JP2024015051A - PROFILAGGRIN mRNA EXPRESSION PROMOTER, SERINE PALMITOYL TRANSFERASE mRNA EXPRESSION PROMOTER, AND HYALURONAN SYNTHASE 3 mRNA EXPRESSION PROMOTER - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel composition that is superior in skin-whitening action and/or anti-aging action and offers high safety, a skin-whitening agent that has superior skin-whitening action and offers high safety, an anti-aging agent that has superior anti-aging action and offers high safety, skin cosmetics that are superior in skin-whitening action and/or anti-aging action and offer high safety, and food and drink that are superior in skin-whitening action and/or anti-aging action and offer high safety.

SOLUTION: Licorice extract ferment is a ferment of licorice extract by a microbe. The licorice is Glychyrrhiza glabra. The microbe is Lactobacillus plantarum. Provided are also herein a skin-whitening agent or an anti-aging agent containing the licorice extract ferment, as well as skin cosmetics or food and drink containing at least one selected from the group consisting of the licorice extract ferment, skin-whitening agent and anti-aging agent.

SELECTED DRAWING: None

COPYRIGHT: (C)2024,JPO&INPIT

Description

The present invention relates to a fermentation product of Glychyrrhiza glabra extract with Lactobacillus plantarum , a whitening agent and an anti-aging agent containing the same, and skin cosmetics and food and drink products.

Conventionally, to prevent, treat, or improve skin pigmentation, age spots, freckles, etc., treatments have been carried out by externally applying whitening agents containing chemically synthesized products such as hydroquinone as an active ingredient. However, chemically synthesized products such as hydroquinone may have side effects such as skin irritation and allergies. Therefore, there is a desire to develop a skin whitening agent that contains highly safe natural raw materials as active ingredients, and for example, willow extract (see Patent Document 1) is known as a skin whitening agent that has a tyrosinase activity inhibiting effect. ing.

Filaggrin is a component of the skin and is thought to be involved in the barrier function of the skin, having the function of preventing the invasion of allergens, toxins, and infectious organisms. Decreased function of filaggrin due to genetic mutations is associated with the risk of developing atopic diseases, including atopic dermatitis (eczema, skin inflammation, skin itching, etc.), allergies, asthma, etc. It is known that this can lead to skin diseases such as ichthyosis vulgaris (for example, see Non-Patent Document 1).

On the other hand, amino acids, which are the main components of Natural Moisturizing Factors (NMF), are produced when filaggrin derived from keratohyalin granules is decomposed within the stratum corneum. This filaggrin is expressed as profilaggrin in epidermal keratinocytes present in the granular layer just below the stratum corneum. Thereafter, it is immediately phosphorylated, accumulated in keratohyalin granules, dephosphorylated, hydrolyzed, and decomposed into filaggrin, and transferred to the stratum corneum, increasing the aggregation efficiency of keratin filaments and participating in the internal structure of corneocytes. This is known (for example, see Non-Patent Document 2). In recent years, it has been known that this filaggrin is extremely important and essential for retaining moisture in the skin, and that conditions such as dryness reduce the synthetic ability of filaggrin and reduce the amount of amino acids in the stratum corneum ( For example, see Non-Patent Document 3).

Therefore, by promoting the expression of profilaggrin in epidermal keratinocytes, atopic diseases including atopic dermatitis (eczema, skin inflammation, skin itching, etc.), allergies, asthma, etc. can be prevented, treated, or improved. it is conceivable that. Furthermore, by promoting the expression of profilaggrin and thereby increasing the amount of amino acids in the stratum corneum, it is expected that the water environment of the stratum corneum can be essentially improved. Hitherto, as a substance having an effect of promoting profilaggrin mRNA expression, an extract of Aspergillus orientalis (for example, see Patent Document 2) and the like have been known.

The epidermis and dermis of the skin are composed of epidermal cells, fibroblasts, and extracellular matrices such as collagen, elastin, and hyaluronic acid that are outside these cells and support the skin structure. In young skin, fibroblasts proliferate actively, and the interaction between fibroblasts and skin tissues such as extracellular matrix components maintains homeostasis, ensuring water retention, flexibility, elasticity, etc. It is maintained in a fresh state with a firm and glossy appearance.

However, under the influence of certain external factors such as ultraviolet irradiation, extremely dry air, excessive skin cleansing, etc., or as aging progresses, collagen, elastin, and hyaluron, which are the main components of the extracellular matrix, are reduced. The amount of acid produced decreases, causing decomposition and deterioration. As a result, the moisturizing function and elasticity of the skin decrease, and abnormal exfoliation of the keratin occurs, causing the skin to lose its firmness and luster, and to exhibit aging symptoms such as rough skin and wrinkles. As described above, the changes associated with skin aging, such as wrinkles, dullness, changes in texture, and decreased elasticity, are associated with the reduction and denaturation of matrix components such as collagen, elastin, and hyaluronic acid. Therefore, promoting the production of hyaluronic acid and the like is important in preventing, treating, or improving skin aging.

Among the extracellular matrix components mentioned above, hyaluronic acid is a type of mucopolysaccharide and has the function of retaining cells by filling the intercellular spaces, and also retains water in the intercellular spaces and transfers it to tissues. It has many functions, such as providing lubricity and flexibility, and resisting external forces such as mechanical disturbances. It is believed that if the production of hyaluronic acid can be promoted, it will be possible to prevent, treat, or improve skin aging symptoms such as rough skin, wrinkles, dullness, changes in texture, decreased elasticity, and decreased moisturizing function. Furthermore, it is thought that skin aging can be prevented, treated, or improved by promoting the expression of hyaluronic acid synthase 3 (HAS3), which is involved in promoting the synthesis of epidermal hyaluronic acid.

In addition to skin tissue, hyaluronic acid is present in cartilage, synovial fluid, umbilical cord, vitreous body of the eye, and other connective tissues. Among these, hyaluronic acid contained in synovial fluid coats the surface of articular cartilage and is useful for the smooth operation of joints due to its lubricating function, covering and protecting function for cartilage, etc. On the other hand, it is known that the concentration of hyaluronic acid in joint fluid decreases in arthritis such as rheumatoid arthritis. Therefore, it is thought that by promoting the production of hyaluronic acid, arthritis such as rheumatoid arthritis, osteoarthritis, septic arthritis, gouty arthritis, traumatic arthritis, or osteoarthritis can be prevented or treated. Furthermore, during the healing process of a wound or burn, granulation (tissue) is formed, and it is known that hyaluronic acid increases significantly in the granulation. Therefore, it is thought that by promoting the production of hyaluronic acid, healing of wounds or burns can be promoted. As a substance having a hyaluronic acid production-promoting effect, an extract from camphorax (for example, see Patent Document 3) is known.

Furthermore, among the stratum basale, stratum spinosum, stratum granulosum, and stratum corneum that make up the epidermis, especially in the stratum granulosum, the cell membrane thickens to form a thickened cell membrane, and due to the action of transglutaminase-1, protein Intermolecular glutamyl-lysine crosslinks form strong keratin protein fibers. Furthermore, ceramide or the like is covalently bonded to a part of it, forming a hydrophobic structure, which provides the foundation for the lamellar structure of intercellular lipids, forming the basis of the stratum corneum barrier function.

Ceramide is produced from serine and palmitoyl-CoA during the keratinization process of epidermal cells by the action of enzymes including serine palmitoyltransferase (SPT), which is known as the rate-limiting enzyme for ceramide synthesis. Ceramide exists specifically as a main component of the interkeratinocyte lipids that cover the outermost layer of the skin, and plays an important role in maintaining the skin's inherent function as a barrier membrane between the living body and the outside world.

The structure of the stratum corneum can be compared to that of bricks and mortar, with intercellular lipids connecting the stratum corneum cells stacked in about 15 layers to form a strong barrier membrane. Corneocytes retain moisture by containing natural moisturizing factors containing amino acids as their main components, while interkeratinocyte lipids contain approximately 50% ceramide as a main component and contain cholesterol, fatty acids, etc. It is composed of medium lipids and is characterized by a lamellar structure, a so-called lamellar structure, in which hydrophobic parts and hydrophilic parts are alternately repeated.

Deterioration of the skin barrier function due to various internal and external factors increases the amount of transepidermal water evaporation, causing skin dryness, scaling, itching, etc., resulting in so-called dry skin. Furthermore, a decrease in the skin's barrier function increases skin inflammation, leading to a vicious cycle in which the defense function against various stimuli from the outside world decreases. Recent studies have reported a decrease in keratin ceramide components (so-called intercellular lipids) and changes in their composition due to aging or in patients with atopic dermatitis, which is known as barrier disorder (for example, see Non-Patent Document 4). It has become widely known that ceramides are important in maintaining and improving skin barrier function. As methods for improving the barrier function of the skin, methods for supplementing ceramide from the outside (for example, see Non-Patent Document 5) and methods for increasing ceramide production ability within the skin (for example, see Non-Patent Document 6) are known. .

However, there is still a strong demand for substances that have better whitening or anti-aging effects, are highly safe, and can be used as active ingredients in whitening agents, anti-aging agents, skin cosmetics, or food and beverages. The current situation is that prompt development is required.

JP2004-083488A Japanese Patent Application Publication No. 2012-219047 Japanese Patent Application Publication No. 2003-146837

“Nat Genet.”, 2006, Vol. 38, No. 4, p. 441-446 "Fragrance Journal Extra Edition", 2000, Vol. 17, p. 14-19 “Arch. Dermatol. Res.”, 1996, Vol. 288, p. 442-446 J. Dermatol. , 1993, Vol. 20, No. 1, p. 1-6 "Fragrance Journal", 2004, Vol. 32, No. 11, p. 23-32 Br. J. Dermatol. , 2000, Vol. 143, Issue 3, p. 524-531

An object of the present invention is to solve the problems in the conventional art and to achieve the following objects. That is, an object of the present invention is to provide a novel composition that has excellent whitening effect and/or anti-aging effect and is highly safe.
Another object of the present invention is to provide a whitening agent that has an excellent whitening effect and is highly safe.
Another object of the present invention is to provide an anti-aging agent that has excellent anti-aging effects and is highly safe.
Another object of the present invention is to provide a highly safe skin cosmetic that has at least one of excellent whitening effect and anti-aging effect.
Another object of the present invention is to provide highly safe foods and drinks that have at least one of excellent whitening effect and anti-aging effect.

As a result of intensive studies by the present inventors to solve the above problems, we found that a fermented product of Glychyrrhiza glabra extract with Lactobacillus plantarum has excellent whitening and anti-aging effects. The present invention was completed based on the knowledge that the present invention has an effect.

The present invention is based on the above findings of the present inventors, and means for solving the above problems are as follows. That is,
<1> A fermented product of licorice extract by microorganisms,
The daylily is Glychyrrhiza glabra ,
The fermented liquorice extract is characterized in that the microorganism is Lactobacillus plantarum .
<2> A whitening agent characterized by containing the fermented licorice extract according to <1> above.
<3> The whitening agent according to <2> above, which has a tyrosinase activity inhibiting effect.
<4> An anti-aging agent characterized by containing the fermented licorice extract according to <1> above.
<5> The anti-aging agent according to <4>, which has at least one selected from the group consisting of a profilaggrin mRNA expression promoting effect, a serine palmitoyltransferase mRNA expression promoting effect, and a hyaluronic acid synthase 3 mRNA expression promoting effect. .
<6> From the fermented licorice extract according to <1>, the whitening agent according to any one of <2> to <3>, and the anti-aging agent according to any one of <4> to <5>. This skin cosmetic is characterized by containing at least one member selected from the group consisting of:
<7> From the fermented licorice extract according to <1>, the whitening agent according to any one of <2> to <3>, and the anti-aging agent according to any one of <4> to <5>. It is a food/beverage product characterized by containing at least one kind selected from the group consisting of:

According to the present invention, it is possible to solve the above-mentioned conventional problems and provide a novel composition that has excellent whitening effect and/or anti-aging effect and is highly safe.
According to the whitening agent of the present invention, it is possible to solve the above-mentioned conventional problems and provide a whitening agent that has an excellent whitening effect and is highly safe.
According to the anti-aging agent of the present invention, it is possible to solve the above-mentioned conventional problems, and to provide an anti-aging agent that has an excellent anti-aging effect and is highly safe.
According to the skin cosmetic of the present invention, it is possible to provide a highly safe skin cosmetic that solves the various conventional problems and has at least one of excellent whitening effect and anti-aging effect.
According to the food and drink products of the present invention, it is possible to solve the above-mentioned conventional problems, and to provide highly safe food and drink products that have at least one of an excellent whitening effect and an anti-aging effect.

(Fermented licorice extract)
The fermented licorice extract of the present invention is a fermented product of an extract from licorice using microorganisms.

<Licorice extract>
Licorice is a perennial herb belonging to the Fabaceae family, genus Glycyrrhiza , and has been used for medicinal purposes or as a raw material for sweeteners since ancient times.
The daylily in the present invention is Glychyrrhiza glabra .

As the licorice extract, one prepared from the extraction site used as an extraction raw material may be used, or a commercially available product may be used.
There are no particular restrictions on the part to be extracted from the licorice, and it can be selected as appropriate depending on the purpose. Examples include above-ground parts, roots, rhizomes, and mixtures of these parts. Among these, the roots, leaves, and rhizomes are preferred.
The method for preparing the extraction parts of the licorice is not particularly limited and can be selected as appropriate depending on the purpose. For example, after drying each part, it may be subjected to solvent extraction as it is or by pulverizing it using a coarse crusher. This can be obtained by The drying may be performed under the sun or using a commonly used dryer.

The licorice extract can be easily obtained by a method commonly used for extracting plants. The licorice extract is not particularly limited and can be selected as appropriate depending on the purpose, and examples include diluted extracts, concentrated solutions, dried extracts, crudely purified products, purified products, etc. .

The method for extracting the licorice is not particularly limited and can be selected as appropriate depending on the purpose. Examples include a method of obtaining an extract by eluting soluble components with appropriate stirring and then filtering to remove extraction residues.
Alternatively, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a nonpolar solvent such as hexane. By performing pretreatment such as degreasing, extraction treatment using a polar solvent can be performed efficiently.

There are no particular restrictions on the conditions (extraction time and extraction temperature), extraction solvent, and amount used in the extraction of the licorice, and they can be appropriately selected depending on the purpose.

The extraction solvent is not particularly limited and can be appropriately selected depending on the purpose, and includes, for example, water, a hydrophilic organic solvent, or a mixed solvent thereof.

The water is not particularly limited and can be appropriately selected depending on the purpose, such as pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, purified water, hot water, Examples include ion-exchanged water, physiological saline, phosphate buffer, and phosphate buffered saline.

The hydrophilic solvent is not particularly limited and can be appropriately selected depending on the purpose. Examples include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; acetone, methyl ethyl ketone, etc. Lower aliphatic ketones; examples include polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin.

The mixed solvent is not particularly limited and can be appropriately selected depending on the purpose, but when using a lower alcohol, 1 part by mass to 90 parts by mass, lower aliphatic ketone per 10 parts by mass of water. When using, it is preferable to add 1 part by mass to 40 parts by mass per 10 parts by mass of water, and when using a polyhydric alcohol, it is preferably added from 1 part by mass to 90 parts by mass per 10 parts by mass of water.

The liquorice extraction solvent is preferably used at a temperature ranging from room temperature to the boiling point of the solvent.

The obtained licorice extract is subjected to treatments such as dilution, concentration, drying, and purification according to conventional methods in order to obtain diluted, concentrated, dried, crudely purified, and purified licorice extracts. It's okay.

The licorice extract prepared as described above is subjected to fermentation using microorganisms described below.

<Fermentation>
The fermentation method is not particularly limited as long as Lactobacillus plantarum is used, and can be appropriately selected from known fermentation methods depending on the purpose.

-Lactobacillus plantarum-
The Lactobacillus plantarum is not particularly limited and can be appropriately selected depending on the purpose. Here, Lactobacillus plantarum is a type of lactic acid bacteria, but since it is mainly isolated from vegetable fermented foods such as pickled vegetables, kimchi, and miso, it is included in vegetable lactic acid bacteria, and is included in fermented milk such as yogurt. This is different from the animal lactic acid bacteria used to produce lactic acid bacteria drinks. The Lactobacillus plantarum may be used alone or in combination of two or more. When using two or more kinds of Lactobacillus plantarum in combination, fermentation may be performed simultaneously with two or more kinds of Lactobacillus plantarum, or fermentation may be performed separately.

Among the Lactobacillus plantarum, Lactobacillus plantarum 22A-1 (FERM BP-21409), Lactobacillus plantarum 22A-3 (FERM BP-21411), and Lactobacillus plantarum 22B-2 (FERM It is preferable to use at least one species selected from the group consisting of BP-21410), and it is particularly preferable to use Lactobacillus plantarum 22A-3 (FERM BP-21411). The three strains, Lactobacillus plantarum 22A-1 (FERM BP-21409), Lactobacillus plantarum 22A-3 (FERM BP-21411), and Lactobacillus plantarum 22B-2 (FERM BP-21410) are , is a strain isolated and identified from pickles by the present applicant, and an application was filed for deposit with the Patent Organism Depositary Center of the National Institute of Advanced Industrial Science and Technology, and the deposit was received on October 22, 2007.

-Fermentation treatment-
The fermentation treatment can be carried out, for example, by dissolving the concentrated and dried licorice extract in water, or by using the licorice extract as it is without concentrating and drying it and inoculating it with the Lactobacillus plantarum.

The fermentation treatment using Lactobacillus plantarum can be carried out, for example, by placing an aqueous solution of licorice extract and the Lactobacillus plantarum in a fermenter at a temperature range of 25°C to 35°C, preferably 28°C to 32°C. , by treating for 12 to 72 hours, preferably 18 to 48 hours. Furthermore, when the pH of the reaction solution is adjusted to 5.0 to 7.0, preferably 5.5 to 6.5 at the start of the fermentation process, the fermentation process will proceed suitably. Such fermentation treatment is terminated by subjecting the fermentation liquid to a desired means such as cooling, heat sterilization, and filtration to inactivate fermentation bacteria.

The fermented liquid obtained in this way may be used as a fermented product as it is, or may be diluted or concentrated as appropriate and used as a fermented product. Furthermore, the concentrate may be further dried, and may be subjected to rough purification, purification, etc.

Note that, before the above-mentioned extraction treatment and fermentation treatment, the extraction raw material and the extract (fermentation raw material) may be subjected to treatment to increase extraction efficiency and fermentation efficiency. Preferred examples of such treatment include, for example, enzymatic treatment using glucanase, cellulase, and the like. For example, it is particularly preferable to subject the extract obtained by the extraction treatment to an enzyme treatment, since this increases the efficiency of the subsequent fermentation treatment.

The fermented licorice extract obtained in this way exhibits excellent whitening and anti-aging effects, and is therefore suitable as an active ingredient in whitening agents and anti-aging agents, which will be described later, or as a compounding ingredient in skin cosmetics and food and drink products. Can be used.
The fermented licorice extract can be used as it is as an active ingredient in skin whitening agents and anti-aging agents, which will be described later, or as a compounding ingredient in skin cosmetics and food and drink products. The dried product is preferred. When obtaining the dried product, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity.

(Whitening agent and anti-aging agent)
The whitening agent and anti-aging agent of the present invention contain the above-mentioned fermented licorice extract of the present invention, and further contain other components as necessary.

The whitening agent has a tyrosinase activity inhibiting effect.

The anti-aging agent has at least one selected from the group consisting of a profilaggrin mRNA expression promoting effect, a serine palmitoyltransferase mRNA expression promoting effect, and a hyaluronic acid synthase 3 mRNA expression promoting effect.

The details of the substance contained in the fermented licorice extract that exhibits at least one of the following effects are unknown: tyrosinase activity inhibition, profilaggrin mRNA expression promotion, serine palmitoyl transferase mRNA expression promotion, and hyaluronic acid synthase 3 mRNA expression promotion. However, it was not previously known that the fermented licorice extract had such excellent effects and was useful as a whitening agent and an anti-aging agent, and the present inventors' new findings It is.

<Fermented liquorice extract>
The fermented licorice extract is the above-mentioned fermented licorice extract of the present invention.
The content of the fermented licorice extract in the whitening agent and anti-aging agent is not particularly limited, and can be adjusted as appropriate depending on the physiological activity of the extract. The whitening agent and anti-aging agent may consist only of the fermented licorice extract.

<Other ingredients>
The other components are not particularly limited and can be appropriately selected depending on the usage form of the whitening agent and anti-aging agent. For example, excipients, moisture-proofing agents, preservatives, strengthening agents, thickeners, emulsifiers, antioxidants, sweeteners, acidulants, seasonings, colorants, fragrances, whitening agents, humectants, oily ingredients, ultraviolet absorption agents, surfactants, alcohols, powder components, coloring agents, aqueous components, water, skin nutrients, and the like. These may be used alone or in combination of two or more.
The content of the other components is not particularly limited and can be appropriately selected depending on the purpose.

<Application>
The use of the whitening agent and anti-aging agent of the present invention is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include pharmaceuticals, quasi-drugs, cosmetics, food and beverages, and the like.

The skin whitening agent and anti-aging agent of the present invention are preferably applied to humans, but as long as the respective effects are achieved, they can also be applied to animals other than humans (e.g. mice, rats, hamsters, dogs, etc.). It can also be applied to cats, cows, pigs, monkeys, etc.).

Furthermore, the whitening agent and anti-aging agent of the present invention can also be used as a reagent for research on the mechanism of whitening and anti-aging effects.

(skin cosmetics)
The skin cosmetic contains at least one member selected from the group consisting of the fermented licorice extract of the present invention, a whitening agent, and an anti-aging agent, and further contains other ingredients as necessary.

The content in the at least one skin cosmetic selected from the group consisting of the fermented licorice extract, a whitening agent, and an anti-aging agent is not particularly limited, and may be adjusted as appropriate depending on the physiological activity of the fermented licorice extract. However, it is preferably 0.0001% by mass to 20% by mass, more preferably 0.0001% by mass to 10% by mass in terms of the fermented licorice extract. The skin cosmetic may consist of at least one selected from the group consisting of the fermented licorice extract, a whitening agent, and an anti-aging agent.

Other ingredients in the skin cosmetics are not particularly limited and can be appropriately selected depending on the purpose from among the main ingredients, auxiliary agents, and other ingredients used in the production of ordinary skin cosmetics, such as: Astringents, bactericidal/antibacterial agents, whitening agents, ultraviolet absorbers, humectants, cell activators, anti-inflammatory/antiallergic agents, antioxidants/active oxygen removers, oils and fats, waxes, hydrocarbons, fatty acids, alcohol esters, surfactants, fragrances, etc. These may be used alone or in combination of two or more.
The content of the other components is not particularly limited and can be appropriately selected depending on the purpose.

The skin cosmetics of the present invention can be used on a daily basis, and due to the action of fermented licorice extract, which is an active ingredient, it has extremely effective various physiologically active effects, including whitening and anti-aging effects. Therefore, it can be suitably used for at least one of whitening applications and anti-aging applications.

The type of skin cosmetics is not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include ointments, creams, milky lotions, serums, lotions, packs, foundations, and the like.

Although the skin cosmetics of the present invention are suitably applied to humans, they can also be applied to animals other than humans (for example, mice, rats, hamsters, dogs, cats, and cows) as long as the respective effects are achieved. , pigs, monkeys, etc.).

(Food and beverages)
The food/beverage product contains at least one member selected from the group consisting of the fermented licorice extract of the present invention, a whitening agent, and an anti-aging agent, and further contains other ingredients as necessary.

Here, the above-mentioned food and beverages refer to foods that have little risk of harming human health and are ingested orally or through gastrointestinal administration in normal social life, and include foods, drugs, and non-medicinal products according to administrative classifications. It is not limited to categories such as products. Therefore, the above-mentioned foods and drinks include general foods that are orally ingested, health foods (functional foods and drinks), foods with health claims (foods for specified health uses, foods with nutritional function claims, foods with functional claims), quasi-drugs, and pharmaceuticals. This term refers to a wide range of food and beverages that make up food and beverages.

The type of food and drink is not particularly limited and can be selected as appropriate depending on the purpose; for example, beverages such as tea drinks, soft drinks, carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks; ice cream; Frozen desserts such as ice sorbet and shaved ice; Noodles such as soba, udon, Harusame, Gyoza skin, Shumai skin, Chinese noodles, and instant noodles; Candy, candies, gum, chocolate, tablets, snacks, biscuits, jellies, jams, etc. Confectionery such as cream, baked goods, and bread; Marine products such as crab, salmon, clams, tuna, sardines, shrimp, bonito, mackerel, whale, oyster, saury, squid, red clam, scallop, abalone, sea urchin, salmon roe, and tokobushi; Fishery and livestock processed foods such as kamaboko, ham, and sausage; Dairy products such as processed milk and fermented milk; Fats and oil processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressing; sauces, sauces, etc. Seasonings: curry, stew, oyakodon, porridge, rice porridge, Chinese bowl, katsudon, tempura bowl, eel bowl, hayashi rice, oden, marbodorf, beef bowl, meat sauce, egg soup, omelet rice, gyoza, shumai, hamburger steak, meatball Deli foods such as salads and pickles; Various forms of health, beauty, and nutritional supplements; Pharmaceuticals such as tablets, granules, capsules, drinks, and troches, and quasi-drugs.

The content in at least one food or drink selected from the group consisting of the fermented licorice extract, whitening agents, and anti-aging agents is not particularly limited, and may be changed as appropriate in consideration of the purpose of use, symptoms, gender, etc. However, for example, considering the general intake of food and drink to which the addition is to be made, the intake of the fermented licorice extract per day for an adult should be approximately 1 mg to 1,000 mg. preferable. In addition, when the food/beverage products to be added are in the form of granules, tablets, or capsules, the amount of at least one selected from the group consisting of the fermented licorice extract, whitening agents, and anti-aging agents is The amount is usually 0.1% to 100% by weight, preferably 5% to 100% by weight based on the food or drink.

Other ingredients in the food/beverage products are not particularly limited and can be appropriately selected depending on the purpose from among auxiliary raw materials, additives, or other ingredients commonly used in the production of food/beverage products, such as: Glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, 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 ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide, calcium pantothenate, amino acids, calcium Examples include salts, dyes, fragrances, preservatives, etc. These may be used alone or in combination of two or more.
The amount of the other components to be blended is not particularly limited and can be appropriately selected depending on the purpose.

The food and drink products of the present invention can be ingested orally on a daily basis, and through the action of fermented licorice extract, which is an active ingredient, they have extremely effective various physiologically active effects, including whitening and anti-aging effects. Therefore, it can be suitably used for at least one of whitening applications and anti-aging applications.

The food and drink products of the present invention are suitably applied to humans, but as long as the respective effects are achieved, they can also be applied to animals other than humans (e.g. mice, rats, hamsters, dogs, cats, cows, etc.). It can also be applied to pigs, monkeys, etc.).

Hereinafter, production examples and test examples of the present invention will be described, but the present invention is not limited to these production examples and test examples.

(Comparative manufacturing example 1)
-Production of water extract of G. glabra-
As an extraction raw material, 30 g of ground Glycyrrhiza glabra ( G. glabra ) roots were added to 1,000 mL of water, and then sterilized to prepare G. glabra extract (hereinafter referred to as " G. glabra" ). (1,000 g) was obtained.

(Manufacturing example 1)
-Production of Glycyrrhiza glabra ( G. glabra ) extracted fermented product-
G. obtained in Comparative Production Example 1. Lactobacillus plantarum strain 22A-3 (accession number: FERM BP-21411) was inoculated into glabra fermentation liquid (1,000 g) and fermented at 30° C. for 24 hours. The obtained fermentation liquid was filtered and the filtrate was concentrated to dryness to obtain a Glycyrrhiza glabra ( G. glabra ) extracted fermented product (hereinafter sometimes referred to as " G. glabra fermentation liquid") ( 11g).

(Comparative production example 2)
-Production of water extract of Glycyrrhiza uralensis ( G. uralensis )-
Glycyrrhiza uralensis ( G. uralensis ) was prepared in the same manner as in Comparative Production Example 1, except that the ground product of G. glabra roots was replaced with the ground product of G. uralensis roots. An extract (hereinafter sometimes referred to as " G. uralensis fermentation liquid") was obtained.

(Comparative production example 3)
-Production of Glycyrrhiza uralensis ( G. uralensis ) extracted fermented product-
In Production Example 1, G. G. glabra fermentation liquid obtained in Comparative Production Example 2. A Glycyrrhiza uralensis ( G. uralensis ) extracted and fermented product (hereinafter sometimes referred to as " G. uralensis fermentation liquid") was obtained in the same manner except that the G. uralensis fermentation liquid was not used.

(Test Example 1: Tyrosinase activity inhibition test)
Using the extracts or fermented extracts obtained in Production Example 1 and Comparative Production Examples 1 to 3 as test samples, the inhibitory effect on tyrosinase activity was tested by the following test method.

In a 48-well plate, test samples dissolved in 0.2 mL of Mcllvaine buffer (pH 6.8), 0.06 mL of 0.3 mg/mL tyrosine solution, and 25% DMSO solution (sample concentrations are shown in Tables 1-1 and 1-2 below). 0.18 mL was added and left at 37°C for 10 minutes. To this, 0.02 mL of 800 units/mL tyrosinase solution was added, followed by reaction at 37° C. for 15 minutes. After the reaction was completed, the absorbance at a wavelength of 475 nm was measured.
Further, as a blank, the same operation and absorbance measurement were performed in the case where no enzyme solution was added. Furthermore, as a control, similar measurements were performed in the case where distilled water was added without adding the sample solution. From the obtained measurement results, the tyrosinase activity inhibition rate (%) was calculated using the following formula 1. The results are shown in Tables 1-1 and 1-2.
<Formula 1>
Tyrosinase activity inhibition rate (%) = {1-(AB)/(CD)}×100
A to D in Formula 1 represent the following, respectively.
A: Absorbance at a wavelength of 475 nm with test sample added and enzyme added B: Absorbance at a wavelength of 475 nm with test sample added and no enzyme added C: Absorbance at a wavelength of 475 nm with no sample added and enzyme added D: No sample added and enzyme Absorbance at wavelength 475 nm without additives

From the results in Tables 1-1 and 1-2, by fermenting Glychyrrhiza glabra extract with Lactobacillus plantarum , a fermented licorice extract with an excellent tyrosinase activity inhibitory effect can be obtained. It has been confirmed that it can be obtained.

(Test Example 2: Profilaggrin mRNA expression promotion effect test)
Using the extracts or fermented extracts obtained in Production Example 1 and Comparative Production Examples 1 to 3 as test samples, profilaggrin mRNA expression promoting effects were tested by the following test method.

Normal human neonatal epidermal keratinocytes (NHEK) were cultured using normal human epidermal keratinocyte growth medium (KGM), and then the cells were collected by trypsin treatment. The collected cells were seeded in 2 mL portions in a 35 mm petri dish using KGM (40 x 10 ⁴ cells/petri dish) and cultured overnight at 37° C. and 5% CO ₂ .
After culturing, the medium was replaced with normal human epidermal keratinocyte basal medium (KBM, the above-mentioned KGM medium to which no growth factors (hEGF, BPE, insulin) were added). After 24 hours, the culture solution was discarded, and 2 mL of the test sample dissolved in KBM (see Table 2 below for sample concentration) was added to each petri dish, and cultured at 37° C. and 5% CO ₂ for 24 hours. As a control, KBM medium to which no test sample was added was used and cultured in the same manner.
After culturing, discard the culture solution, extract total RNA using ISOGEN II (manufactured by Nippon Gene Co., Ltd., Cat. No. 311-07361), measure the amount of each RNA with a spectrophotometer, and adjust the amount to 200 ng/μL. Total RNA was prepared.
Using this total RNA as a template, the expression levels of profilaggrin and GAPDH mRNA, which was an internal standard, were measured. Detection was performed using a real-time PCR device Smart Cycler (registered trademark) (manufactured by Cepheid) using TaKaRa SYBR (registered trademark) Prime Script (trademark) RT-PCR kit (Perfect Real Time) (manufactured by Takara Bio, code No. RR063A). ) was performed using a real-time two-step RT-PCR reaction. The expression level of profilaggrin mRNA was determined by correcting the value of GAPDH mRNA based on total RNA preparations prepared from cells cultured with "test sample addition" and "no test sample addition", respectively. From the obtained values, profilaggrin mRNA expression promotion rate (%) was calculated using the following formula 2. The results are shown in Table 2.
<Formula 2>
Profilaggrin mRNA expression promotion rate (%) = A/B x 100
A to B in Formula 2 represent the following, respectively.
A: Correction value when test sample is added B: Correction value when test sample is not added

From the results in Table 2, it can be seen that by fermenting Glychyrrhiza glabra extract with Lactobacillus plantarum , a fermented licorice extract having an excellent profilaggrin mRNA expression promoting effect can be obtained. confirmed.

(Test Example 3: Serine palmitoyltransferase (SPT) mRNA expression promotion effect test)
Using the extracts or fermented extracts obtained in Production Example 1 and Comparative Production Examples 1 to 3 as test samples, the serine palmitoyltransferase (SPT) mRNA expression promoting effect was tested by the following test method.

Normal human neonatal epidermal keratinocytes (NHEK) were cultured using normal human epidermal keratinocyte growth medium (KGM), and then the cells were collected by trypsin treatment. The collected cells were seeded in 2 mL portions in a 35 mm petri dish using KGM (40 x 10 ⁴ cells/petri dish) and cultured overnight at 37° C. and 5% CO ₂ .
After culturing, the medium was replaced with normal human epidermal keratinocyte basal medium (KBM, the above-mentioned KGM medium to which no growth factors (hEGF, BPE, insulin) were added). After 24 hours, the culture solution was discarded, and 2 mL of the test sample dissolved in KBM (see Table 3 below for sample concentration) was added to each petri dish, and cultured at 37° C. and 5% CO ₂ for 24 hours. As a control, KBM medium to which no test sample was added was used and cultured in the same manner.
After culturing, discard the culture solution, extract total RNA using ISOGEN II (manufactured by Nippon Gene Co., Ltd., Cat. No. 311-07361), measure the amount of each RNA with a spectrophotometer, and adjust the amount to 200 ng/μL. Total RNA was prepared.
Using this total RNA as a template, the expression levels of SPT and GAPDH mRNA, which was an internal standard, were measured. Detection was performed using a real-time PCR device Smart Cycler (registered trademark) (manufactured by Cepheid) using TaKaRa SYBR (registered trademark) Prime Script (trademark) RT-PCR kit (Perfect Real Time) (manufactured by Takara Bio, code No. RR063A). ) was performed using a real-time two-step RT-PCR reaction. The expression level of SPT mRNA was determined by correcting the value of GAPDH mRNA based on total RNA preparations prepared from cells cultured with "test sample addition" and "no test sample addition", respectively. From the obtained values, the SPT mRNA expression promotion rate (%) was calculated using the following formula 3. The results are shown in Table 3.
<Formula 3>
SPT mRNA expression promotion rate (%) = A/B x 100
A to B in Formula 3 represent the following, respectively.
A: Correction value when test sample is added B: Correction value when test sample is not added

From the results in Table 3, by fermenting Glychyrrhiza glabra extract with Lactobacillus plantarum , a fermented licorice extract with an excellent serine palmitoyltransferase (SPT) mRNA expression promoting effect was produced. It has been confirmed that it can be obtained.

(Test Example 4: Hyaluronic acid synthase 3 (HAS3) mRNA expression promotion effect test)
Using the extracts or fermented extracts obtained in Production Example 1 and Comparative Production Example 1 as test samples, the effect of promoting hyaluronic acid synthase 3 (HAS3) mRNA expression was tested by the following test method.

Normal human neonatal epidermal keratinocytes (NHEK) were cultured using normal human epidermal keratinocyte growth medium (KGM), and then the cells were collected by trypsin treatment. The collected cells were seeded in 2 mL portions in a 35 mm petri dish using KGM (40 x 10 ⁴ cells/petri dish) and cultured overnight at 37° C. and 5% CO ₂ .
After culturing, the medium was replaced with normal human epidermal keratinocyte basal medium (KBM, the above-mentioned KGM medium to which no growth factors (hEGF, BPE, insulin) were added). After 24 hours, the culture medium was discarded, and 2 mL of the test sample dissolved in KBM (see Table 4 below for sample concentration) was added to each petri dish, and cultured at 37° C. and 5% CO ₂ for 24 hours. As a control, KBM medium to which no test sample was added was used and cultured in the same manner.
After culturing, discard the culture solution, extract total RNA using ISOGEN II (manufactured by Nippon Gene Co., Ltd., Cat. No. 311-07361), measure the amount of each RNA with a spectrophotometer, and adjust the amount to 200 ng/μL. Total RNA was prepared.
Using this total RNA as a template, the expression levels of HAS3 and GAPDH mRNA, which was an internal standard, were measured. Detection was performed using a real-time PCR device Smart Cycler (registered trademark) (manufactured by Cepheid) using TaKaRa SYBR (registered trademark) Prime Script (trademark) RT-PCR kit (Perfect Real Time) (manufactured by Takara Bio, code No. RR063A). ) was performed using a real-time two-step RT-PCR reaction. The expression level of HAS3 mRNA was determined by correcting the value of GAPDH mRNA based on total RNA preparations prepared from cells cultured with "test sample addition" and "no test sample addition", respectively. From the obtained values, the HAS3 mRNA expression promotion rate (%) was calculated using the following formula 4. The results are shown in Table 4.
<Formula 4>
HAS3 mRNA expression promotion rate (%) = A/B x 100
A to B in Formula 4 represent the following, respectively.
A: Correction value when test sample is added B: Correction value when test sample is not added

From the results in Table 4, it was found that by fermenting Glychyrrhiza glabra extract with Lactobacillus plantarum , licorice extract and fermentation having an excellent effect of promoting hyaluronic acid synthase 3 (HAS3) mRNA expression was obtained. It was confirmed that something was obtained.

(Combination example 1)
A milky lotion having the following composition was prepared by a conventional method.
・G. glabra extracted fermented product (manufacturing example 1) 0.01g
・Jojoba oil 4.00g
・1,3-butylene glycol 3.00g
・Arbutin 3.00g
・Polyoxyethylene cetyl ether (20E.O.) 2.50g
・Olive oil 2.00g
・ Squalane 2.00g
・Setanol 2.00g
・Glyceryl monostearate 2.00g
・Polyoxyethylene sorbitan oleate (20E.O.) 2.00g
・Methyl paraoxybenzoate 0.15g
・ Stearyl glycyrrhizinate 0.10g
・ Huangji extract 0.10g
・ Dipotassium glycyrrhizinate 0.10g
・Ginkgo biloba extract 0.10g
・Conchiolin 0.10g
・ Aubaku extract 0.10g
・ Chamomile extract 0.10g
・Fragrance 0.05g
・Remaining purified water (total amount is 100g)

(Combination example 2)
A cream having the following composition was produced by a conventional method.
・G. glabra extracted fermented product (manufacturing example 1) 0.05g
・ Kujin extract 0.1g
・ Scutellariae extract 0.1g
・Liquid paraffin 5.0g
・ White beeswax 4.0g
・Squalane 10.0g
・Setanol 3.0g
・ Lanolin 2.0g
・Stearic acid 1.0g
・Polyoxyethylene sorbitan oleate (20E.O.) 1.5g
・Glyceryl monostearate 3.0g
・Oil-soluble licorice extract 0.1g
・1,3-butylene glycol 6.0g
・Methyl paraoxybenzoate 1.5g
・Fragrance 0.1g
・Remaining purified water (total amount is 100g)

(Combination example 3)
A beauty serum having the following composition was produced by a conventional method.
・G. glabra extracted fermented product (manufacturing example 1) 0.01g
・ Chamomile extract 0.1g
・ Carrot extract 0.1g
・Xanthan gum 0.3g
・Hydroxyethylcellulose 0.1g
・Carboxyvinyl polymer 0.1g
・1,3-butylene glycol 4.0g
・ Dipotassium glycyrrhizinate 0.1g
・Glycerin 2.0g
・ Potassium hydroxide 0.25g
・Fragrance 0.01g
・Preservative (methyl paraoxybenzoate) 0.15g
・Ethanol 2.0g
・Remaining purified water (total amount is 100g)

(Combination example 4)
Tablets having the following composition were manufactured by a conventional method.
・G. glabra extracted fermented product (manufacturing example 1) 5.0 mg
・Dolomite (contains 20% calcium and 10% magnesium) 83.4mg
・Casein phosphopeptide 16.7mg
・Vitamin C 33.4mg
・Maltitol 136.8mg
・Collagen 12.7mg
・Sucrose fatty acid ester 12.0mg

(Combination example 5)
An oral liquid preparation having the following composition was produced by a conventional method.
・G. glabra extracted fermented product (Production Example 1) 0.3% by mass
・Sorvit 12.0% by mass
・Sodium benzoate 0.1% by mass
・Fragrance 1.0% by mass
・Calcium sulfate 0.5% by mass
・ Purified water remainder (100% by mass)

FERM BP-21409
FERM BP-21411
FERM BP-21410

Claims (3)

Contains fermented licorice extract,
The fermented licorice extract is a fermented product of licorice extract by microorganisms,
The daylily is Glychyrrhiza glabra ,
The licorice extract is an aqueous extract of the root of licorice,
The microorganism is Lactobacillus plantarum ,
The Lactobacillus plantarum is Lactobacillus plantarum 22A-1 (FERM BP-21409), Lactobacillus plantarum 22A-3 (FERM BP-21411), and Lactobacillus plantarum 22B-2 (FERM BP -21410) A promoter of profilaggrin mRNA expression, which is at least one selected from the group consisting of: Contains fermented licorice extract,
The fermented licorice extract is a fermented product of licorice extract by microorganisms,
The daylily is Glychyrrhiza glabra ,
The licorice extract is an aqueous extract of the root of licorice,
The microorganism is Lactobacillus plantarum ,
The Lactobacillus plantarum is Lactobacillus plantarum 22A-1 (FERM BP-21409), Lactobacillus plantarum 22A-3 (FERM BP-21411), and Lactobacillus plantarum 22B-2 (FERM BP A serine palmitoyltransferase mRNA expression promoter, characterized in that the agent is at least one selected from the group consisting of: Contains fermented licorice extract,
The fermented licorice extract is a fermented product of licorice extract by microorganisms,
The daylily is Glychyrrhiza glabra ,
The licorice extract is an aqueous extract of the root of licorice,
The microorganism is Lactobacillus plantarum ,
The Lactobacillus plantarum is Lactobacillus plantarum 22A-1 (FERM BP-21409), Lactobacillus plantarum 22A-3 (FERM BP-21411), and Lactobacillus plantarum 22B-2 (FERM BP -21410)).