JP2021169541A - Weak alkaline stable liquid - Google Patents

Abstract

To provide a weak alkaline stable liquid.SOLUTION: A weak alkaline stable liquid is stable in a weak alkaline state with a pH of 8 or more and 10.5 or less. Extract of citrus seeds of 0.15 mass% or more and 3.0 mass% or less and a pH modifier comprising strong alkali and salt of weak acid are dissolved in water.SELECTED DRAWING: Figure 1

Description

The present invention relates to a weak alkaline stabilizer.

Conventionally, various virus inactivating agents have been used in order to prevent infectious gastroenteritis and food poisoning caused by norovirus, for example. For example, as disclosed in Patent Document 1, an anti-norovirus composition containing a grapefruit seed extract and alkaline electrolyzed water and having an overall pH of 11.5 to 14 is known.

Japanese Patent No. 5388325

By the way, the present inventor has found that by blending a citrus seed extract with a weak alkali having a pH of a predetermined value or higher, a virus inactivating agent capable of exerting sufficient efficacy against norovirus even if it is non-alcoholic can be obtained. I found it.

In order to make the virus inactivating agent a weak alkali having a pH of 8 or more, a method using alkaline electrolyzed water of Patent Document 1 can be considered. Since the alkaline electrolyzed water is an electrolyzed NaCl aqueous solution, it is essentially a NaOH aqueous solution and a strong base aqueous solution. Therefore, when the anti-norovirus composition of Patent Document 1 is stored for a long period of time, carbon dioxide in the air dissolves in the composition and H ⁺ ions flow in, so that OH ⁻ ions decrease and the pH becomes acidic. Tends to change to.

Here, if the pH of the aqueous solution is in the strong alkaline region, the aqueous solution ^{contains abundant OH-} ions, so even if carbon dioxide is slightly dissolved in the aqueous solution, it is considered that the pH of the aqueous solution does not fluctuate significantly. ^{Since the OH-} ion concentration is low in the weak alkaline region, when the pH is adjusted to weak alkali with alkaline electrolyzed water, the pH may fluctuate significantly when the ^{OH-ion decreases due to the dissolution of carbon dioxide.} Therefore, the weakly alkaline virus inactivating agent using alkaline electrolyzed water has low stability over time, and it may be difficult to maintain the desired performance for a long period of time.

A buffer solution can be considered as a general method for stabilizing the pH of an aqueous solution, but it is not always easy to find an optimum buffer solution as a virus inactivating agent, and the pH is stabilized by a simpler method. There is a demand for a virus inactivating agent that has been used.

The present invention has been made in view of this point, and an object of the present invention is to provide a weak alkali stabilizer that can maintain a weak alkali for a long period of time by a simple method without using a buffer solution. To provide.

In order to achieve the above object, in the present invention, a weak alkaline stabilizer having a pH of 8 or more and 10.5 or less and stable with a weak alkalinity, and citrus seeds having a pH of 0.15% by mass or more and 3.0% by mass or less. A weak alkali stabilizer in which the extract and a pH adjuster composed of a strong alkali and a salt of a weak acid were dissolved in water was prepared.

According to this configuration, not only the high sterilizing effect of the citrus seed extract but also the synergistic action of the citrus seed extract and the alkali of the strong alkali and the salt of the weak acid can obtain a high virus removing effect against norovirus and the like.

Here, the pH of a salt is determined by the combination of acids and bases constituting the salt. For example, a salt of a strong acid (hydrogen hydrochloride) and a strong base (sodium hydroxide) such as sodium ^{chloride is ionized into sodium ion (Na +} ) and chloride ion (Cl ⁻ ) when dissolved in water, and more. Reaction does not occur.

On the other hand, salts of weak acids (acetic acid) and strong bases (sodium hydroxide) such as sodium acetate are first almost completely ionized in water to become acetate ions (CH ₃ C00 ⁻ ) and sodium ions (Na ⁺ ). At this time, sodium ions are almost completely ionized in water and do not act as acids or bases. On the other hand, the equilibrium shown in the following formula 1 exists between acetic acid ion and acetic acid in water, and the acetate ion exhibits behavior as a base.

CH ₃ COO ⁻ + H ₂ O ← → CH ₃ COOH + OH ⁻ Equation 1

Due to the existence of an equilibrium that produces hydroxide ions in the aqueous solution in this way, salts of weak acids and strong bases become basic when dissolved in water. Then, the pH at this time settles at a constant value according to the equilibrium constant.

Due to the existence of such equilibrium, an aqueous solution of a salt of a weak acid and a strong base is an aqueous solution of a strong base (sodium hydroxide, etc.) having the same pH when an acid source such as carbon dioxide comes into the liquid from the outside. It is relatively difficult for the pH to drop as compared with the above.

When the acid enters the aqueous solution, hydrogen ions (H ⁺ ) will flow into the aqueous solution. In the case of a normal strong base aqueous solution, when hydrogen ions increase, hydroxide ions decrease and pH decreases, but for the above-mentioned weak acid and strong base salts, the consumed hydroxide ions are Due to the presence of equilibrium, weak acid ions in the solution are supplied by combining with water, and the decrease in pH becomes gentle.

In particular, this pH stability is very useful for this drug, which is closely linked to pH and efficacy.

Further, the pH is adjusted to 8 or higher.

According to this configuration, the efficacy against not only fungi such as Escherichia coli but also non-enveloped viruses having no lipid membrane called envelope can be enhanced.

There is also a configuration in which the pH adjuster produces carbonate ions when ionized.

There is also a configuration in which the pH adjuster produces hydrogen carbonate ions when ionized.

There is also a configuration in which the pH adjuster is an amphoteric electrolyte. Examples of the amphoteric electrolyte include sodium hydrogen carbonate (baking soda), and the pH is further stabilized by using the amphoteric electrolyte.

There is also a configuration in which the pH is adjusted to 11.0 or less.

According to this configuration, strong alkali is not exhibited, so that the safety during handling is improved. Moreover, the virus inactivating agent may be adjusted to pH 10.5 or less. Moreover, the virus inactivating agent may be adjusted to pH 8.5 or higher. Moreover, the virus inactivating agent may be adjusted to pH 10.0 or higher. By setting the pH to 8.5 or higher or pH 10.0 or higher, a high virus removing effect can be obtained even if the contact time with the non-enveloped virus is short, for example.

There is also a configuration that does not contain alcohol.

According to the present invention, a sterilization effect of 99.99% or more can be obtained.

It is a graph which shows the relationship between the concentration of a pH adjuster and pH. It is a graph which shows the antiviral test result.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings. It should be noted that the following description of the preferred embodiment is essentially merely an example and is not intended to limit the present invention, its application or its use.

The virus inactivating agent according to the embodiment of the present invention contains at least a grapefruit seed extract as a citrus seed extract, a pH adjuster composed of a salt of a strong alkali and a weak acid, and water. The virus inactivating agent is adjusted to pH 8 or higher by a pH adjusting agent. It can also be said to be a virus inactivating agent in which a pH adjuster is contained in an aqueous solution of grapefruit seed extract. The aqueous solution of grapefruit seed extract is obtained by dissolving the grapefruit seed extract in ion-exchanged water. The concentration of the grapefruit seed extract in this aqueous solution can be set in the range of 0.1% by mass to 5.0% by mass. The lower limit of the concentration of the grapefruit seed extract is preferably 0.15% by mass, more preferably 0.2% by mass. The upper limit of the concentration of the grapefruit seed extract is preferably 3.0% by mass, more preferably 0.8% by mass.

Grapefruit seed extract is extracted and purified from the seeds of grapefruit fruit and is generally accepted as a food additive. When the grapefruit seed extract is obtained from grapefruit, seeds can be taken out from the harvested grapefruit, the extracted seeds can be crushed, and the crushed one can be extracted. At this time, the grapefruit seed extract may be extracted from the undried crushed product, or the grapefruit seed extract may be extracted from the lyophilized crushed product.

When extracting the grapefruit seed extract, a solution such as water or alcohol can be used. Examples of the alcohol used as the solvent for extraction include ethanol and the like. When extracting the grapefruit seed extract, the seeds may be heated to, for example, 30 ° C. or higher. Grapefruit seed extract contains fatty acids, flavonoids and the like. The grapefruit seed extract is preferably food grade, but not necessarily food grade.

The citrus seed extract may be other than the grapefruit seed extract, and a seed extract similarly extracted from citrus seeds such as lemon can also be used.

As the pH adjuster, those that generate carbonate ions when ionized or those that generate hydrogen carbonate ions when ionized can be used. An amphoteric electrolyte can also be used as the pH adjuster, and an amphoteric electrolyte such as sodium hydrogen carbonate (baking soda) is preferable for pH stabilization. As the pH adjuster, for example, sodium hydrogen carbonate or sodium carbonate can be used.

The pH of the virus inactivating agent can be adjusted by the amount of the pH adjusting agent. In this embodiment, the content of the pH adjuster is set so that the pH of the virus inactivating agent is 8 or more. The content of the pH adjuster is preferably set so that the pH of the virus inactivating agent is 8.5 or more, and more preferably the pH of the virus inactivating agent is 10.0 or more. It is to set. When determining the content of the pH adjuster, the pH adjuster is added while measuring the pH of the virus inactivating agent, and the content of the pH adjuster at the time when the desired pH is reached is grasped. You can leave it.

The upper limit of the pH of the virus inactivating agent can be, for example, 11.5, and the content of the pH adjuster is preferably set so that the pH is 11.5 or less. More preferred is pH 11.0. As a result, the virus inactivating agent does not show strong alkalinity, which enhances safety during handling.

By using a salt of a strong alkali and a weak acid as the pH adjuster, it is possible to improve the stability of the pH over time as compared with the case where the pH is adjusted with alkaline electrolyzed water without using a buffer solution. When a salt of a strong alkali and a weak acid is used, it is not stable at a constant pH like a buffer solution, but the weak acid ^{creates an equilibrium to supply OH −} ions in water, so even if carbon dioxide in the air dissolves. The pH does not fluctuate easily.

That is, when a salt of a strong acid (hydrogen hydrochloride) and a strong base (sodium hydroxide) such as sodium chloride is dissolved in water, it is ionized into ^{sodium ion (Na +} ) and chloride ion (Cl ^{−), and more.} However, the salt of weak acid (acetic acid) and strong base (sodium hydroxide) such as sodium acetate is first almost completely ionized in water, and then acetate ion (CH ₃ C00 ⁻ ) and sodium ion (Na). ⁺ ). At this time, sodium ions are almost completely ionized in water and do not act as acids or bases. On the other hand, the equilibrium shown in the above formula 1 exists between acetic acid ion and acetic acid in water, and the acetate ion exhibits behavior as a base.

Due to the existence of an equilibrium that produces hydroxide ions in the aqueous solution in this way, salts of weak acids and strong bases become basic when dissolved in water. Then, the pH at this time settles at a constant value according to the equilibrium constant.

Due to the existence of such equilibrium, an aqueous solution of a salt of a weak acid and a strong base has a strong base (sodium hydroxide, etc.) having the same pH when an acid source such as carbon dioxide flows into the aqueous solution from the outside. Compared with an aqueous solution, the pH is relatively difficult to lower.

When the acid enters the aqueous solution, hydrogen ions (H ⁺ ) will flow into the aqueous solution. In the case of a normal strong base aqueous solution, when hydrogen ions increase, hydroxide ions decrease and pH decreases, but for the above-mentioned weak acid and strong base salts, the consumed hydroxide ions are Due to the presence of equilibrium, weak acid ions in the solution are supplied by combining with water, and the decrease in pH becomes gentle.

Since the speed at which carbon dioxide in the air dissolves in the virus inactivating agent is limited, the decrease in pH becomes extremely gradual in the normal storage environment and usage environment of the virus inactivating agent.

In particular, in the vicinity of pH 8, when trying to adjust with alkaline electrolyzed water, ^{the concentration of OH −} is too low to be stable, but according to the pH adjuster according to the present embodiment, the decrease in pH becomes extremely slow. The effect becomes even more remarkable.

By using a pH adjuster as a salt that produces carbonate ion or bicarbonate ion by ionization, that is, sodium carbonate or sodium hydrogen carbonate, a large amount of carbonate ion or hydrogen carbonate ion is present in the aqueous solution when ionized in the aqueous solution. Therefore, it is difficult for the equilibrium to move in the direction in which carbonic acid is dissolved and carbonate ions or hydroxide ions are generated. As a result, carbon dioxide is less likely to dissolve and is less susceptible to the effects of carbon dioxide, which is preferable.

FIG. 1 is a graph showing a case where the pH is adjusted by using sodium hydrogen carbonate as a pH adjusting agent and a case where the pH is adjusted by alkaline electrolyzed water at around pH 8. When sodium hydrogen carbonate is used as a pH adjuster, the pH hardly changes even if the sodium hydrogen carbonate concentration is changed in the vicinity of pH 8, especially in the vicinity of pH 8.3. That is, since the concentration range of pH 8.3 is wide, it is stable at pH 8.3.

^{On the other hand, if OH-} ions are consumed when carbon dioxide is dissolved in the sodium hydroxide aqueous solution, the pH will fluctuate immediately because there is no supply ^{of OH-} ions as in the case of sodium hydrogen carbonate. Therefore, it is extremely difficult to adjust the sodium hydroxide aqueous solution to such a low concentration.

Further, since the electrolyzed water is obtained by electrolyzing the NaCl aqueous solution, the electrolyzed water on the alkaline side is in the same state as the NaOH aqueous solution. Therefore, alkaline electrolyzed water can be considered in terms of NaOH, and the same reasoning as above holds, and it is extremely unstable near pH 8.3.

The virus inactivating agent can be used by being housed in a container having a spraying lever and sprayed on various articles and the like. Examples of the container having the spray lever include various containers conventionally used, and any container may be used. The virus inactivating agent can also be sprayed by a spraying device equipped with a hand-push pump or an electric pump. The virus inactivating agent can also be used by applying it to an article or dropping it. The virus inactivating agent can also be used by directly spraying it on, for example, cooking utensils such as cutting boards and kitchen knives, countertops, tableware, towels, and towels. The virus inactivating agent can also be used by spraying on clothing, floors, walls, toilet bowls, wash basins, and automobile interiors. The virus inactivating agent may be sprayed on the hands.

In addition, the virus inactivating agent does not contain alcohol. That is, the virus inactivating agent does not have a bactericidal effect or an antiviral effect due to alcohol, and exhibits a bactericidal effect and an antiviral effect depending on the pH value and the grapefruit seed extract.

(PH stability test)
The citrus seed extract contained in the virus inactivating agent according to Example 1 of the present invention is, for example, a grapefruit seed extract (grapefruit seed extract). The pH adjuster is sodium bicarbonate and the concentration is 0.21%. The rest is ion-exchanged water. The initial pH of Example 1 is adjusted to around 8.3. Further, as Comparative Example 1, a solution using alkaline electrolyzed water as a pH adjuster was prepared, and the initial pH of this Comparative Example was set to 10.0.

The pH stability test method is shown below.
1. 1. Place each sample in a glass vial.
2. Store the glass vial containing the sample in a constant temperature chamber at 60 ° C.
3. 3. Take out the glass vial in the constant temperature chamber at regular intervals, measure the pH and check the appearance.
The reason for using a 60 ° C. constant temperature chamber is to obtain so-called accelerated test results.

In the case of Example 1 of the present invention, the pH after 3 weeks was about 8.0, and there was almost no difference from the initial pH. On the other hand, in the case of Comparative Example 1 using alkaline electrolyzed water, the pH after 1 week was about 9.3, the pH after 3 weeks was about 8.2, and the rate of decrease from the initial pH was extremely high. It was big. From the above, it can be seen that the virus inactivating agent according to the present embodiment has high stability over time.

(Antiviral test)
Next, the virus infectious titer measurement test before and after the treatment with the virus inactivating agent will be described. Feline calicivirus is used in this test, and this feline calicivirus is used in the test as an alternative to norovirus, which has a similar structure. This is because norovirus is difficult to culture and a simple method for evaluating the infectious titer has not yet been established. That is, it is generally considered that any agent that exhibits sufficient antiviral properties in a test using feline calicivirus will also exhibit sufficient antiviral properties against norovirus.

When performing a virus infectivity titer measurement test, first, cells are monolayer-cultured in a cell culture microplate (96 holes) using a cell proliferation medium. The cells are CRFK cells. Then, the monolayer cultured cells were inoculated with a diluted virus suspension solution of feline calicivirus (FCV) and adsorbed to the cells in a carbon dioxide gas incubator (CO2 concentration: 5%) at 37 ° C. ± 1 ° C. for 1 hour. After that, remove the virus inoculum, add cell maintenance medium, and incubate for 4 to 7 days. Then, amide black staining is performed, the life and death of the cells are confirmed, and the 50% tissue culture infectious titer (TCID50 / ml) is calculated by the Reed-Muench method. The lower this value, the lower the infectivity.

In general, non-enveloped viruses such as feline calicivirus have stronger resistance to various disinfectants and antibacterial agents than enveloped viruses such as influenza virus. Therefore, any agent that is effective against non-enveloped viruses is likely to be effective against enveloped viruses in a shorter period of time.

The test agents are as shown in Table 1. The rest is ion-exchanged water.

The results of the virus infectious titer measurement test are shown in FIG. In the graph, "30 seconds" indicates that the contact time between the test agent and the virus is 30 seconds, and "120 seconds" means that the contact time between the test agent and the virus is 120 seconds. Is shown. In the case of "30 seconds", it can be called a short-time contact test, and in the case of "120 seconds", it can be called a long-time contact test. The value in the graph is a log value (log TCID 50 / ml) having an infectious value of TCID 50 / ml. As a control, sterilized water was used. It can be said that the lower the log TCID 50 / ml of the test agent as compared with the control, the higher the antiviral property.

As shown in FIG. 2, in Comparative Example 2 of pH 7.0, the decrease in logTCID 50 / ml from the control was 0.5 or less at both “30 seconds” and “120 seconds”. On the other hand, in Example 2 of pH 8.0, the decrease in logTCID 50 / ml from the control in the case of "120 seconds" shows an extremely large value of 2.5. In Example 2, the liquid preparation of Example 1 was diluted with a 0.36% aqueous solution of grapefruit seed extract to adjust the pH to 8.0.

Further, in Example 3 of pH 8.5, Example 4 of pH 9.0, and Example 5 of pH 10.0, the decrease in log TCID 50 / ml from the control was 3.0 or more in the case of "120 seconds", respectively. Yes, it had sufficient antiviral properties. The pH adjuster of Example 3 is sodium carbonate.

Further, in Example 3 of pH 8.5, Example 4 of pH 9.0, and Example 5 of pH 10.0, logTCID50 / ml was 3.0 or more in the case of "120 seconds", respectively, which is sufficient antiviral. Had sex. The pH adjuster of Example 3 is sodium carbonate.

Furthermore, in Example 3 of pH 8.5, Example 4 of pH 9.0, and Example 5 of pH 10.0, the decrease in log TCID 50 / ml from the control was 1.5 or more at "30 seconds", respectively. It had sufficient antiviral properties even if the contact time was short. In particular, in Example 5 of pH 10.0, the decrease in log TCID 50 / ml from the control was 3.0 or more in the case of "30 seconds", and even if the contact time was short, it had extremely high antiviral properties. Was there. Further, although not shown, the cases of pH 10.5 and pH 11.0 also have high antiviral properties similar to those of Example 5.

In the case of a preparation containing sodium carbonate and sodium hydrogen carbonate aqueous solution having a pH of 10 and not containing the grapefruit seed extract, logTCID50 / ml was not decreased as compared with the control, and no antiviral effect was observed. Although not shown, in the case of a preparation containing 0.18% by mass of grapefruit seed extract at pH 3, the decrease in log TCID 50 / ml from the control is about 0.3 at “120 seconds”, and the grapefruit seed at pH 3. In the case of a preparation containing 0.36% by mass of the extract, the decrease of logTCID50 from the control is about 0.5 at "120 seconds", and 0.54% by mass of the grapefruit seed extract is contained at pH3. In the case of the present formulation, the decrease in log TCID 50 / ml from the control was about 1.0 at "120 seconds". In addition, in the case of a preparation containing sodium carbonate and sodium hydrogen carbonate aqueous solution having a pH of 10 and not containing the grapefruit seed extract, the value was -0.5, and the antiviral effect was low.

Further, in the case of a test using influenza virus (A / Udon / 72 (H3N2)), trypsin may be added to the cell maintenance medium using the cells as MDCK cells. The liquid preparations of Examples 1 to 5 exhibited antiviral properties equivalent to those of feline calicivirus against influenza virus.

As described above, the virus inactivating agent of this example exerts sufficient efficacy not only against enveloped viruses such as influenza virus but also against non-enveloped viruses such as feline calicivirus. Moreover, since it showed sufficient antiviral properties against feline calicivirus, it can be said that the virus inactivating agent of the present embodiment is an anti-norovirus agent having sufficient anti-norovirus properties.

(Antibacterial test)
Next, the antibacterial test will be described. When performing the antimicrobial testing, ^first, a 10 9 cfu / ml of E. coli bacterial solution 0.1ml added to test preparation 10 ^ml, and 10 7 cfu / ml. At this time, as a control, a product using 10 ml of physiological saline instead of the test agent is also prepared. After 10 seconds have passed by liquid-liquid contact, 1 ml is withdrawn and placed in 9 ml of SCDLP liquid medium to inactivate. Then, serial dilution is performed and 200 μl is seeded on SCDLP agar medium. The number of colonies is counted for the control and each test agent, and the sterilization rate is measured. The sterilization rate is calculated from the formula of the number of colonies of the test agent / the number of colonies of the control. Examples 1 to 5 and Comparative Examples 1 and 2 were prepared as test agents. The antibacterial test result was 99.99% or more in all of Examples 1 to 5 and Comparative Examples 1 and 2.

(Pollutivity)
Next, the pollutability will be described. Contaminability can be determined by, for example, spraying a test agent onto a black object, completely drying it, and then visually observing whether or not powder residue is observed. If no powder residue is found, it can be determined that there is contamination, and if no powder residue is found, it can be determined that there is no contamination. Regarding the contaminating property, all of Examples 1 to 5 and Comparative Examples 1 and 2 were non-staining.

(Action and effect of the embodiment)
As described above, since the virus inactivating agent according to this embodiment contains at least a citrus seed extract, a pH adjuster composed of a salt of a strong alkali and a weak acid, and water, a buffer solution is used. Weak alkali can be maintained for a long period of time by a simple method without using it, and particularly high efficacy against non-enveloped viruses such as norovirus can be stably obtained over time.

In particular, when sodium hydrogen carbonate is used as the pH adjuster, the stability when the pH of the virus inactivating agent is adjusted between 8 and 8.5 can be increased.

The above embodiments are merely exemplary in all respects and should not be construed in a limited way. Furthermore, all modifications and modifications that fall within the equivalent scope of the claims are within the scope of the present invention.

As described above, the virus inactivating agent according to the present invention can be used, for example, by spraying it on a cooking utensil or the like.

Claims (1)

A weakly alkaline stabilizing liquid with a pH of 8 or more and 10.5 or less, which is stable with weak alkalinity.
Citrus seed extract of 0.15% by mass or more and 3.0% by mass or less,
A weak alkali stabilizer in which a pH adjuster consisting of a strong alkali and a salt of a weak acid is dissolved in water.

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