Coronavirus killing agent

Abstract

To provide a coronavirus killing agent.SOLUTION: The present disclosure provides coronavirus killing agents. In particular, the present disclosure provides a coronavirus disinfectant comprising a chlorous acid aqueous solution. In particular, the present disclosure provides a method for killing or disinfecting coronavirus using a chlorous acid aqueous solution. The concentration of free chlorine (assuming Cl = 35.45) in a chlorous acid aqueous solution can be at least 5ppm or higher in the absence of organic matter. The content of chlorous acid in the chlorous acid aqueous solution (HClO2 = 68.46) can be at least 200ppm or more under the presence of organic matter including disinfection of hands and the like. The coronavirus may be SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), or 2019 novel coronavirus (SARS-CoV-2).SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to a coronavirus killing agent. The present disclosure also relates to a method for killing or inactivating coronaviruses. The present disclosure also relates to a chlorous acid solution for killing or inactivating coronaviruses. [Background technology]

[0002] In recent years, coronavirus infections have become a problem. Four types of coronaviruses (HCoVs) commonly infect humans: HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. While most infected individuals experience mild symptoms, some may develop high fevers. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in Guangdong Province, China, in 2002 and spread to over 30 countries and regions between November 2002 and July 2003 (case fatality rate: 9.6%). Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that causes cold symptoms in dromedaries. It is believed to cross the species barrier and cause severe pneumonia in humans (case fatality rate: 34.4%). The 2019 novel coronavirus, caused by the SARS-CoV-2 virus (also known as COVID-19), has become a global pandemic, presenting the world with an unprecedented threat.

[0003] Chlorous acid water contains chlorous acid (HClO2) as the main active ingredient (Patent Document 1). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2008 / 026607 Summary of the Invention [Means for solving the problem]

[0005] As a result of intensive research, the present inventors have discovered that chlorous acid water is effective in killing coronaviruses, and have completed the present disclosure. The present inventors have also discovered that chlorous acid water is effective in killing the 2019 novel coronavirus, and have completed the present disclosure.

[0006] According to the Ministry of Health, Labor and Welfare, sodium hypochlorite is considered inappropriate for use on hands as a chlorine-based disinfectant, bactericide, and sanitizer, and the effectiveness of hypochlorous acid water on hands is unknown, so it is also considered unsuitable for use.

[0007] For example, the present invention provides the following items.

[0008] (Item 1) A coronavirus killer containing chlorous acid water.

[0009] (Item 2) Item 2. The disinfectant according to item 1, wherein the free chlorine concentration (assuming Cl=35.45) of the chlorous acid water is at least 1 mg / L in the absence of organic matter.

[0010] (Item 3) Item 2. The disinfectant according to item 1, wherein the content of the chlorous acid water is at least 100 ppm in terms of chlorous acid (HClO2 = 68.46) in the absence of organic matter.

[0011] (Item 4) The disinfectant according to item 1, wherein the free chlorine concentration (as Cl = 35.45) of the chlorous acid water is at least 5 mg / L or more in the presence of organic matter, including disinfectants for hands, etc.

[0012] (Item 5) The disinfectant according to item 1, wherein the content of the chlorous acid water as chlorous acid (HClO2 = 68.46) is at least 200 ppm or more in the presence of organic matter, including disinfectants for hands, etc.

[0013] (Item 6) Item 2. The disinfectant according to item 1, wherein the free chlorine concentration (assuming Cl=35.45) of the chlorous acid water is at least 10 mg / L or more in the presence of organic matter including filth equivalent to 0.5% BSA or more.

[0014] (Item 7) Item 2. The disinfectant according to item 1, wherein the content of the chlorous acid water is at least 400 ppm or more in terms of chlorous acid (HClO2=68.46) in the presence of organic matter including filth equivalent to 0.5% or more of BSA.

[0015] (Item 8) 8. The disinfectant according to item 7, wherein the standard value of the chlorous acid water is 4 to 6%.

[0016] (Item 9) 9. The disinfectant according to any one of items 1 to 8, wherein the coronavirus is a member of the subfamily Letovirinae or Orthocoronavirus.

[0017] (Item 10) 10. The disinfectant according to any one of items 1 to 9, wherein the coronavirus is of the genus Alphacoronavirus, Betacoronavirus, Gammacoronavirus, or Deltacoronavirus.

[0018] (Item 11) 11. The disinfectant according to any one of items 1 to 10, wherein the coronavirus is a virus belonging to the genus Betacoronavirus.

[0019] (Item 12) 12. The disinfectant according to any one of Items 1 to 11, wherein the coronavirus is the subgenus Coracovirus, Decacovirus, Duvinacovirus, Ruchacovirus, Minacovirus, Minunacovirus, Myotakovirus, Niktakovirus, Pedakovirus, Rhynacovirus, Setracovirus, Soracovirus, Sunacovirus, Tegacovirus, Enbecovirus, Hibecovirus, Merbecovirus, Nobecovirus, Sarbecovirus, Andecovirus, Burdecovirus, Heldecovirus, Brangacovirus, Segacovirus, or Igakovirus.

[0020] (Item 13) 13. The disinfectant according to any one of items 1 to 12, wherein the coronavirus is a coronavirus that infects humans.

[0021] (Item 14) 14. The killing agent according to any one of items 1 to 13, wherein the coronavirus is HCoV-HKU1, HCoV-OC43, SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), or 2019 novel coronavirus (SARS-CoV-2).

[0022] (Item 15) 15. The killing agent according to any one of items 1 to 14, wherein the coronavirus is SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), or 2019 novel coronavirus (SARS-CoV-2).

[0023] (Item 16) 16. The disinfectant according to any one of items 1 to 15, wherein the disinfectant is a disinfectant for use on hands and fingers, and the free chlorine concentration (assuming Cl=35.45) of the chlorous acid water is at least 5 mg / L.

[0024] (Item 17) How to kill coronavirus using chlorous acid water.

[0025] (Item 18) Item 18. The method according to item 17, wherein the coronavirus is contacted with the chlorous acid water in the absence of organic matter.

[0026] (Item 19) Item 19. The method according to item 17 or 18, wherein the free chlorine concentration (assuming Cl=35.45) of the chlorous acid water is at least 1 mg / L.

[0027] (Item 20) 20. The method according to any one of items 17 to 19, wherein the coronavirus is contacted with the chlorous acid water in the presence of an organic substance.

[0028] (Item 21) 21. The method according to any one of items 17 to 20, wherein the free chlorine concentration (assuming Cl=35.45) of the chlorous acid water is at least 10 mg / L.

[0029] (Item 22) Chlorous acid water to kill coronavirus. (Item 23) Use of chlorous acid water as a coronavirus killer. (Item 24) Use of chlorous acid water to manufacture coronavirus killer.

[0030] It is contemplated that the present disclosure may provide one or more of the above-described features in combinations other than those explicitly stated. Still further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary. [Effects of the Invention]

[0031] It can kill the coronavirus. [Brief explanation of the drawings]

[0032] [Figure 1]Figure 1 shows the results of an antiviral test against SARS-CoV-2 using chlorous acid water in the absence of organic matter. For each condition, the left side shows no virus and the right side shows SARS-CoV-2. [Figure 2] Figure 2 shows the results of an antiviral test against SARS-CoV-2 using chlorous acid water in the presence of organic matter. Under these conditions, the left side shows no virus and the right side shows SARS-CoV-2. DETAILED DESCRIPTION OF THE INVENTION

[0033] The present disclosure will be described in more detail below. Throughout this specification, unless otherwise specified, singular expressions should be understood to include the plural concept. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, it should be understood that terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the case of conflict, the present specification (including definitions) will prevail.

[0034] Abbreviations used herein have their conventional meaning within the art unless otherwise specified.

[0035] References herein to "about" a value or parameter include the variation that is directed to the value or parameter itself. For example, "about X" includes "X" itself as well as values ​​that allow for ±10% error, unless otherwise specified.

[0036] In this specification, "chlorous acid water" refers to an aqueous solution containing chlorous acid (HClO2) used as a disinfectant, which can stably maintain chlorous acid (HClO2) for a long period of time. When a sample of chlorous acid water is measured with a spectrophotometer, the acidic chlorous acid ion (H + +ClO2 - If two absorption regions, one containing chlorine dioxide (ClO2) and the other containing chlorine dioxide (ClO2) with a peak around 350 nm, can be confirmed simultaneously, i.e., if a double nodule is observed, the presence of chlorous acid water can be confirmed.

[0037] In this specification, the "standard value of chlorous acid water" refers to the value calculated by a predetermined method for the concentration of chlorous acid in chlorous acid water, and the same value is calculated using the method described in the Examples. Usually, chlorous acid water having a standard value of 4 to 6 can be used as a drug substance, and the chlorous acid water formulation using this can contain this raw material chlorous acid water 4 to 6% product.

[0038] As a definition of chlorous acid content (HClO2 = 68.46), in this specification, "chlorous acid content (HClO2 = 68.46)" is used in the same sense as commonly used in the art, and when referring to chlorine-based products (e.g., chlorous acid water), it refers to the value obtained by iodometric titration. This value is converted to chlorous acid (HClO2 = 68.46), and this concentration (e.g., ppm, etc.) is expressed as the content.

[0039] Chlorous acid water can be produced by the methods disclosed in International Publication Nos. WO2008 / 026607, WO2014 / 188310, WO2014 / 188311, WO2014 / 188312, WO2015 / 093062, and WO2017 / 170904.

[0040] "Chlorous acid water" was designated as a food additive on February 1, 2013, and is a disinfectant with chlorous acid (HClO2) as its main active ingredient. Chlorous acid (HClO2), the main active ingredient of this "chlorous acid water," is a metastable chemical substance that has been recognized as a particularly safe substance by the U.S. USDA and FDA as a food additive: processing aid. The chlorous acid water used in this disclosure may or may not be a food additive, and may be provided as a pharmaceutical, quasi-drug, or miscellaneous item.

[0041] Moreover, hypochlorous acid water is capable of exerting a strong bactericidal effect even in the presence of organic matter, and was highly praised by the National Institute of Health Sciences (commonly known as the National Institute of Health Sciences) in its "2015 Survey on Inactivation Conditions for Norovirus," which stated that "hypochlorous acid water was the only substance that was able to inactivate norovirus to below the detection limit under all loading conditions." As the Food Sanitation Act Enforcement Regulations have been revised, hypochlorous acid water has been increasingly included in publications such as the "Cooking Manual for Mass Cooking Facilities" and "Hygiene Standards for Pickles," in the order in which large-scale food poisoning incidents have occurred.

[0042] Additionally, it was approved as a Class 2 disinfectant in 2019, with a target release date in 2020. Additions and revisions are constantly being made to various guidelines, such as the "Q&A Regarding Norovirus" and the "Guidelines for Infectious Disease Prevention in Daycare Centers" administered by the Ministry of Health, Labor and Welfare, as well as related manuals such as the "Manual for Infection Prevention in Elderly Care Support Facilities" and hygiene standards such as the "Hygiene Standards for Lunchboxes and Prepared Dishes," and it is a substance that is supplied to a wide range of markets in Japan's food hygiene and environmental hygiene markets.

[0043] Chlorous acid water, whose primary active ingredient is hypochlorous acid, has been found to have superior coronavirus killing (disinfection and sterilization) properties compared to other chlorine-based chemicals, such as hypochlorous acid water and sodium hypochlorite. While hypochlorous acid water possesses strong germicidal properties, its reactivity is gradual, making it suitable for use on hands. While it lacks instantaneous bactericidal activity, it possesses both precise germicidal power and gradual reactivity, and its bactericidal properties are also stable and sustained. Hypochlorous acid water exerts a slow but reliable and effective germicidal effect in contaminated environments with high levels of organic matter, which has traditionally been considered the weakest point for chlorine oxide-based chemicals. (Its bactericidal properties against microorganisms lurking in the dirt.) For example, the effectiveness of hypochlorous acid water in the presence of organic matter is reported on the Ministry of Health, Labor, and Welfare's website in the "2015 Research Report on the Inactivation Conditions for Norovirus (National Institute of Health Food Sanitation Control Division)."

[0044] Hypochlorous acid water does not need to be prepared before use, and does not require any special generator; it can be used by anyone, anywhere, whenever they want, and is safe.

[0045] In this specification, "chlorous acid water preparation" refers to a preparation prepared using chlorous acid water as a drug substance. Depending on the application, additional ingredients, pH, chlorous acid content, free chlorine concentration, etc. can be adjusted.

[0046] As used herein, "active ingredient chlorous acid water" refers to chlorous acid water used as an active ingredient. The chlorous acid water can be prepared by the method described herein.

[0047] The "chlorous acid water formulation" used in the present disclosure has low irritation and may not cause damage even when it comes into direct contact with animals. The chlorous acid water formulation used in the present disclosure may have no corrosive reaction, no erythema, or edema when applied to the skin, and may have normal cornea, iris, and conjunctiva when applied to the eyes, and may not exhibit skin sensitization.

[0048] In this specification, the content of hypochlorous acid water is measured by iodometric titration, and "free chlorine," "free chlorine concentration," or "free residual chlorine concentration" is a value measured by Appendix 3 of the "Testing Method for Free Residual Chlorine and Combined Chlorine Established by the Minister of Health, Labour and Welfare Pursuant to Article 17, Paragraph 2 of the Enforcement Regulations of the Water Supply Act" (hereinafter referred to as "colorimetric method (DPD indicator)"), and is a value obtained by oxidizing the DPD indicator.

[0049] In this specification, "filth equivalent to 0.5% BSA or more" refers to the filth equivalent to the organic matter used in the challenge test described in the "2015 Report on the Inactivation Conditions of Norovirus, Food Sanitation Control Division, National Institute of Health Sciences." In this organic matter challenge test, a virus solution was mixed 1:1 with bovine serum albumin (BSA) (Sigma, A9576-50ML), meat extract (Nacalai Tesque, 15837-55), and polypeptone (Nihon Pharmaceutical, Hypopolypeptone N, 397-02121) diluted with MEM medium to contain 10% BSA, and the resulting mixture was used as a 5% organic matter-added virus solution. BSA is an abbreviation for bovine serum albumin.

[0050] In this specification, "in the presence of organic matter, including disinfectant for hands, etc." refers to a condition in which organic matter that may normally be present on hands, etc. is present. This corresponds to the presence of "filth equivalent to 0.5% BSA or more."

[0051] In this specification, "in the absence of organic matter" refers to the complete absence of organic matter, as well as the substantial absence of organic matter (including below a threshold). It refers to all "states in which no organic matter is present."

[0052] (Preferred embodiment) In one aspect of the present disclosure, a coronavirus disinfectant containing chlorous acid water is provided. According to the Ministry of Health, Labor and Welfare's website, sodium hypochlorite is considered inappropriate for use on hands as a chlorine-based disinfectant, disinfectant, or sanitizer, and its effectiveness on hands is unknown, making it unsuitable for use on hands. Therefore, the use of the disclosed chlorous acid water as a coronavirus disinfectant was unexpected, even considering its status as a chlorine-based disinfectant. Even considering the previously known effects of chlorous acid water, its ability to kill coronaviruses, including SARS-CoV-2, was unexpected. Furthermore, it has been shown that when used for daily disinfection, like alcohol, it can be sprayed or immersed directly on hands, making it significantly different and advantageous from other chlorine-based disinfectants.

[0053] The present disclosure also provides a disinfectant in which the free chlorine concentration (as Cl = 35.45) of the chlorous acid water is at least 1 mg / L or more in the absence of organic matter. The present disclosure also provides a disinfectant in which the content of the chlorous acid water (as chlorous acid (HClO2 = 68.46)) is at least 100 ppm or more in the absence of organic matter. The free chlorine concentration (assuming Cl=35.45) of the chlorous acid water in the absence of organic matter can be at least 1 mg / L, at least 5 mg / L, at least 10 mg / L, at least 20 mg / L, at least 30 mg / L, at least 40 mg / L, at least 50 mg / L, at least 60 mg / L, at least 70 mg / L, at least 80 mg / L, at least 90 mg / L, at least 100 mg / L, at least 500 mg / L, at least 1000 mg / L, at least 2000 mg / L, at least 3000 mg / L, at least 4000 mg / L, at least 5000 mg / L, at least 6000 mg / L, at least 7000 mg / L, at least 8000 mg / L, at least 9000 mg / L, or at least 10,000 mg / L.

[0054] The present disclosure also provides a disinfectant in which the free chlorine concentration (as Cl = 35.45) of the chlorous acid water is at least 5 mg / L to 200 mg / L or more in the presence of organic matter, including disinfectants for hands, etc. The present disclosure also provides a disinfectant in which the content of the chlorous acid water, as chlorous acid (HClO2 = 68.46), is at least 200 ppm or more in the presence of organic matter, including disinfectants for hands, etc. The free chlorine concentration of chlorous acid water (assuming Cl = 35.45) in the presence of organic matter, including hand disinfectants, can be at least 5 mg / L, at least 10 mg / L, at least 20 mg / L, at least 30 mg / L, at least 40 mg / L, at least 50 mg / L, at least 60 mg / L, at least 70 mg / L, at least 80 mg / L, at least 90 mg / L, at least 100 mg / L, at least 110 mg / L, at least 120 mg / L, at least 130 mg / L, at least 140 mg / L, at least 150 mg / L, at least 160 mg / L, at least 170 mg / L, at least 180 mg / L, at least 190 mg / L, or at least 200 mg / L.

[0055] The present disclosure also provides a disinfectant in which the free chlorine concentration (Cl = 35.45) of the chlorous acid water is at least 10 mg / L or more in the presence of organic matter containing filth equivalent to 0.5% BSA or more. The present disclosure also provides a disinfectant in which the content of the chlorous acid water (as chlorous acid (HClO2 = 68.46)) is at least 400 ppm or more in the presence of organic matter containing filth equivalent to 0.5% BSA or more. The free chlorine concentration of chlorous acid water (assuming Cl=35.45) is at least 10mg / L, at least 20mg / L, at least 30mg / L, at least 40mg / L, at least 50mg / L, at least 60mg / L, at least 70mg / L, at least 80mg / L, at least 90mg / L, at least 100mg / L, at least 200mg / L, at least 300mg / L, at least 400mg / L, in the presence of organic matter, including filth, equivalent to 0.5% BSA or more. L, at least 500 mg / L, at least 600 mg / L, at least 700 mg / L, at least 800 mg / L, at least 900 mg / L, at least 1000 mg / L, at least 2000 mg / L, at least 3000 mg / L, at least 4000 mg / L, at least 5000 mg / L, at least 6000 mg / L, at least 7000 mg / L, at least 8000 mg / L, at least 9000 mg / L, at least 10000 mg / L.

[0056] In the present disclosure, the standard value of the chlorous acid water may be 4 to 6%.

[0057] The present disclosure also provides that the coronavirus may be a virus belonging to the subfamily Letovirinae or Orthocoronavirus. The present disclosure also provides that the coronavirus may be a virus belonging to the genus Alphacoronavirus, Betacoronavirus, Gammacoronavirus, or Deltacoronavirus. The present disclosure also provides that the coronavirus may be a virus belonging to the genus Betacoronavirus.

[0058] The present disclosure also provides that the coronavirus may be of the subgenus Coracovirus, Decacovirus, Duvinacovirus, Ruchacovirus, Minacovirus, Minunacovirus, Myotakovirus, Niktakovirus, Pedakovirus, Rhynacovirus, Setracovirus, Soracovirus, Sunacovirus, Tegacovirus, Enbecovirus, Hibecovirus, Merbecovirus, Nobecovirus, Sarbecovirus, Andecovirus, Burdecovirus, Herdecovirus, Brangacovirus, Segacovirus, or Igakovirus.

[0059] The present disclosure also provides that the coronavirus may be a coronavirus that infects humans.

[0060] The present disclosure also provides that the coronavirus may be HCoV-HKU1, HCoV-OC43, SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), or 2019 novel coronavirus (SARS-CoV-2).

[0061] The present disclosure also provides that the coronavirus may be SARS coronavirus (SARS-CoV), MERS coronavirus (MERS-CoV), or 2019 novel coronavirus (SARS-CoV-2).

[0062] The present disclosure also provides that the killing agent may be a killing agent for fingers.

[0063] The present disclosure also provides a method for killing coronaviruses using chlorous acid water.

[0064] The present disclosure also relates to a method for contacting the coronavirus with the chlorous acid solution in the absence of organic matter.

[0065] The present disclosure also provides that the free chlorine concentration (as Cl=35.45) of the chlorous acid water is at least 1 mg / L.The free chlorine concentration (as Cl=35.45) of the chlorous acid water is at least 1 mg / L, at least 2 mg / L, at least 3 mg / L, at least 4 mg / L, at least 5 mg / L, at least 6 mg / L, at least 7 mg / L, at least 8 mg / L, at least 9 mg / L, at least 10 mg / L, at least 15 mg / L, at least 20 mg / L, at least 25 mg / L, at least 30 mg / L, at least 35 mg / L, at least 40 mg / L, It can be at least 45 mg / L, at least 50 mg / L, at least 60 mg / L, at least 70 mg / L, at least 80 mg / L, at least 90 mg / L, at least 100 mg / L, at least 110 mg / L, at least 120 mg / L, at least 130 mg / L, at least 140 mg / L, at least 150 mg / L, at least 160 mg / L, at least 170 mg / L, at least 180 mg / L, at least 190 mg / L, at least 200 mg / L.

[0066] The present disclosure also relates to a method for contacting the coronavirus with the chlorous acid solution in the presence of organic matter.

[0067] The present disclosure also provides a method for treating a chlorous acid water having a free chlorine concentration (assuming Cl=35.45) of at least 10 mg / L, at least 20 mg / L, at least 30 mg / L, at least 40 mg / L, at least 50 mg / L, at least 60 mg / L, at least 70 mg / L, at least 80 mg / L, at least 90 mg / L, at least 100 mg / L, at least 200 mg / L, at least 300 mg / L, at least 40 ... The concentration may be 0 mg / L, at least 600 mg / L, at least 700 mg / L, at least 800 mg / L, at least 900 mg / L, at least 1000 mg / L, at least 2000 mg / L, at least 3000 mg / L, at least 4000 mg / L, at least 5000 mg / L, at least 6000 mg / L, at least 7000 mg / L, at least 8000 mg / L, at least 9000 mg / L, or at least 10000 mg / L.

[0068] The present disclosure also provides chlorous acid water for killing coronaviruses.

[0069] (Chlorous acid water and its manufacturing example) The chlorous acid water used in this disclosure has characteristics discovered by the present inventors. Chlorous acid water produced by any known method, such as those described in the above-mentioned literature, can be used. A typical composition, for example, a mixture of 61.40% chlorous acid water, 1.00% potassium dihydrogen phosphate, 0.10% potassium hydroxide, and 37.50% purified water (sold by the applicant; 72% chlorous acid water corresponds to 30,000 ppm chlorous acid), can be used, but is not limited to this. This agent reduces the decay of chlorous acid due to contact with organic matter under acidic conditions while maintaining its bactericidal effect. Furthermore, it generates only a small amount of chlorine gas and suppresses the amplification of odors caused by the mixture of chlorine and organic matter.

[0070] In one embodiment, the chlorous acid water of the present disclosure can be produced by adding sulfuric acid or an aqueous solution thereof to an aqueous sodium chlorate solution in an amount and concentration sufficient to maintain the pH value of the aqueous solution at 3.4 or less, thereby generating chloric acid, and then adding hydrogen peroxide in an amount equal to or greater than the amount required for the reduction reaction of the chloric acid.

[0071] In another embodiment, the chlorous acid water of the present disclosure can be produced by adding sulfuric acid or an aqueous solution thereof to an aqueous sodium chlorate solution in an amount and concentration sufficient to maintain the pH value of the aqueous solution at 3.4 or less, to generate chloric acid, and then adding hydrogen peroxide in an amount equal to or greater than the amount required for the reduction reaction of the chloric acid to generate chlorous acid.Then, any one of an inorganic acid or an inorganic acid salt alone, or two or more of them alone or a combination of these, is added to the aqueous solution to adjust the pH value to within the range of 2.3 to 8.5.

[0072] Furthermore, in another embodiment, the chlorous acid water of the present disclosure can be produced by adding sulfuric acid or an aqueous solution thereof to an aqueous sodium chlorate solution in an amount and concentration sufficient to maintain the pH value of the aqueous solution at 3.4 or less, to generate chloric acid by reaction, and then adding hydrogen peroxide in an amount equal to or greater than the amount required for the reduction reaction of the chloric acid to generate chlorous acid.Then, any one or two or more of an inorganic acid, an inorganic acid salt, an organic acid, or an organic acid salt, or a combination of these, is added to the aqueous solution to adjust the pH value to within the range of 2.3 to 8.5.

[0073] Furthermore, in another embodiment, the chlorous acid water of the present disclosure can be produced by adding sulfuric acid or an aqueous solution thereof to an aqueous sodium chlorate solution in an amount and concentration sufficient to maintain the pH value of the aqueous solution at 3.4 or less, to generate chloric acid by reacting the solution, and then adding hydrogen peroxide in an amount equal to or greater than the amount required for the reduction reaction of the chloric acid to generate chlorous acid in the aqueous solution, and then adding any one or more of an inorganic acid or an inorganic acid salt, or any one or more of an inorganic acid or an inorganic acid salt, or any one or more of an organic acid or an organic acid salt, or any one or more of an inorganic acid or an inorganic acid salt, or any one or more of an organic acid or an organic acid salt, to adjust the pH value to within the range of 2.3 to 8.5.

[0074] In another embodiment, the inorganic acid used in the above method may be carbonic acid, phosphoric acid, boric acid, or sulfuric acid.

[0075] Furthermore, in another embodiment, the inorganic acid salt may be a carbonate, an inorganic hydroxide, a phosphate, or a borate.

[0076] In another embodiment, the carbonate may be sodium carbonate, potassium carbonate, sodium bicarbonate, or potassium bicarbonate.

[0077] Furthermore, in another embodiment, the inorganic hydroxide may be sodium hydroxide, potassium hydroxide, calcium hydroxide, or barium hydroxide.

[0078] Furthermore, in another embodiment, the phosphate may be disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, or potassium dihydrogen phosphate.

[0079] In another embodiment, the borate may be sodium borate or potassium borate.

[0080] Furthermore, in another embodiment, the organic acid may be succinic acid, citric acid, malic acid, acetic acid, or lactic acid.

[0081] Furthermore, in another embodiment, the organic acid salt may be sodium succinate, potassium succinate, sodium citrate, potassium citrate, sodium malate, potassium malate, sodium acetate, potassium acetate, sodium lactate, potassium lactate, or calcium lactate.

[0082] In a method for producing an aqueous solution containing chlorous acid (HClO2) (chlorous acid water) that can be used as a bactericide, sulfuric acid (H2SO4) or its aqueous solution is added to an aqueous solution of sodium chlorate (NaClO3) to create acidic conditions, resulting in chloric acid (HClO3).Chlorous acid (HClO2) is then produced by adding the amount of hydrogen peroxide (H2O2) required to convert this acid to chlorous acid through a reduction reaction.The basic chemical reactions in this production method are represented by the following formulas A and B.

[0083] [ka]

[0084] Equation A shows that chloric acid can be obtained by adding sulfuric acid (H2SO4) or its aqueous solution in an amount and concentration that will maintain the pH value of a sodium chlorate (NaClO3) aqueous solution within the acidic range. Equation B then shows that chloric acid (HClO3) is reduced with hydrogen peroxide (H2O2) to produce chlorous acid (HClO2).

[0085] [ka]

[0086] During this process, chlorine dioxide gas (ClO2) is generated (formula C), but when it coexists with hydrogen peroxide (H2O2), it undergoes reactions D to F to produce chlorous acid (HClO2).

[0087] By the way, the generated chlorous acid (HClO2) undergoes a decomposition reaction between multiple chlorous acid molecules, and chloride ions (Cl - In the presence of chlorine dioxide (HClO2), hypochlorous acid (HClO), and other reducing agents, it quickly decomposes into chlorine dioxide gas and chlorine gas. Therefore, to be useful as a bactericide, it must be prepared in a way that allows it to remain in the chlorous acid (HClO2) state for a long time.

[0088] Therefore, by adding any one of inorganic acids, inorganic acid salts, organic acids or organic acid salts, or two or more of them alone or in combination, to chlorous acid (HClO2) or chlorine dioxide gas (ClO2) obtained by the above method or an aqueous solution containing them, a transition state is created and the decomposition reaction is delayed, making it possible to maintain chlorous acid (HClO2) stably for a long period of time.

[0089] In one embodiment, chlorous acid (HClO) or chlorine dioxide gas (ClO) obtained by the above method or an aqueous solution containing these may be used with an inorganic acid or an inorganic acid salt, specifically a carbonate or an inorganic hydroxide, either alone or in combination.

[0090] In another embodiment, an aqueous solution containing an inorganic acid or an inorganic acid salt, specifically a carbonate or an inorganic hydroxide, either alone or in combination, to which an inorganic acid, an inorganic acid salt, an organic acid or an organic acid salt, either alone or in combination, can be added.

[0091] In addition, in yet another embodiment, an aqueous solution prepared by the above method can be used in which an inorganic acid, an inorganic acid salt, an organic acid or an organic acid salt is added alone or in combination with two or more kinds of inorganic acid, an inorganic acid salt, an organic acid or an organic acid salt.

[0092] Examples of the inorganic acid include carbonic acid, phosphoric acid, boric acid, and sulfuric acid. Examples of inorganic acid salts include carbonates, inorganic hydroxides, and phosphates and borates. More specifically, examples of carbonates include sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate. Examples of inorganic hydroxides include sodium hydroxide, potassium hydroxide, calcium hydroxide, and barium hydroxide. Examples of phosphates include disodium hydrogen phosphate, sodium dihydrogen phosphate, trisodium phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, and potassium dihydrogen phosphate. Examples of borates include sodium borate and potassium borate. Examples of the organic acid include succinic acid, citric acid, malic acid, acetic acid, and lactic acid. Examples of organic acid salts that are suitable include sodium succinate, potassium succinate, sodium citrate, potassium citrate, sodium malate, potassium malate, sodium acetate, potassium acetate, sodium lactate, potassium lactate, and calcium lactate.

[0093] When acid and / or its salt is added, Na + +ClO2 - ⇔ Na-ClO2 or K + +ClO2 - ⇔ K-ClO2 or H + +ClO2 - This creates a transition state such as H-ClO2, which slows down the progression of chlorous acid (HClO2) to chlorine dioxide (ClO2). This allows chlorous acid (HClO2) to be maintained for a long period of time, making it possible to produce an aqueous solution containing chlorous acid (HClO2) that generates little chlorine dioxide (ClO2).

[0094] The decomposition of chlorite in acidic solution is shown below.

[0095] [ka]

[0096] As shown in this equation, the decomposition rate of a chlorite aqueous solution increases as the pH decreases, i.e., the acidity increases. In other words, the absolute rates of reactions (a), (b), and (c) in the above equation increase. For example, the proportion of reaction (a) decreases as the pH decreases, but the total decomposition rate fluctuates greatly, i.e., increases. Therefore, the amount of chlorine dioxide (ClO2) generated also increases as the pH decreases. Therefore, the lower the pH value, the faster the sterilization and bleaching process, but the irritating and harmful chlorine dioxide gas (ClO2) makes work difficult and has adverse effects on human health. Furthermore, the reaction of chlorous acid to chlorine dioxide proceeds quickly, making chlorous acid unstable and shortening the time it can maintain its bactericidal activity.

[0097] Therefore, when the inorganic acid, inorganic acid salt, organic acid, or organic acid salt is added to an aqueous solution containing chlorous acid (HClO), the pH value is adjusted to within the range of 2.3 to 8.5 from the viewpoint of the balance between the inhibition of chlorine dioxide generation and the bactericidal power.

[0098] The chlorous acid water of the present disclosure may also be an aqueous solution obtained by adding hydrochloric acid to a saturated sodium chloride solution, electrolyzing the solution under acidic conditions in a membraneless electrolytic cell (meaning a cell consisting of an anode and a cathode not separated by a membrane), adding sulfuric acid to the resulting aqueous solution to make it strongly acidic, and then adding hydrogen peroxide to the resulting chlorous acid to react with it. The chlorous acid water may be one listed in the 9th edition of the Official Specification of Food Additives 2018 (Ministry of Health, Labor and Welfare, Consumer Affairs Agency).

[0099] Hypochlorous acid water preparations that can be used in the present disclosure include "Care for Hands," "Care for Hands Pro-Free," "Care for Fresh," "Outlock Super," "New Outlock SP," "Care forpis Pro-Free," "Care for No. 3," "Care for Norobarrier Plus," "Chlorus Care 8," and "Chlorus Care 10," all manufactured by Motobu Sankei Co., Ltd.

[0100] (Problems in comparing and evaluating the antimicrobial effects of chlorous acid water and sodium hypochlorite) One problem with comparing and evaluating the antimicrobial effects of chlorous acid water and sodium hypochlorite is that chlorine oxide concentrations are expressed as either effective chlorine concentration or free chlorine, and antimicrobial effectiveness depends on free chlorine, which is the source of oxidizing power. While the relationship between free chlorine and effective chlorine concentration for sodium hypochlorite is nearly 1:1, the effective chlorine concentration and free chlorine for chlorous acid water do not coincide like for sodium hypochlorite. Therefore, when comparing the bactericidal power of the two chemicals on the same level, it is necessary to compare the oxidizing power, which indicates antimicrobial effectiveness, i.e., free chlorine, rather than effective chlorine concentration.

[0101] The oxidizing power of chlorine oxide agents is typically determined by free chlorine concentration or colorimetric methods such as the DPD method or TMB method. However, unlike sodium hypochlorite, there are no standards for measuring free chlorine in chlorous acid water. Therefore, a calibration curve is created by setting oxidizing power to 1 mg / L of sodium hypochlorite's free chlorine (assuming Cl = 35.45). Furthermore, oxidizing power can be expressed in terms of free chlorine (assuming Cl = 35.45). When comparing the two using the same free chlorine, the free chlorine in sodium hypochlorite (assuming Cl = 35.45) is generated from Cl radicals, whereas the free chlorine in chlorous acid water is generated from HClO2. Therefore, as with sodium hypochlorite, oxidizing power 1 = 1 mg / L of free chlorine (assuming Cl = 35.45). By using the same standard, chlorous acid water can be compared on the same basis as sodium hypochlorite.

[0102] To measure free chlorine (based on Cl = 35.45), a buffer solution and DPD indicator are added to the sample and the concentration is measured at 510 nm using an absorptiometer. To measure free chlorine (based on Cl = 35.45) in the presence of organic matter, TMB reagent is used at 655 nm, and the concentration is calculated from the measured value. To confirm the bactericidal effect, the free chlorine (based on Cl = 35.45) of the test agent is prepared using the DPD method. Each agent is contacted with a bacterial solution containing organic matter, and after a certain period of time, the solution is neutralized with sodium thiosulfate. The number of surviving bacteria in the neutralized solution is then counted. The available chlorine content can be determined using iodine reduction titration.

[0103] [ka]

[0104] (How to use chlorous acid water for COVID-19) Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by SARS-CoV-2 (COVID-19 virus). The COVID-19 virus is primarily transmitted through close physical contact and respiratory droplets, but airborne transmission is also possible during aerosol-generating medical procedures. Currently, no conclusive studies are available on the relationship between COVID-19 virus transmission and contamination of environmental surfaces (facilities, equipment, surfaces, etc.). However, there is evidence of contamination of equipment and materials in health care facilities, and an association between contamination of environmental surfaces by other coronaviruses and subsequent infection transmission. Therefore, the goal is to minimize the role of fomites in COVID-19 transmission in health care and non-health care settings.

[0105] Environmental surfaces in healthcare facilities include furniture and fixed objects inside and outside patient rooms and bathrooms, such as tables, chairs, walls, light switches, computer peripherals, electronic devices, sinks, and toilets, as well as noncritical (medical) equipment, such as blood pressure cuffs, stethoscopes, wheelchairs, and incubators. Environmental surfaces in non-healthcare facilities include sinks, toilets, electronic devices (touchscreens and buttons), furniture, and fixed objects, such as countertops, stair railings, floors, and walls.

[0106] Healthcare facilities where medical procedures are performed are prone to surface contamination by COVID-19. Therefore, to prevent further transmission, surfaces must be properly cleaned and disinfected, especially where COVID-19 patients are cared for, as well as alternative isolation settings for uncomplicated, mildly ill COVID-19 patients, such as at home or in nontraditional facilities.

[0107] Transmission of the COVID-19 virus is thought to be associated with close contact in enclosed spaces, such as homes, health care facilities, and assisted living and residential care facilities. COVID-19 transmission events have also been identified in community settings outside of health care facilities, including publicly accessible buildings, religious institutions, shops, transportation, and workplaces. While the exact role of fomite transmission outside of health care facilities and the need for disinfection remain unclear, measures to limit the spread of the virus, including cleaning and disinfection measures, are necessary for non-health care settings. (For example, WHO currently has interim guidance for non-health care settings, including recommendations for environmental cleaning and disinfection, that includes places of worship, funeral homes, workplaces, the food industry, the hospitality industry, the aviation industry, the shipping industry, schools, prisons, and other detention facilities.) In all settings, including those where regular cleaning and disinfection are not possible due to resource limitations, frequent handwashing and avoiding touching the face are key preventative measures to reduce the likelihood of transmission associated with surface contamination.

[0108] Like other coronaviruses, SARS-CoV-2 is an enveloped virus with a fragile lipid outer membrane, making it more susceptible to disinfectants than non-enveloped viruses such as rotavirus, norovirus, and poliovirus. Several studies have evaluated the duration of infectiousness of the COVID-19 virus on various environmental surfaces. One study reported that the virus survived for 1 day on fabric and wood surfaces, 2 days on glass, 4 days on stainless steel and plastic surfaces, and 7 days on the outer layer of a medical mask. Another study reported that the COVID-19 virus survived for 4 hours on copper surfaces, 24 hours on cardboard, and 72 hours on plastic and stainless steel surfaces. The COVID-19 virus also survives over a wide range of pH values ​​and ambient temperatures, but is highly sensitive to heat and standard disinfection methods. However, these studies were conducted under laboratory conditions without cleaning or disinfection procedures and should be interpreted with caution before applying to real-world environments.

[0109] The present disclosure provides for cleaning and disinfecting environmental surfaces in light of COVID-19.

[0110] This disclosure may be of interest to health professionals, public health experts, and authorities developing and implementing policies and standard operating procedures (SOPs) for cleaning and disinfecting environmental surfaces in light of COVID-19. Comprehensive guidance on environmental cleaning and disinfection practices is provided in the WHO publication "Essential Standards for Environmental Health in Health-Care Facilities" and "Best Practices for Environmental Cleaning in Resource-Limited Health-Care Facilities," jointly published by the U.S. Centers for Disease Control and Prevention and the African Network for Infection Control. Procedures for decontamination of equipment and semi-critical and critical instruments are provided in the WHO publication "Decontamination and Reuse of Medical Equipment in Health-Care Facilities."

[0111] Cleaning and disinfection principles Cleaning helps eliminate or significantly reduce viruses on contaminated environmental surfaces and is a necessary first step in any disinfection process. Cleaning with water, soap (or mild detergent), and mechanical action (brushing and scrubbing) can completely or partially remove dirt, dust, and organic matter such as blood, secretions, and excretions, but it does not kill microorganisms. Organic matter can prevent the disinfectant from directly contacting the surface, inhibiting the antiviral efficacy or mechanism of action of some disinfectants. Therefore, cleaning should be followed by disinfection with chemicals such as chlorine or alcohol to kill any remaining microorganisms.

[0112] Disinfectants should be prepared and used in solutions according to the manufacturer's recommendations for volume and contact time. Improper dilution (too high or too low) during preparation can reduce efficacy. High concentrations can increase chemical exposure to users and potentially damage environmental surfaces. Sufficient disinfectant solutions should be used according to the manufacturer's recommendations to ensure surfaces remain moist and untouched for a sufficient time to inactivate viruses. Training Environmental cleaning in health care facilities is a complex infection prevention and control intervention that requires a multi-pronged approach, including training, monitoring, audits, feedback, memoranda, and posting of SOPs in key locations.

[0113] Training for cleaning staff should be based on the health-care facility's policies and SOPs and national guidelines. It should be structured, targeted, and conducted in an appropriate manner (e.g., participatory, appropriate literacy level) and is mandatory when staff are assigned to a new job. Training programs should cover risk assessment and ensure the safe preparation of disinfectants, the use of mechanical cleaning and cleaning equipment, standard precautions, and transmission-based precautions. Refresher courses are also recommended to promote good practice. Posters and instructions should be made available in health-care facilities and public buildings to remind cleaning and other staff to follow proper procedures for disinfectant preparation and use.

[0114] Cleaning and disinfection techniques and supplies Cleaning should be done from the cleanest (cleanest) to the dirtiest (dirtiest) areas and from high to low, in a systematic way that leaves no uncleaned areas, with any dust that has fallen on the floor being cleaned last. Use new wipes for each cleaning job (e.g. daily cleaning in general wards). Wipes that are no longer saturated with solution should be discarded. In areas considered to be at high risk of contamination with the COVID-19 virus, new wipes should be used after each patient bed is cleaned. Soiled wipes should be reused using appropriate methods after use, and SOPs should be consulted for the frequency of wipe changes.

[0115] Cleaning equipment (e.g., buckets) must be properly maintained. Cleaning equipment used in COVID-19 patient isolation areas should be color-coded and separated from other equipment. Detergents and disinfectants become contaminated during cleaning and become less effective over time with excessive organic matter, so continued use of the same solution may result in microbial contamination on the next surface to be cleaned. Therefore, in areas used by suspected / confirmed COVID-19 patients, detergent and / or disinfectant solutions must be discarded after each use. Solutions should preferably be prepared fresh daily or after each cleaning shift. It is recommended that buckets be washed with detergent, rinsed, dried, and stored upside down to drain completely when not in use.

[0116] Cleaning and disinfection supplies Prepare and handle disinfectants safely according to manufacturer's instructions and wear appropriate personal protective equipment (PPE) to avoid chemical exposure. Disinfectant selection should take into account the target microorganism, recommended concentration and contact time, availability of the disinfectant chemicals on the surface, toxicity, ease of use, and product stability. Also, local authority requirements for marketing authorization should be met, including any regulations applicable to specific industries, such as healthcare or food.

[0117] Cleaning and disinfecting health care facilities Cleaning and disinfecting environments in healthcare facilities, non-traditional facilities, and at home should follow detailed SOPs that clarify job responsibilities (e.g., for cleaners and healthcare staff) regarding surface classification and cleaning frequency. Particular attention should be paid to frequent environmental cleaning of high-touch surfaces, such as light switches, bed frames, door handles, infusion pumps, tables, water and drink pitchers, trays, cart handles, and sinks; however, all touchable surfaces should be disinfected. Cleaning practices and cleanliness should be monitored regularly. Cleaning staff numbers should be established to optimize cleaning efforts. Healthcare workers should be informed of cleaning schedules and completion times and be made aware of risk assessments for touching surfaces and equipment to avoid contamination of hands and equipment while caring for patients.

[0118] Cleaning and disinfection of non-healthcare facilities There is no evidence to suggest that the risk of COVID-19 virus transmission through fomites is equivalent in health-care and non-health-care settings. However, it is also important to reduce the potential for COVID-19 virus contamination in non-health-care settings, such as homes, workplaces, schools, gyms, and restaurants. High-touch surfaces in these non-health-care settings should be considered priority areas for disinfection. These include door and window handles, kitchen and food preparation areas, countertops, bathroom surfaces, toilets and faucets, touchscreen personal digital assistants, computer keyboards, and work surfaces. Disinfectants and their concentrations should be carefully selected to avoid surface damage and to avoid or minimize toxic effects to households and users of public spaces. Environmental cleaning methods and cleaning principles should be followed whenever possible. Surfaces can be cleaned with soap and water or detergent to remove organic matter before applying the disinfectant.

[0119] Ensure safety when preparing and using disinfectants Cleaning personnel must be trained in the safe use of personal protective equipment (PPE) and wear it properly. When working in areas occupied by suspected or confirmed COVID-19 cases or in areas where screening, triage, or consultations are taking place, they must wear PPE, namely, gowns, work gloves, medical masks, eye protection (if there is a risk of organic or chemical splashes), and work shoes or boots that cover the feet. Disinfectant solutions should always be prepared in a well-ventilated area. Mixing disinfectants, especially hypochlorite solutions, can produce gases that can irritate the respiratory system and can be fatal. Specific PPE is required when preparing or using disinfectants by health-care facility personnel due to the high concentrations of disinfectants used in health-care facilities and the extended exposure times during the work shift. Thus, PPE required for the preparation or use of disinfectants in health-care settings includes long-sleeved uniforms, work shoes with closed feet, gowns and / or impervious aprons, rubber gloves, medical masks, and eye protection (face shields are preferred). In non-health-care settings where disinfectants are prepared and used, a minimum of rubber gloves, impervious aprons, and closed feet are recommended, if resources are available. Eye protection and medical masks may also be required if there is a risk of splashes or for chemical protection.

[0120] (Comparison of chlorous acid water and other disinfectants) It has been reported that sodium hypochlorite and hypochlorous acid water have no antiviral effect unless the free chlorine concentration is 35 ppm or higher, which is impossible to achieve with electrolytic hypochlorous acid water, and organic matter has not been sufficiently removed. pH-adjusted sodium hypochlorite, which is not recognized as a food additive, was included in the evaluation under the name "high-concentration hypochlorous acid water," and the activation effect of hypochlorous acid water itself has not been demonstrated.

[0121] The inactivation effect of hypochlorous acid water on the novel coronavirus has not been confirmed except under the limited conditions of the absence of organic matter. On the other hand, it is known that hypochlorous acid water can achieve at least 99.9% inactivation effect even at an 8x dilution in the presence of organic matter, and can achieve complete inactivation of the novel coronavirus even at a 20x dilution in the absence of organic matter.

[0122] Furthermore, alcohol must be at a concentration of 70% (v / v) or higher to be effective in inactivating enveloped viruses. Such high concentrations of alcohol also remove oils from the user's hands. Furthermore, measures such as prohibiting entry to public facilities without using alcohol-based preparations installed at the entrances have resulted in severe hand irritation, which has already developed into a major social problem.

[0123] This is explained in more detail below.

[0124] 1. Sodium hypochlorite (sodium hypochlorite): a food additive disinfectant.

[0125] Sodium hypochlorite solution is made by injecting chlorine gas into sodium hydroxide (caustic soda), making it highly alkaline. Products with effective chlorine concentrations ranging from 4% (40,000 ppm) to 12% (120,000 ppm) are commonly sold commercially and are diluted according to the purpose.

[0126] It has a wide range of bactericidal activity against bacteria, fungi, viruses, etc., and is used so much in Japan that it can be said to be the basic disinfectant for virus prevention.

[0127] Generally, as a virus countermeasure, it is used at a concentration of 200 ppm or more by wiping or immersion to sterilize, disinfect, and sanitize doorknobs, cooking utensils, and general facilities such as cooking facilities and kitchens.

[0128] Furthermore, it is recommended to use it at 500 ppm or more to combat non-enveloped viruses, and to treat feces, vomit, etc., which contain large amounts of viruses and organic matter, it is necessary to use it at 1000 ppm or more, and in some cases 5000 ppm.Since it has a mechanism of sterilization by denaturing proteins and lipids in a highly alkaline range, it is highly irritating to the skin and mucous membranes and can damage the skin on the hands, so great care must be taken when handling it.

[0129] Moreover, in addition to the pungent odor during processing, the terrible lingering odor after processing is one of the reasons why its use is avoided on site.

[0130] 2. Hypochlorous acid water The official one is listed in the 9th edition of the Official Codex of Food Additives, and "hypochlorous acid water" is a new name established when the government designated acidic electrolyzed water, together with a dedicated generator (electrolysis device), as a food additive disinfectant. When dilute salt water or hydrochloric acid water is electrolyzed in an electrolysis device, chloride ions (Cl) are produced by an anodic reaction. -) is produced, which reacts with water molecules (H2O) to produce acidic electrolyzed water containing hypochlorous acid (HClO) and hydrochloric acid (HCl). This is the original "hypochlorous acid water," which is why it was originally called acidic electrolyzed water. Furthermore, this "hypochlorous acid water" is characterized by its low concentration but high activity, showing activity against a wide range of bacteria, fungi, and viruses, and being extremely safe. However, in the presence of organic matter, it reacts immediately with the organic matter and its activity is significantly reduced, so it is very important to remove any organic matter, or dirt, before using it. Furthermore, this "hypochlorous acid water" itself is not commercially available. The only thing that should be called "hypochlorous acid water" is what the user purchases a generator and operates it themselves at the site of use, and the concentration of effective chlorine at use is 10 ppm to 80 ppm. Furthermore, if the generator is legitimate (JIS standard: JISB-8701 was established in 2017), it is set to always produce "hypochlorous acid water" of this concentration, and as a general rule, it should be used without dilution while it is as fresh as possible, in a running water state (so-called pouring or overflow). Since it is produced continuously from a running water type generator connected to a water faucet, it can be used with running water, or it can be stored in a large tank and used with running water from there through piping.

[0131] Currently, three types of acidic electrolyzed water are approved as "hypochlorous acid water": "strongly acidic (pH 2.7 or less), weakly acidic (pH 2.7 to 5.0), and slightly acidic (pH 5.0 to 6.5)." The effective chlorine concentrations are 20 to 60 ppm for strongly acidic, 10 to 60 ppm for weakly acidic, and 10 to 80 ppm for slightly acidic electrolyzed water. Therefore, if we round these up, the pH is 6.5 or less, and the effective chlorine concentration is 10 ppm to 80 ppm.

[0132] [Table 1]

[0133] Excerpted with permission from Functional Water Newsletter No. 95 (published May 7, 2020) published by the Functional Water Research Foundation (General Incorporated Foundation), with additional information (hypochlorous acid water section).

[0134] 3. Pseudo hypochlorous acid water (not officially approved) An acidic solution made by mixing and diluting "sodium hypochlorite" with acid is sold under the name "hypochlorous acid water." However, this is not the same as the food additive "hypochlorous acid water," but is a "pseudohypochlorous acid water."

[0135] The biggest problem is that there are no concentration standards in the notification from the Ministry of Health, Labor and Welfare, so hypochlorous acid water with concentrations significantly higher than the standard concentration is being sold.

[0136] As the COVID-19 pandemic continues to spread, we have received numerous inquiries and complaints regarding health hazards (such as sore throats and eyes) caused by this "pseudo hypochlorous acid water."

[0137] The problem with "pseudo hypochlorous acid water" is that it is not designated as a food additive and there are no official standards. Furthermore, there is no objective evidence of its safety and no concentration regulations. As a result, products sold contain high concentrations of over 200 ppm, with some even reaching 1,000 ppm.

[0138] It is obvious that the fact that such products are being sold under the name "hypochlorous acid water" serves to undermine the credibility of the original "hypochlorous acid water."

[0139] Therefore, it seems that a method of differentiation using category names is being considered.

[0140] The name "acidified hypochlorous water" is thought to be more easily understood by the market for the following reasons: In the section titled "Regarding the Use of Sodium Hypochlorite Mixed with Acid" in the Notice No. 0825001 (Notice from the Director of the Standards and Inspection Division, Food Safety Department, Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare) dated August 25, 2004, it states, "2. Furthermore, in Section 2 of the Notice No. 31 from the Director of the Food Chemicals Division, Environmental Health Bureau, Ministry of Health and Welfare dated June 25, 1999, "Regarding the Handling of So-called Electrolyzed Water," so-called electrolyzed water, which is considered to be equivalent to diluted sodium hypochlorite, shall be treated in the same way as "hypochlorous acid water" above." Therefore, shortly after the notice was issued, the name "electrolyzed hypochlorous water" became established. This is because "hypochlorous water" had become a common name for diluted sodium hypochlorite."

[0141] [Table 2]

[0142] Excerpted and expanded with permission from Functional Water Newsletter Extra Edition R2-1 (published May 29, 2020) published by the Functional Water Research Foundation (General Incorporated Foundation) (acidified hypochlorous water is not approved).

[0143] 4. Chlorous acid water It is the most recent disinfectant approved as a food additive, and its manufacturing method is defined in the 9th edition of the Japanese Standards for Food Additives. Its main active ingredient, chlorous acid, is widely documented to be highly active against a wide range of bacteria, fungi, and viruses. A report from the National Institute of Health Sciences in 2015 stated that it "was the only one to show strong inactivation activity against the non-enveloped, highly drug-resistant norovirus, in the presence of high levels of organic matter." This brought it into the spotlight, and with its approval as a Class 2 disinfectant in 2018, expectations are high for its many potential uses.

[0144] Furthermore, "hypochlorous acid water," which has chlorous acid as its main active ingredient and has succeeded in stabilizing this chlorous acid in liquid for an extended period of time, is available in products with a content of 40,000 to 60,000 ppm, the same as "sodium hypochlorite solution." [Note that the concentration of "hypochlorous acid water" is expressed not as "chlorous acid content (HClO2 = 68.46)" but as content (HClO2 = 68.46) determined by iodometric titration, and its oxidizing power is indicated as free chlorine concentration determined by DPD colorimetry, so caution is required. While chlorous acid is available as a pharmaceutical ingredient in some markets, its handling is quite inconvenient. Taking advantage of chlorous acid's exceptional stability in liquid, it is available in diluted formulations at 400 ppm or 8000 ppm, allowing anyone, anywhere, anytime, anywhere, and for convenient, on-demand use. These formulations are available as products, either directly or further diluted, for use as wipes, dipping, or dripping. In addition, because low concentrations are less corrosive to metals and non-irritating to skin and mucous membranes, spray sterilization (spray sterilization of foodstuffs) is approved. In the United States, it is widely used not only by dipping but also by spraying to kill pathogenic microorganisms (e.g., Campylobacter, Salmonella, and enterohemorrhagic coliform bacteria) in meat and poultry, as well as to kill heat-resistant spore-forming bacteria that are commonly present in vegetables, spices, grains, and beans, and to kill mold, yeast, and other fungi. In Japan, it has begun to appear in the "Mass Cooking Hygiene Management Manual" and various hygiene standards.

[0145] 5. Recommended Use Areas First, regarding how to choose a disinfectant to combat viruses, rubbing alcohol or alcohol preparations are the most suitable for disinfecting and sterilizing hands and fingers, and are generally placed in dry areas such as building entrances, facilities, public transportation, and other places where an unspecified number of people come and go. Furthermore, alcohol concentrations of 50% v / v, and preferably 75% v / v or higher, are effective against bacteria, fungi, and viruses to a certain extent.

[0146] However, alcohol's drawback is that its effectiveness decreases dramatically as its concentration decreases. Its effectiveness drops dramatically below 50% v / V. This is due to alcohol's germicidal mechanism, which relies on the heat of vaporization to denaturate and kill lipids and proteins. This makes it effective against enveloped viruses, such as influenza viruses and coronaviruses, which are composed of proteins and lipids, but less effective against non-enveloped viruses, such as noroviruses. Furthermore, its concentration drops significantly in humid environments or places with high humidity, making it unsuitable for use near water, in places with high humidity, or in places where large amounts of water are used. Even if 1cc to 2cc of 99% v / v rubbing alcohol is sprayed for sterilization, if there are 1cc to 2cc of water droplets present, the alcohol concentration will drop below 50%, resulting in no germicidal effect.

[0147] This needs to be used with great care.

[0148] Sodium hypochlorite, commonly known as bleach or bleach, is a suitable disinfectant for sterilization and sanitization in such wet environments. Soaking or wiping with a 200 ppm solution of sodium hypochlorite is highly effective against bacteria, fungi, and viruses, with a 500 ppm solution recommended for non-enveloped viruses. It is also said that in environments with a high organic matter content, particularly in highly soiled areas, 1000 ppm or more is required, and 5000 ppm is required for feces and vomit disposal. However, sodium hypochlorite's disinfecting mechanism, similar to alcohol, is said to kill proteins and lipids in a highly alkaline range. However, it is irritating to the skin and mucous membranes, potentially causing skin and hand irritation and mucosal damage, making it very difficult to handle.

[0149] Furthermore, it causes severe metal corrosion, emits a strong chlorine odor during treatment, and leaves a severe post-treatment reaction odor, preventing immediate use of the area after sterilization. This is said to be a major problem in infectious disease prevention. It is no exaggeration to say that hypochlorous acid water was developed to sterilize large areas, regardless of their size, using large amounts of water, such as kitchens, cooking facilities, food processing plants, and central kitchens. This hypochlorous acid water can be used in an acidic electrolyzed water generator, first washed with a large amount of water, and then rinsed and sterilized throughout the facility, instantly creating a hygienic environment. However, in dirty environments with a high concentration of organic matter, its effectiveness is significantly reduced as it quickly reacts with organic matter and dirt. In such cases, it is recommended to use hypochlorous acid water for sterilization and disinfection. The unique feature of hypochlorous acid water is that it can be carried and used anywhere, whenever and wherever needed. It is the only liquid product available, which can be easily installed and obtained by electrolyzing table salt. Therefore, it is very suitable for installation and use in toilets, washrooms, bathrooms, kitchens, and other places that are prone to moisture and dirt, and is extremely convenient.

[0150] In short, alcohol is recommended in places with a large number of people coming and going, but its effectiveness disappears in humid places, so sodium hypochlorite is recommended in humid places. However, sodium hypochlorite is highly alkaline and remains alkaline no matter how diluted it is, causing skin and mucous membrane damage and rough skin and hands. In such cases, hypochlorous acid water and hypochlorous acid water are very effective. Furthermore, hypochlorous acid water is especially recommended for use in kitchens, food processing plants, and other areas where large amounts of water are used. However, hypochlorous acid water requires the installation of a generator, and the acidic electrolyzed water produced from this generator is as fresh as possible to be effective; hypochlorous acid water bottled and installed will not be effective. Hypochlorous acid water is best for refilling and installing. The use of hypochlorous acid water is highly recommended, especially in dirty environments with a high concentration of organic matter, such as toilets, kitchens, bathrooms, and hand-washing areas.

[0151] Undiluted alcohol (99% (v / v)) has a bactericidal effect (generally 75% or more). On the other hand, if water is mixed in (including when diluted), the bactericidal effect is lost. Therefore, treatment with alcohol should be limited to dry places, and it is not effective in wet areas such as hand washing areas.

[0152] Therefore, in places where water is available, chlorine-based disinfectants are commonly used instead of alcohol. Sodium hypochlorite, a typical example, is a strong alkaline agent whose disinfecting effect is the alkaline denaturation of proteins and other substances. Even when diluted extremely thinly with water, it remains alkaline, causing skin and mucosal disorders, including rough skin, when used by humans. However, hypochlorous acid water and hypochlorous acid water, which are chlorine oxide disinfectants with a pH close to neutral, are less irritating to the skin and do not irritate the skin. However, hypochlorous acid water is merely an aqueous solution obtained from an electrolyzer, and the free chlorine in the hypochlorous acid water discharged from the electrolyzer immediately disappears, making it impossible to bottle and use. Furthermore, it cannot be transported. Unlike hypochlorous acid water, hypochlorous acid water can be transported while maintaining free chlorine, an advantage not found in other disinfectants. This portable form of hypochlorous acid water has been shown to inactivate the novel coronavirus.

[0153] Furthermore, there are many cases where acidic sodium hypochlorite, which is sodium hypochlorite with an adjusted pH, is sold as "hypochlorous acid water," but these are not all hypochlorous acid water. Moreover, since it does not contain food additives, its safety and effectiveness have not been recognized.

[0154] (use) The coronavirus killing agents of the present disclosure have a variety of uses, including pharmaceutical and non-pharmaceutical uses.

[0155] Medical applications include killing coronaviruses on body surface tissues such as skin and mucous membranes. The coronavirus disinfectant of the present disclosure is hypoallergenic to skin and mucous membranes and can be used in medical settings to sterilize the hands of doctors, nurses, dentists, pharmacists, veterinarians, and others. It can also be used to kill coronaviruses in humans, livestock, pets, and others.

[0156] Non-medicinal uses include sterilizing the surfaces of everyday items, etc. They can be used on cooking utensils (including wooden ones), containers, cutting boards, colanders, cooking machines, sinks, workers' hands, kitchens, doorknobs, work surfaces, knives, tableware (including chopsticks), sponges, dishcloths, washbasins, bathrooms, drains, drainage pipes, toilets, toilet seats, toilet paper holders, hand-washing facilities, walls, floors, ceilings, tables, furniture, toys, baby bottles, breast pumps, polished rice, beans, fruits, seaweed, fresh seafood (including whale meat), meat, meat products and whale meat products, and foods including these preserved by salting, drying or other methods.

[0157] (lethal) The present disclosure discloses the use of chlorous acid water as a coronavirus killer. It can be used to kill coronaviruses in any location where coronaviruses may be present. The coronavirus killer of the present disclosure has stable and sustained bactericidal activity and can be used for a variety of purposes.

[0158] (killing law) The present disclosure discloses a method for killing coronaviruses using chlorous acid water. The coronavirus killing agent containing chlorous acid water of the present disclosure can be used as is or after being appropriately diluted depending on the application.

[0159] For kitchens, sinks, doorknobs, work tables, etc., they can be washed with a neutral detergent or the like, rinsed with running water, sprayed with the undiluted coronavirus killing agent of the present disclosure, and then wiped up with a cloth or the like.

[0160] Cookware, cutting boards, knives, tableware, etc. can be washed with dishwashing detergent, rinsed with running water, and then immersed in a solution of the coronavirus disinfectant of the present disclosure diluted 2 to 10 times or 2 to 20 times for 10 minutes or more, preferably 30 minutes. Alternatively, the undiluted solution of the coronavirus disinfectant of the present disclosure can be directly sprayed (approximately 10 cm 2 The area may be left for approximately 5 minutes, 10 minutes or more, or 30 minutes, after which it may be rinsed with running water and dried.

[0161] For sponges, cloths, etc., they can be washed with a neutral detergent, rinsed with running water, and then immersed in a solution of the coronavirus killing agent of the present disclosure diluted 2 to 10 times for 30 minutes, after which the water can be removed and the item can be left to dry.

[0162] For cooking machinery, parts can be removed from the machine body, washed with a neutral detergent, rinsed with running water, and then immersed in a 2- to 20-fold diluted solution of the coronavirus disinfectant of the present disclosure for at least 10 minutes, preferably 30 minutes. Alternatively, the undiluted solution can be sprayed on the machine body, left for at least 10 minutes, preferably 30 minutes, and then wiped. The machine body can be sprayed with the undiluted solution of the coronavirus disinfectant of the present disclosure, left for at least 10 minutes, preferably 30 minutes, and then wiped. Alternatively, the machine body can be wiped with a cloth or the like soaked in a 2- to 20-fold diluted solution of the coronavirus disinfectant of the present disclosure.

[0163] After cleaning the workbench with a neutral detergent or the like and rinsing it with running water, the undiluted solution of the coronavirus disinfectant of the present disclosure can be sprayed on and left for 10 minutes or more, preferably 30 minutes, before wiping. Alternatively, the workbench can be wiped with a cloth or the like soaked in a 2- to 20-fold diluted solution of the coronavirus disinfectant of the present disclosure.

[0164] For tableware (under normal circumstances), it can be washed with dish detergent, immersed in a 20-fold diluted solution of the coronavirus killing agent of the present disclosure for 30 minutes or more, rinsed with water, and then dried and stored in a hot air disinfection cabinet.

[0165] Tableware (suspected of infection or persistent infection) can be soaked in an undiluted solution of the coronavirus killer of the present disclosure for 30 minutes or more, washed with detergent, then soaked in a 10-fold diluted solution of the coronavirus killer of the present disclosure for 30 minutes or more, rinsed with water, and dried and stored in a hot air disinfection storage cabinet.

[0166] For baby bottles and breast pumps, disassemble them, soak them in lukewarm water, wash them with a mild detergent, rinse them with running water, and then soak them in a 2- to 20-fold diluted solution of the coronavirus killing agent of the present disclosure for at least 60 minutes, preferably 2-3 hours.

[0167] In the case of a sink or bathroom, the area can be washed with a mild detergent, rinsed with running water, and sprayed with the undiluted coronavirus killing agent of the present disclosure. After that, the area can be rinsed with running water or thoroughly wiped with a cloth or nonwoven fabric.

[0168] The undiluted coronavirus killing agent of the present disclosure can be poured directly into drains, drainage pipes, etc., and left for about 5 minutes, after which it can be thoroughly rinsed away with running water.

[0169] Toilets, toilet seats, toilet paper holders, doorknobs, hand-washing facilities, etc. can be cleaned with toilet detergent or the like, and then directly sprayed (approximately 2-3 times) with the undiluted coronavirus disinfectant of the present disclosure. The surfaces can then be wiped with a cloth, nonwoven fabric, paper towel, or the like. Alternatively, the coronavirus disinfectant of the present disclosure can be diluted 2-4 times (although for daily disinfection, a solution diluted 2-10 times can also be used), and this solution can be soaked into a clean cloth or nonwoven fabric before wiping.

[0170] After thoroughly cleaning the walls, floors, ceilings, etc. of the toilet with toilet detergent, etc., spray the undiluted solution of the coronavirus disinfectant of this disclosure directly (approximately 1m 2 Alternatively, the coronavirus disinfectant of the present disclosure may be diluted 2 to 4 times (however, for everyday cleaning, a solution diluted 2 to 10 times may also be used), and a mop, rag, or the like may be thoroughly saturated with this solution before wiping thoroughly.

[0171] When treating vomit or other wet substances, the vomit or other wet substance can be wiped up with a disposable cloth, the trash can be placed in a plastic bag, and the undiluted coronavirus disinfectant of the present disclosure can be poured over the bag. The floor and surrounding area where the vomit or other wet substance was attached can be covered with a cloth or other cloth soaked in the undiluted coronavirus disinfectant of the present disclosure, and the area can be wiped up by soaking.

[0172] It should be understood that all references cited herein, including scientific literature, patents, patent applications, and the like, are incorporated by reference in their entirety to the same extent as if each were specifically set forth.

[0173] The present disclosure has been described above by showing preferred embodiments for ease of understanding. Hereinafter, the present disclosure will be described based on examples. However, the above description and the following examples are provided for illustrative purposes only, and are not intended to limit the present invention. Therefore, the scope of the present invention is not limited to the embodiments or examples specifically described herein, but is limited only by the claims. [Example]

[0174] (Quantitative method for chlorous acid water) Accurately weigh out approximately 5 g of this product and add water to make exactly 500 ml to use as the sample solution. Accurately measure 20 ml of the sample solution and place it in an iodine flask. Add 10 ml of sulfuric acid (1 → 10), then add 1 g of potassium iodide. Immediately seal and shake well. Add 5 ml of potassium iodide TS to the top of the iodine flask and leave in the dark for 15 minutes. Next, loosen the stopper and pour in the potassium iodide TS. Immediately seal and shake well. Titrate the liberated iodine with 0.1 mol / L sodium thiosulfate (indicator: 5 ml of starch TS). However, add the starch when the solution turns pale yellow near the endpoint; the endpoint is when the blue color of the solution disappears. Perform a separate blank test to correct for the value. 1 ml of 0.1 mol / L sodium thiosulfate solution = 1.711 mg HClO2).

[0175] (Manufacturing example) The chlorous acid water formulations used in the following examples were produced as follows. In this specification, chlorous acid water may be abbreviated as "subaqua," but these terms have the same meaning.

[0176] Hypochlorous acid water component analysis table

[0177] [Table 3A]

[0178] Using this chlorous acid water, a chlorous acid water preparation was produced based on the following formulation.

[0179] [Table 3B]

[0180] [Table 3C]

[0181] The "chlorous acid water preparation produced with chlorous acid water" prepared according to the above preparation method was used to measure the concentration of the "chlorous acid water" according to the above "quantitative method for chlorous acid water," and the chlorous acid water of each example was prepared using a buffer solution (phosphate buffer containing dipotassium hydrogen phosphate and potassium dihydrogen phosphate) prepared to have the free chlorine concentration described in each example.

[0182] (Effectiveness verification test of hypochlorous acid water) An antiviral test was conducted on hypochlorous acid water against SARS-CoV-2 (2019 novel coronavirus). Test sample: Chlorous Acid N Barrier (Honbu Sankei): [Components / Amount] 20g of hypochlorous acid water in 100mL; 0.8% content (hypochlorous acid HClO2 = 68.46) [at the time of manufacture], free chlorine concentration (Cl = 35.45) 200mg / L or more Virus: SARS-CoV-2 (2019-nCoV / Japan / AI / I-004 / 2020) strain (provided by the National Institute of Infectious Diseases) Cells: VeroE6 / TMPRSS2 cells (JCRB1819) FBS concentration in virus solution: 0% Reagents: Dulbecco's Modified Eagle Medium (DMEM) (Fujifilm Wako Pure Chemical Industries), Hypolypeptone N (Fujifilm Wako Pure Chemical Industries), Bovine Serum Albumin, Fraction V, Special Grade (Katayama Chemical Industry) Test method: Chlorus Acid·N·Barrier was diluted with distilled water in a polystyrene tube. The reaction with the virus was also carried out in a polystyrene tube.

[0183] A 10% (w / v) aqueous solution of polypeptone for protein loading was prepared and sterilized by filtration through a 0.1 μm filter. An equal volume of this solution was mixed with the virus solution and used in the test. In the mixture with the virus, the polypeptone concentration was 5%, and the virus was diluted 1 / 2. When this virus mixture was mixed with reagents such as Chlorus N Barrier in a ratio of 1:9 and reacted, the final polypeptone concentration in the reaction solution was 0.5%. A 0.6% (w / v) aqueous solution of bovine serum albumin (BSA) was similarly prepared, and the final concentration in the reaction solution was 0.03%.

[0184] The virus and reagent were mixed at a ratio of (1:9) and allowed to react at room temperature for a specified time. The reaction was then stopped by diluting the mixture 10-fold with DMEM, and the virus infectivity was measured using the TCID50 method after further serial dilutions of 10-fold (Table 4, Figure 1).

[0185] [ka]

[0186] result: [Antiviral test]

[0187] [Table 4]

[0188] The viral infectivity was reduced to the detection limit when the Chlorus Acid·N·Barrier solution was diluted 1 / 10. This is the detection limit, and since no virus-infected cells were observed, the actual infectivity is likely lower than this, and the virus can be considered to have been completely inactivated. The Chlorus Acid·N·Barrier solution diluted 1 / 20 reduced the viral infectivity to less than 1 / 1000 compared to untreated (DMEM), suggesting that it has inactivation properties. [Protein challenge antiviral test]

[0189] [Table 5]

[0190] In the presence of 0.5% polypeptone, virus infection occurred in only one well with the undiluted Chlorus Acid N Barrier solution. Although the effect did not reach the detection limit, strong inactivation occurred, reducing the virus infectivity titer to less than 1 / 1000. However, considering that almost complete virus inactivation occurred with the aforementioned 1 / 10 diluted Chlorus Acid N Barrier solution, it is inferred that the effect of Chlorus Acid N Barrier was weakened by protein loading (Table 5, Figure 2).

[0191] In the presence of 0.03% BSA, the virus was inactivated to the detection limit in the 2x, 4x, and 8x dilutions of chloras acid N barrier, and no effect of protein load was observed.

[0192] Chlorus acid·N·Barrier completely inactivated SARS-CoV-2 when diluted 1 / 10 and reacted for 10 minutes.

[0193] As described above, the present invention has been illustrated using preferred embodiments thereof, but it should be understood that the scope of the present invention should be interpreted solely by the claims. This application claims priority to Japanese Patent Application No. 2020-125824 (filed July 22, 2020), the contents of which are incorporated herein by reference in their entirety. It is understood that the patents, patent applications, and other documents cited herein are incorporated herein by reference in their entirety as if the contents themselves were specifically set forth herein. [Industrial Applicability]

[0194] The present disclosure provides for coronavirus killing.

Claims

[Claim 1] The invention described in the specification.

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