JP6546316B1 - Polyphenol derivatives exhibiting eyelash proliferation and hair growth - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a polyphenol derivative exhibiting eyelash proliferation action and hair growth action. SOLUTION: The target polyphenol derivative is a molecule consisting of polyphenol and a derivative consisting of cysteine, methionine and turanose. This derivative acts on a growth factor receptor, proliferates eyelash cells and hair growth cells, and also increases keratin. This production method is based on a culture method of human hair root cells. That is, human hairy root cells are cultured using a yellow rose flower fermented extract having a ceramide generating activity as a culture solution to collect a conditioned culture solution. The desired polyphenol derivative is contained in the human hair root cell acclimation culture solution. The obtained polyphenol derivative can be used for health foods, cosmetics, medicines and quasi-drugs for the purpose of skin care and hair growth. [Selected figure] None

Description

The present invention relates to polyphenol derivatives that exhibit eyelash proliferation and hair growth.

Eyelashes are necessary to protect the eyes, but their number decreases with aging. With eyelash reduction, eyelash growth is also necessary to pay attention to foreign body invasion. Also, in order to prevent eye diseases, it is important to promote eyelash growth. In addition, eyelashes are also attracting attention in the beauty field, and false eyelashes and eyelash beauty are being performed, and their use has increased in recent years.

In addition, although various researches have been made on hair growth using medicines, chemicals, and natural products, no results have been obtained for industrial use.

For these purposes, treatments and cosmetics that exhibit eyelash proliferation and hair growth are required, and various studies have been made.

Although the invention regarding eyelashes includes an applicator, a kit, and a method of applying mascara to the eyelashes, no mention is made here of the proliferation of eyelashes. (For example, refer to patent document 1.)

There is also an invention relating to compositions, methods and kits for enhancing hair, but no mention is made here of eyelash growth. (For example, refer patent document 2).

Furthermore, there are inventions of ectoin and ectoin derivatives as moisturizers in cosmetics, and the moisturizing action of synthetic components and staining of eyelashes are presented (see, for example, Patent Document 3). However, no mention is made here of the lashing action of the eyelashes.

As such, there is no invention regarding methods, ingredients or substances for growing eyelashes in the medical area, skin area or cosmetic area. Moreover, inventions concerning hair growth are also limited.

In addition, if the substance that causes eyelashes and hair growth and exhibits hair growth effects is a chemical substance, there is a risk that side effects will occur, and industrial use is limited.

Therefore, a substance which is derived from a natural product and which causes eyelashes to grow and which exhibits a hair growth effect is desired.

Patent No. 5587326 Special table 2013-534222 Patent No. 3635703

As described above, there is a problem that the existing eyelashes and hair growth effects of natural products are mild, and their application to industrial use is limited, and there is a problem in safety with chemically synthesized substances. Is limited.

In order to achieve the above object, the invention according to claim 1 relates to a polyphenol derivative exhibiting eyelash proliferation action and hair growth action shown in the following formula (1).

Since the present invention is configured as described above, the following effects can be obtained.

According to the derivative according to claim 1, it is possible to exert an excellent eyelash proliferation action and a hair growth action.

Hereinafter, embodiments of the present invention will be described in detail.

First, the polyphenol derivative exhibiting eyelashes proliferation and hair growth shown by the following formula (1) is composed of one molecule of polyphenol, one molecule of turanose, one molecule of cysteine and one molecule of methionine.

The polyphenol moiety of this derivative is a polyphenol similar to delphinidin.

The hydroxyl group at position 3 of the mother nucleus of polyphenol is bound to thuranose. It is a bond with the hydroxyl group of fructofuranose of turanose.

The 5-position of the mother nucleus of polyphenol remains a hydroxyl group. The 7-position hydroxyl group is bound to the methionine carboxyl group.

This methionine is linked to cysteine. Cysteine is at the N-terminal side.

The sulfur of methionine and cysteine remains unreacted. The side chain polyphenols of polyphenols have hydroxyl groups at the 3, 4 and 5 positions. There is no bond to these hydroxyl groups.

Turanose is D-type and is a natural type. Structurally, it is glucosyl fructose. The glycosyl group is of the pyranose type. Fructose is furanose type.

In addition, turanose is a disaccharide generated from beans such as soybeans and azuki beans in the fermentation process of microorganisms, and is also used as a cosmetic. It has excellent moisturizing and skin cell proliferation effects.

Methionine and cysteine are both L-type and natural. The components of this polyphenol derivative are all derived from natural products and contained in plants. In addition, this polyphenol derivative can be synthesized organically from polyphenol, methionine, cysteine and turanose.

This organically synthesized derivative is used for analysis as a standard substance. However, the production is expensive, and the use of an organic solvent has the disadvantage that it is difficult to use in the cosmetic and food fields.

With regard to the structure of this polyphenol derivative, the position of the peak is 0.96, 1.01, 1.26, according to 400 MHz H-NMR (1H-NMR) analysis in deuterated dimethyl sulfoxide of this derivative (manufactured by Bruker). 1.29, 1.30, 1.31, 1.47, 1.65, 1.68, 2.07, 2.12, 2.23, 2.25, 2.29, 2.91, 3. 12, 3.18, 3.19, 3.37, 4.14, 5.21, 5.33, 5.64, 5.68, 5.92, 5.98, 6.03, 6.15, It is found at 8.38 and 8.63 ppm.

In addition, in C-NMR (13C-NMR) analysis of this derivative in deuterated dimethyl sulfoxide, the positions of peaks are 14.8, 23.6, 24.1, 24.5, 25.6, 25.9, 28.3, 28.5, 30.0, 30.1, 32.8, 32.9, 35.1, 54.0, 56.1, 57.5, 57.8, 63.9, 71. 7, 73.7, 124.3, 126.7, 126.9, 135.3, 136.6, 141.9, 142.7, 153.7, 156.6, 165.9, 169.2, It is found at 172.9, 173.3, 173.7 and 174.9 ppm.

Since this polyphenol derivative is of natural origin, it has high absorbability and safety. In particular, from the viewpoint of safety, this polyphenol derivative is degraded by in vivo enzymes, in particular, peptidases and esterases, and is highly safe because it is degraded even if it is ingested in large quantities.

This polyphenol derivative exerts a hair growth effect. In particular, it exerts a proliferative effect on eyelashes and hair.

The mechanism of eyelashes proliferation and hair growth by this polyphenol derivative is to serve as a growth factor for eyelashes and hair cells. The function of this polyphenol derivative as a growth factor is by acting as a ligand by binding to both EGF (Epidermal Growth Factor) and VEGF (Vascular Endothelial Growth Factor) receptors.

EGF and VEGF are proteins that show growth action, but the active site is a peptide. This polyphenol derivative is similar to these growth factor peptides and activates the receptor. This derivative is soluble in both water and oil soluble solvents. This amphiphilic nature is preferred as it broadens the use of this derivative.

The receptor stimulation action of this polyphenol derivative is transient and does not bind to the receptor. Because it is a transient reaction, it is highly safe.

Furthermore, cysteine is also required to increase keratin, and this polyphenol derivative has an effect of increasing keratin. This polyphenol derivative activates keratin synthesis enzymes to increase keratin levels. This keratin increasing action is preferable because it strengthens the hair and eyelashes.

As a method for extracting or producing this polyphenol derivative, any method such as a culture method, a fermentation method, an enzyme reaction method or a chemical synthesis method is used.

Also, this polyphenol derivative can be obtained from a conditioned medium obtained by culturing human hairy root cells. The age at which the hair root cells are collected is preferably lower since the growth of hair root cells is enhanced. Furthermore, baby-derived hair root cells are more preferable because they are excellent in growth action. In addition, it can be extracted from fermented soybeans such as soybeans and azuki beans. In this extraction method, it is preferable to use a digestive enzyme such as a protease or a lipase because the extraction efficiency is enhanced.

In particular, there is a production method in which human hairy root cells are cultured using a yellow rose flower fermented extract rich in polyphenol as a culture solution to collect a conditioned culture solution. The yellow rose flower fermented extract used herein is produced by the production method disclosed in Japanese Patent No. 5621330, and it is preferable that ceramide formation be increased.

Furthermore, when manufacturing by an enzyme reaction method, it is preferable to utilize the plant containing polyphenol as a raw material. Alternatively, the microorganism can be biosynthesized by fermentation.

Furthermore, fermenting azuki beans is useful as a method for producing this polyphenol derivative.

Furthermore, as a method of purification of the obtained substance, it is preferable to utilize purification operation such as separation resin.

For example, it is preferable that they be separated and separated by a carrier for separation or resin. As the carrier or resin for separation, porous polysaccharides, silicon oxide compounds, polyacrylamides, polystyrenes, polypropylenes, styrene-vinylbenzene copolymers, etc. coated on the surface are used. Those having a particle size of 0.1 to 300 μm are preferable. The finer the particle size, the higher the precision of separation, but the longer the separation time.

For example, reverse phase carriers or resins coated with a hydrophobic compound on the surface are used for separation of highly hydrophobic substances. Those coated with cationic substances are suitable for the separation of anionically charged substances. Also, those coated with anionic materials are suitable for separating cationically charged materials. When a specific antibody is coated, it is used as an affinity carrier or resin that separates only specific substances.

Affinity carriers or resins are utilized for specific preparation of antigens utilizing antigen-antibody reactions. A distributive carrier or resin is used for isolation of substances if there is a difference in the partition coefficient between the substance and the separating solvent, such as silica gel (manufactured by Merck).

Among these, from the viewpoint of being able to reduce the production cost, adsorptive carriers or resins, partitionable carriers or resins, carriers or resins for molecular sieves and resins and ion exchange carriers or resins are preferred. Furthermore, reverse phase carriers or resins and partitionable carriers or resins are more preferable in that they have a large difference in distribution coefficient with respect to the separation solvent.

When an organic solvent is used as a separation solvent, a carrier or resin resistant to the organic solvent is used. Also preferred are carriers or resins utilized for pharmaceutical or food production. From these points, Diaion (manufactured by Mitsubishi Chemical Corporation, HP-20 and HP-21) and XAD-2 or XAD-4 (manufactured by Rohm and Haas) as adsorptive carriers, and Sephadex LH as a carrier for molecular sieves -20 (manufactured by Amersham Pharmacia), silica gel as a carrier for distribution, IRA-410 (manufactured by Rohm and Haas) as an ion exchange carrier, and DM1020T (manufactured by Fuji Silysia) as a reverse phase carrier are more preferable.

Among these, Diaion HP-20, Sephadex LH-20 and DM1020T are more preferable.

The obtained extract is dissolved in a separation carrier or a solvent for swelling the resin before separation. The amount thereof is preferably 1 to 40 times, and more preferably 4 to 20 times the weight of the extract in terms of separation efficiency. The separation temperature is preferably 4 to 30 ° C., and more preferably 10 to 25 ° C., from the viewpoint of the stability of the substance.

As the separation solvent, water or a lower alcohol containing water, a hydrophilic solvent or a lipophilic solvent is used. As the lower alcohol, methanol, ethanol, propanol and butanol are used, but ethanol used for food is preferable.

When Sephadex LH-20 is used, lower alcohols are preferred as separation solvents. When silica gel is used, chloroform, methanol, acetic acid or a mixture thereof is preferred as the separation solvent.

When Diaion HP-20 and DM1020T are used, the separation solvent is preferably a lower alcohol such as methanol or ethanol or a mixed solution of lower alcohol and water.

In addition, it is preferable to collect the fractions containing the activity and remove the solvent by drying or vacuum drying to obtain a powder or a concentrate because the influence of the solvent can be excluded.

This polyphenol derivative causes the growth of human eyelashes and hair, and also directly acts on cells present in skin and skin cells to biosynthesize keratin, and exhibits a skin-refining action, a hair-growing action and a skin regenerating action. It can also be used as an eyelash growth agent and a hair growth agent.

The addition of fats and oils to polyphenol derivatives is preferred as the resulting active moiety remains stable in the oil. For example, extraction with soybean oil, rice bran oil, grape seed oil, olive oil, jojoba oil is preferred. This derivative is soluble in both water and oil soluble solvents. This amphiphilic nature is preferred as it broadens the use of this derivative.

It is used as a medicine as a parenteral injection such as injection or oral preparation or a coating, and as a quasi-drug, it is used by being formulated into tablets, capsules, drinks, soaps, coatings, gels, tooth powders etc. Ru.

The oral preparation includes tablets, capsules, powders, syrups, drinks and the like. When mixed in the above-mentioned tablets and capsules, they can be used together with binders, excipients, swelling agents, lubricants, sweeteners, flavors and the like. The tablets may also be coated with shellac or sugar.

In the case of the above-mentioned capsule preparation, the above-mentioned material can further contain a liquid carrier such as oil and fat. In the case of the above-mentioned syrups and drinks, sweeteners, preservatives, coloring and flavoring agents and the like can be added.

Parenteral preparations include injections as well as external preparations such as ointments, creams and aqueous preparations. As a base of the external preparation, petrolatum, paraffin, fats and oils, lanolin, macrogold and the like are used, and they can be made into an ointment, a cream and the like by a usual method.

Injections include solutions, and also lyophilizers. At the time of use, it is used as it is aseptically dissolved in distilled water for injection, physiological saline and the like.

As a food preparation, it is used as a cosmetic food for hair growth and beauty, a food for beauty and hair growth, and a cell activator for maintenance of healthy cells. Moreover, it is preferable to use it as a nutraceutical food or food for specified health use as a health food.

When the obtained food preparation is used for pets and domestic animals such as dogs and cats, it is used as a feed or pet supplement for the purpose of maintaining skin and tissue health.

It can be used together with a surfactant, a solvent, a thickener, an excipient, etc. according to a conventional method as a cosmetic. For example, it may be in the form of a cream, a gel for hair, a face wash, a cosmetic solution, a lotion, etc., and it is a cosmetic for promoting hair growth and keratin production.

The form of the cosmetic is arbitrary, and can be used as a solution, a cream, a paste, a gel, a gel, a solid or a powder. This derivative is soluble in both water and oil soluble solvents. This amphiphilic nature is preferred as it broadens the use of this derivative.

Next, the method for producing the polyphenol derivative represented by the above-mentioned formula (1) exhibiting the eyelash proliferation action and the hair growth action, which comprises the acclimatizing step of culturing human hair root cells using the yellow rose flower fermented extract as a culture solution will be described.

The polyphenol derivative represented by the above-mentioned formula (1) mentioned here comprises one molecule of polyphenol, one molecule of turanose, one molecule of cysteine and one molecule of methionine.

Hair root cells are collected by exfoliation from the root of human head hair free from viral and bacterial infections. The step comprises culturing the obtained hair root cells in a culture solution comprising a yellow rose flower fermented extract.

The yellow rose flower fermented extract manufactured by Anri Japan Co., Ltd. is preferable because it is excellent in quality and effectiveness. Yellow rose flower fermented extract is added as 50 to 95% volume, 2 times concentrated phosphate buffered saline (pH 6.8) as a solvent, and the pH is adjusted to 6.4 to 7.0 by making the osmotic pressure isotonic. This is used as a culture solution for hairy root cells. In addition, it is preferable not to use additives including antibiotics and preservatives from the viewpoint of quality and safety.

After autoclaving this culture solution, isolated human hairy root cells are cultured in the culture solution. After the cells have grown, the culture fluid is harvested as a conditioned media. The obtained human hairy root cell conditioned medium can be powdered as it is or lyophilized.

It is preferable to separate and purify the target polyphenol derivative from the above-mentioned reaction product, since the intake can be reduced as a highly pure substance. As a method of this purification, it is preferable to utilize a purification operation such as separation resin. In addition, in order to raise purity, it is preferable to repeat and implement the purification process mentioned above.

It is preferable to collect the fraction containing the polyphenol derivative and remove the solvent by drying or vacuum drying to obtain the target polyphenol derivative as a powder or a concentrate, because the influence of the solvent can be excluded.

Also, it is preferable to powderize this polyphenol derivative for the purpose of preservation. In addition, hair root cells can also be used from porcine, bovine and ovine. In particular, when food is used, it is preferable to use hair root cells derived from food animals.

Hereinafter, the embodiment will be specifically described using examples and test examples. In addition, these are examples and it is possible to change conditions within the range of common sense according to the difference of a raw material, a raw material, and a test substance.

Hair root cells were collected from the root of human head hair free of virus and bacterial infection by exfoliation. This exfoliation method has been established as a method for harvesting hairy root cells.

The obtained hair root cells were cultured in a culture solution consisting of a yellow rose flower fermented extract. A yellow rose flower fermented extract manufactured by Anri Japan Co., Ltd. was used. It is manufactured by the manufacturing method disclosed in Japanese Patent No. 5621330, exhibits high quality, and is excellent in ceramide increasing action.

Adjust the pH to 6.4 to 7.0 by making the osmotic pressure isotonic by adding 10% of 2-fold concentrated phosphate buffered saline (pH 6.8) to this yellow rose flower fermented extract as 90% volume did. This was used as a culture solution. In addition, additives including antibiotics and preservatives were not used.

The culture solution was transferred to a glass culture medium bottle, autoclaved at 121 ° C. for 10 minutes by an autoclave (manufactured by Hirayama Seisakusho Co., Ltd.), and cooled.

The above-mentioned human hair root tissue was transferred to the above-mentioned sterile culture solution and washed, and then transferred to a cell dispersion to which 0.1% of collagenase (manufactured by Nitta gelatin) was added. The collagenase solution containing this hair root tissue was digested at 37 ° C. for 10 minutes, the tissue was separated, and hair root cells were separated.

The hair root cell dispersion was collected from the hair root cell dispersion through a cell strainer (Funakoshi, 43-50005-03). The hair root cells obtained were dispersed in a culture solution and centrifuged (1500 rpm, 5 minutes, room temperature) to precipitate cells. Again, the culture solution was added to the centrifuge tube, dispersed, centrifuged, the supernatant was discarded, and the precipitated hair root cells were dispersed in the culture solution to collect a cell suspension.

This hair root cell suspension was seeded together with a culture solution on a 35 mm diameter culture petri dish (manufactured by Falcon). The number of hair root cells was adjusted to about 1000. The hair root cells were cultured at 37 ° C. for 5 to 7 days in a carbon dioxide gas incubator (manufactured by Yamato Scientific Co., Ltd., CO 2 incubator NU-5800) under 5% carbon dioxide gas / 95% air.

Hair root cells were conditioned and cultured while visually observing the proliferation of hair root cells under a phase contrast microscope (manufactured by Olympus). The acclimatization refers to the growth process of growth factors, proteins and lipids released by the hair root cells, and the cells are proliferated by the conditioned medium. When the culture is continued and the hair root cells become confluent (one layer on the petri dish surface), the culture fluid is collected, centrifuged (3000 rpm, 5 minutes) to collect only the supernatant, which is autoclaved and cooled. The resulting solution was used as a hair root cell conditioned medium. This is Sample 1.

In addition, the cells that became confluent were detached according to a conventional method using trypsin and an EDTA solution, dispersed in a culture solution, and then approximately 1000 cell numbers were reseeded in a culture petri dish and conditioned.

70 g of the liquid of the obtained sample 1 was suspended in 200 mL of purified water and subjected to 500 g of Diaion HP-20 (manufactured by Mitsubishi Chemical Co., Ltd.) swollen with 5% ethanol. After washing with 700 mL of 5% ethanol, it was further washed with 50% ethanol.

To this, 500 mL of 80% ethanol was added to fractionate the target polyphenol derivative. The obtained fraction was dried by a vacuum drier. This purification operation was carried out four times to obtain 1.7 g as a final purified product. This is Sample 2.

Hereinafter, test methods and results regarding structural analysis of polyphenol derivatives are described.
(Test Example 1)

The sample 2 obtained as described above was dissolved in purified water, filtered, and analyzed by high performance liquid chromatography (HPLC, Shimadzu Corporation).

Furthermore, analysis was performed using a deuterated dimethyl sulfoxide core magnetic resonance apparatus (NMR, manufactured by Bruker). As a result of structural analysis, polyphenol, turanose, and a derivative in which cysteine and methionine were bound were detected from sample 2 and sample 1.

The bond was one molecule at a time. In addition, cysteine and methionine were L-type.

In the H-NHR analysis results of 400 MHz, 0.96, 1.01, 1.26, 1.29, 1.30, 1.31, 1.47, 1.65, 1.68, 2.07, 2 .12, 2.23, 2.25, 2.29, 2.91, 3.12, 3.18, 3.19, 3.37, 4.14, 5.21, 5.33, 5.64 Peaks were observed at 5.68, 5.92, 5.98, 6.03, 6.15, 8.38 and 8.63 ppm.

Furthermore, in C-NMR analysis results, 14.8, 23.6, 24.1, 24.5, 25.6, 25.9, 28.3, 28.5, 30.0, 30.1, 32 .8, 32.9, 35.1, 54.0, 56.1, 57.5, 57.8, 63.9, 71.7, 73.7, 124.3, 126.7, 126.9 , 135.3, 136.6, 141.9, 142.7, 153.7, 156.6, 165.9, 169.2, 172.9, 173.3, 173.7 and 174.9 ppm. Was recognized.

Below, the chart of the analysis result of C-NMR is shown. (The horizontal axis unit is ppm, and the vertical axis unit is peak intensity.)

The above analysis values are identical to the peaks of organically synthesized polyphenol derivatives, and polyphenol derivatives were identified. This derivative contained in sample 2 was 98.9%, ie, 98.9% pure, and sample 1 was 77.2%.

Hereinafter, a confirmation test of keratinogenesis using human eyelash-derived cells is described.
(Test Example 2)

Healthy male 56-year-old lashes were collected and cells were separated by collagenase method. These cells were used as eyelash cells. The eyelash cells were cultured in MEM basic medium at 37 ° C. under 5% carbon dioxide gas. Cells in growth phase were detached with trypsin-containing medium. First, the number of viable cells was counted under a microscope by trypan blue dye exclusion method. The number of cells was adjusted to 1000 cells per mL, and 5 mL of each was seeded on a culture petri dish and further cultured at 37 ° C. under 5% carbon dioxide gas. The cells were damaged by irradiating them with ultraviolet light using an ultraviolet irradiation device (Loctite, output: 88 MH). Irradiation was performed for 1 hour with the lid of the petri dish removed.

The ultraviolet radiation damaged the eyelash cells, and recovery from this injury was tested. In addition, this method is a method implemented to evaluation of a test substance in the skin and hair area.

Here, Sample 2 as a test substance and human EGF (manufactured by Funakoshi) as a control substance were all suspended in physiological saline, diluted and added to a final concentration of 0.1 mg / mL. In addition, physiological saline was used as a solvent control. The cells were cultured at 37 ° C. for 3 days, and the number of viable cells was counted under a microscope. Furthermore, the cells were dispersed in purified water, and a cell dispersion was obtained by an ultrasonic disrupter. The amount of keratin contained in this cell dispersion was quantified by ELISA (Cosmo Bio Co., Ltd.).

As a result, the number of eyelash cells increased to 344% by the addition of the sample 2 with the number of cells of the solvent control being 100%. On the other hand, it is 147% in EGF. Sample 2 was superior in eyelash growth. With regard to the amount of keratin, the amount of keratin increased to 466% by addition of the sample 2 with the value of the solvent control being 100%. On the other hand, EGF was 218%, and sample 2 was superior in keratinogenesis.

Hereinafter, a confirmation test of keratinogenesis using human hair-derived cells is described.
(Test Example 3)

Healthy male 56-year-old hair cells were collected and separated by collagenase method. These cells were used as hair cells. The hair cells were cultured in MEM basic medium at 37 ° C. under 5% carbon dioxide gas. Cells in growth phase were detached with trypsin-containing medium. First, the number of viable cells was counted under a microscope by trypan blue dye exclusion method.

The number of cells was adjusted to 1000 cells per mL, and 5 mL of each was seeded on a culture petri dish and further cultured at 37 ° C. under 5% carbon dioxide gas. The cells were damaged by irradiating them with ultraviolet light using an ultraviolet irradiation device (Loctite, output: 88 MH). Irradiation was performed for 1 hour with the lid of the petri dish removed.

This UV radiation damaged the hair cells and tested for recovery from this damage. In addition, this method is a method implemented to evaluation of a test substance in the hair area.

Here, Sample 2 as a test substance and human EGF (manufactured by Funakoshi) as a control substance were all suspended in physiological saline, diluted and added to a final concentration of 0.1 mg / mL.

In addition, physiological saline was used as a solvent control. The cells were cultured at 37 ° C. for 3 days, and the number of viable cells was counted under a microscope. Furthermore, the cells were dispersed in purified water, and a cell dispersion was obtained by an ultrasonic disrupter. The amount of keratin contained in this cell dispersion was quantified by ELISA (Cosmo Bio Co., Ltd.).

As a result, the number of hair cells increased to 311% by the addition of the sample 2 with the number of cells of the solvent control being 100%. On the other hand, it is 149% in EGF. Sample 2 was superior to hair cell growth.

With regard to the amount of keratin, the amount of keratin increased to 433% by the addition of the sample 2 with the value of the solvent control being 100%. On the other hand, EGF was 188%, and sample 2 was superior in keratinogenesis.

The polyphenol derivative obtained by the present invention exhibits eyelash proliferation action and hair growth action and has few side effects, so it can be used for treatment and prevention and improve the QOL of the people.

The method for producing the polyphenol derivative obtained in the present invention can be used as a food, and thus contributes to the development of the food industry.

The polyphenol derivative obtained by the present invention is also used as a cosmetic to improve the skin and contributes to the development of the cosmetic industry.

Claims (1)

The polyphenol derivative which exhibits the eyelash proliferative effect and hair-growth effect shown by following formula (1).