JP2021155411A - Mineral metabolism disorder inhibitor - Google Patents

Abstract

To provide a material which can proliferate cells and normalize epidermal turnover, and prevent and improve spots by improving mineral metabolism disorder in an upper epidermis.SOLUTION: A mineral metabolism disorder inhibitor applied to an upper epidermis of a spots portion of a skin, has, as an active ingredient, at least one kind selected from a group consisting of mulberry, Sanguisorba officinalis, licorice leaf, Arnica montana, mugwort, Rubus ellipticus, Isodon japonicus, Alpinia katsumadai, Clove, ginseng, rosa roxburghii, peony, tannic acid, artichoke, phellodendron bark, Gentiana lutea, oolong tea, Hedera helix, hematin, Rosae fructus, star fruit leaf, Aspalathus linearis, sage, bilberry leaf, hypericum erectum, rosemary, Houttuynia cordata, litchi, Scutellariae radix, Lonicera japonica, mangosteen, Sophora flavescens, black tea, thea sinensis, gambir, niacinamide, heparinoid, tranexamic acid, and placenta.SELECTED DRAWING: Figure 1

Description

The present invention relates to a mineral metabolism disorder inhibitor, a TFRC1 production inhibitor, a DMT1 production inhibitor, an ACO1 production inhibitor, an SLC40A1 production promoter, an SLC31A1 production promoter, and an SLC25A37 production inhibitor.

Minerals are one of the five major nutrients along with proteins, carbohydrates, fats, and vitamins. It plays an important role as a cofactor of enzymes, regulation of excitability of nerves and muscles, and heart, and a component of physiologically active substances.

Minerals are roughly classified into two types: large elements and trace elements. Major elements include calcium, phosphorus, potassium, sodium, sulfur, magnesium and the like. Trace elements include iron, copper, zinc, selenium, manganese, iodine and the like.

That is, in order for humans to maintain their health, daily intake of various minerals is indispensable. For example, it is well known that iron deficiency causes anemia. In addition, zinc deficiency causes skin ulcers, decreased immune response, and sexual dysfunction dwarf disease, and copper deficiency causes anemia and increased plasma cholesterol concentration. Conversely, it is known that, for example, excessive intake of iron causes skin pigmentation and liver damage, and excess copper causes brain damage (Non-Patent Document 1).

There is a mechanism to maintain the mineral balance in the living body. For example, the sodium pump of the cell membrane consumes energy to pump out intracellular sodium ions, and there are many potassium ions inside the cells and sodium ions outside the cells. Maintains a large number of.

Of course, mineral balance is also important for maintaining skin health, and it has been reported that the presence of a large amount of magnesium ions in the stratum granulosum and calcium ions in the stratum granulosum is important for skin homeostasis (maintenance of homeostasis). Has been done. It is also known that calcium ions affect the enzyme balance related to stratum corneum exfoliation (→ keratinization), that is, the digestion of desmosomes.

Furthermore, it is known that trace amounts of minerals are localized in the epidermis. Iron, zinc, copper, etc. are all necessary for the activity of various enzymes involved in cell proliferation and antioxidants. Among them, iron and copper, in particular, have a narrow physiological optimum concentration and are likely to cause oxidative damage to tissues. It is known that there is. Abnormal localization of these minerals is considered to lead to abnormal skin turnover and oxidative pathology (Non-Patent Document 2).

It is generally known that epidermal turnover is initiated by the proliferation of basal cells and is responsible for the excretion of melanin.
So-called spots such as senile pigment spots are the most common spots on the face, and many people cite them as cosmetic problems. It has been reported that the epidermis is thickened and melanin is accumulated in the affected area of the stain, the expression of molecules involved in melanin production is increased, and the proliferation of basal cells is decreased.

Therefore, if the proliferation of epidermal cells in the reduced skin can be activated or the expression of molecules involved in melanin production can be reduced, the original skin function can be restored, and melanin is excreted by epidermal turnover to prevent stains. Alternatively, it is considered that treatment, improvement, etc. can be realized.

Therefore, the present inventors have focused on improving mineral metabolism in the skin as a method for improving such abnormalities in epidermal turnover and suppressing the expression of molecules involved in melanin production.
This time, it was clarified that the expression of iron and copper metabolism-related genes is altered in the upper epidermis of the spot condition, the utilization of iron is promoted, and the excretion of copper is decreased. For example, TFRC1, ACO1 and SLC25A37 (Mitoferrin1) involved in iron utilization are increased in the upper epidermis in the spot pathological part (pigmented part), and CTR1 involved in copper utilization is increased in the skin in the normal part. It was found that when it was expressed in the upper granule layer, the expression in the granule layer was decreased in the spot pathological part. It was considered that these abnormal mineral metabolism causes abnormal turnover of the epidermis, and melanin is not excreted to form stains.

Therefore, if the expression of molecules related to iron and copper metabolism can be brought close to normal, that is, if a component that suppresses iron utilization and promotes copper excretion in the upper epidermis can be found, epidermal cell proliferation and melanin turn. I thought that it would be possible to improve the stains by returning the overcoat to normal.

Hiroshi Kawabata (2010) Journal of the Japan Society 99: 1173-1179. Inoue Y et al (2014) J Biol chem., 1; 289 (31): 21451-62. Asano M D et al (2017) J Dermatol Sci., 87 (2): 101-9. Kazuhiro Iwai et al. (2007) Biochemistry Vol. 79, No. 11 1021-31 Hideo Zhang (2013) Journal of Japan 102: 2699-2704 Yasumitsu Ogura (2014) Niei Magazine Vol. 69, No. 2, 136-45

An object of the present invention is to provide a material capable of normalizing cell proliferation and epidermal turnover and preventing / ameliorating stains by improving the abnormal metabolism of minerals in the upper part of the epidermis.

As a result of diligent studies, the present inventors regulated the production of proteins involved in the uptake and excretion of iron and copper in the cells of the upper epidermis, and suppressed the use of iron. It was also found that it has an effect of promoting excretion of copper.

That is, the present invention
(1) Kuwa, crackle, licorice leaf, Arnica, yomogi, oni strawberry, hikiokoshi, alpinia kamatsudai, chouji, carrot, isayoibara, button, tannic acid, artichoke, sardine, gentiana, oolong tea, sage, hematin, ages, star fruit From leaves, asparasas linearis, sage, bilberry leaves, otogirisou, rosemary, dokudami, lychee, ogong, watermelon, mangosteen, clara, black tea, cha, assenyaku, niacinamide, heparin analogs, tranexamic acid, and placenta An agent for suppressing abnormal mineral metabolism in the upper part of the epidermis of the spotted part of the skin, which contains at least one selected from the group as an active ingredient.
(2) The active ingredient is at least one selected from the group consisting of mulberry, crackle leaf, licorice leaf, arnica, yomogi, oni strawberry, isodon japonicus, alpinia tripletail, chow, carrot, and rosa roxburghii, and has an effect of suppressing TFRC1 production. Based on (1) Mineral metabolism abnormality inhibitor,
(3) The active ingredient is at least one selected from the group consisting of Arnica, onistrawberry, chowji, button, mulberry, licorice leaf, sanguisorba officinalis, tannic acid, artichoke, alpinia tripletail, isodon japonicus, sardine, gentiana, and oolong tea. The agent for suppressing abnormal mineral metabolism of (1) based on the inhibitory effect on DMT1 production,
(4) The active ingredient is at least one selected from the group consisting of onistrawberry, sardine, mulberry, butterfly, button, licorice leaf, sanguisorba officinalis, and tannic acid, and the mineral of (1) based on the ACO1 production inhibitory action. Metabolic disorder inhibitor,
(5) The active ingredients are heparinoid, ages, star fruit leaves, asparasas linearis, alpinia honeysuckle, sage, bilberry leaves, honeysuckle, izayoi rose, oolong tea, carrots, rosemary, dokudami, lychee, crackle, honeysuckle, honeysuckle, honeysuckle. At least one selected from the group consisting of honeysuckle, mangosteen, niacinamide, heparinoid, tranexamic acid, and placenta, and the mineral metabolism abnormality inhibitor (1) based on the SLC40A1 production promoting action.
(6) The active ingredient is at least one selected from the group consisting of button, hematine, tannic acid, hypericum erectum, star fruit leaf, and clara, and the mineral metabolism abnormality inhibitor of (1) based on the SLC31A1 production promoting action. ,
(7) The active ingredient is at least one selected from the group consisting of button, tannic acid, sanguisorba officinalis, gambir, onistrawberry, arnica, mulberry, licorice leaf, black tea, tea, oolong tea, asenyaku, and ages, and produces SLC25A37. (1) Inhibitor of abnormal mineral metabolism based on inhibitory action,
.
(9) DMT1 containing at least one selected from the group consisting of Arnica, onistrawberry, chowji, button, mulberry, licorice leaf, sanguisorba officinalis, tannic acid, artichoke, alpinian tripletail, isodon japonicus, gentian, and oolong tea as active ingredients. Production inhibitor,
(10) An ACO1 production inhibitor containing at least one selected from the group consisting of oni strawberry, blue-green algae, morus alba, clove, button, licorice leaf, sanguisorba officinalis, and tannic acid as an active ingredient.
(11) Heparin, ages, star fruit leaves, asparagus linearis, alpinia pine, sage, bilberry leaves, otogirisou, isayoibara, oolong tea, carrots, rosemary, dokudami, lychee, crackle, honeysuckle, mangosteen, mangosteen An SLC40A1 production promoter containing at least one selected from the group consisting of niacinamide, heparinoid, tranexamic acid, and placenta as an active ingredient.
(12) SLC31A1 production promoter containing at least one selected from the group consisting of button, hematine, tannic acid, hypericum, star fruit leaf, and clara as an active ingredient.
(13) SLC25A37 production inhibitor containing at least one selected from the group consisting of buttons, tannic acid, sanguisorba officinalis, chowji, onistrawberry, arnica, mulberry, licorice leaf, black tea, tea, oolong tea, asenyaku, and agetsu as an active ingredient.
(14) One or more selected from the group consisting of TFRC1 gene, DMT1 gene, ACO1 gene, SLC40A1 gene, SLC31A1 gene, and SLC25A37 gene when the test substance is allowed to act on differentiated human epidermal keratinized cells. A method for screening a stain-preventing or improving agent using the expression level of a gene in the above as an index.
Is.

The mineral metabolism abnormality inhibitor of the present invention suppresses the utilization of iron in the cells of the upper epidermis by regulating the production of proteins involved in the utilization of minerals such as TFRC1, DMT1, ACO1, SLC40A1, SLC31A1 and SLC25A37. By promoting the excretion of copper, the proliferation of epidermal cells and epidermal turnover can be normalized, and the effect of preventing / ameliorating stains can be obtained. Further, through the suppression of TFRC1 production, the suppression of DMT1 production, the suppression of ACO1 production, the promotion of SLC40A1 production, the promotion of SLC31A1 production, and the suppression of SLC25A37 production, it is possible to obtain therapeutic / ameliorating effects on various symptoms and diseases based on the excess or decrease of these proteins. Can be done. Furthermore, it can also be used as a positive control agent when screening materials involved in the expression of these proteins or genes. Further, according to the screening method of the present invention, components that can prevent / improve stains can be efficiently screened.

FIG. 1 is a graph showing the ΔΔCt value of the TFRC1 gene in Test Example 1. FIG. 2 is a graph showing the ΔΔCt value of the DMT1 gene in Test Example 1. FIG. 3 is a graph showing the ΔΔCt value of the ACO1 gene in Test Example 1. FIG. 4 is a graph showing the ΔΔCt value of the SLC40A1 gene in Test Example 1. FIG. 5 is a graph showing the ΔΔCt value of the SLC31A1 gene in Test Example 1. FIG. 6 is a graph showing the ΔΔCt value of the SLC25A37 gene in Test Example 1.

In the present invention, the following components are used as active ingredients.

The morus alba used in the present invention is a raw medicine or plant derived from the root bark of Morusa alba Linne or other plants of the same genus (Moraceae) of the Rosales family Morus alba, and is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. NS. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The quail extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.). A solvent such as acetone) or a mixture of the above solvents can be used, but water, lower aliphatic alcohols, polyhydric alcohols, or a mixture thereof is most preferable.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of mulberry extract include "Sohakuhi extract-J", "Sohakuhi extract BG", and "Sohakuhi extract BG100" manufactured by Maruzen Pharmaceuticals Co., Ltd.

The Sanguisorba officinalis used in the present invention is a raw medicine or plant derived from the roots and rhizomes of Sanguisorba officinalis Linne (Rosaceae) of the Rosales family, Sanguisorba officinalis Linne (Rosaceae), and is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The crackle extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Sanguisorba extract include Maruzen Pharmaceuticals' Jiyu Extract-R, Jiyu Extract BG-R, and Jiyu Extract Powder.

The licorice leaf used in the present invention is a crude drug or plant derived from the leaf of Glycyrrhiza glabra (Leguminosae), a licorice genus of the family Fabales, and is used in the form of a crude drug or plant powder, a crude drug extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The licorice leaf extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic alcohols. A solvent extracted from a solvent such as ketone (acetone or the like) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available licorice leaf extract include Maruzen Pharmaceuticals' licorice leaf extract BG.

Arnica used in the present invention is a crude drug or plant derived from the flowers of Arnica montana Linne (compositae) of the family Asteraceae, Arnica, and is used in the form of crude drug or plant powder, crude drug extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The Arnica extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Arnica extract include Maruzen Pharmaceuticals' "Arnica extract BG" and Ichimaru Falcos (registered trademark) "Falcorex (registered trademark) Arnica".

The mugwort used in the present invention is a crude drug or plant derived from the leaves of Artemisia princeps Pampanini, Artemisia mongolia Fischer or Artemisia montana Pampanini (Compositae) of the Asteraceae family, Artemisia princeps Pampanini, Artemisia montana Pampanini (Compositae). Used in the form of. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The yomogi extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of mugwort extract include Maruzen Pharmaceuticals' "Mugwort extract", "Mugwort extract BG", "Wa ism (registered trademark) <Mugwort>", and Ichimaru Falcos' "Mugwort liquid".

The onistrawberry used in the present invention is a crude drug or plant derived from the root of Rubus ellipticus, a genus Rubus ellipticus of the Rosales family, and is used in the form of a crude drug or plant powder, a crude drug extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The onistrawberry extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic alcohols. A solvent extracted from a solvent such as ketone (acetone or the like) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available oni strawberry extract include Maruzen Pharmaceuticals' Himalayan Raspberry Extract BG80.

Isodon japonicus Hara (Amethystamtus japonicus Nakai, Plectranthus japonicus (Burm.) Koidz) or Isodon japonicus Kudo (Plectranthus trichocarpus) Alternatively, it is a plant and is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The hikiokoshi extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Isodon japonicus extract include Maruzen Pharmaceuticals' Enmeisou Extract-JC and Enmeisou Extract BG.

The Alpinia katsumadai used in the present invention is a crude drug or plant derived from the seeds of Alpinia katsumadai Hayata (Zingiberaceae) of the Zingiberales family Alpinia, and is used in the form of a crude drug or plant powder, a crude drug extract or a plant extract. .. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The alpinia kamatsudai extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower fats. A solvent extracted from a solvent such as a group ketone (such as acetone) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of the tripletail extract of Alpinia are "Alpinia White" and "Alpinia White HS" of Ichimaru Falcos.

The clove used in the present invention is a raw medicine or plant derived from dried buds of Myrtaceae, Myrtaceae, Myrtaceae, Cyzygium aromaticum Merrill et Perry (Eugenia caryophyllata Thunberg), and is a raw medicine or plant powder, raw medicine extract or plant. Used in the form of extracts. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The chowdi extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available clove extract include Maruzen Pharmaceuticals' Clove Extract-J and Ichimaru Falcos' Clove Rex Clove.

The ginseng used in the present invention is a ginseng or plant derived from steamed and dried roots or roots (raw) of Panax ginseng CAMeyer (Panax schinseng Nees) (Araliaceae) of the Araliaceae family Araliaceae. It is used in the form of powder, ginseng extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The carrot extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available carrot extracts include Maruzen Pharmaceuticals'carrot extract, carrot extract LA-20, ginseng extract powder MF, ginseng extract D (N), and Ichimaru Falcos' Shinhon. Ginseng® LV ”,“ Shinhong Ginseng LV-2 ”,“ Falcolex Carrot B ”, etc. can be mentioned.

Rosa roxburghii Rosa roxburghii Tratt.f.normalis Rehd.et Wils (Rosaceae) is a crude drug or plant derived from the fruit of Rosa roxburghii Tratt.f.normalis Rehd.et Wils (Rosaceae). Used in. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The Izayoi rose extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. Those extracted with a solvent such as (acetone, etc.) or a mixed solution of the above solvents can be used. Most preferably, it is extracted with a polyhydric alcohol or a mixed solution thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Izayoi rose extract include Maruzen Pharmaceuticals' "Togenashi Extract BG" and "Togenashi Extract Powder C", and Ichimaru Falcos' "IZAYOI" and "IZAYOI G".

The button used in the present invention is a raw medicine or plant derived from the root bark of Paeonia suffruticosa Andrews (Paeonia moutan Sims) (Paeonia ceae), which is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. Will be done. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The button extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. It is possible to use a solvent such as (acetone or the like) or a mixture of the above solvents, and it is most preferable to extract with water, a lower aliphatic alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available button extracts include Maruzen Pharmaceuticals's "Peony Extract" and Ichimaru Falcos' "Falcolex Buttonpi B" and "Falcolex Buttonpi E".

The tannic acid used in the present invention is used in the form of crude drug powder or plant powder of rhus chinensis or gall apple, crude drug extract or plant extract, in addition to purified compounds. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

Examples of the quintuple or galvanic extract used in the present invention include water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and the like. A solvent extracted from a solvent such as a lower aliphatic ketone (such as acetone) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying.

The artichoke used in the present invention is a crude drug or plant derived from the leaves of Cynara scolymus Linne (Compositae) of the Asteraceae family Cynara genus Artichoke, and is used in the form of crude drug powder or plant powder, crude drug extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The artichoke extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acemonate or the like) or a mixture of the above solvents can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of artichoke extract include Ichimaru Falcos's "Bio-Benefity (registered trademark)", "Bio-Benefity G", "Bio-Benefity HS", "Cynaropicrin F", "Bio-Benefity F" and the like. ..

The amber used in the present invention is a crude drug or plant derived from the bark of Phellodendron amurense Ruprecht or other plants of the same genus (Rutaceae) excluding the peripheral bark of the family Rutaceae, Phellodendron amurense, and is a crude drug or plant powder, a crude drug extract or a plant extract. Used in form. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The Oubaku extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Oubaku extract include Maruzen Pharmaceuticals' Oubaku Extract-J and Oubaku Extract BG-J, and Ichimaru Falcos' Ouba Liquid B and Ouba Liquid E.

The gentiana used in the present invention is a raw medicine or plant derived from the root and rhizome of Gentiana lutea Linne (Gentianaceae) of the Gentianales family Gentianaceae, and is used in the form of a raw medicine or plant powder, a raw medicine extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The gentiana extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. Solvents such as (acetone, etc.), diethylene glycol ethyl ether, and those extracted with a mixed solution of the above solvents can be used. Of these, water, lower aliphatic alcohols, polyhydric alcohols, diethylene glycol ethyl ether, or a mixed solution thereof can be used. Most preferably.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available gentiana extract products include Maruzen Pharmaceuticals' Gentiana extract BG-J and Ichimaru Falcos' Falcorex gentiana B.

The oolong tea used in the present invention is a crude drug or plant derived from the leaves of Thea sinensis Linne (Theaceae), Theaceae, Theaceae, Theaceae, and is used in the form of crude drug or plant powder, crude drug extract or plant extract. .. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The oolong tea extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. Those extracted with a solvent such as (acetone or the like) or a mixed solution of the above solvents can be used, but it is most preferable to extract with low water, a higher aliphatic alcohol or a mixed solution thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of oolong tea extract include Maruzen Pharmaceuticals' oolong tea extract, oolong tea extract BG, oolong tea extract M powder, oolong tea extract M aqueous, and Ichimaru Falcos' Falcolex oolong E. Can be mentioned.

The ivy used in the present invention is a crude drug or plant derived from the leaves and stems of Hedera helix Linne (Araliaceae) of the family Araliaceae, Araliaceae, and is used in the form of a crude drug or plant powder, a crude drug extract or a plant extract. .. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The oilseed shavings extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic alcohols. A solvent such as a ketone (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available ivy extract include Maruzen Pharmaceuticals' ivy extract BG-J and Ichimaru Falcos' Falcolex ivy B.

The hematin used in the present invention is a component derived from porcine blood, and is used as an extract of porcine blood in addition to purified compounds.

The hematine extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acemonate or the like) or a mixture of the above solvents can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available hematine extracts include "Gloss Philin (registered trademark) P (PF)" from Ichimaru Falcos.

The ages used in the present invention are crude drugs or plants derived from the fruits of Rosa multiflora Thunberg or other related plants (Rosaceae), and are used in the form of crude drug powder or plant powder, crude drug extract or plant extract. Will be done. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The agetsu extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of Agetsu Extract include Maruzen Pharmaceuticals' Agetsu Extract-R, Agetsu Extract BG-R, Agetsu Extract BG-01, and Ichimaru Falcos' Falcolex Agetsu B. Can be mentioned.

The star fruit leaf used in the present invention is a crude drug or plant derived from the leaf of Averrhoa carambola, which belongs to the genus Carambola of the family Oxalidales, and is used in the form of crude drug powder or plant powder, raw drug extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The star fruit leaf extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), lower fats. A solvent extracted from a solvent such as a group ketone (such as acetone) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available star fruit leaf extracts include Maruzen Pharmaceuticals' Star Fruit Leaf Extract BG30 and Star Fruit Leaf Extract Powder MF.

The aspalathus linearis used in the present invention is a crude drug or plant derived from the whole plant of Cape gorses linearis (NLBurm.) R. Dahlgren (Leguminosae) of the genus Cape gorses of the family Fabales, and is a crude drug or plant powder, a crude drug extract. Or used in the form of plant extracts. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The asparasus linearis extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower fats. A solvent extracted from a solvent such as a group ketone (acetone or the like) or a mixed solution of the above solvents can be used, but it is most preferable to extract with water, a polyhydric alcohol or a mixed solution thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of cape gorses linearis extract include Maruzen Pharmaceuticals' Rooibos Tea Extract Powder MF, Rooibos Tea Dried Extract F, and Ichimaru Falcos' Falcolex Rooibos B (N).

The sage used in the present invention is a raw medicine or plant derived from the flowers, leaves or whole plants of Salvia officinalis Linne (Labiatae) of the Labiatae family Lamiales, and is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. NS. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The sage extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone, etc.), a mixed solution of the solvent, or a mixed solution of the solvent containing urea can be used, and among them, water, a lower aliphatic alcohol, a polyhydric alcohol, or a mixed solution thereof or urea can be used. It is most preferable to extract with a mixed solution of these containing.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available sage extract products include Maruzen Pharmaceutical's "Salvia Extract" and "Salvia Extract BG-J", and Ichimaru Falcos' "Eco Farm (Registered Trademark) Sage B", "Eco Farm Sage E", and "Falco". Examples include "Rex Sage B" and "Falco Rex Sage E".

The blueberries leaf used in the present invention is a raw medicine or plant derived from the leaves of Vaccinium myrtillus L. (Ericaceae) of the family Ericaceae, Azalea, and is used in the form of raw medicine powder or plant powder, raw medicine extract or plant extract. .. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The bilberry leaf extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic alcohols. A solvent extracted from a solvent such as ketone (acetone or the like) or a mixed solution of the solvent can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of blueberries leaf extract include "Ecofarm Bilberry Leaf E", "Ecofarm Bilberry Leaf G", and "Cureberry (registered trademark)" of Ichimaru Falcos.

The Hypericum erectum used in the present invention is a raw medicine or plant derived from the above-ground part of Hypericum perforatum Linne or Hypericum erectum Thunberg (Guttiferae) of the order Hypericum erectum Thunberg (Guttiferae). Used in form. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The otogirisou extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Hypericum extract include Maruzen Pharmaceuticals' "Hypericum extract BG", Ichimaru Falcos' "Falcolex Hypericum B", and "Falcolex Hypericum E".

Rosemary used in the present invention is a raw medicine or plant derived from leaves or leaves and flowers of Rosmarinus officinalis Linne (Labiatae) of the genus Rosmarinus of the Labiatae family, Lamiales, and is used in the form of raw medicine or plant powder, raw medicine extract or plant extract. NS. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The rosemary extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), lower aliphatic alcohols. A solvent such as ketone (acetone, etc.), a mixed solution of the solvent, or a mixed solution of the solvent containing urea can be used, and among them, water, a lower aliphatic alcohol, a polyhydric alcohol, or a mixed solution thereof can be used. Most preferably, it is extracted with a mixed solution of these containing urea.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available rosemary extracts include Maruzen Pharmaceuticals' Rosemary Extract BG-J and Rosemary Extract MF, and Ichimaru Falcos' Ecofarm Rosemary B, Ecofarm Rosemary E, and "Ecofarm Rosemary E." "Falcolex Rosemary B", "Falcolex Rosemary E" and the like.

The Houttuynia used in the present invention is a Houttuynia cordata Thunberg (Saururaceae), which is derived from the above-ground part of the flowering period of the Houttuynia cordata Thunberg (Saururaceae). Will be done. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The dokudami extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of Houttuynia cordata extract include Maruzen Pharmaceutical's "Houttuynia cordata extract", "Houttuynia cordata extract BG", "Houttuynia cordata extract powder MF", and Ichimaru Falcos "Falcolex Houttuynia cordata B", "Falcolex Houttuynia cordata E", "Falcolex Houttuynia cordata E". Falcolex Dokudami W ”,“ Dokudami DXP100 ”, etc. can be mentioned.

The lychee used in the present invention is a raw medicine or plant derived from the fruit of Litchi chinensis Sonn. (Sapindaceae) of the family Sapindales, Sapindaceae, and is used in the form of raw medicine powder or plant powder, raw medicine extract or plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The lychee extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acemonate or the like) or a mixture of the above solvents can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available lychee extracts include Ichimaru Falcos's "ADS-Oligonol" and "Oligonol-CS".

The ginger used in the present invention is a raw medicine or plant derived from the roots of Scutellaria baicalensis Georgi (Labiatae), which belongs to the genus Scutellaria baicalensis, Lamiales, in the form of raw medicine powder or plant powder, raw medicine extract or plant extract. used. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The augon extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Scutellaria baicalensis include Maruzen Pharmaceuticals' Scutellaria extract-J, Ichimaru Falcos' Scutellaria extract powder, Scutellaria baicalensis liquid B, Scutellaria baicalensis liquid G, and Scutellaria baicalensis liquid SE. ..

The honeysuckle used in the present invention is a honeysuckle or plant derived from the flowers, leaves or stems of Lonicera japonica Thunberg or other similar plants (Caprifoliaceae) of the honeysuckle family, honeysuckle family, honeysuckle family, in the form of honeysuckle or plant powder, honeysuckle extract or plant extract. Used in. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The watermelon extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Commercially available products of honeysuckle extract include Maruzen Pharmaceuticals' "Kinginka Extract-J", Ichimaru Falcos' "Falcolex Honeysuckle FB", and "Falcolex Honeysuckle FE".

The mangosteen used in the present invention is a raw medicine or plant derived from the peel of Garcinia mangostana, which belongs to the family Guttiferae of the order Malpighiales, and is used in the form of a raw medicine or plant powder, a raw medicine extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The mangostin extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acemonate or the like) or a mixture of the above solvents can be used.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available mangosteen extracts include Nippon Shinyaku's "Mangosteen Aqua" and "Mangosteen α20".

The clara used in the present invention is a crude drug or plant derived from the root of Sophora flavescens Aiton (Laguminosae), which belongs to the genus Sophora flavescens Aiton (Laguminosae). Used in the form of plant extracts. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The clara extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol, a polyhydric alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Clara extract include Maruzen Pharmaceuticals' Kujin Extract Liquid and Kujin Extract BG-J, and Ichimaru Falcos' Falcolex Clara and Falcolex Clara B.

The tea used in the present invention is a crude drug or plant derived from tea made from the leaves of Thea sinensis L. var. Used in the form of. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The tea extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones. A solvent such as (acetone or the like) or a mixture of the above solvents can be used, but it is most preferable to extract with water, a lower aliphatic alcohol or a mixture thereof.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available black tea extracts include Maruzen Pharmaceuticals' "Black Tea Extract BG" and "Black Tea Extract LA-J", and Ichimaru Falcos' "Black Tea Liquid".

The tea used in the present invention is a crude drug or plant derived from the leaves of Thea sinensis Linne (Theaceae), the genus Camellia, Theaceae, Theaceae, in the form of crude drug or plant powder, crude drug extract or plant extract. used. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The cha extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic ketones (such as glycerin). A solvent such as acetone) or a mixture of the above solvents can be used, but water, lower aliphatic alcohols, polyhydric alcohols, or a mixture thereof is most preferable.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available tea extracts include Maruzen Pharmaceuticals' "Wa ism <green tea>", "Wa ism <Uji tea>", "Green tea extract MF", and Ichimaru Falcos' "Green tea liquid".

The Asenyaku used in the present invention is a crude drug or plant derived from the leaves and shoots of Uncaria gambir Roxburgh (Rubiaceae) of the family Rubiaceae, Uncaria, and is used in the form of a crude drug or plant powder, a crude drug extract or a plant extract. The crude drug powder or plant powder used in the present invention may be, for example, a powdered dried product obtained by further finely crushing a dried chopped product.

The assenyaku extract used in the present invention includes water, lower aliphatic alcohols (methanol, ethanol, isopropyl alcohol, etc.), polyhydric alcohols (1,3-butylene glycol, propylene glycol, dipropylene glycol, glycerin, etc.), and lower aliphatic alcohols. A solvent extracted with a solvent such as ketone (acetone, etc.) or a mixed solution of the above solvents can be used. Of these, a lower aliphatic alcohol or a lower aliphatic alcohol or a liquid obtained by extracting and drying with water (Asenyaku) can be used. Most preferably, it is extracted with a polyhydric alcohol.

The form of the extract is not particularly limited, and dried extract powder, extract powder, soft extract, stream extract and the like can be obtained by heat treatment, freeze-drying or vacuum-drying. Examples of commercially available products of Asenyaku extract include Maruzen Pharmaceuticals' Asenyaku extract and Asenyaku extract BG.

The niacinamide used in the present invention is Cas No. 98-92-0, and tranexamic acid is a compound defined by Cas No. 1197-18-8. Heparinoids are one of the mucopolysaccharide polysulfates. Placenta is obtained by aseptically extracting with water from the placenta of a pig or the like by a method such as freezing or thawing. Examples of the origin include humans, cows, pigs, horses, sheep and the like, but pigs are preferable. Moreover, you may use the product (for example, biocatalyzer placenta APF (G)) which is commercially available as placenta extract.

The skin is roughly divided into three layers: epidermis, dermis, and subcutaneous tissue. The major constituent cells of the epidermis are keratinocytes (keratinocytes), which undergo morphologically four-step changes during differentiation. The basal cells in the lowermost layer are in contact with the basement membrane, synthesize DNA, and divide and proliferate. The divided cells move upward and become stabbed cells. As the differentiation progresses, it becomes granule cells, and finally it differentiates from granule cells to stratum corneum cells to form the uppermost stratum corneum. Keratinocytes at each of these differentiation stages are stacked in the epidermis. The stratum corneum cells that form the stratum corneum are adhered to each other by desquamation, but in healthy skin, the adhesion mechanism gradually declines, and the stratum corneum spontaneously detaches due to physical stimulation. (Peeling the stratum corneum). In this way, the epidermis repeats proliferation, differentiation, and exfoliation at a constant rhythm (epidermis turnover). In addition to keratinocyte cells, melanocyte cells are present in the epidermis and produce melanin pigment. Normally, the melanin pigment is transferred to the keratinocytes and excreted during epidermal turnover with exfoliation of the stratum corneum. .. However, if abnormal epidermal turnover occurs, such as decreased differentiation / proliferation from basal cells or hyperproliferation of keratinocytes, resulting in stratification / thickening, melanin pigment is not excreted and accumulates in the epidermis to cause stains. Is formed. In the present specification, the subepidermal part means a layer containing basal cells among the keratinocytes constituting the epidermis, and the upper part of the epidermis means a layer containing keratinocyte cells.

The transferrin receptor (TFRC1) is expressed in various cells in the living body, and after iron in serum is bound to transferrin and transported, iron is taken up into the cells via TFRC1. When cells are deficient in iron, the expression of TFRC1 is reduced, which plays an important role in the intracellular uptake of iron. When TFRC1 production is suppressed in keratinocytes in the upper epidermis, intracellular iron uptake is suppressed and intracellular iron concentration is reduced, thereby normalizing epidermal turnover and epidermal layer regeneration. Therefore, the effect of preventing and / or improving stains can be obtained (Non-Patent Documents 1 and 3).

Among the above active ingredients, morus alba, sanguisorba officinalis, licorice leaf, arnica, mugwort, mugwort, oni strawberry, isodon japonicus, tripletail, clove, carrot, and rosa roxburghii have a TFRC1 production inhibitory effect.

DMT1, one of the divalent metal transporters, is responsible for the uptake of iron from the intestinal tract and the transport of iron from endosomes. DMT1 binds to various divalent metals including cadmium (Cd 2+), copper (Cu 2+), and zinc (Zn 2+), but is best known for its role in the transport of iron (Fe 2+). ing. Expression of DMT1 is regulated by iron stores in the body to maintain iron homeostasis. In the gastrointestinal tract, it is located in the apical membrane of enterocytes and is known to bind and transport divalent metal cations from the intestinal cavity to cells. In recent years, it has been reported that it is also expressed in the epidermis of skin tissues. When DMT1 production is suppressed in keratinocytes in the upper part of the epidermis, iron uptake into the cells is suppressed, the intracellular iron concentration is lowered, and epidermal turnover and epidermal layer regeneration are normalized. The effect of preventing and / or improving stains can be obtained.

Among the above active ingredients, Arnica, Oni strawberry, Chouji, Button, Kuwa, licorice leaf, Sanguisorba officinalis, Tannic acid, Artichoke, Alpinia tripletail, Isodon japonicus, Oubaku, Gentiana, and Oolong tea have a DMT1 production inhibitory effect.

ACO1 is an enzyme that functions as an essential enzyme in the TCA cycle and catalyzes the reaction of citric acid to isocitric acid through aconitate. At high intracellular iron levels, this protein functions as an aconitase. When cells have low iron levels, proteins bind to the iron-responsive element (IRE). Suppression of ACO1 production in keratinocytes in the upper epidermis suppresses the activation of mitochondria in the cells and normalizes iron utilization by stabilizing intracellular iron concentration, thereby normalizing the epidermis. Since turnover and epidermal layer regeneration are normalized, the effect of preventing and / or improving stains can be obtained (Non-Patent Document 4).

Among the above active ingredients, oni strawberry, ivy, morus alba, clove, button, licorice leaf, sanguisorba officinalis, and tannic acid have an ACO1 production inhibitory effect.

SLC40A1 (ferroportin) is responsible for the excretion of iron from cells. The expression of ferroportin is regulated according to the excess or deficiency of intracellular iron and the protein level by hepcidin according to the excess or deficiency of iron at the individual level. Ferroportin is known to be a protein that excretes iron from intestinal epithelial cells and macrophages into blood, but in recent years, it has been reported that it is also expressed in skin tissues. When SLC40A1 production is promoted in keratinocytes in the upper part of the epidermis, the intracellular iron concentration of the cells is lowered and epidermal turnover and epidermal layer regeneration are normalized, so that the effect of preventing and / or improving stains is obtained. (Non-Patent Documents 1, 3 and 5).

Among the above active ingredients, heparin, ages, star fruit leaves, asparasas linearis, alpinia tripletail, sage, bilberry leaves, otogirisou, rosa roxburghii, oolong tea, carrots, rosemary, dokudami, lychee, crackle, sardines, watermelons , Mangosteen, niacinamide, heparinoid, tranexamic acid, and placenta have SLC40A1 production promoting action.

In SLC25A37 (Mitoferrin1), mitochondria are the main intracellular iron-utilizing organelles, and they function as iron uptake transporters in the inner mitochondrial membrane. It exists as a major molecule of iron metabolism in intracellular mitochondria. When SLC25A37 production is suppressed in keratinocytes in the upper part of the epidermis, the intracellular iron concentration is lowered based on the suppression of iron transport to intracellular mitochondria, and epidermal turnover and epidermal layer regeneration are normalized. (Non-Patent Document 5).

Among the above active ingredients, button, tannic acid, sanguisorba officinalis, clove, oni strawberry, arnica, mulberry, licorice leaf, black tea, tea, oolong tea, asenyaku, and agetsu have an SLC25A37 production inhibitory effect.

SLC31A1 (CTR1) functions as a transporter that takes up copper into cells. It is expressed in all tissues in mice, especially in the liver, small intestine, heart and kidneys. In addition, the expression of CTR1 has been found to change depending on the nutritional status of copper. When SLC31A1 production is promoted, the uptake of copper in keratinocytes is promoted, oxidative stress is reduced, and epidermal turnover and epidermal layer regeneration are normalized, so that the effect of preventing and / or improving stains is obtained. (Non-Patent Document 6).

Among the above active ingredients, button, hematine, tannic acid, hypericum erectum, carambola leaf, and clara have an SLC31A1 production promoting action.

As described above, in the present invention, the TFRC1 production inhibitory action by at least one selected from the group consisting of mulberry, sanguisorba officinalis, licorice leaf, arnica, yomogi, oni strawberry, hikiokoshi, alpinia pine, chow, carrot, and izayoi rose. DMT1 production inhibitory effect, onistrawberry, seiyo ACO1 production inhibitory effect by at least one selected from the group consisting of scratches, mulberry, chow, button, licorice leaf, sanguisorba officinalis, and tannin acid, hematin, ages, star fruit leaves, asparasas linearis, alpinia pine tree, sage, bill SLC40A1 production by at least one selected from the group consisting of belly leaves, otogirisou, isayoibara, oolong tea, carrots, rosemary, dokudami, lychee, sanguisorba officinalis, ginger, watermelon mangostin, niacinamide, heparin analogs, tranexamic acid and placenta. SLC31A1 production promoting action by at least one selected from the group consisting of promoting action, button, hematin, tannic acid, otogirisou, star fruit leaf, and clara, or button, tannic acid, sanguisorba officinalis, chow, onistrawberry, arnica, quail, SLC25A37 inhibitory action by at least one selected from the group consisting of tannin leaf, tea, cha, oolong tea, asenyaku, and agetsu, a mineral metabolism abnormality inhibitor in the upper part of the epidermis of the skin stain site, suppression of TFRC1 production by each of the above active ingredients Agents, DMT1 production inhibitors, ACO1 production inhibitors, SLC40A1 production promoters, SLC31A1 production promoters, SLC25A37 production inhibitors, and further due to excess of TFRC1, DMT1, ACO1 or SLC25A37, reduction of SLC40A1 or SLC31A1. Has the effect of preventing and improving diseases and symptoms.

The mineral metabolism abnormality inhibitor, TFRC1 production inhibitor, DMT1 production inhibitor, ACO1 production inhibitor, SLC40A1 production promoter, SLC31A1 production promoter, or SLC25A37 production inhibitor of the present invention is a cosmetic, quasi-drug, pharmaceutical product, or It can be provided as food and drink. The dosage form is not particularly limited, but an external preparation applied to the skin is preferable from the viewpoint of acting on the keratinocytes in the upper part of the epidermis to normalize the abnormal mineral metabolism. Although it is preferably applied to humans, it can also be applied to animals other than humans as long as the action and effect are exhibited.

The mineral metabolism disorder inhibitor, TFRC1 production inhibitor, DMT1 production inhibitor, ACO1 production promoter, SLC40A1 production promoter, SLC31A1 production promoter, or SLC25A37 production inhibitor of the present invention is, for example, a study of related symptoms and diseases. To normalize mineral metabolism disorders at the spot site, or to suppress TFRC1 production, suppress DMT1 production, promote ACO1 production, promote SLC40A1 production, promote SLC31A1 production, or suppress SLC25A37 production. It can also be used as a reagent for this purpose, and preferably can be used as a positive control agent when performing material screening and the like.

The present invention includes a method for suppressing TFRC1 production, DMT1 production, ACO1 production or SLC25A37 production, and a method for promoting SLC40A1 and SLC31A1 production in such tests and studies. As a method for suppressing TFRC1 production, epidermal keratinized cells or cells for which TFRC1 production is desired to be suppressed are subjected to mulberry, sanguisorba officinalis, licorice leaf, arnica, yomogi, oni strawberry, isodon japonicus, alpinia tripletail, chouji, carrot, rosa roxburghii or their respective extracts. Includes the step of adding. As a method for suppressing DMT1 production, epidermal keratinized cells or cells for which DMT1 production is desired to be suppressed include Arnica, onistrawberry, chouji, button, mulberry, licorice leaf, sanguisorba officinalis, tannic acid, artichoke, alpinia tripletail, isodon japonicus, gentiana lutea. , Including the step of adding oolong tea or each extract. The method for suppressing ACO1 production includes a step of adding onistrawberry, sardine, mulberry, clove, button, licorice leaf, sanguisorba officinalis, tannic acid or extracts thereof to epidermal keratinized cells or cells for which ACO1 production is desired to be suppressed. The method for promoting SLC40A1 production includes heparinoid, ages, star fruit leaves, asparagus linearis, alpinia pine, sage, bilberry leaves, otogirisou, isayoibara, and oolong tea in epidermal keratinized cells or cells for which SLC40A1 promotion is desired to be promoted. , Carrot, rosemary, dokudami, lychee, crackle, sage, watermelon, mangosteen, niacinamide, heparinoid, tranexamic acid, placenta or extracts of each. The method for promoting SLC31A1 production includes a step of adding a button, hematin, tannic acid, hypericum, star fruit leaf, clara or an extract thereof to epidermal keratinized cells or cells for which SLC31A1 production is desired to be promoted. The method for suppressing SLC25A37 production includes epidermal keratinized cells or cells for which SLC25A37 production is desired to be suppressed, such as button, tannic acid, sanguisorba officinalis, chow, onistrawberry, arnica, mulberry, licorice leaf, black tea, cha, oolong tea, asenyaku, agetsu or each. Includes the step of adding the extract of.

The administration form is not particularly limited, but a skin-applied preparation is preferable. Examples of the dosage form of the skin-applied preparation include lotions, creams, patches, sprays, gels, ointments, lotions, milky lotions, and beauty essences. These can be produced by known methods. In the production, various additives that can be contained in quasi-drugs, pharmaceuticals, foods and drinks, or reagents can be blended as long as the effects of the present invention are not impaired.

The blending amount of the above active ingredient in the present invention is not particularly limited, but when provided as cosmetics, quasi-drugs, pharmaceuticals, foods and drinks or reagents, 0.000001 to 10% by mass with respect to the entire composition, respectively. %, preferably 0.0001 to 5% by mass, more preferably 0.001 to 1% by mass.

Mineral metabolism abnormality inhibitor, TFRC1 production inhibitor, DMT1 production inhibitor, ACO1 production inhibitor, SLC40A1 production promoter, SLC31A1 production promoter, or SLC25A37 production inhibitor (pharmaceutical products, quasi-drugs, etc.) Foods and drinks, reagents, etc.) and their instructions indicate that they are used to suppress TFRC1 production, that they are used to suppress DMT1 production, that they are used to suppress ACO1 production, and that they are used to suppress SLC40A1 production. It may have an indication that it is used for promotion, an indication that it is used for promoting SLC31A1 production, or an indication that it is used for suppressing SLC25A37 production. Here, "indicated" means to describe on the main body, container, packaging, etc. of the product containing the production promoter or reduction promoter, or to disclose the product information, such as instructions, package inserts, pamphlets, and others. Includes writing on documents such as printed matter, and writing on various leaflets and advertisements used for advertising including the Internet.

The screening method of the present invention uses differentiated human epidermal keratinocytes. The medium used for cell culture is not particularly limited, known ones can be used, and the cells can be cultured under normal culture conditions. A group consisting of the TFRC1 gene, DMT1 gene, ACO1 gene, SLC40A1 gene, SLC31A1 gene, and SLC25A37 gene after adding the test substance to the medium of undifferentiated human epidermal keratinized cells cultured in this way and culturing for a predetermined time. The expression level of one or more genes selected from the above is measured. The expression level of the gene is not particularly limited, and a known method can be used. The untreated group to which the test substance is not added is also cultured in the same manner, the expression level of each gene is measured, and the expression level of each gene is compared with the expression level of each gene in the test substance treated group. Can be determined. Further, for example, TFRC1, ACO1, and SLC25A37 (Mitopherrin1), which are involved in the utilization of iron, are mainly expressed in the subepidermal part in the normal part, whereas are increased in the upper part of the epidermis in the spot pathological part (pigmented part). Therefore, by comparing the gene expression levels when the test substance is added based on the expression levels of these genes in the stain pathological model, it is possible to determine the presence or absence of the stain prevention / ameliorating effect of the test substance. In addition, a test substance was similarly tested using undifferentiated human epidermal keratinized cells, and a test substance that reduced the expression of these genes in differentiated cells but did not reduce the expression of these genes in undifferentiated cells. By combining an index of the amount of change in gene expression specific to the pathological part of a stain, such as selection, it becomes possible to select a component having a more excellent effect of preventing / ameliorating the stain.

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited to the Examples.

(Test Example 1) Evaluation of promotion or suppression of gene expression in differentiated human epidermal keratinocytes <Test method>
Human epidermal keratinocytes (the Kurabo) were seeded at a density of 3.8 × 10 ⁴ cells / well in 12-well plates, 37 ° C., and cultured in an incubator set at CO ₂ 5%. Humedia-KG2 (Kurabo Industries Ltd.) was used as the medium. Three days after sowing, the medium was replaced with a medium containing the test substance, and the cells were cultured in a _{CO 2 incubator for 1 day.} Then, lysate buffer was added to lyse the cells, and the cytolytic solution was collected. RNA was recovered from the cell lysate according to the attached protocol using RNeasy Mini Kit (Qiagen), and cDNA was synthesized by reverse transcription reaction using Prime Script RT Master mix (Takara Bio) using this as a template. From the synthesized cDNA, the expression levels of RPLP0, TFRC1, DMT1, ACO1, SLC40A1, SLC31A1 and SLC25A37 mRNAs were measured by the SYBR Green method using a real-time PCR system (Step One Plus, Thermo Fisher Scientific). The Ct value of each sample of TFRC1, DMT1, ACO1, SLC40A1, SLC31A1 and SLC25A37 was subtracted from the Ct value of RPLP0, which is an internal standard gene, to obtain the ΔCt value. Further, the value obtained by subtracting the ΔCt value of the sample in the untreated group from the ΔCt value of the sample in the test substance-added group was defined as the ΔΔCt value. For example, a ΔΔCt value of -1 indicates a 2-fold change in gene expression, and a 1 value indicates a 1/2-fold change.
As the primer, the one having the following sequence or model number was used. RPLP0: (F) 5'-GAAGCCACGCTGCTGAACA-3'(R) 5'-CTGGCAACATTGCGGACA-3', SLC25A37: (F) 5'-GAAGCAGCAGTACATTTGTCATTCA-3'(R) 5'-CTGGCAACATTGCGGACA-3'(primer synthesis) TFRC1 : HA277353, DMT1: HA142595, ACO1: HA210761, SLC40A1: HA161921, SLC31A1: HA158357 (Takara Bio).
The test substances were all used at a final concentration of 1% except for tannic acid 0.1%, lychee 0.01%, mangosteen 0.01%, clara 0.01%, niacinamide 0.05%, and heparinoid 0.05%. The untreated group was cultured in a medium without adding the test substance, and all other conditions were the same as those in the test substance-added group.

<Test results>
FIG. 1 is a graph showing the ΔΔCt value of the TFRC1 gene. Compared with the untreated group, Arnica, Oni strawberry, licorice leaf, Kuwa, Isodon japonicus, Yomogi, Sanguisorba officinalis, Rosa roxburghii, Alpinia tripletail, Clove, and Carrot reduced TFRC1 gene expression.
FIG. 2 is a graph showing the ΔΔCt value of the DMT1 gene. Compared with the untreated group, Arnica, Oubaku, Oni strawberry, licorice leaf, Sohakuhi, Isodon japonicus, Button, Sanguisorba officinalis, Artichoke, Alpinia tripletail, Ouron tea, Gentiana, Tannic acid, and Chouji reduced DMT1 gene expression.
FIG. 3 is a graph showing the ΔΔCt value of the ACO1 gene. Compared with the untreated group, oni strawberry, licorice leaf, morus alba, button, sanguisorba officinalis, sardine, tannic acid, and clove reduced ACO1 gene expression.
FIG. 4 is a graph showing the ΔΔCt value of the SLC40A1 gene. Compared to the untreated group, ages, oysters, star fruit leaves, crackle, isayoi rose, alpinia pine, oolong tea, otogirisou, blueberries leaves, hematin, lychee, asparasas linearis, carrots, lychees, rosemary, sage, mangosteen, Watermelon, niacinamide, heparinoids, tranexamic acid and placenta increased SLC40A1 gene expression.
FIG. 5 is a graph showing the ΔΔCt value of the SLC31A1 gene. Clara, carambola leaves, kale, hypericum, tannic acid, and hematin increased SLC31A1 gene expression compared to the untreated group.
FIG. 6 is a graph showing the ΔΔCt value of the SLC25A37 gene. Compared with the untreated group, Asenyaku, Arnica, Agetsu, Onistrawberry, Gambir, Kwa, Button, Sanguisorba officinalis, Oolong tea, Tannic acid, Tea, Chouji, and Black tea reduced SLC25A37 gene expression.

The mineral metabolism abnormality inhibitor in the upper epidermis of the stain site of the present invention is based on the TFRC1 production inhibitory effect, DMT1 production inhibitory effect, ACO1 production inhibitory effect, SLC40A1 production promoting effect, SLC31A1 production promoting effect, or SLC25A37 production suppressing effect. It can be used in the fields of quasi-drugs, pharmaceuticals, and foods and drinks because it has a preventive / improving effect. Furthermore, the TFRC1 production inhibitor, DMT1 production inhibitor, ACO1 production inhibitor, SLC40A1 production promoter, SLC31A1 production promoter, and SLC25A37 production inhibitor of the present invention can be used as positive control agents in material screening and the like. can.

Claims (14)

Kwa, crackle, licorice leaf, arnica, yomogi, oni strawberry, hikiokoshi, alpinia kamatsudai, chowji, carrot, isayoibara, button, tannic acid, artichoke, sardine, gentian, oolong tea, sage, hematin, ages, star fruit leaves, asparagus From the group consisting of sasline alice, sage, bilberry leaves, otogirisou, rosemary, dokudami, lychee, ogong, watermelon, mangosteen, clara, black tea, cha, assenyaku, niacinamide, heparin analog, tranexamic acid, and placenta. An agent for suppressing abnormal mineral metabolism in the upper part of the epidermis of a spot on the skin containing at least one selected active ingredient. The active ingredient is at least one selected from the group consisting of mulberry, crackle leaf, licorice leaf, arnica, yomogi, oni strawberry, isodon japonicus, alpinia tripletail, chow, carrot, and rosa roxburghii, and is based on TFRC1 production inhibitory action. The agent for suppressing abnormal mineral metabolism according to claim 1. The active ingredient is at least one selected from the group consisting of Arnica, onistrawberry, chowji, button, mulberry, licorice leaf, sanguisorba officinalis, tannic acid, artichoke, alpinian tripletail, isodon japonicus, gentian, and oolong tea, and is DMT1. The agent for suppressing abnormal mineral metabolism according to claim 1, which is based on a production inhibitory action. 13. Inhibitor of abnormal mineral metabolism. The active ingredients are hematin, ages, star fruit leaves, asparasas linearis, alpinia pine, sage, bilberry leaves, otogirisou, isayoibara, oolong tea, carrots, rosemary, dokudami, lychee, crackle, honeysuckle, mangosteen. The mineral metabolism abnormality inhibitor according to claim 1, which is at least one selected from the group consisting of, niacinamide, heparinoid, tranexamic acid, and placenta, and is based on the SLC40A1 production promoting action. The inhibition of mineral metabolism abnormality according to claim 1, wherein the active ingredient is at least one selected from the group consisting of button, hematine, tannic acid, hypericum, star fruit leaf, and clara, and is based on the SLC31A1 production promoting action. Agent. The active ingredient is at least one selected from the group consisting of button, tannic acid, sanguisorba officinalis, chow, oni strawberry, arnica, mulberry, licorice leaf, black tea, tea, oolong tea, asenyaku, and agetsu, and has an SLC25A37 production inhibitory effect. The agent for suppressing abnormal mineral metabolism according to claim 1. A TFRC1 production inhibitor containing at least one selected from the group consisting of mulberry, sanguisorba officinalis, licorice leaf, arnica, yomogi, oni strawberry, isodon japonicus, alpinia tripletail, chow, carrot, and rosa roxburghii as an active ingredient. A DMT1 production inhibitor containing at least one selected from the group consisting of Arnica, Oni strawberry, Chouji, Button, Kuwa, licorice leaf, Sanguisorba officinalis, Tannic acid, Artichoke, Alpinia tripletail, Isodon japonicus, Oubaku, Gentiana, and Oolong tea as active ingredients. .. An ACO1 production inhibitor containing at least one selected from the group consisting of oni strawberry, sardine, morus alba, clove, button, licorice leaf, sanguisorba officinalis, and tannic acid as an active ingredient. Heparin, Agetsu, Star Fruit Leaf, Asparasas Linearis, Alpinia Kamatsudai, Sage, Bilberry Leaf, Otogirisou, Rosa Roxburghii, Oolong Tea, Carrot, Rosemary, Dokudami, Lychee, Waremokou, Ogon, Watermelon, Mangosteen, Niacin An SLC40A1 production promoter containing at least one selected from the group consisting of heparinoids, tranexamic acid, and placenta as an active ingredient. An SLC31A1 production promoter containing at least one selected from the group consisting of button, hematin, tannic acid, hypericum, star fruit leaf, and clara as an active ingredient. An SLC25A37 production inhibitor containing at least one selected from the group consisting of button, tannic acid, sanguisorba officinalis, gambir, onistrawberry, arnica, mulberry, licorice leaf, black tea, tea, oolong tea, asenyaku, and agetsu as an active ingredient. One or more genes selected from the group consisting of TFRC1 gene, DMT1 gene, ACO1 gene, SLC40A1 gene, SLC31A1 gene, and SLC25A37 gene when the test substance is allowed to act on differentiated human epidermal keratinized cells. A method for screening a stain-preventing or improving agent using the expression level as an index.

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