JP2014208606A - Sterilization and/or antiviral compositions - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide sterilization and/or antiviral compositions excellent in prompt effectiveness and sustainability.SOLUTION: A sterilization and/or antiviral composition contains nano particles consisting of a silver halide with a particle diameter of 1 nm or more to 100 nm or less, a halide ion of the same element as a halogen which constitutes the silver halide, and at least one or more water-soluble polymers. And a molar ratio of the silver in the silver halide to the halide ion is 1:1-1:20.

Description

  The present invention relates to silver compound nanoparticles having both high bactericidal and antiviral properties.

  The antibacterial and antibacterial effects of silver have been empirically known since the days of Greece and Rome. In recent years, antibacterial functions have been imparted by dispersing fine particles in paints or kneading them into resins. It is used by adding to paints and resin products. In particular, amine-based antibacterial agents have been widely used for fibers used in clothing and the like, but silver-based antibacterial agents have been used in consideration of health. In addition, various antibacterial products have been flooded, and it has been pointed out that the use of antibacterial agents may cause adverse effects on the human body. It is strongly desired to reduce the amount of

  Recently, infectious diseases caused by viruses such as new influenza and norovirus have also become a problem. In particular, because of the development of traffic, the rate of spread of infection has become much faster than in the past, so the awareness of crisis about the pandemic is very high. Accordingly, various studies have been conducted on the antiviral effect of silver and silver compounds.

  Under such circumstances, for example, a silver colloid having a high bactericidal effect and a medical device coated with the colloid have been reported (Patent Document 1), and a bactericidal and antiviral agent using silver bromide and an iodine complex have been reported. (Patent Document 2).

Japanese Patent Publication No. 2003-529630 Japanese Patent Laid-Open No. 2002-338481

  However, in the case of Patent Document 1, it is considered that the addition amount of the metal salt is preferably excessive as compared with the salt containing an anion. As a result, the synthesized silver-based colloid is in a state where the silver ion is excessive. Become. Since bactericidal properties are proportional to the amount of elution of silver, an excess of silver ions is excellent in immediate effect, but lacks sustainability. Moreover, in patent document 2, since an active ingredient exists as a complex, similarly to patent document 1, it is easily soluble in a dispersion medium and lacks sustainability.

  Therefore, the present invention provides a bactericidal / antiviral composition which is excellent in immediate effect and sustainability.

  That is, according to the first aspect of the present invention, there is provided a nanoparticle made of silver halide having a particle diameter of 1 nm or more and 100 nm or less, a halide ion of the same element as the halogen constituting the silver halide, and at least one water-soluble high And a molar ratio of silver in the silver halide to the halide ion is from 1: 1 to 1:20.

  The second invention is the antibacterial / antiviral composition according to the first invention, further comprising an organic acid having a carboxyl group and / or a salt thereof.

  Furthermore, a third invention is the bactericidal / antiviral composition according to the second invention, wherein the organic acid having a carboxyl group is an oxycarboxylic acid.

  Furthermore, a fourth invention is the bactericidal / antiviral composition according to any one of the first to third inventions, wherein the silver halide is silver iodide.

  It is possible to provide a bactericidal / antiviral composition excellent in immediate effect and sustainability.

2 is a transmission electron microscope image of the bactericidal / antiviral composition obtained in Example 1. FIG.

Hereinafter, embodiments of the bactericidal / antiviral composition of the present invention will be described in detail. The bactericidal / antiviral composition of the present embodiment comprises nanoparticles composed of silver halide (hereinafter referred to as silver halide nanoparticles), halide ions that are the same element as the halogen constituting the silver halide, Functional polymers.
The bactericidal / antiviral composition of the present embodiment can be produced, for example, by mixing a silver salt, a halide, and a water-soluble polymer in a solution. By mixing the silver salt and the halide, the silver salt and the halide react to produce silver halide. The ratio of each component is not particularly limited, but the ratio of silver salt to halide so that the molar ratio of silver to halide ions contained in the produced silver halide is 1: 1 to 1:20 ( It is preferable to set the ratio of silver ions constituting the silver salt to halide ions constituting the halide.

  The antibacterial properties of silver halide have been known for some time and have been developed as various antibacterial compositions, but in this embodiment, those having a particle size of 1 nm or more and 100 nm or less are very small. Available. Further, from the viewpoint of efficiently exhibiting bactericidal properties and antiviral properties even in a small amount, the silver halide nanoparticles are preferably as small as possible. On the other hand, when the particle diameter is 1 nm or less, the stability of the silver halide substance is lowered. Therefore, the grain size of the silver halide nanoparticles is preferably 1 nm or more and 30 nm or less, and more preferably 1 nm or more and 10 nm or less. The particle size can be controlled, for example, by adjusting the ratio of silver ions to halide ions when the silver salt and halide are reacted. Further, these silver halides have low crystallinity, and amorphous crystals having low crystallinity are synthesized by synthesis at low temperature, and nanoparticles having good crystallinity can be obtained by synthesis at high temperature. Any crystal can be used in the present embodiment, and is not particularly limited.

As described above, silver halide nanoparticles can be obtained, for example, by reacting a silver salt with a halide.
Examples of the silver salt include silver nitrate, silver nitrite, silver chlorate, silver perchlorate, silver acetate and silver sulfate, and halides include sodium chloride, potassium chloride, potassium iodide, lithium chloride, copper chloride ( II), silver chloride, chlorine fluoride, and the like. These combinations can be freely selected according to the silver halide to be actually used.

In the preparation of the bactericidal / antiviral composition of the present embodiment, regarding the ratio of the silver salt to the halide, it is desirable that the halide is stoichiometrically excessive with respect to the silver salt. Specifically, silver in the silver halide present in the bactericidal / antiviral composition of the present embodiment and halide ions (halides present as ions in the composition without reacting with silver ions). The molar ratio of silver ions constituting the silver salt and halide ions constituting the halide is preferably set so that the molar ratio of ions) is 1: 1 to 1:20. In particular, in the present embodiment, the larger the difference in molar ratio between silver ions and halide ions, the more preferable are silver halide nanoparticles having a smaller particle diameter.
If the proportion of halide ions is less than 1: 1, all halide ions will react with silver ions in the preparation of the composition, or the amount of halide ions that do not react with silver ions will be too small, The halide ions for forming the electric double layer to be described later are lost or insufficient. On the other hand, when the ratio of halide ions is larger than 1:20, halide ions become excessive and complex with silver is formed.
In this specification, halide ion means fluoride ion (F-), chloride ion (Cl-), bromide ion (Br-), iodide ion (I-), astatine ion (At- ) And the like.
In addition, when preparing the composition includes a step of mixing a silver salt solution and a halide solution, the shorter the contact time between the two solutions, the smaller the silver halide nanoparticles can be obtained. Is preferably performed in as short a time as possible.

  Here, the electric double layer formed around the silver halide nanoparticles in this embodiment will be described. The halide exists as a halide ion in the solution, and reacts with the silver ion formed by dissolving the silver salt in water to produce silver halide nanoparticles. The produced silver halide nanoparticles adsorb excess halide ions present in the solution and have a negative charge, and the adsorbed halide ions adsorb counter ions of excess halide ions. Thereby, an electric double layer is formed around the silver halide nanoparticles. The silver halide nanoparticles having the electric double layer formed around them are stabilized by having a high zeta potential.

In this embodiment, the silver iodide nanoparticles thus dispersed and stabilized are protected by a water-soluble polymer as a dispersant. The dispersion stability of the silver halide nanoparticles can be further enhanced by protecting the dispersion-stabilized silver halide nanoparticles with a water-soluble polymer as a dispersant. Therefore, even if the grain size is several nm, aggregation of silver halide nanoparticles can be suppressed for a long period of time.
The water-soluble polymer is not particularly limited as long as it increases the dispersibility of the nanoparticles, and examples thereof include water-soluble polymer dispersants such as hydroxypropyl cellulose, polyvinyl pyrrolidone, and polyvinyl alcohol. These water-soluble polymers have various molecular weights, but as the molecular weight increases, nanoparticles having a smaller particle diameter are obtained, and therefore water-soluble polymers having a molecular weight of 500 or more are preferably used.

Furthermore, in the bactericidal / antiviral composition of the present embodiment, an organic acid having a carboxyl group (—COOH) may be further contained, and among them, oxycarboxylic acid is particularly preferably used.
In the case of synthesizing a dispersion containing silver halide nanoparticles that are stable in the present embodiment, it is important to prevent aggregation of the silver halide nanoparticles. Aggregation of silver halide nanoparticles is greatly affected by the zeta potential of the grains, so organic acids and / or salts thereof are used to make the pH of the dispersion acidic and increase the zeta potential of silver halide nanoparticles. Therefore, aggregation can be suppressed and the dispersion stability can be further enhanced. The addition amount of the organic acid having a carboxyl group and / or a salt thereof is preferably an amount for adjusting the pH of the aqueous solution to 2.0 to 6.0. Further, in order to control the particle diameter of the silver halide nanoparticles, it is important how to control the supply of silver ions, which are the main components of the silver halide nanoparticles, from the solution. In other words, how to inhibit the growth of nanoparticles due to silver ions remaining in the composition that do not contribute to the reaction during the synthesis of silver halide nanoparticles, or silver ions eluted from the nanoparticles due to changes over time. Is important. Since an organic acid having a carboxyl group and / or a salt thereof easily forms a complex with silver ions and is stabilized, the above-described silver ions can be inhibited from participating in particle growth. Among these, oxycarboxylic acid (particularly citric acid) among organic acids having a carboxyl group easily forms a complex with silver ions and is stabilized. Therefore, the use of oxycarboxylic acid (more preferably citric acid) as a pH adjuster is useful for synthesizing silver halide nanoparticles having an extremely small particle diameter of several nm and a particle diameter excellent in dispersion stability. And more preferable.

  Specific examples of the oxycarboxylic acid include citrate, lactic acid, malic acid, tartaric acid, succinic acid, ascorbic acid, glycolic acid, and salts thereof, which have a carboxy group other than oxycarboxylic acid. Examples of the organic acid include sorbic acid, propionic acid, benzoic acid, adipic acid, gluconic acid, acetic acid, and salts thereof. These may be used alone or in combination.

  The bactericidal / antiviral composition of the present embodiment obtained by mixing each of the above components is not particularly limited in its form. For example, in addition to the solution form, the composition such as sol and gel flows. It can be set as the aspect which has property.

  The bactericidal / antiviral composition of the present embodiment can sterilize various bacteria regardless of properties such as gram positive, negative, aerobic, and anaerobic. For example, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus, Streptococcus pneumoniae, Haemophilus influenzae, Bordetella pertussis, Enterococcus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Vibrio and the like can be mentioned.

  In addition, various viruses can be inactivated without regard to the type of genome or the presence or absence of an envelope. For example, rhinovirus, poliovirus, rotavirus, foot-and-mouth disease virus, norovirus, feline calicivirus, enterovirus, hepatovirus, astrovirus, sapovirus, hepatitis E virus, A, B, C influenza virus, parainfluenza virus, Mumps virus, Measles virus, Human metapneumovirus, RS virus, Nipah virus, Hendra virus, Yellow fever virus, Dengue virus, Japanese encephalitis virus, West Nile virus, Type B, Hepatitis C virus, Eastern and western equine encephalitis Virus, Onyeonnyon virus, rubella virus, Lassa virus, Junin virus, Machupo virus, Guanarito virus, Sabia virus, Crimea Congo hemorrhagic fever virus, Snubber fever Irs, Hantavirus, Sinnombre virus, Rabies virus, Ebola virus, Marburg virus, Bat lyssa virus, Human T cell leukemia virus, Human immunodeficiency virus, Human coronavirus, SARS coronavirus, Human porvovirus, Polyoma virus , Human papillomavirus, adenovirus, herpes virus, varicella-zoster virus, EB virus, cytomegalovirus, smallpox virus, monkeypox virus, cowpox virus, molasipox virus, parapox virus, and the like.

  The bactericidal / antiviral composition thus obtained can be developed for various uses. For example, the composition can be used as it is as a disinfectant, cleaning agent, life-extending agent for cut flowers, deodorant, and the like. Furthermore, since it is a very stable composition, it can also be mixed with a binder etc. and used as a coating material. In addition, it can be used in diapers and sanitary products in combination with water-absorbing polymers to reduce inflammation, and can be easily mixed with ordinary resins and molded by injection molding to easily obtain antibacterial resin products. . Furthermore, since it is possible to have a very high configuration, even when a transparent material is used as a coating agent for medical devices, bactericidal and antiviral performance can be imparted without impairing the transparency. .

As described above, in this embodiment, an electric double layer is formed around the silver halide nanoparticles by adsorbing halide ions to the silver halide nanoparticles, and the electric double layer is formed around the silver double nanoparticles. The formed silver halide nanoparticles are protected with a water-soluble polymer. Therefore, a bactericidal / antiviral composition containing silver halide nanoparticles excellent in dispersion stability can be obtained. Dispersion of silver halide grains in the form of nanoparticles effectively provides a bactericidal effect and a virus inactivating effect.
Further, in the bactericidal / antiviral composition of the present embodiment, by containing a carboxyl group-containing carboxylic acid, preferably oxycarboxylic acid, more preferably citric acid, the dispersion stability of silver halide nanoparticles is further enhanced. Can do.
Further, the sterilizing / antiviral composition of the present embodiment contains carboxylic acid having a carboxyl group, preferably oxycarboxylic acid, more preferably citric acid, so that the silver halide nanoparticles in the sterilizing / antiviral composition are Since re-aggregation can be prevented, the effect that performance can be maintained for a longer period is obtained.

  Next, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to only these examples.

Example 1
To 320 mL of 0.8 M potassium iodide solution (purity KI 99% (manufactured by Wako Pure Chemical Industries)), 1 vol% of polyvinylpyrrolidone (manufactured by Across organics, molecular weight 3500) was added and stirred until completely dissolved. In a separate container, 50 mL of 0.5 M silver nitrate solution (purity 99.8% (manufactured by Wako Pure Chemical Industries)) was prepared in a shielding container. The above two solutions were stirred and mixed instantaneously with a silver ion: iodide molar ratio of 1:10, and the bactericidal / antiviral composition of Example 1 was obtained. Here, the particle size of silver iodide nanoparticles contained in the obtained bactericidal / antiviral composition is determined by measuring the zeta potential and particle diameter (system of Otsuka Electronics, laser Doppler method (dynamic and electrophoretic light scattering method)). The average particle size at this time was 5.1 nm. In addition, the average particle diameter here means a volume average particle diameter. Furthermore, this silver iodide nanoparticle composition was observed using a transmission electron microscope (JEM-2100 manufactured by JEOL Ltd.). The photograph is shown in FIG.

(Example 2)
A potassium iodide solution was prepared in the same manner as in Example 1, and 0.02% of citric acid (purity 98% (manufactured by Wako Pure Chemical Industries)) was added to the total amount of this solution, followed by stirring until complete dissolution. In a separate container, a 0.5M silver nitrate solution was made in a shielded container. The above solution was set so that the molar ratio of silver ion: iodine ion was 1:10, and the above two solutions were stirred and mixed instantaneously to obtain the bactericidal / antiviral composition of Example 2. The average particle diameter of the silver iodide nanoparticles contained was 4.2 nm.

Example 3
The bactericidal / antiviral composition of Example 3 was obtained in the same manner except that the molar ratio of silver ion: iodine ion of Example 2 was 1: 5. The average particle diameter of the silver iodide nanoparticles contained was 27.3 nm.

Example 4
The bactericidal / antiviral composition of Example 4 was obtained in the same manner except that the molar ratio of silver ion: iodine ion of Example 2 was changed to 1: 2. The average particle diameter of the silver iodide nanoparticles contained was 80.0 nm.

(Example 5)
To 32 mL of 0.08M potassium chloride solution (purity KCl 99% (manufactured by Wako Pure Chemical Industries)), 1 vol% of polyvinylpyrrolidone (Across organics, molecular weight 3500) was added and stirred until completely dissolved. In another container, 5 mL of 0.05 M silver nitrate solution (purity 99.8% (manufactured by Wako Pure Chemical Industries)) was prepared in a shielding container. The molar ratio of silver ions: chloride ions was set to 1:10, and the above two solutions were stirred and mixed instantaneously to obtain the bactericidal / antiviral composition of Example 5. When the particle diameter of the silver chloride nanoparticles contained was measured, the average particle diameter was 95.7 nm.

(Comparative Example 1)
A potassium iodide solution was prepared in the same manner as in Example 1, and a 5M silver nitrate solution was prepared in another container in a shielding container. The two solutions were stirred and mixed so that the molar ratio of silver ions: iodine ions was 1: 1 to obtain a silver iodide nanoparticle composition. The average particle diameter of the silver iodide nanoparticles contained was 180.8 nm.

(Comparative Example 2)
A potassium iodide solution was prepared in the same manner as in Example 1, and a 10M silver nitrate solution was prepared in another container in a shielding container. The above two solutions were stirred and mixed while setting the molar ratio of silver ions: iodine ions to 2: 1 to obtain a silver iodide nanoparticle composition. The average particle diameter of the silver iodide nanoparticles contained was 626.9 nm. In addition, the obtained silver iodide nanoparticle composition was precipitated immediately after synthesis.

(Comparative Example 3)
A potassium iodide solution was prepared in the same manner as in Example 1, and a 0.1 M silver nitrate solution was prepared in another container in a shielding container. When the silver ion: iodide molar ratio was set to 1:50 and the above two solutions were stirred and mixed, the nanoparticles could not be obtained because the silver iodide nanoparticles were dissolved. It was.

(Evaluation of bactericidal properties against E. coli)
Next, the bactericidal properties against Escherichia coli in the samples of the above Examples and Comparative Examples 1 and 2 were measured using a conventional method. Note that Comparative Example 3 was not measured because silver iodide nanoparticles were not obtained.

Specifically, first, the compositions of Examples and Comparative Examples were adjusted using ultrapure water so that the AgI concentration or the AgCl concentration was 1400 ppm. Each diluted solution (0.1 mL) and E. coli suspension (0.1 mL) were mixed to prepare a test sample. Each sample was reacted at room temperature for 60 minutes while stirring using a microtube rotator. After stirring for a predetermined time, 1.8 mL of SCDLP medium was added to stop the reaction between E. coli and the compound derived from each composition. Thereafter, each sample was diluted 10 ² to 10 ⁵ times using SCDLP medium (diluted in 10 steps), applied to a 1 mL petri dish, mixed with dissolved NB agar medium, and cultured at 37 ° C. The number of colonies formed (CFU / 1ml, Log10); (CFU: colony-forming unit) was calculated to evaluate the bactericidal properties of each composition against Escherichia coli. The results are shown in Table 1.

(Antiviral evaluation against influenza virus and feline calicivirus)
Furthermore, antiviral properties against influenza virus (influenza A / Kitakyushu / 159/93 (H3N2)) and feline calicivirus (feline calicivirus (F9 strain)) in each of the compositions of Examples and Comparative Examples 1 and 2 above Was measured. The measurement used the plaque method which can detect a virus with high precision. Note that Comparative Example 3 was not measured because silver iodide nanoparticles were not obtained.

Specifically, first, each composition of Examples and Comparative Examples other than Example 5 was adjusted using ultrapure water so that the AgI concentration was 2000 ppm. About the composition containing the silver chloride nanoparticle of Example 5, it adjusted using the ultrapure water so that AgCl density | concentration might be 2000 ppm under light-shielding conditions. Each 0.1 mL of each diluted solution and 0.1 mL of each virus suspension of influenza virus and feline calicivirus were mixed to prepare a test sample. Each sample according to Examples 1 to 4 and Comparative Examples 1 and 2 was reacted at room temperature for 60 minutes while stirring using a microtube rotator. In addition, each sample according to Example 5 was reacted for 60 minutes in the dark at room temperature. As a control, 0.1 mL of each virus suspension was added to 0.1 mL of PBS, and the mixture was stirred for 60 minutes using a microtube rotator in the same manner as each sample. After stirring for a predetermined time, 1.8 mL of SCDLP medium was added in order to stop the reaction between the virus and the compound in each sample. Thereafter, each sample was diluted 10 ² to 10 ⁵ times with a MEM diluent (10-step dilution), and influenza virus was inoculated into MDCK cells and feline calicivirus was inoculated into CrFK cells by 0.1 mL. After adsorbing virus for 60 minutes, overlay with 0.7% agar medium, culture for 48 hours in 34 ° C, 5% CO ₂ incubator, fix with formalin, stain with methylene blue and count the number of plaques formed. Antiviral properties were evaluated by calculating infectivity titers (PFU / 0.1 ml, Log 10); (PFU: plaque-forming units). The results are shown in Table 1.

  From the above results, the bactericidal properties against Escherichia coli were confirmed to have a high effect of not more than the detection limit value in 60 minutes for all Examples (approximately 20 times that of Comparative Example 1). As for influenza virus, in Examples 1 to 3, the detection limit value was 60 minutes or less (approximately 800 times that of Comparative Example 1), and in Example 4, 99.9998% (approximately 400 times that of Comparative Example 1) in 60 minutes. In 60 minutes, 99.9950% (about 15 times that of Comparative Example 1) was confirmed to be highly effective. As for feline calicivirus, in Examples 1 to 3, the detection limit value is 60% or less (approximately 4000 times that of Comparative Example 1), and in Example 4, 99.9996% (approximately 1000 times that of Comparative Example 1) in 60 minutes. In No. 5, a high effect of 99.99% in 60 minutes (about 40 times that of Comparative Example 1) was confirmed. Further, in Comparative Example 2 in which the silver ions were excessive, both the bactericidal and antiviral effects were not effective.

(Evaluation of long-term stability)
Changes over time were observed in the samples of Examples 1 and 2 and Comparative Example 1. Specifically, 50 mL of each sample solution adjusted to an AgI concentration of 2000 ppm was placed in a vial with a lid and stored at 28 ° C. in the dark. When the state of the liquid was confirmed by visual observation, precipitation was observed in Comparative Example 1 on the next day. On the other hand, in Example 1, no precipitation was observed on the next day, and only a slight precipitation was confirmed at the bottom of the bottle after 1 week. In Example 2 to which citric acid was added, no precipitate was observed after one month, and the liquid was transparent. Bactericidal and antiviral effects were measured on samples stored at 28 ° C. in the dark for 1 month. The results are shown in Table 2.

From the above results, Comparative Example 1 in which precipitation was observed on the next day had almost no effect on both bactericidal and antiviral properties. About Example 1, it has confirmed that it had higher bactericidal property and antiviral property than the comparative example 1 also after one month. Furthermore, Example 2 to which citric acid was added showed high bactericidal and antiviral effects as in the initial stage.

Claims (4)

Nanoparticles composed of silver halide having a particle size of 1 nm to 100 nm,
A halide ion of the same element as the halogen constituting the silver halide;
Including at least one or more water-soluble polymers,
The bactericidal and antiviral composition, wherein the molar ratio of silver in the silver halide to the halide ion is from 1: 1 to 1:20.   The germicidal / antiviral composition according to claim 1, further comprising an organic acid having a carboxyl group and / or a salt thereof.   The germicidal / antiviral composition according to claim 2, wherein the organic acid having a carboxyl group is an oxycarboxylic acid. The antibacterial / antiviral composition according to any one of claims 1 to 3, wherein the silver halide is silver iodide.