JP2023035137A - FGF-7 mRNA EXPRESSION PROMOTER, VEGFmRNA EXPRESSION PROMOTER, IGF-1 mRNA EXPRESSION PROMOTER, HGFmRNA EXPRESSION PROMOTER, BMP-2 mRNA EXPRESSION PROMOTER AND KAP5.1 mRNA EXPRESSION PROMOTER - Google Patents

Abstract

To find out compositions having FGF-7 mRNA expression-promoting effect, VEGFmRNA expression-promoting effect, IGF-1 mRNA expression-promoting effect, HGFmRNA expression-promoting effect, BMP-2 mRNA expression-promoting effect and KAP5.1 mRNA expression-promoting effect out of compositions derived from high-safety natural products, and provide FGF-7 mRNA expression promoter, VEGFmRNA expression promoter, IGF-1 mRNA expression promoter, HGFmRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter which have the compositions as active ingredients.SOLUTION: FGF-7 mRNA expression promoter, VEGFmRNA expression promoter, IGF-1 mRNA expression promoter, HGFmRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter are allowed to contain an extract from one or more kinds of plant selected from the group consisting of Sophora root, Panax ginseng C.A. Meyer, Zanthoxylum piperitum De Candolle and Stephania cephalantha as active ingredients.SELECTED DRAWING: None

Description

The present invention relates to FGF-7 mRNA expression promoters, VEGF mRNA expression promoters, IGF-1 mRNA expression promoters, HGF mRNA expression promoters, BMP-2 mRNA expression promoters and KAP5.1 mRNA expression promoters.

Hair repeats growth and shedding according to a periodic hair cycle (hair cycle) consisting of a growth phase, a regression phase, and a rest phase. Of this hair cycle, the stage from the resting phase to the anagen phase, in which new hair follicles are formed, is considered to be the most important for hair growth. Dermal papilla cells are thought to play an important role in the proliferation and differentiation of hair follicle epithelial cells at this stage. Dermal papilla cells are cells located inside hair follicle epithelial cells consisting of outer root sheath cells and matrix cells in the vicinity of the hair root, and located at the root portion of the hair root surrounded by the basement membrane. It plays an important role in hair differentiation, such as acting on epithelial cells to promote their proliferation (see Non-Patent Document 1).

Fibroblast growth factor-7 (FGF-7) is one of the family of fibroblast growth factors (FGF), also called KGF (keratinocyte growth factor). It is known that there are more than 20 families of FGFs. FGF is a factor that promotes the proliferation of a wide range of cells generated from mesoderm and neuroectoderm. induce growth. FGF is known to have an angiogenic effect, an inhibitory effect on the synthesis of collagen and fibronectin, and the like, and to have a strong affinity for heparin.

In addition, it has been shown that FGF-7 is expressed in dermal papilla cells of hair follicles (see, for example, Non-Patent Document 2), and it is clear that FGF-7 has a hair growth effect via activation of hair roots. Became. Further, studies using knockout mice suggest that FGF-7 is involved in the direction of hair growth. So far, Clara and the like have been known as plant extracts that have the effect of promoting FGF-7 production (see Non-Patent Document 3).

Vascular endothelial growth factor (VEGF) is a glycoprotein with a molecular weight of 34-46 kDa, and is found in the culture medium of pituitary follicular cells as a growth factor specific to vascular endothelial cells. It was found to be the same substance. VEGF is produced not only in pituitary cells but also in normal cells such as smooth muscle cells, macrophages, alveolar epithelial cells, hepatocytes, and dermal papilla cells, and is also used in glioma, breast cancer, gastric cancer, colon cancer, and the like. is also known to be produced by many tumor cells of VEGF acts on vascular endothelial cells to promote cell proliferation and migration, and to promote angiogenesis. VEGF is known to be strongly expressed during embryonic heart formation. It has been reported that defects in the VEGF gene cause abnormalities in the vascular system and death in the embryonic period, suggesting that VEGF plays an extremely important role in individual development and tissue formation. Recently, it was reported that a new member of the VEGF family, VEGF-C, mediates the growth of lymphatic vessels in the skin as a potent lymphangiogenic factor.

In addition, in hair follicles, it is known that outer root sheath cells and dermal papilla cells produce VEGF (see, for example, Non-Patent Documents 4 and 5). Inhibition of VEGF production in hair follicles has been found to lead to a delay in the anagen phase of the hair cycle and a dwarfing of the hair follicle size (see, for example, Non-Patent Document 6). VEGF has been shown to be important. So far, plant extracts that promote VEGF production include morning glory plants of the Convolvulaceae family (see Patent Document 1), royal jelly (see Patent Document 2), L-glutamic acid or its salts, L-serine, PCA ( pyrrolidone carboxylic acid) or its salts, mononitroguaiacol sodium, Chlorella vulgaris extract, Citrus junos fruit extract, Citrus unshiu peel extract, Rosa multiflora and Ginkgo biloba leaf extract (see Patent Document 3).

Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a molecular weight of about 7,500 that has a structure and action very similar to insulin. IGF-1 is known to actively maintain cells in a healthy state, such as promoting cell differentiation and helping cell proliferation (see Non-Patent Documents 7 and 8), and inhibiting the progression of aging. (See Non-Patent Document 9).

In addition, it has been shown that IGF-1 is expressed in dermal papilla cells of hair follicles (see Non-Patent Document 10), and it has been clarified that IGF-1 has a hair growth effect via activation of hair roots. rice field. At present, a hair restorer containing IGF-1 as an active ingredient is already known (see Patent Document 4). However, since IGF-1 is an animal-derived component and has a large molecular weight, there are problems such as difficulty in percutaneous absorption by external application. Plant-derived extracts have also been found that exhibit an IGF-1 production-promoting effect, but there is a need for a more superior IGF-1 production-promoting effect.

Hepatocyte growth factor (HGF) was discovered from the plasma of fulminant hepatitis patients as a factor that promotes proliferation of hepatocytes. HGF is known to promote proliferation of epithelial cells, endothelial cells, hematopoietic cells, and the like derived from various organs, not limited to the liver. It has been reported that the blood concentration of HGF increases in various diseases such as liver disease, pneumonia, leukemia, cancer, and myocardial infarction. In addition, HGF has been found to be effective in suppressing organ damage and fibrosis and promoting regeneration. Patent Literature 5 discloses a technique of using HGF as an active ingredient of a pulmonary fibrosis preventive agent.

In addition, HGF was shown to be expressed in dermal papilla cells of hair follicles (see Non-Patent Document 2), revealing that HGF has a hair growth effect via activation of hair roots. For example, rice and the like have been known as a plant extract that has an effect of promoting HGF production (see Patent Document 6).

Bone morphogenetic protein (BMP) was discovered as a protein that induces bone formation ectopically. It has become known to be a multifunctional factor that plays a role. In the skin, it has been reported that BMPs are actively involved in the formation of hair follicles, which are the organs that form body hair. BMPs are reported to have about 20 types of subunits. The subunits are basically conserved in sequence in a wide range of biological species, and have been shown to be involved in morphogenesis of each biological species. Among the subunits, bone morphogenetic protein-2 (BMP-2) has been reported to have reduced gene expression in dermal papilla cells at sites of androgenetic alopecia. Therefore, attention has been focused on hair restorer research focusing on this gene (see Patent Document 7).

In addition to problems related to the state of hair roots and hair follicles such as hair loss and thinning hair, problems related to hair include hair quality (hair quality) such as hard, soft, thin, lack of elasticity, split ends, and frizzy hair. There are things related to. Furthermore, problems related to hair quality include those caused by daily hair care, hair makeup, damage to hair due to exposure to ultraviolet rays, etc., and problems caused by problems in hair shaft formation. factors are involved.

Conventionally, in order to improve the fineness of hair and the lack of elasticity and stiffness, it is conceivable to use, for example, a hair restorer or a hair tonic containing a hair restorer active ingredient. However, the use of hair growth agents, hair tonics, and the like has the problem that the hair does not become thick, and the effect of imparting elasticity and stiffness cannot be expected. In order to improve these problems, a method has been proposed in which a silanol compound produced by hydrolysis of alkoxysilane is permeated into the hair and polymerized inside the hair (see Patent Document 8). However, this method of modifying hair using chemical substances is not sufficient in terms of imparting natural elasticity and stiffness to hair.

On the other hand, attempts have also been made to improve hair quality biochemically and molecularly biologically. Hair is composed of a cuticle covering its surface, a cortex inside it, and a medulla occupying the center of the hair. Among these, it is known that the cuticle covering the surface plays an important role in hair damage (see Non-Patent Document 11). Therefore, it is believed that if the cuticle can be effectively regenerated, it will be possible to improve the quality of hair such as hardness, elasticity, and stiffness.

Recently, among keratin-associated proteins (KAP), it has been revealed that there is a correlation between the mRNA expression level of the KAP5 family gene and the strength of hair elasticity (see Patent Document 9). ). It has also been reported that KAP5.1, one of the KAP5 families, is localized in the growing cuticle (see Non-Patent Document 12). Therefore, if the expression of the KAP5 family, particularly KAP5.1 mRNA can be promoted, it is expected to lead to regeneration of cuticles and improvement of hair quality such as hardness, elasticity, and stiffness of hair.

Conventionally, Camellia genus plant extracts (see Patent Document 10), walnut shell extracts, persimmon tannins, iris root extracts, Gennoshokou extract and wheat germ extracts (see Patent Document 11) have been used as substances that promote the expression of KAP5.1 mRNA. Are known.

Japanese Patent Application Laid-Open No. 2003-160503 Japanese Patent Application Laid-Open No. 2003-192541 Japanese Unexamined Patent Application Publication No. 2005-2068 Japanese Patent Publication No. 4-60567 JP 2006-131649 A JP-A-2004-99503 Japanese Patent Application Laid-Open No. 2005-002068 JP 2005-320314 A JP 2006-014721 A JP 2014-080409 A JP 2008-162922 A

"Trends Genet", Vol. 8, 56-61 (1992) Anti-Aging Series (1), Actual Gray Hair/Depilation/Hair Growth, NTS, 1-18 (2005) J. Derm. Sci. , 30, 43-49 (2002) J. Invest. Dermatol. , 106, 17-23 (1996) Arch. Dermatol. Res. , 209, 661-668 (1998) J. Clin. Invest. , 107, 409-417 (2001) J. Biol. Chem. , 271, 28853-28860 (1996) Dermatology, 20, 325-329 (2002) Am. J. Med. , 115, 501-502 (2003) J. Invest. Dermatol. , 99, 343-349 (1992) Journal of Japanese Society of Cosmetic Engineers, Vol.36, No.3, 207-216 (2002) Int. J. Trichology, 2(2), 89-95 (2010)

The present invention provides FGF-7 mRNA expression-enhancing action, VEGF mRNA expression-enhancing action, IGF-1 mRNA expression-enhancing action, HGF mRNA expression-enhancing action, BMP-2 mRNA expression-enhancing action, and KAP5. FGF-7 mRNA expression enhancer, VEGF mRNA expression enhancer, IGF-1 mRNA expression enhancer, HGF mRNA expression enhancer, BMP-2 mRNA expression enhancer and KAP5.1 mRNA containing the same as an active ingredient An object of the present invention is to provide an expression promoter.

In order to solve such problems, the present invention provides an FGF-7 mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of kujin and Japanese pepper. do.

The present invention also provides a VEGF mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Chinese ginseng, Panax ginseng and Japanese pepper.

The present invention also provides an IGF-1 mRNA expression promoter containing, as active ingredients, extracts from one or more plants selected from the group consisting of Panax ginseng and Japanese pepper.

The present invention also provides an HGF mRNA expression promoter containing, as active ingredients, extracts from one or more plants selected from the group consisting of Panax ginseng and Japanese pepper.

The present invention also provides a BMP-2 mRNA expression promoter containing an extract from Japanese pepper as an active ingredient.

The present invention also provides a KAP5.1 mRNA expression-enhancing agent containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Chinese ginseng, Panax ginseng, Japanese pepper and Rhododendron japonicum.

According to the present invention, extracts from one or more plants selected from the group consisting of Chinese ginseng, Panax ginseng, Japanese pepper, and Rhododendron japonicum among highly safe compositions derived from natural products are used as active ingredients. To provide a safe FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter can be done.

An embodiment of the present invention will be described.
The FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter according to the present embodiment are ginseng, Panax ginseng, Japanese pepper and extracts from one or two or more plants selected from the group consisting of Rhododendron spp.

Extract raw materials used to obtain the above various extracts as active ingredients in the present embodiment are clara (scientific name: Sophora flavescens Aiton), panax ginseng (scientific name: Panax ginseng C.A. Meyer), and Japanese pepper (Zanthoxylum piperitum De Candolle). and Tamasakitsuzufuji (Scientific name: Stephania cephalantha).

Kujin (herbal drug name) is the root of Clara (scientific name: Sophora flavescens Aiton), a perennial herb belonging to the genus Clara of the family Fabaceae, which is distributed throughout Japan, Korea and China, and is easily obtained from these regions. can be done. Kujin has been used as a stomachic, diuretic, antipyretic, analgesic, and the like.

Panax ginseng (scientific name: Panax ginseng C.A. Meyer, also known as Korean ginseng, Korean ginseng) is a perennial herb belonging to the family Araliaceae, genus Panax ginseng, cultivated in the Tohoku region of China, Japan, etc., and is easily obtained from these regions. be able to. Constituent parts of Panax ginseng that can be used as raw materials for extraction include, for example, leaves, stems, flowers, roots, and mixtures of these parts, with roots being preferred.

Japanese pepper (Zanthoxylum piperitum De Candolle) is a plant belonging to the genus Zanthoxylum of the family Rutaceae, distributed in the Japanese archipelago and the Korean Peninsula, and can be easily obtained from these regions. Parts that can be used as raw materials for extraction include, for example, leaves, stems, flowers, buds, fruits, pericarp, fruit kernels, aerial parts, and mixtures thereof, preferably pericarp. be.

Stephania cephalantha (scientific name: Stephania cephalantha) is a climbing plant belonging to the genus Stephania cephalantha, which grows naturally in southern China, Taiwan, etc., and can be easily obtained from these regions. Examples of parts of Tamasakitsutsurafuji that can be used as raw materials for extraction include leaves, branches, stems, flowers, buds, roots, tuberous roots, and mixtures of these parts. This is the root tuber.

FGF-7 mRNA expression promoting effect, VEGF mRNA expression promoting effect, IGF-1 mRNA expression promoting effect, HGF mRNA expression promoting effect, BMP-2 mRNA expression promoting effect and KAP5.1 mRNA expression promoting effect contained in the extract from the above extraction raw material Although the details of the substance are unknown, by the extraction method generally used for plant extraction, etc., the above-mentioned extraction raw material has an FGF-7 mRNA expression promoting effect, a VEGF mRNA expression promoting effect, an IGF-1 mRNA expression promoting effect, and an HGF mRNA expression promoting effect. , an extract having a BMP-2 mRNA expression-enhancing effect and a KAP5.1 mRNA expression-enhancing effect can be obtained. In addition, the extract includes an extract obtained from the raw material for extraction by extraction, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crude or purified product thereof. is included.

The above-mentioned extract can be obtained by drying the raw material for extraction as it is, or pulverizing it using a crusher and subjecting it to extraction with an extraction solvent. Drying may be performed in the sun or using a commonly used dryer. In addition, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a non-polar solvent such as hexane. By performing a pretreatment such as degreasing, the plant can be efficiently extracted with a polar solvent.

Solvents used for extraction include water, hydrophilic organic solvents, mixtures thereof, and the like, and are preferably used at room temperature or at temperatures below the boiling point of the solvent. Components having FGF-7mRNA expression-enhancing action, VEGFmRNA expression-enhancing action, IGF-1mRNA expression-enhancing action, HGFmRNA expression-enhancing action, BMP-2mRNA expression-enhancing action and KAP5.1mRNA expression-enhancing action contained in each extraction raw material are can be easily extracted by an extraction treatment using as an extraction solvent.

Water that can be used as an extraction solvent includes, for example, pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and water subjected to various treatments. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, water that can be used as an extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered physiological saline, and the like.

Hydrophilic organic solvents that can be used as extraction solvents include, for example, lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; - polyhydric alcohols having 2 to 5 carbon atoms such as butylene glycol, propylene glycol and glycerin;

When using a mixture of two or more polar solvents as the extraction solvent, the mixture ratio can be adjusted as appropriate. For example, when using a mixture of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by volume of the lower aliphatic alcohol with 10 parts by volume of water. When using a mixture of water and an aliphatic ketone, it is preferable to mix 1 to 40 parts by volume of lower aliphatic ketone with 10 parts by volume of water. When using a mixture of water and polyhydric alcohol, it is preferable to mix 1 to 90 parts by volume of polyhydric alcohol with 10 parts by volume of water.

The extraction treatment does not need to adopt a special extraction method as long as the soluble components contained in the raw material for extraction can be eluted into the extraction solvent, and the extraction can be performed at room temperature or under reflux heating. For example, each extraction raw material is put into a treatment tank filled with an extraction solvent, and left to stand for 30 minutes to 4 hours while stirring as necessary to elute soluble components, and then filtered to remove solids. An extract can be obtained by The extraction solvent is distilled off from the resulting extract to obtain a paste-like concentrate, which is further dried to obtain a dried product. The extraction conditions are about 50 to 95° C. for 1 to 4 hours when water is used as the extraction solvent. Further, when a mixed solvent of water and ethanol is used as the extraction solvent, the time is about 30 minutes to 4 hours at 40 to 80°C.

The extract obtained as described above is diluted, concentrated, diluted, concentrated, or Treatments such as drying and purification may be applied.

The obtained extract is used as it is as an FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter. can be used, but is preferably in the form of a concentrate or a dry product. In obtaining a dry product, a carrier such as dextrin, cyclodextrin, etc. may be added in order to improve hygroscopicity.

In addition, since each extraction raw material has a unique smell and taste, it is possible to carry out purification for the purpose of decolorization, deodorization, etc. within the range that does not cause a decrease in the life activity of the raw material, but it is added to cosmetics. Since it is not used in a large amount when used, there is no practical problem even if it is left unrefined. Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like.

Extracts from one or more plants selected from the group consisting of Chinese ragweed, Panax ginseng, Chinese pepper, and Rhubarb japonicum obtained as described above have an FGF-7 mRNA expression-enhancing effect, a VEGF mRNA expression-enhancing effect, and an IGF -1 mRNA expression promoting effect, HGF mRNA expression promoting effect, BMP-2 mRNA expression promoting effect, and KAP5.1 mRNA expression promoting effect, so by using the effect, FGF-7 mRNA expression promoting agent, VEGF mRNA expression promoting agent, IGF -1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter.

In addition, in the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter, and KAP5.1 mRNA expression promoter according to the present embodiment, extraction of Kujin Any one of the above-mentioned active ingredients may be used as the above-mentioned active ingredient, or two or more of them may be mixed to obtain the above-mentioned effective ingredients. You may use it as an ingredient. When a mixture of two or more of the extract of the ragweed, the extract of the Panax ginseng, the extract of the Japanese pepper, and the extract of the Rhododendron dilatatum is used as the above-mentioned active ingredient, the mixing ratio is determined according to the degree of action thereof. It may be determined as appropriate.

The FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter according to the present embodiment are extracts of ginseng, Panax ginseng one or two or more selected from extracts of C. japonicum, extracts of Japanese pepper, and extracts of Tamasakitsutsurafuji.

The above extract can be formulated into any dosage form such as powder, granules, liquid, etc., according to a conventional method, using a pharmaceutically acceptable carrier such as dextrin, cyclodextrin, or any other adjuvant. can. At this time, as auxiliary agents, for example, excipients, stabilizers, corrigents and the like can be used. Forms of the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter formulated from the above extract include, for example: , ointments, liquids for external use, and the like.

The FGF-7 mRNA expression-promoting agent in this embodiment can promote the expression of FGF-7 mRNA through the FGF-7 mRNA expression-promoting action of the kujin extract and the Japanese pepper extract. As a result, for example, it induces the division and growth of fibroblasts, vascular endothelial cells, myoblasts, chondrocytes, glial cells, osteoblasts, etc., promotes hair growth through activation of hair roots, and depilates. It can improve or cure diseases. Therefore, the extract of Kujin and the extract of Japanese pepper can also be used as active ingredients such as hair-restoring cosmetics. However, the FGF-7 mRNA expression-enhancing agent of the present embodiment can be used for all other applications in which the FGF-7 mRNA expression-enhancing action is significant.

The VEGF mRNA expression-promoting agent in the present embodiment can promote the expression of VEGF mRNA through the VEGF mRNA expression-promoting action of the kujin extract, the carrot extract, and the Japanese pepper extract. This promotes, for example, the proliferation and migration of vascular endothelial cells, angiogenesis, blood coagulation, blood pressure regulation, and the growth of lymphatic vessels in the skin. Angiogenesis imperfecta, ischemic leg disease, etc. can be improved or treated. Therefore, the extract of kujin, the extract of carrot and the extract of Japanese pepper can also be used as active ingredients of scalp cosmetics and the like. However, the VEGF mRNA expression-enhancing agent of the present embodiment can be used for all other applications in which the VEGF mRNA expression-enhancing action is significant.

The IGF-1 mRNA expression-promoting agent in this embodiment can promote the expression of IGF-1 mRNA through the IGF-1 mRNA expression-promoting action of carrot extract and Japanese pepper extract. As a result, for example, it promotes differentiation, proliferation, and growth of cells in general, suppression of aging progress, blood sugar reduction, regulation of reproductive function, sulfate ion uptake into cartilage, etc., alopecia, skin aging, diabetes, and pituitary gland. Hypofunction, pituitary dwarfism, etc. can be improved or treated. Therefore, the carrot extract and the Japanese pepper extract can also be used as active ingredients in hair nourishing cosmetics and the like. However, the IGF-1 mRNA expression-enhancing agent of the present embodiment can be used for all other applications that are significant in exhibiting the IGF-1 mRNA expression-enhancing effect.

The HGF mRNA expression promoter in the present embodiment can promote HGF mRNA expression through the HGF mRNA expression promoting action of carrot extract and Japanese pepper extract. This, for example, promotes the proliferation of epithelial cells, endothelial cells, hematopoietic cells, etc. derived from each organ, suppresses organ damage and fibrosis, promotes regeneration, alopecia, fibrosis, liver disease. , arteriosclerosis obliterans, etc. can be improved or treated. Therefore, carrot extracts and Japanese pepper extracts can also be used as active ingredients in hair-restoring cosmetics and the like. However, the HGF mRNA expression-enhancing agent of the present embodiment can be used for all applications other than these applications that are significant in exhibiting the HGF mRNA expression-enhancing action.

The BMP-2 mRNA expression-promoting agent in this embodiment can promote the expression of BMP-2 mRNA through the BMP-2 mRNA expression-promoting action of the Japanese pepper extract. As a result, for example, it can be suitably used for alopecia, skin aging, induction of bone formation, regulation of differentiation and proliferation of cells in general, body axis formation and almost all organ formation, differentiation of nerve cells and maintenance of function. can. Therefore, the Japanese pepper extract can also be used as an active ingredient in hair nourishing cosmetics and the like. However, the BMP-2 mRNA expression-enhancing agent of the present embodiment can be used for all other applications in which the BMP-2 mRNA expression-enhancing action is significant.

The KAP5.1 mRNA expression promoter in the present embodiment enhances the expression of KAP5.1 mRNA through the KAP5.1 mRNA expression-enhancing action possessed by the extract of kujin, the extract of Panax ginseng, the extract of Japanese pepper, and the extract of Tsubakitsutsurugi. can be promoted. As a result, it is possible to regenerate the cuticle and improve the hair quality such as hardness, elasticity, and stiffness of the hair. Therefore, the extract of Kujin, the extract of Panax ginseng, the extract of Japanese pepper, and the extract of Tamasaki Tsutsurugi can also be used as an active ingredient such as a hair quality improving agent. However, the KAP5.1 mRNA expression-enhancing agent of the present embodiment can be used for all other uses that are significant in exhibiting the KAP5.1 mRNA expression-enhancing action, in addition to these uses.

The method of administering the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter to patients according to this embodiment includes: Intrasubcutaneous administration, intramuscular administration, intravenous administration, oral administration, transdermal administration and the like can be mentioned, and a method suitable for prevention, treatment, etc. of the disease may be appropriately selected according to the type of disease. In addition, the dosage of the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter according to the present embodiment also affects the disease The dose may be increased or decreased as appropriate depending on the type, severity, individual patient differences, administration method, administration period, etc.

In addition, the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter according to the present embodiment are excellent FGF- 7 mRNA expression promoting effect, VEGF mRNA expression promoting effect, IGF-1 mRNA expression promoting effect, HGF mRNA expression promoting effect, BMP-2 mRNA expression promoting effect and KAP5.1 mRNA expression promoting effect, skin cosmetic, scalp cosmetic and hair cosmetic It is suitable for blending in cosmetics such as

Examples of cosmetics in which the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter can be incorporated include ointments, Creams, emulsions, lotions, packs, foundations, hair tonics, hair lotions, shampoos, rinses, soaps and the like. FGF-7 mRNA expression enhancer, VEGF mRNA expression enhancer, IGF-1 mRNA expression enhancer, HGF mRNA expression enhancer, BMP-2 mRNA expression enhancer and KAP5.1 mRNA expression enhancer. Although it can be appropriately adjusted according to the type of cosmetic, a suitable blending ratio is about 0.0001 to 10% by mass in terms of a standard extract, and a particularly suitable blending ratio is the standard It is about 0.001 to 1% by mass in terms of a simple extract. Cosmetics should not interfere with the FGF-7 mRNA expression-enhancing action, VEGF mRNA expression-enhancing action, IGF-1 mRNA expression-enhancing action, HGF mRNA expression-enhancing action, BMP-2 mRNA expression-enhancing action, and KAP5.1 mRNA expression-enhancing action possessed by the extract. , main agents, auxiliaries or other ingredients used in the production of ordinary cosmetics, such as astringents, bactericidal / antibacterial agents, whitening agents, UV absorbers, moisturizing agents, cell activators, anti-inflammatory / anti-allergic agents, anti- Oxidizing/active oxygen removing agents, oils and fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances, and the like can be used in combination. Such combination may result in a more generalized product and may provide greater benefits than would normally be expected due to synergy between the other active ingredients used in combination.

Food and drink are those that are less likely to harm human health and are taken orally or through the gastrointestinal tract in normal social life. is not limited to Therefore, the "food and drink" according to the present embodiment includes orally ingested general food, health food (functional food and drink), food with health claims (food for specified health use, food with nutrient function claims, food with function claims), It includes a wide range of compositions that constitute quasi-drugs, pharmaceuticals, and the like. The food and drink in this embodiment are the FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter, and KAP5.1 mRNA expression promoter contained in the extract. may be labeled, and the food and drink may be a food with health claims (food for specified health use, food with function claims, food with nutrient claims), quasi-drug, or pharmaceutical.

FGF-7 mRNA expression enhancer, VEGF mRNA expression enhancer, IGF-1 mRNA expression enhancer, HGF mRNA expression enhancer, BMP-2 mRNA expression enhancer and KAP5.1 mRNA expression enhancer formulated from the extract are blended into food and drink. In such cases, the amount of the active ingredient in them can be changed as appropriate in consideration of the purpose of use, symptoms, gender, etc. It is preferable to make the intake amount about 1 to 1000 mg per. In addition, when the food and drink to be added are in the form of granules, tablets or capsules, FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter formulated from the above extract The amount of the agent, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter to be added is usually 0.1 to 100% by mass, preferably 5 to 100% by mass, relative to the target food and drink.

Food and drink to which FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter formulated from the above extract can be blended is not particularly limited, but specific examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (including concentrated stock solutions and powders for preparation of these drinks); ice cream, ice sherbet, Frozen desserts such as shaved ice; Noodles such as soba, udon, vermicelli, gyoza skin, steamed dumpling skin, Chinese noodles, instant noodles; candy, chewing gum, candy, gum, chocolate, tablets, snacks, biscuits, jelly, jam, cream , confectionery such as baked confectionery; seafood and livestock processed foods such as kamaboko, ham, sausage; processed milk, fermented milk and other dairy products; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressings Oil and fat processed foods; seasonings such as sauces and sauces; soups, stews, salads, side dishes, pickles; other health and nutritional supplements in various forms; When blending the extract and / or FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter and KAP5.1 mRNA expression promoter, usually Auxiliary raw materials and additives used can be used in combination.

The FGF-7 mRNA expression promoter, VEGF mRNA expression promoter, IGF-1 mRNA expression promoter, HGF mRNA expression promoter, BMP-2 mRNA expression promoter, and KAP5.1 mRNA expression promoter according to the present embodiment are suitable for humans. However, FGF-7 mRNA expression promoting effect, VEGF mRNA expression promoting effect, IGF-1 mRNA expression promoting effect, HGF mRNA expression promoting effect, BMP-2 mRNA expression promoting effect and KAP5.1 mRNA expression promoting effect are exhibited. As long as it can be applied to animals other than humans.

Hereinafter, the present invention will be described in more detail with reference to test examples and the like, but the present invention is not limited to the following test examples and the like. In addition, as the test samples in the following test examples, the extract of Chinese ginseng is the Chinese ginseng extract liquid, the panax ginseng extract is the carrot extract LA-20, the Japanese pepper extract is the Japanese pepper extract-J, and the Tamasakitsurafuji extract is cepharanthine N ( All of them were manufactured by Maruzen Pharmaceutical Co., Ltd.).

[Test Example 1] FGF-7, VEGF, IGF-1, HGF and BMP-2 mRNA expression promoting activity test 2 mRNA expression promoting effect was tested.

Human normal dermal papilla cells (HFDPC: derived from the parietal region) were seeded in a 60 mm petri dish and cultured at 37° C. under 5% CO ₂ using a medium for human normal dermal papilla cells (PCGM).

After culturing, 3 mL of the test sample dissolved in serum-free Dulbecco's Modified Eagle's Medium (DMEM) was added to each petri dish and cultured at 37° C. under 5% CO ₂ for 2 hours. As a control, cells were cultured in the same manner using DMEM to which no sample was added. After culturing, the medium was removed, total RNA was extracted with ISOGEN II (manufactured by Nippon Gene), the amount of RNA was calculated from absorbance at a wavelength of 260 nm, and total RNA was adjusted to 200 ng/μL.

Using this total RNA as a template, the mRNA expression levels of FGF-7, VEGF, IGF-1, HGF, BMP-2 and GAPDH as an internal standard were measured. Detection was performed using a real-time PCR device Thermal Cycler Dice (registered trademark) Real Time System III (manufactured by Takara Bio Inc.) using PrimeScript ^™ RT Master Mix (Perfect Real Time) (manufactured by Takara Bio Inc.) and TB Green (registered trademark) Fast. A real-time 2-step RT-PCR reaction was performed using qPCR Mix (manufactured by Takara Bio Inc.). The expression level of each mRNA was corrected and calculated with the expression level of GAPDH mRNA. FGF-7, VEGF, IGF-1, HGF and BMP-2 mRNA expression enhancement rates (%) were calculated by the following formulas.

FGF-7, VEGF, IGF-1, HGF and BMP-2 mRNA expression promotion rate (%) = A / B × 100
"A" in the formula represents the correction value when the test sample is added, and "B" represents the correction value when the test sample is not added.

The results of the above tests are shown in Tables 1 and 2. In the above formula, each mRNA expression promotion rate with no test sample added is 100%.

[Table 1]
mRNA expression promotion rate (%)
Sample name Concentration (μg/mL) FGF-7 VEGF IGF-1
Kujin extract 3.13 130.9 148.5 -
12.5 132.9 185.0 -
Panax ginseng extract 3.13 - 116.1 -
12.5 - 133.6 154.1
50 - 127.3 200.9
Japanese pepper extract 12.5 - 131.4 113.5
50 191.6 293.3 107.2

[Table 2]
mRNA expression promotion rate (%)
Sample name Concentration (μg/mL) HGF BMP-2
Panax ginseng extract 3.13 142.7 -
12.5 110.9 -
50 124.6 -
Japanese pepper extract 3.13 - -
12.5--
50 144.0 319.4

As shown in Table 1, the extract of Chinese ginseng and the extract of Japanese pepper have a high FGF-7 mRNA expression promotion rate, Both the panax ginseng extract and the Japanese pepper extract showed a high IGF-1 mRNA expression promotion rate. These results confirmed that these extracts have excellent FGF-7, VEGF, and IGF-1 mRNA expression-enhancing effects.

In addition, as shown in Table 2, both the panax ginseng extract and the Japanese pepper extract showed a high HGF mRNA expression promotion rate, and the Japanese pepper extract showed a high BMP-2 mRNA expression promotion rate. These results confirmed that these extracts have excellent HGF and BMP-2 mRNA expression promoting effects.

[Test Example 2] KAP5.1 mRNA expression promoting action test The KAP5.1 mRNA expression promoting action was tested for each of the above extract samples by the following method.

Normal human neonatal epidermal keratinocytes (NHEK) were pre-cultured with normal human epidermal keratinocyte growth medium (KGM) and harvested by trypsinization. The collected cells were seeded in a 6-well plate using KGM at a cell density of 3.0×10 ⁵ cells/2 mL, and cultured overnight at 37° C. under 5% CO ₂ .

After culturing, the medium was replaced with a growth factor-free medium (KBM). After 24 hours, the culture medium was discarded, 2 mL of the test sample dissolved in KBM to the required concentration was added to each well, and cultured at 37° C. under 5% CO ₂ for 24 hours. As a control, KBM to which no sample was added was used and cultured in the same manner. After culturing, the medium was removed, total RNA was extracted with ISOGEN II (manufactured by Nippon Gene), the amount of RNA was calculated from absorbance at a wavelength of 260 nm, and total RNA was adjusted to 200 ng/μL.

Using this total RNA as a template, the expression level of mRNA was measured for KAP5.1 and GAPDH as an internal standard. Detection was performed using a real-time PCR device Thermal Cycler Dice (registered trademark) Real Time System III (manufactured by Takara Bio Inc.) using PrimeScript ^™ RT Master Mix (Perfect Real Time) (manufactured by Takara Bio Inc.) and TB Green (registered trademark) Fast. A real-time 2-step RT-PCR reaction was performed using qPCR Mix (manufactured by Takara Bio Inc.). The expression level of KAP5.1 mRNA was calculated after correcting it with the expression level of GAPDH mRNA. KAP5.1 mRNA expression promotion rate (%) was calculated by the following formula.

KAP5.1 mRNA expression promotion rate (%) = A / B × 100
"A" in the formula represents the correction value when the test sample is added, and "B" represents the correction value when the test sample is not added.

Table 3 shows the results of the above tests. In addition, in the above formula, the KAP5.1 mRNA expression promotion rate without addition of the test sample is 100%.

[Table 3]
Sample name Concentration (μg/mL) KAP5.1 mRNA expression promotion rate (%)
Kujin Extract 3.13 119.3
12.5 199.9
50 172.8
Panax ginseng extract 3.13 164.4
12.5 161.0
50 161.5
Japanese pepper extract 3.13 131.3
12.5 195.0
50 191.7
3.13 139.9
Extract 12.5 133.4
50 185.4

As shown in Table 3, all of the extracts of Kujin, Panax Ginseng, Japanese Peppermint, and Rhododendron dilatatum exhibited high KAP5.1 mRNA expression promotion rates. These results confirmed that these extracts had an excellent KAP5.1 mRNA expression promoting effect.

The FGF-7mRNA expression promoter, VEGFmRNA expression promoter, IGF-1mRNA expression promoter, HGFmRNA expression promoter, BMP-2mRNA expression promoter and KAP5.1mRNA expression promoter of the present invention are used in cosmetics, foods and drinks, and the like. It can be suitably used as a component and further as a research reagent.

Claims (6)

An FGF-7 mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of kujin and Japanese pepper. A VEGF mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Chinese ginseng, Panax ginseng and Japanese pepper. An IGF-1 mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Panax ginseng and Japanese pepper. An HGF mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Panax ginseng and Japanese pepper. A BMP-2 mRNA expression promoter containing an extract from Japanese pepper as an active ingredient. A KAP5.1 mRNA expression promoter containing, as an active ingredient, an extract from one or more plants selected from the group consisting of Chinese ginseng, Panax ginseng, Japanese pepper and Tamasakitsutsurafuji.