WO2022034911A1

WO2022034911A1 - Composition for leave-on-type skin external preparation

Info

Publication number: WO2022034911A1
Application number: PCT/JP2021/029712
Authority: WO
Inventors: 安弘岡田; 利哉森川; 由紀西岡; 千尋田本; 温子早瀬; 竣久保
Original assignee: 花王株式会社
Priority date: 2020-08-13
Filing date: 2021-08-12
Publication date: 2022-02-17
Also published as: TW202214222A; JP2022033040A; CN116096368A

Abstract

A composition for a leave-on-type skin external preparation, the composition comprising (A) at least one acid selected from the group consisting of lactic acid, pyruvic acid and urocanic acid or a salt of the acid and (B) a nonionic surfactant having a C-12 lipophilic group having an HLB value of 8.0 to 17.0, inclusive, in which the content of the component (A) is 0.02 to 20.0% by mass, inclusive, the content of the component (B) is 0.006 to 5.0% by mass, inclusive, and the pH value of the composition is 3.5 to 5.0, inclusive.

Description

Leave-on skin external preparation composition

The present invention relates to a leave-on skin external preparation composition.

According to recent surveys, it has become known that contact infection is the most common transmission route for bacteria or viruses in human daily life. Contact infection mainly occurs when a person infected with a bacterium or a virus, a doorknob, a handle, tableware, a toy, other daily necessities, an interior item, or the like is brought into contact with a finger.

There is a need for a method for preventing contact infection of bacteria or viruses due to such contact behavior in daily life.
As a method for preventing contact infection of bacteria or viruses via fingers, a method of sterilizing and disinfecting fingers by applying an alcohol-based disinfectant or the like is known. However, alcohol such as ethanol used as a sterilizing or disinfecting component is highly volatile, and the sustainability of the effect is not sufficient from the viewpoint of imparting a bactericidal and virus-killing effect to fingers.

Therefore, a method of imparting a protective function against bacteria or viruses to the fingers is being studied in advance. According to this method, since the effect of preventing infection with bacteria or viruses can be continuously obtained, contact infection can be prevented even in an environment where there is no hand-washing place such as when going out. In particular, it is preferable in that infection can be prevented even when the contact object to which bacteria or viruses are attached is repeatedly contacted.

It is also known to use an organic acid or a salt thereof as a component for realizing sterilization or virus killing.
For example, in Patent Document 1 (Japanese Patent Laid-Open No. 2008-523064), a compound or composition capable of reducing the skin pH to less than about 4 as a method for suppressing bacteria and viruses present on the skin surface of mammals. Disclosed are methods comprising contacting the skin with the skin for at least about 0.5 hours. Examples of the compound or composition capable of reducing the skin pH include those containing an organic acid such as a monocarboxylic acid or a polycarboxylic acid.
In Patent Document 2 (US Pat. No. 6,034,133), a virus-killing composition (hand lotion) containing citric acid, malic acid, and C1-6 alcohol is identified as having a rhinovirus cold. , Or a method of applying to the hands of a patient before exposure to rhinovirus to kill the rhinovirus and prevent the spread of the cold by the rhinovirus is disclosed.

It is also known that surfactants have antibacterial activity (Non-Patent Document 1: Shoichiro Watanabe "Current Status and Trends of Antibacterial Surfactants", Oil Chemistry, Vol. 29, No. 8, p536-542, 1980. ). In Non-Patent Document 1, among the surfactants, cationic surfactants such as quaternary ammonium salts or amphoteric surfactants show strong antibacterial properties, but anionic surfactants have weak antibacterial properties and are polyethylene glycol type. It has been stated that nonionic surfactants have no or extremely weak antibacterial properties.

The present invention provides the following [1] and [2].
[1] It has (A) one or more acids selected from the group consisting of lactic acid, pyruvate and urocanic acid or salts thereof, and (B) a parent oil group having 12 carbon atoms and an HLB of 8.0 or more. It contains a nonionic surfactant of 17.0 or less, the content of the component (A) is 0.02% by mass or more and 20.0% by mass or less, and the content of the component (B) is 0.006. A leave-on skin external preparation composition having a mass% or more and 5.0% by mass or less and a pH of 3.5 or more and 5.0 or less.
[2] A method for protecting the skin from bacteria or viruses, which comprises a step of applying the leave-on skin external preparation composition according to the above [1] to the skin.

Detailed description of the invention

[Leave-on skin external preparation composition]
The leave-on skin external preparation composition of the present invention (hereinafter, also referred to as “the composition of the present invention”) is
(A) One or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid or salts thereof, and
(B) A nonionic surfactant having a lipophilic group having 12 carbon atoms and having an HLB of 8.0 or more and 17.0 or less.
The content of the component (A) is 0.02% by mass or more and 20.0% by mass or less, and the content of the component (B) is 0.006% by mass or more and 5.0% by mass or less. The pH is 3.5 or more and 5.0 or less.
By having the above composition, the composition of the present invention becomes a skin external preparation composition having high bactericidal or virus-killing activity, low skin irritation, and high safety to the human body.

Examples 2 of Patent Document 1 disclose compositions 2A to 2C containing citric acid and malic acid, of which the composition showing anti-rhinovirus activity has a composition pH of 2.3. Only thing 2A. Further, the pH of the anti-rhinovirus composition 2D containing citric acid and malic acid disclosed in Example 3 is 3.1. However, applying a low pH composition to the skin is not preferable from the viewpoint of skin irritation.
The hand lotion described in Patent Document 2 requires citric acid, malic acid, and C1-6 alcohol, and has not been shown to be virus-killing by hand lotions having other compositions. In addition, there is a concern that the hand lotion may cause skin irritation due to the inclusion of an alcohol component.

The nonionic surfactant such as the polyethylene glycol type nonionic surfactant described in Non-Patent Document 1 is a component generally used as an emulsifier for foods, cosmetics, etc., and may be included in the leave-on skin external preparation composition. Although it is less irritating to the skin, it has a weak bactericidal and virus-killing effect by itself.

In view of such a situation, the present inventors have low concern about skin irritation even when the organic acid is used under mild conditions such as pH 3.5 or higher and is included in the leave-on skin external preparation composition. It was aimed to provide a leave-on skin external preparation composition showing high bactericidal or virus-killing activity while using a sex surfactant and without using an alcohol component.

That is, the present invention relates to a leave-on skin external preparation composition having high bactericidal or virus-killing activity, low skin irritation, and high safety to the human body.

The present inventors have a nonionic surfactant having one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid or salts thereof, and a lipophilic group having 12 carbon atoms and having an HLB in a predetermined range. A composition containing a predetermined amount of an activator and having a pH in a relatively high range of 3.5 or more is less irritating to the skin and highly safe to the human body even when used as a leave-on skin external preparation, and is sterilized or sterilized. It was found that the virus-killing activity could be improved.
Here, one or more acids selected from the group consisting of lactic acid, pyruvate and urocanic acid are organic acids originally present on human skin and are skin irritating when used as a composition having a pH of 3.5 or higher. It is highly safe for the human body, but its own bactericidal or virus-killing effect is weak. In addition, as described above, nonionic surfactants generally have a weak bactericidal and virus-killing effect.

However, the present inventors have described that a nonionic surfactant having a lipophilic group having 12 carbon atoms and having an HLB in a predetermined range permeates the cell membrane of a fungus or virus to increase the fluidity of the cell membrane. It was thought that the organic acid component would be easily taken up by the fungus or virus. Then, by using the organic acid component in combination with the nonionic surfactant, the organic acid component is efficiently incorporated into the bacterium or virus, and even if the composition has a pH of 3.5 or more, the bacterium or It has led to an improvement in the effect of inactivating or killing the virus.

According to the present invention, it is possible to provide a leave-on skin external preparation composition having high bactericidal or virus-killing activity, low skin irritation, and high safety to the human body.

As used herein, the term "leave-on skin external preparation composition" means a skin external preparation composition that is applied to the skin and then used without being removed by washing with water or the like.
The composition of the present invention can impart a bactericidal or virus-killing effect to the skin surface by leaving the component (A) and the component (B), which are bactericidal or virus-killing components, on the skin surface. From the viewpoint of obtaining the effect, the composition of the present invention is used after being applied to the skin by application or the like, and the composition is not removed by washing with water or the like, but remains on the skin surface.
From the viewpoint of preventing contact infection by bacteria or viruses, the composition of the present invention is more preferably a leave-on skin external preparation composition for fingers.

As used herein, the term "bactericidal or virus-killing activity" means the bactericidal or virus-killing activity of the composition itself. For example, the bactericidal activity against Escherichia coli and the virus-killing activity against coronavirus can be specifically evaluated by the method described in Examples. The activity against other bacteria and viruses can be evaluated in consideration of common general technical knowledge.

In the present specification, "to impart a bactericidal or virus-killing effect to the skin surface" is expressed (1) against bacteria / viruses adhering to the skin surface after applying the composition of the present invention to the skin surface. Bactericidal / virus-killing effect, (2) Bactericidal / virus-killing effect developed by applying the composition to bacteria / viruses adhering to the skin, (3) Effect of preparing the skin to be non-bacterial / virus-borne. , (4) The effect of protecting the skin from bacteria / viruses and keeping them hygienic, (5) The effect of preventing the transmission of bacteria / viruses through the skin and contact infection, and (6) Infection of the skin against bacteria / viruses. It includes the concept of imparting the effect of enhancing the defense power, etc.

Further, in the present specification, it is assumed that skin irritation can be suppressed if the pH of the composition at 25 ° C. is 3.5 or higher.

The fungus or virus to which the composition of the present invention exhibits bactericidal or virus-killing activity is not particularly limited as long as it is inactivated or killed by contact with an acid, for example, in a nursery center of the Ministry of Health, Labor and Welfare. It is considered that the microorganisms described in the infectious disease control guidelines can be applied.
Specifically, the bacteria include anthrax, tuberculosis, hemolytic streptococcus, yellow staphylococcus, pneumoniae, etc., which are gram-positive bacteria, or Francisella tularensis, pest, brusella, and nasal bacillus, which are gram-negative bacteria. , Cholera, Salmonella, Shigella, Intestinal hemorrhagic Escherichia coli, Bordetella pertussis and the like. The viruses include arenavirus, ebola virus, porosity virus, Nyrovirus, Marburg virus, coronavirus, monkey pox virus, beta coronavirus, influenza virus, RS virus, herpesvirus, mumps virus, and varicella. -The herpes zoster virus, wind shin virus, hemp virus and the like, and non-enveloped viruses entererovirus, adenovirus, coxsackie virus, norovirus, rotavirus and the like can be mentioned.
In this example, Escherichia coli and coronavirus are taken as examples to evaluate the bactericidal and virus-killing activities, but the fungus or virus targeted by the present invention is not limited thereto.

The reason why the composition of the present invention exerts the above effect is not clear, but it is considered as follows.
Lactic acid, pyruvic acid, and urocanic acid, which are components (A), originally exist on human skin by being supplied from sweat glands, and have a bactericidal and virus-killing function against bacteria, viruses, etc., especially on fingers. The present inventors have found that they are responsible. Therefore, it is considered that the skin external preparation composition containing the component (A) can be a composition having bactericidal or virus-killing activity, less skin irritation, and high human safety.
Regarding the above-mentioned bactericidal or virus-killing activity, it is known that even in the composition containing the component (A), the lower the pH, the higher the bactericidal or virus-killing activity. For example, lactic acid, which is the component (A), can take the form of an acid type (CH ₃ CH (OH) COOH) and a dissociated type (CH ₃ CH (OH) COO ⁻ ) in an aqueous solution, but the acid type is more charged. It is considered that the acid type exhibits higher bactericidal or virus-killing activity because it is easily taken up by bacteria or viruses. The acid type / dissociation type ratio of lactic acid depends on the pH, and when the pH exceeds 5, the acid type presence ratio decreases, and the ratio of lactic acid present in the acid type to the total amount of lactic acid blended is, for example, 5. It will be below the mol% level. The composition of the present invention exhibits high bactericidal or virus-killing activity when the pH is 5.0 or less.

On the other hand, even when the component (A) is used, there is a concern that the composition in the low pH range may cause skin irritation.
Therefore, as a result of studies by the present inventors, by using a predetermined amount of each of the component (A) and the component (B) which is a predetermined nonionic surfactant, the pH is in a relatively high range of 3.5 or more. It has been found that the bactericidal or virus-killing activity can be improved even in a certain composition.
As described above, even if a nonionic surfactant such as a polyethylene glycol-type nonionic surfactant is contained in the leave-on skin external preparation composition, its bactericidal and virus-killing effect by itself is weak. However, the component (B), which is a nonionic surfactant having a lipophilic group having 12 carbon atoms and having an HLB in a predetermined range, has an effect of penetrating the cell membrane of a bacterium or a virus and increasing the fluidity of the cell membrane. As a result, the component (A) is easily taken up into the fungus or virus. Therefore, it is considered that by using the component (A) and the component (B) in combination, the effect of the component (A) being efficiently taken up into the bacterium or the virus and inactivating or killing the bacterium or the virus is improved.
From the above mechanism of action, it is considered that a composition for external use on the skin having a pH of 3.5 or more, less skin irritation, and high bactericidal / virus-killing activity can be obtained.

<Ingredient (A)>
The component (A) used in the composition of the present invention is one or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid, or salts thereof. The component (A) acts as a bactericidal / virus-killing component.
Examples of the salts of lactic acid, pyruvate and urocanic acid include alkali metal salts of lactic acid, pyruvate and urocanic acid such as potassium salt and sodium salt; alkaline earth metal salts such as calcium salt and magnesium salt; amine salt; ammonium salt. And so on. Among these, at least one selected from the group consisting of alkali metal salts and alkaline earth metal salts of lactic acid, pyruvate and urocanic acid is preferable from the viewpoint of improving bactericidal or virus-killing activity and availability. , One or more selected from the group consisting of potassium salt, sodium salt, and calcium salt is more preferable, and one or more selected from the group consisting of potassium lactate, sodium lactate, and calcium lactate is further preferable.
From the viewpoint of improving bactericidal or virus-killing activity, lactic acid or a salt thereof is preferable as the component (A), and one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate is more preferable, and contains lactic acid. Is even more preferable.
When the component (A) contains lactic acid, the content of lactic acid or a salt thereof in the total amount of the component (A) is preferably 80% by mass or more, more preferably 90% by mass, from the viewpoint of improving bactericidal or virus-killing activity. % Or more, most preferably 100% by mass.

The content of the component (A) in the composition of the present invention is 0.02% by mass or more, preferably 0.05% by mass or more, more preferably 0.1, from the viewpoint of improving bactericidal or virus-killing activity. It is by mass or more, more preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more. Further, from the viewpoint of suppressing skin irritation, it is 20.0% by mass or less, preferably 15.0% by mass or less, more preferably 10.0% by mass or less, still more preferably 5.0% by mass or less, and more. It is more preferably 3.0% by mass or less, and even more preferably 2.0% by mass or less. The content of the component (A) in the composition of the present invention is 0.02% by mass or more and 20.0% by mass or less, preferably 0.05% by mass or more and 15.0% by mass or less, more preferably. Is 0.1% by mass or more and 10.0% by mass or less, more preferably 0.3% by mass or more and 5.0% by mass or less, still more preferably 0.3% by mass or more and 3.0% by mass or less, still more preferably. It is 0.5% by mass or more and 2.0% by mass or less.
In the present specification, when the component (A) contains a salt, the "content of the component (A)" means an amount converted into an acid.

The content of the component (A) present in the acid form in the composition of the present invention is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, from the viewpoint of improving bactericidal or virus-killing activity. Is. Further, from the viewpoint of suppressing skin irritation, it is preferably 15% by mass or less, more preferably 10% by mass or less, still more preferably 7% by mass or less, still more preferably 1% by mass or less. The content of the component (A) present in the acid form in the composition of the present invention is preferably 0.01% by mass or more and 15% by mass or less, more preferably 0.01% by mass or more and 10% by mass or less. It is more preferably 0.01% by mass or more and 7% by mass or less, and even more preferably 0.1% by mass or more and 1% by mass or less.

The molar ratio of the component (A) present in the acid type to the total of the component (A) present in the acid type and the component (A) present in the dissociated type in the composition of the present invention [acid type / (acid type). + Dissociation type)] is preferably 0.068 or more, more preferably 0.12 or more, from the viewpoint of sterilization or improvement of virus-killing activity. Further, from the viewpoint of suppressing skin irritation, it is preferably 0.7 or less, more preferably 0.5 or less. The molar ratio [acid type / (acid type + dissociation type)] in the composition is preferably 0.068 or more and 0.7 or less, and more preferably 0.12 or more and 0.5 or less.
Specifically, the molar ratio can be calculated by the method described in Examples.

In the present specification, the "component (A) existing in the acid form in the composition" means the component (A) existing as lactic acid, pyruvic acid and urocanic acid in the composition. The “dissociated component (A) in the composition” means a component (A) that is present as a lactic acid ion, a pyruvate ion, and a urocanate ion in the composition.

<Ingredient (B)>
The component (B) used in the composition of the present invention has a lipophilic group having 12 carbon atoms and has an HLB (hydrophilic-lipophilic balance) of 8.0 or more and 17.0 or less. It is a nonionic surfactant. The composition of the present invention contains the component (A) and the component (B) so that the component (A), which is a bactericidal / virus-killing component, is efficiently incorporated into the bacterium or virus by the synergistic effect of these components. Therefore, it is considered that high bactericidal and virus-killing activity can be obtained.

Examples of the parent oil group having 12 carbon atoms in the component (B) include a monohydric alcohol residue having 12 carbon atoms and a fatty acid residue having 12 carbon atoms. From the viewpoint of improving bactericidal or virus-killing activity and availability, the parent oil group having 12 carbon atoms is preferably a group having a linear aliphatic group, and the linear aliphatic group is a linear group. More preferably, it is a saturated aliphatic group.
More specifically, the lipophilic group having 12 carbon atoms in the component (B) includes R11-O-, R12- ^COO- , and R11-O-, and R12- ^COO- from the viewpoint of improving bactericidal or virus-killing activity and availability. One or more selected from the group consisting of groups represented by R ¹² -CONH- is preferable, and one or more selected from the group consisting of groups represented by R ¹¹ -O- and R ¹² -COO-is more preferable. , R ¹¹ -O-, more preferably a group. Here, R ¹¹ is an aliphatic group having 12 carbon atoms, and R ¹² is an aliphatic group having 11 carbon atoms.
The aliphatic group in R ¹¹ and R ¹² is preferably a linear aliphatic group, and more preferably a linear saturated aliphatic group from the viewpoint of improving bactericidal or virus-killing activity.

The component (B) may have only one lipophilic group having 12 carbon atoms, or may have two or more lipophilic groups. From the viewpoint of improving bactericidal or virus-killing activity, it is preferable that the component (B) is mainly composed of a nonionic surfactant having only one lipophilic group having 12 carbon atoms. The term "main component" as used herein means that the component (B) occupies preferably 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more, and is 100% by mass. You may.

Specific examples of the component (B) include polyoxyethylene lauryl ether, sucrose lauric acid ester, polyoxyethylene lauric acid ester, polyglyceryl lauryl ether, polyglyceryl laurate, lauryl glucoside, polyoxyethylene laurylamine, and polyoxyethylene sorbitan. Examples thereof include lauric acid ester and polyoxyethylene sorbit lauric acid ester, and one or more of these can be used. Among these, from the viewpoint of sterilizing or improving virus-killing activity, the component (B) is polyoxyethylene lauryl ether, sucrose lauric acid ester, polyoxyethylene lauric acid ester, polyglyceryl lauryl ether, polyglyceryl laurate, lauryl glucoside and poly. One or more selected from the group consisting of oxyethylene laurylamine is preferable.

Of the above, polyoxyethylene lauric ether, polyoxyethylene lauric acid ester, polyoxyethylene laurylamine, polyoxyethylene sorbitan lauric acid ester, and polyoxyethylene sorbit lauric acid ester, preferably polyoxyethylene lauryl ether and polyoxy. The average number of moles of oxyethylene groups added in the ethylene lauric acid ester and polyoxyethylene laurylamine (hereinafter referred to as "the average number of moles of EO added") is preferably from the viewpoint of improving the solubility and stability of the composition. It is 2 or more, more preferably 3 or more, and is preferably 20 or less, more preferably 15 or less, still more preferably 10 or less, from the viewpoint of improving bactericidal or virus-killing activity and obtaining a desired HLB value. The average number of moles of EO added is preferably 2 or more and 20 or less, more preferably 3 or more and 20 or less, still more preferably 3 or more and 15 or less, and further preferably 3 or more and 10 or less. The EO average number of moles added is a number average value.

Among the above, lauric acid esters in sucrose lauric acid ester, polyoxyethylene lauric acid ester, polyoxyethylene sorbitan lauric acid ester, and polyoxyethylene sorbit lauric acid ester include diesters, triesters, etc. in addition to monoesters. The polyester can be mentioned, and a mixture of a monoester and a polyester can also be used. From the viewpoint of improving bactericidal or virus-killing activity and obtaining a desired HLB value, it is preferable that the lauric acid ester contains a monoester as a main component. The term "main component" as used herein means that the total amount of the lauric acid ester is preferably 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more.

As the component (B), one kind or two or more kinds of nonionic surfactants can be used. Among the above, from the viewpoint of improving bactericidal or virus-killing activity, the component (B) is more preferably one or more selected from the group consisting of polyoxyethylene lauryl ether, sucrose lauric acid ester, and polyoxyethylene lauric acid ester. It is more preferably one or more selected from the group consisting of polyoxyethylene lauryl ether and sucrose lauric acid ester, and even more preferably polyoxyethylene lauryl ether. The average number of moles of EO added in the polyoxyethylene lauryl ether and the polyoxyethylene lauric acid ester is in the above range (preferably 2 or more and 20 or less, more preferably 3 or more and 15 or less, still more preferably 3 or more and 10 or less), and sucrose. The lauric acid ester and the polyoxyethylene lauric acid ester preferably contain a monoester as a main component.

(HLB)
The component (B) used in the composition of the present invention has an HLB of 8.0 or more from the viewpoint of improving the solubility and stability of the composition. Further, from the viewpoint of sterilization or improvement of virus-killing activity, the HLB is 17.0 or less, preferably 16.5 or less, more preferably 16.0 or less, still more preferably 15.5 or less, still more preferably 14. It is 0 or less, more preferably 13.5 or less.
HLB indicates the ratio of the molecular weight of the hydrophilic group portion to the total molecular weight of the surfactant, and is determined by the formula of Griffin.
The component (B) of the present invention refers to a nonionic surfactant having a lipophilic group having 12 carbon atoms and having an HLB in the above range, and the content of the component (B) contained in the composition. Refers to the total amount of components of a nonionic surfactant having a lipophilic group having 12 carbon atoms and satisfying the above HLB range.

The content of the component (B) in the composition of the present invention is 0.006% by mass or more, preferably 0.01% by mass or more, and more preferably 0.05 from the viewpoint of improving bactericidal or virus-killing activity. It is by mass or more, more preferably 0.1% by mass or more, and even more preferably 0.2% by mass or more. Further, from the viewpoint of suppressing skin irritation and improving the usability, it is 5.0% by mass or less, preferably 3.0% by mass or less, more preferably 2.5% by mass or less, still more preferably. It is 2.0% by mass or less, more preferably 1.5% by mass or less. The content of the component (B) in the composition of the present invention is 0.006% by mass or more and 5.0% by mass or less, preferably 0.01% by mass or more and 5.0% by mass or less, more preferably. Is 0.05% by mass or more and 5.0% by mass or less, more preferably 0.1% by mass or more and 5.0% by mass or less, still more preferably 0.1% by mass or more and 3.0% by mass or less, still more preferably. Is 0.2% by mass or more and 2.5% by mass or less, more preferably 0.2% by mass or more and 2.0% by mass or less, still more preferably 0.2% by mass or more and 1.5% by mass or less.

The total content of the component (A) and the component (B) in the composition of the present invention is preferably 0.026% by mass or more, more preferably 0.15% by mass or more, from the viewpoint of improving bactericidal or virus-killing activity. It is more preferably 0.2% by mass or more, still more preferably 0.35% by mass or more, still more preferably 0.4% by mass or more, still more preferably 1.0% by mass or more. Further, from the viewpoint of suppressing skin irritation, it is preferably 15.0% by mass or less, more preferably 10.0% by mass or less, still more preferably 5.0% by mass or less, still more preferably 3.0% by mass. It is as follows. The specific range of the total content of the component (A) and the component (B) in the composition of the present invention is preferably 0.026% by mass or more and 15.0% by mass or less, more preferably 0.15% by mass. % Or more and 15.0% by mass or less, more preferably 0.2% by mass or more and 15.0% by mass or less, still more preferably 0.2% by mass or more and 10.0% by mass or less, still more preferably 0.35% by mass. % Or more and 5.0% by mass or less, more preferably 0.4% by mass or more and 5.0% by mass or less, still more preferably 1.0% by mass or more and 3.0% by mass or less.

The composition of the present invention may contain a surfactant other than the component (B). Examples of the surfactant other than the component (B) include anionic surfactants, cationic surfactants (excluding quaternary ammonium salts), and amphoteric surfactants (excluding alkyldiaminoethylglycine chloride and alkylpolyaminoethylglycine). ), And nonionic surfactants other than the component (B) can be mentioned. Examples of the anionic surfactant include an alkyl phosphate ester salt and a polyoxyethylene alkyl ether sulfate ester salt, and examples of the amphoteric surfactant include lauroamphoacetate and laurylbetaine.
However, the proportion of the component (B) in the surfactant in the composition of the present invention is preferably 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass from the viewpoint of bactericidal or virus-killing properties. It occupies% or more and may be 100% by mass.
In the composition of the present invention, the total content of the surfactant containing the component (B) is preferably 5.0% by mass or less, more preferably 3.0% by mass or less, from the viewpoint of suppressing skin irritation. be.
Further, in the composition of the present invention, the total content of the anionic surfactant and the cationic surfactant is preferably 1.0% by mass or less, more preferably 0, from the viewpoint of suppressing skin irritation. It is 5.5% by mass or less, more preferably 0.1% by mass or less.
Further, the content of the amphoteric tenside is preferably 3.0% by mass or less, more preferably 1.0% by mass or less, still more preferably 0.5% by mass or less, from the viewpoint of suppressing skin irritation. be.
Further, in the composition of the present invention, the content of the nonionic surfactant containing the component (B) is preferably 5.0% by mass or less, more preferably 3.0% by mass or less, still more preferably 1. It is 5.5% by mass or less. The proportion of the component (B) in the nonionic surfactant preferably occupies 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more from the viewpoint of bactericidal or virus-killing properties. , 100% by mass.

The mass ratio of the component (B) to the component (A) in the composition of the present invention (component (B) / component (A)) is preferably 0.005 or more from the viewpoint of improving bactericidal or virus-killing activity. It is preferably 0.1 or more, more preferably 0.1 or more, still more preferably 0.2 or more, and preferably 20 or less, more preferably 10 or less, still more preferably 5 or less, still more preferably 2. It is as follows. The mass ratio (component (B) / component (A)) in the composition of the present invention is preferably 0.005 or more and 20 or less, more preferably 0.1 or more and 20 or less, still more preferably 0.1. It is 20 or more, more preferably 0.2 or more and 10 or less, still more preferably 0.2 or more and 5 or less, still more preferably 0.2 or more and 2 or less.

The composition of the present invention preferably further contains water from the viewpoint of dissolving the component (A) and the component (B) and facilitating application to the skin surface. The content of water in the composition of the present invention is preferably 10% by mass or more, more preferably 30% by mass or more, still more preferably 50% by mass or more, still more preferably 70% by mass or more, and more preferably. Is 99.8% by mass or less, more preferably 99% by mass or less. The content of water in the composition of the present invention is preferably 10% by mass or more and 99.8% by mass or less, more preferably 30% by mass or more and 99.8% by mass or less, and further preferably 50% by mass or more and 99. It is 8.8% by mass or less, more preferably 70% by mass or more and 99% by mass or less.

The total content of the component (A), the component (B) and water in the composition of the present invention is preferably 50% by mass or more, more preferably 70% by mass or more, still more preferably, from the viewpoint of obtaining the effect of the present invention. Is 80% by mass or more, more preferably 90% by mass or more, still more preferably 95% by mass or more, and may be 100% by mass.

In addition to the above, the composition of the present invention includes other components, for example, acids other than the component (A) or salts thereof (citric acid, adipic acid), thickeners (polysaccharides, polymers, etc.), as required. Acidity regulators (citric acid, sodium hydroxide, etc.), UV absorbers (titanium oxide, zinc oxide, etc.), antioxidants (ascorbic acid, tocopherol, etc.), preservatives (methylparaben, benzoic acid, etc.), antiperspirants (antiperspirants, etc.) Zinc laphenol sulfonate, aluminum chloride hydrate, etc.), fragrances (eucalyptus, geraniol, etc.), moisturizers (polyol, natural fats, etc.), touch regulators (silicone, higher fats, etc.), anti-inflammatory agents (glycyrrhizinic acid, etc.) ) Etc. can also be contained.

When the composition of the present invention contains the polyol, the content of the polyol in the composition is preferably 20% by mass or less, more preferably 10% by mass or less, and further, from the viewpoint of improving the usability of the composition. It is preferably 5% by mass or less, and even more preferably 3% by mass or less.

From the viewpoint that the composition of the present invention is a composition using the component (A) as a bactericidal or virus-killing component, it exhibits bactericidal or virus-killing activity without blending ethanol. From this viewpoint and from the viewpoint of suppressing skin irritation, the content of ethanol in the composition is preferably 70% by mass or less, more preferably 50% by mass or less, still more preferably 30% by mass or less, still more preferably. Is 10% by mass or less, more preferably 3% by mass or less, still more preferably 1% by mass or less, still more preferably 0.07% by mass or less, still more preferably 0.05% by mass or less, still more preferably. It is 0.03% by mass or less, more preferably less than 0.01% by mass, and most preferably 0% by mass.

The ratio of the total content of polyol and ethanol to the content of water in the composition of the present invention [(polypoly + ethanol) / water] is a mass ratio from the viewpoint of suppressing skin irritation and improving usability. It is preferably 2 or less, more preferably 1 or less, still more preferably 0.5 or less, still more preferably 0.1 or less.

The composition of the present invention is a quaternary ammonium salt such as benzalkonium chloride and benzethonium chloride; alkyldiaminoethylglycine chloride and alkylpolyamino from the viewpoint that the composition (A) is used as a bactericidal or virus-killing component. Amphoteric surfactants such as ethylglycine; biguanides such as chlorhexidine gluconic acid; sodium hypochlorite; aldehydes such as glutaral, phthalal, formalin; It exhibits bactericidal or virus-killing activity without the addition of agents. From this viewpoint and from the viewpoint of suppressing skin irritation, the content of the bactericidal agent in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, still more. It is preferably 3% by mass or less, more preferably 1% by mass or less, still more preferably 0.08% by mass or less, still more preferably 0.07% by mass or less, still more preferably 0.05% by mass or less, and more. It is more preferably 0.03% by mass or less, still more preferably less than 0.01% by mass, and most preferably 0% by mass. On the other hand, when the above-mentioned fungicide is blended, the content of the fungicide in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, from the viewpoint of improving the bactericidal or virus-killing activity. be.
The mass ratio of the bactericidal agent to the component (A) (bactericidal agent / component (A)) is preferably 0.1 or less, more preferably 0.05 or less, still more preferably, from the viewpoint of suppressing skin irritation. Is 0.03 or less, more preferably 0.01 or less, and most preferably substantially 0. On the other hand, when the above-mentioned bactericidal agent is blended, the mass ratio of the above-mentioned bactericidal agent to the component (A) (bactericidal agent / component (A)) is preferably 0.01 or more, from the viewpoint of improving bactericidal or virus-killing activity. It is preferably 0.05 or more.
In addition, in this specification, an agent which is the above-mentioned fungicide and also acts as a surfactant is defined as a fungicide.

From the viewpoint that the composition of the present invention is a composition using the component (A) as a bactericidal or virus-killing component, the bactericidal or virus-killing activity can be achieved without blending an organic acid other than the component (A) or a salt thereof. Can be expressed. From this viewpoint and from the viewpoint of suppressing skin irritation, the content of the acid or a salt thereof other than the component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, still more preferably. Is 5% by mass or less, more preferably 3% by mass or less, still more preferably 1% by mass or less, still more preferably 0.5% by mass or less, still more preferably less than 0.5% by mass, still more preferably. It is less than 0.1% by mass, and most preferably 0% by mass.
From the viewpoint of suppressing skin irritation, the composition of the present invention has a content of succinic acid or a salt thereof, preferably less than 1% by mass, more preferably, among organic acids other than the component (A) or salts thereof. It is 0.7% by mass or less, more preferably less than 0.5% by mass, and most preferably 0% by mass.

<pH>
The composition of the present invention has a pH of 3.5 or higher, preferably 3.7 or higher, from the viewpoint of suppressing skin irritation. Further, from the viewpoint of sterilization or improvement of virus-killing activity, it is 5.0 or less, preferably 4.5 or less. The specific pH range of the composition of the present invention is 3.5 or more and 5.0 or less, preferably 3.7 or more and 4.5 or less.
The pH is a value at 25 ° C., and can be specifically measured by the method described in Examples.

The form of the composition of the present invention is not particularly limited, and may be, for example, solid, liquid, gel, or cream. From the viewpoint of ease of application to the skin, it is preferably in the form of a gel or cream. The composition may be in the form of an emulsified composition, and the emulsified composition may be either an oil-in-water emulsified composition or a water-in-oil emulsified composition.

As long as the composition of the present invention is a leave-on skin external preparation composition, the dosage form of the preparation is not particularly limited. The dosage form of the composition of the present invention includes, for example, a stick preparation provided with a solid composition; a roll-on preparation or a spray preparation filled with a liquid composition; a liquid, gel-like or cream-like composition in a bottle, tube, or dispenser. Examples thereof include a formulation filled in a formula container and the like, a sheet product impregnated with a composition, and the like.

From the viewpoint of preventing contact infection by bacteria or viruses, the composition of the present invention is preferably a skin external preparation composition for fingers. Examples of the product form include hand sanitizers, hand cream cosmetics and the like.

[Defense method]
The present invention also provides a method for protecting the skin from bacteria or viruses, which comprises the step of applying the leave-on skin external preparation composition of the present invention to the skin.
According to the method of the present invention, it is possible to suppress skin irritation and protect the skin from bacteria or viruses by a method having high human safety. The fungus or virus to be protected by the method of the present invention is the same as described above.
The method of applying the composition to the skin can be appropriately selected depending on the dosage form, application site, etc. of the composition, and for example, the composition can be applied to the skin surface by application, spraying, or the like.

In the method of the present invention, it is preferable that the composition is not removed by washing with water or the like after being applied to the skin, but remains on the skin surface. This is because the composition can be used as a leave-on preparation to leave the component (A), which is a bactericidal or virus-killing component, on the skin surface, thereby imparting a bactericidal or virus-killing effect to the skin surface.

In this step, the amount of the composition applied is not particularly limited as long as it can impart a bactericidal / virus-killing effect to the skin surface.
From the viewpoint of imparting a high bactericidal / virus-killing effect, in the step, the amount of the composition applied is such that the amount of the component (A) present in the acid form on the skin surface to which the composition is applied is 1 cm of the skin. The amount per ² is preferably 1.5 μg or more, more preferably 1.7 μg or more, still more preferably 2 μg or more. Further, from the viewpoint of suppressing skin irritation, the amount is preferably 200 μg or less, more preferably 100 μg or less, still more preferably 50 μg or less. The amount of the component (A) present in the acid form on the skin surface to which the composition is applied is preferably 1.5 μg or more and ²⁰⁰ μg or less, more preferably 1.7 μg or more and 100 μg or less, still more preferably. Is an amount of 2 μg or more and 50 μg or less.
The "amount of the acid-type component (A) present on the skin surface to which the composition is applied" is the acid-type component derived from the composition on the skin surface at the time when the composition is applied (the composition). It is the total amount of A) and the acid-type component (A) that is naturally present on the skin surface.

The composition may be applied to the skin after washing the skin with water, soap, body soap, hand soap or the like in advance, or may be applied to the unwashed skin. Since the naturally existing components such as lactic acid are washed away from the washed skin and the defense power of bacteria and viruses existing in the outside world is reduced, the above composition is applied to the washed skin. It is more preferable to carry out the method of the present invention.

Hereinafter, the present invention will be described by way of examples, but the present invention is not limited to the scope of the examples. In this example, various measurements and evaluations were performed by the following methods.

(PH)
The pH of the composition was measured at 25 ° C. with an electrode 6637-10D (manufactured by HORIBA, Ltd.).

(Mole ratio of component (A) [acid type / (acid type + dissociation type)])
The molar ratio of the component (A) in the composition was calculated from the following formula. The acid type is referred to as "HA" and the dissociated type is referred ^to as "A-".
pH = pKa + log (A- ^/ HA)
log (A- ^/ HA) = pH-pKa
A- ^/ HA = 10 ^ (pH-pKa)
A- = 10 ^ (pH ^- pKa) x HA
From the above, the molar ratio [acid type / (acid type + dissociation type)] is HA / (HA + A- ⁾ = HA / (HA + 10 ^ (pH-pKa) × HA).
= 1 / (1 + 10 ^ (pH-pKa))
Here, when lactic acid is used as the component (A) (pKa = 3.86),
Mole ratio [lactic acid / (lactic acid + lactic acid ion)] = 1 / (1 + 10 ^ (x-3.86))
(X indicates the pH of the composition or the pH of the skin surface.)
When the component (A) is composed of a plurality of components, the following calculation method is defined in the present invention. By measuring the pH of the composition by the method described above and substituting the pKa of each of the plurality of components into the above formula, the molar ratio [acid type / (acid type + dissociation type)] of each component is obtained. Next, by adding the molar ratios [acid type / (acid type + dissociation type)] of each component, the molar ratio [acid type] of the component (A) when a plurality of types of components (A) are used. / (Acid type + dissociation type)] can be obtained.

[Evaluation 1: Evaluation of bactericidal property of composition]
(Preparation of bacterial solution)
The Escherichia coli solution prepared by the following method was used for the bactericidal evaluation.
As Escherichia coli, NBRC3301 strain was used. This bacterium was cultured in an LB liquid medium, and after collecting the bacterial cells by centrifugation, the OD600 was adjusted to 10 using pure water.

(Bactericidal activity of composition)
200 μL of the composition prepared in each Example and Comparative Example was warmed to 30 ° C. with a heat block, and then 2 μL of the bacterial solution was mixed with a vortex mixer and allowed to stand and contact on the heat block at 30 ° C. for 60 seconds. Then, 15 μL of the mixed solution was transferred to 1500 μL of LP-PBS and ice-cooled to stop the reaction (action of the composition prepared in each Example and Comparative Example on the bacterial solution).
Next, the number of surviving bacteria was measured by the following method using an incubation leader "HiTS" (manufactured by Sinix Co., Ltd.), and the amount of decrease in the number of bacteria (number of surviving bacteria / initial number of viable bacteria) was confirmed. Liquid culture was performed at 37 ° C. in an incubation leader "HiTS", and the absorbance (turbidity) at a wavelength of 600 nm was measured over time to create a growth curve of the viable cell count in the bacterial solution. At the same time, the bacterial solution having a known viable cell count was serially diluted, and the culture and growth curve were similarly prepared to prepare a calibration curve between the time to reach a certain turbidity and the viable cell count. From the relationship between the time required to reach a certain turbidity of each sample and the calibration curve, the number of surviving bacteria in the bacterial solution after the reaction was stopped was estimated, and the decrease in the number of bacteria was confirmed.
Regarding the degree of decrease in the number of bacteria, the -log value (logarithmic decrease value) of the amount of decrease in the number of bacteria was taken and shown in Table 1 (evaluation result a). The higher the value of the "logarithmic reduction value" for E. coli, the higher the bactericidal activity.

On the other hand, the compositions in which the component (A) was removed from each of the compositions of Examples 1 to 26, Comparative Examples 1 to 7, and 9 to 10 shown in Tables 1 to 4 (that is, the composition to which the component (A) was not added). Was prepared, and the pH was further adjusted to the same value as that of the composition using a hydrochloric acid aqueous solution having a concentration of 1 mol / L, and the bactericidal activity was evaluated by the same method as described above (evaluation result b).
Further, the difference (ab) between the evaluation results a and b was calculated and shown in Tables 1 to 4. The larger the value of ab, the higher the synergistic effect on the bactericidal activity by using the component (A) and the component (B) in combination, and the component (A) by using the component (B). It is suggested that the effect of promoting the uptake into the cells is high.

[Evaluation 2: Evaluation of virus-killing property of composition]
(Preparation of virus solution)
Human coronavirus ^OC43 (ATCC VR-1558) was infected and propagated in HCT-8 cells (ATCC CCL-244) in a tissue culture flask, and then the cell culture supernatant was purified by centrifugation and had a virus infectivity of 107.9. A TCID ₅₀ / mL virus solution was prepared.

(Viral killing activity of composition)
5 μL of the above virus solution was added to a test tube into which 45 μL of the composition of each example was dispensed, and immediately after that, the mixture was mixed with a vortex mixer for 15 seconds. The reaction mixture was allowed to stand at room temperature, and the reaction solution 1 was defined as 3 minutes after the addition of the virus solution. A 950 μL SCDLP solution (manufactured by Nihon Pharmaceutical Co., Ltd.) was added thereto and mixed with a vortex mixer for 10 seconds (reaction solution 2). The reaction was stopped by cooling the reaction solution 2 with ice. The ice-cooled reaction solution was serially diluted 10-fold with RPMI medium (manufactured by Sigma-Aldrich) supplemented with 2% deactivated horse serum and 50 mg / L gentamicin, and seeded into the HCT-8 cells. After culturing this in a 5% -CO ₂ incubator at a temperature of 33 ° C. for 4 days, infected cells were confirmed by the following antibody staining method, and the virus infectivity titer (TCID ₅₀ / mL) was calculated.
Regarding the virus-killing activity, the theoretical value of the virus infectious titer after the reaction was stopped was 10 ^5.59 TCID ₅₀ / mL (the initial viral load of 10 ^7.9 TCID ₅₀ / mL was 1/10 at the time of the reaction solution 1, the reaction solution. The -log value (log reduction value) of the above virus infectious titer (TCID ₅₀ / mL) with respect to the value which became 1/20 at the time point 2 was taken and shown in Tables 1 to 4. The higher the value of "logarithmic reduction value", the higher the virus-killing activity.

(Antibody staining method)
After seeding the virus and culturing for 4 days, the cells were immobilized with methanol, washed with phosphate buffered saline (PBS), and blocked with 0.5% -bovine serum albumin (BSA) for 2 hours. went. After washing this with PBS again, a primary antibody (Anti-Coronavirus Group Antigen Antibody, nucleoprotein of OC-43, clone 542-7D, manufactured by Merck) and a secondary antibody (HRP-) that specifically bind to coronavirus are used. Conjugated goat antibody IgG + IgM (H + L), manufactured by Jackson immunoresearch) were reacted for 2 hours each. The virus was then stained with DEPDA colorant (2 mM 4-chloronaphthol, 2 mM N, N-diethyl-p-phenylenediamine sulfate, 40 mM citrate buffer containing 0.01% hydrogen peroxide solution). The presence or absence of viral infection in cells was determined using the blue color as an index.

Examples 1 to 26, Comparative Examples 1 to 10 (Preparation and evaluation of leave-on finger external preparation composition)
For Examples 1 to 26, Comparative Examples 1 to 7, 9 to 10, each component in the amounts shown in Tables 1 to 4 was blended, mixed at room temperature, and then hydroxideed at a concentration of 1 mol / L as a pH adjuster. The pH was adjusted to the values shown in each table using an aqueous sodium solution to prepare a leave-on finger external preparation composition. The blending amounts shown in Tables 1 to 4 are the amount of the active ingredient (% by mass) of each component.
Various evaluations were carried out by the above method using the obtained composition. In Comparative Example 8, evaluation was performed using only water (purified water). The results are shown in Tables 1 to 4. Details of the components * 1 to * 16 shown in Tables 1 to 4 are shown in Table 5.
In the compositions of Examples 1 to 26, Comparative Examples 1 to 7, and 9 to 10, the molar ratio of lactic acid [acid type / (acid type + dissociation type)] and the acid type lactic acid in the composition. The content is as shown in the table.

* 2-9, 11-16: The numerical values in parentheses in the component names indicate the average number of moles added in EO.
* 10: The sucrose lauric acid ester has a monoester content of about 80% by mass and other polyesters of about 20% by mass.

From Tables 1 to 4, it can be seen that the composition of this example has higher bactericidal activity than the composition of Comparative Example (evaluation result a of evaluation 1). Further, the composition of this example contains the component (A) and the component (B) because the value of the difference (ab) between the evaluation results a and b is larger than that of the composition of the comparative example. The synergistic effect of is also high.
Similarly, it can be seen that the composition of this example has significantly improved virus-killing activity as compared with Comparative Example 8 (evaluation 2).

As the composition of the present invention, the formulations shown in Table 6 can be prepared by a conventional method.

The components listed in Table 6 are as follows.
Lactic acid: Lactic acid (active: 90%) Fuji Film Wako Pure Chemical Industries, Ltd. Succinic acid: Succinic acid Fuji Film Wako Pure Chemical Industries, Ltd. Polyoxyethylene (6) Lauryl ether: Emargen 108 Kao Corporation, HLB12 .1, EO average number of added moles 6
Polyoxyethylene (9) Lauryl ether: Emulgen 109P, manufactured by Kao Corporation, HLB 13.6, EO average number of moles added 9
Sodium hydroxide: NaOH (sodium hydroxide aqueous solution) 48% Kanto Chemical Co., Ltd. was used after adjusting to a 1 mol / L aqueous solution of sodium hydroxide.

Claims

(A) One or more acids selected from the group consisting of lactic acid, pyruvic acid and urocanic acid or salts thereof, and
(B) A nonionic surfactant having a lipophilic group having 12 carbon atoms and having an HLB of 8.0 or more and 17.0 or less.
The content of the component (A) is 0.02% by mass or more and 20.0% by mass or less, and the content of the component (B) is 0.006% by mass or more and 5.0% by mass or less. A leave-on skin external preparation composition having a pH of 3.5 or more and 5.0 or less.
The leave-on skin external preparation composition according to claim 1, wherein the lipophilic group having 12 carbon atoms is a group having a linear aliphatic group.
The leave-on skin external preparation composition according to claim 2, wherein the linear aliphatic group is a linear saturated aliphatic group.
The component (B) is one or more selected from the group consisting of polyoxyethylene lauryl ether, sucrose lauric acid ester, polyoxyethylene lauric acid ester, polyglyceryl lauryl ether, polyglyceryl laurate, lauryl glucoside and polyoxyethylene lauryl amine. The leave-on skin external preparation composition according to any one of claims 1 to 3.
The leave-on skin external preparation composition according to claim 4, wherein the average number of moles of oxyethylene groups added in polyoxyethylene lauryl ether, polyoxyethylene lauric acid ester, and polyoxyethylene lauryl amine is 2 or more and 20 or less.
The leave-on skin external preparation composition according to claim 4, wherein the component (B) is at least one selected from the group consisting of polyoxyethylene lauryl ether and sucrose lauric acid ester.
A method for protecting the skin from bacteria or viruses, which comprises a step of applying the leave-on skin external preparation composition according to any one of claims 1 to 6 to the skin.