JP7315940B2 - fibroblast growth factor-5 expression inhibitor - Google Patents

Description

TECHNICAL FIELD The present invention relates to a fibroblast growth factor-5 (FGF-5) expression inhibitor containing a natural product-derived component as an active ingredient.

Fibroblast growth factor (FGF) is a morphogenetic factor that not only has proliferative activity on fibroblasts but also has cell proliferation and differentiation activity on various cells, a tissue repair factor that acts at the time of tissue damage, and a homeostasis of the body. It is a multifunctional secretory factor that plays an important role as a metabolic regulator for maintaining sex. FGF is known to have more than 20 families, among which fibroblast growth factor-5 (FGF-5) is known to be involved in the hair cycle. .

Hair repeats growth and shedding according to a periodic hair cycle (hair cycle) consisting of a growth phase, a regression phase and a resting phase. If the anagen period is short, the hair does not grow sufficiently and falls out while it is thin and short. Furthermore, it is believed that once the anagen period is shortened, the next anagen period will also be shortened, resulting in increasingly finer and shorter hair.
Here, it is known that the above-mentioned FGF-5 acts on the dermal papilla and has the effect of causing the transition from the growth phase to the regression phase in the hair cycle (see Non-Patent Document 1).

Therefore, if the function of FGF-5 can be suppressed, it is possible to inhibit the transition from the growth phase to the regression phase in the hair cycle, extend the hair growth phase, prevent thinning hair, and prevent or improve hair loss. It is considered to be useful for hair growth and hair nourishing applications.
Known components that inhibit the function of FGF-5 include burnet extract (see Non-Patent Document 2), phytic acid (see Patent Document 1), and the like.

JP 2017-043594 A

Cell, 1994, vo.78, no.6, pp.1017-1025 West Japan Dermatology, 2007, vol.69, no.1, pp.81-86

The present invention finds a natural product-derived component with excellent safety that has the effect of suppressing the expression of fibroblast growth factor-5, and uses it as an active ingredient to express fibroblast growth factor-5. The object is to provide an inhibitor.

In order to solve the above problems, a fibroblast growth factor-5 expression inhibitor according to the present invention is characterized by containing an extract from hawthorn as an active ingredient.

According to the present invention, by using an extract from hawthorn as an active ingredient, it is possible to provide a highly safe fibroblast growth factor-5 expression inhibitor with excellent effects.

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below.
The fibroblast growth factor-5 (FGF-5) expression inhibitor of the present embodiment contains an extract from hawthorn as an active ingredient.

In addition, in the present embodiment, the "extract" includes an extract obtained from hawthorn as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crude purification thereof. either the product or the purified product.

The raw material for extraction used in this embodiment is hawthorn (scientific name: Crataegus cuneata).
Hawthorn (Crataegus cuneata) is a deciduous shrub of the genus Crataegus of the Rosaceae family, and is readily available from regions in central and southern China. Hawthorn stems are 30-90 cm high, and purple or white flowers bloom in August-September. The medicinal part of hawthorn is the fruit, which is widely used as a stomachic and digestive medicine. Constituent parts of hawthorn that can be used as raw materials for extraction include, for example, leaves, branches, stems, bark, flowers, fruits, and mixtures of these parts. Leaves are preferred.

The above hawthorn extract can be obtained by drying the raw material for extraction, either as it is or pulverizing it using a coarse 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 pretreatment such as degreasing, the extraction treatment of the raw material for extraction with a polar solvent can be efficiently performed.

As the extraction solvent, it is preferable to use a polar solvent, for example, water, a hydrophilic organic solvent, etc., which are used alone or in combination of two or more at room temperature or at a temperature below the boiling point of the solvent. is preferred.

Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic adjustment, buffering, and the like. Therefore, water that can be used as an extraction solvent in the present embodiment 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 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 include polyhydric alcohols having 2 to 5 carbon atoms such as 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 a mixture of water and a lower aliphatic alcohol is used as the extraction solvent, the mixing ratio of water and the lower aliphatic alcohol is preferably 9: 1 to 1: 9 (volume ratio), More preferably, it is 7:3 to 2:8 (volume ratio). When using a mixture of water and lower aliphatic ketone, the mixing ratio of water and lower aliphatic ketone is preferably 9:1 to 2:8 (volume ratio). In the case of using a mixed solution with a hydric alcohol, the mixing ratio of water and polyhydric alcohol is preferably 8:2 to 1:9 (volume ratio).

The extraction treatment is not particularly limited as long as the soluble components contained in the raw material for extraction can be eluted into the extraction solvent, and can be carried out according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent of 5 to 15 times the amount (mass ratio) of the extraction raw material, the soluble component is extracted at room temperature or under reflux heating, and then filtered to remove the extraction residue. liquid can be obtained. A paste-like concentrate is obtained by distilling off the solvent from the obtained extract, and a dried product is obtained by further drying the concentrate.

The extract from hawthorn obtained as described above (hereinafter sometimes simply referred to as "hawthorn extract") has an excellent fibroblast growth factor-5 (FGF-5) expression inhibitory effect. Therefore, it can be used as an active ingredient of a fibroblast growth factor-5 expression inhibitor (hereinafter sometimes abbreviated as “FGF-5 expression inhibitor”). The FGF-5 expression inhibitor according to this embodiment can be used in a wide range of applications such as pharmaceuticals, quasi-drugs and cosmetics.

The FGF-5 expression inhibitor according to the present embodiment may consist of only the hawthorn extract, or may be a formulation of the hawthorn extract.

FGF-5 expression inhibitor according to the present embodiment, dextrin, using a pharmaceutically acceptable carrier such as cyclodextrin and any other adjuvant, according to a conventional method, powder, granules, tablets, liquid, etc. can be formulated into any dosage form. At this time, as auxiliary agents, for example, excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents and the like can be used. The FGF-5 expression inhibitor can be used by blending it with other compositions (eg, skin cosmetics), and can also be used as tablets, capsules, and the like.

When the FGF-5 expression inhibitor according to the present embodiment is formulated, the content of the hawthorn extract is not particularly limited, and can be appropriately set according to the purpose.

In addition, the FGF-5 expression suppressing agent according to the present embodiment can be used as an active ingredient by blending other natural extracts having an FGF-5 expression suppressing effect with the hawthorn extract, if necessary. .

Examples of the administration method of the FGF-5 expression inhibitor according to the present embodiment to patients include transdermal administration, oral administration, etc. Depending on the type of disease, a method suitable for its prevention or treatment is appropriately selected. do it. In addition, the dose of the FGF-5 expression inhibitor according to this embodiment may also be increased or decreased as appropriate depending on the type and severity of disease, individual patient differences, administration method, administration period, and the like.

The FGF-5 expression suppressing agent according to the present embodiment can suppress the expression of FGF-5 through the action of the hawthorn extract, which is an active ingredient. This can prevent the transition from the growth phase to the regression phase in the hair cycle, extend the growth phase, prevent, treat or improve thinning hair and hair loss, and can be used for hair growth and hair restoration. . However, the FGF-5 expression-suppressing agent of the present invention can be used for all applications other than these uses in which it is significant to exert the FGF-5 expression-suppressing action.

Since the FGF-5 expression inhibitor of the present embodiment has an excellent FGF-5 expression inhibitory action, it is suitable for blending in, for example, hair and skin external preparations and foods and drinks. In this case, the hawthorn extract may be blended as it is, or an FGF-5 expression inhibitor formulated from the hawthorn extract may be blended.

Here, there are no restrictions on the category of external preparations for hair and skin, and they include a wide range of hair cosmetics, quasi-drugs, pharmaceuticals, etc. that are transdermally applied to the scalp with hair. Specific examples include hair tonics, hair lotions, hair creams, hair styling agents, shampoos, rinses, treatments and the like.

Food and drink are those that are less likely to harm human health and are taken orally or through the digestive tract in normal social life. is not limited to Therefore, the "food and drink" in 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), quasi-drugs, pharmaceuticals etc. The food or drink according to the present embodiment is preferably a food or drink that can display the favorable effects of the hawthorn extract on the food or its packaging, and is a food with health claims (food for specified health use, functional labeling). foods, nutrient functional foods), quasi-drugs and pharmaceuticals are particularly preferred.

In addition, since the FGF-5 expression inhibitor according to the present embodiment has an excellent FGF-5 expression inhibitory action, it can be suitably used as a reagent for research on these mechanisms of action.

The FGF-5 expression inhibitor according to the present embodiment is preferably applied to humans, but as long as the effects of each are exhibited, animals other than humans (eg, mice, rats, It can also be applied to dogs, cats, cows, pigs, monkeys, etc.).

The present invention will be specifically described below with reference to test examples, but the present invention is not limited to the following examples. In this test example, a hawthorn extract (manufactured by Maruzen Pharmaceutical Co., Ltd., sample 1) was used as a test sample.

[Test Example 1] Fibroblast growth factor-5 (FGF-5) mRNA expression inhibitory activity test The hawthorn extract (Sample 1) was tested for FGF-5 mRNA expression inhibitory activity as follows.

Human normal dermal papilla cells (HFDPC, derived from male parietal region) were seeded in a 60 mm petri dish at a cell density of 1.25 × 10 ⁴ cells/mL, and cultured using human normal dermal papilla cell medium (PCGM) until confluent. cultured.

Thereafter, the medium was removed, and 3 mL of medium containing the test sample (Sample 1, see Table 1 below for the sample concentration) dissolved in serum-free DMEM medium was added to each petri dish and cultured for 6 hours. After culturing, the medium was removed, total RNA was extracted with ISOGEN II (manufactured by Nippon Gene, Cat. No. 311-07361), and the amount of each RNA was measured with a spectrophotometer to reach 200 ng/μL. Total RNA was prepared as follows.

Using this total RNA as a template, the expression levels of FGF-5 and internal standard GAPDH mRNA were measured. Detection was performed by real-time 2-Step RT-PCR reaction using a real-time PCR device Smart Cycler (manufactured by Cepheid) and TaKaRa SYBR PrimeScript ^™ RT-PCR Kit (Perfect Real Time) (manufactured by Takara Bio Inc., code No. RR063A). . The expression level of FGF-5 mRNA was calculated by correcting it with the expression level of GAPDH mRNA. From the obtained values, the FGF-5 mRNA expression suppression rate (%) was calculated according to the following formula.

FGF-5 mRNA expression suppression rate (%) = {1-(A/B)} × 100
A: Correction value when test sample is added B: Correction value when test sample is not added Table 1 shows the results.

As shown in Table 1, it was confirmed that the hawthorn extract (Sample 1) has an excellent FGF-5 expression inhibitory effect.

The FGF-5 expression inhibitor according to the present invention can greatly contribute to the prevention, treatment, or improvement of thinning hair or hair loss, and hair growth/restoration applications.

Claims (1)

A fibroblast growth factor-5 expression inhibitor containing an extract obtained by extracting hawthorn (Crataegus cuneata) with a polar solvent as an active ingredient ,
The polar solvent is a solvent selected from the group consisting of water, lower aliphatic alcohols having 1 to 5 carbon atoms, lower aliphatic ketones having 3 to 4 carbon atoms and polyhydric alcohols having 2 to 5 carbon atoms, or It is a mixed solvent of two or more
A fibroblast growth factor-5 expression inhibitor characterized by: