method described in (2-i) above, and use a vortex mixer VYX-3000 L for about 3 minutes. Mixed. The solution was colorless and transparent, and the solution was transferred to an eggplant flask and solidified using a lyophilizer EYELA FDS-1000. A white solid TBP-Ag (MPS) yielded a yield of 200 mg.

<FT-IR measurement>
FT-IR measurement was performed to confirm the binding state of Ag ⁺ , ligand (MPS), and organic compound (TOPB, TBPB) in the antibacterial agent.
In this example, FT-IR measurement of MPS, TOPB, TBPB, Ag (MPS) complex, TOP-Ag (MPS) and TBP-Ag (MPS) was performed. For the FT-IR measurement of the Ag (MPS) complex, an aqueous solution of the Ag (MPS) complex (sample D') was produced by the method described in (2-i) of Example 1, and the solution was freeze-dried to solidify. A modified sample was used.
A small amount of measurement sample (reagent or solid sample) was taken, and FT-IR measurement was performed using JASCO FT / IR-4200.

(About TOP-Ag (MPS))
FIG. 5 shows the IR spectra of MPS, TOPB, Ag (MPS) complex and TOP-Ag (MPS). Further, FIG. 6 shows the structural formula of TOP-Ag (MPS).
In the MPS IR spectrum, peaks were found at ^{2561 cm -1} , 1341 cm ^-1 , 1201 cm ^-1 , 1036 cm ^-1 , and 721 cm ^-1. _{These belong to SH, S-CH 2} , R-SO ₃ , R-SO ₃ , and CS, which are possessed by MPS, respectively.
In the TOPB IR spectrum, peaks were found at ^{2961 cm -1} , 2927 cm ^-1 , 2855 cm ^-1 , 1380 cm ^-1 , 852 cm ^-1 , and 811 cm ^-1. Each of these, -CH ₃ has the topB (stretching), - CH ₃ (stretching), - CH ₂ - (stretching), it is assigned to _{P-CH 3, P-CH} 3, P-CH 3.
In the IR spectrum of the Ag (MPS) complex in FIG. 5, most of the peaks confirmed in the IR spectra of MPS and TOPB are confirmed, but the SH peak (2561 cm ^-1 ) of MPS has disappeared. From this, in FIG. 5, it was confirmed that when the complex was formed, the SH group of MPS (see FIG. 3 (a)) ^{reacted with the silver ion Ag +} to form an Ag-S bond. rice field.

(About TBP-Ag (MPS) antibacterial agent)
FIG. 7 shows the IR spectra of MPS, TBPB, Ag (MPS) complex and TBP-Ag (MPS). Further, FIG. 8 shows the structural formula of TBP-Ag (MPS).
Similar to FIG. 5, peaks were observed in the IR spectrum of MPS at 2561 cm ^-1 , 1341 cm ^-1 , 1218 cm ^-1 , 1199 cm ^-1 , 1055 cm ^-1 , and 721 cm ^-1. _{These belong to SH, S-CH 2} , R-SO ₃ , R-SO ₃ , R-SO ₃ , and CS, which are possessed by MPS, respectively.
In the TBPB IR spectrum, peaks were found at ^{2961 cm -1} , 2927 cm ^-1 , 2855 cm ^-1 , 1341 cm ^-1 , 852 cm ^-1 , and 811 cm ^-1. Each of these, -CH ₃ has the TBPB (stretching), - CH ₃ (stretching), - CH ₂ - (stretching), is assigned to _{P-CH 3, P-CH} 3, P-CH 3.
In the IR spectrum of the Ag (MPS) complex in FIG. 7, most of the peaks confirmed in the IR spectra of MPS and TBPB are confirmed, but the SH peak (2561 cm ^-1 ) of MPS has disappeared. From this, it was also confirmed in FIG. 7 that the SH group of MPS (see FIG. 3 (b)) ^{reacted with the silver ion Ag +} to form an Ag-S bond when forming the complex. rice field.

<Thermal stability>
Thermogravimetric differential thermal analysis (TG-DTA) measurements were performed to investigate the thermal stability of the antibacterial agent.
In this example, Rigaku Thermo plus EVO TG8120 was used for TG-DTA measurement in which TG-DTA measurement of MPS, Ag (MPS) complex, TOP-Ag (MPS) and TBP-Ag (MPS) was performed. For the TG-DTA measurement of the Ag (MPS) complex, an aqueous solution of the Ag (MPS) complex (sample D') was produced by the method described in (2-i) of Example 1, and the solution was freeze-dried to solidify. A lyophilized sample was used.

(About MPS, Ag (MPS) complex)
Take about 7 mg each of solid samples of MPS and Ag (MPS) complexes, set the temperature rise rate to 5 ° C / min, and measure TG-DTA from room temperature to 900 ° C under nitrogen flow (0.7 L / min). went.
The start temperature of weight loss in the TG measurement was defined as the "pyrolysis start temperature".
The TG curve of the MPS and Ag (MPS) complex is shown in FIG. 9, and the DTA curve is shown in FIG.
In FIG. 9, the weight loss of MPS was confirmed from around 214 ° C. (that is, the thermal decomposition start temperature of MPS was 214 ° C). In the Ag (MPS) complex, weight loss was confirmed from around 269 ° C (that is, the thermal decomposition start temperature of MPS was 269 ° C). From this, it can be seen that the heat resistance of MPS was increased by complexing with Ag.
In FIG. 10, an endothermic reaction was observed at 229 ° C for MPS and 290 ° C for the Ag (MPS) complex. This is considered to be because the endothermic peak shifted to the high temperature side due to the increase in molecular weight.

(About TOPB and TBPB)
Approximately 7.0 mg of each of the TOPB and TBPB solid samples was taken, the temperature rise rate was set to 5 ° C / min, and TG-DTA measurement was performed from room temperature to 500 ° C under nitrogen flow (0.7 L / min).
The TOPB TG and DTA curves are shown in FIG. 11, and the TBPB TG and DTA curves are shown in FIG.
From FIG. 11, it was found that the thermal decomposition start temperature of TOPB was 326 ° C. Further, from FIG. 12, it was found that the thermal decomposition start temperature of TBPB was 323 ° C.

(About TOP-Ag (MPS) and TBP-Ag (MPS))
Take about 7.5 mg each of TOP-Ag (MPS) and TBP-Ag (MPS) solid samples, set the temperature rise rate to 5 ° C / min, and under nitrogen flow (0.7 L / min) from room temperature to 500 ° C. TG-DTA measurement was performed up to.
The TOP-Ag (MPS) TG curve and DTA curve are shown in FIG. 13, the TBP-Ag (MPS) TG curve is shown in FIG. 14, and the DTA curve is shown in FIG.
From FIG. 13, it was found that the thermal decomposition start temperature of TOP-Ag (MPS) was about 295 ° C. Further, from FIG. 14, it was found that the thermal decomposition start temperature of TBP-Ag (MPS) was about 290 ° C.
From this, it was found that all the antibacterial agents have a heat resistance of about 290 ° C.

(Solubility in organic solvent)
TOP-Ag (MPS) produced by the method described in (2-ii) of Example 1 was placed in 8 microtubes in an amount of about 5 mg each. Pure water, methanol, ethanol, ethyl acetate, acetone, THF, acetonitrile, and DMF were added to each microtube in an amount of 1 mL each, and the solubility in each solution was examined.
Similarly, the same test was performed on TBP-Ag (MPS) produced by the method described in (3) of Example 1.
The test results are shown in Table 1. "OK" was given when all the solid samples were dissolved, and "NG" was given when all the solid samples remained undissolved.

TOP-Ag (MPS) was dissolved in ethyl acetate, acetone, THF, acetonitrile and DMF. This is because the alkyl group contained in the organic compound TOP contained in TOP-Ag (MPS) is C ₈ and the number of carbon atoms is 7 or more, so that the hydrophobicity is relatively high. From this, it is considered that TOP-Ag (MPS) is suitable for dissolving in an organic solvent and kneading with a resin material.

On the other hand, TBP-Ag (MPS) was dissolved in pure water and DMF, but not in other organic solvents. This is because the alkyl group contained in the organic compound TBP contained in TBP-Ag (MPS) is C ₄ and the number of carbon atoms is 6 or less, so that the hydrophobicity is relatively low. From this, it is considered that TBP-Ag (MPS) is suitable for, for example, kneading into a water-soluble resin material and adding to an antibacterial aqueous solution that can be used in the medical field and the like.

<Dispersibility in resin materials (kneading)>
The dispersibility of TOP-Ag (MBISA), TOP-Ag (MPS), and TBP-Ag (MPS) in resin materials was investigated.
As the resin material, a photocurable acrylic resin and a polyvinyl alcohol-based resin (PVOH-based resin) were used.
First, a method for preparing an aqueous solution (resin aqueous solution) in which a resin material is dissolved will be described, and then a dispersion test of an antibacterial agent in the resin material will be described.

(Preparation of aqueous resin solution)
Take 1 g, 2 g, 3 g and 4 g of polyvinyl alcohol resin (PVOH resin, model number AZF8035W), put it in a test tube, add pure water, and add 10 wt%, 20 wt%, 30 wt%, and A 40 wt% PVOH resin aqueous solution was prepared. A Dimroth condenser was attached, the temperature was set to 60 ° C. at 500 rpm, and the mixture was stirred for 2 hours using a parallel reactor SIBATA CP-100. The 40 wt% aqueous resin solution was further stirred at 80 ° C. for 1 hour. As a result, a PVOH aqueous solution was obtained.

Each antibacterial agent was dispersed in the resin material in the following combinations.
・ TOP-Ag (MBISA): Photocurable acrylic resin, PVOH resin ・ TOP-Ag (MPS): PVOH resin ・ TBP-Ag (MPS): PVOH resin

(About TOP-Ag (MBISA) + photocurable acrylic resin)
TOP-Ag (MBISA) produced by the method described in Example 1 (1-ii) was used as a solvent in a photocurable acrylic resin solution (Shofu Inc., Resin Glaze Liquid, Model No. GS1-128). ) Was mixed according to the following procedure.
First, 2000 mg of a photocurable acrylic resin solution x 3 times was taken out. Next, 6 mg, 20 mg, and 60 mg were taken out so that TOP-Ag (MBISA) was 0.3 wt%, 1 wt%, and 3 wt% with respect to the photocurable acrylic resin solution, respectively. These were dissolved in a photocurable acrylic resin solution and ethanol (507 μL) with a weight ratio of 1: 0.2, and finally TOP-Ag (MBISA) was 15 wt%, 5 wt%, 1.5 with respect to ethanol. A wt% TOP-Ag (MBISA) ethanol solution was prepared. Add each of these to a photocurable acrylic resin solution (2000 mg), and knead for 5 minutes and defoam for 5 minutes using Awatori Kentarou (THINKY Rotating / Revolving Mixer Awatori Kentarou ARE-310). rice field.

In order to investigate the dispersibility of TOP-Ag (MBISA), a resin film was formed using a photocurable acrylic resin solution containing TOP-Ag (MBISA).
After washing a 5 cm square glass plate with acetone, 200 μL of a photocurable acrylic resin solution containing TOP-Ag (MBISA) was added dropwise to the glass plate. This solution was applied to the entire glass plate using a 46 μm bar coater. This was heated to dry at 70 ° C. for 5 minutes with a hot stirrer REXIM RSH-1DN. Then, blue light irradiation was carried out for 2 minutes to cure the resin, and a resin film was obtained.
The resin film formed from any of the photocurable acrylic resins having a TOP-Ag (MBISA) concentration of 0.3 wt%, 1 wt%, or 3 wt% was visually colorless and transparent with no observation of aggregation or coloring. rice field. As described above, the dispersibility of TOP-Ag (MBISA) in the resin was good.

(About TOP-Ag (MBISA) + PVOH resin)
TOP-Ag (MBISA) produced by the method described in (1-ii) of Example 1 was mixed with a PVOH-based resin aqueous solution by the following procedure using ethanol as a solvent.
First, 2000 mg × 5 times of a 30 wt% PVOH resin aqueous solution was taken out.
Next, TOP-Ag (MBISA) was weighed at 18 mg, 6 mg, 3.6 mg, 1.2 mg, and 0.3 mg, and placed in 9 mL screw tubes, respectively. To each screw tube, 152 μL of ethanol was added and dissolved. The obtained TOP-Ag (MBISA) ethanol solution was added to 2000 mg of each PVOH-based resin aqueous solution. As a result, a PVOH resin mixed solution was prepared by adding TOP-Ag (MBISA) to a PVOH resin solid at 3 wt%, 1 wt%, 0.6 wt%, 0.2 wt%, and 0.05 wt%. All the solutions became cloudy.

A resin film was formed using the obtained PVOH-based resin mixed solution.
After washing the 5 cm square glass plate with acetone, 500 μL of the PVOH resin mixed solution was dropped onto the glass plate. This solution was applied to the entire glass plate using a 100 μm bar coater. This was heated to dry at 70 ° C. for 5 minutes with a hot stirrer REXIM RSH-1DN. Again, 500 μL of the PVOH-based resin mixed solution was dropped onto the glass plate, applied to the entire glass plate using a bar coater, heated at 70 ° C. for 5 minutes with a hot stirrer, and dried to obtain a resin film.

Resin films formed from any of the PVOH-based resin mixed solutions with TOP-Ag (MBISA) concentrations of 3 wt%, 1 wt%, 0.6 wt%, 0.2 wt%, and 0.05 wt% are cloudy before heating. rice field. However, it changed to colorless and transparent by heating, and no aggregation or coloring was observed. As described above, the dispersibility of TOP-Ag (MBISA) in the resin was good.

(About TOP-Ag (MPS) + PVOH resin)
TOP-Ag (MPS) produced by the method described in (2-ii) of Example 1 was mixed with a PVOH-based resin aqueous solution using THF as a solvent in the following procedure.
First, 2000 mg × 3 times of a 30 wt% PVOH resin aqueous solution was taken out.
Next, TOP-Ag (MPS) was weighed 3.6 mg, 1.2 mg, and 0.3 mg and placed in a 9 mL screw tube, respectively. 135 μL of THF was added to each screw tube to dissolve it. The obtained TOP-Ag (MPS) THF solution was added to 2000 mg of each PVOH-based resin aqueous solution. As a result, a PVOH-based resin mixed solution was prepared by adding 0.6 wt%, 0.2 wt%, and 0.05 wt% of TOP-Ag (MPS) to the PVOH-based resin solid.

A resin film was formed using the obtained PVOH-based resin mixed solution.
After washing the 5 cm square glass plate with acetone, 500 μL of the PVOH resin mixed solution was dropped onto the glass plate. This solution was applied to the entire glass plate using a 100 μm bar coater. This was heated to dry at 70 ° C. for 5 minutes with a hot stirrer REXIM RSH-1DN. Again, 500 μL of the PVOH-based resin mixed solution was dropped onto the glass plate, applied to the entire glass plate using a bar coater, heated at 60 ° C. for 5 minutes with a hot stirrer, and dried to obtain a resin film.

No aggregation or coloring was observed in the resin film formed from any of the PVOH-based resin mixed solutions having TOP-Ag (MPS) concentrations of 0.6 wt%, 0.2 wt%, and 0.05 wt%, and they were visually colorless and transparent. rice field. As described above, the dispersibility of TOP-Ag (MPS) in the resin was good.

(About TBP-Ag (MPS) + PVOH resin)
The TBP-Ag (MPS) produced by the method described in (3) of Example 1 was mixed with a PVOH-based resin aqueous solution by the following procedure.
First, 2000 mg × 3 times of a 30 wt% PVOH resin aqueous solution was taken out.
Next, TBP-Ag (MPS) was weighed 3.6 mg, 1.2 mg, and 0.3 mg and placed in a 9 mL screw tube, respectively. 2000 mg of a 30 wt% PVOH resin aqueous solution was directly added to each screw tube. As a result, a PVOH-based resin aqueous solution was prepared by adding 0.6 wt%, 0.2 wt%, and 0.05 wt% of TBP-Ag (MPS) to the PVOH-based resin solid.

A resin film was formed using the obtained PVOH-based resin mixed solution.
After washing the 5 cm square glass plate with acetone, 500 μL of the PVOH resin mixed solution was dropped onto the glass plate. This solution was applied to the entire glass plate using a 100 μm bar coater. This was heated to dry at 70 ° C. for 5 minutes with a hot stirrer REXIM RSH-1DN. Again, 500 μL of the PVOH-based resin mixed solution was dropped onto the glass plate, applied to the entire glass plate using a bar coater, heated at 70 ° C. for 5 minutes with a hot stirrer, and dried to obtain a resin film.

The resin film formed from any of the PVOH-based resin mixed solutions having a TBP-Ag (MPS) concentration of 0.6 wt%, 0.2 wt%, or 0.05 wt% was visually colorless and transparent with no observation of aggregation or coloring. rice field. As described above, the dispersibility of TBP-Ag (MPS) in the resin was good.

<Measurement of transmittance>
Transmittance was measured to examine the tintability of TOP-Ag (MBISA), TOP-Ag (MPS), and TBP-Ag (MPS).
TOP-Ag (MBISA) + PVOH resin mixed solution (TOP-Ag (MBISA) concentration: 0.6 wt%), TOP-Ag (MPS) + PVOH resin mixed solution (TOP-Ag (MPS)) prepared in Example 5 Concentration: 0.6 wt%), TBP-Ag (MPS) + PVOH resin mixed solution (TBP-Ag (MPS) concentration: 0.6 wt%) was applied to the glass plate by the method described in Example 5. A resin film was formed. Then, the transmittance of the glass plate on which the resin film was formed was measured. The measurement was performed using an ultraviolet-visible spectrophotometer JASCO V-670 spectrophotometer, and the measurement conditions were response Fast, bandwidth 2.0 nm, scanning speed 400 nm / min, start wavelength 900 nm, end wavelength 400 nm, data acquisition interval 1.0. It was set to nm.

The measurement conditions for transmittance measurement are shown below. The measured transmission spectrum is shown in FIG.
From the transmission spectrum shown in FIG. 15, it can be seen that each sample maintains a transmittance of 99% or more in the visible light wavelength region (400 nm or more). Therefore, it was found that even if TOP-Ag (MBISA), TOP-Ag (MPS), and TBP-Ag (MPS) were added to the resin, the resin was not colored.

<Antibacterial test>
The antibacterial properties of antibacterial agents (TOP-Ag (MBISA), TOP-Ag (MPS) and TBP-Ag (MPS)) were examined. The antibacterial test of each antibacterial agent will be described in detail below.

(1) TOP-Ag (MBISA) antibacterial test (Staphylococcus aureus, Klebsiella pneumoniae)
As the sample for the antibacterial test, a glass plate coated with a resin film containing an antibacterial agent was used. Specifically, a photocurable acrylic resin solution containing TOP-Ag (MBISA) was prepared and applied to a glass plate to prepare a sample according to the procedure described in Example 6.

Staphylococcus aureus NBRC 12732 and Klebsiella pneumonie IAM 12015 in 5 mL of ordinary bouillon medium (Eiken Kagaku Co., Ltd.) were cultured with shaking overnight at 27 ° C, and then the final concentration was 1/50. Diluted with sterile water containing a concentration of normal bouillon medium. A test piece (antibacterial agent-coated glass plate) was placed in a petri dish, and 0.4 mL of the bacterial suspension was placed on the test piece (antibacterial agent-coated glass plate). After covering this bacterial suspension with a polyethylene sheet (4 cm × 4 cm), the petri dish was covered and left at 30 ° C. After 24 hours, the bacterial suspension on the test piece was collected in 4.5 mL sterile physiological saline and diluted 10-fold in 4 steps. The viable cell count in 1 mL of the diluent was measured.
FIG. 16 shows the experimental results of the TOP-Ag (MBISA) antibacterial test against Staphylococcus aureus, and FIG. 17 shows the experimental results of the TOP-Ag (MBISA) antibacterial test against Klebsiella pneumoniae. The concentration in each figure is the concentration of the antibacterial agent in the photocurable acrylic resin solution for which the resin film was prepared.

(Antibacterial against Staphylococcus aureus)
As shown in FIG. 16, the viable number of Staphylococcus aureus increased about 4-fold in the sample (control) not containing TOP-Ag (MBISA) 24 hours after inoculation.
On the other hand, in the resin film having a TOP-Ag (MBISA) concentration of 0.3 wt%, the viable cell count was reduced to 1% or less as compared with the time of inoculation. Usually, if the viable cell count 24 hours after inoculation is 1/100, it is recognized as having antibacterial activity. Therefore, it was confirmed that TOP-Ag (MBISA) exhibits antibacterial activity against Staphylococcus aureus at a concentration of 0.3 wt% or more.
Furthermore, in the resin film having a TOP-Ag (MBISA) concentration of 1 wt% or more, the viable cell count decreased to below the detection limit 24 hours after inoculation. In other words, it was confirmed that TOP-Ag (MBISA) shows bactericidal activity against Staphylococcus aureus at a concentration of 1 wt% or more.

(Antibacterial against Klebsiella pneumoniae)
As shown in FIG. 17, the viable cell count of Klebsiella pneumoniae increased about 10-fold in the sample (control) not containing TOP-Ag (MBISA) 24 hours after inoculation.
On the other hand, with resin films having TOP-Ag (MBISA) concentrations of 0.3 wt%, 1 wt%, and 3 wt%, the viable cell count decreased to below the detection limit 24 hours after inoculation. In other words, it was confirmed that TOP-Ag (MBISA) shows bactericidal activity against Klebsiella pneumoniae at a concentration of 0.3 wt% or more.

(2) Antibacterial test of TOP-Ag (MPS) and TBP-Ag (MPS) (Staphylococcus aureus)
As the sample for the antibacterial test, a glass plate coated with a resin film containing an antibacterial agent was used. Specifically, a PVOH-based resin solution containing TOP-Ag (MPS) and TBP-Ag (MPS) was prepared according to the procedure described in Example 6, and applied to a glass plate to apply a sample (antibacterial agent coating). Glass plate) was prepared.
For comparison, a sample (comparative glass plate) in which a PVOH-based resin solution was prepared using a commercially available silver-based antibacterial agent (silver zeolite) in the same procedure as described in Example 6 and applied to a glass plate. Prepared.
In addition, a sample (control glass plate) in which a PVOH-based resin solution containing no antibacterial agent was applied to a glass plate was also prepared.

Staphylococcus aureus NBRC 12732 is cultured in 5 mL of ordinary bouillon medium (Eiken Kagaku Co., Ltd.) with shaking at 27 ° C overnight, and then in sterile water containing 1/50 of the final concentration of ordinary bouillon medium. Diluted. Test pieces (antibacterial agent-coated glass plate, comparison glass plate, and control glass plate) were placed in the petri dish, respectively, and 0.4 mL of the bacterial suspension was placed on the test pieces. After covering this bacterial suspension with a polyethylene sheet (4 cm × 4 cm), the petri dish was covered and left at 30 ° C. After 24 hours, the bacterial suspension on the test piece was collected in 4.5 mL sterile physiological saline and diluted 10-fold in 4 steps. The viable cell count in 1 mL of the diluent was measured.

The obtained viable cell count was substituted into the following formula to determine the antibacterial activity value. The higher the antibacterial activity, the better the antibacterial property.

Antibacterial activity value = log (A / B)
here,
A: Viable cell count after 24-hour culture of unprocessed product (glass plate for blank)
B: Viable cell count after 24-hour culture of antibacterial processed products (antibacterial agent-coated glass plate, comparative glass plate).

The antibacterial activity values of each sample are summarized in FIGS. 18 and 19.
FIG. 18 shows the antibacterial property of the sample having an antibacterial agent concentration of 0.05 wt% in the PVOH-based resin solution in which the resin film was prepared, and FIG. 19 shows the antibacterial property of the sample having an antibacterial agent concentration of 0.2 wt%. ing.
Hydrophobic TOP-Ag (MPS) has an excellent antibacterial activity value of 2.0 or more (kill rate of 99% or more) at both antibacterial agent concentrations of 0.05 wt% (Fig. 18) and 0.2 wt% (Fig. 19). It showed antibacterial properties. From this, it was confirmed that TOP-Ag (MPS) exhibits antibacterial activity against Staphylococcus aureus at a concentration of 0.05 wt%.
It was also found that TOP-Ag (MPS) exerts a higher antibacterial effect than commercially available silver-based antibacterial agents at any concentration.

Hydrophilic TBP-Ag (MPS) has antibacterial properties, but it was found to have lower antibacterial properties than TOP-Ag (MPS) because of its low solubility in the hydrophobic lipid membrane on the bacterial surface. ..

The present invention relates to, for example, medical equipment, baby products, nursing care products, bath products, kitchen products, tableware, drinking water piping parts, household hygiene products, home appliances, clothing, building materials, agricultural materials, automobile interior parts, etc. It can be used to impart antibacterial properties to various products such as stationery.

Claims (9)

It contains a silver ion, a ligand bound to the silver ion, and an organic compound bonded to the ligand.
The ligand has a thiol group and an acidic functional group.
The organic compound is an antibacterial agent that is a quaternary phosphonium ion. The antibacterial agent according to claim 1, wherein the acidic functional group of the ligand is a sulfonic acid group. The antibacterial agent according to claim 1 or 2, wherein the ligand is an aliphatic thiolsulfonate ion. Claims 1 to claim 1, wherein the ligand comprises at least one selected from 2-mercaptoethanesulfonate ion, 2-mercapto-5-benzimidazole sulfonate ion, and 3-mercapto-1-propanesulfonate ion. The antibacterial agent according to any one of 3. The organic compound is any of claims 1 to 4, which is an aliphatic quaternary phosphonium ion containing an alkyl group _{having C 4 to} C _{18 carbon atoms or an aromatic quaternary phosphonium ion containing at least one aromatic ring.} The antibacterial agent according to item 1. The quaternary phosphonium ion is tetraethylphosphonium ion, tetrabutylphosphonium ion, tetraoctylphosphonium ion, tributyldodecylphosphonium ion, tributylhexadecylphosphonium ion, tributyl-n-octylphosphonium ion, tetraphenylphosphonium ion, benzyltriphenylphosphonium. The antibacterial agent according to any one of claims 1 to 5, selected from the group consisting of an ion, a methyltriphenylphosphonium ion, an amyltriphenylphosphonium ion, and a hexyltriphenylphosphonium ion. A step of synthesizing a silver ion complex containing a silver ion and a ligand bound to the silver ion,
Including a step of reacting the silver ion complex with the organic compound in order to bond the ligand and the organic compound.
The ligand has a thiol group and an acidic functional group.
A method for producing an antibacterial agent, wherein the organic compound is a quaternary phosphonium ion. The organic compound is an aliphatic quaternary phosphonium ion.
The alkyl group contained in the aliphatic quaternary phosphonium salt has C _{4 to} C ₆ carbon atoms.
The production method according to claim 7, further comprising a step of solidifying the reactant from the aqueous solution layer after the step of reacting. The organic compound is an _{aliphatic quaternary phosphonium ion containing at least one alkyl group having C 7 to} C ₁₈ carbon atoms, or an aromatic quaternary phosphonium ion containing at least one aromatic ring.
The production method according to claim 7, further comprising a step of extracting the reaction product into an organic solvent layer after the step of reacting.

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