JP7723969B2 - Virus inactivation composition - Google Patents

Description

The present invention relates to a virus inactivating composition. More specifically, it relates to a virus inactivating composition that has an inactivating effect on viruses and contains a specific amount or less of a lower alcohol.

The threat of various pathogenic viruses has a major impact on our lives. For example, the outbreak of COVID-19 virus infection poses a threat to humans and is completely changing the way we live. In addition to seasonal influenza, which recurs annually, mainly in winter, new viruses can enter the human world from birds or pigs and acquire the ability to infect humans, so it can be said that we are constantly exposed to new dangers when it comes to viruses.

Viruses evolve by changing their capabilities through natural mutations and escape mutations. Virus-neutralizing antibodies have been frequently reported, and treatments exist, but given the constantly changing nature of viruses, it is considered extremely important to prevent infection before it occurs, and there is a growing need for drugs with antiviral properties.

Currently, lower alcohols are widely used in virus inactivation compositions. For example, a disinfectant/virus inactivation composition characterized by containing a lower alcohol, a cationic surfactant, and an alkaline agent has been proposed (Patent Document 1).

Japanese Patent Application Laid-Open No. 2021-155368

The frequent use of products containing ethanol and other lower alcohols can lead to problems such as rough skin and deterioration or changes in the properties of the object to which they are applied. For example, many sprays that are effective against viruses contain high concentrations of ethanol, and when sprayed onto an object, the quality of the object can be altered depending on the material it is made of.

The objective of the present invention is to provide a highly safe virus inactivation composition that has minimal effect on the skin and other objects.

As a result of extensive research to solve this problem, the inventors discovered that by adding specific concentrations of acid and salt and adjusting the pH, it is possible to achieve a virus inactivation effect even when the concentration of lower alcohols such as ethanol is kept low, leading to the completion of the present invention.

That is, the present invention provides the following virus inactivation compositions.
Item 1.
A virus inactivation composition comprising (A) 0.15 to 1 w/v % of an acid, (B) 0.05 to 2 w/v % of a salt, and (C) a lower alcohol content of 10 w/v % or less and a pH of 3 to 5.
Item 2.
Item 2. The virus inactivating composition according to Item 1, wherein the component (A) is one or more acids selected from the group consisting of citric acid, malic acid, gluconic acid, lactic acid, phosphoric acid, sorbic acid, and phytic acid.
Item 3.
Item 3. The virus inactivation composition according to Item 1 or 2, wherein component (B) is one or more selected from the group consisting of sodium citrate, potassium citrate, sodium gluconate, sodium malate, sodium tartrate, sodium lactate, and trisodium phosphate.
Item 4.
Item 4. The virus inactivating composition according to any one of Items 1 to 3, which does not contain component (C).
Item 5.
Item 5. The virus inactivating composition according to any one of Items 1 to 4, wherein the virus is an enveloped RNA virus.

Furthermore, the present invention provides the following methods.
Item 6.
A method for imparting to a composition containing (A) 0.15 to 1 w/v % of acids and (B) 0.05 to 2 w/v % of salts an inhibitory effect on rough or deteriorated skin of a subject to which the composition is applied, by adjusting the content of (C) a lower alcohol to 10 w/v % or less and the pH to 3 to 5.

The present invention makes it possible to provide a highly safe virus inactivation composition that has minimal effect on the skin or target objects.

In this specification, the content unit "w/v%" is synonymous with "g/100 ml."

[Virus inactivation composition]
The virus inactivating composition of the present invention contains (A) 0.15 to 1 w/v % of an acid, (B) 0.05 to 2 w/v % of a salt, (C) a lower alcohol content of 10 w/v % or less, and a pH of 3 to 5.

((A) Acids)
The virus inactivating composition of the present invention contains (A) an acid. The acid is preferably either an organic acid or an inorganic acid, and examples thereof include hydroxy acids such as citric acid, malic acid, gluconic acid, and lactic acid, as well as other acids such as phosphoric acid, sorbic acid, and phytic acid. These acids may be used alone or in combination of two or more. Of these, one or more acids selected from the group consisting of citric acid, malic acid, gluconic acid, and phosphoric acid are particularly preferred.

From the viewpoint of achieving the effects of the present invention, the content of acids relative to the total amount of the virus inactivating composition of the present invention is preferably 0.15 w/v% or more and 1 w/v% or less, more preferably 0.2 w/v% or more and 0.8 w/v% or less, and even more preferably 0.4 w/v% or more and 0.8 w/v% or less.

((B) Salts)
The virus inactivating composition of the present invention contains salts. Salts are preferably salts of organic acids or inorganic acids, and examples thereof include sodium salts, potassium salts, magnesium salts, calcium salts, and ammonium salts. As salts, sodium salts and potassium salts are preferred, and sodium salts are more preferred.

For example, in the present invention, salts include, but are not limited to, sodium citrate, potassium citrate, sodium malate, sodium gluconate, potassium gluconate, sodium succinate, sodium tartrate, trisodium phosphate, sodium lactate, etc. These may be used alone or in combination of two or more. Of these, one or more selected from the group consisting of sodium citrate, potassium citrate, sodium gluconate, sodium malate, sodium tartrate, sodium lactate, and trisodium phosphate are particularly preferred. Although not limited thereto, salts of the same acid as the acid of component (A) are also preferred.

From the viewpoint of achieving the effects of the present invention, the content of salts relative to the total amount of the virus inactivating composition of the present invention is preferably 0.05 w/v% or more and 2 w/v% or less, more preferably 0.1 w/v% or more and 1.5 w/v% or less, and even more preferably 0.5 w/v% or more and 1.2 w/v% or less.

In the virus inactivating composition of the present invention, the ratio of salts to acids is preferably 0.3 parts by mass or more and 3 parts by mass or less, more preferably 0.5 parts by mass or more and 2 parts by mass or less, and even more preferably 1 part by mass or more and 1.5 parts by mass or less, per 1 part by mass of acids.

(lower alcohol)
As used herein, the term "lower alcohol" refers to C1-3 alcohols, specifically methanol, ethanol, isopropyl alcohol, and propanol.

In the virus inactivation composition of the present invention, the content of lower alcohol relative to the total amount of the virus inactivation composition is 10 w/v% or less, preferably less than 10 w/v%, more preferably 5 w/v% or less, and even more preferably 1 w/v% or less. It is particularly preferable that the virus inactivation composition of the present invention contains substantially no lower alcohol or no lower alcohol at all. Here, "substantially no lower alcohol" means that the content of lower alcohol relative to the total amount of the virus inactivation composition is, for example, 0.1 w/v% or less, preferably 0.01 w/v% or less.

In the virus inactivation composition of the present invention, the ethanol content relative to the total amount of the virus inactivation composition can be 10 w/v% or less, preferably less than 10 w/v%, more preferably 5 w/v% or less, and even more preferably 1 w/v% or less. It is particularly preferable that the virus inactivation composition of the present invention contains substantially no ethanol or no ethanol at all. Here, "substantially no ethanol" means that the ethanol content relative to the total amount of the virus inactivation composition is, for example, 0.1 w/v% or less, preferably 0.01 w/v% or less.

From the perspective of achieving the effects of the present invention, the content of the lower alcohol relative to the total amount of the virus inactivating composition of the present invention may be, for example, 0.01 w/v% or more and 10 w/v% or less, 0.01 w/v% or more and 10 w/v% or less, or 0.0 w/v% or more and 5 w/v% or less.

(water)
The virus inactivating composition of the present invention can be blended with water, such as purified water such as ion-exchanged water, ordinary tap water, or industrial water.
The content of water relative to the total amount of the virus inactivating composition is preferably 80 w/v % or more, more preferably 90 w/v % or more, even more preferably 95 w/v % or more, and even more preferably 97 w/v % or more.

(Polyhydric alcohol)
The virus inactivating composition of the present invention can contain a polyhydric alcohol in place of or together with water. Examples of such polyhydric alcohols include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, butylene glycol, propanediol, glycerin, and trimethylolpropane. The content of the polyhydric alcohol relative to the total amount of the virus inactivating composition can be 80 w/v % or more, 90 w/v % or more, or even 95 w/v % or more.

(virus)
The term "virus" as used herein includes, but is not limited to, both non-enveloped viruses that do not have an envelope and are resistant to alcohol, and enveloped viruses.Preferably, enveloped viruses are the target, and among them, RNA viruses such as Coronaviridae, Orthomyxoviridae, Flaviviridae, Togaviridae, Paramyxoviridae, Rhabdoviridae, Bunyaviridae, or Filoviridae, or DNA viruses such as Herpesviridae, Poxviridae, or Hepadnaviridae are more preferred targets, enveloped RNA viruses are even more preferred targets, and Orthomyxoviridae viruses are even more preferred targets.

(pH)
From the viewpoint of component stability and safety, the virus inactivating composition of the present invention preferably has a pH of 3 to 5. More preferably, the virus inactivating composition has a pH of 3 to 4.5. The pH of the virus inactivating composition can be measured at 20°C using a commercially available pH meter (for example, Model F-52 (registered trademark) manufactured by Horiba, Ltd.).

(viscosity)
From the viewpoint of component stability and the like, the viscosity of the virus inactivating composition of the present invention at 25°C, SPINDLES No. M1, and 100 rpm is preferably about 0.5 to 1000 mPa·s, and more preferably about 3 to 100 mPa·s. The viscosity of the virus inactivating composition can be measured at 25°C using a commercially available viscometer (for example, Model TVB-10M, manufactured by Toki Sangyo Co., Ltd.).

(Other ingredients)
In addition to (A) acids, (B) salts, and (C) lower alcohols, the virus inactivating composition of the present invention may contain optional ingredients as appropriate, provided that the ingredients do not impair the effects of the present invention. Examples of optional ingredients include surfactants, chelating agents, polymers, preservatives, natural product extracts, dispersants, antioxidants, thickeners, viscosity reducers, stabilizers, deodorizers, fragrances, and colorants.

It is also preferable that the virus inactivating composition of the present invention is a composition that is completely free or substantially free of chlorine oxides (chlorine, hypochlorous acid, chlorous acid, chlorine dioxide, etc.).

Here, "substantially free" means that the content of the relevant component is, for example, 0.1 w/v% or less, preferably 0.01 w/v% or less.

(Applications, etc.)
The virus inactivating composition of the present invention can be applied directly to, but is not limited to, skin or objects where changes in properties are undesirable, particularly to the skin of fingers, arms, etc.; tableware, countertops, cooking utensils, etc.; toilet areas such as toilet seats, toilet bowls, toilet lids, flush levers, doorknobs, electric switches, and handrails; or tables, chairs, medical equipment, mobile phones, smartphones, tablet PCs, and computer peripherals such as mice and keyboards.

The virus inactivating composition of the present invention is provided in a form that can be brought into contact with an object by coating, immersion, spraying, or other methods. The virus inactivating composition of the present invention can preferably be brought into contact with an object by spraying.

The virus inactivating composition of the present invention can be provided in the form of, but is not limited to, an aerosol, a spray, or a sheet impregnated into fibers, nonwoven fabric, etc. In the case of an aerosol or spray, the virus inactivating composition of the present invention can be preferably contained in a container such as a trigger spray or dispenser. When provided in the form of a sheet impregnated into nonwoven fabric, etc., preferred examples of the sheet material include recycled fibers, synthetic fibers, plant fibers, nonwoven fabrics, woven fabrics, and mesh fabrics.

The virus inactivating composition of the present invention can be used 1 to 20 times per day, preferably 2 to 15 times per day, and more preferably 5 to 10 times per day. In light of the characteristics of the virus inactivating composition of the present invention, it can also be used more frequently, for example, 5 to 15 times per day.

From the standpoint of antiviral effect, the amount of the virus inactivation composition of the present invention used per administration is preferably, for example, approximately 0.2 to 3 ml, and even more preferably approximately 0.5 to 2 ml.

[Method for preventing rough or deteriorated skin]
The present invention also relates to a method for imparting to a composition containing 0.15 to 1 w/v % of (A) acids and 0.05 to 2 w/v % of (B) salts an effect of inhibiting rough skin or deterioration of a target object by adjusting the content of (C) a lower alcohol to 10 w/v % or less and the pH to 3 to 5. In the deterioration inhibition method of the present invention, the (A) acids, (B) salts, (C) lower alcohol, pH, and other conditions are the same as those described for the virus inactivating composition.

Next, the present invention will be described in detail using examples, but the present invention is not limited to the following examples. Note that the unit of each component amount in the table is w/v % unless otherwise specified in the table.

[1] Test for evaluating virus inactivation effect Compositions of Examples and Comparative Examples shown in Table 1 were prepared by a conventional method, and the virus inactivation effect of these compositions was evaluated.

The virus inactivation effect was evaluated as follows:

(Target virus)
Influenza virus type A (H1N1) (A/PR/8/1934; ATCC VR-1469)

(Cells used)
MDCK cells

(Culture medium used for culture)
E-MEM medium supplemented with fetal bovine serum (FBS) was used.

(Method for preparing virus solution)
The virus was added to cells prepared in advance, and after culturing for a certain period of time, the culture medium was subjected to a freeze-thaw treatment, and the supernatant obtained by centrifugation was used as the virus solution.

(Experimental Method)
0.1 mL of the virus solution was added to 0.9 mL of the solution of the Examples and Comparative Examples shown in Table 1, and the reaction was stopped after 30 seconds, followed by serial dilutions. 0.1 mL of this diluted solution was placed in a plate on which cells had been cultured in advance, and the cells were cultured for 3 to 4 days at 37°C and 5% _CO2 . After culture, the cytopathic effect was confirmed by microscopic observation, and the 50% tissue culture infectious dose of virus (TCID ₅₀ : the amount of virus that infects 50% of infected cultured cells is called TCID ₅₀ ) was determined by the Reed-Muench method, and converted to the virus infectivity per mL of the solution (TCID ₅₀ /mL).

The difference between the logarithm ( _log TCID /mL) of the virus infectivity ( _TCID /mL) before the action and the logarithm (log _TCID /mL) of the virus infectivity ( _TCID /mL) after the action was calculated and used as the reduction in virus infectivity. A reduction in the virus infectivity of 4.0 or more was evaluated as ⊚, a reduction in the virus infectivity of 2.0 or more but less than 4.0 was evaluated as ◯, and a reduction in the virus infectivity of less than 2.0 was evaluated as x. Of these, ⊚ and ◯ were judged to be good, and x was judged to be poor.

The results are shown in Table 1.

The results of the evaluation test showed that the compositions of the examples exhibited a higher virus inactivation effect than the compositions of the comparative examples.

[2] Test to evaluate the effect on the object The compositions of the examples and comparative examples shown in Table 2 were prepared by a conventional method, and about 0.5 ml of each composition was sprayed onto the object, and the changes were checked immediately afterwards without wiping it off. The evaluation criteria are as shown in Table 3. Evaluation was carried out according to the following evaluation criteria. A comprehensive judgment was made, and those that were all rated ◯ were given an overall evaluation of ◯, which was considered good.

The results of the evaluation test showed that the compositions of the examples had no effect on the objects compared to the compositions of the comparative examples, and maintained the objects in good condition.

[3] Skin Irritation Evaluation Test 0.5 mL of each composition from the Examples and Comparative Examples was applied to the forearm five times at one-hour intervals, and then (1) irritation and (2) dryness (chapping) of the skin were evaluated using a sensory evaluation system on a three-point scale from 1 to 3. The test was conducted by five people, and the average score was calculated. The evaluation criteria are shown below.

<Evaluation items and evaluation criteria>
(1) Irritation (burning sensation, pain, itching, etc.)
No feeling = 3 points, slight feeling = 2 points, feeling = 1 point (2) Dry (rough) skin
No feeling = 3 points, slight feeling = 2 points, feeling = 1 point

◎: Average score of 2.5 or more ○: Average score of 2.0 or more but less than 2.5 ×: Average score less than 2.0 (1) Irritation and (2) Dry (chapped) skin were evaluated as good when scored as ○ or more.

The results are shown in Table 4 below.

The results of the evaluation test showed that the compositions of the examples were less likely to cause skin irritation or dryness than the compositions of the comparative examples.

Claims (4)

A virus inactivation composition comprising: (A) 0.15 to 1 w/v % of one or more selected from the group consisting of citric acid , malic acid, and phosphoric acid; (B) 0.05 to 2 w/v % of one or more selected from the group consisting of sodium citrate, potassium citrate, sodium malate, and trisodium phosphate; and (C) a lower alcohol content of 10 w/v % or less and a pH of 3 to 5. The virus inactivation composition according to claim 1, which does not contain component (C). The virus inactivation composition according to claim 1 or 2, wherein the virus is an enveloped RNA virus. A method for imparting to a composition an inhibitory effect on rough or deteriorated skin of a subject to be applied, the composition comprising (A) 0.15 to 1 w/v % of one or more selected from the group consisting of citric acid, malic acid, and phosphoric acid, and (B) 0.05 to 2 w/v % of one or more selected from the group consisting of sodium citrate , potassium citrate, sodium malate, and trisodium phosphate, and (C) a lower alcohol content of 10 w/v % or less and a pH of 3 to 5.