JP7674804B2 - Transepidermal water loss inhibitor - Google Patents

Description

NPMD NITE P-02751

Article 30, paragraph 2 of the Patent Act applied. Presentation by an exhibitor at the Food Development Exhibition (2020) on September 2, 2020 https://www.informa-japan.com/hi/seminar/present.php?_ga=2.11593084.932877770.1604281293-1082705831.1604281293

The present invention relates to a transepidermal water loss inhibitor. The present invention is widely used in foods and beverages, pharmaceuticals, quasi-drugs, supplements, cosmetics, etc.

Maintaining and improving the condition of the skin is of interest to both men and women, regardless of time or age. Transepidermal water loss, also known as TEWL (trans epidermal water loss), is used to evaluate the skin's barrier, and keeping TEWL low is considered to indicate a strong barrier.

In order to enhance the skin barrier, Patent Document 1 proposes a skin topical preparation containing an extract of a plant of the genus Prunus in the family Rosaceae to further enhance the TEWL-inhibiting effect of organically modified clay minerals. Patent Document 2 also proposes an oil-in-water emulsion composition that contains a propylene polymer with a weight-average molecular weight of 25,000 to 100,000 and a melting point of 60°C to 100°C, a hydrocarbon oil with a melting point of less than 60°C, and an ester oil that is pasty at 25°C, in which the total oil amount is 5 to 20% by mass and the content of the paste-like ester oil relative to the total oil amount is 10 to 50% by mass (Patent Document 3).

Ulcerative colitis and Crohn's disease are inflammatory bowel diseases (IBDs) whose causes remain unclear and are difficult to treat. Factors involved in inflammatory bowel diseases include abnormalities in the intestinal flora, impaired secretory IgA production by intestinal epithelial cells, and cytokines under the intestinal mucosa (Patent Document 4).
It has also been reported that Lactobacillus casei strain GG increases IgA immune responses in the intestine, which may enhance the intestinal immunological barrier, and that intranasal administration of Lactobacillus rhamnosus GG enhances cell-mediated immune responses in the respiratory tract, thereby protecting mice from influenza virus infection. This indicates that IgA has a function of protecting against influenza infection and the like, and is also known to have a function of protecting against foreign substances such as viruses in the oral cavity (Patent Document 4).

JP 2007-153809 A JP 2016-79183 A JP 2018-177764 A JP 2018-008980 A

Under such circumstances, the present inventors have found that lactic acid bacteria derived from kudzu vines have the effect of suppressing transepidermal water loss and promoting the expression of proteins for improving skin barrier function (expression levels of involucrin, filaggrin, and transglutaminase 1), and have completed the present invention. Furthermore, through clinical trials, they have found that the lactic acid bacteria have the effect of suppressing transepidermal water loss, improving collagen density, and increasing IgA, and have completed the present invention.
That is, the present invention aims to provide a novel transepidermal water loss inhibitor, a skin barrier function improving protein expression promoter, an IgA increaser, and a collagen density improver, as well as a barrier improving agent using these.

The features of the present invention for solving the above problems are as follows.
1. A transepidermal water loss inhibitor with the active ingredient being lactic acid bacteria (Leuconostoc mesenteroides) derived from kudzu vines.
2. The transepidermal water loss inhibitor according to 1. above, characterized in that the lactic acid bacteria (Leuconostoc mesenteroides) derived from the kudzu vine is a strain of lactic acid bacteria (Leuconostoc mesenteroides) (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) and/or a mutant strain thereof.
3. A rough skin improving agent comprising the transepidermal water loss inhibitor described in 1 or 2 above as an active ingredient.
4. A moisturizing agent comprising the transepidermal water loss inhibitor described in 1 or 2 above as an active ingredient.
5. A stratum corneum moisturizing and barrier protein (involucrin, filaggrin, transglutaminase 1) expression promoter comprising a lactic acid bacterium (Leuconostoc mesenteroides) strain (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) derived from kudzu vine and/or a mutant strain thereof as an active ingredient.
6. A dermal collagen density improving agent comprising a lactic acid bacterium (Leuconostoc mesenteroides) strain derived from kudzu vine (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) and/or a mutant strain thereof as an active ingredient.
7. A skin quality improving agent containing, as an active ingredient, a lactic acid bacterium (Leuconostoc mesenteroides) strain derived from kudzu vine (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) and/or a mutant strain thereof.
8. An IgA enhancer comprising a lactic acid bacterium (Leuconostoc mesenteroides) strain derived from kudzu vine (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) and/or a mutant strain thereof as an active ingredient.

1 is a graph showing the transepidermal water loss inhibitory effect of "Kuzunotsuru lactic acid bacteria" (before SDS application). 1 is a graph showing the transepidermal water loss inhibitory effect of "Kuzunotsuru lactic acid bacteria" (after application of SDS). 1 is a graph showing the inhibitory effect of "Kuzunotsuru Lactic Acid Bacteria" on transepidermal water loss (amount of change before and after application of SDS). 1 is a graph showing the transepidermal water loss inhibitory effect of "Kuzunotsuru Lactic Acid Bacteria" (the difference between the applied area after SDS application and the unapplied area). 1 is a graph showing the amount of involucrin mRNA expression in skin caused by "Kuzunotsuru lactic acid bacteria." 1 is a graph showing the amount of skin filaggrin mRNA expression in "Kuzunotsuru Lactic Acid Bacteria." 1 is a graph showing the amount of skin transglutaminase 1 mRNA expression in "Kuzunotsuru Lactic Acid Bacteria." The nucleic acid sequence of the 16S rDNA gene of the "Kuzunotsuru Lactobacillus" strain is shown. This is an alignment comparing the 16S rDNA gene of the "Kuzunotsuru Lactobacillus" strain (the sequence of SIID23149-01 in the upper row) with the comparative Leuconostoc mesenteroides RIB.9186 strain (obtained from the National Research Institute of Brewing, the sequence of SIID23149-02 in the lower row). The 1243rd nucleic acid is "G" in SIID23149-01, whereas it is "A" in SIID23149-02 (shown in Figures 9A to 9C). This is an alignment comparing the 16S rDNA gene of the "Kuzunotsuru Lactobacillus" strain (the sequence of SIID23149-01 in the upper row) with the comparative Leuconostoc mesenteroides RIB.9186 strain (obtained from the National Research Institute of Brewing, the sequence of SIID23149-02 in the lower row). The 1243rd nucleic acid is "G" in SIID23149-01, whereas it is "A" in SIID23149-02 (shown in Figures 9A to 9C). This is an alignment comparing the 16S rDNA gene of the "Kuzunotsuru Lactobacillus" strain (the sequence of SIID23149-01 in the upper row) with the comparative Leuconostoc mesenteroides RIB.9186 strain (obtained from the National Research Institute of Brewing, the sequence of SIID23149-02 in the lower row). The 1243rd nucleic acid is "G" in SIID23149-01, whereas it is "A" in SIID23149-02 (shown in Figures 9A to 9C). This is a simplified molecular phylogenetic tree based on the nucleic acid sequence of the 16S rDNA gene of the "Kuzunotsuru Lactobacillus" strain. This is a graph showing the change in TEWL (cheek) between the placebo group and the lactic acid bacteria intake group in a clinical trial of ``Kuzunotsuru Lactic Acid Bacteria.'' This is a graph showing the change in TEWL (arm) between the placebo group and the lactic acid bacteria intake group in a clinical trial of ``Kuzunotsuru Lactic Acid Bacteria.'' This is a graph showing the change in saliva IgA in the placebo and lactobacillus intake groups in a clinical trial of "Kuzunotsuru lactobacillus" This is a graph showing the change in DermaLab (collagen score) in a clinical trial of "Kuzunotsuru Lactic Acid Bacteria."

The present invention will be described in detail below.
The present invention is characterized by using lactic acid bacteria (Leuconostoc mesenteroides) derived from kudzu vines as an active ingredient.

Kudzu (kudzu) is a creeping plant of the legume family, and its roots are widely used as an ingredient in traditional Chinese medicines such as kakkonto and as an ingredient in kudzu starch, known as Yoshino kudzu. Kudzu flowers have also been used since ancient times as an ingredient in traditional Chinese medicines, such as for preventing hangovers, the vines for kudzu cloth and handicrafts, and the leaves as livestock feed. There are no particular limitations on the lactic acid bacteria (Leuconostoc mesenteroides) derived from kudzu vines, so long as they are obtained from kudzu vines, but lactic acid bacteria (Leuconostoc mesenteroides) strain (Patent Microorganisms Deposit Center Accession Number NITE P-02751) and its mutant strains are preferred, as they have a more excellent effect of suppressing transepidermal water loss.

The lactic acid bacteria (Patent Microorganisms Depository Center Accession Number: NITE P-02751) strain can be obtained by enriching and culturing the kudzu vines in a liquid medium for lactic acid bacteria containing antibiotics at 25°C to 37°C for 24 to 48 hours, smearing the resulting culture on a BCP-added plate count agar medium, and selecting five new vine strains (Patent Microorganisms Depository Center Accession Number: NITE P-02751) belonging to Leuconostoc mesenteroides.

The typical culture conditions for the present lactic acid bacteria "Kuzunotsuru lactic acid bacteria" (Leuconostoc mesenteroides) (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) isolated from kudzu vines (note that in this specification, the lactic acid bacteria with Patent Microorganisms Deposit Center Accession Number: NITE AP-02601 will also be referred to as "Kuzunotsuru lactic acid bacteria") are static culture in MRS medium at 25-37°C for 24-48 hours, but are not limited thereto.

(Mycological characteristics)
The novel "Kuzunotsuru lactic acid bacteria" (accession number NITE P-02751) belonging to Leuconostoc mesenteroides of the present invention has the following bacteriological characteristics characteristic of Leuconostoc mesenteroides and is used in fermented foods such as sauerkraut. This bacterium has the following bacteriological characteristics:
- It is a gram-positive cocci that has a chain-like or diplococci morphology.
- They are classified into lactic acid bacteria and heterolactic acid bacteria that break down sugar and produce short-chain fatty acids such as acetic acid, ethanol, and _CO2 other than lactic acid bacteria.
(Definition of terms)
Listed below are definitions of terms specifically used in this specification.
The term "heated cells" as used herein refers to cells that have been heat-sterilized after cultivation. Typically, but not limited to, the term refers to cells that have been cultured at 20 to 40° C. for 10 to 40 hours and then heat-sterilized at 70 to 121° C. for 10 to 60 minutes.

A mutant strain of "Kuzunotsuru Lactic Acid Bacteria" can be prepared, for example, by carrying out a general mutation treatment, or by adaptation through successive culture or natural mutation.
The mutation treatment can be carried out using a common mutagen. Examples of mutagens include drugs having mutagenic activity, ultraviolet light, etc. Examples of drugs having mutagenic activity include streptomycin, ofloxacin, ethyl methanesulfonate, nucleotide base analogues such as N-methyl-N'-nitro-N-nitrosoguanidine, bromouracil, and acridines.

The transepidermal water loss inhibitor of the present invention can be used as an ingredient in various foods and beverages. Examples of foods and beverages include general foods such as confectionery (gum, candy, caramel, chocolate, cookies, snacks, jellies, gummies, candy tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, black tea, green tea, carbonated drinks, sports drinks, etc.), health foods (tablets, capsules, etc.), and nutritional supplements (nutritional drinks, etc.). The transepidermal water loss inhibitor of the present invention can be appropriately blended into these foods and beverages.

These foods and beverages can contain various ingredients depending on the type, for example, the following food ingredients can be used: glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorings, flavorings, and preservatives.

Specific manufacturing methods include spray-drying or freeze-drying the transepidermal water loss inhibitor together with powdered cellulose, and forming this into a powder, granules, tablets, or solution, which can be easily incorporated into food and beverages (instant foods, etc.). The transepidermal water loss inhibitor can also be dissolved in, for example, fats and oils, ethanol, glycerin, or a mixture of these to form a liquid, which can be added to beverages or solid foods. If necessary, it can also be mixed with a binder such as gum arabic or dextrin to form a powder or granules, which can be added to beverages or solid foods.

When the transepidermal water loss inhibitor of the present invention is applied to food and beverages, the amount of the active ingredient added is preferably 1 to 20 wt% or less in total relative to the food and beverage.

The transepidermal water loss inhibitor of the present invention may be used as a material for medicines (including pharmaceuticals and quasi-drugs). The medicines can be produced by appropriately blending the transepidermal water loss inhibitor of the present invention with raw materials for pharmaceutical preparations. Examples of pharmaceutical raw materials that can be incorporated into the transepidermal water loss inhibitor of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cacao butter, hardened vegetable oil, kaolin, talc, etc.), binders (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrants (sodium alginate, agar, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearate monoglyceride, starch, lactose, powdered gum arabic, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cacao butter, hydrogenated oil, etc.), absorption enhancers (quaternary ammonium base, sodium lauryl sulfate, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), and lubricants (purified talc, stearates, polyethylene glycol, etc.).

The transepidermal water loss inhibitor of the present invention can generally be administered orally in the form of tablets, pills, soft or hard capsules, fine granules, powders, granules, liquids, etc., but may also be administered parenterally. When administered parenterally, it may be administered in the form of a solution or with the addition of a dispersing agent, suspending agent, stabilizer, etc., by local tissue administration, intradermal, subcutaneous, intramuscular, or intravenous injection. It may also be in the form of a suppository, etc. Furthermore, it may be administered as an eye drop.

The dosage may vary depending on the method of administration, the condition, the age of the patient, etc., but typically, an adult may be administered 0.5 to 200 mg of the active ingredient per day, and a child may be administered 0.5 to 50 mg.
The blending ratio of the transepidermal water loss inhibitor can be appropriately changed depending on the dosage form, but it is usually about 0.3 to 15.0 wt% when administered orally or via mucosal absorption, and about 0.01 to 10 wt% when administered parenterally. Note that the dosage varies depending on various conditions, so in some cases a smaller dosage than the above is sufficient, and in other cases it is necessary to administer an amount exceeding the range.

The transepidermal water loss inhibitor of the present invention can be expected to have a transepidermal water loss inhibitory effect even when used as an external skin preparation (including cosmetics, medicines and quasi-drugs).
Examples of the form of external skin preparations that can be blended with the transepidermal water loss inhibitor of the present invention include milk lotions, soaps, facial cleansers, bath additives, creams, milk lotions, skin toners, colognes, shaving creams, shaving lotions, cosmetic oils, suntan/sunscreen lotions, face powders, foundations, perfumes, packs, nail creams, enamel, enamel removers, eyebrow pencils, blushers, eye creams, eye shadows, mascaras, eyeliners, lipsticks, lip balms, shampoos, rinses, hair dyes, dispersions, cleansers, etc. Examples of the form of pharmaceuticals or quasi-drugs that can be blended with the transepidermal water loss inhibitor of the present invention include ointments, creams, external liquids, etc.

In addition to the transepidermal water loss inhibitor of the present invention, the above-mentioned skin topical preparations can contain ingredients that are incorporated into skin topical preparations such as cosmetics and quasi-drugs, as long as the transepidermal water loss inhibitory effect is not impaired, such as oils, higher alcohols, fatty acids, UV absorbers, powders, pigments, surfactants, polyhydric alcohols/sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, and preservatives. Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oils Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, diisopropyl adipate, isoarachidyl neopentanoate, tri(caprylic/capric)glyceryl, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, tetra-2-ethylhexanoate Pentaerythritol phosphate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isostearyl laurate, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl oleate, octyldodecyl linoleate, isopropyl isostearate, cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate, ethylene glycol dioleate, propylene glycol dicaprate , propylene glycol dicaprylate, propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, glyceryl triisopalmitate, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyldecyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleate, polyglycerin isostearate, dipropyl carbonate, dialkyl carbonate (C12-18), triisocetyl citrate, triisoarachyl citrate, triisooctyl citrate, milk lauryl lactate, myristyl lactate, cetyl lactate, octyldecyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, isocetyl 12-stearoyl hydroxystearate, stearyl 12-stearoyl hydroxystearate, and isostearyl 12-stearoyl hydroxystearate.
Hydrocarbon-based oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum, etc.
Animal and vegetable oils and their hydrogenated oils, and natural waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated lard, horse oil, hydrogenated horse oil, mink oil, orange roughy oil, fish oil, hydrogenated fish oil, egg yolk oil, and other animal oils and their hydrogenated oils, avocado oil, almond oil, olive oil, cocoa butter, kiwi seed oil, apricot kernel oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, Examples of such oils include vegetable oils and their hydrogenated oils such as hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil, sunflower oil, grape seed oil, jojoba oil, hydrogenated jojoba oil, macadamia nut oil, medicamentoil, cottonseed oil, hydrogenated cottonseed oil, coconut oil, and hydrogenated coconut oil; and waxes such as beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax, and montan wax.
Silicone-based oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethylsiloxane-methylcetyloxysiloxane copolymer, dimethylsiloxane-methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic silicone, trimethylsiloxysilicate, silicone RTV rubber, and the like.
Fluorine-based oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl-polyoxyalkylene-co-modified organopolysiloxane, and the like.

(2) Examples of higher alcohols include lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, and octyldodecanol.

(3) Examples of fatty acids include caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid, erucic acid, and 2-ethylhexanoic acid.

(4) Examples of ultraviolet absorbers: para-aminobenzoic acid, amyl para-aminobenzoate, dihydroxypropyl ethyl para-aminobenzoate, glyceryl para-aminobenzoate, ethyl para-aminobenzoate, octyl para-aminobenzoate, octyldimethyl para-aminobenzoate, ethylene glycol salicylate, octyl salicylate, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl para-methoxycinnamate, 2-ethylhexyl para-methoxycinnamate, glyceryl di-para-methoxycinnamate mono-2-ethylhexanoate, isopropyl para-methoxycinnamate, diethanolamine salt of para-methoxyhydrocinnamate, mixture of diisopropyl and diisopropyl cinnamate, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid, and and its salts, dihydroxymethoxybenzophenone, sodium dihydroxymethoxybenzophenone disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, butylmethoxydibenzoylmethane, 2,4,6-trianilino-p-(carbo-2-ethylhexyl-1-oxy)-1,3,5-triazine, 2-(2-hydroxy-5-methylphenyl)benzotriazole, methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenylacrylate, phenylbenzimidazole sulfate, 3-(4-methylbenzylidene)camphor, isopropyldibenzoylmethane, 4-(3,4-dimethoxyphenylmethylene)-2,5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, as well as polymer derivatives and silane derivatives thereof.

(5) Examples of powders and pigments: Dyes such as Red No. 104, Red No. 201, Yellow No. 4, Blue No. 1, Black No. 401, lake dyes such as Yellow No. 4 AL Lake and Yellow No. 203 BA Lake, nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polymers such as polyethylene powder, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, colored pigments such as ultramarine and Prussian blue, zinc oxide, oxide Examples include white pigments such as titanium and cerium oxide, extender pigments such as talc, mica, sericite, kaolin, and plate-like barium sulfate, pearl pigments such as titanium mica, metal salts such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, and magnesium silicate, inorganic powders such as silica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, and zinc undecylenate, bentonite, smectite, boron nitride, etc. There are no particular limitations on the shape (spherical, rod-like, needle-like, plate-like, irregular, flaky, spindle-like, etc.) and particle size of these powders. These powders may or may not have been previously surface-treated by a conventionally known surface treatment, such as a fluorine compound treatment, a silicone treatment, a silicone resin treatment, a pendant treatment, a silane coupling agent treatment, a titanium coupling agent treatment, an oil treatment, an N-acylated lysine treatment, a polyacrylic acid treatment, a metal soap treatment, an amino acid treatment, a lecithin treatment, an inorganic compound treatment, a plasma treatment, or a mechanochemical treatment.

(6) Examples of surfactants Anionic surfactants: fatty acid soaps, α-acylsulfonates, alkylsulfonates, alkylarylsulfonates, alkylnaphthalenesulfonates, alkyl sulfates, POE alkyl ether sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyloylalkyl taurine salts, N-acylamino acid salts, POE alkyl ether carboxylates, alkylsulfosuccinates, sodium alkylsulfoacetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like.
Cationic surfactants: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride, behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearate diethylaminoethylamide, stearate dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, etc.
Amphoteric surfactants: Examples of amphoteric surfactants include carboxybetaine type, amidobetaine type, sulfobetaine type, hydroxysulfobetaine type, amidosulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, and amidoamine type.
Nonionic surfactants: propylene glycol fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE sorbitan fatty acid esters, POE glycerin fatty acid esters, POE alkyl ethers, POE fatty acid esters, POE hydrogenated castor oil, POE castor oil, POE-POP copolymers, POE-POP alkyl ethers, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipids, etc.
Natural surfactants: Examples of natural surfactants include lecithin, saponin, and sugar-based surfactants.

(7) Examples of polyhydric alcohols and sugars include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3-butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan, etc. Chemically modified versions of these can also be used.

(8) Examples of polymers: acrylic acid ester/methacrylic acid ester copolymer (Plussize, manufactured by GOO Chemical Co., Ltd.), vinyl acetate/crotonic acid copolymer (Resin 28-1310, manufactured by NSC Co., Ltd.), vinyl acetate/crotonic acid/vinyl neodecanoate copolymer (28-2930, manufactured by NSC Co., Ltd.), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP Co., Ltd.), t-butyl acrylate/ethyl acrylate/methacrylic acid copolymer (Rubymer, manufactured by BASF Co., Ltd.), vinylpyrrolidone/vinyl acetate/vinyl propionate copolymer (Ruviscol VAP, manufactured by BASF Co., Ltd.), vinyl Acetate/crotonic acid copolymer (Rubyset CA, BASF), vinyl acetate/crotonic acid/vinyl pyrrolidone copolymer (Rubyset CAP, BASF), vinyl pyrrolidone/acrylate copolymer (Rubyflex, BASF), acrylate/acrylamide copolymer (Ultrahold, BASF), vinyl acetate/butyl maleate/isobornyl acrylate copolymer (Advantage, ISP), carboxyvinyl polymer (Carbopol, BFGoodrich), acrylic acid/alkyl methacrylate copolymer (Pemulen, BF Examples of such polymers include anionic polymers such as acetic acid amphoteric product of dialkylaminoethyl methacrylate polymer (Yukaformer, manufactured by Mitsubishi Chemical Corporation) and amphoteric polymers such as octylacrylamide acrylate/hydroxypropyl acrylate/butylaminoethyl methacrylate copolymer (AMPHOMER, manufactured by NSC Corporation); cationic polymers such as quaternized product of vinylpyrrolidone/dimethylaminoethyl methacrylate (GAFQUAT, manufactured by ISP Corporation) and methylvinylimidazolium chloride/vinylpyrrolidone copolymer (Rubycoat, manufactured by BASF Corporation); and nonionic polymers such as polyvinylpyrrolidone (Ruviscol K, manufactured by BASF Corporation), vinylpyrrolidone/vinyl acetate copolymer (Ruviscol VA, manufactured by BASF Corporation), vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP Corporation), and vinylcaprolactam/vinylpyrrolidone/dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP Corporation). Also suitable for use are naturally occurring polymeric compounds such as cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharides, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth gum, alginic acid, albumin, casein, curdlan, gellan gum, and dextran.

(9) Examples of physiologically active ingredients: Examples of physiologically active ingredients include substances that impart some kind of physiological activity to the skin when applied to the skin, such as whitening ingredients, immune activators, anti-aging agents, UV protection agents, slimming agents, tightening agents, antioxidants, hair growth agents, moisturizers, blood circulation promoters, antibacterial agents, germicides, drying agents, cooling agents, warming agents, vitamins, amino acids, wound healing promoters, irritation mitigators, painkillers, cell activators, enzyme ingredients, etc. Examples of suitable ingredients include angelica extract, avocado extract, amacha extract, althea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo extract, fennel extract, turmeric extract, oolong tea extract, angelica tree extract, echinacea leaf extract, scutellaria extract, phellodendron bark extract, coptis japonica extract, barley extract, hypericum extract, white lamb's foot extract, watercress extract, orange extract, dried seawater, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, artemisia capillaris extract, licorice extract, kalkade extract, and kakyokueki. , Cinchona extract, Cucumber extract, Guanosine, Gardenia extract, Sasa kuma extract, Sophora arbutus extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract, Mulberry extract, Gentian extract, Black tea extract, Yeast extract, Burdock extract, Fermented rice bran extract, Rice germ oil, Comfrey extract, Collagen, Cowberry extract, Saishin extract, Saiko extract, Umbilical cord extract, Salvia extract, Soapwort extract, Bamboo grass extract, Hawthorn extract, Japanese pepper extract, Shiitake mushroom extract, Rehmannia root extract, Lithospermum root extract, Shiso extract, Linden extract, Spirea extract, Peony extract, Calamus root extract, White gnats Kiss, Horsetail extract, English ivy extract, Hawthorn extract, Elderberry extract, Yarrow extract, Peppermint extract, Sage extract, Mallow extract, Cnidium officinalis extract, Swertia japonica extract, Soybean extract, Chinese laurel extract, Thyme extract, Tea extract, Clove extract, Imperata cylindrica extract, Citrus aurantium extract, Angelica acutiloba extract, Calendula officinalis extract, Peach kernel extract, Spruce extract, Houttuynia cordata extract, Tomato extract, Natto extract, Carrot extract, Garlic extract, Wild rose extract, Hibiscus extract, Bacchus chinensis extract, Parsley extract, Honey, Witch hazel extract, Parietaria officinalis extract, Japanese knotweed extract, Bisabo extract Examples of such extracts include roll, loquat extract, coltsfoot extract, butterbur bud extract, poria extract, butcher's broom extract, grape extract, propolis, loofah extract, safflower extract, peppermint extract, linden extract, peony extract, hop extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract, peach extract, cornflower extract, eucalyptus extract, saxifrage extract, coix seed extract, mugwort extract, lavender extract, apple extract, lettuce extract, lemon extract, astragalus extract, rose extract, rosemary extract, Roman chamomile extract, and royal jelly extract.
In addition, it contains biopolymers such as deoxyribonucleic acid, mucopolysaccharides, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, and hydrolyzed eggshell membrane, moisturizing ingredients such as amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate, betaine, whey, and trimethylglycine, oily ingredients such as sphingolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, and phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, hydrolyzed eggshell membrane, and other components. Immune stimulants such as cortisone, vitamins such as vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoids, flavonoids, tannins, lignans, saponins, cell stimulants such as alpha-hydroxy acids and beta-hydroxy acids, blood circulation promoters such as gamma-oryzanol and vitamin E derivatives, retinol, wound healing agents such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, whitening agents such as glutathione, cepharanthine, licorice extract, capsicum tincture, hinokitiol, iodized garlic extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivatives, calcium pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropyl methylphenol, estradiol, ethinyl estradiol, Examples of hair growth agents include capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, tacanal, camphor, salicylic acid, vanillylamide nonylate, vanillylamide nonanoate, piroctone olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormones, cantharides tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polyoxyethylene sorbitan monostearate, peppermint oil, and Sasanishiki extract.

(10) Examples of antioxidants include sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolylbiguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxytoluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, tannins, lignans, saponins, and plant extracts having antioxidant effects such as apple extract and clove extract.

(11) Examples of solvents include purified water, ethanol, lower alcohols, ethers, LPG, fluorocarbons, N-methylpyrrolidone, fluoroalcohols, volatile linear silicones, next-generation fluorocarbons, etc.

The transepidermal water loss inhibitor of the present invention can be used as a raw material for food and drink compositions, pharmaceutical compositions, and external skin preparations.
The pharmaceutical raw materials that can be blended with these can be the same as those used in the transepidermal water loss inhibitor described above, and the manufacturing and administration methods can also be the same as those for the transepidermal water loss inhibitor.

The following are examples of the present invention. Note that the examples are provided to confirm the various actions and effects of the transepidermal water loss inhibitor obtained by the present invention, and the scope of the present invention is not limited to these products and manufacturing methods.

Example (1) Isolation of "Kuzunotsuru Lactic Acid Bacteria""Kuzunotsuru Lactic Acid Bacteria" belonging to Leuconostoc mesenteroides was isolated by the following procedure.
Kudzu vines were enriched in a liquid medium for lactic acid bacteria containing antibiotics at 25°C to 37°C for 24 to 48 hours. The resulting culture was smeared onto a BCP-added plate count agar medium, and five new strains of vines belonging to Leuconostoc mesenteroides were selected.
The "Kuzunotsuru lactic acid bacteria" belonging to Leuconostoc mesenteroides obtained as described above was deposited at the National Institute of Technology and Evaluation, Biotechnology Center, Patent Organism Depositary (NITE-IPOD) on July 11, 2018 (accession number NITE P-02751).
(2) 16S rDNA Gene Analysis of "Kuzunotsuru Lactic Acid Bacteria" The base sequence of the 16S rDNA gene of the isolated "Kuzunotsuru Lactic Acid Bacteria" was determined. The results are shown in Figure 8 (SEQ ID NO: 1). Figure 9 shows an alignment comparing the 16S rDNA gene of the "Kuzunotsuru Lactic Acid Bacteria" strain (SIID23149-01 in the upper row, SEQ ID NO: 1) with the comparative RIB.9186 strain belonging to Leuconostoc mesenteroides (obtained from the National Research Institute of Brewing, SIID23149-02 in the lower row, SEQ ID NO: 2).
Figure 10 is a simplified molecular phylogenetic tree based on the nucleic acid sequence of the 16S rDNA gene of "Kuzunotsuru Lactobacillus casei". The line in the upper left corner is a scale bar, the numbers at the branches of the phylogenetic branches are bootstrap values, and the "T" at the end of the strain name indicates the type strain of that species.

Test Example 1: Transepidermal Water Loss (TEWL) Evaluation Test Method for "Kuzunotsuru Lactic Acid Bacteria" Hairless mice were orally administered "Kuzunotsuru Lactic Acid Bacteria" powder (Patent Microorganisms Deposit Center Accession Number: NITE NITE P-02751) (50 or 100 mg/kg) for 28 days, and the TEWL of the dorsal skin was measured. After that, a sodium dodecyl sulfate solution (SDS solution) was applied to the right side of the midline for 5 minutes and then wiped clean. This procedure was repeated for a total of 3 days, and the TEWL was measured again the next day. The skin was then sampled the next day to examine the mRNA expression levels of involucrin, filaggrin, and transglutaminase 1.
The results are shown in Figure 1 (before SDS application), Figure 2 (after SDS application), Figure 3 (changes before and after SDS application), and Figure 4 (difference between the application site and the non-application site after SDS application). Figure 5 shows the expression level of involucrin, Figure 6 shows the expression level of filaggrin, and Figure 7 shows the expression level of transglutaminase 1. These are proteins present in the cornified envelope of the stratum corneum; involucrin promotes the keratinization of epidermal cells, filaggrin binds to keratin to strengthen the stratum corneum, and transglutaminase 1 promotes the cross-linking of keratin proteins.

Measurement results and effects of the embodiment in Test Example 1 As shown in Figures 1 and 2, it was confirmed that TEWL was suppressed by administration of "Kuzunotsuru Lactic Acid Bacteria", and especially at the SDS application site. In addition, as shown in Figure 3, it was confirmed that the TEWL suppression effect was excellent in a concentration-dependent manner at the SDS application site. In addition, as shown in Figure 4, when the difference between the SDS application site and the non-application site was examined, it was found that TEWL was significantly reduced at 100 mg/kg administration compared to the control. Furthermore, as shown in Figures 5 and 7, the expression levels of involucrin and transglutaminase 1 were significantly increased, and the expression level of filaggrin also showed an increasing tendency as shown in Figure 6, so it is considered that "Kuzunotsuru Lactic Acid Bacteria" increases the expression level of stratum corneum proteins involved in moisturizing and barrier function.
From the above, it was confirmed that "Kuzunotsuru Lactobacillus" is useful as a TEWL inhibitor, and therefore useful as a moisturizer. In addition, since TEWL was particularly suppressed in the SDS application area, it was also confirmed to be useful as an agent for improving rough skin.

Test Example 2: Clinical trial of "Kuzunotsuru Lactic Acid Bacteria"
1. Test outline ・Test period: May 14th - June 25th (6 weeks)
・Subjects: 27 (20 men, 8 women)
- Study design: Double-blind comparative study (placebo group: 14 people, lactobacillus group: 14 people)
One woman in the placebo group dropped out due to ill health.
Test method: Salivary IgA, dermal collagen density, TEWL (transepidermal water loss), questionnaire (questionnaire on skin quality). The above dermal collagen density was measured by measuring the collagen score (which represents the density of collagen in the dermis in DermaLab. The higher the value, the more abundant the collagen and the better the condition of the dermal collagen).
*The questionnaire was created based on the article entitled "Effects of taking lactic acid bacteria fermentation filtrate PS-B1 on bowel movements, stool characteristics, and skin quality" published in the Journal of the Japanese Society for Food and Nutrition, Vol. 30, No. 3, pp. 112-122 (2020), and participants were asked to fill out the form shown in Table 1 below.
The results are shown in Figure 11 (TEWL (cheek)), Figure 12 (TEWL (arm)), Figure 13 (salivary IgA), Figure 14 (change in DermaLab (collagen score)), and Table 2 (skin type questionnaire).

Results and Effects of Examples in Test Example 2 (1) Transepidermal Water Loss (TEWL) (cheek)
As shown in Figure 11, both the placebo group and the lactobacillus intake group showed significant reductions after 4 weeks (4W) and 6 weeks (6W) of intake compared to before intake (0W) in each group. There was no significant difference between the groups, but the lactobacillus intake group showed a greater tendency for improvement. This confirmed that Kuzunotsuru lactobacillus has an effect of improving TEWL in the cheeks.
(2) Transepidermal water loss (TEWL) (arm)
As shown in Figure 12, compared to before intake (0W), both the placebo group and the lactobacillus intake group showed a significant decrease at 4W and 6W intake within each group. Although there was no significant difference between the groups, there was a tendency for improvement in the lactobacillus intake group. This confirmed that Kuzunotsuru lactobacillus has an effect of improving TEWL in the arms as well.
(3) Salivary IgA
As shown in Figure 13, only in the lactobacillus intake group, IgA levels increased significantly at 4W compared to before intake (0W). Although there was no significant difference between the groups, there was a tendency for IgA to increase in the lactobacillus intake group (see Figure 13). This confirmed that Kuzunotsuru lactobacillus has the effect of increasing IgA.
(4) DermaLab (Dermal Collagen Density)
As shown in FIG. 14, the collagen score, an index showing the density of dermal collagen, was significantly increased at both 4W and 6W compared to before intake (0W) only in the lactic acid bacteria intake group.
In addition, although there was no significant difference between the groups, an increasing trend was observed in the lactobacillus intake group. This confirmed that Kuzunotsuru lactobacillus has the effect of improving the density of dermal collagen.

(5) Questionnaire (skin type related)
As shown in Table 2, in the category of "glowing skin," only the lactobacillus intake group showed significant improvement at 4W compared to before intake (0W), and there was also a tendency for improvement at 6W.
Additionally, in the category of "firm skin," only the lactic acid bacteria intake group showed a significant improvement at 6W compared to before intake (0W).
Additionally, in the category of "even skin tone," only the lactic acid bacteria intake group showed a tendency for improvement at 4W compared to before intake (0W).
Furthermore, in the category of "skin that is not sticky," although there was no significant difference in the lactic acid bacteria group, the condition worsened in the placebo group, whereas there was no change in the lactic acid bacteria group, so it can be said that there was a tendency for improvement when compared with the placebo.
In addition, in the category of "skin that is not bothered by dryness," only the lactobacillus intake group showed significant improvement at 4W and 6W compared to before intake (0W). These results confirmed that Kuzunotsuru lactobacillus has the effect of improving skin quality.

The above results confirmed that Kuzunotsuru Lactic Acid Bacteria has a dual barrier function for both the skin and the immune system, in addition to improving transepidermal water loss (TEWL) and collagen density, and increasing salivary IgA, as determined by a questionnaire (related to skin type).

The following are examples of formulations of the transepidermal water loss inhibitor (Kuzunotsuru lactic acid bacteria) according to the present invention. Note that the following formulation examples do not limit the present invention.
Formulation example 1: Chewing gum
Sugar 53.0wt%
Gum base 20.0
Glucose 10.0
Syrup 16.0
Fragrance 0.5
Transepidermal water loss inhibitor 0.5
100.0wt%

Mixture Example 2: Gummies
Reduced starch syrup 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Yuzu juice 4.0
Yuzu flavor 0.6
Pigment 0.02
Transepidermal water loss inhibitor 1.0
100.0wt%

Mixture example 3: Candy
Sugar 50.0wt%
Syrup 33.0
Water 14.4
Organic acids 2.0
Fragrance 0.2
Transepidermal water loss inhibitor 0.4
100.0wt%

Mixture example 4: Yogurt (hard/soft)
Milk 41.5wt%
Skim milk powder 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Transepidermal water loss inhibitor 0.4
Fragrance: Trace
Water Residual
100.0wt%

Mixture example 5: Soft drinks
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Transepidermal water loss inhibitor 0.3
Fragrance (appropriate amount)
Purified water Residual
100.0wt%

Mixture Example 6: Tablets
Sugar 76.4wt%
Glucose 19.0
Sucrose fatty acid ester 0.2
Transepidermal water loss inhibitor 0.5
Purified water 3.9
100.0wt%

Formulation Example 7: Soft Capsule
Brown rice germ oil 47.0wt%
Yuzu seed oil 40.0
Emulsifier 12.0
Transepidermal water loss inhibitor 1.0
100.0wt%

Formulation Example 8: Tablets
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch hydrolysate 10.0
Glycerin fatty acid ester 5.0
Transepidermal water loss inhibitor 1.0
100.0wt%

Formulation Example 9: Cosmetic cream Squalane 20.0 wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerin Monostearate 2.0
Polyoxyethylene (20) Sorbitan-
Monostearate 2.0
Transepidermal water loss inhibitor 2.0
Preservatives: appropriate amount Fragrance: appropriate amount
Purified water Residual
100.0wt%

Formulation Example 10: Lotion Ethanol 5.0 wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Transepidermal water loss inhibitor 0.1
Purified water Residual
100.0wt%

Formulation Example 11: Body Gel Macadamia nut oil 2.0 wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Polyoxyethylene sorbitol 2.0 tetraoleate
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol Palmitate 0.1
Preservatives: Appropriate amount Centella asiatica extract: 1.0
Transepidermal water loss inhibitor 1.0
1,3-butylene glycol 5.0
Purified water Residual
100.0wt%

Formulation Example 12: Milky Lotion Squalane 4.0 wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-Arginine 1.0
Transepidermal water loss inhibitor 0.5
Potassium hydroxide 0.1
Fragrance: Trace
Purified water Residual
100.0wt%

Formulation Example 13: Bath additive (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
Transepidermal water loss inhibitor 0.5
Lanolin 0.5
Avocado oil 0.5
Pigment 1.5
Fragrance 22.0
100.0wt%

As a result, the present invention can provide a novel transepidermal water loss inhibitor.

The "Tsuru 5" strain, belonging to Leuconostoc mesenteroides, was deposited at the National Institute of Technology and Evaluation, Biotechnology Center, Patent Organism Depositary (NITE-IPOD) on July 11, 2018 (accession number NITE P-02751).

SEQ ID NO: 1: Nucleic acid sequence of the 16S rDNA gene of the "Tsuru 5" strain SEQ ID NO: 2: Nucleic acid sequence of the 16S rDNA gene of the RIB. 9186 strain belonging to Leuconostoc mesenteroides

Claims (3)

A transepidermal water loss inhibitor comprising a lactic acid bacterium (Leuconostoc mesenteroides) strain (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) as an active ingredient. A skin roughness improving agent containing the transepidermal water loss inhibitor described in claim 1 as an active ingredient. A stratum corneum moisturizing and barrier protein expression promoter containing a lactic acid bacterium (Leuconostoc mesenteroides) strain derived from kudzu vine (Patent Microorganisms Deposit Center Accession Number: NITE P-02751) as an active ingredient.