Agent for improving resident flora balance of skin and / or mucous membrane, method for improving resident flora balance of skin and / or mucous membrane, and external composition for delicate region

Abstract

Provided are: an agent for improving the resident flora balance of skin and / or a mucous membrane, the agent containing at least one component selected from the group consisting of component (A) and component (B); and a method for improving the resident flora balance by applying, to the skin and / or a mucous membrane, a composition containing at least one component selected from the group consisting of component (A) and component (B).　(A) At least one selected from the group consisting of hyaluronic acid, derivatives of hyaluronic acid, and salts thereof (B) At least one selected from the group consisting of nonionic surfactants and amino acid-based surfactants

Description

Agent for improving the balance of the resident flora of the skin and / or mucosa, method for improving the balance of the resident flora of the skin and / or mucosa, and external composition for delicate sites

[0001] The present invention relates to an agent for improving the balance of the resident flora of the skin and / or mucosa, a method for improving the balance of the resident flora of the skin and / or mucosa, and an external composition for delicate sites.

[0002] A variety of microorganisms called resident bacteria inhabit the human skin and mucosa, and play an important role in maintaining the health of the skin and mucosa. For example, Lactobacillus, also known as Dederlein's bacillus, is known as a major resident bacterium in the vagina, which is a delicate site. Lactobacillus is a Gram-positive facultative anaerobic non-spore-forming bacillus, which decomposes sugar to produce lactic acid, keeping the vagina acidic (about pH 3.5 to 4.5), preventing the invasion and abnormal growth of pathogenic bacteria. In addition, Lactobacillus is known to produce defense factors such as protein compounds with excellent bactericidal properties (see Non-Patent Document 1).

[0003] It is known that various problems occur when the balance of the resident flora of the skin and mucosa is disrupted. For example, when the balance of the resident flora in the vagina, which is a delicate site, is disrupted and Lactobacillus is not dominant (dysbiosis), the risk of developing bacterial vaginosis (BV) and other diseases caused by the growth of harmful bacteria such as Gardnerella increases (Non-Patent Document 1). The disruption of the balance of the resident flora in the vagina is also known to be involved in a variety of diseases such as sexually transmitted infections, premature birth, premature rupture of membranes, chorioamnionitis, fallopian tube obstruction, salpingitis, endometriosis, chronic endometritis, repeated implantation failure, implantation disorder, infertility, etc. (see Non-Patent Document 1). In addition, for example, it is also known that when the balance of the resident flora at a delicate site is disrupted, the risk of developing contact dermatitis (rash) caused by the growth of Staphylococcus increases (Patent Document 1).

[0004] Japanese Patent Publication No. 2018-88843

[0005] Latest findings on vaginal and uterine flora involved in the origin of life, Yoko Nagai, Yoshiyuki Sakuraba, Bio Clinica 36(2), 2021(139), pp. 47-52.

[0006] The present invention has been made in view of the above circumstances, and provides an agent for improving the balance of the normal flora of the skin and / or mucous membranes.

[0007] Furthermore, the present invention has been made in view of the above circumstances, and provides a topical composition for use on delicate areas.

[0008] In view of the above circumstances, the inventors conducted extensive research and, as a result, discovered a specific component that has the effect of improving the balance of the normal flora of the skin and / or mucous membranes, leading to the present invention.

[0009] In other words, the present invention provides the following [1] to

[14] : [1] A skin and / or mucous membrane microbiome balance improving agent containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, derivatives of hyaluronic acid, and salts thereof; (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants. [2] The skin and / or mucous membrane balance improving agent according to [1], wherein the skin and / or mucous membrane is the skin and / or mucous membrane of a delicate area. [3] The skin and / or mucous membrane balance improving agent according to [1] or [2], wherein the skin and / or mucous membrane is the skin and / or mucous membrane of a delicate area. [4] The skin and / or mucous membrane balance improving agent according to [3], wherein the harmful bacteria are of the genus Gardnerella. [5] The skin and / or mucous membrane balance improving agent according to [1] or [2], wherein the skin and / or mucous membrane balance improves the balance of the skin and / or mucous membrane by increasing the ratio of beneficial bacteria. [6] The resident microbiota balance improving agent according to [5], wherein the beneficial bacteria are of the Lactobacillus genus. [7] The resident microbiota balance improving agent according to any one of [1] to [6], wherein the pH is 4.0 to 6.0. [8] The resident microbiota balance improving agent according to any one of [1] to [7], wherein component (A) is one or more selected from the group consisting of fermented hyaluronic acid, high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, and salts thereof. [9] A method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of the following components (A) and (B) to the skin and / or mucous membranes. (A) One or more selected from the group consisting of hyaluronic acid, derivatives of hyaluronic acid, and salts thereof. (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

[10] A topical composition for delicate areas containing one or more selected from the group consisting of the following components (A) and (B). (A) One or more selected from the group consisting of hyaluronic acid, derivatives of hyaluronic acid, and salts thereof (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants

[11] The topical composition for delicate areas according to

[10] , for cleansing the skin and / or mucous membranes.

[12] A topical composition for delicate areas according to

[10] or

[11] that is substantially free of preservatives.

[13] A method for maintaining the pH balance of skin and / or mucous membranes by applying a composition containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

[14] A pH balance maintenance agent for skin and / or mucous membranes containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

[0010] Furthermore, the present invention provides the following

[15] to

[30] :

[15] A method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof to the skin and / or mucous membranes.

[16] A method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants to the skin and / or mucous membranes.

[17] A method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of (A) hyaluronic acid, hyaluronic acid derivatives, and salts thereof, and (B) one or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants to the skin and / or mucous membranes.

[18] A method for preventing or treating symptoms caused by an imbalance in the resident microbiota by applying a composition containing one or more selected from the group consisting of the following components (A) and (B) to the skin and / or mucous membranes.

[19] A method for preventing or treating symptoms caused by an imbalance in the resident microbiota by applying a composition containing (A) one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof, and (B) one or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

[20] A method for preventing or treating symptoms caused by an imbalance in the resident microbiota by applying a composition containing (A) one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof, to the skin and / or mucous membranes.

[21] A method for preventing or treating symptoms caused by an imbalance in the resident microbiota by applying a composition containing (A) one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof, and (B) one or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants, to the skin and / or mucous membranes.

[22] The method according to any one of

[15] to

[21] , wherein the skin and / or mucous membrane is skin and / or mucous membrane in a delicate area.

[23] The method according to any one of

[15] to

[22] , wherein the harmful bacteria improve the balance of the resident microbiota by reducing harmful bacteria.

[24] The method according to

[23] , wherein the harmful bacteria are of the genus Gardnerella.

[25] The method according to any one of

[15] to

[22] , wherein the proportion of beneficial bacteria improves the balance of the resident microbiota.

[26] The method according to

[25] , wherein the beneficial bacteria are of the genus Lactobacillus.

[27] The method according to any one of

[15] to

[26] , wherein the pH of the composition is 4.0 to 6.0.

[28] The method according to any one of

[15] to

[27] , wherein the (A) component is one or more selected from the group consisting of fermented hyaluronic acid, high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, and salts thereof.

[29] The method according to any one of

[15] to

[28] , wherein the composition is substantially free of preservatives.

[30] A method for preventing or treating bacterial vaginosis by applying a composition containing one or more selected from the group consisting of the following components (A) and (B) to the skin and / or mucous membranes: (A) One or more selected from the group consisting of hyaluronic acid, derivatives of hyaluronic acid, and salts thereof; (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

[0011] According to the present invention, the balance of the commensal microbiota in the skin and / or mucous membranes can be improved.

[0012] According to the present invention, by improving the balance of the resident microbiota on the skin and / or mucous membranes, it is possible to guide the skin and mucous membranes in delicate areas, for example, back to a healthy state.

[0013] This figure shows the results of Test Example 1-1. This figure shows the results of Test Example 1-2. This figure shows the results of Test Example 1-3. This figure shows the results of Test Example 2-1. This figure shows the results of Test Example 2-2. This figure shows the results of Test Example 2-3. This figure shows the results of Test Example 2-4. This figure shows the results of Test Example 3. This figure shows the results of Test Example 5. This figure shows the results of Test Example 5. This figure shows the results of Test Example 5.

[0014] Embodiments of the present invention will be described in detail below. However, the present invention is not limited to the following embodiments.

[0015] In this specification, when expressed as "X to Y" (where X and Y are any numbers), unless otherwise specified, it includes the meaning of "greater than or equal to X and less than or equal to Y," as well as "preferably greater than X" or "preferably less than Y." Also, in this specification, "α or / and β" (where α and β are any components or elements) means one of three combinations: "α only," "β only," or "both α and β," unless otherwise specified. Furthermore, in this specification, for numerical ranges described in steps, the upper or lower limit of one step in the numerical range can be arbitrarily combined with the upper or lower limit of another step in the numerical range. In addition, in numerical ranges described in this specification, the upper or lower limit of that range can be replaced with the values ​​shown in the examples or formulation examples.

[0016] <Microbial flora balance improving agent and topical composition for delicate areas> A microbial flora balance improving agent for skin and / or mucous membranes according to one embodiment of the present invention (hereinafter sometimes referred to as "this microbial flora balance improving agent") contains one or more selected from the group consisting of component (A) and component (B). Furthermore, a topical composition for delicate areas according to one embodiment of the present invention (hereinafter sometimes referred to as "this topical composition for delicate areas") contains one or more selected from the group consisting of component (A) and component (B). (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants That is, this microbial flora balance improving agent contains one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, salts thereof, nonionic surfactants, and amino acid-based surfactants.

[0017] This resident microbiota balance improving agent or this topical composition for delicate areas (hereinafter, "this resident microbiota balance improving agent or this topical composition for delicate areas" may be abbreviated as "this resident microbiota balance improving agent, etc.") can improve the balance of the resident microbiota of the skin and mucous membranes, and can, for example, lead the skin and mucous membranes of delicate areas to a healthy state. Specifically, this resident microbiota balance improving agent, etc. can, for example, prevent or treat symptoms caused by an imbalance in the resident microbiota.

[0018] Let's explain using bacterial vaginosis as an example. As mentioned above, Lactobacillus species, which are major commensal bacteria in the vagina, maintain an acidic environment in the vagina through their lactic acid production, preventing the invasion and abnormal proliferation of pathogenic bacteria. Bacterial vaginosis is known to develop when the balance of the vaginal microbiota, which is dominated by Lactobacillus species, is disrupted, leading to the proliferation of Gardnerella species. This commensal microbiota balance improving agent contains one or more components selected from the group consisting of components (A) and (B), thereby reducing Gardnerella species in the vaginal microbiota and improving the balance of the vaginal microbiota, making it useful in preventing or treating bacterial vaginosis. For example, a preferred embodiment of this commensal microbiota balance improving agent is useful in preventing or treating bacterial vaginosis by suppressing the growth of Gardnerella species while not suppressing the growth of Lactobacillus species, thereby improving the balance of the vaginal microbiota.

[0019] Specifically, in diseases involving an imbalance in the vaginal flora, such as bacterial vaginosis, lactic acid production decreases, while amines and ammonia, metabolites of other bacteria, increase, leading to unpleasant odors such as amine odor (also known as fishy odor). This raises concerns about a decline in women's quality of life (QOL). This resident flora balance improving agent is useful in that it can prevent or treat these problems.

[0020] Furthermore, in diseases involving an imbalance in the vaginal flora, such as bacterial vaginosis, it is known that symptoms such as rashes, irritation, and gray vaginal discharge may occur in delicate areas such as the vulva. This resident flora balance improving agent is useful in that it can prevent or treat these symptoms.

[0021] Furthermore, it is known that excessive cleansing of the skin and mucous membranes of delicate areas is highly likely to disrupt the balance of the normal flora. Using this normal flora balance improving agent for cleansing purposes is extremely useful because it can cleanse delicate areas while improving the balance of the normal flora. In particular, cleansing the vaginal mucosa is a concern as it is likely to strongly disrupt the balance of the normal flora. Using this normal flora balance improving agent for cleansing purposes, for example by injecting it into the vaginal cavity and allowing it to flow out from the vaginal opening, is extremely useful because it can cleanse the vagina while improving the balance of the vaginal normal flora.

[0022] In this invention, improving the balance of the resident microbiota means at least suppressing the growth of bacteria (harmful bacteria) that have a harmful effect on the skin and mucous membranes, thereby reducing the number of harmful bacteria. Furthermore, in this invention, the balance of the resident microbiota may be improved by, for example, reducing the ratio of harmful bacteria to beneficial bacteria (good bacteria) that have a favorable effect on the skin and mucous membranes (harmful bacteria / good bacteria). Alternatively, the balance of the resident microbiota may be improved by, for example, selectively suppressing the growth of harmful bacteria without suppressing the growth of good bacteria. Alternatively, the balance of the resident microbiota may be improved by, for example, selectively promoting the growth of good bacteria, and the effects may be more pronounced with long-term use of about one month.

[0023] Furthermore, in this invention, "for cleansing" means use for the purpose of cleansing the skin or mucous membranes, and encompasses "for washing."

[0024] Embodiments of the present invention will be described in further detail below.

[0025] [(A) Hyaluronic acid, hyaluronic acid derivatives, and salts thereof] This resident microbiota balance improving agent contains one or more selected from the group consisting of component (A) and component (B). These may be used individually or in combination of two or more. Among these, from the viewpoint of significantly exhibiting the effects of the present invention, it is preferable to use one or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof, which are component (A).

[0026] Hyaluronic acid is a type of acidic mucopolysaccharide, a polysaccharide containing glucuronic acid and N-acetylglucosamine as constituent units. Hyaluronic acid can be extracted and recovered from animal tissues such as chicken combs, shark skin, umbilical cords, eyeballs, skin, and cartilage, as well as from hyaluronic acid-producing microorganisms such as Streptococcus, and from cultures of animal or plant cells. Commercially available hyaluronic acid may also be used.

[0027] As mentioned above, hyaluronic acid extracted from animal tissues or microorganisms is usually a high molecular weight with a weight-average molecular weight of approximately 1 million or more. In this resident microbiota balance improving agent, high molecular weight hyaluronic acid may be used, or low molecular weight hyaluronic acid obtained by decomposing high molecular weight hyaluronic acid may be used. Low molecular weight hyaluronic acid can be obtained by hydrolysis of high molecular weight hyaluronic acid in the presence of an acid or alkali such as hydrochloric acid, treatment with an enzyme such as hyaluronidase, physical cutting by ultrasound or shearing, or fermentation by microorganisms. In addition, commercially available low molecular weight hyaluronic acid may be used.

[0028] Derivatives of hyaluronic acid are not particularly limited as long as they are pharmacologically or physiologically acceptable, and examples include acetylated hyaluronic acid in which the hydroxyl group is acetylated, sulfated hyaluronic acid in which the hydroxyl group is sulfated, cationized hyaluronic acid, hydrolyzed hydrolyzed hyaluronic acid (such as alkyl (C12-13) glyceryl hydrolyzed hyaluronate), cross-linked hyaluronic acid, carboxymethyl hyaluronic acid, alkylene glycol hyaluronate, and silanol hyaluronate.

[0029] The salts of hyaluronic acid or its derivatives are not particularly limited as long as they are pharmacologically or physiologically acceptable, and examples include salts with alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium, metals such as zinc and aluminum, ammonium salts, basic amino acid salts, and amine salts such as triethanolamine. Preferably, sodium salts, potassium salts, and zinc salts are used as salts of hyaluronic acid or its derivatives. Specific examples of salts of hyaluronic acid or its derivatives include sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, ammonium hyaluronate, monoethanolamine hyaluronic acid, acetylated sodium hyaluronate, acetylated potassium hyaluronate, acetylated calcium hyaluronate, acetylated magnesium hyaluronate, acetylated zinc hyaluronate, acetylated ammonium hyaluronate, sodium hyaluronate crosspolymer, and hydroxypropyltrimonium hyaluronate.

[0030] Commercially available hyaluronic acid derivatives include: Sodium acetylated hyaluronate (trade name) (manufactured by Shiseido; weight-average molecular weight 1 to 100,000), Hyaloveil (trade name) (manufactured by Kewpie Corporation; weight-average molecular weight 500,000 to 800,000), Hyalorerepair (trade name) (manufactured by Kewpie Corporation; weight-average molecular weight less than 10,000), Hyalocatch (trade name) (manufactured by Kewpie Corporation; weight-average molecular weight 800,000 to 1,200,000), Hyalujohn (trade name) (manufactured by Kikkoman Biochemifa; propylene glycol hyaluronate), Hyalcage System (trade name) (manufactured by I.R. Asrl; cross-linked 3D hyaluronic acid; weight-average molecular weight 7,000,000), D.S.H. CN6 (trade name) (manufactured by EXSYMOL S.A.M; dimethylsilanol hyaluronate), D.S.H. Examples include CN (trade name) (manufactured by EXSYMOL S.A.M.; dimethylsilanol hyaluronate), etc.

[0031] The weight-average molecular weight of component (A) is not particularly limited as long as it achieves the effects of the present invention, and may be, for example, 1 million to 5 million. From the viewpoint of significantly achieving the effects of the present invention, the weight-average molecular weight of component (A) is preferably 1 million to 4 million, more preferably 2 million to 3 million, more preferably 10 million to 1 million, even more preferably 40 million to 500,000, even more preferably 50 million to 400,000, particularly preferably 80 million to 200,000, and most preferably 10,000 to 200,000. The weight-average molecular weight of component (A) may be 100,000 or less, 50,000 or less, or 10,000 or less. Note that in the lower limit of the above numerical range, if "million" is not attached, it means the numerical value itself, for example, "100" means "100" and not "1 million".

[0032] In preferred embodiments of the present invention, it is preferable to use fermented hyaluronic acid, high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, or salts thereof as component (A), and among these, it is preferable to use fermented hyaluronic acid or a salt thereof. Fermented hyaluronic acid is obtained by fermenting hyaluronic acid as a substrate with bacteria such as Lactococcus, and then filtering it. Among fermented hyaluronic acid, it is preferable to use lactic acid bacteria-fermented hyaluronic acid or a salt thereof.

[0033] The weight-average molecular weight of high molecular weight hyaluronic acid or its salt is preferably 50,000 to 7 million, more preferably 100,000 to 6 million, even more preferably 200,000 to 4 million, particularly preferably 300,000 to 3 million, and most preferably 500,000 to 2 million.

[0034] Commercially available high molecular weight hyaluronic acid products include: Sodium Hyaluronate HA12N (product name) (manufactured by Shiseido; weight-average molecular weight 1.1 million to 1.6 million), Hyaluronic Acid IW120 (product name) (manufactured by Iwaki Pharmaceutical Co., Ltd.; weight-average molecular weight 1.1 million to 1.6 million), Hyaluronic Acid FCH-150 (product name) (manufactured by Kikkoman Biochemifa Co., Ltd.; weight-average molecular weight 1.4 million to 1.8 million), Bio Hyaluronic Acid Sodium SZE (product name) (manufactured by Shiseido; weight-average molecular weight 1.1 million to 1.6 million), Hyaluronic Acid FCH-120 (product name) (Kikkoman Examples include: Biochemifa Co., Ltd. (weight-average molecular weight 1 million to 1.4 million), Hyaluronic Acid HA-LQ (trade name) (Kewpie Corporation; weight-average molecular weight 850,000 to 1.6 million), Hyaluronic Acid FCH-80 (trade name) (Kikkoman Biochemifa Co., Ltd.; weight-average molecular weight 600,000 to 1 million), Hyaluronic Acid FCH-60 (trade name) (Kikkoman Biochemifa Co., Ltd.; weight-average molecular weight 500,000 to 700,000), Hyaluronic Acid FCH-SU (trade name) (Kikkoman Biochemifa Co., Ltd.; weight-average molecular weight 50,000 to 110,000), etc.

[0035] The weight-average molecular weight of low molecular weight hyaluronic acid or its salt is preferably 100 to 50,000, more preferably 200 to 40,000, even more preferably 500 to 30,000, and particularly preferably 500 to 20,000. The weight-average molecular weight of low molecular weight hyaluronic acid or its salt may also be 10,000 or less. Note that in the lower limits of the above numerical ranges, values ​​without the prefix "ten thousand" refer to the numerical value itself; for example, "100" means "100" and not "one million."

[0036] Examples of commercially available low-molecular-weight hyaluronic acid products include Hyalo-Oligo (trade name) (manufactured by Kewpie Corporation; weight-average molecular weight less than 10,000), Hyaluronic Acid (SL) (trade name) (manufactured by FAP Japan Co., Ltd.; weight-average molecular weight less than 10,000), Micro Hyaluronic Acid FCH (trade name) (manufactured by Kikkoman Biochemifa Co., Ltd.; weight-average molecular weight less than 5,000), and HAbooster (trade name) (manufactured by Kewpie Corporation; weight-average molecular weight 2,000).

[0037] The weight-average molecular weight of fermented hyaluronic acid or its salt is preferably 1 to 2 million, more preferably 10 to 1.5 million, even more preferably 10,000 to 1 million, and most preferably 10,000 to 500,000. Note that in the lower limit of the above numerical range, values ​​without the prefix "ten thousand" refer to the numerical value itself; for example, "100" means "100" and not "one million."

[0038] The salts of high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, and fermented hyaluronic acid are not particularly limited as long as they are pharmacologically or physiologically acceptable, and as described above, alkaline earth metals and the like can be used as appropriate.

[0039] Note that the weight-average molecular weight refers to the viscosity-average molecular weight, which can be determined by known measurement methods. Specifically, hyaluronic acid (dried) is dissolved in a 0.2 M sodium chloride solution, and the intrinsic viscosity (η) at 30 ± 0°C is determined using an Ubbelohde viscometer, and Laurent's formula (η (intrinsic viscosity) = 3.6 × 10) is used. -4 ・M 0.78 The viscosity-average molecular weight is calculated based on (where M is the viscosity-average molecular weight). The intrinsic viscosity (η) is measured according to Method 1 of the General Test Methods for Viscosity Measurement in the 18th Revised Japanese Pharmacopoeia: Capillary Viscometer Method.

[0040] [(B) Nonionic surfactant, amino acid-based surfactant] As component (B), any nonionic surfactant or amino acid-based surfactant commonly used in external compositions or cosmetics may be used without particular limitation.

[0041] (Nonionic surfactant) Specific examples of nonionic surfactants include, but are not limited to, sorbitan fatty acid esters such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan diglycerol penta-2-ethylhexyl sorbitan, and sorbitan diglycerol tetra-2-ethylhexyl sorbitan; propylene glycol fatty acid esters such as propylene glycol monostearate; hydrogenated castor oil derivatives such as polyoxyethylene hydrogenated castor oil 40 (HCO-40), polyoxyethylene hydrogenated castor oil 50 (HCO-50), polyoxyethylene hydrogenated castor oil 60 (HCO-60), and polyoxyethylene hydrogenated castor oil 80; polyoxyethylene (20) sorbitan monolaurate (polysorbate 20), polyoxyethylene (20) sorbitan monostearate (polysorbate 60), polyoxyethylene (20) sorbitan monooleate (polysorbate 80), iso Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene (20) sorbitan stearate; glycerin fatty acid esters such as glyceryl oleate, glyceryl myristate, glyceryl stearate, and glyceryl isostearate; polyglycerin fatty acid esters such as polyglyceryl-2 oleate, polyglyceryl-2 stearate, polyglyceryl-10 oleate, polyglyceryl-10 stearate, polyglyceryl-10 laurate, polyglyceryl-10 distearate, polyglyceryl-10 trioleate, polyglyceryl-10 pentaoleate, and polyglyceryl-10 pentastearate; polyoxyethylene fatty acid esters such as polyoxyl 40 stearate and polyoxyl 55 stearate; alkyl glucosides having alkyl groups with 1 to 24 carbon atoms (preferably 8 to 18) such as lauryl glucoside; polyoxyalkylene alkyl glucosides such as polyoxypropylene methyl glucoside;Sucrose caprylate, sucrose capric acid ester, sucrose laurate, sucrose myristate, sucrose palmitate, sucrose stearate, sucrose oleate, sucrose isostearate, sucrose linoleate, sucrose linolenate, sucrose coconut fatty acid ester, sucrose behenate, sucrose erucate and other sucrose fatty acid esters; polyoxyalkylene alkyl ethers such as polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene behenyl ether; polyoxyethylene-polyoxypropylene block copolymers such as polyoxyethylene (196) polyoxypropylene (67) glycol, polyoxyethylene (200) polyoxypropylene (70) glycol, polyoxyethylene (20) polyoxypropylene (4) cetyl ether, polyoxyethylene (10) polyoxypropylene (4) cetyl ether; silicone surfactants such as polyoxyethylene-methylpolysiloxane copolymer, lauryl PEG-9 polydimethylsiloxyethyl dimethicone, PEG-9 polydimethylsiloxyethyl dimethicone and the like. These can be used alone or in combination of two or more.

[0042] As the nonionic surfactant, a sugar-based nonionic surfactant is preferred. A sugar-based nonionic surfactant is a nonionic surfactant having a sugar moiety as a hydrophilic group, and examples thereof include alkyl glucoside, polyoxyalkylene alkyl glucoside, sucrose fatty acid ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester and the like. Among these, alkyl glucoside is preferred.

[0043] Examples of the alkyl glucoside include octyl glucoside, nonyl glucoside, decyl glucoside, octyl maltoside, octyl thioglucoside, lauryl glucoside, coconut oil glucoside and the like. The number of carbon atoms of the alkyl group in the alkyl glucoside is not particularly limited, but is preferably, for example, 8 to 12.

[0044] The HLB value (Hydrophile-Lipophile Balance value) of the nonionic surfactant is not particularly limited, but for example, it is 8 to 22, and from the viewpoint of significantly exhibiting the effects of the present invention, 9 to 20 is preferable, 10 to 18 is more preferable, and 11 to 16 is even more preferable.

[0045] The HLB value is an index indicating the balance between hydrophilicity and lipophilicity, and for example, it is calculated by the following (Formula 1) by Oda, Teramura, etc. HLB = (Σ inorganic value / Σ organic value) × 10... (Formula 1) Σ inorganic value / Σ organic value is called IOB (Inorganic-Organic Balance), and based on the "inorganic value" and "organic value" set for each type of atom and functional group, the "inorganic value" and "organic value" of the atoms and functional groups constituting an organic compound such as a surfactant can be calculated by integrating them (see "Organic Conceptual Diagram - Basics and Applications -" by Yoshio Koda, pages 11 to 17, Sankyo Publishing, issued in 1984).

[0046] (Amino acid-based surfactant) An amino acid-based surfactant is a surfactant containing amino acids (for example, amino acids, sulfur-containing amino acids or their derivatives, and alkylated derivatives thereof having about 1 to 4 carbon atoms) in a part of the structure of the surfactant. Specific examples include, but are not limited to, for example, N-acyl amino acid-based surfactants being suitable.

[0047] As the amino acid constituting the N-acyl amino acid-based surfactant, it may be any of neutral, acidic, and basic, and may be any of the L-form, D-form, or DL-form. Specifically, for example, glycine, alanine, sarcosine, valine, leucine, isoleucine, aspartic acid, glutamic acid, etc. can be mentioned.

[0048] Examples of acyl groups constituting N-acylamino acid surfactants include acyl groups derived from saturated or unsaturated linear or branched fatty acids having 6 to 22 carbon atoms. Preferably, acyl groups derived from saturated fatty acids having 6 to 18 carbon atoms are used. The acyl group may be a single acyl group, an acyl group derived from beef tallow fatty acid, or a mixture thereof. Specifically, examples of fatty acids include lauric acid, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, behenic acid, coconut oil fatty acid, palm oil fatty acid, beef tallow fatty acid, and the like.

[0049] Examples of basic components that make up N-acyl amino acid surfactants include alkali metals such as sodium and potassium, alkaline earth metals such as magnesium and calcium, organic amines such as monoethanolamine, diethanolamine, triethanolamine, and 2-amino-2-methyl-1-propanol, basic amino acids such as lysine, ornithine, and arginine, and ammonia.

[0050] Specific examples of N-acyl amino acid-based surfactants include, for example, N-acyl glutamate-based surfactants, N-acyl glycine-based surfactants, N-acyl alanine-based surfactants, N-acyl sarcosinate-based surfactants, and N-acyl aspartate-based surfactants.

[0051] Examples of N-acyl glutamate surfactants include N-coconut oil fatty acid acyl glutamate triethanolamine, N-coconut oil fatty acid sodium acyl glutamate, N-coconut oil fatty acid potassium acyl glutamate, and other N-coconut oil fatty acid acyl glutamate salts; N-beef tallow fatty acid acyl glutamate sodium, N-beef tallow fatty acid potassium acyl glutamate, N-beef tallow fatty acid acyl glutamate triethanolamine, and other N-beef tallow fatty acid acyl glutamate salts; N-palm oil fatty acid acyl glutamate sodium, N-palm oil fatty acid potassium acyl glutamate, N-palm oil fatty acid acyl glutamate triethanolamine, and other N-palm oil fatty acid acyl glutamate salts; N-palm kernel oil fatty acid acyl glutamate sodium, N-palm kernel oil fatty acid potassium acyl glutamate, N-palm kernel oil fatty acid acyl Examples include N-palm kernel oil fatty acid acyl glutamates such as glutamic acid triethanolamine; N-lauroyl glutamates such as sodium N-lauroyl glutamate, potassium N-lauroyl glutamate, and N-lauroyl glutamate triethanolamine; N-myristoyl glutamates such as sodium N-myristoyl glutamate, potassium N-myristoyl glutamate, and N-myristoyl glutamate triethanolamine; N-palmitoyl glutamates such as sodium N-palmitoyl glutamate, potassium N-palmitoyl glutamate, and N-palmitoyl glutamate triethanolamine; and N-stearoyl glutamates such as sodium N-stearoyl glutamate, potassium N-stearoyl glutamate, and N-stearoyl glutamate triethanolamine.

[0052] Examples of N-acylglycine surfactants include N-coconut oil fatty acid acylglycine salts such as N-coconut oil fatty acid acylglycine triethanolamine, N-coconut oil fatty acid sodium, and N-coconut oil fatty acid acylglycine potassium; N-beef tallow fatty acid acylglycine salts such as N-beef tallow fatty acid acylglycine sodium, N-beef tallow fatty acid acylglycine potassium, and N-beef tallow fatty acid acylglycine triethanolamine; N-palm oil fatty acid acylglycine salts such as N-palm oil fatty acid acylglycine sodium, N-palm oil fatty acid acylglycine potassium, and N-palm oil fatty acid acylglycine triethanolamine; N-palm kernel oil fatty acid acylglycine sodium, N-palm kernel oil fatty acid acylglycine potassium, and N-palm kernel oil fatty acid Examples include N-palm kernel oil fatty acid acylglycine salts such as acylglycinetriethanolamine; N-lauroyl glycine salts such as N-lauroyl glycine sodium, N-lauroyl glycine potassium, and N-lauroyl glycinetriethanolamine; N-myristoyl glycine salts such as N-myristoyl glycine sodium, N-myristoyl glycine potassium, and N-myristoyl glycinetriethanolamine; N-palmitoyl glycine salts such as N-palmitoyl glycine sodium, N-palmitoyl glycine potassium, and N-palmitoyl glycinetriethanolamine; and N-stearoyl glycine salts such as N-stearoyl glycine sodium, N-stearoyl glycine potassium, and N-stearoyl glycinetriethanolamine.

[0053] Examples of N-acylalanine-based surfactants include N-coconut oil fatty acid acylalanine triethanolamine, N-coconut oil fatty acid sodium acylalanine, N-coconut oil fatty acid potassium acylalanine, N-coconut oil fatty acid sodium methylalanine, N-coconut oil fatty acid potassium methylalanine, and other N-coconut oil fatty acid alanine salts; N-beef tallow fatty acid acylalanine sodium, N-beef tallow fatty acid potassium acylalanine, N-beef tallow fatty acid acylalanine triethanolamine, and other N-beef tallow fatty acid acylalanine salts; N-palm oil fatty acid acylalanine sodium, N-palm oil fatty acid potassium acylalanine, N-palm oil fatty acid acylalanine triethanolamine, and other N-palm oil fatty acid acylalanine salts; N-palm kernel oil fatty acid acylalanine sodium, N-palm kernel oil fatty acid potassium acylalanine, N-palm kernel oil fatty acid acylalanine triethanolamine, and other N-palm kernel oil fatty acid acylalanine salts; N-palm kernel oil fatty acid acylalanine sodium, N-palm kernel oil fatty acid potassium acylalanine, and N-palm kernel oil fatty acid acylalanine triethanolamine. Examples include N-palm kernel oil fatty acid acylalanine salts such as sialamine; N-lauroylalanine sodium, N-lauroylalanine potassium, N-lauroylalanine triethanolamine, N-lauroylmethylalanine sodium, N-lauroylmethylalanine potassium, N-lauroylmethylalanine triethanolamine, and other N-lauroylalanine salts; N-myristoylalanine sodium, N-myristoylalanine potassium, N-myristoylalanine triethanolamine, and other N-myristoylalanine salts; N-palmitoylalanine sodium, N-palmitoylalanine potassium, N-palmitoylalanine triethanolamine, and other N-palmitoylalanine salts; N-stearoylalanine sodium, N-stearoylalanine potassium, N-stearoylalanine triethanolamine, and other N-stearoylalanine salts; and others.

[0054] Examples of N-acylsarcosinate surfactants include N-coconut oil fatty acid acylsarcosine salts such as N-coconut oil fatty acid acylsarcosine triethanolamine, N-coconut oil fatty acid sodium acylsarcosine, and N-coconut oil fatty acid potassium acylsarcosine (potassium cocoylsarcosine); N-beef tallow fatty acid acylsarcosine salts such as N-beef tallow fatty acid sodium acylsarcosine, N-beef tallow fatty acid potassium acylsarcosine, and N-beef tallow fatty acid acylsarcosine triethanolamine; N-palm oil fatty acid acylsarcosine salts such as N-palm oil fatty acid sodium acylsarcosine, N-palm oil fatty acid potassium acylsarcosine, and N-palm oil fatty acid acylsarcosine triethanolamine; N-palm kernel oil fatty acid acylsarcosine sodium, N-palm kernel oil fatty acid potassium acylsarcosine, and N-palm Examples include N-palm kernel oil fatty acid acyl sarcosine salts such as palm kernel oil fatty acid acyl sarcosine triethanolamine; N-lauroyl sarcosine salts such as N-lauroyl sarcosine sodium, N-lauroyl sarcosine potassium, and N-lauroyl sarcosine triethanolamine; N-myristoyl sarcosine salts such as N-myristoyl sarcosine sodium, N-myristoyl sarcosine potassium, and N-myristoyl sarcosine triethanolamine; N-palmitoyl sarcosine salts such as N-palmitoyl sarcosine sodium, N-palmitoyl sarcosine potassium, and N-palmitoyl sarcosine triethanolamine; and N-stearoyl sarcosine salts such as N-stearoyl sarcosine sodium, N-stearoyl sarcosine potassium, and N-stearoyl sarcosine triethanolamine.

[0055] Examples of N-acyl aspartate-based surfactants include N-coconut oil fatty acid acyl aspartate sodium, N-coconut oil fatty acid acyl aspartate potassium, N-coconut oil fatty acid acyl aspartate triethanolamine, and other N-coconut oil fatty acid acyl aspartates; N-beef tallow fatty acid acyl aspartate sodium, N-beef tallow fatty acid acyl aspartate potassium, N-beef tallow fatty acid acyl aspartate triethanolamine, and other N-beef tallow fatty acid acyl aspartates; and N-lauroyl aspartate sodium, N-lauroyl aspartate potassium, and N-lauroyl aspartate triethanolamine. Examples include N-lauroyl aspartates such as sodium N-stearoyl aspartate, potassium N-stearoyl aspartate, and triethanolamine N-stearoyl aspartate; N-palmitoyl aspartates such as sodium N-palmitoyl aspartate, potassium N-palmitoyl aspartate, and triethanolamine N-palmitoyl aspartate; and N-myristoyl aspartates such as sodium N-myristoyl aspartate, potassium N-myristoyl aspartate, and triethanolamine N-myristoyl aspartate.

[0056] The total content of component (A) in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of component (A) is not limited to the following, but for example, relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., it is usually 0.000001 to 5% by mass, 0.000005 to 4% by mass, 0.00001 to 3% by mass, 0.0001 to 2% by mass, 0.001 to 1% by mass, 0.01 to 0.5% by mass, 0.1% to 0.3% by mass, etc. It may also be 0.1% by mass or less.

[0057] The total content of fermented hyaluronic acid and its salts in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of fermented hyaluronic acid and its salts is not limited to the following, but for example, relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., it is usually 0.000001 to 5% by mass, 0.000005 to 4% by mass, 0.00001 to 3% by mass, 0.0001 to 2% by mass, 0.001 to 1% by mass, 0.005 to 0.5% by mass, 0.01 to 0.3% by mass, etc. It may also be 0.1% by mass or less.

[0058] The total content of high molecular weight hyaluronic acid and its salts in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of high molecular weight hyaluronic acid and its salts is not limited to the following, but for example, relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., it is usually 0.000001 to 5% by mass, 0.000005 to 3% by mass, 0.00001 to 2% by mass, 0.0001 to 1.5% by mass, 0.0005 to 1% by mass, 0.001 to 0.5% by mass, 0.01 to 0.3% by mass, etc. It may also be 0.1% by mass or less.

[0059] The total content of low molecular weight hyaluronic acid and its salts in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of low molecular weight hyaluronic acid and its salts is not limited to the following, but for example, relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., it is usually 0.000001 to 5% by mass, 0.000005 to 3% by mass, 0.00001 to 2% by mass, 0.0001 to 1% by mass, 0.001 to 0.5% by mass, 0.01 to 0.3% by mass, etc. It may also be 0.1% by mass or less.

[0060] The total content of component (B) in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of component (B) is not limited to the following, but for example, it is usually 0.01 to 15% by mass, 0.1 to 15% by mass, 1 to 13% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., preferably 2 to 10% by mass, and more preferably 3 to 8% by mass, etc. It may also be 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0061] The total content of nonionic surfactants in this resident microbiota balance improving agent can be appropriately set depending on the type and amount of other components, dosage form, etc. The total content of nonionic surfactants is not limited to the following, but for example, it is usually 0.01 to 15% by mass, 0.1 to 13% by mass, 1 to 12% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., preferably 2 to 10% by mass, and more preferably 3 to 8% by mass, etc. It may also be 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0062] The total content of amino acid-based surfactants in this resident microbiota balance improving agent can be appropriately set depending on the type and amount of other components, dosage form, etc. The total content of amino acid-based surfactants is not limited to the following, but for example, it is usually 0.01 to 15% by mass, 0.1 to 13% by mass, 1 to 12% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc., preferably 2 to 10% by mass, and more preferably 3 to 8% by mass, etc. It may also be 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0063] The total content of component (A) and component (B) in this resident microbiota balance improving agent can be appropriately set according to the type and amount of other components, dosage form, etc. The total content of component (A) and component (B) is not limited to the following, but is usually 0.01 to 15% by mass, 0.1 to 13% by mass, 1 to 12% by mass, etc., with 2 to 10% by mass being preferred and more preferably 3 to 8% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent. It may also be 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0064] [Other Ingredients] In this resident microbiota balance improving agent, other ingredients may be added as desired, as long as they do not impair the effects of the present invention. While not limited to the following, for example, bases or carriers, surfactants (excluding nonionic surfactants), thickeners, preservatives, pH adjusters, chelating agents, colorants, etc., may also be added. These may be used individually or in combination of two or more.

[0065] (Base or carrier) Examples of bases or carriers include lower alcohols such as ethanol and isopropanol; glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; polyhydric alcohols such as polyethylene glycol, propylene glycol, 1,3-butylene glycol, glycerin, concentrated glycerin, isoprene glycol, diglycerin, dipropylene glycol, and sorbitol; hydrocarbons such as liquid paraffin, squalane, gelling hydrocarbons (such as Plastibase), ozokerite, and light liquid paraffin; methylpolysiloxane, cross-linked methylpolysiloxane, highly polymerized methylpolysiloxane, cyclic silicone, alkyl-modified silicone, and cross-linked alkyl Examples of silicone oils include silicone-modified silicones, amino-modified silicones, polyether-modified silicones, polyglycerin-modified silicones, cross-linked polyether-modified silicones, cross-linked alkyl polyether-modified silicones, silicone-alkyl chain-comodified polyether-modified silicones, silicone-alkyl chain-comodified polyglycerin-modified silicones, polyether-modified branched silicones, polyglycerin-modified branched silicones, acrylic silicones, phenyl-modified silicones, and silicone resins; oils and fats such as coconut oil, olive oil, rice bran oil, shea butter, rosehip oil, and almond oil; waxes such as jojoba oil, beeswax, candelilla wax, and lanolin; higher alcohols such as cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, and cholesterol; dioxane; esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra-2-ethylhexanoate.These can be used individually or in combination of two or more types.

[0066] The total content of the base or carrier can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 45-90% by mass, 50-85% by mass, 55-80% by mass, 60-75% by mass, etc., relative to the total amount (100% by mass) of the commensal microbiota balance improving agent, etc.

[0067] The total content of polyhydric alcohols can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 0.1 to 15% by mass, 1 to 10% by mass, 3 to 8% by mass, etc., relative to the total amount (100% by mass) of the commensal microbiota balance improving agent, etc. It may also be 5% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0068] (Surfactants) Examples of surfactants include anionic surfactants (excluding the "amino acid-based surfactants" of component (B)), amphoteric surfactants, cationic surfactants, and naturally derived surfactants. These can be used individually or in combination of two or more.

[0069] The total amount of surfactant can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited thereto. However, from the viewpoint of significantly achieving the effects of the present invention, it is, for example, 0.1 to 45% by mass, 0.1 to 20% by mass, 0.1 to 10% by mass, etc., relative to the total amount (100% by mass) of the resident microbiota balance improving agent, etc. Alternatively, it may be 0.1 to 5% by mass, 0.2 to 4% by mass, 0.3 to 3% by mass, 0.4 to 2% by mass, etc.

[0070] Examples of anionic surfactants include higher fatty acids such as palmitic acid, lauric acid, myristic acid, and stearic acid; higher fatty acid salts such as sodium palmitate, potassium laurate, sodium myristate, and potassium stearate; alkyl sulfate ester salts such as sodium lauryl sulfate, triethanolamine lauryl sulfate, sodium laureth sulfate, sodium myristyl sulfate, sodium stearyl sulfate, sodium oleyl sulfate, and sodium cetyl sulfate; polyoxyethylene alkyl ether sulfates such as sodium polyoxyethylene lauryl ether sulfate and sodium polyoxyethylene myristyl ether sulfate; alkyl sulfosuccinates such as sodium dioctyl sulfosuccinate and disodium lauryl sulfosuccinate; polyoxyethylene alkyl sulfosuccinates such as polyoxyethylene disodium lauryl sulfosuccinate; sodium lauryl phosphate, sodium cetyl phosphate, and cetyl phosphate. Examples include monoalkyl phosphate salts such as diethanolamine; polyoxyethylene alkyl ether phosphate salts such as sodium polyoxyethylene lauryl ether phosphate, sodium polyoxyethylene cetyl ether phosphate, sodium polyoxyethylene oleyl ether phosphate, sodium polyoxyethylene alkylphenyl ether phosphate, and triethanolamine polyoxyethylene alkylphenyl ether phosphate; and alkyl ether glycol acetates such as sodium lauryl glycol acetate (dodecane-1,2-diol acetate), potassium lauryl glycol acetate, sodium myristyl glycol acetate, potassium myristyl glycol acetate, sodium palmityl glycol acetate, potassium palmityl glycol acetate, sodium stearyl glycol acetate, potassium stearyl glycol acetate, sodium behenyl glycol acetate, and potassium behenyl glycol acetate.

[0071] The total content of anionic surfactants can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited to these, but is typically 0.1 to 45% by mass, 0.5 to 40% by mass, 1 to 35% by mass, 2 to 30% by mass, 2.5 to 25% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent.

[0072] Examples of amphoteric surfactants include coconut oil fatty acid amidopropyl betaine, lauryl hydroxysulfobetaine, lauric acid amidopropyl betaine, 2-alkyl-N-carboxymethyl-N-hydroxyethylimidazolinium betaine, N-lauroyl-N'-carboxymethyl-N'-hydroxyethylethylenediamine sodium, lauramidopropyl hydroxybetaine, lauric acid amidopropyl dimethylamine oxide, and hydroxyalkyl (C12-14) hydroxyethyl sarcosine.

[0073] The total content of amphoteric surfactants can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited to these, but is typically 0.1 to 20% by mass, 0.5 to 15% by mass, 1 to 12% by mass, 2 to 10% by mass, 2.5 to 8% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent.

[0074] Examples of cationic surfactants include stearyltrimethylammonium chloride, alkyltrimethylammonium chloride, cetyltrimethylammonium chloride, behenyltrimethylammonium chloride, behenyldimethylhydroxyethylammonium chloride, stearyldimethylbenzylammonium chloride, distearyldimethylammonium chloride, dicetylmethylammonium chloride, cetyltriethylammonium methyl sulfate, stearyltrimethylammonium bromide, and cetyltrimethylammonium bromide.

[0075] The total content of cationic surfactants can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited to any particular amount, but is typically 0.1 to 5% by mass, 0.2 to 4% by mass, 0.3 to 3% by mass, 0.4 to 2% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent.

[0076] Examples of naturally derived surfactants include lecithin, hydrogenated lecithin, saponins, sodium surfactant, and bile acids.

[0077] The total amount of naturally derived surfactants can be set appropriately depending on the type and amount of other ingredients, dosage form, etc., and is not limited to these, but is typically 0.1 to 5% by mass, 0.2 to 4% by mass, 0.3 to 3% by mass, 0.4 to 2% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent.

[0078] (Thickening agents) Examples of thickening agents include gums (gellan gum, xanthan gum, sclerotium gum, locust bean gum, biosaccharide gum, tamarind gum, quince seed gum, gum arabic, tara gum, guar gum, galactan, gum arabic, tragacanth gum, etc.), carrageenan, curdlan, succinoglucan, heparinoids, alginates (alginic acid, sodium alginate, propylene glycol alginate, etc.), agar (including agarose), gelatin, pectin, pullulan, mannan, vinyl-based thickeners (polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, etc.), and cellulose-based thickeners (methylcellulose, ethylcellulose). Examples of thickeners include rose, hydroxyethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, hydrophobized hydroxypropylmethylcellulose, etc.), dextran, dextrin, alkyl acrylate methacrylate copolymer, sodium polyacrylate, bentonite, dextrin fatty acid ester, dimethyldistearylammonium hectorite, polyethylene glycol, macrogol, (hydroxyethyl acrylate / sodium acryloyldimethyltaurate) copolymer, (ammonium acryloyldimethyltaurate / vinylpyrrolidone) copolymer, etc. The total content of the thickener can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 5% by mass, or 0.01 to 3% by mass, 0.05 to 1% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc.

[0079] (Preservatives) Preservatives include benzoic acid, benzoates, alkyldiaminoethylglycine hydrochloride, photosensitizer, chlorcresol, chlorobutanol, salicylic acid, salicylates, sorbic acid and its salts, dehydroacetic acid and its salts, trichlorohydroxydiphenyl ether (also known as triclosan), parahydroxybenzoic acid esters and their sodium salts (methyl parahydroxybenzoate, ethyl parahydroxybenzoate, etc.), phenoxyethanol, sodium lauryldiaminoethylglycine, resorcinol, zinc-ammonia-silver complex substituted zeolite, pantothenyl ethyl benzoate, isopropylmethylphenol, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, chlorhexidine hydrochloride, orthophenylphenol, orthophenylphenol Examples include sodium chloroisothiazolinone, silver-copper zeolite, chlorhexidine gluconate, cresol, chloramine T, chloroxylenol, chlorphenesin, chlorhexidine, 1,3-dimethylol-5,5-dimethylhydantoin, alkylisoquinolinium bromide, thianthol, thymol, trichlorocarbanilide, parachlorophenol, halocarban, hinokitiol, zinc pyrithione, piroctone olamine, iodide propynyl butylcarbamate, polyaminopropyl biguanide, methylisothiazolinone, methylchloroisothiazolinone / methylisothiazolinone solution, N,N"-methylenebis[N'-(3-hydroxymethyl-2,5-dioxo-4-imidazolidinyl)urea], and iodide-paradimethylaminostyrylheptylmethylthiazolium.

[0080] In preferred embodiments of this resident microbiota balance improving agent, it is preferable that the agent is substantially free of preservatives from the viewpoint of suppressing irritation to the skin and / or mucous membranes. "Substantially free of preservatives" means that the total amount of preservatives is 0.5% by mass or less of the total amount (100% by mass) of this resident microbiota balance improving agent, and is preferably 0.1% by mass or less, more preferably 0.01% by mass, even more preferably 0.001% by mass or less, even more preferably 0.0001% by mass, and most preferably 0% by mass.

[0081] (pH adjuster) The pH adjuster is not particularly limited, but examples include inorganic bases such as potassium hydroxide, sodium hydroxide, and sodium carbonate; organic bases such as triethanolamine, diisopropanolamine, and triisopropanolamine; inorganic acids such as hydrochloric acid and sulfuric acid; and organic acids such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid, and sodium succinate. These can be used alone or in combination of two or more. The total content of the pH adjuster can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 2.5% by mass, preferably 0.005 to 2% by mass, and more preferably 0.01 to 1% by mass, based on the total amount (100% by mass) of the resident microbiota balance improving agent, etc.

[0082] (Chelating agents) Examples of chelating agents include EDTA disodium salt, EDTA calcium disodium salt, gluconolactone, and caprylhydroxamic acid. The total content of chelating agents can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 2.5% by mass, preferably 0.005 to 2% by mass, and more preferably 0.01 to 1% by mass, based on the total amount (100% by mass) of this resident microbiota balance improving agent.

[0083] (Coloring agents) Examples of coloring agents include inorganic pigments and natural pigments. The total content of coloring agents can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 1% by mass, preferably 0.005 to 0.1% by mass, and more preferably 0.01 to 0.05% by mass, based on the total amount (100% by mass) of this resident microbiota balance improving agent, etc.

[0084] This resident microbiota balance improving agent may contain other active ingredients as long as it does not impair the effects of the present invention. Specific examples of active ingredients, but not limited to those listed below, include moisturizing ingredients, scrubbing agents, blood circulation promoters, astringent ingredients, UV-absorbing ingredients, anti-inflammatory agents, vitamins, peptides or their derivatives, amino acids or their derivatives, and cell-activating ingredients. These can be used alone or in combination of two or more.

[0085] (Moisturizing ingredients) Examples of moisturizing ingredients include chondroitin sulfate or its salts (sodium chondroitin sulfate, potassium chondroitin sulfate, sodium dermatan sulfate, potassium dermatan sulfate, etc.); glycosyl trehalose, trehalose; ceramide, glucosylceramide, cholesterol, phytosterol, cholesterol derivatives, phytosterol derivatives; 2-methacryloyloxyphosphorylcholine-butyl methacrylate copolymer solution, polymethacryloyloxyethyl phosphorylcholine and other 2-methacryloyloxyphosphorylcholine-containing polymers; NMF-derived components such as lactic acid, sodium lactate, sodium pyrrolidone carboxylate, and urea; collagen, elastin, keratin, chitin, chitosan, etc. and their hydrolysates; and hydroxyethyl urea. The total content of moisturizing ingredients can be appropriately set according to the type and amount of other ingredients, dosage form, etc., and is not limited to these, but is, for example, 0.001 to 60% by mass, 0.01 to 50% by mass, preferably 0.03 to 40% by mass, and more preferably 0.05 to 30% by mass, etc., relative to the total amount (100% by mass) of the resident microbiota balance improving agent, etc.

[0086] (Scrubbing agent) Examples of scrubbing agents include apricot kernel powder, almond shell powder, sodium chloride granules, olive kernel powder, candelilla wax, walnut shell powder, cherry kernel powder, coral powder, charcoal powder (paulownia charcoal, binchotan charcoal, bamboo charcoal, cypress charcoal, coconut shell charcoal and activated charcoal thereof, and medicinal charcoal thereof), hazelnut shell powder, polyethylene powder, etc. The total content of the scrubbing agent can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.01 to 15% by mass, preferably 0.05 to 10% by mass, and more preferably 0.1 to 5% by mass, etc., relative to the total amount (100% by mass) of the resident microbiota balance improving agent, etc.

[0087] (Blood circulation promoters) Examples of blood circulation promoters include acetylcholine, ichthammol, caffeine, capsaicin, cantharis tincture, γ-oryzanol, gingerol, cepharanthine, swertia japonica extract, tannic acid, capsicum tincture, trazoline, tocopherol nicotinate, and benzyl nicotinate. The total content of blood circulation promoters can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 5% by mass, preferably 0.005 to 3% by mass, and more preferably 0.01 to 1% by mass, relative to the total amount (100% by mass) of the resident microbiota balance improving agent, etc.

[0088] (Astringent components) Examples of astringent components include zinc sulfate, hydroxyaluminum, aluminum chloride, zinc sulfocarbohydrate, and tannic acid. The total content of astringent components can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 20% by mass, preferably 0.01 to 15% by mass, and more preferably 0.1 to 10% by mass, based on the total amount (100% by mass) of this resident microbiota balance improving agent.

[0089] (UV Absorbing Components) Examples of UV absorbing components include octyl triazone, diethylamino hydroxybenzoyl hexyl benzoate, octyl dimethoxybenzylidene dioxoimidazolidine propionate, 2-ethylhexyl paramethoxycinnamate, t-butyl methoxydibenzoylmethane, phenylbenzimidazole sulfonic acid, octyl methoxycinnamate, and ethylhexyl methoxycinnamate. The total content of UV absorbing components can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 1 to 30% by mass, preferably 3 to 25% by mass, and more preferably 5 to 20% by mass, based on the total amount (100% by mass) of this resident microbiota balance improving agent.

[0090] (Anti-inflammatory agents) Examples of anti-inflammatory agents include non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. Specifically, examples include glycyrrhizic acid, glycyrrhetinic acid, stearyl glycyrrhetinate, allantoin, epsilon-aminocaproic acid, indomethacin, felbinac, ibuprofen, ibuprofen piconol, ketoprofen, bufexamac, flufenamate butyl, bendazac, piroxicam, suprofen, azulene, guaiazulene, dexamethasone acetate valerate, dexamethasone, prednisolone acetate valerate (prednisolone valerate acetate), prednisolone acetate, prednisolone, hydrocortisone acetate, hydrocortisone, ufenamate, bufexamac, and salts thereof. The total amount of anti-inflammatory agents can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited to these, but is, for example, 0.001 to 5% by mass, preferably 0.005 to 4.5% by mass, and more preferably 0.01 to 3% by mass, based on the total amount (100% by mass) of the commensal microbiota balance improving agent, etc.

[0091] (Vitamins) Vitamins include vitamin E compounds such as dl-α-tocopherol, dl-α-tocopherol succinate, and dl-α-tocopherol calcium succinate; vitamin B2 compounds such as riboflavin, flavin mononucleotide, flavin adenine dinucleotide, riboflavin butyrate, riboflavin tetrabutyrate, riboflavin 5'-phosphate sodium, and riboflavin tetranicotinate; and dl-α-tocopherol nicotinate, benzyl nicotinate, methyl nicotinate, β-butoxyethyl nicotinate, and nicotin. Nicotinic acids such as 1-(4-methylphenyl)ethyl acid; vitamin C compounds such as ascorbigen-A, ascorbic acid stearate, ascorbic acid palmitate, and L-ascorbyl dipalmitate; vitamin D compounds such as methyl hesperidin, ergocalciferol, and cholecalciferol; vitamin K compounds such as phylloquinone and farnoquinone; γ-oryzanol, dibenzoylthiamine, dibenzoylthiamine hydrochloride; thiamine hydrochloride, thiamine cetyl hydrochloride, thiamine thiocyanate, thiamine lauryl hydrochloride, and thiamine sulfate. Vitamin B1 compounds such as salts, thiamine monophosphate, thiamine lysine salt, thiamine triphosphate, thiamine monophosphate phosphate, thiamine monophosphate, thiamine diphosphate, thiamine diphosphate hydrochloride, thiamine triphosphate, thiamine triphosphate monophosphate; Vitamin B6 compounds such as pyridoxine hydrochloride, pyridoxine acetate, pyridoxal hydrochloride, pyridoxal 5'-phosphate, pyridoxamine hydrochloride; Vitamin B12 compounds such as cyanocobalamin, hydroxocobalamin, deoxyadenosylcobalamin. Vitamin C derivatives such as folic acid and pteroylglutamic acid; nicotinic acid derivatives such as nicotinic acid and nicotinamide; pantothenic acid derivatives such as pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesine, D-pantethine, coenzyme A, and pantothenyl ethyl ether; biotin derivatives such as biotin and biotisine; and vitamin C derivatives such as ascorbic acid, sodium ascorbate, dehydroascorbic acid, sodium ascorbate phosphate, and magnesium ascorbate phosphate.Examples include vitamin-like factors such as carnitine, ferulic acid, alpha-lipoic acid, and orotic acid. The total vitamin content can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 25% by mass, preferably 0.01 to 20% by mass, and more preferably 0.05 to 15% by mass, relative to the total amount (100% by mass) of this resident microbiota balance improving agent.

[0092] (Peptides or their derivatives) Examples of peptides or their derivatives include keratin-degrading peptides, hydrolyzed keratin, collagen, fish-derived collagen, atelocollagen, gelatin, elastin, elastin-degrading peptides, collagen-degrading peptides, hydrolyzed collagen, hydroxypropylammonium chloride hydrolyzed collagen, elastin-degrading peptides, conchiolin-degrading peptides, hydrolyzed conchiolin, silk protein-degrading peptides, hydrolyzed silk, sodium lauroyl hydrolyzed silk, soy protein-degrading peptides, hydrolyzed soy protein, wheat protein, wheat protein-degrading peptides, hydrolyzed wheat protein, casein-degrading peptides, acylated peptides (palmitoyl oligopeptides, palmitoyl pentapeptides, palmitoyl tetrapeptides, etc.). The total content of peptides or their derivatives can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited to these, but is, for example, 0.001 to 5% by mass, preferably 0.01 to 3% by mass, and more preferably 0.05 to 1% by mass, based on the total amount (100% by mass) of the commensal microbiota balance improving agent, etc.

[0093] (Amino acids or their derivatives) Examples of amino acids or their derivatives include betaine (trimethylglycine), proline, hydroxyproline, arginine, lysine, serine, glycine, alanine, phenylalanine, β-alanine, threonine, glutamic acid, glutamine, asparagine, aspartic acid, cysteine, cystine, methionine, leucine, isoleucine, valine, histidine, taurine, γ-aminobutyric acid, γ-amino-β-hydroxybutyric acid, carnitine, carnosine, creatine, etc. The total content of amino acids or their derivatives can be appropriately set depending on the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 5% by mass, preferably 0.01 to 3% by mass, more preferably 0.05 to 1% by mass, etc., relative to the total amount (100% by mass) of this resident microbiota balance improving agent, etc.

[0094] (Cell-activating components) Examples of cell-activating components include α-hydroxy acids such as glycolic acid and lactic acid, tannins, flavonoids, and saponins. The total content of cell-activating components can be appropriately set according to the type and amount of other components, dosage form, etc., and is not limited, but is, for example, 0.001 to 5% by mass, preferably 0.01 to 3% by mass, and more preferably 0.05 to 1% by mass, based on the total amount (100% by mass) of this resident microbiota balance improving agent.

[0095] [pH] The pH of this resident microbiota balance improving agent can be set appropriately depending on the dosage form, etc., and is not limited thereto, but for example, pH 3.5 to 11.0 is preferred, more preferably pH 4.0 to 9.0, even more preferably pH 4.0 to 7.5, and even more preferably pH 4.5 to 7.0. The pH is measured at room temperature (25°C) using a pH meter (for example, pH METER F-52 (manufactured by HORIBA)).

[0096] When using this resident microbiota balance improving agent, for example, on delicate areas, the pH is not limited, but for example, pH 3.5 to 8.0 is preferred, more preferably pH 4.0 to 7.0, even more preferably pH 4.0 to 6.5, even more preferably 4.0 to 6.0, and particularly preferably pH 4.5 to 6.0.

[0097] [Viscosity] The viscosity (at 25°C) of this resident microbiota balance improving agent can be appropriately set depending on the dosage form, etc. For example, it is 0.1 to 1,000,000 mPa·s, preferably 1 to 500,000 mPa·s, more preferably 10 to 100,000 mPa·s, even more preferably 100 to 50,000 mPa·s, even more preferably 100 to 30,000 mPa·s, even more preferably 100 to 10,000 mPa·s, and most preferably 100 to 5,000 mPa·s.

[0098] The viscosity (at 25°C) is measured in accordance with the viscosity measurement method described in the General Test Methods of the 18th Revised Japanese Pharmacopoeia. If the value exceeds 100 mPa·s, it refers to the viscosity measured using a single-cylinder rotational viscometer (Brookfield type viscometer). Specifically, it refers to the value measured using, for example, a TV-10M (manufactured by Toki Sangyo Co., Ltd.). The selection of conditions such as rotor and rotation speed is in accordance with the instruction manual for this instrument, and the viscosity at 25°C is measured. More specifically, the viscosity at 25°C is measured using an M4 rotor, under conditions of a rotation speed of 0.3 rpm and a measurement time of 180 seconds.

[0099] The following is a description of a single-cylinder rotational viscometer. A single-cylinder rotational viscometer is a viscometer that measures the torque when a cylinder in a liquid is rotated at a constant angular velocity. The viscosity η of the liquid is calculated by the following formula, after experimentally determining the instrument constant KB using a viscometer calibration standard solution: η = KB × T / ω η: viscosity of the liquid (mPa·s) KB: instrument constant (rad / cm) 3 ω: angular velocity (rad / s) T: torque acting on the cylindrical surface (10 -7 N・m)

[0100] Furthermore, values ​​below 100 mPa·s refer to viscosity measured using a cone-plate type rotational viscometer. Specifically, this refers to values ​​measured using, for example, the TV-20 (manufactured by Toki Sangyo Co., Ltd.), and the selection of conditions such as rotor and rotation speed shall conform to the instruction manual of this instrument, and the viscosity shall be measured at 25°C. More specifically, a cone rotor (1°34' × R24) shall be used, and the viscosity shall be measured at 25°C under the conditions of a rotation speed of 50 rpm and 3 minutes after the start of measurement.

[0101] [Manufacturing Method] This resident microbiota balance improving agent can be manufactured by known methods. For example, it can be manufactured by mixing each component in accordance with or in accordance with the 18th edition of the Japanese Pharmacopoeia.

[0102] [Formulation Forms, etc.] This resident microbiota balance improving agent is provided in any form that can be widely used as a cosmetic, quasi-drug, pharmaceutical, etc. The formulation forms of this resident microbiota balance improving agent are not particularly limited and include liquids, oils, suspensions, emulsions, creams, emulsion ointments, ointments, gels, liniments, lotions, foams, sprays, aerosols, mists, pump foams, sheets impregnated with the drug solution (such as nonwoven fabric), sticks, powders, etc.

[0103] This resident microbiota balance improving agent can be suitably used as, for example, external skin compositions such as lotions, mists, moisturizing oils, emulsions, creams, gels, serums, sunscreens, antiperspirants, and powders; skin cleansing compositions such as body soaps (also called body shampoos), hand soaps, facial cleansing foams, makeup removers, shampoos for the scalp, dry shampoos, and rinse-in shampoos; and mucosal cleansing compositions such as vaginal cleansers.

[0104] [Container] This resident microbiota balance improving agent can be filled into a container of appropriate choice depending on the purpose and use. Examples of such containers include bottles, tubes, jars, mist types, spray types, aerosol types, dispenser types, pump-formers, pouches, spout pouches, and injection-type containers that are inserted into body cavities such as the vaginal cavity to inject the contents into the body cavity. Examples of materials that make up the container include polyethylene terephthalate, polypropylene, polyethylene (HDPE, LDPE, LLDPE, etc.), ABS resin, ethylene vinyl alcohol resin, polystyrene, glass, and metals (aluminum, etc.), and mixtures thereof. Furthermore, containers molded from these materials may be coated with various coatings on the surface of the container, taking into consideration strength, flexibility, weather resistance, or stability of the components. In addition, containers can be formed by laminating films or the like made from the above materials.

[0105] [Application Sites] The areas to which this resident microbiota balance improving agent can be applied are not particularly limited. For example, one or more areas selected from the group consisting of the face (including around the eyes and mouth), neck, chest, back, arms, elbows, hands, armpits, abdomen, genitals, buttocks, anal area, legs, fingers, toes, and soles of the feet can be applied. In particular, this resident microbiota balance improving agent is preferable to apply to delicate areas where the stratum corneum is thinner and more sensitive to irritation than other parts of the body, and where the balance of the resident microbiota tends to be easily disrupted. Specifically, it is preferable to apply it to one or more delicate areas selected from the group consisting of the genitals (internal and external genitalia), buttocks, anal area, groin, and lower back. Furthermore, it is preferable to apply it to one or more delicate areas selected from the group consisting of the labia majora, labia minora, clitoris, vaginal vestibule, vestibular bulbs, Bartholin's glands, perineum, and vagina (vaginal mucosa). The delicate area is also referred to as the "delicate area," "intimate area," or "private area." When applying this resident microbiota balance improving agent to the skin and / or mucous membranes, it is sufficient for the skin and / or mucous membranes to come into contact with the resident microbiota balance improving agent. For example, this may be done by applying the agent to the skin and / or mucous membranes and allowing it to come into contact (leave-on), or by applying the resident microbiota balance improving agent to the skin and / or mucous membranes and then removing it (leave-off).

[0106] [Target Users] There are no particular restrictions on who can be targeted by this resident microbiota balance improving agent. For example, this includes individuals whose resident microbiota balance is easily disrupted due to lifestyle habits, individuals whose resident microbiota balance is disrupted, individuals whose resident microbiota balance is disrupted due to aging, and individuals with diseases caused by disruption of the resident microbiota balance, such as bacterial vaginosis (BV). For example, this includes individuals who are experiencing symptoms such as rashes, irritation, or gray discharge in delicate areas such as the vulva, individuals who are troubled by odor in delicate areas, and individuals who are troubled by dampness in delicate areas.

[0107] [Uses] This resident microbiota balance improving agent is used to improve the balance of the resident microbiota of the skin and / or mucous membranes. Specifically, it is suitable for applications such as improving the balance of the resident microbiota by suppressing the growth of harmful bacteria and reducing the number of harmful bacteria, improving the balance of the resident microbiota by reducing the ratio of harmful bacteria to beneficial bacteria (harmful bacteria / beneficial bacteria), or improving the balance of the resident microbiota by selectively suppressing the growth of harmful bacteria without suppressing the growth of beneficial bacteria.

[0108] There are no particular limitations to the beneficial bacteria (good bacteria) that have a favorable effect on the skin and mucous membranes, but examples include the genera Lactobacillus and Staphylococcus. Specifically, these include Lactobacillus crispatus, Lactobacillus paragasseri, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus fermenti, Lactobacillus cellobiosus, Lactobacillus iners, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus vaginalis, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus brevis, Lactobacillus plantarum, and Staphylococcus epidermidis.

[0109] Examples of bacteria that have harmful effects on the skin and mucous membranes (bad bacteria) include Gardnerella vaginalis and Prevotella bivia, which are involved in bacterial vaginosis (BV). Other examples of bacteria that have harmful effects on the skin and mucous membranes (bad bacteria) include Staphylococcus aureus, which is involved in skin infections; Streptococcus species, which is involved in vulvovaginitis; uropathogenic E. coli (UPEC), which is involved in vulvovaginitis; Neisseria gonorrhoeae, which is involved in gonorrhea (STI); and Chlamydia trachomatis, which is involved in gonorrhea (STI).

[0110] In one preferred embodiment of the present invention, it is preferable to use it to improve the balance of the commensal flora by reducing the amount of Gardnerella vaginalis in a commensal flora that includes Lactobacillus crispatus and Gardnerella vaginalis.

[0111] Furthermore, in a preferred embodiment of the present invention, it is preferable to use it for the prevention or treatment of at least one symptom selected from the group consisting of bacterial vaginosis, contact dermatitis (rash), sexually transmitted infections, premature birth, premature rupture of membranes, chorioamnionitis, fallopian tube obstruction, salpingitis, endometriosis, chronic endometritis, recurrent implantation failure, implantation disorder, and infertility.

[0112] Furthermore, a preferred use of one embodiment of the present invention is a topical composition for delicate areas. Among these, a topical composition for delicate areas used for cleansing is preferred from the viewpoint of suppressing disruption of the balance of resident microbiota caused by cleansing of the skin and mucous membranes of delicate areas. For example, from the viewpoint of suppressing disruption of the balance of resident microbiota caused by cleansing of the area near the vagina, it can be used for cleansing by being injected into the vaginal cavity and discharged from the vaginal opening. From this viewpoint, another preferred use of one embodiment of the present invention is as a topical composition for mucous membranes such as the vaginal mucosa. The mucous membrane is not limited to the vaginal mucosa, but also includes body cavity mucous membranes such as the oral mucosa, pharyngeal mucosa, nasal mucosa, and ear cavity mucosa.

[0113] Furthermore, the embodiment of this product can be used for purposes such as normalizing the skin, normalizing the skin environment, improving the skin environment, regulating the skin environment, regulating the skin condition, making the skin environment comfortable, regulating the skin condition, regulating the skin barrier function, suppressing itching, and suppressing rashes. It is also suitable for application to delicate areas, and can be used in particular for normalizing the skin of delicate areas, normalizing the skin environment, improving the skin environment, regulating the skin environment, regulating the skin condition, making the skin environment comfortable, regulating the barrier function, making the delicate area environment comfortable, suppressing itching in delicate areas, suppressing rashes in delicate areas, reducing unpleasant odors in delicate areas, reducing dampness in delicate areas, lactic acid bacteria care for delicate areas, maintaining lactic acid bacteria in delicate areas, and maintaining the pH balance of delicate areas.

[0114] One embodiment of the present invention can be used to prevent or treat specific symptoms of contact dermatitis (rash), such as erythema, papules, edema, vesicles, and blisters, which may be accompanied by itching.

[0115] In one embodiment of the present invention, the product may be a resident microbiota balance improving agent, etc., containing one or more selected from the group consisting of component (A) and component (B) as an active ingredient.

[0116] <Antibacterial agents, bacterial growth inhibitors> Embodiments of the present invention include an antibacterial agent against harmful bacteria, or a selective antibacterial agent against harmful bacteria, which contains one or more selected from the group consisting of component (A) and component (B) as an active ingredient, etc. Another embodiment of the present invention includes a bacterial growth inhibitor against harmful bacteria, or a selective bacterial growth inhibitor against harmful bacteria, which contains one or more selected from the group consisting of component (A) and component (B) as an active ingredient, etc.

[0117] Furthermore, embodiments of the present invention include a bacterial growth promoter for beneficial bacteria, or a selective bacterial growth promoter for beneficial bacteria, which contains one or more selected from the group consisting of component (A) and component (B) as an active ingredient, etc.

[0118] <Use> Embodiments of the present invention include the use of one or more components selected from the group consisting of (A) and (B) to produce a resident microbiota balance improving agent. Embodiments of the present invention include the use of one or more components selected from the group consisting of (A) and (B) to produce an external composition for delicate areas. Embodiments of the present invention include the use of a composition containing one or more components selected from the group consisting of (A) and (B) to improve the balance of resident microbiota.

[0119] <Method for imparting an effect of improving the balance of resident microbiota> An embodiment of the present invention is a method for imparting an effect of improving the balance of resident microbiota to an external composition, which includes incorporating one or more components selected from the group consisting of component (A) and component (B) into the external composition.

[0120] <Method for improving the balance of resident microbiota> Embodiments of the present invention include a method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of component (A) and component (B) to the skin and / or mucous membranes.

[0121] <Method for maintaining the pH balance of the skin and / or mucous membranes> Embodiments of the present invention include a method for maintaining the pH balance of the skin and / or mucous membranes by applying a composition containing one or more selected from the group consisting of component (A) and component (B) to the skin and / or mucous membranes.

[0122] <pH balance maintenance agent for skin and / or mucous membranes> Embodiments of the present invention include a pH balance maintenance agent for skin and / or mucous membranes that contains one or more selected from the group consisting of component (A) and component (B).

[0123] <Method for preventing or treating symptoms caused by disruption of the balance of commensal microbiota> Embodiments of the present invention include a method for preventing or treating symptoms caused by disruption of the balance of commensal microbiota by applying a composition containing one or more selected from the group consisting of component (A) and component (B) to the skin and / or mucous membranes. For example, although not limited to the following, an example of a method for preventing or treating bacterial vaginosis by applying a composition containing one or more selected from the group consisting of component (A) and component (B) to the skin and / or mucous membranes is included.

[0124] The present invention will be described in detail below based on examples, but the present invention is not limited to these examples. The units of content shown in the examples and formulation examples are based on mass.

[0125] <Test Example 1-1> First, L. crispas (DSM4944) and G. vaginalis (DSM20584) were prepared as bacterial strains. From the culture plates of the bacterial strains (L. crispas or G. vaginalis), 25 ml of BHI liquid medium (BHI 37.0 g / L, hemin 5.0 mg / L, maltose 1.0%) was inoculated and cultured at 37 ± 2 °C under anaerobic conditions without shaking for 24 to 48 hours. The obtained bacterial culture solution was centrifuged at 4 °C, 4500 x g, for 5 minutes, and the precipitate was resuspended in 10 to 20 ml of 1 x PBS to prepare a bacterial suspension with an OD600 of 1.0 ± 0.2 / ml. Fermented hyaluronic acid (obtained by fermenting hyaluronic acid with Lactococcus as a substrate and then filtering it) was prepared in 180 μl volumes in the liquid medium of a 96-well plate, with final concentrations of 0.015%, 0.03%, or 0.06%. These volumes were then added to the wells, and 20 μl of the bacterial suspension (OD600 = 1.0 ± 0.2 / ml) was added to obtain the measurement samples. Samples without added fermented hyaluronic acid were used as controls. The fermented hyaluronic acid raw material was dissolved in a 30% 1,3-butylene glycol aqueous solution. A blank for absorbance measurement was prepared by adding 20 μl of 1x PBS to 180 μl of the fermented hyaluronic acid solution prepared as described above. Furthermore, a positive control for absorbance measurement was prepared by adding 20 μl of the bacterial suspension (OD600 = 1.0 ± 0.2 / ml) to 180 μl of the liquid culture medium. A negative control for absorbance measurement was prepared by adding 20 μl of 1x PBS to 180 μl of the liquid culture medium.

[0126] Each of the measurement samples and control samples obtained above were cultured under anaerobic conditions at 37±2°C without shaking for 24 hours. Then, the absorbance was measured at 600 nm at t=0 and t=24h using a plate reader (TECAN Infinite 200 Pro M-Series). Three measurements were performed for each concentration. Next, the ratio of the absorbance of the measurement sample (180 μl of fermented hyaluronic acid solution at a predetermined concentration + 20 μl of bacterial suspension) to the absorbance of the control (180 μl of liquid medium + 20 μl of bacterial suspension) (measurement sample / control) was determined. The results are shown in Figure 1. In Figure 1, the horizontal axis represents the final concentration of fermented hyaluronic acid in the liquid medium, and the vertical axis represents the absorbance ratio.

[0127] (Results of Test Example 1-1) As shown in Figure 1, fermented hyaluronic acid showed a tendency to suppress the growth of the harmful bacterium G. vaginalis. On the other hand, it did not show a tendency to suppress the growth of the beneficial bacterium L. crispas. Thus, it was confirmed that fermented hyaluronic acid can improve the balance of the commensal microbiota by exhibiting a selective antibacterial effect against harmful bacteria.

[0128] <Test Example 1-2> In Test Example 1-1, the fermented hyaluronic acid was replaced with low molecular weight hyaluronic acid (hydrolyzed hyaluronic acid) (weight-average molecular weight of 10,000 or less, product name: Hyalo-Oligo (manufactured by Kewpie Corporation)), and the final concentration of low molecular weight hyaluronic acid in the liquid culture medium in the wells was changed to three different concentrations: 0.0075%, 0.015%, or 0.03%. The same test was conducted as in Test Example 1-1. The results are shown in Figure 2. The low molecular weight hyaluronic acid raw material was used in a state dissolved in a 30% 1,3-butylene glycol aqueous solution.

[0129] (Results of Test Example 1-2) As shown in Figure 2, low molecular weight hyaluronic acid showed a tendency to suppress the growth of the harmful bacterium G. vaginalis. On the other hand, it did not show a tendency to suppress the growth of the beneficial bacterium L. crispas. Thus, it was confirmed that low molecular weight hyaluronic acid can improve the balance of the commensal microbiota by exhibiting a selective antibacterial effect against harmful bacteria.

[0130] <Test Example 1-3> In Test Example 1-1, the fermented hyaluronic acid was replaced with high molecular weight hyaluronic acid (weight-average molecular weight 1.1 million to 1.6 million, Hyaluronic Acid IW120B (manufactured by Iwaki Pharmaceutical Co., Ltd.)), and the final concentration of high molecular weight hyaluronic acid in the liquid culture medium in the wells was changed to three different concentrations: 0.0075%, 0.015%, or 0.03%. The same test was conducted as in Test Example 1-1. The results are shown in Figure 3. The high molecular weight hyaluronic acid raw material used was dissolved in a 30% 1,3-butylene glycol aqueous solution.

[0131] (Results of Test Examples 1-3) As shown in Figure 3, high molecular weight hyaluronic acid showed a tendency to suppress the growth of the harmful bacterium G. vaginalis. On the other hand, it showed a tendency to be less effective in suppressing the growth of the beneficial bacterium L. crispas. Thus, it was confirmed that high molecular weight hyaluronic acid can improve the balance of the commensal microbiota by exhibiting a selective antibacterial effect against harmful bacteria.

[0132] <Test Example 2-1> The same test as in Test Example 1-1 was performed, except that the fermented hyaluronic acid was replaced with a nonionic surfactant (Plantacare 2000UP (decyl glucoside), manufactured by BASF), and the final concentration of the nonionic surfactant in the liquid culture medium in the wells was changed to five different concentrations: 0.5%, 1%, 3%, 5%, or 7%. The results are shown in Figure 4. The vertical axis of Test Examples 2-1 to 2-4 shows the ratio of absorbance to control (measurement sample / control) as a percentage.

[0133] <Test Example 2-2> The same test as in Test Example 1-1 was conducted, except that the fermented hyaluronic acid was replaced with an amino acid-based surfactant (AMISOFT CS-22 (disodium cocoyl glutamate), manufactured by Ajinomoto Co., Ltd.), and the final concentration of the amino acid-based surfactant in the liquid culture medium in the wells was changed to four different concentrations: 0.5%, 1%, 3%, or 7%. The results are shown in Figure 5.

[0134] <Test Example 2-3> The same test as in Test Example 1-1 was performed, except that the fermented hyaluronic acid was replaced with an anionic surfactant (E-27C (sodium laureth sulfate), manufactured by Kao Corporation), and the final concentration of the anionic surfactant in the liquid culture medium in the wells was changed to five different concentrations: 0.5%, 1%, 3%, 5%, or 7%. The results are shown in Figure 6.

[0135] <Test Example 2-4> The same test as in Test Example 1-1 was performed, except that the fermented hyaluronic acid was replaced with an amphoteric surfactant (Genagen CAB818 (cocamidopropyl betaine), manufactured by Clariant Japan), and the final concentration of the amphoteric surfactant in the liquid culture medium in the wells was changed to five different concentrations: 0.5%, 1%, 3%, 5%, or 7%. The results are shown in Figure 7.

[0136] Note that the surfactant concentrations shown in Test Examples 2-1 to 2-4 represent the pure amounts of each surfactant contained in the product.

[0137] (Results of Test Examples 2-1 to 2-4) As shown in Figure 4, decyl glucoside, a nonionic surfactant, showed a tendency to inhibit the growth of the harmful bacterium G. vaginalis. On the other hand, L. crispas, a beneficial bacterium, showed less inhibition of its growth than G. vaginalis. Also, as shown in Figure 5, disodium cocoyl glutamate, an amino acid-based surfactant, showed a tendency to inhibit the growth of the harmful bacterium G. vaginalis. On the other hand, L. crispas, a beneficial bacterium, showed less inhibition of its growth than G. vaginalis. From the above, it was confirmed that nonionic surfactants and amino acid-based surfactants can improve the balance of the resident microbiota by exhibiting selective antibacterial activity against harmful bacteria. On the other hand, as shown in Figures 6 and 7, it was confirmed that anionic surfactants and amphoteric surfactants do not exhibit selective antibacterial activity against harmful bacteria.

[0138] <Test Example 3> Bacterial strains (L. crispas or G. vaginalis) were inoculated from culture plates into 20-30 ml of BHI liquid medium (BHI 37.0 g / L, hemin 5.0 mg / L, maltose 1.0%) and cultured at 37±2°C under anaerobic conditions without shaking for 24-48 hours. The resulting bacterial culture was centrifuged at 4°C, 4500x g, for 5 minutes, and the precipitate was resuspended in 1x PBS for approximately 10 minutes. 4 The bacterial count was adjusted to CFU / ml. Using the bacterial suspensions obtained above, bacterial suspensions were prepared so that L. crispas and G. vaginalis were in a ratio of 5:1 (L. crispas:G. vaginalis), and a master mix was created so that the ratio of the obtained bacterial suspension to BHI liquid medium was 1:8 (bacterial suspension:BHI liquid medium). The ratio of L. crispas and G. vaginalis (5:1) was selected to follow the natural balance usually found in the vaginal microbiota.

[0139] Next, a formulation (cleaning composition) (pH: 5.5) containing fermented hyaluronic acid, hydrolyzed hyaluronic acid, polyglyceryl-10 laurate (nonionic surfactant), and decyl glucoside (nonionic surfactant) was prepared. This formulation was diluted to 33% with purified water to obtain a formulation test solution (final concentration 33%). A sample for measurement was prepared by adding 500 u of the formulation test solution to 4.5 mL of the master mix. A control was prepared by adding 500 u of PBS to 4.5 mL of the master mix.

[0140] The measurement samples and controls were incubated at 37±2°C for 15 minutes with shaking. Time point t=0 (stock solution, 10 -1 ) and time point t = 15 min (undiluted solution, 10 -1 Cultured L. crispaus and G. vaginalis were spread onto sheep blood agar (5% sheep blood) using a spiral plater (Eddy Jet 2W, IUL Instruments) and cultured under anaerobic conditions at 37°C ± 2°C for 48 to 72 hours. Colony-forming units (CFUs) were then counted, and the ratio of each bacterium to the total L. crispaus and G. vaginalis was determined. The results are shown in Figure 8. Colonies of L. crispaus and G. vaginalis were identified by shape, color, and size.

[0141] (Results of Test Example 3) As shown in Figure 8, the proportion of L. crispas in the control group was approximately 68%, and the proportion of G. vaginalis was approximately 32%. On the other hand, when a formulation containing fermented hyaluronic acid, hydrolyzed hyaluronic acid, or a nonionic surfactant was applied, the proportion of L. crispas was approximately 81%, and the proportion of G. vaginalis was approximately 19%. Thus, it was confirmed that formulations containing fermented hyaluronic acid, hydrolyzed hyaluronic acid, or a nonionic surfactant can significantly reduce the proportion of the harmful bacterium G. vaginalis, and can improve the balance of the commensal microbiota by exerting a selective antibacterial effect.

[0142] <Test Example 4> A toxicity test was conducted on vaginal mucosal cells of the formulation (cleansing composition) from Test Example 3. The same test was performed on two cleansing compositions with higher pH levels than the formulation from Test Example 3 (pH 6.5, pH 9.5-10.0).

[0143] (Results of Test Example 4) The formulation (cleaning composition) of Test Example 3 was found to have lower toxicity compared to two other cleaning compositions with higher pH levels (pH 6.5, pH 9.5-10.0).

[0144] <Test Example 5> Twenty-three healthy female panelists used the formulation (cleansing composition) from Test Example 3 as a cleansing composition for delicate areas for four weeks (used at least once a day during bathing). The pH of the delicate area (vulva) was measured before use and after four weeks of use.

[0145] (Result 1 of Test Example 5) It was confirmed that there was no change in pH before and after use. Based on the above, it was confirmed that the original pH balance of the delicate area was not disrupted by using the formulation (cleaning composition) of Test Example 3. Note that when comparing the pH before and after use, if the change was within the range of 0 or ±1.0, it was evaluated that there was no change in pH and that the pH was maintained.

[0146] Furthermore, the total amount of lactic acid bacteria, various beneficial bacteria, and harmful bacteria in the delicate area (vulva) before use of the formulation (cleansing composition) of Test Example 3 was measured, as well as the total amount of lactic acid bacteria, various beneficial bacteria, and harmful bacteria in the delicate area (vulva) after one week and after four weeks of use. Bacterial samples were collected by wiping each side of the vulva eight times back and forth with a sterile cotton swab.

[0147] (Results 2 of Test Example 5) It was confirmed that the total amount of lactic acid bacteria in the delicate area remained unchanged before use (Day 0), at 1 week (Day 7), and after 4 weeks of use (Day 28) (Figure 9). It was confirmed that the amount of G. vaginalis in the total bacteria was decreasing from before use (Day 0), at 1 week (Day 7), and after 4 weeks of use (Day 28) (Figure 10). It was confirmed that the amount of L. crispas in the total bacteria was significantly increasing from before use (Day 0) to after 4 weeks of use (Day 28) (Figure 11).

[0148] Furthermore, a questionnaire survey was conducted among 23 female panelists in Test Example 5, asking about their concerns regarding their delicate areas before use (Day 0) and whether those concerns had lessened after 4 weeks of use (Day 28). The evaluation criteria for the questionnaire after 4 weeks are shown below. <Evaluation Criteria> 7: No longer bothered at all. 6: No longer bothered. 5: Slightly less bothered. 4: No change. 3: Slightly bothered. 2: Became bothered. 1: Very bothered.

[0149] (Results 3 of Test Example 5) Of the 23 expert panelists, 17 reported being concerned about odor in their delicate areas and 16 reported being concerned about dampness before use. After 4 weeks of use, 14 people selected a rating of 5 to 7 on the aforementioned evaluation criteria (number of people whose problems were reduced) for the odor item and 14 people for the dampness item. From these results, it was found that applying the formulation from Test Example 2 to the delicate area reduces concerns about odor and dampness in the delicate area.

[0150] Examples of formulations of the present invention are shown below.

[0151] <Formulation Example 1: Body Soap (Gel Type) (pH 6.0 (Undiluted))> Glycerin 5.0% by mass BG 3.0% by mass Polyglyceryl-10 Laurate 3.0% by mass Decyl Glucoside 3.0% by mass Sodium Cocoyl Glutamate 1.5% by mass Lauryl Hydroxysultaine 2.0% by mass Viscosity Modifier 2.0% by mass Fermented Hyaluronic Acid Solution 0.1% by mass Dipotassium Glycyrrhizate 0.1% by mass EDTA-2Na 0.1% by mass Appropriate amount of pH adjuster Purified water residue

[0152] <Formulation Example 2: Body Soap (Foam Type) (pH 5.8 (Undiluted))> Propylene Glycol 5.0% by mass Concentrated Glycerin 2.0% by mass Polyglyceryl-10 Laurate 3.0% by mass Sodium Cocoyl Methyl Taurate 3.0% by mass Sodium Lauroyl Glutamate 3.0% by mass Sodium Lauroamphoacetate 3.0% by mass Glyceryl Caprate 1.0% by mass Fermented Hyaluronic Acid Solution 1.0% by mass Dipotassium Glycyrrhizate 0.1% by mass EDTA-2Na 0.1% by mass Appropriate amount of pH adjuster Purified water residue

[0153] <Formulation Example 3: Lotion (pH 5.0 (undiluted solution))> Tocopherol acetate 0.1% by mass Isostearyl alcohol 3.0% by mass Triethylhexanoin 1.0% by mass Sorbitan oleate 0.5% by mass PEG-30 glyceryl isostearate 1.0% by mass PEG-40 glyceryl isostearate 0.8% by mass PCA glycereth-25 isostearate 0.6% by mass BG 8.0% by mass Concentrated glycerin 4.0% by mass Fermented hyaluronic acid solution 0.5% by mass Dipotassium glycyrrhizate 0.1% by mass EDTA-2Na 0.1% by mass Appropriate amount of pH adjuster Purified water residue

[0154] While the above examples and formulations illustrate specific embodiments of the present invention, these examples and formulations are merely illustrative and should not be interpreted restrictively. Various modifications that are obvious to those skilled in the art are intended to fall within the scope of the present invention.

Claims

1. A skin and / or mucous membrane microbiome balance improving agent containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof; (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

2. The commensal microbiota balance improving agent according to claim 1, wherein the skin and / or mucous membranes are skin and / or mucous membranes in a delicate area.

3. A resident microbiota balance improving agent according to claim 1 or 2, which improves the balance of the resident microbiota by reducing harmful bacteria.

4. The commensal microbiota balance improving agent according to claim 3, wherein the harmful bacteria are of the genus Gardnerella.

5. A resident microbiota balance improving agent according to claim 1 or 2, wherein the pH is 4.0 to 6.

0.

6. The resident microbiota balance improving agent according to claim 1 or 2, wherein component (A) is one or more selected from the group consisting of fermented hyaluronic acid, high molecular weight hyaluronic acid, low molecular weight hyaluronic acid, and salts thereof.

7. A method for improving the balance of resident microbiota by applying a composition containing one or more selected from the group consisting of the following components (A) and (B) to the skin and / or mucous membranes. (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants 8. A topical composition for delicate areas containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof; (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

9. The topical composition for delicate areas according to claim 8, for cleansing the skin and / or mucous membranes.

10. A topical composition for delicate areas according to claim 8 or 9, which is substantially free of preservatives.

11. A method for maintaining the pH balance of skin and / or mucous membranes by applying a composition containing one or more selected from the group consisting of the following components (A) and (B): (A) One or more selected from the group consisting of hyaluronic acid, hyaluronic acid derivatives, and salts thereof; (B) One or more selected from the group consisting of nonionic surfactants and amino acid-based surfactants.

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