Antiviral composition

Abstract

To provide an excellent antiviral composition.SOLUTION: An antiviral composition contains a cyclic organic phosphoric acid ester compound. Preferably, the cyclic organic phosphoric acid ester compound is at least one kind selected from the group consisting of 2,2'-methylenebis(4,6-di-tert-butylphenyl)sodium phosphate and 2,2'-methylenebis(4,6-di-tert-butylphenyl)zinc phosphate.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an antiviral composition.

Background Art

[0002] Viruses such as influenza virus and norovirus cause various diseases, and thus compositions having an antiviral effect against such viruses are desired. [[ID=第十三条]]

Summary of the Invention

Problems to be Solved by the Invention

[0003] An object of the present invention is to provide an antiviral composition that exhibits antiviral performance against a wide range of viruses.

Means for Solving the Problems

[0004] As a result of intensive studies to solve such problems, the present inventor has arrived at the present invention. That is, the present invention is: (1) A cyclic organophosphate compound represented by formula (I) TIFF0007854173000001.tif6 (where R 1 , R 2 and R 3 each independently represents a hydrogen atom or a linear or branched alkyl group having 1 to 18 carbon atoms, R 4 represents a hydrogen atom or a methyl group, n represents an integer of 1 to 3, and M represents an alkali metal atom, a silver atom, ammonium, an alkaline earth metal atom, a zinc atom, a lanthanum atom, an aluminum atom, a cerium atom, an alkaline earth metal compound, a zinc compound, a lanthanum compound or an aluminum compound). An antiviral composition containing the cyclic organophosphate compound represented by the formula. (2) At least one antiviral composition in which the above-mentioned cyclic organic phosphate compound is selected from the group consisting of sodium 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate, zinc 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate, and silver 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate. (3) A processed product obtained by processing the above-mentioned antiviral composition. To provide. [Effects of the Invention]

[0005] According to the present invention, it is possible to provide an antiviral composition having excellent antiviral performance. [Best Mode for Carrying Out the Invention]

[0006] In the cyclic organophosphate compound represented by the general formula (I) used in the antiviral composition of the present invention, R 1 , R 2 and R 3 Examples of alkyl groups represented by include methyl, ethyl, propyl, isopropyl, butyl, 2-butyl, 3-butyl, amyl, 3-amyl, hexyl, octyl, 2-ethylhexyl, isooctyl, 3-octyl, nonyl, decyl, dodecyl, tridecyl, isotridecyl, tetradecyl, hexadecyl, and octadecyl.

[0007] In the cyclic organophosphate ester compound represented by the above general formula (I) used in the antiviral composition of the present invention, M is an alkali metal atom, a silver atom, an ammonium atom, an alkaline earth metal atom, a zinc atom, a lanthanum atom, an aluminum atom, a cerium atom, an alkaline earth metal compound, a zinc compound, a lanthanum compound, or an aluminum compound. Examples of alkaline earth metal compounds include hydroxides, chlorides, phosphates, and sulfates of calcium and magnesium; examples of zinc compounds include hydroxides, chlorides, phosphates, and sulfates; examples of lanthanum compounds include hydroxides, chlorides, phosphates, and sulfates; and examples of aluminum compounds include hydroxides, chlorides, phosphates, and sulfates.

[0008] Of these, the cyclic organic phosphate compound represented by the above general formula (I) is preferably sodium 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate, zinc 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate, or silver 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate.

[0009] The antiviral composition of the present invention can be added directly to the target substance, or it can be formulated by adding a solvent or the like before use. Examples of such formulations include oils, emulsions, solubilized formulations, wettable powders, powders, flowable formulations (such as suspensions in water and emulsions in water), and suspend emulsions.

[0010] Solvents used in such formulations include water, monohydric alcohols such as ethanol, isopropanol, phenoxyethanol, and benzyl alcohol, glycol solvents and their derivatives such as ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, butylene glycol, diethylene glycol monomethyl ether, diethylene glycol monobutyl ether, dipropylene glycol monomethyl ether, and tripropylene glycol monomethyl ether, glycerin solvents and their derivatives such as glycerin and diglycerin, sulfur-containing solvents such as dimethyl sulfoxide, cyclic organic solvents such as N-methylpyrrolidone, N-ethylpyrrolidone, and γ-butyrolactone, ester solvents such as phthalates, adipicates, and sebacates, aromatic solvents such as methylnaphthalene, phenylxylethane, and alkylbenzene, aliphatic hydrocarbon solvents such as normal paraffin and isoparaffin, and rapeseed oil, cottonseed oil, soybean oil, and castor oil. These solvents may be used individually or in combination of two or more types.

[0011] When formulating the above-mentioned product, surfactants, pH adjusters, defoamers, rust inhibitors, viscosity modifiers, light stabilizers, UV absorbers, dispersants, emulsifiers, buffers, antioxidants, and other antibacterial components may be added.

[0012] The antiviral composition of the present invention can be processed into fibers, nonwoven fabrics, paints, surface treatment agents, coating agents, adhesives, films, furnishings, plastics, etc., and used as processed products.

[0013] Examples of viruses targeted by the antiviral composition of the present invention include enveloped influenza viruses and non-enveloped noroviruses. Of these, it exhibits particularly excellent antiviral activity against influenza viruses. Here, antiviral properties mean suppressing viral replication, killing viruses, and reducing viral infectivity. [Examples]

[0014] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples. [Example 1]

[0015] An emulsion was obtained by mixing 0.1 parts by weight of sodium 2,2′-methylenebis(4,6-di-tert-butylphenyl)phosphate (manufactured by Tokyo Chemical Industry Co., Ltd.) and 99.9 parts by weight of urethane emulsion (U-Coat® UX-2510, manufactured by Sanyo Chemical Industries, Ltd.). The emulsion was applied to A4-sized PPC paper using an applicator to form a 50 μm thick film, and then heated and dried in a 110°C dryer for 3 minutes. The dried PPC paper was cut into 5 cm squares to obtain test specimens. [Example 2]

[0016] 5 g of sodium 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate (manufactured by Tokyo Chemical Industry Co., Ltd.) was added and dissolved in 395 g of dimethyl sulfoxide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). While stirring the solution, 100 g of a 2% by weight aqueous solution of zinc chloride was added dropwise and stirred for 2 hours to obtain zinc 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate. The solution was filtered by suction, thoroughly washed with warm deionized water, and dried at 60°C for 24 hours. The dried material was placed in a mortar and mixed with 0.1 parts by weight of powdered zinc 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate and 99.9 parts by weight of urethane emulsion (U-Coat UX-2510, manufactured by Sanyo Chemical Industries, Ltd.) to obtain an emulsion. The mixture was applied to A4-sized PPC paper using an applicator to create a coating with a thickness of 50 μm, and then heated and dried at 110°C for 3 minutes. The dried PPC paper was cut into 5 cm squares to obtain test specimens. [Example 3]

[0017] 5 g of sodium 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate (manufactured by Tokyo Chemical Industry Co., Ltd.) was added to and dissolved in 395 g of dimethyl sulfoxide (manufactured by Fujifilm Wako Pure Chemical Corporation). While stirring such a solution, 100 g of a 2 wt% aqueous silver nitrate solution was added dropwise and stirred for 2 hours to obtain silver 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate. It was separated by suction filtration, thoroughly washed with warm deionized water, and then dried at 60 °C for 24 hours. Such a dried product was put into a mortar and pulverized with a pestle. 0.1 part by weight of a powder of silver 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate and 99.9 parts by weight of a urethane emulsion (Eucort UX-2510, manufactured by Sanyo Chemical Industries, Ltd.) were mixed to obtain an emulsion. Such a mixture was applied to A4-sized PPC paper using an applicator to form a coating film with a film thickness of 50 μm, and then heated and dried at 110 °C for 3 minutes. The dried PPC paper was cut into 5 cm squares to obtain test pieces. Comparative Example

[0018] A urethane emulsion (Eucort UX-2510, manufactured by Sanyo Chemical Industries, Ltd.) was applied to A4-sized PPC paper using an applicator to form a coating film with a film thickness of 50 μm, and then heated and dried at 110 °C for 3 minutes. The dried PPC paper was cut into 5 cm squares to obtain test pieces.

[0019] (Antiviral activity test against influenza virus) Influenza virus H3N2 strain (influenza A virus: A / Hong Kong / 8 / 68: TC adapted ATCC VR-1679) was cultured in MDCK cells (dog kidney-derived cells), and the virus infectious titer was 2×10 7A test influenza virus suspension with a PFU / ml (PFU = plaque forming units) was obtained. A test specimen was placed in a plastic petri dish, and 0.4 ml of the above-mentioned test influenza virus suspension was dropped onto the approximate center of the specimen. A 4 cm square polyethylene film was then placed over the entire test virus suspension, and the specimen was stored at 25°C and 95% humidity for 24 hours. Next, the test influenza virus suspension between the specimen and the polyethylene film was washed with 10 ml of SCDLP medium (manufactured by Nippon Pharmaceutical Co., Ltd.). This wash solution was diluted 10-fold repeatedly using EMEM medium, and the logarithmic value of the influenza virus infectivity titer was measured on MDCK cells using the plaque assay method.

[0020] Table 1 shows the results of the viral infectivity titer measurement.

[0021] [Table 1]

[0022] (Tests against cedar pollen allergens) 1. Cry j1 monoclonal antibody 013 (manufactured by Biodynamics Laboratories, Inc.), diluted to 2 μg / mL in PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), was added to each well of an F16 MAXISORP NUNC-IMMUNO MODULE plate (manufactured by NUNC Corporation) at a concentration of 100 μL, and the plates were left standing at 4°C for 1 day. 2. After standing, the solution was discarded, and 200 μL of blocking reagent {PBS containing 1% by weight of bovine serum albumin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.)} was added to each well, and the mixture was left to stand at 37°C for 60 minutes. 3. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 4. To 1 mL of a cedar pollen allergen solution containing 12.5 ng / mL of Cry j1 (cedar pollen allergen), prepared using PBS-T (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) to a concentration of 12.5 μg / mL (hereinafter referred to as the standard cedar pollen allergen solution), 150 μL of a 1% ethanol solution of 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate sodium (manufactured by Tokyo Chemical Industry Co., Ltd.) was mixed. As a control, the standard cedar pollen allergen solution was mixed with 150 μL of deionized water. 5. 100 μL of these mixtures were added dropwise to each well and allowed to stand at 37°C for 60 minutes. 6. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 7. Peroxidase-labeled Cry j1 monoclonal antibody 053 (manufactured by Biodynamics Laboratories, Inc.) was dissolved in distilled water at a concentration of 200 μg / mL, and the solution, diluted 1200-fold with PBS-T (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) containing 1% by weight bovine serum albumin, was added to each well at a concentration of 100 μL, and the mixture was allowed to stand at 37°C for 60 minutes. 8. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 6.5 mL of 9.0.2 mol / L phosphate buffer (pH 6.2) was mixed with ortho-phenylenediamine dihydrochloride (13 mg Tablet, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and 6.5 μL of 30% hydrogen peroxide solution. 100 μL of this mixture was added to each well, and the mixture was allowed to stand at 37°C for 5 minutes. 50 μL of 10.2 mol / L sulfuric acid aqueous solution was added to each well, and the absorbance (OD490 nm) was measured using a microplate spectrophotometer (manufactured by Tecan Japan Co., Ltd.). 11. The Cry j1 concentration was determined from the absorbance, and the cedar pollen allergen reduction rate was calculated using equation (2).

[0023] Cedar pollen allergen reduction rate (%) = (12.5 - (Cry j1 amount)) / 12.5 × 100 (2)

[0024] Table 2 shows the reduction rate of cedar pollen allergens.

[0025] (Tests for dust mite allergens) 1. Anti-Der f2 monoclonal antibody 15E11 (manufactured by Fujifilm Wako Shibayagi Co., Ltd.), diluted to 2 μg / mL in PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), was added to each well of an F16 MAXISORP NUNC-IMMUNO MODULE plate (manufactured by NUNC Corporation) at a concentration of 100 μL and allowed to stand at 4°C for 3 days. 2. After standing, the solution was discarded, and 200 μL of blocking reagent {PBS containing 1% by weight of bovine serum albumin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.)} was added to each well, and the mixture was left to stand at 37°C for 60 minutes. 3. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 4. To 1 mL of an allergen solution containing the dust mite allergen Der f2 (prepared using PBS-T (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) to a Der f2 equivalent protein content of 900 ng / mL), 200 μL of a 1% ethanol solution of 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate sodium (manufactured by Tokyo Chemical Industry Co., Ltd.) was mixed. As a control, 200 μL of deionized water was used instead of 2,2′-methylenebis(4,6-di-tert-butylphenyl) phosphate sodium (manufactured by Tokyo Chemical Industry Co., Ltd.). 5. 100 μL of these mixtures were added dropwise to each well and allowed to stand at 37°C for 60 minutes. 6. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 7. Peroxidase-labeled anti-Der f2 monoclonal antibody 13A4 (manufactured by Fujifilm Wako Shiba Yagi Co., Ltd.) was dissolved in 200 μg / mL of PBS-T containing 1% bovine serum albumin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), and then diluted 1200-fold with PBS-T containing 1% bovine serum albumin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 100 μL of a solution diluted 8.1200 times was added to each well, and the mixture was allowed to stand at 37°C for 60 minutes. 9. Discard the liquid in the wells and rinse the plate with PBS (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.). 6.5 mL of 10.0.2 mol / L phosphate buffer (pH 6.2) was mixed with one 13 mg tablet of ortho-phenylenediamine dihydrochloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) and 6.5 μL of 30% hydrogen peroxide solution. 100 μL of this solution was added to each well, and the mixture was allowed to stand at 37°C for 3 minutes. 50 μL of 11.2 mol / L sulfuric acid aqueous solution was added to each well, and the absorbance (OD490 nm) was measured using a microplate spectrophotometer (Tekan Japan Co., Ltd.). The Der f2-equivalent protein concentration was determined from the absorbance, and the mite allergen reduction rate was calculated using equation (1).

[0026] Dust mite allergen reduction rate (%) = (900 - (Der f2 equivalent protein amount)) / 900 × 100 (1)

[0027] Table 2 shows the reduction rate of dust mite allergens.

[0028] [Table 2] TIFF0007854173000003.tif2382

Claims

1. An anti-influenza virus composition containing sodium 2,2'-methylenebis(4,6-di-tert-butylphenyl)phosphate.

2. An antiviral processed article obtained by processing the anti-influenza virus composition described in claim 1.

Images