JP2000016905A - Antibacterial-fungal agent and antibacterial-fungal material - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject agent having a wide range of antibacterial-fungal activity and high safety e.g. in terms of cutaneous irritation by including a compound formed by binding an amino acid to silver ion as an active ingredient. SOLUTION: This agent includes a compound, as an active ingredient, formed by binding (A) an amino acid (histidine, alanine, glycine, leucine, phenylalanine, glutamic acid, aspartic acid or the like or a derivative thereof or the like) to (B) silver ion. The compound is obtained by reacting the component (A) with the component (B) in a solution and precipitating a solid by treating the resultant solution with an organic solvent, such as IPA or acetone. It is preferable that about 0.5-2 mol(s) of the component A is added to 1 mol of the component B to conduct the reaction. The compound can be used as an antibacterial antifungal agent as it is and furthermore, can be used as an antibacterial-fungal material or an antibacterial-fungal composition by being carried by various carriers (solid carriers, liquid carriers, mixtures thereof or the like).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antifungal agent having a wide range of antibacterial and antifungal activities and having high safety such as skin irritation, and an antibacterial antifungal material using the same.

[0002]

2. Description of the Related Art In recent years, a functional material having a new function by applying a drug having an antibacterial and antifungal activity to various living-related materials has been actively developed and used. These functional materials are provided with new functions by adding a drug having an antibacterial and antifungal activity to the materials.

[0003] In the application of antibacterial and antifungal agents to the field of these functional materials, the drugs are required to have a broad antibacterial spectrum and safety, and the drugs adversely affect the quality of the materials. It is required that they have no properties, that they have excellent durability, residual effects, and economic efficiency. Therefore, the drugs used in antibacterial antifungal agents so far include benzimidazole, nitrile, isothiazoline, haloallylsulfone, iodopropargyl, benzothiazole, phenol, organotin,
Pyridine, diphenyl ether and chlorhexidine are mentioned.

[0004]

Many of such antibacterial and antifungal agents do not show a sufficient antibacterial and antifungal effect with only one kind of agent. In addition, even if the drug itself has excellent antibacterial and antifungal activity, a problem arises in compatibility with the material, and it does not always show a sufficient antibacterial and antifungal effect after application to the material.

Further, regarding the safety of these antibacterial and antifungal agents, many of them show acute oral toxicity, skin irritation, mucous membrane irritation and the like. Strongly, there were problems in applying such antibacterial antifungal agents to living environments.

[0006]

SUMMARY OF THE INVENTION The present invention is an antibacterial / antifungal agent comprising an amino acid and a silver ion bonded to each other, and an antibacterial / antifungal material having the compound supported on a solid carrier or a liquid carrier. In this compound, it is considered that the ligand of the amino acid is coordinated to silver to form a complex, or the amino acid and silver form a salt.

The above compound is produced by reacting an amino acid with silver ions in a solution, and precipitating the resulting solution with an organic solvent such as IPA or acetone to precipitate a solid.
In the reaction, for example, an amino acid is added in an amount of 0.
The reaction is carried out by adding about 5 to 2 mol.
The amino acids used are histidine, alanine, glycine, leucine, isoleucine, phenylalanine, valine, aspartic acid, glutamic acid, serine, threonine, tyrosine, arginine, asparagine, glutamine, lysine, tryptophan, proline and the like, and derivatives thereof. .

As the silver ion to be used, a silver compound which can react with the amino acid to be used can be used without limitation.
Specific examples include silver nitrate, silver nitrite, silver perchlorate, silver acetate, and silver borofluoride. Further, as a solvent used for producing the compound, a known solvent can be used without limitation as long as it dissolves the above-mentioned silver ion and / or amino acid. Specifically, for example, water, an aqueous solution of an alkali metal hydroxide such as sodium hydroxide, lithium hydroxide, potassium hydroxide or cesium hydroxide, alcohols such as methanol, ethanol or IPA, benzene, toluene, xylene, hexane Or hydrocarbons such as cyclohexane, ethers such as diethyl ether, ketones such as acetone, and the like,
It can be used alone or in combination.

The compound thus obtained has an excellent antibacterial and antifungal activity and can be used as it is as an antibacterial and antifungal agent. Object or the like. Therefore, as the carrier used in this manner, any of a solid carrier, a liquid carrier, and a mixture thereof can be used.

Examples of the solid carrier include an inorganic solid carrier and an organic solid carrier. Examples of the inorganic solid carrier include silica, hydroxyapatite, zeolite, and titanium oxide. In the composition containing the inorganic solid carrier and the compound of the present invention, the compound of the present invention is preferably immobilized on the solid carrier. Such an antibacterial and antifungal material containing the inorganic solid carrier and the compound of the present invention has an antibacterial activity due to a substitution reaction of silver in the presence of a salt, which is a drawback of existing silver-containing antibacterial agents represented by zeolite-silver, for example. No decrease, no discoloration by silver ion light, etc.

[0011] Organic solid carriers include waxes such as waxes, varnishes, lacquers, and synthetic resin paints, polyethylene, polyvinyl chloride, polystyrene, polyethylene terephthalate, acrylic resins, epoxy resins, phenolic resins, melamine resins, and the like. A resin such as a urea resin is exemplified. Examples of the liquid carrier include organic solvents such as water, alcohols, hydrocarbons, ethers, and ketones.

The compounding amount of the compound of the present invention in the antibacterial antifungal agent or the material of the present invention is not particularly limited.
1-90% by weight is preferred.

[0013]

Embodiments of the present invention will be described below. First Embodiment 3.40 g (20 mmol) of silver nitrate is dissolved in 50 ml of water (solution A). 3.20 g of L-histidine (21 mm
ol) and 0.90 g (22 mmol) of sodium hydroxide
Is dissolved in 20 ml of water (solution B).

The solution A is stirred, and the solution B is gradually added. The obtained solution was dropped into 1,000 ml of acetone under stirring to obtain 5.80 g of a white precipitate. For this compound, formation of an L-histidine-silver compound was confirmed by FT-IR analysis. Second Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A).

1.78 g (20 mmol) of L-alanine
And 0.80 g (20 mmol) of sodium hydroxide in water 1
Dissolve in 0 ml (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution is stirred 10
It was dropped into 00 ml of acetone to obtain 2.50 g of a white precipitate. For this compound, formation of an L-alanine-silver compound was confirmed by FT-IR analysis.

Third Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 1.50 g of L-glycine (20 mmo
l) and 0.80 g (20 mmol) of sodium hydroxide are dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The obtained solution was dropped into 1000 ml of acetone under stirring to obtain 2.42 g of a white precipitate.

For this compound, formation of an L-glycine-silver compound was confirmed by FT-IR analysis. Fourth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 2.62 g of L-leucine (20 mmo
l) and 0.80 g (20 mmol) of sodium hydroxide are dissolved in 10 ml of water (solution B).

The solution A is stirred, and the solution B is gradually added. The resulting solution was dropped into 1000 ml of stirring acetone to obtain 3.44 g of a white precipitate. For this compound, formation of an L-leucine-silver compound was confirmed by FT-IR analysis. Fifth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A).

2.62 g of L (+)-isoleucine (20
mmol) and 0.80 g (20 mmol) of sodium hydroxide.
1) is dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone, and 3.53 g was added.
A white precipitate was obtained. This compound was identified as L
Formation of (+)-isoleucine-silver compound was confirmed.

Sixth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 3.30 g of L (-)-phenylalanine
(20 mmol) and 0.80 g of sodium hydroxide (20
mmol) in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. 2. The resulting solution was added dropwise to 1000 ml of stirring acetone, and
96 g of a white precipitate was obtained.

This compound was found to have L (-) by FT-IR analysis.
-The formation of a phenylalanine-silver compound was confirmed. Seventh Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 2.34 g (20 mmol) of L-valine
And 0.80 g (20 mmol) of sodium hydroxide in water 1
Dissolve in 0 ml (solution B).

The solution A is stirred, and the solution B is gradually added. The resulting solution was dropped into 1000 ml of stirring acetone to obtain 3.10 g of a white precipitate. For this compound, formation of an L-valine-silver compound was confirmed by FT-IR analysis. Eighth Embodiment 3.40 g (10 mmol) of silver nitrate is dissolved in 20 ml of water (solution A).

5.32 g (40 mm) of L-aspartic acid
ol) and 3.20 g (80 mmol) of sodium hydroxide
Is dissolved in 20 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone to obtain 8.10 g of a white precipitate. This compound was confirmed to be L-aspartic acid-silver compound by FT-IR analysis.

Ninth Embodiment 3.40 g (20 mmol) of silver nitrate is dissolved in 20 ml of water (solution A). 5.88 g of L-glutamic acid (40 m
mol) and sodium hydroxide 3.20 g 780 mmo
1) is dissolved in 20 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone, and 8.49 g of acetone was added.
A white precipitate was obtained.

For this compound, formation of an L-glutamic acid-silver compound was confirmed by FT-IR analysis. Tenth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 2.10 g (20 mmol) of L-serine
And 0.80 g (20 mmol) of sodium hydroxide in water 1
Dissolve in 0 ml (solution B).

The solution A is stirred, and the solution B is gradually added. The resulting solution was dropped into 1000 ml of stirring acetone to obtain 3.48 g of a white precipitate. For this compound, formation of an L-serine-silver compound was confirmed by FT-IR analysis. Eleventh Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A).

2.38 g of L (-)-threonine (20 m
mol) and 0.80 g of sodium hydroxide (20 mmo
1) is dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone, and 3.71 g of acetone was added.
A white precipitate was obtained. This compound was identified as L
Formation of the (-)-threonine-silver compound was confirmed.

Twelfth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 3.62 g of L-tyrosine (20 mmo
l) and 0.80 g (20 mmol) of sodium hydroxide are dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The obtained solution was dropped into 1000 ml of acetone under stirring to obtain 4.74 g of a white precipitate.

This compound was confirmed by FT-IR analysis to form an L-tyrosine-silver compound. Thirteenth Embodiment 3.40 g (20 mmol) of silver nitrate is dissolved in 20 ml of water (solution A). 6.97 g of L (+)-arginine (4
0 mmol) and 1.60 g (40 mm) of sodium hydroxide.
ol) in 20 ml of water (solution B).

The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone to obtain 7.52 g of a yellow precipitate. For this compound, formation of an L (+)-arginine-silver compound was confirmed by FT-IR analysis. Fourteenth Embodiment 3.40 g (20 mmol) of silver nitrate is dissolved in 20 ml of water (solution A).

L-asparagine hydrate 6.01 g (4
0 mmol) and 1.60 g (40 mm) of sodium hydroxide.
ol) in 20 ml of water (solution B). Solution A above
And slowly add solution B. The resulting solution was added dropwise to 1000 ml of acetone with stirring, and 8.16
g of a yellow precipitate were obtained. For this compound, formation of an L-asparagine-silver compound was confirmed by FT-IR analysis.

Fifteenth Embodiment 3.40 g (20 mmol) of silver nitrate is dissolved in 20 ml of water (solution A). 5.85 g of L (+)-glutamine (4
0 mmol) and 1.60 g (40 mm) of sodium hydroxide.
ol) in 20 ml of water (solution B). Solution A above
And slowly add solution B. The resulting solution was dropped into 1000 ml of stirring acetone, and 8.02
g of a yellow precipitate were obtained.

This compound was identified as L (+) by FT-IR analysis.
-The formation of a glutamine-silver compound was confirmed. Sixteenth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 3.65 g (20 mmol) of L-lysine
And 0.80 g (20 mmol) of sodium hydroxide in water 1
Dissolve in 0 ml (solution B).

The solution A is stirred, and the solution B is gradually added. The resulting solution was added dropwise to 1000 ml of stirring acetone to obtain 4.40 g of a yellow precipitate. For this compound, formation of an L-lysine-silver compound was confirmed by FT-IR analysis. Seventeenth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A).

L-tryptophan 4.08 g (20 mm
ol) and 0.80 g (20 mmol) of sodium hydroxide
Is dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was dropped into 1000 ml of stirring acetone to obtain 4.21 g of a yellow precipitate. For this compound, formation of an L-tryptophan-silver compound was confirmed by FT-IR analysis.

Eighteenth Embodiment 1.70 g (10 mmol) of silver nitrate is dissolved in 5 ml of water (solution A). 2.30 g of L (-)-proline (20 m
mol) is dissolved in 10 ml of water (solution B). The solution A is stirred, and the solution B is gradually added. The resulting solution was dropped into 1000 ml of stirring acetone, and 3.2
0 g of a white precipitate was obtained.

This compound was analyzed by FT-IR analysis to obtain L (-)
-The formation of a proline-silver compound was confirmed. The antibacterial property of the silver compound obtained as described above was confirmed by the following method. Bacteria: Soybean Casein Digest (SCD)
Inoculate 5 ml of liquid medium, pre-culture at 35 ° C for 24 hours,
0.1 ml of a 100-fold diluted solution of the precultured bacterial solution was inoculated into an SCD medium containing 2 ml of a specimen. After shaking culture at 35 ° C. for 72 hours, the presence or absence of proliferation was confirmed.

Yeast: Inoculated into 5 ml of glucose / peptone (GP) liquid medium, pre-cultured at 35 ° C. for 24 hours, and inoculated with 0.1 ml of a 100-fold dilution of the pre-cultured bacterial liquid into a GP medium containing 2 ml of a sample. did. After shaking culture at 35 ° C. for 72 hours, the presence or absence of proliferation was confirmed. Mold: Inoculated on a glucose / peptone (GP) agar medium, pre-cultured at 24 ° C. for 1 week, and 0.1 ml of the pre-cultured spore suspension was inoculated on a GP agar medium containing 2 ml of a specimen. After shaking culture at 24 ° C. for 168 hours, the presence or absence of proliferation was confirmed.

The antibacterial activity was measured for the following bacterial species. Fungi 1. 1. Candida albicans (Candida albicans) Aureobasidium pullulans
(Aureobasidium pull lance) 3. Aspergillus niger 4. Pharma glomerata Alternaria dianticola
(Alternaria di Anticora) 6. Trichoderma 7. Penicillium citrinum 8. Chaetomium globosum Cladosporium sphaerospe
rmum (Cladosporium suylospermum) 10. 10. Fusarium moniliforme Bacteria 11. Escherichia coli (Escherichia coli) 12. Staphylococcus aureus
(Staphylococcus aureus) 13. Pseudomonas aeruginosa
(Pseudomonas alginosa) The results are shown in Table 1.

[0040]

[Table 1]

[0041]

According to the present invention described in detail above, an antibacterial and antifungal agent is constituted as a compound obtained by combining an amino acid and silver ion, so that this compound can be used as an inorganic or organic solid carrier or liquid carrier. It has the effect of being able to be carried and not having any adverse effect on these carriers.

Further, it has excellent antibacterial and antifungal effects, excellent weather resistance, heat resistance, water resistance, and strength, and has excellent effects on the human body, as well as durability, residual effects, and economy. It is also effective against antibiotic-resistant bacteria.

Claims (3)

[Claims] 1. An antibacterial and antifungal agent comprising a compound comprising an amino acid and silver ion as an active ingredient. 2. An antibacterial and antifungal material comprising a solid carrier carrying a compound comprising an amino acid and silver ion. 3. An antibacterial and antifungal material comprising a liquid carrier carrying a compound comprising an amino acid and silver ions.