JP2847529B2 - Method for improving antibacterial property of silver-containing compound - Google Patents

Description

The present invention relates to a method for improving the antibacterial property of a silver-containing compound and an antibacterial agent utilizing the method. By using the method and the antibacterial agent of the present invention, it is possible to provide a drug and an antibacterial polymer having excellent antibacterial properties.

[Conventional technology]

It has long been known that silver is a metal having antibacterial properties. So, in order to use this effect more effectively,
It is also known that the antibacterial property is maintained for a long period of time by being retained in the form of silver ions in an aluminosilicate or an ion exchange resin (JP-A-60-181002, JP-A-58-156074). Furthermore, various antibacterial molded articles can be provided by kneading the aluminosilicate holding silver ions into a polymer to prepare an antibacterial polymer (JP-A-61-138658).

[Problems to be solved by the invention]

However, the antibacterial effect of silver varies depending on the amount of silver ions contained.
About 500 ppm. This MIC value is considerably larger than the MIC value of a conventionally known antibiotic of 1 to 10 ppm. Therefore, when kneading silver or a silver compound into a polymer to obtain an antibacterial polymer, it is necessary to add about 0.4 to 5% by weight, which is not efficient.

Accordingly, an object of the present invention is to provide a method for improving the antibacterial activity of silver or a silver compound to an antibacterial effect substantially equivalent to that of an antibiotic, and an antibacterial agent using this method.

[Means for solving the problem]

The present inventors have intensively studied the energy metabolism of microorganisms and the behavior of silver ions at the cell level. As a result, they have found that the coexistence of the phosphoric acid-containing compound with the silver-containing compound can provide a higher antibacterial property than the silver-containing compound originally has, and completed the present invention.

Therefore, the present invention relates to a method for improving the antibacterial property of a silver-containing compound, wherein the phosphoric acid-containing compound is allowed to coexist with the silver-containing compound.

Further, the present invention provides an antibacterial agent containing a silver-containing compound and a phosphoric acid-containing compound and an antibacterial agent containing a compound containing silver and phosphoric acid.

 Hereinafter, the present invention will be described in detail.

In the present invention, the silver-containing compound may be silver nitrate, silver sulfate, silver perchlorate, silver acetate, a complex salt containing silver such as silver chloride, diamine silver nitrate, or diammine silver sulfate; silver-supported activated carbon; silver-supported zeolite; Examples of the carrier include silver ion-supported carriers such as aluminosilicates, silver-containing glasses, silver-containing solid solutions, silver clusters, silver alloys, metallic silver, and silver-containing minerals.

On the other hand, the phosphoric acid-containing compound is orthophosphoric acid, metaphosphoric acid, pyrophosphoric acid, phosphoric anhydride, sodium hydrogen phosphate,
Inorganic phosphate compounds such as potassium phosphate, calcium phosphate, ammonium phosphate, magnesium ammonium phosphate, sodium tripolyphosphate, sodium hexametaphosphate, sodium phosphotungstate, ammonium phosphomolybdate, -n-tributyl phosphate, tricresyl phosphate, Triphenyl phosphate, glucose-1-
Phosphoric acid, triethyl phosphate, trimethyl phosphate, tributyl phosphate, ethyl acid phosphate, dialkyl dithiophosphoric acid, trimethyl phosphite, thiophosphate, glucose-6-phosphate,
An organic phosphate compound such as D-fructose-6-phosphate,
Phosphatidylcholine (lecithin), plasmalogen,
Examples include phospholipids such as ether lipids and cardiolipin.

In the method and the antibacterial agent of the present invention, an antibacterial agent which is excellent in coexistence or incorporation of 1 to 50, preferably 1 to 10 phosphoric acid-containing compounds as phosphorus with respect to 1 as a silver-containing compound in terms of silver by weight is excellent. It is desirable from the viewpoint of obtaining the effect.

Further, the compounds containing silver and phosphoric acid used in the present invention include silver phosphate (Ag ₃ PO ₄ ), silver pyrophosphate (Ag ₄ P
₂ O ₇ ), silver metaphosphate (AgPO ₃ ), silver uranyl phosphate (Ag
UO ₂ PO ₄ ), silver hydrogen phosphate (Ag ₂ HPO ₄ ), ammonium silver phosphate (Ag ₂ (NH ₄ ) PO ₄ ), silver phosphotungstate (Ag
₆ [(PO ₄ W ₉ O ₂₇ ) ₂ ]), silver phosphomolybdate (Ag ₆ [(PO ₄
Mo ₉ O ₂₇ )] _{2 and the} like, among which silver phosphate, silver pyrophosphate and ammonium silver phosphate are preferred.

The antimicrobial properties of the method and the antibacterial agent of the present invention are different in various environments, but the MIC value is about 30 ppm of silver. further,
In any case, about 100 ppm can provide a sufficient effect.

It is considered that the method of the present invention is effective because phosphate ions efficiently take in silver ions having antibacterial properties into cells, but it is not limited to such a theory.

The form of the antibacterial agent of the present invention includes liquids, emulsions, suspensions and other powders, gels, granules, papers, pellets, sheets, films and other molded products, sprays, porous materials, fibrous materials, and the like. Non-woven fabric, foam sheet,
It can also be in the form of a combination with a support such as paper, plastic, or an inorganic plate.

The method and antibacterial agent of the present invention can be used in various fields such as pharmaceuticals and antibacterial polymers. For example, it can be used in the fields of medicine, agriculture, forestry and fisheries, cosmetics, food processing, textile and clothing, bedding, construction materials, ships, electronics, water treatment, and the like. In the medical field, external disinfectants in various forms such as ointments, gels, oily suspensions, emulsions, etc., and medical environmental disinfectants for non-humans such as catheters, forceps, linens, measuring instruments, etc .; Disinfectants for pathogens, livestock disinfectants, fishing net antifouling agents for livestock, cosmetics in the cosmetics field, cosmetic preservatives, hair cleaners; food processing in the food processing equipment, working clothes, plastic packaging, food packaging materials such as paper, food preservation Materials: Sanitary processing socks, training garments, hospital garments, surgical gowns in the textile clothing field, bed covers, sheets, futons, blankets in the bedding field, paints for walls and floors, adhesives, furniture linings, showers in the building materials field Curtains: Ships: Ship bottom paints, anti-algae paints for underwater structures; Electronic industry: Electronic component packaging materials, chemical disinfectants for electronic industry; Water treatment: water and sewage disinfectants, water purifiers, cold air fans, cooling towers , Piping, filtration membrane, fill Chromatography, slime control agent of the packing are preferably used for the water-soluble metalworking fluid preservatives and the like.

Examples of the polymer that can be an antibacterial polymer using the method and the antibacterial agent of the present invention include polyethylene,
Polypropylene, vinyl chloride resin, ABS resin, nylon, polyester, polyvinylidene chloride, polystyrene, polyacetal, polycarbonate, acrylic resin, fluorine resin, polyurethane elastomer, polyester elastomer, phenol resin, urea resin, melamine resin, unsaturated polyester resin, epoxy Thermoplastic or thermosetting resins such as resins, urethane resins, natural and synthetic rubbers can be mentioned. The amount of the antimicrobial agent added is 0.01 to 3% by weight relative to the polymer, preferably
It is appropriate to set it to 0.05 to 0.5%.

When the method and the antibacterial agent of the present invention are used as pharmaceuticals, it is appropriate to match the known use form of the silver-containing compound as a main component. For example, oral administration, transdermal administration,
Enteral administration and the like can be mentioned. In particular, an external preparation can be an aqueous solution or a solution of alcohol or glycerin, an ointment, a cream or a cataplasm.

The microorganisms which are effective by the method and the antibacterial agent of the present invention are those in which a silver-containing compound inherently exerts antibacterial properties. For example, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus (Staphyloccocus aureus), Streptococcus faecals (Streptococcus faecal)
is), Vibrio parahedicus
aemdyticus), Candida albicans (Candida al
bicans), Aspergillus flava (Aspergillus fl)
avas), Penicillium citrnum
inum), Trichoderma virid
e), Propionibacteriu
m), Chlamydia trachom
atis), bacteria, fungi (mold), yeast, actinomycetes,
Most microorganisms such as rickettsia and viruses are included.

〔The invention's effect〕

The method and antibacterial agent of the present invention improve the intrinsic antibacterial property of the silver-containing compound, and can provide almost the same antibacterial effect as an antibiotic. As a result, the method and antibacterial agent of the present invention can be used for pharmaceuticals, antibacterial polymers, and the like.

〔Example〕

 Next, the present invention will be described with reference to examples.

Example 1 (Preparation of antibacterial agent) Various antibacterial agents were prepared by mixing a silver-containing compound, a phosphoric acid-containing compound, a carrier, a medium, and the like. Table 1 shows the compounding ratio. No. 1-1 to 1-4 in Table 1 mixed each liquid. No.1-5-1
-8 was obtained by reacting a carrier with a silver nitrate solution, carrying silver, and drying and mixing a phosphoric acid compound. No.1-9 is 1
The silver-supported zeolite prepared in -8 was further blended. N
o.1-10 is silver 2% prepared in accordance with JP-B-46-28099.
The glass containing No. 1-11 is silver 0 from Hishikari mine, Kagoshima Prefecture.
Each ore containing 05% was mixed. As a comparative example, an example containing no phosphoric acid compound was also prepared.

Example 2 (Molding of antibacterial agent-containing polymer) The antibacterial agent (powder) prepared in Example 1 was blended with various polymers, and a prototype plate (60 × 35 × 2 mm) was injected with an injection molding machine.
It was created. Table 2 shows the mixing ratio and molding conditions.

Example 3 (Preparation of antibacterial agent spray) Phenyl alcohol suspension 80 prepared in Experiment No. 1-9
ml was sealed in a metal spray can along with freon gas to make an antimicrobial spray. As a comparative example, a spray containing no antibacterial agent was also prepared.

Example 4 (Preparation of antimicrobial ointment) The antimicrobial agents prepared in Experiment Nos. 1-6 and 1-8 were added to the following ointment components to prepare external ointments. Ointment was added to 80 ° C water with a well-mixed suspension of antibacterial agent and glycerin, and further heated to 70 ° C for sitosteryl alcohol,
White petrolatum and liquid paraffin were added to make it.
An ointment containing no antibacterial agent was also prepared as a comparative example.

(Ointment formulation) Liquid paraffin 10 parts Sitosteryl alcohol 5 parts White petrolatum 20 parts Glycerin 15 parts Water 50 parts Antibacterial agent 1 part Test example 1 (MIC measurement test) Antimicrobial effect of the antimicrobial agent prepared in Example 1 was measured by MIC evaluated. The assay was performed using Pseudomonas aeruginosa IID P-
1. Aspergillus niger IFO
4407, Candida albican
s) Three types of IFO 1594 were used. Prepare a dilution step suspension of each antibacterial agent with sterile purified water, dissolve this in a culture medium for sensitivity measurement at 50-60 ° C, add 1/9 of the medium, mix well, and dispense into petri dishes, It was solidified to obtain a plate for sensitivity measurement. The sensitivity measurement medium is Mueller Hinton M for bacteria.
An edium medium and a Sabouraud agar medium were used for fungi and yeasts, respectively. The inoculum was adjusted to 10 ⁶ / ml. The inoculum is smeared linearly at intervals of 2 cm with a platinum loop on a plate for sensitivity measurement, bacteria are 37 ° C, 20 hours, fungi and yeast are
The cells were cultured at 25 ° C for 7 days. Judgment was made by measuring the change in the number of bacteria after culturing, and the concentration in a state where the number was reduced by 10 ² or more from the initial number of bacteria was defined as MIC. Table 3 shows the results. Comparative Examples 1 to 3 and an antibiotic (Streptomycin, manufactured by Sankyo; Comparative Example 4) were similarly tested.

Test Example 2 (Antibacterial test of polymer molded article) The polymer formed in Example 2 was cut into 50 x 50 mm, and the Escherichia coli count (10 ⁵
/ Ml) and Pseudomonas aeruginosa (Pseudomon
as aeruginosa) (10 ⁵ cells / ml) was dropped onto each of 15 ml and cultured at 37 ° C for 18 hours. The bacterial solution was washed away with physiological saline, and the number of Escherichia coli and the number of Pseudomonas aeruginosa present in this solution were measured. Table 2 shows the results. Generally, when the number of bacteria after 18 hours is reduced by two digits or more due to the added initial number of bacteria, it can be said that the bacteria have antibacterial properties.

Test Example 3 (Antibacterial test of antibacterial agent spray) An antibacterial test was performed on the antibacterial agent spray prepared in Example 3. As a test sample, the same spray was sprayed on a cotton cloth for 3 seconds and dried at 60 ° C. for 1 hour. The following operation was performed in the same manner as in Test Example 2. Table 4 shows the results
Shown in

Test Example 4 (Antimicrobial test of antimicrobial ointment) An antimicrobial test was performed on the antimicrobial ointment prepared in Example 4. As a test product, a product obtained by applying the same ointment to a cotton cloth at 10 g / m ² was prepared. The following operation was performed in the same manner as in Test Example 2. Table 5 shows the results.

Example 5 With respect to aqueous solutions of silver nitrate and disodium hydrogen phosphate at various concentrations, the dissolution concentrations (elution amounts) of silver and phosphorus and the antibacterial activity against Escherichia coli were determined. Table 6 shows the results. From the results in Table 6, in the system using silver nitrate, which is a water-soluble silver salt, by allowing disodium hydrogen phosphate to coexist,
The same effect was obtained with an addition amount of about 1/5000 of the silver salt (comparison between No. 7 and No. 13). In addition, in the presence of phosphate, antimicrobial properties appeared when the amount of silver eluted was 0.053 ppm (see No. 8).

Example 6 With respect to phenyl alcohol solutions of various concentrations of silver-supported (10%) zeolite and sodium phosphate, the dissolution concentrations of silver and phosphorus (elution amount) and antibacterial activity against Escherichia coli were determined. Table 7 shows the results. From the results shown in Table 7, even in a system using phenyl alcohol having low solubility of silver ions and phosphate ions, the same effect can be obtained by adding sodium phosphate in an amount of about 1/1000 of the silver salt. (Comparison between No.3 and No.15). In the presence of phosphate,
The antibacterial properties appeared when the amount of silver eluted was 0.070 to 0.10 ppm (see Nos. 8 and 11). In addition, the ratio of phosphate to silver is 1:
It is understood that the effect is effective in the range of 1 (No. 12) to 1:50 (No. 9).

Example 7 With respect to aqueous solutions of silver chloride and calcium phosphate having various concentrations, the dissolution concentrations (elution amounts) of silver and phosphorus and the antibacterial activity against Escherichia coli were determined. Table 8 shows the results. From the results shown in Table 8, in the system using silver chloride, which is a water-insoluble silver salt, the same effect was obtained with the addition of about 1 / 100,000 silver salt by coexisting calcium phosphate (No. 7 and No. 7). No.12
And comparison). Also, in the presence of phosphate, the amount of silver eluted
From 0.068 ppm (see No. 8), antibacterial properties appeared.

──────────────────────────────────────────────────続 き Continuation of front page (72) Inventor Yasuo Kurihara 3-35, Toyooka-dori, Mizuho-ku, Nagoya-shi, Aichi (56) References JP-A-63-88109 (JP, A) JP-A-63-170497 ( JP, A) JP-A-59-231006 (JP, A) JP-A-2-96508 (JP, A) JP-A-4-503018 (JP, A) JP-A-2-306904 (JP, A) (58) 6) Fields surveyed (Int. Cl. ⁶ , DB name) A01N 59/16 A01N 59/26 CA (STN) REGISTRY (STN) WPIDS (STN)

Claims (2)

(57) [Claims] 1. A method for improving the antibacterial property of a silver-containing compound, comprising at least one selected from the group consisting of diamine silver nitrate, diamine silver sulfate, silver-supported zeolite, and silver-supported amorphous aluminosilicate. A silver-containing compound, metaphosphate, sodium phosphate, potassium phosphate, ammonium phosphate, sodium hydrogenphosphate, disodium hydrogenphosphate, sodium tripolyphosphate, triphenyl phosphate, D-fructose-6-phosphate, and A method comprising coexisting at least one phosphorus-containing compound selected from the group consisting of phosphatidylcholines. 2. At least one silver-containing compound selected from the group consisting of diamine silver nitrate, diamine silver sulfate, silver-supported zeolite, and silver-supported amorphous aluminosilicate, metaphosphoric acid, sodium phosphate, phosphoric acid potassium,
At least one selected from the group consisting of ammonium phosphate, sodium hydrogen phosphate, disodium hydrogen phosphate, sodium tripolyphosphate, triphenyl phosphate, D-fructose-6-phosphate, and phosphatidylcholine
An antimicrobial agent containing various phosphorus-containing compounds.