JP2011093867A - Spray product for preventing influenza virus infection - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a spray product for preventing influenza virus infection. <P>SOLUTION: The spray product for preventing influenza virus infection is obtained by filling (1) an antiviral solution and (2) a propellant in a spray can. Here, the antiviral solution is an aqueous solution or a water-alcohol solution containing a mixture comprising hinokitiol and zinc chloride in an amount corresponding to 0.4-0.6 molar equivalent of hinokitiol, provided that the water-alcohol solution has an alcohol content of 10-60%, and the amount of the mixture contained in the solution is 0.001-1 mass% based on the mass of the antiviral solution. The volume ratio of the antiviral solution to the propellant is within the range of from 30:70 to 50:50. The spray can is equipped with a spraying means continuously sprayable and is made of aluminum or is made of tin with an anticorrosive resin coating provided on an inner surface of the can. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a spray product for preventing influenza virus infection, in particular,
1) Antivirus which is an aqueous solution containing a mixture of hinokitiol and zinc chloride in an amount of 0.4 to 0.6 molar equivalents of the hinokitiol, or a water-alcohol solution having an alcohol content of 10 to 60% Influenza virus infection, which is a solution, wherein the content of the mixture is 0.001 to 1% by mass based on the mass of the antiviral solution, and 2) a spray can is filled in a spray can Spray products to prevent
The ratio of the antiviral solution to the propellant is in the range of 30:70 to 50:50 by volume ratio, and the spray can comprises spray means capable of continuous spray and is made of aluminum or can The present invention relates to a spray product made of tinplate having an inner surface coated with a corrosion-resistant resin.

In recent years, anti-influenza virus drugs have been actively researched and developed, and drugs capable of suppressing the growth of influenza viruses such as Tamiflu (registered trademark) and Zanamiville (registered trademark) have been developed. However, these anti-influenza virus drugs are not limited to a narrow range in which they can be used, and are not necessarily suitable for general use in terms of side effects. Although it has the effect of suppressing the growth of the virus at the individual level, it cannot prevent the spread of influenza virus infection.
In particular, when most humans do not have immunity to the virus, such as new influenza viruses (type A, H1N1 subtype), it is very difficult to prevent the spread of the virus infection. It is.
If a patient is infected with the new influenza virus, the patient will be isolated or transported to a hospital or health care center for treatment, but the place where the patient occurred, such as a home, classroom, Viruses are likely to remain in offices, hospital rooms, beds, etc. even if there are no patients, so they remain in these places to prevent the spread of virus infection. It is necessary to kill the virus.
Naturally, the work of killing viruses remaining in homes, classrooms, offices, hospital rooms, beds, etc. is a method that can effectively remove viruses, and there is a risk that workers themselves will be infected with viruses. Therefore, it should be a method that can minimize this risk. In addition, considering that there is a high possibility that virus infection will occur simultaneously in many places, it should be as simple as possible. .

On the other hand, it is known that a composition containing hinokitiol and a zinc compound is useful as an antibacterial agent (see, for example, Reference 1).
It has also been reported that a composition containing hinokitiol and a zinc compound exhibits antiviral activity against HIV virus (see, for example, cited document 2).
However, there is no mention of spray products that can exhibit antiviral activity against influenza viruses.

International Publication No. 93/17559 Pamphlet JP 08-259439 A

  The present invention can effectively remove influenza viruses remaining in homes, classrooms, offices, hospital rooms, beds, etc. with a simple operation, and can minimize the risk that the operator himself will be infected with the viruses. The issue is to provide spray products to prevent influenza virus infection.

As a result of intensive studies to solve the above problems, the present inventors have found that an aqueous solution or a water-alcohol solution containing a mixture of hinokitiol and zinc chloride has anti-influenza virus activity and is excellent in safety, At that time, when the amount of hinokitiol and zinc chloride used is in the range of 1: 0.4 to 1: 0.6 in terms of molar ratio, it exhibits excellent anti-influenza virus activity, and a spray equipped with an injection means capable of continuous injection. The spray product in which the solution and the propellant are filled in a can at a volume ratio of 30:70 to 50:50 is a solution having excellent anti-influenza virus activity in a space closed by continuous spraying with a simple one-touch operation. Can be filled with the mist of the virus, so that the influenza virus remaining in the space can be effectively killed. Heading was.
On the other hand, when using a spray can that is widely used, the solution may be modified in the can and the antiviral activity may decrease, but the can is made of aluminum or the inner surface of the can is coated with a corrosion-resistant resin. It has also been found that this modification can be suppressed by using the tin plate.
As described above, the spray product obtained above can effectively remove influenza viruses remaining in homes, classrooms, offices, hospital rooms, beds, etc. with simple operations. The present invention has been completed by finding that it is possible to provide an excellent spray product capable of minimizing the risk of being infected by a virus because it is not necessary to carry out virus killing work in the remaining space.
In particular, the spray product of the present invention is considered to be useful for preventing the spread of new influenza viruses (type A, H1N1 subtype).

That is, the present invention
(1)
1) Antivirus which is an aqueous solution containing a mixture of hinokitiol and zinc chloride in an amount of 0.4 to 0.6 molar equivalents of the hinokitiol, or a water-alcohol solution having an alcohol content of 10 to 60% Influenza virus infection, which is a solution, wherein the content of the mixture is 0.001 to 1% by mass based on the mass of the antiviral solution, and 2) a spray can is filled in a spray can Spray products to prevent
The ratio of the antiviral solution to the propellant is in the range of 30:70 to 50:50 by volume ratio, and the spray can comprises spray means capable of continuous spray and is made of aluminum or can Spray products made of tinplate coated with corrosion-resistant resin on the inner surface,
(2) The antiviral solution is a spray product for preventing influenza virus infection according to (1) above, which contains a naturally-derived deodorant,
(3) The spray product for preventing influenza virus infection according to (1) or (2) above, wherein the mixture comprises hinokitiol and zinc chloride in an amount of 0.45 to 0.55 molar equivalent of the hinokitiol. ,
(4) The spray product for preventing influenza virus infection according to any one of (1) to (3), wherein the antiviral solution has a pH adjusted to 5.5 to 7,
(5) A spray product for preventing influenza virus infection according to any one of (1) to (4), which contains 0.01 to 1% by mass of the mixture based on the mass of the antiviral solution,
(6) The influenza virus infection according to any one of (1) to (5), wherein the propellant is HFC152a, HFC134a, carbon dioxide gas, liquefied propane gas, dimethyl ether, or a mixture of two or more thereof. Spray products to prevent,
(7) The spray product for preventing influenza virus infection according to any one of (1) to (6), wherein the corrosion-resistant resin is a fluororesin, a polyethylene resin, a polyimide resin, or an epoxy resin,
(8) A spray product for preventing influenza virus infection according to any one of (1) to (7), wherein the influenza is avian influenza or human influenza,
About.

According to the present invention, influenza viruses remaining in homes, classrooms, offices, hospital rooms, beds, etc. can be effectively removed with simple operations, and workers themselves enter the spaces where influenza viruses remain and kill them. It is possible to provide a spray product for preventing influenza virus infection that does not require virus work and minimizes the risk of virus infection.
Therefore, the spray product for preventing influenza virus infection of the present invention is useful for preventing the spread of influenza virus infection, and particularly useful for preventing the spread of new influenza viruses (type A, H1N1 subtype). it is conceivable that.

It is the schematic which shows 1 aspect of an injection apparatus. It is a graph which shows the virus titer of avian influenza virus with respect to the density | concentration of hinokitiol and a hinokitiol zinc chloride mixture. It is a figure which shows the external appearance of the spray product used in Example 1. FIG.

The present invention will be described in more detail.
The spray product for preventing influenza virus infection of the present invention,
1) Antivirus which is an aqueous solution containing a mixture of hinokitiol and zinc chloride in an amount of 0.4 to 0.6 molar equivalents of the hinokitiol, or a water-alcohol solution having an alcohol content of 10 to 60% Influenza virus infection, which is a solution, wherein the content of the mixture is 0.001 to 1% by mass based on the mass of the antiviral solution, and 2) a spray can is filled in a spray can Spray products to prevent
The ratio of the antiviral solution to the propellant is in the range of 30:70 to 50:50 by volume ratio, and the spray can comprises spray means capable of continuous spray and is made of aluminum or can It is made of tinplate with an inner surface coated with a corrosion-resistant resin.

The hinokitiol used in the present invention may be a natural product extracted from an essential oil derived from a raw material plant such as Thai cypress, hiba, asunaro, or a chemically synthesized product. Commercially available hinokitiol may be used as it is. As a raw material plant, hiba is preferable from the viewpoint of availability. Extraction and purification of hinokitiol from the raw material plant can be performed by a known method. As the essential oil, Hiba oil is preferable. Chemically synthesized products can also be obtained by known methods. Examples of commercially available products include those sold by Takasago Fragrance Co., Ltd. and Osaka Organic Chemical Industry Co., Ltd.

In the spray product for preventing influenza virus infection of the present invention, a mixture comprising hinokitiol and zinc chloride in an amount corresponding to 0.4 to 0.6 molar equivalent of the hinokitiol is used.
The mixture is preferably a mixture of hinokitiol and zinc chloride in an amount that provides 0.45 to 0.55 molar equivalent of the hinokitiol, more preferably 0.5 molar equivalent of hinokitiol and the hinokitiol. A mixture of a quantity of zinc chloride.

The amount of the mixture used is in the range of 0.001 to 10% by mass based on the mass of the antiviral solution, preferably 0.01 to 1% by mass based on the mass of the antiviral solution, Used in the range of 15 to 1% by mass.
Moreover, the zinc chloride used for the spray product for preventing the influenza virus infection of this invention can be obtained commercially, for example.

The antiviral solution containing the mixture is an aqueous solution in which the mixture is dissolved, or a water-alcohol solution having an alcohol content of 10 to 60%.
The water used for the aqueous solution and the water-alcohol solution can be tap water or purified water such as deionized water or distilled water, but it is preferable to use purified water such as deionized water.
Examples of the alcohol used in the water-alcohol solution include methanol, ethanol, ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, polyethylene glycol, and glycerin. These may be used alone or in combination. A preferred alcohol is ethanol.

  When the water-alcohol solution is used as the antiviral solution containing the mixture, the amount of water and alcohol used relative to the total amount of the solution is not particularly limited, but in total, for example, 10 to 99.8% by mass Range.

The antiviral solution may also contain glycerin.
Examples of glycerin include glycerin and various derivatives of glycerin.

The antiviral solution may include citric acid and / or an alkali metal salt of citric acid. Sodium citrate is preferred as the alkali metal salt of citric acid.
The antiviral solution may include ethylenediaminetetraacetic acid or an alkali metal salt thereof. An alkali metal salt of ethylenediaminetetraacetic acid is preferred, and disodium ethylenediaminetetraacetic acid is preferred.
The antiviral solution may include etidronic acid or an alkali metal salt thereof. An alkali metal salt of etidronic acid is preferred, and tetrasodium etidronate is preferred.
In addition to the zinc compound, the antiviral solution may further contain a sodium compound or an aluminum compound.
Examples of the sodium compound include sodium hydroxide, and examples of the aluminum compound include aluminum oxide, aluminum hydroxide, aluminate, chlorohydroxyaluminum, aluminum chloride, aluminum fluoride, aluminum sulfate, aluminum nitrate, Examples thereof include aluminum borate, aluminum phosphate, potassium alum, ammonium alum and sodium alum.

The antiviral solution preferably contains a naturally-derived deodorant.
The mixture of hinokitiol and zinc chloride is odorless, so it is difficult to determine whether the mist of the antiviral solution is sufficiently distributed throughout the space.
Therefore, the naturally-derived deodorant can also be used to determine whether or not the mist is sufficiently distributed throughout the space from the scent.
Naturally-derived deodorants include, for example, cedar, cocoon, cocoon, nettle, cocoon, black pine, red pine, spruce, cocoon, bear moth, mugwort, tea, birch, perilla, aloe, salamander, amacha sull, etc. Examples thereof include an arbitrary mixture of extracted extracts as raw materials.
In addition, as the natural deodorant, a commercially available natural deodorant can be used. For example, a phytoncide (trade name “Smernark”) manufactured by Tokai Kosan Co., Ltd. can be used.
Examples of the naturally-occurring deodorant include ougon extract, yeast extract, eucalyptus extract, cucumber extract, rosemary extract, clove extract, asparasanelia extract, kumazasa extract, nettle extract, black tea extract, oolong tea extract, sweet tea extract, persimmon Deodorant extracts such as extracts can also be used.
The amount of the natural deodorant used may be 0.001 to 5% by mass based on the mass of the antiviral solution.

The antiviral solution may also include at least one plant extract selected from the group consisting of aloe, green tea, kumaromi, and dokudami.
The extract of aloe refers to an extract obtained by extracting the jelly-like body (meat meat) possessed by aloe into the leaves by a thick squeezing extraction method and concentrating and stabilizing it by applying heat. Instead of such an aloe extract, the main component anthraquinone derivative aloin or barberloin may be used. The aloe extract includes aloe-emodin, aloesin, aloenin, etc. in addition to aloin and barberloin.
The amount of aloe extract used is 0.002 to 10% by mass, preferably 0.01 to 1% by mass, more preferably 0.05 to 10% by mass based on the mass of the antiviral solution. It can be used in the range of 0.25% by mass.

As an extract of green tea, a crushed green tea extracted with hot water, purified and concentrated is used. The main component of the green tea extract is tea polyphenols. Tea polyphenol is a general term for compounds having a plurality of phenolic hydroxyl groups in the molecule, and includes catechin, epicatechin, gallocatechin, epigallocatechin, epigatechin gallate, epigallocatechin gallate and the like as main components.
The amount of green tea extract used is 0.002 to 10% by mass, preferably 0.01 to 1% by mass, more preferably 0.05 to 10% by mass based on the mass of the antiviral solution. It can be used in the range of 0.25% by mass.

The extract of kumabuchi can be obtained by extracting kumabuchi using a low temperature and high pressure extraction method. The low-temperature and high-pressure squeezing extraction method is a method of extracting without increasing the temperature with a mechanical device in which the bearfish is set to a high pressure, and a liquid obtained by concentrating the liquid squeezed at that time becomes a bearfish extract. Kumagusu is a kind of grass family that is widely distributed in Japan and China. In addition to triterpenol (β-amylin Frieden), which is the main component, kumabuchi extract contains lignin residue, reducing sugars, and sugars such as glucose. A mixture of these synthetic products can also be used in place of the extract of Kumagusu.
The amount of kumabuchi extract used is 0.001 to 5% by mass, preferably 0.005 to 0.3% by mass, and more preferably 0.001 to 5% by mass based on the mass of the antiviral solution. It can be used in the range of 01 to 0.1% by mass.

Dokudami is a perennial that is distributed in Japan, Tai Wan, China, Himalayas, and Java, and is found in mountains and gardens. The dokudami extract is extracted by a method called a low-temperature and high-pressure squeezing extraction method, similar to Kumagusu. Dokudami extract contains quercitrin, afzenin, hyperin, rutin, chlorogenic acid, β-sitosterol, cis and trans-N- (4-hydroxystyryl) . A mixture of these synthetic products can also be used in place of the extract of Kumagusu.
The amount used when using the extract of Dokudami is 0.001 to 5% by mass, preferably 0.001 to 0.3% by mass, more preferably 0.001% based on the mass of the antiviral solution. It can be used in the range of 01 to 0.1% by mass.

  When using the said extract, you may use only 1 type selected from the extract of an aloe, green tea, a bear candy, and a wolfberry, but it is preferable to use 2 or more types together, and said 4 types of extracts are used. More preferably, all are included.

  The antiviral solution may contain other components as long as the effects of the present invention are not impaired. For example, diglycerin, diglycerin derivatives (for example, polyoxypropylene (9) diglyceryl ether, polyoxypropylene ( 14) Diglyceryl ether), ethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, 1,3-butylene glycol, hexylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1, Moisturizers such as 2-octanediol, 1,2-nonanediol, 1,2-decanediol, sorbitol, xylitol, erythritol, sugar, maltitol, trehalose, glucosyltrehalose, hyaluronic acid, sodium hyaluronate , Chitin, chitosan, aloe extract, such as medicinal ingredients, such as Coptis extract can be formulated.

  It is preferable to adjust the final pH of the antiviral solution to a range of 5.5 to 7, more preferably a range of 6.0 to 7.

Preferred embodiments of the antiviral solution include the following.
A solution having a pH of 5.5 to 7 containing 0.01 to 1.0% by mass of a hinokitiol zinc chloride mixture, water, ethanol and glycerin.
PH 5.5 to 7 solution containing 0.15-1.0% by weight of hinokitiol zinc chloride mixture, water, ethanol and glycerin.
0.01-1.0% by weight hinokitiol zinc chloride mixture, 0.01-1.0% by weight hinokitiol aluminum chloride mixture, 0.01-1.0% by weight hinokitiol sodium hydroxide mixture, water, ethanol and PH 5.5 to 7 solution containing glycerin.

Examples of the propellant used in the spray product for preventing influenza virus infection of the present invention include alternative chlorofluorocarbons such as HFC152a and HFC134a, carbon dioxide, liquefied propane gas (LPG), dimethyl ether (DME), or two of these. The above mixture is mentioned.
The ratio of the antiviral solution to the propellant is in the range of 30:70 to 50:50, preferably in the range of 35:65 to 45:55, based on the volume ratio.

The spray product for preventing influenza virus infection according to the present invention is formed by filling a spray can with the antiviral solution and the propellant.
The spray can includes an injection unit capable of continuous injection.
The injection means is not particularly limited as long as it is an injection device capable of continuous injection, and examples thereof include a full-quantity injection type injection device.
Examples of the full-quantity injection type injection device include an injection device that enables full-quantity injection by maintaining the injection state by rotating, and an injection that enables full-quantity injection by maintaining the injection state by pressing the injection button Examples thereof include an apparatus.
In addition, when the injection button is pressed, it is injected only while it is pressed, but when the injection button is pressed beyond a certain angle, the injection button is fixed and the injection state is maintained, and an injection device that enables continuous injection is adopted. You can also.

The spray angle set by the spray device is preferably 45 degrees or more with respect to the installation surface of the spray can, and 90 degrees with respect to the installation surface of the spray can, that is, at an angle in the ceiling direction. There may be.
Moreover, although it is a horizontal injection angle normally, when performing continuous injection, it has a movable injection nozzle which enables injection at an angle of 45 degrees or more with respect to the installation surface of the spray can. An injection device can also be employed.
A preferred injection angle is in the range of 45 to 60 degrees.

One mode of an injection device that can be used for the spray product of the present invention will be described with reference to a schematic view (FIG. 1).
The injection device 1 illustrated in FIG. 1 includes an injection button 3, an injection nozzle 4, a locking portion 5, a protruding portion 6, a step portion 7, and the like.
When the injection button 1 is pressed down, the stem 2 is also pressed down to be in an open state, and the solution and the liquefied gas are sprayed from the injection nozzle 4 by the pressure of the propellant.
At this time, the protrusion 6 is engaged with the stepped portion 7 and fixed so that the injection button 3 does not rise, the open state is maintained, and the solution and the liquefied gas are continuously injected.

The solution may react with, for example, copper or the like to reduce the antiviral activity.
Therefore, the spray can used in the present invention is made of aluminum or the tin coated with a corrosion-resistant resin on the inner surface of the can.
The corrosion-resistant resin is not particularly limited as long as it is a resin having corrosion resistance, but a fluororesin, a polyethylene resin, a polyimide resin, an epoxy resin, and the like are preferable, and a fluororesin is preferable.

The solution containing the zinc chloride mixture used in the spray product for preventing influenza virus infection of the present invention described above has antiviral activity against both avian influenza virus and human influenza virus and is highly safe. Thus, the present invention also relates to a spray product for preventing influenza virus infection directed against avian influenza virus or human influenza virus.
In particular, the spray product of the present invention can be expected to prevent the spread of new influenza viruses (type A, H1N1 subtype).
As the configuration of the spray product for preventing influenza virus infection targeting the avian influenza virus or the human influenza virus, the same configuration as that presented above can be adopted.

  The following examples illustrate the invention in more detail. However, the examples are for illustrating the present invention and are not intended to limit the present invention in any way.

Production Example 1: Preparation of anti-influenza virus solution 150 g of methanol was dissolved dropwise in 32.8 g (0.2 mol) of hinokitiol at 40 ° C. to 50 ° C. and stirred at the same temperature for 1 hour. To this solution, a solution of 13.6 g (0.1 mol) of zinc chloride (ZnCl ₂ ) dissolved in 100 g of methanol was added dropwise at 30 ° C. to 40 ° C. over 1.6 hours, and 5 ° C. at 40 ° C. to 45 ° C. Reacted for hours. After cooling, the precipitate was collected by filtration, and the filtrate was washed twice with 30 g of methanol. Under reduced pressure (133.3 Pa)
By drying at 19 to 48 ° C., 37.1 g of a hinokitiol zinc chloride mixture was obtained as a pale yellow mass.
The following anti-influenza virus solution was prepared by dissolving the hinokitiol zinc chloride mixture (Ht-Zn) obtained above in 30% ethanol (aqueous solution) or 50% ethanol (aqueous solution).
1.0% Ht-Zn 30% ethanol (aqueous solution)
0.3% Ht-Zn 30% ethanol (aqueous solution)
2.0% Ht-Zn 50% ethanol (aqueous solution)
0.15% Ht-Zn 50% ethanol (aqueous solution)

Production Example 2: Preparation of anti-influenza virus solution Synthetic hinokitiol (JCS, lot # 05928602) and zinc chloride were mixed at a ratio of 65:35 (hinokitiol: zinc chloride = 1: 0.54), and this was mixed with 30% ethanol ( The following anti-influenza virus solution was prepared by dissolving in 50% ethanol (aqueous solution). 1.0% Ht-Zn 30% ethanol (aqueous solution)
0.3% Ht-Zn 30% ethanol (aqueous solution)
0.2% Ht-Zn 30% ethanol (aqueous solution)
0.15% Ht-Zn 30% ethanol (aqueous solution)
0.10% Ht-Zn 30% ethanol (aqueous solution)
0.05% Ht-Zn 30% ethanol (aqueous solution)
0.01% Ht-Zn 30% ethanol (aqueous solution)
1.0% Ht-Zn 50% ethanol (aqueous solution)
0.8% Ht-Zn 50% ethanol (aqueous solution)
0.4% Ht-Zn 50% ethanol (aqueous solution)
0.2% Ht-Zn 50% ethanol (aqueous solution)
0.1% Ht-Zn 50% ethanol (aqueous solution)
0.05% Ht-Zn aqueous solution

Production Example 3: Preparation of a solution containing hinokitiol sodium salt A solution of 112 g (0.7 mol) of 25% aqueous sodium hydroxide solution and 121.1 g (0.738 mol) of hinokitiol in 160 g of methanol at 35 ° C. to 40 ° C. Slowly dripped. The solution was reacted at 30 ° C. to 40 ° C. for 2 hours. The solvent (methanol) was distilled off under reduced pressure to precipitate a yellow mass, and the residue was recrystallized with 300 g of acetone, filtered, and dried under reduced pressure (133.3 Pa, 7 hours). The sodium salt (dihydrate, 133 g) was obtained.
The hinokitiol sodium salt obtained above was dissolved in 30% ethanol (aqueous solution) to prepare 3% hinokitiol sodium salt 30% ethanol (aqueous solution).

Test Example 1: Antiviral effect of hinokitiol, hinokitiol zinc chloride mixture and hinokitiol sodium salt against influenza virus (PR-8 strain) Specimen 1.0% Ht—Zn 30% ethanol (aqueous solution) and 0.3% Ht—Zn 30% ethanol (aqueous solution) prepared in Production Example 1, 3% hinokitiol sodium salt 30% ethanol prepared in Production Example 3 (Aqueous solution) and 1% hinokitiol 30% ethanol (aqueous solution) prepared by dissolving hinokitiol in 30% ethanol aqueous solution were used as test solutions.
2. Test purpose An inactivation test of the specimen prepared above against influenza virus (PR-8 strain) is performed.
3. Outline of the test Influenza virus solution was added to and mixed with the sample to prepare a working solution. Inversion mixing was performed at room temperature for 60 minutes, and the virus infectivity of the working solution was measured after the action. As controls, a 30% ethanol aqueous solution and a phosphate buffer (PBS) were used.
4). Test method 1) Test virus Influenza virus (PR-8 strain) (Influenza virus PR8 strain) (inoculated into eggs of growing chickens, collected 2 days later HA: 2048)
2) Cells used MDCK cells (RIKEN BioResource Center)
3) Medium used (1) Cell growth medium A Dulbecco's modified MEM (Sigma) supplemented with kanamycin (0.05 mg / mL) and fetal bovine serum (10%) was used.
(2) Cell maintenance medium What added kanamycin (0.05 mg / mL), trypsin, and BSA (0.1%) to Dulbecco's modified MEM (Sigma) was used.
4) Virus suspension The test virus solution was diluted 100 times with PBS and used.
5) Test operation 0.5 mL of the virus suspension was added to and mixed with 0.5 mL of the sample to prepare a working solution. After acting by inversion mixing at room temperature for 60 minutes, the working solution was serially diluted 10-fold with 0.1% BSA / PBS.
6) Measurement of virus infectivity titer Using cell growth medium, the cells used were monolayer-cultured in a microplate (96 wells), then the cell growth medium was removed, and after washing twice with MEM, each dilution of the working solution Inoculate 0.1 mL in 4 wells, react in a 36 ° C carbon dioxide (5%) incubator for 1 hour, remove the diluted solution, add 0.1 mL of cell maintenance medium to each well, and add 36 ° C carbon dioxide. The cells were cultured for 5 days in a gas (5%) incubator. After culturing, the presence or absence of cell degeneration was observed with an inverted microscope, the presence or absence of HA in the culture medium was confirmed using chicken erythrocytes, and the 50% tissue culture infectious dose (TCID ₅₀ ) was calculated by the Reed-Muench method.
The results are summarized in Table 1.

  From the above results, when hinokitiol, hinokitiol zinc chloride mixture and hinokitiol sodium salt were used, human influenza virus was not detected, thereby confirming that it had an antiviral effect against human influenza virus.

Test example 2: Antiviral effect of hinokitiol zinc chloride mixture (Ht-Zn) against human influenza virus (1) Examination of drug concentration, sensitization time and sensitization temperature Examination of optimal and minimum sensitization concentration time (objective drug concentration) The relationship between sensitization time and sensitization temperature)
1. Test Method Test Agent: 0.3% Ht—Zn 30% ethanol (aqueous solution), 0.2% Ht—Zn 30% ethanol (aqueous solution), 0.15% Ht—Zn 30% ethanol (aqueous solution) prepared in Production Example 2 Aqueous solution), 0.10% Ht—Zn 30% ethanol (aqueous solution), 0.05% Ht—Zn 30% ethanol (aqueous solution) and 0.01% Ht—Zn 30% ethanol (aqueous solution) were used for the test.
1) Cells used and cell culture medium: MDCK cells (RIKEN BioResource Center) were purchased and subcultured in the laboratory for use in experiments. MDCK cells were obtained by adding kanamycin (0.05 mg / mL) and fetal bovine serum (10%) to Dulbecco's modified MEM (DMEM, Sigma) in cell growth medium. KMEM (0.05mg / mL) in DMEM as cell maintenance medium during virus infection
), Trypsin (0.625 g / mL) and BSA (0.1%) were used. On the day before the test, 0.1 mL of MDCK cells adjusted to 2.5 × 10 ⁵ / mL / cell growth medium was cultured overnight in a 37 ° C. CO ₂ (5%) incubator in each hole of a 96-well tissue culture plate. did. 2 in each hole with serum-free MEM
Washed twice and used for testing.
2) Virus used: Human influenza virus A / PR / 8/34 (H1N1) strain should be 1 × 10 ⁶ TCID ₅₀ /0.1 mL when using the virus solution collected 3 days after inoculation on 10-day-old embryonated eggs Adjusted and used.
3) Confirmation of virus growth: Confirmation of virus growth is carried out by culturing MDCK cells for 5 days after sensitizing the virus, then inoculating and culturing the cells (second generation), and the chicken erythrocyte aggregation ability (HA) in the culture supernatant. ) To determine the final decision. Since the A / PR / 8/34 (H1N1) strain has HA, if the virus remains, the child virus that infects and proliferates in the cells is released into the culture supernatant, and as a result, HA in the culture supernatant. Is recognized.
Neutral red uptake test: A toxicity test was conducted using the property that neutral red is taken up and accumulated in ribosomes of sperm cells.
Remove the culture fluid from the test material, add 0.1 mL of neutral red solution (150 μg / mL / PBS), incubate in a 37 ° C CO ₂ ((5%) incubator for 2 hours, remove the neutral red solution, and remove the cells with 0.1 mL of PBS. After washing twice, 0.1 mL of 1% acetic acid / 50% ethanol solution was added and reacted for 20 minutes to extract neutral red incorporated into the cells, and the extract was transferred to a microplate for absorbance measurement and the absorbance was measured at 540 nm.

The following tests were performed at 25 ° C. and 10 ° C. to determine the optimal and minimum sensitization time of the drug.
(Method) Ht-Zn of each concentration is mixed with 30% ethanol (aqueous solution) with an equal amount of virus solution (10 ⁶ TCID ₅₀ /0.1mL) and left at 25 ° C for 10, 20, or 30 minutes for sensitization Then, immediately dilute 1,000 times with ice-cold PBS, inoculate 0.1 mL into a 2-well (96-well plate) MDCK cells, react for 1 hour, and replace the sensitized dilution with trypsin-containing cell maintenance medium at 37 ° C. Cultured for 5 days. After culturing, the hemagglutination (HA) in the culture is checked, and the HA negative culture is further inoculated and cultured in the cell (second generation). Any well that was virus-negative was considered negative. The same procedure was performed using 30% ethanol and PBS as controls.
Furthermore, in order to examine the influence of the sensitization temperature, the same test was performed at a sensitization temperature of 10 ° C.
The effective concentration of Ht-Zn was expressed as the average value of three experiments.
Since the maximum concentration of Ht-Zn used in this study was 0.30% and the final cell sensitization concentration was 0.00015%, the cytotoxicity of Ht-Zn was considered not to affect this study.
result:
The minimum sensitizing concentration of Ht-Zn at a sensitizing temperature of 25 ° C was 0.15% (10 minutes), 0.22% (20 minutes), and 0.15% (30 minutes) (Table 2).
The minimum sensitizing concentration of Ht-Zn at a sensitizing temperature of 10 ° C. was 0.30% (20 minutes) (Table 3).
At a sensitization time of 10 minutes, a virus inactivating effect was observed in Test 1 at the maximum concentration of 0.3% used in the test, but not in Test 2 and in Test 3, an inactivating effect was observed in one well. In addition, when the sensitization time was 30 minutes with 0.3% Ht-Zn, an inactivation effect was observed in Test 2, but in Tests 1 and 3, only one well was inactivated.
When the sensitizing solution was allowed to stand at a sensitizing temperature of 10 ° C., white turbidity and precipitation occurred in the sensitizing solution.
In order to investigate the instability of the results of the inactivation test at a sensitization temperature of 10 ° C, sensitization was performed for 60 minutes while mixing the sensitization solution, and a virus inactivation effect was observed in the 0.3% Ht-Zn solution. .

(2) Confirmation of antiviral effect of Ht-Zn
(Purpose: To investigate the antiviral effect of Ht-Zn)
For the purpose of confirming the antiviral effect of the drug, the effect was compared with other drugs and disinfectants.
In order to confirm the antiviral effect of Ht-Zn, the minimum effective concentration Ht-Zn (0.15%) A: 2 mg (titer) / mL streptomycin 0.0525% zinc chloride in PBS, C1: 100% ethanol solution, C2: 50
% Ethanol solution, C3: 30% ethanol solution, E: 0.0975% HT 30% ethanol solution F: 0.1% BSA / PBS, H: 0.0525% zinc chloride 30% ethanol solution and equivalent virus solution (10 ⁶ TCID ₅₀ /0.1 mL
) And reaction at 25 ° C for 30 minutes, immediately diluted 1,000 times with ice-cold PBS to eliminate the effect of the drug, 0.1 mL was inoculated into a 2-well (96-well plate) MDCK cells and reacted for 1 hour, The sensitized dilution is replaced with trypsin-containing cell maintenance medium and cultured at 37 ° C. for 5 days. After culture, the hemagglutination (HA) in the culture is examined. For HA negative cultures, inoculate and culture the cells (2nd generation) and check for the presence of HA. The final determination is made, and those that are virus negative in both wells are negative (negative confirmation). G minimum effective concentration Ht-Zn (0.15%) was mixed with an equal amount of PBS, reacted at 25 ° C. for 30 minutes, similarly diluted 1000 times and inoculated into MDCK cells.
7 for reference
B: The test using coronavirus (drug-sensitive virus other than influenza virus) could not be performed because it did not show the high virus titer required for the test on MDCK cells (Note 1). We continue to train pig coronavirus to MDCK cells and recover high titer viruses using Vero cells.
Parvovirus was not performed because it cannot grow on MDCK cells (Note 2).

result:
Influenza virus and 0.15% Ht-Zn 30% ethanol solution were sensitized for 30 minutes at 25 ° C, and it was confirmed that no virus growth was observed. In the control group, virus growth in a mixture of drugs other than A virus and HT and zinc chloride, C3 virus and 30% ethanol, E virus and HT single solution, F virus and diluted sensitization solution, and H virus and zinc chloride single solution Was recognized. In addition, no virus growth was observed in the sensitizing solution of C1 virus and 100% or C2 virus and 50% ethanol. As a result, it became clear that the virus inactivation effect of Ht-Zn was recognized by mixing hinokitiol and zinc chloride.

Discussion In the test at a sensitization temperature of 10 ° C, the maximum test concentration of 0.3% Ht-Zn and the virus sensitization solution are:
During the reaction time, white turbidity / precipitation occurred in the sensitizing solution, affecting the test results and reducing the antiviral effect.
Tests using hinokitiol sensitive and insensitive viruses in the control group showed that virus infection in MDCK cells in parvovirus because coronavirus did not grow to a virus titer (virus concentration) that could be tested for antiviral efficacy in MDCK cells. No antiviral effect test was performed as it did not show growth. For coronavirus, we are trying to create a high titer virus.
When white turbidity / precipitation occurred in the Ht-Zn solution or the sensitizing solution, the antiviral effect was rapidly reduced. This coincided well with the phenomenon in which Ht was separated in a diluted solution of PBS with high-concentration Ht ethanol solution and no antiviral effect was observed. It was thought that the virus inactivating action of Ht-Zn required that Ht-Zn was dissolved in the solvent. When thinking about practical use,
It can be used in a state completely dissolved in an ethanol solution.
The minimum sensitizing concentration of Ht-Zn (sensitizing temperature: 25 ° C) is 0.15% (10 minutes), 0.22% (20 minutes), and 0.15% (30 minutes). At a sensitization temperature of 10 ° C, Ht-Zn separation occurred and stable results could not be obtained.
As a result of the test using the control group, a virus inactivating action was observed in the mixed solution of hinokitiol and zinc chloride.

Test Example 3: Antiviral effect against avian influenza virus 1) Avian influenza virus A / whisling swan / Shimane / 499/1983 is a weakly attenuated H5 subtype virus isolated from swan dung that came to Shimane Prefecture in 1983 The 83 (H5N3) strain was successfully intensified by passage with chicks. The attenuated virus was used in the following experiments.
2) SPF 10-day-old embryonated chicken egg A fertilized egg was purchased from Aoki breeding ground in Tochigi Prefecture, incubated and used for experiments.
3) Test 2.0% Ht—Zn 50% ethanol (aqueous solution) and 0.15% Ht—Zn 50% ethanol (aqueous solution) prepared in Production Example 1 were used as test solutions.
An equal amount of virus solution was added to the test solution prepared above and mixed well. As a negative target, a 50% ethanol aqueous solution was used, and similarly, an equal amount of virus solution was added and mixed well.
After each solution was allowed to stand at room temperature for 10 minutes, the test solution-virus mixture was rapidly diluted 10-fold with PBS, and in each chorioallantoic cavity of three 10-day-old chicken eggs for each dilution. Each 0.2 mL was inoculated.
The inoculated growing chicken eggs were cultured at 37 ° C. for 48 hours, and then the presence or absence of virus growth in chorioallantoic fluid was confirmed by a 0.5% chicken hemagglutination (HA) test. Residual virus titer is Reed
and the method of and Muench.
The cumulative negative number, cumulative positive number and cumulative positive rate in each test solution-virus mixture are shown in Tables 5 to 7, and the virus titers are summarized in Table 8.
FIG. 2 is a graph showing the virus titer of avian influenza virus versus the concentration of hinokitiol and hinokitiol zinc chloride mixture.

Based on the above results, no virus survived as long as 10 minutes of contact between the sample liquid and the avian influenza virus at room temperature, and the virus was inactivated at least 1/1000 or less. Became clear. This subject was confirmed to have an antiviral effect against avian influenza virus.
In addition, it was demonstrated that the hinokitiol zinc chloride mixture exhibits an antiviral effect even at a low concentration of 0.15% (Table 6 and FIG. 2).

Test Example 4: Antiviral effect of hinokitiol zinc chloride mixture (Ht-Zn) against avian influenza virus (1) Examination of drug concentration, sensitization time and sensitization temperature (Objective drug concentration, sensitization time and sensitization temperature )
1) Examination of optimal and minimum sensitization concentration time
(Purpose: To investigate the relationship between concentration of antiviral effect and time)
1. Test Method 1) Test Agent: 0.8% Ht-Zn 50% Ethanol (Aqueous Solution), 0.4% Ht-Zn 50% Ethanol (Aqueous Solution), 0.2% Ht-Zn 50% Prepared in Production Example 2 Ethanol (aqueous solution) and 0.1% Ht-Zn 50% ethanol (aqueous solution) were subjected to the test. Eggs used (SPF 10-day-old chick eggs): We purchased fertilized eggs from Aoki breeding grounds in Tochigi Prefecture and incubated them at this research center for experiments.
Virus used: Avian influenza virus A / Whistling swan / Shimane / 499/83 (H5N3) strain was inoculated into 10-day-old embryonated chicken eggs 2 days after inoculation (virus titer 1 × 10 ^8.5 EID ₅₀ /0.1 mL) Was used.
2) Confirmation of virus growth: Virus growth was confirmed by inoculating and cultivating the embryonated hen's egg (2nd generation) after inoculating the chick egg with the virus for 2 days and then incubating and cultivating it. The final judgment was made by examining the presence or absence of HA).

0.8% Ht—Zn 50% ethanol (aqueous solution), 0.4% Ht—Zn 50% ethanol (aqueous solution), 0.2% Ht—Zn 50% ethanol (aqueous solution) prepared in Production Example 2 1% Ht—Zn 50% ethanol (aqueous solution) was used as a test solution. A 50% aqueous ethanol solution was used as a negative control. Mix 400 μL of virus solution diluted 100-fold with PBS and 400 μL of test solution, let stand at 25 ° C or 4 ° C for 1, 10, 20 and 30 minutes, then inoculate 0.2 mL each into 10-day-old chicken egg chorioallantoic membrane did. Since 0.8% test solution is lethal to chicken eggs, dilute 10-fold with PBS, negative control, stand still for 30 minutes, dilute 10-fold with PBS, and inoculate 0.2 mL each into 10-day-old chicken egg chorioallantoic membrane did. After culturing for 2 days, the allantoic fluid was collected and reacted with 0.5% chicken erythrocyte suspension to determine the presence or absence of virus growth based on the presence or absence of chicken erythrocyte aggregation. Samples negative for the hemagglutination test were inoculated with the collected allantoic fluid again into the 10-day-old chicken egg chorioallantoic membrane, and the presence or absence of virus growth was determined in the same manner as described above. The virus titer was calculated by the method of Reed and Muench.

<Result>
(Reaction temperature 25 ℃)
Table 9 shows the virus survival rate when the test solution and the virus solution were reacted at 25 ° C. for each time. Moreover, the virus titer when the negative control and the virus solution were reacted for 30 minutes was 10 ^6.25 EID ₅₀ /0.2 mL or more. When the hinokitiol zinc chloride mixture solution was at a concentration of 0.4%, it was shown to inactivate the virus 100% in 1 minute. When the hinokitiol zinc chloride mixture solution was less than 0.1%, the virus could not be inactivated 100% even after 30 minutes of reaction. In addition, at a concentration of 0.2%, the virus could not be inactivated 100% with a reaction time of 1 minute, but the virus can be completely inactivated by extending the reaction time to 10 minutes or more. Was confirmed.

(Reaction temperature 4 ℃)
Table 10 shows the virus survival rate when the test solution and the virus solution were reacted at 4 ° C. for each time. The virus titer when the negative control and virus solution were reacted for 30 minutes was 10 ^6.42 EID ₅₀ /0.2 mL or more. A concentration of 0.8% hinokitiol zinc chloride mixture was shown to inactivate 100% of the virus in 1 minute. When the hinokitiol zinc chloride mixture was less than 0.2%, the virus could not be inactivated 100% even with a reaction of 30 minutes, but at a concentration of 0.4%, the virus could be inactivated 100% by reacting for 10 minutes or more. Is confirmed to be possible.

<Conclusion>
When the hinokitiol zinc chloride mixture solution and the virus solution were reacted in equal amounts, it was confirmed that the anti-influenza virus effect of the hinokitiol zinc chloride mixture solution was enhanced by increasing the reaction time. Influenza virus by reacting a hinokitiol zinc chloride mixture solution with a concentration of 0.2% when reacted at 25 ° C, or a hinokitiol zinc chloride mixture solution with a concentration of 0.4% when reacted at 4 ° C for 10 minutes with the virus solution. It was shown that it can be inactivated.

2) Examination of sensitization temperature
(Purpose: To investigate the relationship between anti-influenza virus effect and temperature)
0.4% Ht—Zn 50% ethanol (aqueous solution), 0.2% Ht—Zn 50% ethanol (aqueous solution) and 0.1% Ht—Zn 50% ethanol (aqueous solution) hinokitiol zinc chloride prepared in Production Example 2 The mixture was used as a test solution. As controls, a 50% ethanol aqueous solution and 100% ethanol were used. 400 μL of the virus solution diluted 100 times with PBS and 400 μL of the test solution were mixed. As a negative control, 400 μL of a 0.2% hinokitiol zinc chloride mixture solution and 400 μL of PBS were mixed. After standing at 4 ° C., 10 ° C., and 25 ° C. for 10 minutes, 0.2 mL each was inoculated into the chorioallantoic membrane of a 10-day-old chicken. The mixture of 50% ethanol aqueous solution and virus solution was allowed to stand for 10 minutes and then washed with PBS.
The doubling step was diluted, and 0.2 mL was inoculated into the chorioallantoic membrane of 10-day-old chickens. After culturing for 2 days, the allantoic fluid was collected and reacted with 0.5% chicken erythrocyte suspension to determine the presence or absence of virus growth based on the presence or absence of chicken erythrocyte aggregation. For specimens with a negative hemagglutination test, the collected allantoic fluid was again inoculated into the 10-day-old chicken egg chorioallantoic membrane 0.2 mL each, and the presence or absence of virus growth was determined by the same method as described above. The virus titer was calculated by the method of Reed and Muench.

<Result>
Table 11 shows the survival rate of the virus when the test solution and the virus solution were reacted at each temperature for 10 minutes. In addition, when the 50% ethanol aqueous solution and virus solution were reacted at 4 ° C, 10 ° C and 25 ° C, the virus titers were 10 ^6.5 EID ₅₀ /0.2 mL, 10 ⁶ EID ₅₀ /0.2 mL and 10 ^6.5 EID ₅₀ / It was 0.2 mL or more. The 0.4% hinokitiol zinc chloride mixture solution was completely inactivated by reacting with the virus solution for 10 minutes at 4 ° C and 10 ° C. In addition, 0.2% hinokitiol zinc chloride mixture solution and 100% ethanol did not show sufficient anti-influenza virus effect at 4 ° C and 10 ° C, but completely inactivates the virus at 25 ° C. Was confirmed.

<Conclusion>
It was confirmed that the hinokitiol zinc chloride mixture solution had different anti-influenza virus effects depending on the reaction temperature, and the effect was enhanced by increasing the reaction temperature.

3) Confirmation of antiviral effect of Ht-Zn (Objective: To investigate the antiviral effect of Ht-Zn)
0.2% Ht—Zn 50% ethanol (aqueous solution) prepared in Production Example 2 was used as a test solution. As a control, A: Streptomycin zinc chloride mixed solution (0.01% streptomycin: 0.06% zinc chloride: 50% ethanol aqueous solution), C: 100% ethanol, E: 0.2% hinokitiol 50% ethanol aqueous solution and F: 50% ethanol aqueous solution. Using. As described above, avian influenza virus was used as a test virus, and B: Newcastle disease virus (NDV) -La Sota strain and D: Chicken infectious bronchitis virus (IBV) -Beaudette42 strain were used as test viruses. 400 μL of each virus solution diluted 100 times with PBS and 400 μL of the test solution were mixed. As a negative control, 400 μL of a G: 0.2% hinokitiol zinc chloride mixture solution and 400 μL of PBS were mixed and used. After standing at 25 ° C. for 10 minutes, 0.2 mL was inoculated into the chorioallantoic membrane of a 10-day-old chicken. The mixed solution of 50% ethanol aqueous solution and virus solution was allowed to stand for 10 minutes and then diluted 10-fold with PBS to inoculate 0.2 mL each into a 10-day-old chicken egg chorioallantoic membrane. After culturing for 2 days, the allantoic fluid was collected and reacted with 0.5% chicken erythrocyte suspension to determine the presence or absence of virus growth based on the presence or absence of chicken erythrocyte aggregation. For specimens with a negative hemagglutination test, the collected allantoic fluid was again inoculated into the 10-day-old chicken egg chorioallantoic membrane 0.2 mL each, and the presence or absence of virus growth was determined by the same method as described above. The virus titer was calculated by the method of Reed and Muench.

<Result>
Table 12 shows the virus survival rate when the test solution and each virus solution were reacted for 10 minutes. In addition, the virus titer when reacting 50% ethanol aqueous solution with influenza virus, Newcastle disease virus and chicken infectious bronchitis virus solution for 10 minutes is 10 ^6.5 EID _{50 /} 0.2 mL or more, 10 ^2.5 EID ₅₀ /0.2 mL, respectively. And 10 ^3.5 EID ₅₀ /0.2 mL. When influenza virus reacted with a 0.2% hinokitiol zinc chloride mixture solution, there was a slight surviving virus, but the virus was inactivated compared to Newcastle disease virus and chicken infectious bronchitis virus. . Further, the E: 0.2% hinokitiol solution and the A: streptomycin zinc chloride mixture solution could not inactivate the virus.
In Newcastle disease virus and chicken infectious bronchitis virus, the survival of the virus was observed in a reaction with a 0.2% hinokitiol zinc chloride mixture solution for 10 minutes (44.4% and 66.6%).

<Conclusion>
Since 0.2% hinokitiol solution and streptomycin zinc chloride mixture solution did not show antiviral effect under this test condition, the antiviral effect confirmed in this test was not the action of hinokitiol and zinc chloride alone, but hinokitiol zinc chloride It was confirmed that it was due to the mixture.

Test Example 5: Safety test The safety test shown below was carried out on the hinokitiol zinc chloride mixture.
i) 28-day dietary toxicity test using rats ii) Acute oral toxicity test in rats iii) Skin irritation test using rabbits iv) Eye irritation test using rabbits v) Reverse mutation test using bacteria It was found that the toxicity of the hinokitiol zinc chloride mixture was not different from that of highly safe hinokitiol, and it was found that there was no problem in terms of environment and safety. In all tests, no abnormality was observed.

Example 1: Manufacture of spray product To the 0.15% Ht-Zn 30% ethanol (aqueous solution) prepared in Production Example 2, phytoncide (trade name "Smernark") manufactured by Tokai Kosan Co., Ltd. was added. An antiviral solution containing 0.5% by mass was prepared.
A spray can having an internal volume of 180 mL, composed of tin coated with a fluorine resin on the inner surface of the can, having a spraying device capable of continuous spraying and having a spray angle set to 55 degrees with respect to the surface of the can. The appearance of the can is shown in FIG. 3), and 108 mL of the antiviral solution prepared above and 75 mL of dimethyl ether (propellant: solution = 40: 6) are prepared in the spray can.
0 (v / v)) was filled to produce a spray product.
This spray product was installed at a location 1 m from the entrance of the room in a sealed space of 6 tatami flooring so that the injection port was directed toward the center of the room, and the injection button was pressed to inject the entire amount.
After entering the room 30 minutes after the injection of the whole amount, the result of confirming the state of the smell of Smernak at several points in the room was that the Smernak scent was observed in every corner of the room, so Ht-Zn It was confirmed that the solution was sprayed to every corner of the room.
In addition, the amount of Ht—Zn sprayed in the room is considered to be sufficient to kill the avian influenza virus and human influenza virus remaining in the room from the results of the test. The product can effectively remove influenza viruses remaining in homes, classrooms, offices, hospital rooms, beds, etc. with simple operations, and minimizes the risk of workers themselves being infected with viruses. It can be a spray product to prevent influenza virus infection.
From the above results, it is expected that the spray product of the present invention will effectively prevent infection with new influenza viruses (type A, H1N1 subtype).

1: Injection device 2: Stem 3: Injection button 4: Injection nozzle 5: Locking portion 6: Protruding portion 7: Step portion

Claims (8)

1) Antivirus which is an aqueous solution containing a mixture of hinokitiol and zinc chloride in an amount of 0.4 to 0.6 molar equivalents of the hinokitiol, or a water-alcohol solution having an alcohol content of 10 to 60% Influenza virus infection, which is a solution, wherein the content of the mixture is 0.001 to 1% by mass based on the mass of the antiviral solution, and 2) a spray can is filled in a spray can Spray products to prevent
The ratio of the antiviral solution to the propellant is in the range of 30:70 to 50:50 by volume ratio, and the spray can comprises spray means capable of continuous spray and is made of aluminum or can A spray product made of tinplate with an inner surface coated with a corrosion-resistant resin. The spray product for preventing influenza virus infection according to claim 1, wherein the antiviral solution contains a naturally occurring deodorant. The spray product for preventing influenza virus infection according to claim 1 or 2, wherein the mixture comprises hinokitiol and zinc chloride in an amount of 0.45 to 0.55 molar equivalent of the hinokitiol. The spray product for preventing influenza virus infection according to any one of claims 1 to 3, wherein the antiviral solution has a pH adjusted to 5.5 to 7. The spray product for preventing influenza virus infection according to any one of claims 1 to 4, comprising 0.01 to 1% by mass of the mixture based on the mass of the antiviral solution. The spray product for preventing influenza virus infection according to any one of claims 1 to 5, wherein the propellant is HFC152a, HFC134a, carbon dioxide, liquefied propane gas, dimethyl ether, or a mixture of two or more thereof. . The spray product for preventing influenza virus infection according to any one of claims 1 to 6, wherein the corrosion-resistant resin is a fluororesin, a polyethylene resin, a polyimide resin, or an epoxy resin. The spray product for preventing influenza virus infection according to any one of claims 1 to 7, wherein the influenza is avian influenza or human influenza.

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