JP7748103B2 - antiviral agents - Google Patents

Description

The present invention relates to an antiviral agent.

Viruses such as influenza virus and norovirus cause various diseases, so there is a demand for antiviral agents with antiviral properties that are useful for prevention.

The objective of the present invention is to provide an antiviral agent with excellent antiviral properties.

The present inventors have conducted extensive research to solve the above problems and have arrived at the present invention.
(1) An antiviral agent containing a compound represented by formula (I) as an active ingredient.
M(C _n H _2n-1 O ₂ ) ₂ (I)
(n represents an integer of 6 to 10, and M represents Zn or ZrO.)
(2) The above antiviral agent containing zinc octylate as an active ingredient.
(3) The antiviral agent described above, further comprising a powder having an oil absorption in the range of 1.5 to 5 mL/g as measured in accordance with JIS K5101-13-1.
(4) The antiviral agent as described above, wherein the target virus to be controlled is influenza virus and/or norovirus.
(5) An antiviral processed product containing the above antiviral agent.
to provide.

The present invention makes it possible to provide an antiviral agent with excellent antiviral properties.

The antiviral agent according to the present invention contains a compound represented by the following formula (I) as an active ingredient.
M(C _n H _2n-1 O ₂ ) ₂ (I)
(n represents an integer of 6 to 10, and M represents Zn or ZrO.)

The compound represented by general formula (I) may have a linear, branched, or cyclic structure. Specific examples include one or more compounds selected from the group consisting of zinc octoate, zirconium octoate, zinc versatate, and zirconium versatate. Of these, zinc octoate is preferred.

The antiviral agent of the present invention can be a compound represented by general formula (I) that can be used as is, but is usually formulated by adding a solvent or the like. Examples of formulations include oil solutions, emulsions, solubilized formulations, wettable powders, microcapsules, dusts, tablets, aerosols, and carbon dioxide gas formulations.

Solvents used in formulation include water, monohydric alcohols such as ethanol, isopropanol, phenoxyethanol, and benzyl alcohol; glycol-based solvents and derivatives such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, butylene glycol, diethylene glycol monomethyl ether, diethylene glycol monobutyl ether, dipropylene glycol monomethyl ether, and tripropylene glycol monomethyl ether; glycerin-based solvents and derivatives such as glycerin and diglycerin; cyclic organic solvents such as dimethyl sulfoxide, N-methylpyrrolidone, N-ethylpyrrolidone, and γ-butyrolactone; ester-based solvents such as phthalates, adipates, and sebacates; aromatic solvents such as methylnaphthalene, phenylxylylethane, and alkylbenzenes; aliphatic hydrocarbon solvents such as normal paraffin and isoparaffin; rapeseed oil, cottonseed oil, soybean oil, castor oil, turpene, and mineral spirits. These solvents may be used alone or in combination of two or more.

When formulated as a powder, the compound represented by general formula (I) can be supported on a powder having an oil absorption of 1.5 to 5 mL/g as measured according to JIS K5101-13-1. Examples of such powders include calcium silicate and silicon dioxide having the above oil absorption, and commercially available products include Fluorite® R and Fluorite® RT (Tomita Pharmaceutical Co., Ltd.) and Toxil® NR (Oriental Silicas Corporation). When supported on such powders, the weight of the compound represented by general formula (I) is typically no more than four times the weight of the powder.

When formulating the formulation, surfactants, pH adjusters, antifoaming agents, rust inhibitors, viscosity adjusters, sequestering agents, light stabilizers, UV absorbers, antibacterial agents, etc. may be added. These may be added alone or in combination of two or more.

Examples of surfactants include nonionic surfactants such as polyoxyalkylene alkyl ethers, polyoxyalkylene allyl phenyl ethers, block copolymers of polyoxyethylene and polyoxypropylene, glycerin fatty acid esters, sorbitan fatty acid esters, polyoxyalkylene sorbitan fatty acid esters, and polyoxyalkylene hydrogenated castor oil; anionic surfactants such as alkyl sulfate salts, alkyl ether sulfate salts, alkyl sulfosuccinate salts, alkyl sulfonate salts, alkyl aryl sulfonate salts, fatty acid amide sulfonate salts, lignin sulfonate salts, alkyl naphthalene sulfonate salts, alkyl phosphate salts, alkyl ether phosphate salts, and naphthalene sulfonate formaldehyde condensate salts; cationic surfactants such as alkylamine salts and alkylammonium salts; and amphoteric surfactants such as glycine, betaine, and imidazoline types.

The antiviral agent of the present invention can be incorporated into substrates such as resin compounds, plastic agents such as films or sheets, coating agents such as paints and surface treatment agents, adhesives, fibers such as woven fabrics and nonwoven fabrics, and paper, and used as an antiviral finished product. When incorporating an antiviral agent into an antiviral finished product, the amount of the antiviral agent incorporated is preferably 0.01 to 20 parts by weight per 100 parts by weight of the substrate of the antiviral finished product, and more preferably 0.1 to 10 parts by weight per 100 parts by weight of the substrate of the antiviral finished product.

By using the antiviral processed products of the present invention, it is possible to impart antiviral properties to materials related to living environments such as wall materials, handrails, flooring materials, wooden flooring materials, kitchen counters, furniture, and wallpaper; textile products such as refrigerator and air conditioner housings and filters; materials related to electrical products such as protective films for image displays on portable electronic devices; materials related to industrial products such as seats and floor mats for automobiles and trains; and materials related to packaging such as wrapping paper and cardboard.

Antiviral performance means that even if a virus adheres to the material, the viral infectivity is reduced and the material no longer exhibits infectivity.

The antiviral agent of the present invention is particularly effective against influenza viruses and noroviruses. The antiviral agent of the present invention is also expected to be effective in controlling viruses such as coronaviruses, rhinoviruses, respiratory syncytial viruses, adenoviruses, and enteroviruses.

The present invention will be explained in detail below using examples, but the present invention is not limited to these.

Unless otherwise specified, parts mean parts by weight and % means % by weight.

Example 1
An antiviral agent (zinc octoate content: 19.8%) was obtained by mixing 20 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octoate purity: 99%), 16 parts of turpene, 45 parts of Rheodol TW-O106V (manufactured by Kao Corporation, polyoxyethylene sorbitan monooleate), and 19 parts of water.

Example 2
An antiviral agent was obtained by mixing 20 parts of zinc neodecanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 16 parts of turpentine, 45 parts of Rheodol TW-O106V, and 19 parts of water (zinc neodecanoate content: 19.8%).

Example 3
An antiviral agent was obtained by mixing 36 parts of a zirconium(IV) bis(2-ethylhexanoate) mineral spirit solution (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zirconium oxide octylate purity: 55%), 45 parts of Rheodol TW-O106V, and 19 parts of water (zirconium oxide octylate content: 19.8%).

Example 4
An antiviral agent (zinc octoate content: 79.2%) was obtained by mixing 80 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octoate purity: 99%) and 20 parts of Fluorite RT (oil absorption: 4.2 mL/g).

Example 5
An antiviral agent was obtained by mixing 75 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octoate purity 99%) and 25 parts of Fluorite R (oil absorption 4.8 mL/g) (zinc octoate content: 74.3%).

Comparative Example 1
A preparation (zinc laurate content: 20%) was obtained by mixing 20 parts of zinc laurate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 16 parts of turpentine, 45 parts of Rheodol TW-O106V, and 19 parts of water.

Comparative Example 2
20 parts of zinc stearate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 16 parts of turpentine, 45 parts of Rheodol TW-O106V and 19 parts of water were mixed to obtain a preparation (zinc stearate content: 20%).

Comparative Example 3
A preparation was obtained by mixing 16 parts of turpentine, 45 parts of Rheodol TW-O106V, and 39 parts of water.

[Antiviral test against feline calicivirus]
In accordance with ISO 21702, feline calicivirus F-9 strain (ATCC VR-782) was cultured in CRFK cells (feline kidney-derived cells) to obtain a test feline calicivirus suspension with a virus infectivity of 2 x 10 ⁷ Plaque Forming Units/mL (hereinafter referred to as PFU/mL).
The preparation obtained in Example 1 was diluted with sterile distilled water to a concentration of 5%. 0.1 mL of the test feline calicivirus suspension was added to 0.9 mL of this diluted solution, and the mixture was allowed to stand at 25°C for 2 hours.

0.1 mL of the diluted solution containing the test feline calicivirus suspension obtained above was mixed with 0.9 mL of SCDLP medium (manufactured by Nippon Pharmaceutical Co., Ltd.). 0.1 mL of the resulting mixture was mixed with 0.9 mL of E-MEM medium (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) to obtain Sample 1 for measuring the virus infectivity titer. Next, Samples 2 to 6 with different dilution ratios were prepared by a serial dilution method in which 10-fold, 100-fold, 1,000-fold, 100,000-fold, and 1,000,000-fold volumes of E-MEM medium were added to 0.1 mL of Sample 1.
For Samples 1 to 6, the feline calicivirus infectivity titer (logarithmic value of FCV infectivity titer) was measured by plaque assay on CRFK cells.

The same procedure as above was performed for Examples 2 to 3 and Comparative Examples 1 to 3, and the feline calicivirus infectivity titer (FCV infectivity logarithm value) of each formulation was measured. The feline calicivirus infectivity titer (FCV infectivity logarithm value) was also measured using sterile distilled water alone, and this result served as a control. The measurement results are shown in Table 1.

[Antiviral test against influenza virus]
In the antiviral test against feline calicivirus described above, the influenza virus infectivity titer (logarithmic value of IV infectivity titer) was measured in the same manner as in the test, except that the feline calicivirus F-9 strain (F-9 ATCC VR-782) was replaced with influenza virus H3N2 strain (influenza A virus: A/Hong Kong/8/68:TC adapted ATCC VR-1679), CRFK cells (feline kidney-derived cells) were replaced with MDCK cells (canine kidney-derived cells), and the diluent concentration was changed from 5% to 1%. The measurement results are shown in Table 2.

[Preparation of polyvinyl chloride sheet]
100 parts of ZEST-1300 (polyvinyl chloride, manufactured by Shin-Dai-Ichi Vinyl Corporation), 45 parts of diisononyl phthalate, 6.2 parts of epoxidized soybean oil, and 12.3 parts of LBK-793K (manufactured by Sakai Chemical Industry Co., Ltd.) were mixed and then kneaded at 170°C using a Laboplastomill to obtain a vinyl vinyl sol.
This resin composition consisting only of vinyl chloride sol was pressed for 3 minutes in a press molding machine heated to 180°C, and then cooled to obtain Polyvinyl chloride Sheet-0. Also, a resin composition was obtained by kneading 100 parts of this vinyl chloride sol with 1 part or 3 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octoate purity 99%). Each resin composition was pressed for 3 minutes in a press molding machine heated to 180°C, and then cooled to obtain Polyvinyl chloride sheets (Sheets-1 and 2).

[Antiviral test of polyvinyl chloride sheets]
The antiviral activity of the sheets was tested in accordance with ISO 21702. First, the aforementioned polyvinyl chloride sheets-0, 1, and 2 were each cut into 50 mm x 50 mm pieces to obtain test specimens. The test specimens were placed in plastic petri dishes, and 0.4 mL of the aforementioned test feline calicivirus suspension was dropped onto the approximate center of each specimen. A 40 mm x 40 mm polyethylene film was placed on top so as to cover the entire virus suspension, and the specimens were stored at 25°C and 95% humidity for 24 hours. The test feline calicivirus suspension sandwiched between the test specimen and the polyethylene film was then washed out with SCDLP medium. A dilution series of this washed-out solution was prepared by serial dilution using E-MEM medium. The feline calicivirus infectivity titer (FCV infectivity logarithm) of the resulting diluted solutions was measured on CRFK cells using the plaque assay method. The measurement results are shown in Table 3.

In the antiviral test of the polyvinyl chloride sheet described above, the test virus was changed from feline calicivirus to influenza virus, and the influenza virus infectivity titer (logarithmic value of IV infectivity titer) was measured using the plaque assay method on MDCK cells. The measurement results are shown in Table 3.

[Preparation of UV-curable acrylic resin coating film]
Three types of resin compositions were prepared: a resin composition consisting solely of UV-curable acrylic resin, and a resin composition mixing 100 parts of UV-curable acrylic resin with 5 to 10 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octoate purity 99%). Each of these resin compositions was applied to an aluminum bag with an applicator to a concentration of 10 g/ ^m² , and then cured by irradiating with 350 mJ/cm² of UV light using a UV curing device HLR100T- ² (manufactured by AS ONE). The resulting coatings were then left to stand in a 60°C dryer for 24 hours to obtain UV-curable acrylic resin coatings (Coatings-0, 1, 2).

[Antiviral test of ultraviolet-cured acrylic resin coating]
The antiviral properties of the coatings were tested in accordance with ISO 21702. First, the aforementioned coatings-0, 1, and 2 were each cut into 50 mm x 50 mm pieces to obtain test specimens. The obtained test specimens were placed in plastic petri dishes, and 0.4 mL of the aforementioned test feline calicivirus suspension was dropped onto the approximate center of each specimen. A 40 mm x 40 mm polyethylene film was placed on top so as to cover the entire virus suspension, and these were stored at 25°C and 95% humidity for 24 hours. The test feline calicivirus suspension sandwiched between the test specimen and the polyethylene film was then washed out with SCDLP medium. A dilution series of this washed-out solution was prepared by serial dilution using E-MEM medium. The feline calicivirus infectivity titer (FCV infectivity logarithm) of the obtained diluted solutions was measured using a plaque assay on CRFK cells.

The results of the antiviral test on UV-cured acrylic resin coatings are shown in Table 4.

Example 6
An antiviral agent was obtained (zinc octylate content: 69.3%) by mixing 70 parts of zinc 2-ethylhexanoate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd., zinc octylate purity: 99%) and 30 parts of Naroacty (registered trademark) CL70 (polyoxyalkylene alkyl ether) (manufactured by Sanyo Chemical Industries, Ltd.).

[Production of processed fibers]
The formulation obtained in Example 6 was diluted with distilled water to prepare a dispersion. A standard antibacterial test cloth (cotton distributed by the Japan Textile Evaluation Technology Council) was immersed in the formulation to a loading of 1.2 g/ ^m² or 2.4 g/ ^m² . The resultant was then dried at 105°C to obtain processed fibers (Processed Fiber-1, 2). Furthermore, the standard cloth was immersed in distilled water and then dried at 105°C to obtain a comparative processed fiber (Processed Fiber-0).

[Antiviral test of processed fibers]
The antiviral activity of the fibers was tested in accordance with ISO 18184. First, processed fibers 0, 1, and 2 were each cut to a dry weight of 0.4 g and placed in a glass vial. 0.2 mL of the test feline calicivirus suspension was added dropwise to each processed fiber so that it soaked into the entire fiber, and the vial was then capped and stored at 25°C for 2 hours. SCDLP medium was then added to the vial and thoroughly mixed to wash out the feline calicivirus suspension. A dilution series of this washout solution was prepared by serial dilution using E-MEM medium. The feline calicivirus infectivity titer (FCV infectivity titer logarithm) of the resulting diluted solution was measured on CRFK cells by plaque assay. The measurement results are shown in Table 5.

In the antiviral test of the processed fibers described above, the test virus was changed from feline calicivirus to influenza virus, and the influenza virus infectivity titer (logarithmic value of IV infectivity titer) was measured using the plaque assay method on MDCK cells. The measurement results are shown in Table 5.

The embodiments and examples disclosed above should be considered in all respects as illustrative and not restrictive. The scope of the present invention is indicated not by the above embodiments and examples, but by the claims, and includes all modifications and variations within the meaning and scope of the claims.

Because the antiviral agent of the present invention has excellent antiviral properties, it is possible to impart antiviral performance to members related to living environments such as wall materials, handrails, floor materials, wooden floor materials, kitchen counters, furniture, and wallpaper by using antiviral processed products containing the antiviral agent.

Claims (7)

Formula (I)
M(C _n H _2n-1 O ₂ ) ₂
(n represents an integer of 6 to 10, and M represents Zn or ZrO.)
The compound represented by the formula (I) is contained as an active ingredient.
The compound represented by formula (I) is at least one selected from the group consisting of zinc octylate and zirconium oxide octylate.
An antiviral agent for feline calicivirus, norovirus, or influenza virus . The antiviral agent according to claim 1, wherein the active ingredient is zinc octoate. The antiviral agent according to claim 1 or claim 2, further comprising a powder having an oil absorption in the range of 1.5 to 5 mL/g as measured according to JIS K5101-13-1. The antiviral agent according to any one of claims 1 to 3, wherein the virus to be controlled is influenza virus and/or norovirus. An antiviral processed product containing the antiviral agent described in any one of claims 1 to 4. An antiviral processed product formed from an antiviral substrate containing the antiviral agent described in any one of claims 1 to 4. An antiviral substrate containing the antiviral agent described in any one of claims 1 to 4, for imparting antiviral properties to an antiviral processed product.