JP2008169118A - Agent for inhibiting increase in expression of stem cell factor and agent for inhibiting increase in expression of basic fibroblast growth factor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an agent for inhibiting increase in expression of a stem cell factor (SCF) and an agent for inhibiting increase in expression of a basic fibroblast growth factor (bFGF) comprising a substance as an active ingredient having an inhibitory action on increase in expression of a stem cell factor (SCF) and an inhibitory action on increase in expression of a basic fibroblast growth factor (bFGF) by finding the substance from natural products having high safety. <P>SOLUTION: The agent for inhibiting increase in expression of a stem cell factor (SCF) and the agent for inhibiting increase in expression of a basic fibroblast growth factor (bFGF) each comprise an extract from Arnica montana as an active ingredient. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a stem cell growth factor expression increase inhibitor and a basic fibroblast growth factor expression increase inhibitor.

  Spots, buckwheat, skin pigmentation after sunburn, etc. occur as a result of markedly increased melanin production due to activation of pigment cells (melanocytes) present in the skin. It is connected. Conventionally, various therapeutic agents, external preparations for skin, cosmetics and the like are known as having a whitening effect. For example, as a compound that inhibits tyrosinase activity and suppresses melanin production, sulfur compounds represented by colloidal sulfur and glutathione are used. In addition, ascorbic acids, hydrogen peroxide, hydroquinone, catechol and the like are used to lightly bleach the produced melanin.

  However, ascorbic acids are unstable because they are easily oxidized when they are contained in water-rich cosmetics such as water-containing cosmetics, and cause discoloration of the cosmetics. Further, the hydrogen peroxide solution has problems in storage stability and safety in use. Furthermore, sulfur compounds such as glutathione and colloidal sulfur have a problem in that they emit a significant off-flavor. Furthermore, hydroquinone and catechol have skin irritation and allergic properties and have a problem in safety in use. Therefore, the use of these whitening ingredients in products such as cosmetics is restricted, and no whitening ingredients that are sufficiently satisfactory are yet known, and the development of better whitening agents is desired.

  Stem Cell Factor (SCF), also called Must Cell Growth Factor, C-Kit Ligand, Steel Factor, etc., is a protein produced from keratinocytes, fibroblasts, vascular endothelial cells, bone marrow stromal cells, etc. It is. SCF is known to have an action of promoting proliferation and differentiation of pluripotent hematopoietic stem cells, germ cells, mast cells, megakaryocyte progenitor cells, granulocyte / macrophage progenitor cells, pigment cells and the like. Moreover, it is known that the expression of SCF is enhanced by a spot site, ultraviolet irradiation or the like (see Non-Patent Document 1). As SCF, a membrane-bound SCF composed of 273 amino acid residues and a secreted SCF that is cleaved by the action of a proteolytic enzyme and released from the membrane are known. Membrane-bound SCF binds to the SCF receptor of the pigment cell while bound to keratinocytes and promotes the proliferation of the pigment cell. Secreted SCF is cleaved at the binding site, released from the cell membrane, and bound to the SCF receptor of the pigment cell, thereby promoting proliferation of the pigment cell. In addition, SCF is a myeloblast in the presence of interleukin-3 (IL-3) and granulocyte macrophage colony stimulating factor (GM-CSF) in patients with acute myeloid leukemia. It is known to promote the growth of selenium (see Non-Patent Document 2).

  Basic fibroblast growth factor (bFGF), also called FGF-2, is released from keratinocytes by ultraviolet irradiation, and the released bFGF acts on pigment cells to synthesize melanin. It is thought that this also promotes cell division of pigment cells (see Non-Patent Document 3). Further, bFGF is known as an angiogenesis promoting factor, and is known to promote angiogenesis in tumor cells (particularly malignant tumor cells).

  Therefore, abnormal production of SCF and bFGF may lead to abnormal proliferation of pigment cells, increase melanin production, and cause stains, freckles, dullness, and the like. Moreover, abnormal production of SCF is thought to lead to abnormal growth of myeloblasts, thereby causing diseases such as myelodysplastic syndrome, acute myeloid leukemia (AML), and abnormal production of bFGF occurs in tumor cells. It is thought to promote angiogenesis, thereby leading to the growth of tumor cells.

Therefore, suppressing the increase in the expression of SCF and bFGF suppresses the proliferation of pigment cells, suppresses the excessive production of melanin in the skin, and is useful for the prevention or suppression of pigmentation, stains, buckwheat, etc. after sunburn. it is conceivable that. Moreover, suppressing the increase in the expression of SCF suppresses the abnormal growth of myeloblasts and is considered to be useful for the prevention or treatment of myelodysplastic syndrome, acute myeloid leukemia, etc., and suppresses the increase in the expression of bFGF. This is considered to be useful for cancer treatment and the like by suppressing angiogenesis in tumor cells and suppressing the growth of tumor cells.
Hachiya A et al., J. Invest. Dermatol., No.116, 2001, p.578-586 Virginia C. Broudy et al., Blood, Vol.80, No.1, 1992, p.60-67 Halaban R. et al., J. Cell. Biol., No. 107, 1988, p. 1611-1619

  The present invention finds an SCF expression increase inhibitory action and bFGF expression increase suppressive action among highly safe natural products, and stem cell growth factor (SCF) expression increase suppressor and basic fiber containing them as active ingredients It aims at providing the blast cell growth factor (bFGF) expression raise inhibitor.

In order to solve the above-described problems, the stem cell growth factor (SCF) expression increase inhibitor and the basic fibroblast growth factor (bFGF) expression increase inhibitor of the present invention contain an extract from Arnica as an active ingredient. It is characterized by.
In addition, the preventive / therapeutic agent for the disease caused by the increased expression of stem cell growth factor (SCF) and the preventive / therapeutic agent for the disease caused by the increased expression of basic fibroblast growth factor (bFGF) are from Arnica. The extract is contained as an active ingredient.

  According to the present invention, an extract from natural Arnica, which is a natural product, is contained as an active ingredient, and an excellent stem cell growth factor (SCF) expression increase inhibitor and basic fibroblast growth factor (bFGF) expression increase. Inhibitors can be provided.

Hereinafter, the present invention will be described in detail.
[Suppressor of elevated stem cell growth factor expression, suppressor of basic fibroblast growth factor expression]
The stem cell growth factor (hereinafter referred to as “SCF”) expression increase inhibitor and the basic fibroblast growth factor (hereinafter referred to as “bFGF”) expression increase inhibitor of the present invention contain an extract from Arnica as an active ingredient. To do.

  Here, in the present invention, the “extract from Arnica” refers to an extract obtained using Arnica as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or these Both of these crudely purified products and purified products are included.

  The extraction raw material used in the present invention is Arnica (scientific name: Arnica montana L.). Arnica montana L. is an Asteraceae perennial plant that resembles daisy that grows on pastures of acid soils in mountainous regions from Europe to Southern Russia and is easily available from these regions. it can. Examples of the part that can be used as the extraction raw material include a stem part, an above-ground part, a flower part, a root part, a whole grass, and the like, and a flower part is preferable.

  Here, "flower" generally refers to the whole organs involved in sexual reproduction of seed plants, and is composed of flower leaves that are leaf deformations and flower axes that are stem deformations. It includes organs such as pupae, petals, oshibe, and heart skin. The “floral part” that can be used as an extraction raw material in the present invention includes not only the whole organs involved in sexual reproduction of seed plants but also a part thereof, for example, flower leaves, flower coats (buds and corolla), corolla, petals Etc. are also included.

  Although the details of the substance having the inhibitory effect on SCF expression increase and bFGF expression increase contained in the extract from Arnica are unknown, the extraction method generally used for plant extraction suppresses the increase in SCF expression from Arnica. An extract having an action and an action to suppress the increase in bFGF expression can be obtained.

  For example, after drying the plant, it is pulverized as it is or using a crusher, and subjected to extraction with an extraction solvent, whereby an extract having an SCF expression increase inhibitory effect and a bFGF expression increase inhibitory effect can be obtained. Drying may be performed in the sun or may be performed using a commonly used dryer. Moreover, after performing pretreatment, such as degreasing, with a nonpolar solvent such as hexane, it may be used as an extraction raw material. By performing pretreatment such as degreasing, extraction with Arnica's polar solvent can be performed efficiently.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water and hydrophilic organic solvents. These may be used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. Is preferred.

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

  Examples of hydrophilic organic solvents that can be used as extraction solvents include 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; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using a liquid mixture of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by weight of a lower aliphatic alcohol with respect to 10 parts by weight of water. When using a mixed solution, it is preferable to mix 1 to 40 parts by mass of a lower aliphatic ketone with 10 parts by mass of water, and when using a mixed solution of water and a polyhydric alcohol, water 10 It is preferable to mix 10-90 mass parts of polyhydric alcohol with respect to a mass part.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in 5 to 15 times the extraction solvent (mass ratio) of the extraction raw material, the soluble components are eluted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained. The obtained extract is diluted, concentrated, dried, purified, etc. according to a conventional method in order to obtain a diluted or concentrated solution of the extract, a dried product of the extract, or a crude purified product or a purified product thereof. Processing may be performed.

  Purification can be performed by, for example, activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, or the like. The obtained extract can be used as an active ingredient of the SCF expression increase inhibitor and bFGF expression increase inhibitor as it is, but a concentrated solution or a dried product is easier to use.

  Since the extract from Arnica has a characteristic odor and taste, it can be purified for the purpose of decolorization, deodorization, etc. within a range that does not cause a decrease in its physiological activity. Since it is not used in a large amount when blended with a rise inhibitor or a bFGF expression rise inhibitor, there is no practical problem even if it is not purified.

  Since the extract from Arnica obtained as described above has an SCF expression increase inhibitory action or a bFGF expression increase inhibitory action, an SCF expression increase inhibitor or a bFGF expression increase inhibitor using these actions It can be used as an active ingredient. Moreover, the extract from Arnica uses the inhibitory action of SCF expression increase, and the preventive / therapeutic agent of the disease resulting from an increase in the expression of SCF, specifically, the prophylactic / therapeutic agent of myelodysplastic syndrome, acute myeloid It can also be used as an active ingredient such as a leukemia preventive / therapeutic agent and an antitumor agent. Furthermore, the extract from Arnica uses the bFGF expression increase inhibitory action, and the preventive / therapeutic agent for the disease caused by the increase in bFGF expression, specifically, angiogenesis inhibitor, anticancer agent, antitumor It can also be used as an active ingredient such as an agent or a pharmaceutical composition that suppresses metastasis of cancer cells.

  The SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention may be composed solely of an extract from Arnica, or may be a formulation of an extract from Arnica.

  The extract from Arnica is in a dosage form such as powder, granule, tablet, liquid, etc. according to a conventional method using a pharmaceutically acceptable carrier such as dextrin and cyclodextrin and any other auxiliary agent. It can be provided as a formulation. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring agent and the like can be used. In addition, the extract from Arnica can be used by blending with other compositions, and can also be used as an ointment, a liquid for external use, a patch and the like.

  The SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention is blended with other natural extracts having an SCF expression increase inhibitory effect or bFGF expression increase inhibitory effect together with an extract from Arnica as necessary. And can be used as an active ingredient.

  Examples of the method for administering the SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention to a patient include subcutaneous tissue administration, intramuscular administration, intravenous administration, oral administration, and transdermal administration. Depending on the situation, a suitable method for the prevention / treatment or the like may be appropriately selected. In addition, the dose of the SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention may be appropriately increased or decreased depending on the disease type, severity, individual differences among patients, administration method, administration period, and the like.

  The SCF expression increase inhibitor of the present invention can suppress the increase in SCF expression through the SCF expression increase inhibitory action of the extract from Arnica, thereby suppressing the proliferation of pigment cells and the production of melanin, Spots, buckwheat, skin pigmentation and the like can be prevented or improved, and a whitening effect can be obtained. Moreover, abnormal growth of myeloblasts can be suppressed through the SCF expression increase inhibitory action of the extract from Arnica, thereby preventing, treating or improving diseases such as myelodysplastic syndrome and acute myeloid leukemia. be able to. However, the SCF expression increase inhibitor of the present invention can be used for all purposes that are meaningful for exhibiting the SCF expression increase suppression action in addition to these applications.

  The bFGF expression increase inhibitor of the present invention can suppress the increase of bFGF expression through the bFGF expression increase suppression action of the extract from Arnica, thereby suppressing the proliferation of pigment cells and the production of melanin, Spots, buckwheat, skin pigmentation and the like can be prevented or improved, and a whitening effect can be obtained. In addition, the bFGF expression increase inhibitor of the present invention suppresses abnormal angiogenesis in tumor cells through the bFGF expression increase suppressive action of the extract from Arnica, and prevents, treats or improves diseases such as cancer. be able to. However, the bFGF expression increase inhibitor of the present invention can be used for all purposes that are meaningful for exhibiting the bFGF expression increase suppression action in addition to these applications.

[Skin external preparation]
The SCF expression increase inhibitor and bFGF expression increase inhibitor containing the extract from Arnica of the present invention as an active ingredient can be used by blending with an external preparation for skin. Examples of the external preparation for skin to which the SCF expression increase inhibitor and bFGF expression increase suppressor of the present invention can be formulated include, but are not limited to, pharmaceuticals, quasi drugs, general skin cosmetics, medicinal cosmetics, and the like. Is not to be done.

  The amount of SCF expression increase inhibitor or bFGF expression increase inhibitor in the external preparation for skin can be adjusted as appropriate depending on the type of external preparation for skin and the physiological activity of the extract. It is 0.001-10 mass% in conversion to a thing.

  The external preparation for skin to which the SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention can be blended is within the range that does not impair the action of the SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention. Various main agents and auxiliaries usually used in the manufacture of external preparations for skin can be used in combination.

  Examples of those that can be used together with the SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention as a component for external preparation for skin include, for example, glycerin, collagen, hyaluronic acid and its salt, chondroitinic acid and its salt, chitin, chitosan, etc. Moisturizers; UV absorbers such as amyl paradimethylaminobenzoate; complex lipids such as glycerophospholipid and sphingophospholipid; β-carotene, oil-soluble licorice extract, lycochalcone A, baicalin, baicalein, and other active oxygen scavenging action Substances to have; Azulene, glycyrrhizic acid and its salts, glycyrrhetinic acid and its derivatives, anti-inflammatory substances such as zinc oxide; Vitamins and their derivatives such as riboflavin, tropherol, ascorbic acid and folic acid; jojoba oil, lanolin, liquid paraffin , Squalane, iso Oily components such as tealyl alcohol; surfactants such as sodium stearyl sulfate, diethanolamine cecil sulfate, and glyceryl stearate; antioxidants such as sodium erythorbate; preservatives such as ethyl paraben; buckwheat extract, chamomile extract, licorice Cholesterols such as root extract, rosemary extract, maronier extract; plant sterols; lipoproteins; microorganism-derived components such as bifidobacteria cultures, lactic acid bacteria cultures, yeast extract, bucurium extract; brown algae extract Algae extracts such as red alga extract; blood circulation promoters such as γ-oryzanol; anti-seborrheic agents such as sulfur; fragrances; alcohols; thickeners such as carboxy polymers; titanium yellow, safflower, other colorants, etc. Is mentioned. When used in this way, it becomes a more general product, and thereby a synergistic effect with other active ingredients used in combination may lead to a superior effect than would normally be expected.

  The external preparation for skin of the present invention suppresses the proliferation of pigment cells and the production of melanin through the SCF expression increase inhibitory action or bFGF expression increase inhibitory action possessed by the SCF expression increase suppressor or bFGF expression increase suppressor as its constituent components. , Spots, freckles, skin pigmentation, etc. can be prevented or improved, and a whitening effect can be obtained.

[Food and Drink]
It has been confirmed that the extract from Arnica, which is an active ingredient of the SCF expression increase inhibitor and bFGF expression increase inhibitor of the present invention, is not digested in the digestive tract. Therefore, the SCF expression increase inhibitor and the bFGF expression increase inhibitor of the present invention are suitable for blending into any food or drink or dietary supplement. In this case, it is appropriate that the amount of arnica extract per day for adults is 1 to 100 mg in consideration of the general intake of the food and drink to be added.

  Foods and drinks that can be blended with the SCF expression increase inhibitor and bFGF expression increase inhibitor of the present invention are not particularly limited. For example, beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks. (Including concentrated concentrates and powders for preparation of these beverages); frozen confectionery such as ice cream, ice sherbet, oyster ice; noodles such as buckwheat, udon, harusame, gyoza skin, Chinese husk, instant noodles; Candy, chewing gum, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery, etc .; fishery products such as kamaboko, ham, sausage; Dairy products; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, etc. Food; source, the sauce, such as seasoning, soup, can be mentioned stew, salad, prepared foods, the pickles and the like.

  The SCF expression increase inhibitor or bFGF expression increase inhibitor of the present invention is preferably applied to humans, but may be applied to animals other than humans as long as the respective effects are exhibited. You can also

  Hereinafter, although a manufacture example, a test example, and a compounding example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all.

[Production Example 1] Production of Arnica extract To 200 g of dried Arnica flower parts, 2000 mL of 50 mass% ethanol (mass ratio of water to ethanol = 1: 1) was added, and the mixture was refluxed at 80 ° C. For 2 hours, and filtered while hot. The same extraction process was further performed on the residue. The obtained extracts were combined, concentrated under reduced pressure, and dried to obtain 12 g of Arnica extract.

[Test Example 1] SCF and bFGF mRNA expression increase suppressive action test The Arnica extract obtained in Production Example 1 was tested for SCF mRNA expression increase suppressive action and bFGF mRNA expression increase suppressive action as follows.

(1) Preparation of single-stranded DNA Normal neonatal epidermal keratinocytes (NHEK) were seeded in a 35 mm dish and cultured under conditions of 37 ° C., 5% CO 2 -95% air for 24 hours. After completion of the culture, it was washed with 1 mL of a phosphate physiological buffer and replaced with 1 mL of Hanks' solution. Using an ultraviolet irradiation device equipped with four TOREX FL20SE-30 / DMRs as a light source, 50 mJ / cm ^{2 of} ultraviolet rays UV-B was irradiated. Immediately after the irradiation, the medium was replaced with a sample-added medium having a predetermined concentration (see Tables 1 and 2) and cultured for 24 hours. After completion of the culture, total RNA was prepared by a conventional method. In addition, total RNA was similarly prepared for cells cultured with “no sample added / no UV irradiation” and “no sample added / with UV irradiation”. Total RNA was prepared using the following method.

  Cells are lysed with 1 mL of RNA extraction reagent (product name: ISOGEN, manufactured by Nippon Gene), 200 μL of chloroform is added, the upper RNA layer is isolated by centrifugation (12,000 rpm, 4 ° C., 15 minutes), and isopropanol is further added. Concentrated with. Concentrated and precipitated total RNA was dissolved in TE solution (10 mM Tris-HCl / 1 mM EDTA, pH = 8.0) to prepare a total RNA preparation, and a PCR device (product name: TaKaRa PCR Themal Cycler MP, manufactured by Takara Bio Inc.) ) And a real-time PCR-dedicated reverse transcription kit (product name: TaKaRa ExScript RT reagent Kit, manufactured by Takara Bio Inc.), a single-stranded DNA used as a template for measuring the mRNA expression level of SCF and bFGF was synthesized. .

(2) Real-time-PCR reaction using the cyber green method A sense primer and an antisense primer having the following sequences were prepared as primers for SCF gene amplification (manufactured by Takara Bio Inc.).
Sense primer: 5'-cccttaggaatgacagcagtagca-3 '
Antisense primer: 5'-gcccttgtaagacttggctgtctc-3 '

A sense primer and an antisense primer having the following sequences were prepared as primers for amplifying the bFGF gene (manufactured by Takara Bio Inc.).
Sense primer: 5'-gtgtgctaaccgttacctggctatg-3 '
Antisense primer: 5'-ccagttcgtttcagtgccaca-3 '

Moreover, the sense primer and antisense primer which have the following arrangement | sequence were produced as a G3PDH gene amplification primer as an internal standard (made by Takara Bio Inc.).
Sense primer: 5'-gcaccgtcaaggctgagaac-3 '
Antisense primer: 5'-atggtggtgaagacgccagt-3 '

  Single-stranded DNA prepared from total RNA preparations prepared from cells cultured in “No sample added / No UV irradiation”, “No sample added / With UV irradiation” and “Sample added / With UV irradiation”, respectively. Real-time PCR device (Product name: Real Time PCR System Smart Cycler II, manufactured by Cepheid) and Real-time PCR kit (Product name: SYBR Premix Ex Taq, manufactured by Takara Bio Inc.) A real-time PCR reaction was performed. In the single-stranded DNA solution for preparing a calibration curve, the relative value of the stock solution is set to “100,000” for convenience, and the concentration values “100,000”, “10000”, “1000”, “100” are repeatedly diluted 10 times thereafter. ”And“ 10 ”. The reaction was held at 95 ° C. for 10 seconds, followed by 45 cycles of 95 ° C. for 5 seconds and 57 ° C. for 20 seconds, and the amount of luminescence of the cyber green dye was measured for each cycle.

(3) Analysis Amplification curves of DNA fragments encoding each of SCF, bFGF and G3PDH were prepared from the amount of luminescence of the cyber green dye in each cycle. A calibration curve was prepared from the amplification curve of a dilution series of a single-stranded DNA solution for preparing a calibration curve, with the horizontal axis representing the concentration and the vertical axis representing the number of cycles that maximized the second derivative of the amplification curve. For each expression quantification sample, the number of cycles that maximized the second derivative of the amplification curve was plotted on a calibration curve, and the relative expression level was calculated. After correcting the expression level of SCF and bFGF with the value of the expression level of G3PDH in the same sample, when the correction value of “No sample added / No UV irradiation” is set to 100, “No sample added / UV irradiation” And a correction value of “sample addition / with UV irradiation”.

The SCF mRNA expression increase rate (%) and bFGF mRNA expression increase suppression rate (%) were calculated by the following formulas.
mRNA expression increase suppression rate (%) = {(AB) − (AC)} / (AB) × 100
In the formula, A represents “correction value without sample addition / ultraviolet irradiation”, B represents “correction value without sample addition / ultraviolet irradiation”, and C represents “correction value with sample addition / ultraviolet irradiation”. Value ".
The results of the SCF mRNA expression increase inhibitory action test are shown in Table 1, and the results of the bFGF mRNA expression increase inhibitory action test are shown in Table 2.

  As shown in Table 1, it was confirmed that the extract from Arnica has an excellent SCF mRNA expression increase inhibitory effect and bFGF mRNA expression increase suppressive action. In addition, the degree of SCF mRNA expression increase inhibitory effect and bFGF mRNA expression increase suppressive action of the extract from Arnica depends on the concentration of the extract from Arnica, and can be adjusted by the concentration of the extract from Arnica. It is considered a thing.

[Formulation Example 1]
An emulsion having the following composition was produced by a conventional method.
Arnica flower part 50 mass% ethanol extract (Production Example 1) 0.01 g
Jojoba oil 4.0g
Placenta extract 0.1g
Olive oil 2.0g
Squalane 2.0g
Cetanol 2.0g
Glyceryl monostearate 2.0g
2.5 g of polyoxyethylene cetyl ether (20E.0)
Oleic acid polyoxyethylene sorbitan (20E.0) 2.0 g
Stearyl glycyrrhetinate 0.1g
1,3-butylene glycol 3.0 g
Hinokitiol 0.15g
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 2]
A lotion having the following composition was produced by a conventional method.
Arnica flower part 50 mass% ethanol extract (Production Example 1) 2 g
Glycerin 3g
1,3-butylene glycol 3g
Oleic acid polyoxyethylene sorbitan (20E.0) 0.5g
Methyl paraoxybenzoate 0.15g
Citric acid 0.1g
Sodium citrate 0.1g
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Composition Example 3]
A cream having the following composition was produced by a conventional method.
Arnica flower part 50 mass% ethanol extract (Production Example 1) 0.05 g
Aloe extract 0.1g
Liquid paraffin 5.0g
Salami beeswax 4.0g
Squalane 10.0g
Cetanol 3.0g
Lanolin 2.0g
Stearic acid 1.0g
Oleic acid polyoxyethylene sorbitan (20E.0) 1.5g
3.0 g glyceryl monostearate
Oil soluble licorice extract 0.1g
1,3-butylene glycol 6.0 g
1.5 g of methyl paraoxybenzoate
Fragrance 0.1g
Purified water remainder (total amount is 100 g)

[Formulation Example 4]
A pack having the following composition was produced by a conventional method.
Arnica flower part 50 mass% ethanol extract (Production Example 1) 0.05 g
Yokuinin extract 0.1g
Polyvinyl alcohol 15g
Polyethylene glycol 3g
7g of propylene glycol
Ethanol 10g
0.05 g of methyl paraoxybenzoate
0.1g dipotassium glycyrrhizinate
Fragrance 0.05g
Purified water remainder (total amount is 100 g)

[Formulation Example 5]
The following mixture was tableted to produce a tablet-shaped dietary supplement.
Arnica flower part 50 mass% ethanol extract (Production Example 1) 30.0 parts by mass Maltitol 47.0 parts by mass Crystalline cellulose 15.0 parts by mass Sucrose fatty acid ester 8.0 parts by mass

[Composition Example 6]
The following mixture was formed into granules to produce a dietary supplement.
Arnica flower part 50% by weight ethanol extract (Production Example 1) 34 parts by weight Beet oligosaccharide 1000 parts by weight Vitamin C 167 parts by weight Stevia extract 10 parts by weight

  The stem cell growth factor (SCF) expression increase inhibitor and the basic fibroblast growth factor (bFGF) expression increase inhibitor of the present invention are useful for the prevention or improvement of skin pigmentation, sun spots, buckwheat, etc. after sunburn. .

Claims (4)

  A stem cell growth factor (SCF) expression increase inhibitor comprising an extract from Arnica as an active ingredient.   A basic fibroblast growth factor (bFGF) expression increase inhibitor comprising an extract from Arnica as an active ingredient.   A prophylactic / therapeutic agent for diseases caused by increased expression of stem cell growth factor (SCF), comprising an extract from Arnica as an active ingredient.   A prophylactic / therapeutic agent for diseases caused by increased expression of basic fibroblast growth factor (bFGF), comprising an extract from Arnica as an active ingredient.