Bactericidal or virucidal skin topical composition
A skin preparation composition using lactic acid, pyruvic acid, or urocanic acid, combined with an acid or salt of pKa 3.0-5.0, addresses skin irritation issues and maintains effective bactericidal or virucidal protection against various pathogens with minimal irritation.
Patent Information
- Application Number
- JP2021091367
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2020-06-05
- Filing Date
- 2021-05-31
- Publication Date
- 2025-11-04
- Estimated Expiration
- 2041-05-31
AI Technical Summary
Existing methods for preventing bacterial or viral infections through skin contact, such as using alcohol-based disinfectants, are not sustainable and can irritate sensitive skin, while low-pH compositions like citric acid and malic acid hand lotions cause skin irritation and have unclear virucidal properties.
A skin preparation composition containing lactic acid, pyruvic acid, or urocanic acid, along with an acid or salt having a pKa between 3.0 and 5.0, maintains a pH between 3.5 and 5.0, ensuring a sustained bactericidal or virucidal effect with reduced skin irritation.
The composition provides a long-lasting bactericidal or virucidal effect with minimal skin irritation, protecting against a wide range of bacteria and viruses, including enveloped and non-enveloped viruses, and is safe for frequent use.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a bactericidal or virucidal external skin preparation 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 ingredients are highly volatile, and the effect is not sufficiently sustained in terms of imparting a sterilizing or virucidal effect to hands. In addition, the alcohol component has limitations on its applicability to people with sensitive skin or low alcohol tolerance due to its skin irritation.
[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. [Prior art documents] [Patent documents]
[0006] [Patent Document 1] Special Publication No. 2008-523064 [Patent Document 2] U.S. Patent No. 6,034,133 Summary of the Invention [Problem to be solved by the invention]
[0007] 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 contains citric acid, malic acid, and a C1-6 alcohol as essential components, and there is no indication of the virucidal properties of hand lotions with other compositions.
[0008] An object of the present invention is to provide a bactericidal or virucidal external preparation composition for skin that has good bactericidal or virucidal effect and its durability, and is low in skin irritation and highly safe for the human body. [Means for solving the problem]
[0009] The present inventors have discovered that an external skin preparation composition containing one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and an acid or salt thereof having a predetermined pKa and within a predetermined pH range, can solve the above-mentioned problems. That is, the present invention provides the following [1] to [3]. [1] A bactericidal or virucidal external skin preparation 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) an acid other than component (A) or a salt thereof, the acid having a pKa of 3.0 or more and 5.0 or less, wherein the content of component (A) is 0.1% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% by mass or less, and the pH is 3.5 or more and 5.0 or less. [2] A method for protecting skin from bacteria or viruses, comprising the step of applying to the skin a composition containing (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) or a salt thereof having a pKa of 3.0 or more and 5.0 or less, wherein the content of component (A) is 0.1% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% by mass or less, and the pH is 3.5 or more and 5.0 or less. [3] A leave-on composition for external use on hands and fingers, comprising (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof, wherein the content of component (A) is 0.1% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% by mass or less, the pH is 3.5 or more and 5.0 or less, and the content of clay minerals is 3% by mass or less. [Effects of the Invention]
[0010] According to the present invention, it is possible to provide a bactericidal or virucidal external preparation composition for skin, which has a good bactericidal or virucidal effect and its durability, and which is low in skin irritation and highly safe for the human body, and a leave-on external preparation composition for hands and fingers, which has a bactericidal or virucidal effect. [Brief explanation of the drawings]
[0011] [Figure 1] 1 is a graph showing the change in pH on the fingers to which the external preparation compositions for fingers of Example 1, Comparative Example 1, Comparative Example 2, Comparative Example 3, and a control composition are applied. DETAILED DESCRIPTION OF THE INVENTION
[0012] [Bactericidal or virucidal skin topical composition] The bactericidal or virucidal 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) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; The content of component (A) is 0.1% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% 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 an external skin preparation composition that has excellent bactericidal or virucidal effect and its durability, and is less irritating to the skin and highly safe for the human body.
[0013] As used herein, the term "bactericidal or virucidal effect" encompasses concepts such as (1) a bactericidal or virucidal effect exerted against bacteria or viruses adhering to the skin surface after the composition of the present invention is applied to the skin surface, (2) a bactericidal or virucidal effect exerted against bacteria or viruses adhering to the skin by applying the composition of the present invention, (3) an effect of preparing the skin so that bacteria or viruses are not transmitted through the skin, (4) an effect of protecting the skin from bacteria or viruses and keeping it hygienic, (5) an effect of preventing the transmission of bacteria or viruses through the skin and contact infection, and (6) an effect of enhancing the skin's ability to defend against infections by bacteria or viruses. For example, the composition of the present invention can be used in product forms such as hand sanitizers and hand cream cosmetics.
[0014] As used herein, the term "sustained bactericidal or virucidal effect" refers to the ability of the composition of the present invention to maintain its bactericidal or virucidal effect even after a long period of time has passed since application of the composition to the skin. For example, it is preferable that the composition of the present invention maintains its bactericidal or virucidal effect even after preferably 30 minutes or more, more preferably 60 minutes or more, and even more preferably 120 minutes or more have passed since application of the composition to the skin. In the present invention, if the pH of the skin surface to which the composition is applied is maintained at a low pH, the bactericidal or virucidal effect of component (A), which will be described later, will be enhanced. More specifically, it is preferable that the ΔpH be within 0.45 120 minutes after application of the composition.
[0015] 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.
[0016] The bacteria or viruses against which the composition of the present invention exerts a bactericidal or virucidal effect are not particularly limited as long as they are inactivated or killed by contact with acid, and it is believed that, for example, 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 activity is evaluated using Escherichia coli, Enterococcus faecalis, and Serratia marcescens as examples, but this is because these are microorganisms that can be ethically attached to the skin, or the evaluation method of attaching them to human skin is established in official test methods or academic papers, etc., and the bacteria or viruses targeted by the present invention are not limited to these.
[0017] 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 the surface of human skin, for example, as supplied by 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 effects, but is also less irritating to the skin and highly safe for the human body. Regarding the above-mentioned bactericidal or virucidal effect, it is known that the lower the pH, the higher the bactericidal or virucidal effect in 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 exerts a stronger bactericidal or virucidal effect. 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 exerts a good bactericidal or virucidal effect against bacteria or viruses when the pH is 5.0 or less.
[0018] On the other hand, even when component (A) is used, there is a concern that compositions with a low pH range may cause skin irritation. Furthermore, after applying a composition containing component (A) to the skin, the pH of the skin surface increases over time, and the bactericidal or virucidal effect gradually decreases. This is because as the pH increases, the proportion of acidic component (A) on the skin surface also decreases. The inventors have discovered that by using predetermined amounts of component (A) and component (B), which is an acid or its salt having a predetermined pKa, it is possible to maintain the bactericidal or virucidal effect for a long period of time after application to the skin, even in a composition with low skin irritation and a relatively high pH of 3.5 or higher. Component (B) is a weak acid or its salt and has a buffering effect, so by using it in combination with component (A) in a composition, the increase in pH over time is suppressed even after application to the skin, and as a result, the proportion of the acid form of component (A), which is the main bactericidal or virucidal component, is maintained in a high range, which is thought to result in the bactericidal or virucidal effect being maintained for a long period of time.
[0019] The composition of the present invention is preferably a leave-on preparation. This is because the composition of the present invention can improve the bactericidal or virucidal effect against bacteria or viruses and the duration of its effect by leaving component (A), which is a bactericidal or virucidal component, on the skin surface. Therefore, it is preferable to use the composition of the present invention by leaving it on the skin surface after application by application or the like, without removing the composition by washing with water or the like. Furthermore, from the viewpoint of preventing contact infection by bacteria or viruses, it is more preferable to apply it to the skin surface, especially to the fingers.
[0020] <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 or virucidal component. Examples of salts of lactic acid, pyruvic acid, and urocanic acid include alkali metal salts of lactic acid or pyruvic acid, such as potassium salts and sodium salts; alkaline earth metal salts, such as calcium salts and magnesium salts; amine salts; ammonium salts, etc. Among these, from the viewpoints of improving the bactericidal or virucidal effect and its durability, 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 the bactericidal or virucidal effect and its duration, 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. Furthermore, from the viewpoint of improving the bactericidal or virucidal effect and its sustainability, 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.
[0021] The content of component (A) in the composition of the present invention is 0.1% by mass or more, preferably 0.3% by mass or more, more preferably 0.5% by mass or more, and even more preferably 0.8% by mass or more, from the viewpoint of improving the bactericidal or virucidal effect and its duration. Furthermore, from the viewpoint of suppressing skin irritation, it is 10% by mass or less, preferably 8.0% by mass or less, more preferably 6.0% by mass or less, even more preferably 5.0% by mass or less, still more preferably 3.0% by mass or less, and even more preferably 1.5% by mass or less. The content of component (A) in the composition of the present invention is 0.1% by mass or more and 10% by mass or less, preferably 0.3% by mass or more and 8.0% by mass or less, more preferably 0.3% by mass or more and 6.0% by mass or less, even 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 0.3% by mass or more and 1.5% by mass or less, and even more preferably 0.5% by mass or more and 1.5% 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.
[0022] The content of component (A) 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, even more preferably 0.2% by mass or more, and still more preferably 0.3% by mass or more, from the viewpoint of improving the bactericidal or virucidal effect and its duration. Also, from the viewpoint of suppressing skin irritation, it is preferably 7% by mass or less, more preferably 3.5% by mass or less, even more preferably 2.5% by mass or less, still more preferably 2% by mass or less, still more preferably 1.5% by mass or less, and still more preferably 1% by mass or less. The content of component (A) in the acid form in the composition of the present invention is preferably 0.01% by mass or more and 7% by mass or less, more preferably 0.1% by mass or more and 3.5% by mass or less, even more preferably 0.1% by mass or more and 2.5% by mass or less, still more preferably 0.1% by mass or more and 2% by mass or less, even more preferably 0.1% by mass or more and 1.5% by mass or less, still more preferably 0.1% by mass or more and 1% by mass or less, still more preferably 0.2% by mass or more and 1% by mass or less, and still more preferably 0.3% by mass or more and 1% by mass or less.
[0023] 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 the bactericidal or virucidal effect and its duration. 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.
[0024] In this specification, "component (A) present in acid form in the composition" means the component (A) that exists as lactic acid, pyruvic acid, and urocanic acid in the composition, and "component (A) present in dissociated form in the composition" means the component (A) that exists as lactate ions, pyruvic acid ions, and urocanic acid ions in the composition.
[0025] <Ingredient (B)> Component (B) used in the composition of the present invention is an acid other than component (A) or a salt thereof, having a pKa of 3.0 or more and 5.0 or less. The composition of the present invention contains components (A) and (B), which provides a buffering effect, and is thought to suppress an increase in pH on the skin surface over time, even after application of the composition, which has a relatively high pH of 3.5 or more. As a result, the decrease in the proportion of acid-form component (A) on the skin surface is also suppressed, and the bactericidal or virucidal effect is thought to be sustained for a long period of time. In this specification, pKa refers to the acid dissociation constant in an aqueous solution at 25° C. Furthermore, with regard to acids having multiple pKas, such as a first acid dissociation constant (PKa1) and a second acid dissociation constant (PKa2), any acid having a pKa of 3.0 or more and 5.0 or less is considered to be included in the acids defined as component (B).
[0026] From the viewpoint of improving the bactericidal or virucidal effect and its duration on the skin surface to which the composition is applied, and from the viewpoint of suppressing skin irritation, the pKa of the acid in component (B) is 3.0 or more, preferably 3.2 or more, more preferably 3.5 or more, even more preferably 3.7 or more, and still more preferably 4.0 or more. Furthermore, from the viewpoint of exerting a buffering effect when used in combination with component (A), the pKa is 5.0 or less, preferably 4.7 or less, and more preferably 4.5 or less. The pKa of the acid in component (B) is 3.0 or more and 5.0 or less, preferably 3.2 or more and 4.7 or less, more preferably 3.5 or more and 4.5 or less, even more preferably 3.7 or more and 4.5 or less, and still more preferably 4.0 or more and 4.5 or less. In the case of component (B) having multiple pKa values within the pKa range of 3.0 or more and 5.0 or less, the pKa value with the larger value is considered to contribute to maintaining the pH of the composition at 5.0 or less and improving the bactericidal or virucidal effect on the skin surface to which the composition is applied, as well as the duration of that effect.
[0027] The acid in component (B) may be either an organic acid or an inorganic acid as long as it has the above pKa, but from the viewpoint of suppressing skin irritation, an organic acid is preferred. The organic acid may be a monovalent acid or a polyvalent acid, but is preferably a polyvalent acid from the viewpoint of improving the durability of the bactericidal or virucidal effect on the skin surface to which the composition is applied. Preferred examples of organic acids include ascorbic acid and carboxylic acid compounds. These may be either low-molecular-weight compounds or high-molecular-weight compounds, but from the viewpoint of water solubility, they are preferably low-molecular-weight compounds having 8 or less carbon atoms, more preferably 6 or less carbon atoms.
[0028] Specific examples of acids in component (B) include ascorbic acid (first acid dissociation constant pKa1: 4.17, second acid dissociation constant pKa2: 11.6, molecular weight 176.1 g / mol); gluconic acid (acid dissociation constant pKa: 3.86, molecular weight 196 g / mol), citric acid (first acid dissociation constant pKa1: 3.09, second acid dissociation constant pKa2: 4.8, third acid dissociation constant pKa3: 6.41, molecular weight 192.1 g / mol (anhydride)), malic acid (first acid dissociation constant pKa1: 3.4, second acid dissociation constant pKa2: 5.1, molecular weight 134.1 g / mol), and tartaric acid (first acid dissociation constant pKa1: 2.82, second acid dissociation constant pKa2: 3.9 6, molecular weight 150.1 g / mol); polycarboxylic acids having no hydroxy groups such as fumaric acid (first acid dissociation constant pKa1: 3.02, second acid dissociation constant pKa2: 4.38, molecular weight 116.1 g / mol), succinic acid (first dissociation constant pKa1: 4.2, second dissociation constant pKa2: 5.6, molecular weight 118.1 g / mol) and adipic acid (first dissociation constant pKa1: 4.42, second dissociation constant pKa2: 5.42, molecular weight 146.1 g / mol); acidic polymers having a pKa within the above range such as polyacrylic acid; and the like, which can be used alone or in combination of two or more thereof. Among the above, the molecular weight of the acid in component (B) is preferably 50 g / mol or more, more preferably 80 g / mol or more, from the viewpoint of improving the durability of the bactericidal or virucidal effect. Also, from the viewpoint of improving the bactericidal or virucidal effect, it is preferably 300 g / mol or less, more preferably 150 g / mol or less. The molecular weight of the acid in component (B) is preferably 50 g / mol or more and 300 g / mol or less, more preferably 80 g / mol or more and 150 g / mol or less.
[0029] Examples of the acid salt in component (B) include alkali metal salts such as potassium salts and sodium salts of the above acids, alkaline earth metal salts such as calcium salts and magnesium salts, amine salts, ammonium salts, etc. Among these, from the viewpoint of improving the bactericidal or virucidal effect and its durability, one or more selected from the group consisting of alkali metal salts and alkaline earth metal salts of the above acids are preferred, and one or more selected from the group consisting of potassium salts, sodium salts, and calcium salts are more preferred.
[0030] From the viewpoint of improving the bactericidal or virucidal effect and its durability, component (B) is preferably one or more selected from the group consisting of ascorbic acid, hydroxycarboxylic acid, polycarboxylic acid having no hydroxy group, and salts thereof, more preferably polycarboxylic acid having no hydroxy group or salt thereof, even more preferably polycarboxylic acid having no hydroxy group, still more preferably one or more selected from the group consisting of succinic acid and adipic acid, and even more preferably succinic acid.
[0031] The content of component (B) in the composition of the present invention is 0.1% by mass or more, preferably 0.3% by mass or more, more preferably 0.5% by mass or more, and even more preferably 0.7% by mass or more, from the viewpoint of improving the bactericidal or virucidal effect and its duration. Furthermore, from the viewpoint of suppressing skin irritation, it is 10% by mass or less, preferably 7% by mass or less, even more preferably 5% by mass or less, and even more preferably 3% by mass or less. The content of component (B) in the composition of the present invention is 0.1% by mass or more and 10% by mass or less, preferably 0.3% by mass or more and 7% by mass or less, more preferably 0.5% by mass or more and 5% by mass or less, even more preferably 0.7% by mass or more and 5% by mass or less, and even more preferably 0.7% by mass or more and 3% by mass or less. In this specification, when component (B) contains a salt, the "content of component (B)" means the amount converted into the acid.
[0032] From the viewpoint of improving the bactericidal or virucidal effect and its duration, the total content of component (A) and component (B) in the composition of the present invention is preferably 0.2% by mass or more, more preferably 0.3% by mass or more, even more preferably 0.5% by mass or more, still more preferably 0.8% by mass or more, still more preferably 1% by mass or more, still more preferably 1.2% by mass or more, still more preferably 1.5% by mass or more, and still more preferably 1.7% by mass or more. From the viewpoint of suppressing skin irritation, the total content is preferably 15% by mass or less, more preferably 10% by mass or less, even more preferably 8% by mass or less, still more preferably 6% by mass or less, still more preferably 5% by mass or less, and still more preferably 3% 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 0.2% by mass or more and 15% by mass or less, more preferably 0.3% by mass or more and 10% by mass or less, even more preferably 0.5% by mass or more and 8% by mass or less, still more preferably 0.8% by mass or more and 6% by mass or less, even more preferably 1% by mass or more and 6% by mass or less, still more preferably 1.2% by mass or more and 6% by mass or less, still more preferably 1.5% by mass or more and 5% by mass or less, still more preferably 1.7% by mass or more and 5% by mass or less, and still more preferably 1.7% by mass or more and 3% by mass or less.
[0033] Furthermore, from the viewpoint of improving the durability of the bactericidal or virucidal effect, the mass ratio (B / A) of component (B) to component (A) in the composition of the present invention is preferably 0.1 or more, more preferably 0.2 or more, and even more preferably 0.5 or more. From the viewpoint of improving the bactericidal or virucidal effect, the mass ratio (B / A) is preferably 20 or less, more preferably 10 or less, even more preferably 8 or less, still more preferably 7 or less, still more preferably 6 or less, and even more preferably 5 or less. The mass ratio (B / A) in the composition of the present invention is preferably 0.1 or more and 20 or less, more preferably 0.2 or more and 10 or less, even more preferably 0.2 or more and 8 or less, still more preferably 0.2 or more and 7 or less, still more preferably 0.2 or more and 6 or less, still more preferably 0.2 or more and 5 or less, and even more preferably 0.5 or more and 5 or less.
[0034] 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, still 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, still more preferably 70% by mass or more and 99% by mass or less.
[0035] In order to improve the bactericidal or virucidal effect and its durability, it is preferable that the composition of the present invention limit the content of clay minerals used to adsorb and remove oil components, proteins, etc. Examples of clay minerals include silt, marine silt, tanakura clay, smectite clay minerals such as bentonite, montmorillonite, herculite, beidellite, nontonite, saponite, hectorite, lucentite, sauconite, and stevensite, kaolin clay minerals such as kaolin, nacrite, dickite, halloysite, and chrysotile, antigorite clay minerals such as antigorite, amesite, and cronsteadite, pyrophyllite clay minerals such as pyrophyllite and talc, mica clay minerals such as illite, glauconite, celadonite, sericite, mica, muscovite, chromium muscovite, and biotite, vermiculite clay minerals such as vermiculite, and chlorite clay minerals such as chlorite.
[0036] Here, limiting the content of clay minerals means that the content of clay minerals in the composition of the present invention is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably substantially no clay minerals are contained.
[0037] 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, and even more preferably 95% by mass or more, but is 100% by mass or less.
[0038] In addition to the above, the composition of the present invention may also contain other components, if necessary, such as an acid or a salt thereof other than component (A) and component (B), a surfactant, a thickener, a pH adjuster, an ultraviolet absorber, an antioxidant, a preservative, an antiperspirant, a fragrance, a moisturizer, etc. Among the above, it is preferable to include a surfactant in the composition of the present invention from the viewpoint of improving the stability of the composition, improving the shape retention of the composition, enabling the composition to remain on the skin surface better upon application, and further improving the bactericidal or virucidal effect and its duration. Examples of surfactants include nonionic surfactants, anionic surfactants, cationic surfactants (excluding quaternary ammonium salts), amphoteric surfactants (excluding alkyldiaminoethylglycine hydrochloride and alkylpolyaminoethylglycine), etc. Among these, from the viewpoint of further improving the bactericidal or virucidal effect and its durability, one or more surfactants selected from the group consisting of nonionic surfactants and anionic surfactants are preferred.
[0039] From the viewpoint of improving the bactericidal or virucidal effect, the nonionic surfactant is preferably one or more selected from the group consisting of alkyl glucoside, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyglycerin fatty acid ester, polyethylene glycol fatty acid ester, and polyoxyethylene alkyl ether. Furthermore, the average number of moles of ethyleneoxy groups added (hereinafter referred to as "average number of moles of EO added") in the polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyglycerin fatty acid ester, polyethylene glycol fatty acid ester, or polyoxyethylene alkyl ether is more preferably 3 to 20, even more preferably 3 to 15, even more preferably 5 to 9, and even more preferably 5 to 8. The average number of moles of EO added is a number average value. Among the above, polyoxyethylene alkyl ethers are more preferred as nonionic surfactants. From the viewpoint of improving the bactericidal or virucidal effect, polyoxyethylene alkyl ethers in which the alkyl groups constituting the polyoxyethylene alkyl ether are 8 to 20 are preferred, and the average number of EO moles added of the polyoxyethylene alkyl ether is more preferably 3 to 20, even more preferably 3 to 15, still more preferably 5 to 9, and even more preferably 5 to 8.
[0040] Furthermore, from the viewpoint of improving the bactericidal or virucidal effect, the nonionic surfactant preferably has an HLB value of 8 or more and 16 or less, more preferably 10 or more and 14 or less, and even more preferably 10 or more and 13 or less. HLB (Hydrophilic-Lipophilic Balance) indicates the molecular weight of the hydrophilic group portion of the total molecular weight of a surfactant, and for nonionic surfactants, it can be calculated using Griffin's equation. The HLB value of a mixed surfactant consisting of two or more nonionic surfactants is the arithmetic average of the HLB values of each nonionic surfactant based on their blending ratio, and is calculated as follows. Mixed HLB=Σ(HLBx×Wx) / ΣWx HLBx indicates the HLB value of nonionic surfactant X. Wx represents the mass (g) of the nonionic surfactant X having the value of HLBx.
[0041] As the anionic surfactant, from the viewpoint of improving the bactericidal or virucidal effect, one or more types selected from the group consisting of alkyl sulfate ester salts, alkyl phosphate ester salts, polyoxyethylene alkyl ether sulfate ester salts, and polyoxyethylene alkyl ether phosphate salts are preferred.
[0042] When a surfactant is used, the content of the surfactant in the composition of the present invention is 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 0.3% by mass or more, from the viewpoint of improving the bactericidal or virucidal effect and its durability, and is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and still more preferably 2% by mass or less, from the viewpoint of suppressing skin irritation. The specific range of the surfactant content in the composition of the present invention is preferably 0.01% by mass or more and 10% by mass or less, more preferably 0.05% by mass or more and 5% by mass or less, even more preferably 0.1% by mass or more and 3% by mass or less, and even more preferably 0.3% by mass or more and 2% by mass or less.
[0043] The composition of the present invention can be used as a bactericidal or virucidal composition even if it contains a small amount of ethanol, because it is a composition using component (A) as a bactericidal or virucidal component. 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, and even more preferably substantially 0% by mass.
[0044] The composition of the present invention, which uses component (A) as a bactericidal or virucidal component, can be used as a bactericidal or virucidal composition without or with only a small amount of a general-purpose bactericide such as quaternary ammonium salts (e.g., benzalkonium chloride, benzethonium chloride, etc.); amphoteric surfactant bactericides (e.g., alkyldiaminoethylglycine hydrochloride, alkylpolyaminoethylglycine, etc.); biguanides (e.g., chlorhexidine, chlorhexidine gluconate, etc.); sodium hypochlorite; lower alcohols other than ethanol (e.g., isopropanol); aldehydes (e.g., glutaral, phthalal, formalin, etc.); povidone-iodine; iodine tincture; phenol; cresol soap solution; peracetic acid; hydrogen peroxide; etc. When a general-purpose bactericide is added to the composition, it is preferable to use a quaternary ammonium salt (e.g., benzalkonium chloride, benzethonium chloride, etc.) in order to maintain the skin pH in a low range by component (A) and component (B), thereby enhancing the sustained bactericidal effect of the general-purpose bactericide. Furthermore, when a general-purpose disinfectant is blended, the blending amount is preferably 0.01% by mass or more, more preferably 0.03% by mass or more, and even more preferably 0.05% by mass or more, from the viewpoint of improving the bactericidal or virucidal effect and its durability. On the other hand, from the viewpoint of suppressing skin irritation, the blending amount 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 0.07% by mass or less, still more preferably 0.03% by mass or less, and most preferably substantially 0% by mass. In the present invention, an agent that is the above-mentioned general-purpose disinfectant and also functions as a surfactant is defined as a general-purpose disinfectant.
[0045] From the viewpoint of improving the feeling of use, the composition of the present invention preferably has a low polyol content. The polyol referred to here refers to a compound other than component (A) and component (B) that has two or more hydroxy groups in its molecule. From the viewpoint of improving the feeling of use, the polyol content 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, still more preferably 3% by mass or less, and even more preferably substantially 0% by mass.
[0046] Furthermore, the ratio of the total content of ethanol, isopropanol, and polyol to the content of water in the composition of the present invention, expressed as a mass ratio [(ethanol + isopropanol + polyol) / water], is 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 when used.
[0047] <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. Furthermore, from the viewpoint of improving the bactericidal or virucidal effect and its duration, the pH is 5.0 or lower, preferably 4.5 or lower. The specific pH range 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 pH is measured at 25° C., and can be measured by the method described in the Examples.
[0048] The form of the composition of the present invention is not particularly limited, and may be, for example, a solid, liquid, gel, or cream. From the viewpoint of ease of application to the skin, a gel or cream form is preferable. The composition may be in the form of an emulsion composition, and the emulsion composition may be either an oil-in-water emulsion composition or a water-in-oil emulsion composition.
[0049] As described above, the composition of the present invention is preferably used as a leave-on preparation, but the dosage form of the preparation is not particularly limited, and examples thereof include a stick preparation comprising a solid composition; a roll-on preparation or a spray preparation filled with a liquid composition; a preparation in which a liquid, gel, or cream composition is filled in a bottle, a tube, a dispenser-type container, or the like; and a sheet product impregnated with the composition.
[0050] The composition of the present invention may be in the form of a product, such as a lotion, gel, spray, or cream for use on hands or the body.
[0051] [Defense method] The present invention also provides a method for protecting skin from bacteria or viruses, comprising: (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; The present invention provides a method for treating a skin ulcer by applying to the skin a composition containing the above-mentioned components, wherein the content of component (A) is from 0.1 to 10% by mass, the content of component (B) is from 0.1 to 10% by mass, and the pH is from 3.5 to 5.0 (hereinafter, also simply referred to as the "method of the present invention"). According to the method of the present invention, the skin is protected from bacteria or viruses by the bactericidal or virucidal effect and its persistence, and the method is highly safe for the human body because it is less irritating to the skin.
[0052] The composition used in the method of the present invention is preferably the composition of the present invention described above, and its details and preferred ranges are the same as those of the composition. The bacteria or viruses to be protected against by the method of the present invention are also the same as those described above.
[0053] 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. The body part to which the composition is applied is not particularly limited, and it can be applied to any body part, such as the fingers, upper arms, lower legs, neck, trunk, etc. From the viewpoint of blocking the route of infection and transmission of bacteria and viruses through human-to-human and object-to-human contact, it is preferable to apply it to the hands and fingers, which are frequently in contact with public objects and one's own nose and mouth in daily life.
[0054] In this step, the amount of component (A) present in an acid form on the skin surface to which the composition is applied is determined based on the amount of component (A) present in an acid form on the skin surface to which the composition is applied, from the viewpoint of improving the bactericidal or virucidal effect and its duration, per 1 cm of the skin. 2 The amount of component (A) present in an acid form on the skin surface to which the composition is applied is preferably 0.2 μg or more, more preferably 1.5 μg or more, even more preferably 1.7 μg or more, even more preferably 1.8 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 preferably 0.2 μg or more, more preferably 1.5 μg or more, even more preferably 1.7 μg or more, even more preferably 1.8 μg or more, and even more preferably 2 μg or more, per 1 cm of skin. 2 Preferably, the amount is 0.2 μg or more and 200 μg or less, more preferably 1.5 μg or more and 200 μg or less, even more preferably 1.7 μg or more and 100 μg or less, still more preferably 1.8 μg or more and 50 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 has been 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 has been applied, and can be determined specifically by the method described in the Examples.
[0055] 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 on the skin surface to which the composition is applied [acid form / (acid form + dissociated form)] is preferably 0.15 or more, more preferably 0.17 or more, and even more preferably 0.18 or more, from the viewpoint of improving the bactericidal or virucidal effect and its duration. Furthermore, from the viewpoint of suppressing skin irritation, it is preferably 0.70 or less, more preferably 0.50 or less, and even more preferably 0.30 or less. The molar ratio [acid form / (acid form + dissociated form)] on the skin surface to which the composition is applied is preferably 0.15 or more and 0.70 or less, more preferably 0.17 or more and 0.50 or less, and even more preferably 0.18 or more and 0.30 or less. The molar ratio [acid type / (acid type+dissociated type)] takes into account both the component (A) derived from the composition and the component (A) naturally present on the skin surface at the time of application of the composition. The molar ratio can be determined specifically by the method described in the Examples.
[0056] From the viewpoint of suppressing skin irritation, the pH of the skin surface after application of the composition is preferably 3.50 or higher, more preferably 3.70 or higher, and even more preferably 3.90 or higher. Furthermore, from the viewpoint of improving the bactericidal or virucidal effect and its sustainability, the pH of the skin surface after application of the composition is preferably 4.60 or lower, more preferably 4.55 or lower, and even more preferably 4.50 or lower. The pH of the skin surface after application of the composition is preferably 3.50 or higher and 4.60 or lower, more preferably 3.70 or higher and 4.55 or lower, and even more preferably 3.90 or higher and 4.50 or lower. From the viewpoint of improving the durability of the bactericidal or virucidal effect, it is preferable that the pH of the skin surface remains within the above range even after 30 minutes or more, more preferably 60 minutes or more, have passed since application of the composition. The pH of the skin surface is a value measured at the environmental temperature to which the method of the present invention is applied, and specifically can be measured by the method described in the Examples.
[0057] 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 and the bactericidal or virucidal component (A) remains on the skin surface, it is possible to impart a bactericidal or virucidal effect and have that effect persist. The composition may be applied to the skin after washing the skin in advance with water, soap, body soap, hand soap, etc., or may be applied to unwashed skin. After washing, naturally occurring components such as lactic acid are washed away from the skin, and the skin has reduced bactericidal or virucidal activity against bacteria and viruses present in the environment. Therefore, it is more preferable to carry out the method of the present invention by applying the composition to the skin after washing.
[0058] [Leave-on external preparation for hands] The present invention also provides a leave-on external preparation for hands, comprising: (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; The content of component (A) is 0.1% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% by mass or less, and the pH is 3.5 or more and 5.0 or less, Provided is a leave-on composition for external use on hands and fingers, which has a clay mineral content of 3% by mass or less. The leave-on composition for external use on hands of the present invention has a high bactericidal or virucidal effect that lasts for a long time, and is also low in skin irritation, so is highly safe for the human body. The components (A) and (B) used in the leave-on external preparation for hands and fingers, and the clay minerals specified in the leave-on external preparation for hands and fingers, as well as their details and preferred ranges, are the same as those of the composition of the present invention described above.
[0059] From the viewpoint of providing a bactericidal or virucidal external preparation for hands that has a high and long-lasting bactericidal or virucidal effect, is less irritating to the skin, and is highly safe for the human body, the composition of the present invention preferably contains the following components (A) and (B), in which the content of component (A) is from 0.1 to 1.5% by mass, the content of component (B) is from 0.3 to 10% by mass, and the pH is from 3.5 to 5.0. (A) Lactic acid or its salts (B) an acid other than component (A) having a pKa of 3.5 or more and 4.5 or less, or a salt thereof
[0060] From the viewpoint of providing a leave-on composition for external use on hands that has a high and persistent bactericidal or virucidal effect, is less irritating to the skin, and is highly safe for the human body, the composition of the present invention preferably contains the following components (A) and (B), in which the content of component (A) is from 0.1% to 1.5% by mass, the content of component (B) is from 0.3% to 10% by mass, and the pH is from 3.5 to 5.0. (A) Lactic acid or its salts (B) an acid other than component (A) having a pKa of 3.5 or more and 4.5 or less, or a salt thereof
[0061] In addition to the above-described embodiments, the present invention also discloses the following embodiments. <1> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A bactericidal or virucidal external skin preparation composition having a pH of 3.5 or more and 5.0 or less at 25°C. <2> The content of component (A) in the topical skin preparation composition is preferably 0.3% by mass or more and 8.0% by mass or less, more preferably 0.3% by mass or more and 6.0% by mass or less, even 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 0.3% by mass or more and 1.5% by mass or less, and still more preferably 0.5% by mass or more and 1.5% by mass or less, <1> A bactericidal or virucidal external skin preparation composition. <3> The content of component (A) in an acid form in the skin external preparation composition is preferably 0.01% by mass or more and 7% by mass or less, more preferably 0.1% by mass or more and 3.5% by mass or less, even more preferably 0.1% by mass or more and 2.5% by mass or less, still more preferably 0.1% by mass or more and 2% by mass or less, still more preferably 0.1% by mass or more and 1.5% by mass or less, still more preferably 0.1% by mass or more and 1% by mass or less, still more preferably 0.2% by mass or more and 1% by mass or less, and still more preferably 0.3% by mass or more and 1% by mass or less, <1> or <2> A bactericidal or virucidal external skin preparation composition. <4> The pKa of the acid in component (B) is preferably 3.2 or more and 4.7 or less, more preferably 3.5 or more and 4.5 or less, even more preferably 3.7 or more and 4.5 or less, and still more preferably 4.0 or more and 4.5 or less. <1> ~ <3> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <5> The acid in component (B) is one or more selected from the group consisting of ascorbic acid, gluconic acid, citric acid, malic acid, tartaric acid, fumaric acid, succinic acid, adipic acid, and polyacrylic acid. <1> ~ <4> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <6> The molecular weight of the acid in component (B) is preferably 50 g / mol or more and 300 g / mol or less, more preferably 80 g / mol or more and 150 g / mol or less. <1> ~ <5> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <7> The content of component (B) in the skin external preparation composition is preferably 0.3% by mass or more and 7% by mass or less, more preferably 0.5% by mass or more and 5% by mass or less, even more preferably 0.7% by mass or more and 5% by mass or less, and even more preferably 0.7% by mass or more and 3% by mass or less. <1> ~ <6> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <8> The mass ratio (B / A) of component (B) to component (A) in the topical skin preparation composition is preferably 0.1 or more and 20 or less, more preferably 0.2 or more and 10 or less, even more preferably 0.2 or more and 8 or less, still more preferably 0.2 or more and 7 or less, still more preferably 0.2 or more and 6 or less, still more preferably 0.2 or more and 5 or less, and still more preferably 0.5 or more and 5 or less. <1> ~ <7> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <9> The skin external preparation composition further contains water, and the content of water in the composition 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 still more preferably 70% by mass or more and 99% by mass or less. <1> ~ <8> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <10> The content of clay minerals in the topical skin preparation composition is preferably 3% by mass or less, more preferably 1% by mass or less, and even more preferably substantially free of clay minerals. <1> ~ <9> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <11> The content of the general-purpose bactericide in the topical skin preparation 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 0.07% by mass or less, still more preferably 0.03% by mass or less, and is essentially 0% by mass. <1> ~ <10> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above.
[0062] <12> The pH of the topical skin preparation composition at 25°C is preferably 3.7 or more and 4.5 or less. <1> ~ <11> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <13> 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. <1> ~ <12> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <14> Furthermore, the composition contains at least one surfactant selected from the group consisting of a nonionic surfactant, an anionic surfactant, a cationic surfactant (excluding quaternary ammonium salts), and an amphoteric surfactant (excluding alkyldiaminoethylglycine hydrochloride and alkylpolyaminoethylglycine). <1> ~ <13> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <15> The surfactant is at least one selected from the group consisting of nonionic surfactants, anionic surfactants, cationic surfactants (excluding quaternary ammonium salts), and amphoteric surfactants (excluding alkyldiaminoethylglycine hydrochloride and alkylpolyaminoethylglycine), preferably at least one selected from the group consisting of nonionic surfactants and anionic surfactants, more preferably a nonionic surfactant. <14> A bactericidal or virucidal external skin preparation composition. <16> the nonionic surfactant is at least one selected from the group consisting of alkyl glucoside, sucrose fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyglycerin fatty acid ester, polyethylene glycol fatty acid ester, and polyoxyethylene alkyl ether, preferably polyoxyethylene lauryl ether, more preferably polyoxyethylene alkyl ether having 8 to 20 alkyl groups constituting the polyoxyethylene alkyl ether; <15> A bactericidal or virucidal external skin preparation composition. <17> the average number of moles of ethyleneoxy groups added in the polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyglycerin fatty acid ester, polyethylene glycol fatty acid ester, or polyoxyethylene alkyl ether is 3 or more and 20 or less, preferably 3 or more and 15 or less, more preferably 5 or more and 9 or less, and even more preferably 5 or more and 8 or less; <16> A bactericidal or virucidal external skin preparation composition. <18> The nonionic surfactant has an HLB value of 8 or more and 16 or less, preferably 10 or more and 14 or less, and more preferably 10 or more and 13 or less. <15> ~ <17> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <19> The anionic surfactant is at least one selected from the group consisting of alkyl sulfate ester salts, alkyl phosphate ester salts, polyoxyethylene alkyl ether sulfate ester salts, and polyoxyethylene alkyl ether phosphate salts. <15> ~ <18> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <20> The content of the surfactant in the topical skin preparation composition is preferably 0.01% by mass or more and 10% by mass or less, more preferably 0.05% by mass or more and 5% by mass or less, even more preferably 0.1% by mass or more and 3% by mass or less, and even more preferably 0.3% by mass or more and 2% by mass or less. <14> ~ <19> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <21> The content of ethanol in the external skin preparation 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, and even more preferably substantially 0% by mass. <1> ~ <20> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <22> The content of polyol in the topical skin preparation composition is preferably 20% 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, and even more preferably substantially 0% by mass. <1> ~ <21> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <23> the ratio of the total content of ethanol, isopropanol, and polyol to the content of water in the topical skin preparation composition, expressed as a mass ratio [(ethanol + isopropanol + polyol) / water], is preferably 2 or less, more preferably 1 or less, even more preferably 0.5 or less, and still more preferably 0.1 or less; <1> ~ <22> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <24> It is a leave-on formulation, <1> ~ <23> 1. A bactericidal or virucidal topical skin preparation composition according to any one of the above. <25> A method for protecting the skin from bacteria or viruses, comprising: (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A method comprising the step of applying a composition having a pH of 3.5 or more and 5.0 or less at 25°C to the skin, preferably the fingers. <26> The content of component (A) in the composition is preferably 0.3% by mass or more and 8.0% by mass or less, more preferably 0.3% by mass or more and 6.0% by mass or less, even 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 0.3% by mass or more and 1.5% by mass or less, and still more preferably 0.5% by mass or more and 1.5% by mass or less, <25> How to do it. <27> 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. <25> or <26> How to do it. <28> The molecular weight of the acid in component (B) is preferably 50 g / mol or more and 300 g / mol or less, more preferably 80 g / mol or more and 150 g / mol or less. <25> ~ <27> Either one of the following methods. <29> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A leave-on composition for external use on hands and fingers, having a pH of 3.5 or more and 5.0 or less at 25°C. <30> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A skin external preparation composition for inhibiting bacterial or viral transmission, having a pH of 3.5 or more and 5.0 or less at 25°C. <31> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A skin external preparation composition for protecting against bacteria or viruses, having a pH of 3.5 or more and 5.0 or less at 25°C. <32> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A skin external preparation composition for preventing the spread of bacteria or viruses and contact infection, having a pH of 3.5 or more and 5.0 or less at 25°C. <33> (A) one or more acids or salts thereof selected from the group consisting of lactic acid, pyruvic acid, and urocanic acid, and (B) an acid other than component (A) having a pKa of 3.0 or more and 5.0 or less, or a salt thereof; Contains The content of component (A) is 0.1% by mass or more and 10% by mass or less, The content of component (B) is 0.1% by mass or more and 10% by mass or less, A skin external preparation composition for protecting hands and fingers, having a pH of 3.5 or more and 5.0 or less at 25°C. <34> It is used to protect hands from bacteria or viruses. <33> The skin external preparation composition described in 1. [Example]
[0063] 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.
[0064] (pH) The pH of the composition was measured at 25° C. using a 6367-10D electrode (manufactured by Horiba, Ltd.). The pH of the skin surface (palm) was measured using a Skin-pH-Meter PH905 electrode (manufactured by Courage+Khazaka).
[0065] (Mole ratio of component (A) [acid type / (acid type + dissociated type)]) The molar ratio of component (A) in the composition and on the skin surface after application of the composition was calculated using the following formula. The acid form is designated as "HA" and the dissociated form as "A - " 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 of the acid form [acid form / (acid form + dissociated form)] 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)] are added together to obtain the molar ratio of component (A) [acid form / (acid form + dissociated form)] when multiple types of component (A) are used.
[0066] (Preparation of bacterial solution) For the evaluation of bactericidal activity, bacterial suspensions of Escherichia coli, Enterococcus faecalis, or Serratia marcescens prepared by the following method were used. The Escherichia coli strain used was NBRC3301, the Enterococcus strain used was NBRC3181, and the Serratia marcescens strain used was NBRC12648. These bacteria were cultured in LB liquid medium, and the bacterial cells were collected by centrifugation. Then, the OD 600 was adjusted to be 10.
[0067] (Bactericidal evaluation 1: Bactericidal activity against Escherichia coli and enterococci) The subjects' hands were washed with "Biore u Rg" (manufactured by Kao Corporation), then rinsed with tap water for 30 seconds and then with purified water for 10 seconds. After waiting for 1 to 5 minutes, a fixed amount (3 μL / 3 cm) of the prepared compositions of Examples 1 to 11 and Comparative Examples 1 to 4 was applied to the palms of the hands. 2 ), and then left to dry for 3 minutes. At this time, the pH of the skin surface at the site where the composition was applied was measured by the above-mentioned method, and the molar ratio of lactic acid to the total of lactic acid and lactate ions [lactic acid / (lactic acid + lactate ions)] on the skin surface after application of the composition was calculated from this pH value using the above-mentioned calculation formula. Next, a fixed amount (3 μL / 3 cm ) of the Escherichia coli or enterococcus bacterial solution prepared by the above method was applied to the area of the palm where the composition had been applied. 2 After leaving it to stand for 3 minutes, the applied bacterial solution was collected using two swabs, and the number of surviving bacteria was measured using an incubation reader "HiTS" (manufactured by Synix Co., Ltd.) according to the method described below, to confirm the reduction in the number of bacteria (number of surviving bacteria / initial number of live bacteria). [Measurement of reduction in bacterial count] The collected bacterial solution was cultured at 37°C in an incubation reader "HiTS," and the absorbance (turbidity) at a wavelength of 600 nm was measured over time to create a growth curve of the viable bacterial count in the bacterial solution. At the same time, a bacterial solution with a known viable bacterial count was serially diluted, and similarly cultured and a growth curve was created, creating a calibration curve of the time it took to reach a certain turbidity versus the viable bacterial count. From this calibration curve, the number of viable bacteria in the collected bacterial solution was estimated, and the reduction in the bacterial count was confirmed. The degree of reduction in the number of bacteria was calculated as the -log value of the reduction in the number of bacteria, and is shown in Table 1. The higher the "-log (reduction in the number of bacteria)" value for Escherichia coli or enterococcus, the higher the bactericidal activity.
[0068] (Bactericidal evaluation 2: Bactericidal activity against Serratia marcescens) [Bactericidal activity (log reduction value) 5 minutes and 30 minutes after application of the composition] The inner forearm of each subject was washed with "Biore u Rg" (manufactured by Kao Corporation), and then rinsed with tap water for 30 seconds and purified water for 10 seconds in sequence. After waiting for 1 to 5 minutes, a fixed amount (2 μL / cm ) of the compositions of Examples 2 and 12 and Comparative Examples 1 and 5 was applied to the skin surface of the inner forearm. 2 ), and then left to dry for 5 or 30 minutes. At this time, the pH of the skin surface at the site where the composition was applied was measured by the above-mentioned method, and the molar ratio of lactic acid to the total of lactic acid and lactate ions [lactic acid / (lactic acid + lactate ions)] on the skin surface after application of the composition was calculated from this pH value using the above-mentioned formula. Next, a fixed amount (1 μL / cm ) of the Serratia bacteria solution prepared by the above method was applied to the area of the palm where the composition had been applied. 2 After leaving it to stand for 3 minutes, the applied bacterial solution was collected using two swabs, and the number of surviving bacteria was measured using an incubation reader "HiTS" (manufactured by Synix Co., Ltd.) in the same manner as above, to confirm the reduction in the number of bacteria (number of surviving bacteria / initial number of live bacteria). The degree of reduction in the number of bacteria (logarithmic reduction value) was calculated as the -log value of the reduction in the number of bacteria, and is shown in Table 1. The larger this value, the higher the bactericidal activity.
[0069] Examples 1 to 12 and Comparative Examples 1 to 5 (Preparation and Evaluation of Compositions for External Use on Hands) The components shown in Table 1 were blended in the amounts shown and mixed at room temperature. The pH was then adjusted to 4.0 using a 1 mol / L aqueous hydrochloric acid solution and / or a 1 mol / L aqueous sodium hydroxide solution as a pH adjuster, except for Comparative Example 1, to prepare compositions for external use on hands. The blending amounts shown in the table are the active ingredient amounts (% by mass) of each component, except for sodium dihydrogen phosphate. For sodium dihydrogen phosphate, the blending amount in terms of phosphoric acid is shown in Table 1. The pKa values shown in the table are the pKa values of the acid in component (B). The resulting composition was subjected to various evaluations using the methods described above, and the results are shown in Table 1.
[0070] [Table 1]
[0071] The ingredients listed in Table 1 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. Ascorbic acid: Ascorbic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Malic acid: Malic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Citric acid: Citric acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Adipic acid: Adipic acid manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Sodium dihydrogen phosphate: Anhydrous sodium dihydrogen phosphate, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Polyoxyethylene (average EO molar addition number 6) lauryl ether: Emulgen 108, manufactured by Kao Corporation, HLB 12.1 Polyoxyethylene (average EO mole number 9) lauryl ether: Emulgen 109P, manufactured by Kao Corporation, HLB 13.6 Hydrochloric acid solution: Hydrochloric acid (1 mol / L) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Aqueous sodium hydroxide solution: 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. Benzalkonium chloride: Benzalkonium chloride aqueous solution, manufactured by Tokyo Chemical Industry Co., Ltd.
[0072] Table 1 shows that the composition of this example has a higher antibacterial effect on skin than the composition of the comparative example. This is thought to be because the pH of the skin surface is maintained in the range of approximately 4.6 or less, increasing the proportion of the acidic component (A), which is the main antibacterial component, present on the skin surface. Furthermore, a comparison between Comparative Example 1 and Comparative Example 5 shows that the inclusion of benzalkonium chloride does not substantially increase the bactericidal effect, whereas a comparison between Example 2 and Example 12 shows that the inclusion of benzalkonium chloride in the composition of the present invention significantly increases the bactericidal effect. This is believed to be due to the following reasons. A composition containing benzalkonium chloride and adjusted to pH 4.0 with hydrochloric acid (Comparative Example 5) had the same bactericidal effect as pure water. This is because the composition of Comparative Example 5 does not have the ability to buffer the skin pH, and after application, the skin pH rises, causing the skin surface charge to shift to a negative direction, which makes the cationic benzalkonium chloride more likely to be adsorbed onto the skin, thereby suppressing the bactericidal effect of benzalkonium chloride. In the composition of the present invention containing benzalkonium chloride (Example 12), the buffering ability of components (A) and (B) maintains the skin pH at around pH 4, preventing the skin surface charge from becoming negative, thereby suppressing the adsorption of benzalkonium chloride to the skin and allowing the benzalkonium chloride to exert its bactericidal effect. As a result, in addition to the bactericidal effect of components (A) and (B), the inclusion of benzalkonium chloride enhances the bactericidal effect of the composition of the present invention.
[0073] (Low pH sustained effect) The subjects' hands were washed with "Biore u Rg" (manufactured by Kao Corporation), then rinsed with tap water for 30 seconds and then with purified water for 10 seconds. After waiting for 3 minutes, a fixed amount (3 μL / 3 cm) of the composition for evaluation was applied to the palm of the hand. 2 After a certain period of time had passed, the pH of the skin surface at the site where the composition had been applied was measured by the method described above. The compositions of Example 1, Comparative Example 2, and Comparative Example 3 were used for evaluation, and an aqueous hydrochloric acid solution (pH 1.5) was used as a control composition for external use on hands. The change in pH on the fingers after application of the composition is shown in the graph in Figure 1.
[0074] The following can be seen from Figure 1. The compositions of Example 1, Comparative Example 2 and Comparative Example 3 all have a pH of 4.0, but the behavior of the pH on the fingers to which the compositions are applied is different. It can be seen that the initial pH of the fingers to which the composition of Example 1 was applied was low, and the pH remained in a relatively low range even after a long period of time. In contrast, when the composition of Comparative Example 3, which had the same content of component (A) as in Example 1 but did not contain component (B), was used, the initial pH was lower than when Comparative Example 1 (deionized water) and Comparative Example 2 (deionized water adjusted to pH 4.0) were used, but the pH increased over time. When a hydrochloric acid solution with a pH of 1.5 was used, the initial pH also decreased to the same extent as that of the composition of Example 1, but the pH increased significantly over time.
[0075] The compositions of the present invention can be prepared by conventional methods according to the formulations shown in Table 2.
[0076] [Table 2]
[0077] The ingredients listed in Table 2 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 (average EO mole number 6) lauryl ether: Emulgen 108, manufactured by Kao Corporation, HLB 12.1 Polyoxyethylene (average EO mole number 9) lauryl ether: Emulgen 109P, manufactured by Kao Corporation, HLB 13.6 Sodium hydroxide: NaOH (aqueous sodium hydroxide solution) 48% manufactured by Kanto Chemical Co., Inc. was used after adjusting to a sodium hydroxide solution of 1 mol / L. [Industrial Applicability]
[0078] According to the present invention, it is possible to provide a bactericidal or virucidal external skin preparation composition which has a good bactericidal or virucidal effect and its durability, and which is less irritating to the skin and highly safe for the human body.< / ph>
Claims
1. (A) lactic acid, and (B) one or more selected from the group consisting of succinic acid, ascorbic acid, malic acid, citric acid, adipic acid, and salts thereof; The content of component (A) is 0.3% by mass or more and 10% by mass or less, the content of component (B) is 0.1% by mass or more and 10% by mass or less, and the pH is 3.5 or more and 5.0 or less, The content of the general-purpose fungicide is 0.07% by mass or less, A bactericidal or virucidal external skin preparation composition having an ethanol content of 30% by mass or less.
2. 2. The external skin preparation composition according to claim 1, wherein the mass ratio (B / A) of component (B) to component (A) in the composition is 0.1 or more and 20 or less.
3. The skin external preparation composition according to claim 1 or 2, further comprising 0.01% by mass to 10% by mass of a surfactant.
4. The skin external preparation composition according to any one of claims 1 to 3, wherein the content of polyol in the composition is 20% by mass or less.
5. A topical skin composition described in any one of claims 1 to 4, wherein the topical skin composition further contains water, and the water content in the composition is 70% by mass or more and 99% by mass or less.
6. 6. The topical skin preparation composition according to claim 5, wherein when the composition contains ethanol, isopropanol, and / or polyol, the ratio of the total content of ethanol, isopropanol, and polyol to the content of water in the composition is 2 or less in mass ratio [(ethanol + isopropanol + polyol) / water].
7. The external skin preparation composition according to any one of claims 1 to 6, which is a leave-on preparation.
Citation Information
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