Leave-on skin topical composition

Abstract

To provide a leave-on skin external preparation composition having a high activity for killing bacteria or viruses and having low skin irritation and high safety to the human body.SOLUTION: A leave-on skin external preparation composition contains (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 with 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 mass% or more and 20.0 mass% or less, the content of the component (B) is 0.006 mass% or more and 5.0 mass% or less, and pH is 3.5 or more and 5.0 or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a leave-on skin topical composition. [Background technology]

[0002] Recent studies have shown that contact infection is a common route of bacterial or viral infection in people's daily lives. Contact infection occurs primarily when hands come into contact with infected people, doorknobs, handles, tableware, toys, other household items, interior decorations, and other objects.

[0003] There is a need for a method to prevent bacterial or viral infections caused by contact in such everyday life. As a method for preventing contact infection of bacteria or viruses via hands, a method of applying an alcohol-based disinfectant to hands to sterilize and disinfect them is known. However, alcohols such as ethanol used as sterilizing or disinfecting components are highly volatile, and the effect is not sufficiently sustained in terms of imparting a sterilizing or virucidal effect to hands.

[0004] Therefore, methods for providing hands with a defense function against bacteria or viruses have been studied. These methods continuously provide a bacterial or viral infection prevention effect, making it possible to prevent contact infection even in environments where there is no hand-washing facility, such as when out and about. This is particularly preferable because it can prevent infection even when repeatedly coming into contact with an object that has bacteria or viruses attached.

[0005] It is also known to use organic acids or salts thereof as components for achieving bactericidal or virucidal effects. For example, Patent Document 1 discloses a method for suppressing bacteria and viruses present on the skin surface of a mammal, which comprises contacting the skin for at least about 0.5 hours with a compound or composition capable of reducing the skin pH to less than about 4. Examples of the compound or composition capable of reducing the skin pH include those containing organic acids such as monocarboxylic acids and polycarboxylic acids. Patent Document 2 discloses a method for killing rhinoviruses and preventing the spread of colds caused by rhinoviruses by applying a virucidal composition (hand lotion) containing citric acid, malic acid, and a C1-6 alcohol to the hands of a patient after the patient has been diagnosed with a rhinovirus cold or before the patient has been exposed to the rhinovirus.

[0006] It is also known that surfactants have antibacterial properties (Non-Patent Document 1). Non-Patent Document 1 describes that, among surfactants, cationic surfactants such as quaternary ammonium salts or amphoteric surfactants exhibit strong antibacterial properties, while anionic surfactants have weak antibacterial properties, and polyethylene glycol-type nonionic surfactants have no or very weak antibacterial properties. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Special Publication No. 2008-523064 [Patent Document 2] U.S. Patent No. 6,034,133 [Non-patent literature]

[0008] [Non-Patent Document 1] Shoichiro Watanabe, "Current Status and Trends of Antibacterial Surfactants," Oil Chemistry, Vol. 29, No. 8, pp. 536-542, 1980 Summary of the Invention [Problem to be solved by the invention]

[0009] Example 2 of Patent Document 1 discloses Compositions 2A to 2C containing citric acid and malic acid, of which only Composition 2A, which has a pH of 2.3, exhibits antirhinovirus activity. Example 3 discloses Antirhinovirus Composition 2D, which contains citric acid and malic acid, and has a pH of 3.1. However, applying a low-pH composition to the skin is undesirable due to skin irritation. The hand lotion described in Patent Document 2 essentially contains citric acid, malic acid, and a C1-6 alcohol, and does not demonstrate the virucidal properties of hand lotions with other compositions. Furthermore, there are concerns that the alcohol component of this hand lotion may cause skin irritation. Nonionic surfactants such as the polyethylene glycol-based nonionic surfactants described in Non-Patent Document 1 are ingredients generally used as emulsifiers in foods, cosmetics, etc., and although they cause little skin irritation when included in a leave-on topical skin preparation composition, they have weak bactericidal and virucidal effects on their own.

[0010] In view of these circumstances, the present inventors aimed to provide a leave-on topical skin composition that exhibits high bactericidal or virucidal activity, while using an organic acid under mild conditions of a pH of 3.5 or higher, while using a nonionic surfactant that is unlikely to cause skin irritation even when included in the leave-on topical skin composition, and without using an alcohol component.

[0011] That is, the present invention relates to a leave-on skin preparation composition for external use that has high bactericidal or virucidal activity, is less irritating to the skin, and is highly safe for the human body. [Means for solving the problem]

[0012] The present inventors have found that a composition containing a predetermined amount of one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and a nonionic surfactant having a lipophilic group with 12 carbon atoms and an HLB value within a predetermined range, and having a relatively high pH of 3.5 or higher, is less irritating to the skin and is highly safe for the human body even when used as a leave-on skin preparation, and can improve bactericidal or virucidal activity. Here, the one or more acids selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid are organic acids that are naturally present on human skin, and when used in a composition with a pH of 3.5 or higher, they cause little skin irritation and are highly safe for the human body, but their bactericidal or virucidal effects are weak. Furthermore, as mentioned above, nonionic surfactants generally have weak bactericidal or virucidal effects by themselves. However, the present inventors have hypothesized that a nonionic surfactant having a lipophilic group with 12 carbon atoms and an HLB within a specific range can penetrate the cell membrane of bacteria or viruses, increasing the fluidity of the cell membrane and facilitating the incorporation of the organic acid component into the bacteria or viruses. They then discovered that by using the organic acid component in combination with a nonionic surfactant, the organic acid component can be efficiently incorporated into the bacteria or viruses, thereby improving the effect of inactivating or killing bacteria or viruses even in a composition having a pH of 3.5 or higher.

[0013] That is, the present invention provides the following [1] and [2]. [1] A leave-on skin topical composition comprising (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) a nonionic surfactant having a lipophilic group with 12 carbon atoms and an HLB of 8.0 or more and 17.0 or less, wherein the content of component (A) is 0.02% by mass or more and 20.0% by mass or less, the content of component (B) is 0.006% by mass or more and 5.0% by mass or less, and the pH is 3.5 or more and 5.0 or less. [2] A method for protecting the skin from bacteria or viruses, comprising the step of applying the leave-on skin topical composition described in [1] above to the skin. [Effects of the Invention]

[0014] According to the present invention, a leave-on external skin preparation composition can be provided which has high bactericidal or virucidal activity, is less irritating to the skin, and is highly safe for the human body. DETAILED DESCRIPTION OF THE INVENTION

[0015] [Leave-on skin topical composition] The leave-on skin topical composition of the present invention (hereinafter also referred to as "the composition of the present invention") is (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) a nonionic surfactant having a lipophilic group having 12 carbon atoms and an HLB value of 8.0 or more and 17.0 or less; The content of component (A) is 0.02% by mass or more and 20.0% by mass or less, the content of component (B) is 0.006% by mass or more and 5.0% by mass or less, and the pH is 3.5 or more and 5.0 or less. By virtue of the above constitution, the composition of the present invention is a skin external preparation composition that has high bactericidal or virucidal activity, is less irritating to the skin, and is highly safe for the human body.

[0016] As used herein, the term "leave-on skin topical composition" refers to a skin topical composition that is used after application to the skin without being removed by rinsing with water or the like. The composition of the present invention can impart a bactericidal or virucidal effect to the skin surface by leaving the bactericidal or virucidal components, component (A) and component (B), on the skin surface. From the viewpoint of obtaining this effect, the composition of the present invention is used by leaving the composition on the skin surface after application by coating or the like, without removing the composition by rinsing with water or the like. From the viewpoint of preventing contact infection with bacteria or viruses, the composition of the present invention is more preferably a leave-on skin external preparation composition for use on the hands and fingers.

[0017] As used herein, "bactericidal or virucidal activity" refers to the bactericidal or virucidal activity of the composition itself. For example, bactericidal activity against Escherichia coli and virucidal activity against coronaviruses can be specifically evaluated by the methods described in the Examples. Activity against other bacteria and viruses can be evaluated taking into account common technical knowledge.

[0018] As used herein, "imparting a bactericidal or virucidal effect to the skin surface" encompasses concepts such as (1) a bactericidal or virucidal effect that is exerted against bacteria and viruses that adhere to the skin surface after the composition of the present invention is applied to the skin surface, (2) a bactericidal or virucidal effect that is exerted against bacteria and viruses that adhere to the skin by applying the composition, (3) an effect of preparing the skin so that bacteria and viruses are not transmitted, (4) an effect of protecting the skin from bacteria and viruses and keeping it hygienic, (5) an effect of preventing the spread of bacteria and viruses through the skin and contact infection, and (6) an effect of enhancing the skin's ability to defend against infections by bacteria and viruses.

[0019] In this specification, it is considered that skin irritation is suppressed if the pH of the composition at 25°C is 3.5 or higher.

[0020] The bacteria or viruses against which the composition of the present invention exerts bactericidal or virucidal activity are not particularly limited, as long as they are inactivated or killed by contact with acid. For example, it is considered that the microorganisms listed in the Ministry of Health, Labor and Welfare's guidelines for infectious disease control in nurseries can be applied. Specific examples of bacteria include gram-positive bacteria such as Bacillus anthracis, Mycobacterium tuberculosis, hemolytic streptococcus, Staphylococcus aureus, and Streptococcus pneumoniae, as well as gram-negative bacteria such as Francisella tularensis, Yersinia pestis, Brucella, Bacillus mallei, Vibrio cholerae, Salmonella enterica, Shigella, enterohemorrhagic Escherichia coli, and Bordetella pertussis. Examples of viruses include enveloped viruses such as arenaviruses, Ebola viruses, smallpox viruses, nairoviruses, Marburg viruses, coronaviruses, monkeypox viruses, betacoronaviruses, influenza viruses, respiratory syncytial viruses, herpes viruses, mumps viruses, varicella-zoster viruses, rubella viruses, and measles viruses, as well as non-enveloped viruses such as enteroviruses, adenoviruses, coxsackieviruses, noroviruses, and rotaviruses. In this example, bactericidal and virucidal activities are evaluated using Escherichia coli and coronavirus as examples, but the bacteria and viruses targeted by the present invention are not limited to these.

[0021] The reason why the composition of the present invention exhibits the above-mentioned effects is not clear, but is thought to be as follows. The present inventors have found that component (A), lactic acid, pyruvic acid, and urocanic acid, are naturally present on human skin, for example, as supplied from sweat glands, and that they have bactericidal and virucidal functions against bacteria, viruses, etc., particularly on the hands and fingers. Therefore, it is believed that a topical skin preparation composition containing component (A) can be a composition that has bactericidal or virucidal activity, yet is less irritating to the skin and is highly safe for the human body. Regarding the above-mentioned bactericidal or virucidal activity, it is known that the lower the pH, the higher the bactericidal or virucidal activity of a composition containing component (A). For example, lactic acid, which is component (A), exists in an aqueous solution in an acid form (CH3CH(OH)COOH) and a dissociated form (CH3CH(OH)COO -), but the acid form has no electric charge and is more easily taken up by bacteria or viruses, so it is thought that the acid form exhibits higher bactericidal or virucidal activity. The ratio of acid form / dissociated form of lactic acid depends on the pH, and when the pH exceeds 5, the proportion of the acid form decreases, and the proportion of lactic acid present in the acid form relative to the total amount of lactic acid blended falls to, for example, a level below 5 mol%. The composition of the present invention exhibits high bactericidal or virucidal activity when the pH is 5.0 or less.

[0022] On the other hand, even when component (A) is used, there is a concern that compositions in the low pH range may cause skin irritation. As a result of investigations conducted by the present inventors, it was found that by using predetermined amounts of component (A) and component (B), which is a predetermined nonionic surfactant, it is possible to improve the bactericidal or virucidal activity even in compositions having a relatively high pH range of 3.5 or higher. As mentioned above, even when nonionic surfactants such as polyethylene glycol-based nonionic surfactants are included in leave-on skin topical compositions, they alone have weak bactericidal and virucidal effects. However, component (B), a nonionic surfactant having a lipophilic group with 12 carbon atoms and an HLB value within a specific range, penetrates the cell membrane of bacteria or viruses, increasing the fluidity of the cell membrane, thereby making it easier for component (A) to be incorporated into the bacteria or viruses. Therefore, it is believed that using component (A) in combination with component (B) will efficiently incorporate component (A) into the bacteria or viruses, improving the effect of inactivating or killing the bacteria or viruses. The above-mentioned mechanism of action is believed to enable the production of an external skin preparation composition with a pH of 3.5 or higher, which is less irritating to the skin and has high bactericidal and virucidal activity.

[0023] <Component (A)> 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. Component (A) acts as a bactericidal and virucidal component. Examples of salts of lactic acid, pyruvic acid, and urocanic acid include alkali metal salts such as potassium salts and sodium salts of lactic acid, pyruvic acid, and urocanic acid; alkaline earth metal salts such as calcium salts and magnesium salts; amine salts; ammonium salts, etc. Among these, from the viewpoints of improving bactericidal or virucidal activity and easy availability, one or more selected from the group consisting of alkali metal salts and alkaline earth metal salts of lactic acid, pyruvic acid, and urocanic acid are preferred, one or more selected from the group consisting of potassium salts, sodium salts, and calcium salts are more preferred, and one or more selected from the group consisting of potassium lactate, sodium lactate, and calcium lactate are even more preferred. From the viewpoint of improving bactericidal or virucidal activity, component (A) is preferably lactic acid or a salt thereof, more preferably one or more selected from the group consisting of lactic acid, potassium lactate, sodium lactate, and calcium lactate, and even more preferably contains lactic acid. When component (A) contains lactic acid, the content of lactic acid or a salt thereof in the total amount of component (A) is preferably 80% by mass or more, more preferably 90% by mass or more, and most preferably 100% by mass, from the viewpoint of improving bactericidal or virucidal activity.

[0024] From the viewpoint of improving bactericidal or virucidal activity, the content of 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% by mass or more, even more preferably 0.3% by mass or more, and even more preferably 0.5% by mass or more. From the viewpoint of suppressing skin irritation, the content is 20.0% by mass or less, preferably 15.0% by mass or less, more preferably 10.0% by mass or less, even more preferably 5.0% by mass or less, even more preferably 3.0% by mass or less, and even more preferably 2.0% by mass or less. The content of 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 0.1% by mass or more and 10.0% by mass or less, even more preferably 0.3% by mass or more and 5.0% by mass or less, even more preferably 0.3% by mass or more and 3.0% by mass or less, and even more preferably 0.5% by mass or more and 2.0% by mass or less. In this specification, when component (A) contains a salt, the "content of component (A)" means the amount converted into the acid.

[0025] The content of component (A) in 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 virucidal activity. Furthermore, from the viewpoint of suppressing skin irritation, it is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 7% by mass or less, and even more preferably 1% by mass or less. The content of component (A) in 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, even 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.

[0026] In the composition of the present invention, the molar ratio of component (A) present in acid form to the total of component (A) present in acid form and component (A) present in dissociated form [acid form / (acid form + dissociated form)] is preferably 0.068 or more, more preferably 0.12 or more, from the viewpoint of improving bactericidal or virucidal activity. Furthermore, from the viewpoint of suppressing skin irritation, it is preferably 0.7 or less, more preferably 0.5 or less. The molar ratio [acid form / (acid form + dissociated form)] in the composition is preferably 0.068 or more and 0.7 or less, more preferably 0.12 or more and 0.5 or less. Specifically, the above molar ratio can be calculated by the method described in the Examples.

[0027] In this specification, "component (A) present in acid form in the composition" means the component of component (A) present in the composition as lactic acid, pyruvic acid, and urocanic acid, and "component (A) present in dissociated form in the composition" means the component of component (A) present in the composition as lactate ions, pyruvic acid ions, and urocanic acid ions.

[0028] <Ingredient (B)> Component (B) used in the composition of the present invention is a nonionic surfactant having a lipophilic group with 12 carbon atoms and an HLB (Hydrophilic-Lipophilic Balance) of 8.0 or more and 17.0 or less. It is believed that the composition of the present invention contains components (A) and (B), and by virtue of this synergistic effect, component (A), a bactericidal and virucidal component, is efficiently taken up into bacteria or viruses, resulting in high bactericidal and virucidal activity.

[0029] In component (B), the lipophilic group having 12 carbon atoms can be a monohydric alcohol residue having 12 carbon atoms or a fatty acid residue having 12 carbon atoms. From the viewpoint of improving bactericidal or virucidal activity and ease of availability, the lipophilic group having 12 carbon atoms is preferably a group having a straight-chain aliphatic group, and the straight-chain aliphatic group is more preferably a straight-chain saturated aliphatic group. More specifically, as the lipophilic group having 12 carbon atoms in component (B), from the viewpoint of improving the bactericidal or virucidal activity and from the viewpoint of easy availability, R 11 -O-, R 12 -COO-, and R 12 Preferably, R is one or more selected from the group consisting of groups represented by -CONH-. 11 -O- and R 12 More preferably, R is one or more selected from the group consisting of groups represented by -COO-. 11 More preferably, R is a group represented by -O-. 11 is an aliphatic group having 12 carbon atoms, and R 12 is an aliphatic group having 11 carbon atoms. R 11 and R 12 From the viewpoint of improving bactericidal or virucidal activity, the aliphatic group in the formula (I) is preferably a straight-chain aliphatic group, and more preferably a straight-chain saturated aliphatic group.

[0030] Component (B) may have only one lipophilic group having 12 carbon atoms, or may have two or more. From the viewpoint of improving bactericidal or virucidal activity, it is preferable that component (B) is primarily composed of a nonionic surfactant having only one lipophilic group having 12 carbon atoms. Here, "primary component" means that it preferably accounts for 50% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more of component (B), and may be 100% by mass.

[0031] Specific examples of component (B) include polyoxyethylene lauryl ether, sucrose laurate, polyoxyethylene laurate, polyglyceryl lauryl ether, polyglyceryl laurate, lauryl glucoside, polyoxyethylene laurylamine, polyoxyethylene sorbitan laurate, polyoxyethylene sorbitan laurate, etc., and one or more of these can be used. Among these, from the viewpoint of improving bactericidal or virucidal activity, component (B) is preferably one or more selected from the group consisting of polyoxyethylene lauryl ether, sucrose laurate, polyoxyethylene laurate, polyglyceryl lauryl ether, polyglyceryl laurate, lauryl glucoside, and polyoxyethylene laurylamine.

[0032] Of the above, the average number of moles of oxyethylene groups added (hereinafter referred to as "average number of moles of EO added") in polyoxyethylene lauryl ether, polyoxyethylene laurate, polyoxyethylene laurylamine, polyoxyethylene sorbitan laurate, and polyoxyethylene sorbit laurate, preferably polyoxyethylene lauryl ether, polyoxyethylene laurate, and polyoxyethylene laurylamine, is preferably 2 or more, more preferably 3 or more, from the viewpoint of improving the solubility and stability of the composition, and is preferably 20 or less, more preferably 15 or less, and even more preferably 10 or less, from the viewpoint of improving bactericidal or virucidal 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, even more preferably 3 or more and 15 or less, and still more preferably 3 or more and 10 or less. Note that the average number of moles of EO added is a number average value.

[0033] Among the above, the laurates in sucrose laurate, polyoxyethylene laurate, polyoxyethylene sorbitan laurate, and polyoxyethylene sorbit laurate can include polyesters such as diesters and triesters in addition to monoesters, and mixtures of monoesters and polyesters can also be used. From the viewpoint of improving bactericidal or virucidal activity and obtaining a desired HLB value, it is preferable that the laurate be mainly composed of a monoester. Here, "main component" means that the monoester preferably accounts for 50% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more of the total amount of the laurate.

[0034] One or more nonionic surfactants can be used as component (B). Among the above, from the viewpoint of improving bactericidal or virucidal activity, component (B) is more preferably one or more selected from the group consisting of polyoxyethylene lauryl ether, sucrose laurate, and polyoxyethylene laurate, even more preferably one or more selected from the group consisting of polyoxyethylene lauryl ether and sucrose laurate, and even more preferably polyoxyethylene lauryl ether. The average number of moles of EO added in polyoxyethylene lauryl ether and polyoxyethylene laurate is within the above-mentioned range (preferably 2 to 20, more preferably 3 to 15, and even more preferably 3 to 10), and it is preferable that the sucrose laurate and polyoxyethylene laurate are mainly composed of monoesters.

[0035] (HLB) 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. Also, from the viewpoint of improving bactericidal or virucidal activity, the HLB is 17.0 or less, preferably 16.5 or less, more preferably 16.0 or less, even more preferably 15.5 or less, still more preferably 14.0 or less, and even 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 calculated by Griffin's formula. In addition, component (B) of the present invention refers to a nonionic surfactant having a lipophilic group with 12 carbon atoms and having an HLB value within the above range, and the content of component (B) contained in the composition refers to the total amount of nonionic surfactants having a lipophilic group with 12 carbon atoms that satisfy the above HLB range.

[0036] The content of component (B) in the composition of the present invention is 0.006% by mass or more, preferably 0.01% by mass or more, more preferably 0.05% by mass or more, even more preferably 0.1% by mass or more, and still more preferably 0.2% by mass or more, from the viewpoint of improving bactericidal or virucidal activity. Also, from the viewpoint of suppressing skin irritation and improving the feel during use, it is 5.0% by mass or less, preferably 3.0% by mass or less, even more preferably 2.5% by mass or less, still more preferably 2.0% by mass or less, and still more preferably 1.5% by mass or less. The content of component (B) in the composition of the present invention is from 0.006% by mass to 5.0% by mass, preferably from 0.01% by mass to 5.0% by mass, more preferably from 0.05% by mass to 5.0% by mass, even more preferably from 0.1% by mass to 5.0% by mass, still more preferably from 0.1% by mass to 3.0% by mass, even more preferably from 0.2% by mass to 2.5% by mass, still more preferably from 0.2% by mass to 2.0% by mass, and still more preferably from 0.2% by mass to 1.5% by mass.

[0037] The total content of component (A) and 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, even 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, and even more preferably 1.0% by mass or more, from the viewpoint of improving bactericidal or virucidal activity. Also, 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, and even more preferably 3.0% by mass or less. The specific range of the total content of component (A) and 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, even 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, even more preferably 0.35% by mass or more and 5.0% by mass or less, still more preferably 0.4% by mass or more and 5.0% by mass or less, and still more preferably 1.0% by mass or more and 3.0% by mass or less.

[0038] The composition of the present invention may contain a surfactant other than component (B). Examples of surfactants other than component (B) include anionic surfactants, cationic surfactants (excluding quaternary ammonium salts), amphoteric surfactants (excluding alkyldiaminoethylglycine chloride and alkylpolyaminoethylglycine), and nonionic surfactants other than component (B). Examples of the anionic surfactants include alkyl phosphate ester salts and polyoxyethylene alkyl ether sulfate ester salts, and examples of the amphoteric surfactants include lauroamphoacetate and lauryl betaine. However, in the composition of the present invention, the proportion of component (B) in the surfactant is preferably 50% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more, from the viewpoint of bactericidal or virucidal properties, and may be 100% by mass. In the composition of the present invention, the total content of surfactants including 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. Furthermore, 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 0.5% by mass or less, and even more preferably 0.1% by mass or less, from the viewpoint of suppressing skin irritation. Furthermore, from the viewpoint of suppressing skin irritation, the content of the amphoteric surfactant is preferably 3.0% by mass or less, more preferably 1.0% by mass or less, and even more preferably 0.5% by mass or less. Furthermore, the content of the nonionic surfactant including component (B) in the composition of the present invention is preferably 5.0% by mass or less, more preferably 3.0% by mass or less, and even more preferably 1.5% by mass or less. From the viewpoint of bactericidal or viricidal properties, the proportion of component (B) in the nonionic surfactant is preferably 50% by mass or more, more preferably 70% by mass or more, and even more preferably 80% by mass or more, and may be 100% by mass.

[0039] From the viewpoint of improving bactericidal or virucidal activity, the mass ratio of component (B) to component (A) in the composition of the present invention (component (B) / component (A)) is preferably 0.005 or more, more preferably 0.1 or more, even more preferably 0.1 or more, still more preferably 0.2 or more, and is preferably 20 or less, more preferably 10 or less, even more preferably 5 or less, and still more preferably 2 or less. 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, even ... still more preferably 0.2 or more and 10 or less, still more preferably 0.2 or more and 5 or less, and still more preferably 0.2 or more and 2 or less.

[0040] The composition of the present invention preferably further contains water from the viewpoint of dissolving component (A) and component (B) and facilitating application to the skin surface. The water content in the composition of the present invention is preferably 10% by mass or more, more preferably 30% by mass or more, even more preferably 50% by mass or more, and even more preferably 70% by mass or more, and is preferably 99.8% by mass or less, more preferably 99% by mass or less. The water content 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, even more preferably 50% by mass or more and 99.8% by mass or less, and even more preferably 70% by mass or more and 99% by mass or less.

[0041] From the viewpoint of obtaining the effects of the present invention, the total content of component (A), 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, even more preferably 80% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, and may be 100% by mass.

[0042] In addition to the above, the composition of the present invention may also contain other ingredients, as needed, such as an acid or salt thereof other than component (A) (malic acid or adipic acid), a thickener (polysaccharide, polymer, etc.), a pH adjuster (citric acid, sodium hydroxide, etc.), an ultraviolet absorber (titanium oxide, zinc oxide, etc.), an antioxidant (ascorbic acid, tocopherol, etc.), a preservative (methylparaben, benzoic acid, etc.), an antiperspirant (zinc benzoate, aluminum chloride hydrate, etc.), a fragrance (eucalyptus, geraniol, etc.), a moisturizer (polyol, natural fats and oils, etc.), a texture adjuster (silicone, high-quality fats and oils, etc.), an anti-inflammatory agent (glycyrrhizinic acid, etc.), etc.

[0043] 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, even more preferably 5% by mass or less, and still more preferably 3% by mass or less, from the viewpoint of improving the feel of the composition when used.

[0044] The composition of the present invention uses component (A) as a bactericidal or virucidal component, and therefore exhibits bactericidal or virucidal activity without blending ethanol. From this viewpoint, and from the viewpoint of suppressing skin irritation, the ethanol content in the composition is preferably 70% by mass or less, more preferably 50% by mass or less, even more preferably 30% by mass or less, still more preferably 10% by mass or less, even 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 0.03% by mass or less, still more preferably less than 0.01% by mass, and most preferably substantially 0% by mass.

[0045] In the composition of the present invention, the ratio of the total content of polyol and ethanol to the content of water [(polyol + ethanol) / water] is, in terms of mass ratio, preferably 2 or less, more preferably 1 or less, even more preferably 0.5 or less, and still more preferably 0.1 or less, from the viewpoint of suppressing skin irritation and improving the feel during use.

[0046] The composition of the present invention, which uses component (A) as a bactericidal or virucidal component, exhibits bactericidal or virucidal activity without the addition of any of the following disinfectants: quaternary ammonium salts such as benzalkonium chloride and benzethonium chloride; amphoteric surfactants such as alkyldiaminoethylglycine chloride and alkylpolyaminoethylglycine; biguanides such as chlorhexidine gluconate; sodium hypochlorite; aldehydes such as glutaral, phthalal, and formalin; povidone-iodine; iodine tincture; phenol; cresol soap solution; peracetic acid; or hydrogen peroxide. From this viewpoint, and from the viewpoint of suppressing skin irritation, the content of the bactericide in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, still more preferably 3% by mass or less, still 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, still more preferably 0.03% by mass or less, still more preferably less than 0.01% by mass, and most preferably substantially 0% by mass. On the other hand, when the above bactericide is blended, from the viewpoint of improving bactericidal or virucidal activity, the content of the bactericide in the composition is preferably 0.01% by mass or more, more preferably 0.05% by mass or more. Furthermore, from the viewpoint of suppressing skin irritation, the mass ratio of the disinfectant to component (A) (disinfectant / component (A)) is preferably 0.1 or less, more preferably 0.05 or less, even more preferably 0.03 or less, and even more preferably 0.01 or less, and is most preferably substantially 0. On the other hand, when the disinfectant is blended, from the viewpoint of improving the disinfecting or virucidal activity, the mass ratio of the disinfectant to component (A) (disinfectant / component (A)) is preferably 0.01 or more, more preferably 0.05 or more. In this specification, an agent that is the above-mentioned bactericide and also functions as a surfactant is defined as a bactericide.

[0047] The composition of the present invention uses component (A) as a bactericidal or virucidal component, and can therefore exhibit bactericidal or virucidal activity without blending any organic acid or salt thereof other than component (A). From this perspective, and from the perspective of suppressing skin irritation, the content of the acid or salt thereof other than component (A) in the composition is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 5% by mass or less, still more preferably 3% by mass or less, even 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 less than 0.1% by mass, and most preferably substantially 0% by mass. From the viewpoint of suppressing skin irritation, the content of succinic acid or a salt thereof in the composition of the present invention, among organic acids or salts thereof other than component (A), is preferably less than 1% by mass, more preferably 0.7% by mass or less, even more preferably less than 0.5% by mass, and most preferably substantially 0% by mass.

[0048] <ph> From the perspective of suppressing skin irritation, the composition of the present invention has a pH of 3.5 or higher, preferably 3.7 or higher. Also, from the perspective of improving bactericidal or antiviral activity, it is 5.0 or lower, preferably 4.5 or lower. The specific range of the pH of the composition of the present invention is 3.5 or higher and 5.0 or lower, preferably 3.7 or higher and 4.5 or lower. The above pH is the value at 25 °C, and specifically, it can be measured by the method described in the examples.

[0049] The form of the composition of the present invention is not particularly limited, and for example, it can be in a solid form, liquid form, gel form, or cream form. From the perspective of ease of application to the skin, it is preferably in a gel form or cream form. The composition may be in the form of an emulsion composition, and as the emulsion composition, either an oil-in-water type emulsion composition or a water-in-oil type emulsion composition may be used.

[0050] As long as the composition of the present invention is a leave-on skin external preparation composition, there is no particular limitation on the dosage form of the preparation. Examples of the dosage form of the composition of the present invention include a stick preparation having a solid composition; a roll-on preparation or a spray preparation filled with a liquid composition; a preparation filled with a liquid, gel, or cream composition in a bottle, tube, dispenser-type container, etc., a sheet product impregnated with the composition, and the like.

[0051] From the perspective of preventing contact infection by bacteria or viruses, the composition of the present invention is preferably a skin external preparation composition for fingers among skin external preparation compositions. Examples of its product form include a finger disinfectant, a hand cream cosmetic, and the like.

[0052] [Defense Method] The present invention also provides a method for protecting the skin from bacteria or viruses, which includes a 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, skin irritation can be suppressed, and the skin can be protected from bacteria or viruses by a method with high human body safety. The bacteria or viruses to be protected against by the method of the present invention are the same as those described above. The method for applying the composition to the skin can be appropriately selected depending on the dosage form of the composition, the area to be applied, etc. For example, the composition can be applied by painting or spraying it onto the skin surface.

[0053] In the method of the present invention, after applying the composition to the skin, it is preferable to leave the composition on the skin surface without removing it by rinsing with water, etc. This is because when the composition is used as a leave-on preparation, the bactericidal or virucidal component (A) remains on the skin surface, thereby imparting a bactericidal or virucidal effect to the skin surface.

[0054] In this step, the amount of the composition to be applied is not particularly limited as long as it is an amount that can impart bactericidal and virucidal effects to the skin surface. From the viewpoint of imparting a high bactericidal and virucidal effect, the amount of the composition applied in this step is set so that the amount of component (A) present in an acid form on the skin surface to which the composition is applied is equal to or greater than 1 cm of the skin. 2 The amount is preferably 1.5 μg or more, more preferably 1.7 μg or more, and even more preferably 2 μg or more per 1 cm of skin. From the viewpoint of suppressing skin irritation, the amount is preferably 200 μg or less, more preferably 100 μg or less, and even more preferably 50 μg or less. The amount of component (A) present in an acid form on the skin surface to which the composition is applied is 1.5 μg or more, more preferably 1.7 μg or more, and even more preferably 2 μg or more per 1 cm of skin. 2 The amount is preferably 1.5 μg or more and 200 μg or less, more preferably 1.7 μg or more and 100 μg or less, and even more preferably 2 μg or more and 50 μg or less. The "amount of component (A) present in acid form on the skin surface to which the composition is applied" refers to the total amount of acid-form component (A) derived from the composition and acid-form component (A) naturally present on the skin surface at the time the composition is applied.

[0055] The composition may be applied to unwashed skin after washing the skin in advance with water, soap, body soap, hand soap, etc. After washing, naturally occurring components such as lactic acid are washed away from the skin, and the skin's defense against external bacteria and viruses is weakened. Therefore, it is more preferable to carry out the method of the present invention by applying the composition to cleansed skin. [Example]

[0056] The present invention will be described below with reference to examples, but the present invention is not limited to the scope of the examples. In the examples, various measurements and evaluations were carried out by the following methods.

[0057] (pH) The pH of the composition was measured at 25°C using an electrode 6367-10D (manufactured by Horiba, Ltd.).

[0058] (Mole ratio of component (A) [acid type / (acid type + dissociated type)]) The molar ratio of component (A) in the composition was calculated using the following formula: - " is written as ". pH = pKa + log(A - / HA) log(A - / HA) = pH - pKa A - / HA=10^(pH-pKa) A - = 10^(pH-pKa) × HA From the above, the molar ratio [acid type / (acid type + dissociated type)] is HA / (HA+A - )=HA / (HA+10^(pH-pKa)×HA) =1 / (1+10^(pH-pKa)) Here, when lactic acid is used as component (A) (pKa=3.86), Molar ratio [lactic acid / (lactic acid + lactate ion)] = 1 / (1 + 10^(x-3.86)) (x represents the pH of the composition or the pH of the skin surface.) In addition, when component (A) consists of multiple components, the following calculation method is defined in the present invention. The pH of the composition is measured by the method described above, and the pKa of each of the multiple components is substituted into the above calculation formula to determine the molar ratio of each component [acid form / (acid form + dissociated form)]. Next, the molar ratios of each component [acid form / (acid form + dissociated form)] can be added together to obtain the molar ratio of component (A) [acid form / (acid form + dissociated form)] when multiple types of component (A) are used.

[0059] [Evaluation 1: Evaluation of the bactericidal properties of the composition] (Preparation of bacterial solution) For the evaluation of bactericidal activity, a bacterial suspension of Escherichia coli prepared by the following method was used. The Escherichia coli used was the NBRC3301 strain. This bacterium was cultured in LB liquid medium, and the cells were collected by centrifugation and then adjusted to OD600=10 using pure water.

[0060] (Bactericidal activity of the composition) 200 μL of the composition prepared in each Example and Comparative Example was heated to 30° C. in a heat block, and then 2 μL of the bacterial solution was mixed with it using a vortex mixer and allowed to stand for 60 seconds on the heat block at 30° C. Then, 15 μL of the mixed solution was transferred to 1500 μL of LP-PBS and cooled on ice to stop the reaction (the action of the composition prepared in each Example and Comparative Example on the bacterial solution). Next, the number of viable bacteria was measured using an incubation reader "HiTS" (manufactured by Synix Corporation) using the method described below, and the reduction in the number of viable bacteria (number of viable bacteria / initial number of viable bacteria) was confirmed. Liquid culture was performed at 37°C in the incubation reader "HiTS," and the absorbance (turbidity) at a wavelength of 600 nm was measured over time to create a growth curve of the number of viable bacteria in the bacterial solution. At the same time, a bacterial solution with a known number of viable bacteria was serially diluted, and similarly cultured and a growth curve was created, and a calibration curve of the time to reach a certain turbidity and the number of viable bacteria was created. From the relationship between the time to reach a certain turbidity for each sample and the calibration curve, the number of viable bacteria in the bacterial solution after the reaction was stopped was estimated, and the reduction in the number of bacteria was confirmed. The degree of reduction in the number of bacteria was calculated as the -log value (logarithmic reduction) of the reduction in the number of bacteria, and is shown in Table 1 (Evaluation result a). A higher "logarithmic reduction" against E. coli means a higher bactericidal activity.

[0061] On the other hand, compositions were prepared by omitting component (A) from each of the compositions of Examples 1 to 26 and Comparative Examples 1 to 7, and 9 to 10 listed in Tables 1 to 4 (i.e., compositions without component (A) added), and the pH was adjusted to the same value as that of the compositions using a 1 mol / L aqueous hydrochloric acid solution, and the bactericidal activity was evaluated in the same manner as above (evaluation result b). Furthermore, the difference (ab) between the evaluation results a and b was calculated and is shown in Tables 1 to 4. The larger the value of ab, the greater the synergistic effect on bactericidal activity of the combined use of component (A) and component (B), suggesting that the use of component (B) is highly effective in promoting the uptake of component (A) into bacterial cells.

[0062] [Evaluation 2: Virucidal Activity Evaluation of Composition] (Preparation of virus solution) Human coronavirus OC43 (ATCC VR-1558) was infected and propagated in HCT-8 cells (ATCC CCL-244) in tissue culture flasks. The cell culture supernatant was purified by centrifugation and used to produce a virus with a viral infectivity titer of 10. 7.9 TCID 50 A virus solution of 1 / mL was prepared.

[0063] Virucidal Activity of the Composition 5 μL of the virus solution was added to a test tube containing 45 μL of the composition of each example, and immediately mixed for 15 seconds with a vortex mixer. The mixture was left to stand at room temperature, and the reaction mixture 3 minutes after the addition of the virus solution was designated as reaction mixture 1. 950 μL of SCDLP solution (manufactured by Nippon Pharmaceutical Co., Ltd.) was added to the mixture and mixed with a vortex mixer for 10 seconds (reaction mixture 2). The reaction was stopped by cooling reaction mixture 2 on ice. After cooling, the reaction mixture was serially diluted 10-fold with RPMI medium (manufactured by Sigma-Aldrich) supplemented with 2% heat-inactivated horse serum and 50 mg / L gentamicin, and then inoculated onto the HCT-8 cells. After culturing the mixture for 4 days in a 5% CO2 incubator at 33°C, infected cells were confirmed using the antibody staining method described below, and the virus infectivity titer (TCID 50 / mL) was calculated. Regarding virucidal activity, the theoretical value of the virus infectivity after the reaction was stopped was 10 5.59 TCID 50 / mL (initial viral infectivity titer 10 7.9 TCID 50 / mL was 1 / 10 at the time of reaction solution 1 and 1 / 20 at the time of reaction solution 2) 50 The -log values ​​(logarithmic reduction values) of the virus concentration (mg / mL) were taken and are shown in Tables 1 to 4. A higher "logarithmic reduction value" indicates higher virucidal activity.

[0064] (antibody staining method) After inoculation with virus and incubation for 4 days, the cells were fixed with methanol, washed with phosphate-buffered saline (PBS), and blocked with 0.5% bovine serum albumin (BSA) for 2 hours. After washing again with PBS, the cells were incubated with a primary antibody (Anti-Coronavirus Group Antigen Antibody, nucleoprotein of OC-43, clone 542-7D, Merck) specifically binding to coronavirus and a secondary antibody (HRP-conjugated goat anti-mouse IgG+IgM(H+L), Jackson Immuno Research) for 2 hours each. The virus was then stained with DEPDA coloring solution (2 mM 4-chloronaphthol, 2 mM N,N-diethyl-p-phenylenediamine sulfate, 0.01% hydrogen peroxide in 40 mM citrate buffer). The blue color developed was used as an indicator to determine whether the cells were infected with virus.

[0065] Examples 1 to 26 and Comparative Examples 1 to 10 (Preparation and Evaluation of Leave-On Finger Compositions) For Examples 1 to 26 and Comparative Examples 1 to 7 and 9 to 10, the components were blended in the amounts shown in Tables 1 to 4, mixed at room temperature, and then the pH was adjusted to the value shown in each table using a 1 mol / L aqueous sodium hydroxide solution as a pH adjuster to prepare a leave-on composition for external use on hands. The blending amounts shown in Tables 1 to 4 are the amount of active ingredient (% by mass) of each component. The obtained composition was used to carry out various evaluations using the methods described above. In Comparative Example 8, the evaluation was carried out using only water (purified water). The results are shown in Tables 1 to 4. Details of components *1 to *16 listed in Tables 1 to 4 are shown in Table 5. In the compositions of Examples 1 to 26 and Comparative Examples 1 to 7 and 9 to 10, the molar ratio of lactic acid [acid type / (acid type+dissociated type)] and the content of acid type lactic acid in the compositions are as shown in the table.

[0066] [Table 1]

[0067] [Table 2]

[0068] [Table 3]

[0069] [Table 4]

[0070] [Table 5]

[0071] *2-9, 11-16: The numbers in parentheses in the component names indicate the average number of moles of EO added. *10: Sucrose laurate contains approximately 80% by mass of monoesters and approximately 20% by mass of other polyesters.

[0072] Tables 1 to 4 show that the compositions of the present examples have higher bactericidal activity than the compositions of the comparative examples (evaluation result a in evaluation 1). Furthermore, the difference (ab) between evaluation results a and b for the compositions of the present examples is larger than that for the compositions of the comparative examples, indicating that the synergistic effect of containing component (A) and component (B) is also high. Similarly, it is clear that the composition of this example has a significantly improved virucidal activity compared to Comparative Example 8 (Evaluation 2).

[0073] The compositions of the present invention can be prepared by conventional methods according to the formulations shown in Table 6.

[0074] [Table 6]

[0075] The ingredients listed in Table 6 are as follows: Lactic acid: Lactic acid (active: 90%), manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Succinic acid: Succinic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Polyoxyethylene (6) lauryl ether: Emulgen 108, manufactured by Kao Corporation, HLB 12.1, average EO molar number 6 Polyoxyethylene (9) lauryl ether: Emulgen 109P manufactured by Kao Corporation, HLB 13.6, average EO molar number 9 Sodium hydroxide: NaOH (aqueous sodium hydroxide solution) 48% manufactured by Kanto Chemical Co., Inc. was used after adjusting to a 1 mol / L aqueous sodium hydroxide solution. [Industrial Applicability]

[0076] According to the present invention, a leave-on external skin preparation composition can be provided which has high bactericidal or virucidal activity, is less irritating to the skin, and is highly safe for the human body.< / ph>

Claims

1. (A) lactic acid or a salt thereof, and (B) a nonionic surfactant which is one or more selected from the group consisting of polyoxyethylene lauryl ether, sucrose laurate, and polyoxyethylene laurate, each having an average number of moles of oxyethylene groups added of 2 to 15, and which has an HLB of 8.0 to 17.0; wherein the content of component (A) is 0.02% by mass or more and 20.0% by mass or less, the content of 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, and the content of a bactericide is less than 0.01% by mass.

2. The leave-on skin topical composition according to claim 1, wherein the component (B) has a linear aliphatic group.

3. The leave-on skin topical composition according to claim 2, wherein the linear aliphatic group is a linear saturated aliphatic group.

4. The leave-on skin external preparation composition according to any one of claims 1 to 3, wherein the HLB of component (B) is 8.0 or more and 13.5 or less.

5. The leave-on skin topical preparation composition according to any one of claims 1 to 4, wherein component (B) is at least one selected from the group consisting of polyoxyethylene lauryl ether and sucrose laurate, each having an average number of moles of oxyethylene groups added of 2 to 15.

6. The leave-on skin topical composition according to any one of claims 1 to 5, wherein the ethanol content is less than 0.01% by mass.

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