JP2017105723A - Composition having calicivirus inactivation effect - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition less in effect on material or fingers than alkaline compositions, excellent in quick drying property or immediate effectivity and having an excellent inactivation effect on Caliciviridae such as norovirus.SOLUTION: There is provided a composition having pH of 6 to 9, less in effect on material or fingers, excellent in quick drying property or immediate effectivity and having excellent virus inactivation effects on both of feline calicivirus and murine norovirus in Caliciviridae and manufactured by combining lower alcohol of 40 to 90 wt.% and a polyhexamethyleneguanidine compound of 0.05 to 0.5 wt.%.SELECTED DRAWING: None

Description

  A composition having a virus inactivating effect of caliciviridae represented by norovirus, which is applied to daily hygiene management in the fields of food sanitation, medical care and welfare, especially on the surface of an object.

  Norovirus, a typical virus of the Caliciviridae family, is known to be the most common cause of food poisoning in the food poisoning statistics conducted by the Ministry of Health, Labor and Welfare. Cause food poisoning.

  Norovirus has sufficient ability to infect humans even in small amounts (10 to 100), and can survive for a long time even in the environment. Therefore, it can cause secondary infections, and an infected person can cause infections affecting hundreds and thousands of people.

  As an infection route, for example, there is a case where the contamination spreads to other foods through cooking utensils prepared by cooking foods contaminated with norovirus or human hands. In addition, the virus is discharged into the stool of Norovirus patients over a period of several weeks, and the environmental surface (toilet, doorknob, handrail, table, etc.) is contaminated through the patient's hands, causing secondary infection. There is also. Furthermore, when norovirus patients vomit, there are many cases in which the virus remains in the environment due to inadequate treatment, resulting in a large number of secondary infections.

  Therefore, norovirus countermeasures are a very important issue not only in food handling facilities but also in medical facilities, welfare facilities and public facilities, and the invention of a composition having a norovirus inactivating effect is desired.

  However, norovirus that infects humans has not been established in the laboratory. Therefore, in order to evaluate the inactivating effect of norovirus, feline calicivirus of the same Caliciviridae family is used as an alternative virus. In recent years, mouse noroviruses that are more genetically similar to noroviruses can be cultured and used as alternative viruses for noroviruses (Non-patent Documents 1 and 2).

  Calicivirus has strong physicochemical resistance and it is very difficult to inactivate the virus. For example, disinfecting alcohol has a low virus inactivating effect in a short time, and reverse soap has almost no inactivating effect.

  Therefore, as a general method for inactivating norovirus, treatment with sodium hypochlorite (200 ppm or more), heating or hot water (85 ° C. or more) is used. However, sodium hypochlorite and heat treatment may adversely affect the materials and materials on the target environmental surface. Further, the treatment with hot water has a problem that the temperature drops when it is applied to the target surface or material, and it is difficult to maintain the temperature.

  On the other hand, didecyldimethylammonium chloride (DDAC), benzalkonium chloride (BAC), or polyhexamethylene biguanide compound (PHMB) alone does not provide an inactivation effect on calicivirus, but DDAC, ethanol and alkaline agents are used. When combined, there is a report that the inactivation effect on feline calicivirus is enhanced and it can be expected to be used as an environmental surface disinfectant (Non-patent Document 3).

  Patent No. 4975987 also includes a composition having norovirus inactivating effect containing 0.05 to 0.5% by weight of PHMB, 40 to 80% by weight of alcohol, and adjusting the pH to a range of 9 to 12. Is disclosed (Patent Document 1).

  And in patent 5255495, 0.01 mass% or more of 1,4-bis (3,3 ′-(1-decylpyridinium) methyloxy) butanedibromide, which is a bis-type cationic surfactant, ethylenediamine A calicidal virus composition containing 0.000625% by mass or more of tetraacetic acid is disclosed (Patent Document 2).

  The above-mentioned preparations with an alkaline agent added to DDAC, PHMB, and ethanol have a pH of 9 or higher, which may affect the material depending on the intended use and may require safety in handling. There is.

  In addition, when it is assumed to be used for environmental surfaces and fingers, quick drying and immediate effect are often required, but 1,4-bis (3,3 ′-(1-decylpyridinium) methyloxy) butane The combination of dibromide and ethylenediaminetetraacetic acid is inferior in these respects.

Japanese Patent No. 4975987 Japanese Patent No. 5255495

"Murine Norovirus: a Model System To Study Norovirus Biology and Pathogenesis" Journal of Virology, Vol. 80, no. 11, 5104-5112 (2006) “Comparative Efficiency of Seven Hand Santiizers Against Murine Norovirus, Feline Calicirus, and GII.4 Norovirus, Journal of Food Protection. 73, no. 12, 2232-2238 (2010) “Development of norovirus-replacement feline calicivirus and ethanol preparation effective for various microorganisms”, antibacterial and antifungal, Vol. 35, no. 11, 725-732 (2007)

  An object of the present invention is to provide a composition that can inactivate caliciviridae virus in a short time and has an effect of inactivating calicivirus that has little influence on safety and material.

  Ethanol, PHMB, and DDAC had an effect on calicivirus by making them alkaline (pH 9-12), but they were excellent in quick-drying, safe and near neutrality (pH 6- The effectiveness in 9) cannot be obtained.

  In the present invention, as a result of extensive research on a composition having excellent quick-drying properties and having a calicivirus inactivating effect at pH 6-9, 0.01% polyhexamethyleneguanidine compound was added to an aqueous solution containing 40-95 wt% of a lower alcohol. It was found that the composition added with ˜0.05 wt% had a virus inactivating effect within 2 minutes against calicivirus despite the fact that the composition was around pH 6-9.

  According to the present invention, a composition having an inactivating effect on calicivirus can be obtained in a short time even at pH 6-9 by combining a lower alcohol and a polyhexamethylene guanidine compound. In addition, the present invention is a composition having a calicivirus inactivating effect that is superior in quick-drying, safe, and has little influence on the material because it contains a lower alcohol and has a pH of about 6 to 9, which is near neutral. is there.

  The present invention has an effect of inactivating calicivirus containing (a) 0.05 to 0.5 wt% of a polyhexamethyleneguanidine compound, (b) 40 to 95 wt% of a lower alcohol or a mixture of two or more thereof. There is a composition.

  Polyhexamethylene guanidine compounds are usually sold in the form of polyhexamethylene guanidine hydrochloride (PHMGH) or polyhexamethylene guanidine phosphate (PHMGP).

  The compounding quantity of the polyhexamethylene guanidine type compound contained in the composition of this invention is 0.05-0.5 wt%. If the polyhexamethylene guanidine compound is 0.05 wt%, the calicivirus inactivating effect is insufficient, and if it exceeds 0.5 wt%, no significant change is observed in the calicivirus inactivating effect. On the other hand, when it exceeds 0.5 wt%, the gentleness to the hand skin is lowered, and the influence on the material such as the environmental surface is increased.

  The lower alcohol contained in the composition of the present invention is selected from ethanol, isopropanol, and normal propanol, and these are used alone or in combination of two or more. The alcohol content in the composition is preferably 40 to 95 wt%, particularly 50 to 80 wt%. If the alcohol content is less than 40 wt%, the calicivirus inactivating effect is insufficient.

  The pH of the composition of the present invention is important in considering the influence on the material such as safety and environmental surface, and is preferably 6-9, particularly 7-8 neutral. When adjusting the pH, an appropriate amount of a pH adjusting agent is added. As the pH adjuster, an organic acid, an inorganic acid, an organic salt, an inorganic salt, or the like is used. Examples thereof include lactic acid, citric acid, malic acid, gluconic acid, phosphoric acid, sodium lactate, sodium citrate, sodium malate, sodium gluconate, sodium chloride, sodium carbonate, trisodium phosphate, sodium hydrogen carbonate and the like.

  The composition of the present invention can be used for disinfecting human fingers and skin, and disinfecting environmental surfaces and instruments. The environmental surface / appliance is particularly likely to be contaminated with norovirus, and the part that is often touched by human hands, specifically the toilet area (toilet seat, toilet bowl, toilet lid, flush lever), door knob, electricity Switches, handrails, tables, medical instruments, etc.

  In order to confirm the effect of the present invention, an inactivation test of feline calicivirus and mouse norovirus used as a substitute for norovirus in the Caliciviridae family was performed. In order to evaluate the influence on the material, a metal corrosion test was conducted.

(Contents of virus inactivation test)
[Virus used]
Feline calicivirus F9 strain (FCV) and mouse norovirus S7 strain (MNV) were used.
[Used cells]
FCV used cat kidney cells (CRFK). MNV used RAW264 cells (RAW).
[Medium used for culture]
For FCV, Dulbecco's modified Eagle's medium (DMEM) was used, and neonatal calf serum (NCS) was used as the serum. Eagle's minimum essential medium (MEM) was used for MNV, and fetal bovine serum (FBS) was used as the serum.
[Virus inactivation test]
0.1 mL of the virus solution was added to 0.9 mL of the test drug and allowed to act at 20 ° C. for a certain period of time. After the action, FCV was diluted 10-fold with DMEM (containing 10% NCS) and stopped, and then serially diluted with DMEM (containing 2% NCS) and inoculated into CRFK that had been cultured in a 96-well plate in advance. The cells were cultured for 3 days under 5% CO2. MNV was diluted 10-fold with MEM (containing 10% FBS) and stopped, then serially diluted with MEM (containing 10% FBS), and inoculated into RAW previously cultured in a 96-well plate. Cultured for 4 days under conditions. After culturing, the cytopathic effect was confirmed, the virus infection titer (TCID50) was determined, and the log reduction value was calculated.
[Criteria]
A: Log reduction value 4 or more (or log reduction value 3 or more and below detection limit)
○: Log reduction value of 3 or more △: Log reduction value of 2 to 3
×: Logarithmic decrease value of less than 2 ◎, ○ means practically effective.
[Test drug]
As the test drug, the drugs of Examples 1 to 6 and Comparative Examples 1 to 6 were used. The composition of each drug is as shown in Tables 1 and 2 below together with the results. Table 1 shows a preferred embodiment of the present invention. Table 2 shows a comparison of the virus inactivating effect of polyhexamethylene guanidine compound and polyhexamethylene biguanide (PHMB) depending on pH.

  From Table 1, Examples 1 to 6, which are the compositions according to the present invention, showed excellent inactivation effect against FCV even with an action for 1 minute, and Examples 1, 2 and 5 also against MNV It can be seen that an excellent inactivation effect is exhibited. On the other hand, in Comparative Examples 1 and 2 in which ethanol and PHMGP were blended alone, the inactivation effect on FCV was low.

  Further, from Table 2, Examples 1, 5 and 6 in which PHMMH and PHMGP were blended with the lower alcohol according to the present invention, showed a very excellent FCV inactivating effect by the action for 2 minutes, whereas the lower alcohol In Comparative Example 3 in which PHMB was blended and the pH was adjusted to around 7, no excellent effect was obtained. Comparative Examples 4 to 6 in which PHMMH, PHMGP, or PHMB were blended with lower alcohol and the pH was adjusted to an alkali range of 11.7 to 11.8 both showed excellent FCV inactivation effects, and the effects were equivalent. It was.

(Content of metal corrosion test)
[Test method]
Stainless steel (SUS304, SUS430) and aluminum test pieces were immersed in the test agent and allowed to stand at room temperature for 1 week. The appearance change before and after the test was observed to confirm the presence or absence of metal corrosiveness.
[Test drug]
As test agents, Example 5 (pH 7.4) and Comparative Example 6 (pH 11.7, combined with PHMB) that showed a high inactivation effect on FCV were used.
In the above formula, as shown in the table, I is the amount of light emitted from the lamp, X is the distance between the observation surface and the light receiving surface, and V / t is the moving speed of the light receiving surface.

  From Table 3, in Example 5, the metal corrosivity with respect to the test piece of stainless steel and aluminum was not seen. On the other hand, Comparative Example 6 showed no metal corrosivity against the stainless steel test piece, but showed metal corrosivity against the aluminum test piece. As described above, Example 5 was confirmed to have a high effect on calicivirus and a small influence on metal.

  From the above results, the composition in which a polyhexamethylene guanidine compound is blended with a lower alcohol exhibits an excellent effect on both viruses of the Caliciviridae family and has little influence on materials such as metals. And better than the prior art.

  According to the present invention, by combining a lower alcohol and a polyhexamethylene guanidine compound, it is possible to obtain a composition exhibiting an excellent inactivation effect against a caliciviridae virus represented by norovirus. Since the present invention contains a lower alcohol and has a pH of 6 to 9, it is characterized by excellent quick-drying, safety, and little influence on the material. It can be used for disinfection of goods.

Claims (3)

Hereinafter, a composition having a calicivirus inactivating effect, comprising (a) and (b) and having a pH in the range of 6-9 (a) 0.05-0.5 wt% polyhexamethylene Guanidine-based compound (b) 40 to 95 wt% lower alcohol or a mixture thereof The composition of Claim 1 which mix | blended the pH adjuster in consideration of stability of the composition. The composition according to claim 1, which has an excellent virus inactivating effect against both feline calicivirus and mouse norovirus belonging to the family Caliciviridae.