JP5363800B2 - Hair restorer composition - Google Patents

Description

  The present invention relates to a hair restorer composition capable of obtaining an excellent effect of promoting proliferation of epidermal keratinocytes and promoting expression of BMP-2 gene.

  Conventionally, it has been desired to provide a hair-restoring agent that is effective against hair defects caused by a rapid decrease in female hormones. Therefore, isoflavones are known as compounds having a female hormone-like action, and among these, malonyl isoflavone glycosides are known to have an effect of growing epidermal keratinocytes (Patent Document 1). reference). However, the malonyl isoflavone glycoside is susceptible to thermal degradation, and malonyl groups are hydrolyzed during long-term storage.

  On the other hand, BMP-2 is known as a protein that is decreased in the scalp of alopecia (see Non-Patent Document 1). Therefore, the present applicant has already reported 6-benzylaminopurine as a compound that promotes the production of BMP-2 (see Non-Patent Document 2). This 6-benzylaminopurine is a compound known to have a hair-restoring action (see Patent Document 2), but the effectiveness of the hair-restoring agent formulated with 6-benzylaminopurine is confirmed in alopecia females. As a result, a slight improvement effect is observed, but a remarkable improvement effect is not obtained (see Non-Patent Document 3).

  Accordingly, there is a strong demand for prompt provision of a hair-restoring agent composition that is effective against hair problems caused by a rapid female hormone decrease in women.

JP-A-9-59166 JP-A-5-320028 Journal of Dermatological Science (2004) 36, 25-32 The 26th Annual Meeting of the Japan Society for Basic Aging, 2004 Skin, Vol. 40, No. 4, August 1998, Yutaka Mishima et al.

  An object of the present invention is to solve the conventional problems and achieve the following objects. That is, the present invention is effective against hair loss and hair loss seen in women whose female hormone concentration has decreased due to aging, in combination with soy isoflavone glycoside and 6-benzylaminopurine, together with a hair growth effect and an excellent hair loss prevention effect. It aims at providing the hair-restoring agent composition which expresses.

  As a result of intensive studies by the present inventors in order to solve the above-mentioned problems, an excellent epidermal keratinocyte was obtained by a synergistic effect by using (A) soy isoflavone glycoside and (B) 6-benzylaminopurine in combination. Has an effect of preventing hair loss and improving thick and firm hair against thinning hair and hair loss caused by a decrease in female hormones. I found out.

This invention is based on the said knowledge by this inventor, and as a means for solving the said subject, it is as follows. That is,
<1> A hair restorer composition comprising soy isoflavone glycoside and 6-benzylaminopurine.
<2> The hair restorer composition according to <1>, wherein the soybean isoflavone glycoside is at least one of daidzin and genistin.
<3> Any of the above <1> to <2>, wherein the molar ratio (A: B) of soybean isoflavone glycoside (A) to 6-benzylaminopurine (B) is 1: 100000 to 1000: 1 It is a hair restorer composition according to the above.
<4> A composition for promoting keratinocyte proliferation, comprising soybean isoflavone glycoside and 6-benzylaminopurine.
<5> A composition for promoting expression of BMP-2 gene, comprising a soybean isoflavone glycoside and 6-benzylaminopurine.

  According to the present invention, various problems in the prior art can be solved, and soy isoflavone glycoside and 6-benzylaminopurine are used in combination for thinning and hair loss seen in women whose female hormone concentration has decreased due to aging. Can provide a hair-restoring agent composition that exhibits an excellent hair-loss preventing effect as well as a hair-restoring effect.

The hair restorer composition of the present invention contains (A) soybean isoflavone glycoside and (B) 6-benzylaminopurine, and further contains other components as necessary.
In the present invention, since the hair growth effect can be exhibited by the action of promoting the proliferation of epidermal keratinocytes, the hair restorer composition of the present invention may be referred to as a “skin keratinocyte proliferation promoting composition”, and BMP The hair-restoring composition of the present invention may be referred to as a “BMP-2 gene expression-promoting composition” because the hair-restoring effect can be exhibited by the -2 gene expression promoting action.

<(A) Soybean isoflavone glycoside>
Isoflavones belong to flavonoids and have been confirmed to have antioxidant and female hormone-like effects.
The presence of 12 types of isoflavones has been confirmed by measuring isoflavones in soybean. The 12 types of isoflavones include (1) daidzein and its glycoside (2) daidzin, daidin acetylated product (3) acetyldidine, daidin malonylated product (4) malonyl daidzin, (5) Genistein and its glycoside (6) Genistin, an acetylated form of genistin (7) Acetylgenistin, a malonylated form of genistin (8) Malonylgenistine, (9) Glycitein and its glycoside There are (10) glycitin which is a body, (11) acetylglycitin which is an acetylated form of glycitin, and (12) malonylglycitin which is a malonylated form of glycitin.
Among these 12 kinds of isoflavones, dry soy includes genistin represented by the following structural formula (I), daidzin represented by the following structural formula (II), and malonyl represented by the following structural formula (III). Genistin and four malonyl daidines represented by the following structural formula (IV) occupy most of them, and daidzin and genistin are particularly preferable from the viewpoint of the effect of promoting the proliferation of epidermal keratinocytes.

<Structural Formula (I)>
Genistin (Molecular weight: 432.3)

<Structural Formula (II)>
Daidine (molecular weight: 416.38)

<Structural Formula (III)>
Malonyl genistin (molecular weight: 432.38)

<Structural Formula (IV)>
Malonyl daidzin (molecular weight: 432.38)

As the soybean isoflavone glycoside, an appropriately prepared product or a commercially available product may be used.
The soybean isoflavone glycoside is not particularly limited and may be appropriately selected according to the purpose. The soybean isoflavone glycoside is extracted from soybean with a solvent such as water or alcohol, and then filtered or centrifuged. A purified product can be used if necessary.
As a method for preparing the soybean isoflavone glycoside, for example, water is added to soybean and filtered after immersion, then the residue is extracted with hot water, and the liquid extracted with hot water is cooled at 30 ° C. to 38 ° C., By removing the insoluble matter, a soybean extract containing an isoflavone glycoside can be obtained.
As a method for separating soybean isoflavone glycoside from the obtained soybean extract, for example, there is a method using an adsorbent as described in JP-A-11-255792. That is, soybean isoflavone glycoside is adsorbed by passing the soybean extract through a column packed with an adsorbent such as Diaion HP-20 (manufactured by Mitsubishi Chemical Corporation). Subsequently, the soybean isoflavone glycoside adsorbed on the adsorbent is eluted using aqueous solutions having different ethanol concentrations. The obtained solution is concentrated under reduced pressure and freeze-dried to obtain a dry powder of soybean isoflavone glycoside.

  There is no restriction | limiting in particular as a commercial item of the said soybean isoflavone glycoside, According to the objective, it can select suitably, For example, Daidine (made by Fujicco Co., Ltd.), Genistine (made by Fujicco Co., Ltd.), Maronyl Daidine (Wako Pure) Yakuhin Co., Ltd.), malonylgenistin (Wako Pure Chemical Industries, Ltd.), and the like. Moreover, as an extract containing soybean isoflavone glycoside extracted from soybean, for example, “Flavosterone SE” (manufactured by Ichimaru Falcos, Daidine content 0.07 w / v% to 0.15 w / v%, Genistin content 0. 01 w / v% to 0.03 w / v%).

<(B) 6-Benzylaminopurine>
The 6-benzylaminopurine is a white crystalline powder having a molecular weight of 225.26 represented by the following structural formula, and is also called 6-benzyladenine.

The 6-benzylaminopurine is a hair-restoring agent (see JP-A-5-320028 and JP-A-7-233037), skin cosmetics for the purpose of preventing skin aging and activating cells by external application to the scalp. (Refer to Yutaka Mishima et al., Skin No. 40, No. 4, P407-413, August 1998).
As said 6-benzylamino purine, what was synthesize | combined suitably may be used and a commercial item may be used.
There is no restriction | limiting in particular as said synthesis method, According to the objective, it can select suitably, For example, the method of synthesize | combining according to Unexamined-Japanese-Patent No. 2005-35903, the method of refine | purifying from a natural product, etc. are mentioned.
Examples of the commercially available product include 6-benzylaminopurine (manufactured by Sansho Pharmaceutical Co., Ltd., molecular weight = 225.26).

-Mechanism of hair growth by 6-benzylaminopurine-
The present applicant has already reported that 6-benzylaminopurine promotes the production of a protein called BMP-2 in cell culture experiments (The 26th Annual Meeting of the Japan Society for Basic Aging, 2004, Yasuyuki Sasakawa et al. reference). Further, the applicant of the present application shows that BMP-2 is a protein whose production is reduced in the cells of the scalp of a person with alopecia, and exhibits an excellent hair growth effect by promoting the production of BMP-2. (Journal of Dermatological Science (2004) 36, 25-32).

The blending amount of soybean isoflavone glycoside and 6-benzylaminopurine in the hair-growing composition is (B) 6-benzylamino when (A) soybean isoflavone glycoside is 0.000002 mass% to 4 mass%. The purine content is preferably 0.02% by mass to 2% by mass. Among them, (A) soybean isoflavone glycoside is 0.000002% by mass to 0.2% by mass, and (B) 6-benzylaminopurine is More preferably, it is 0.1 mass%-0.5 mass%.
The molar ratio (A: B) of the (A) soybean isoflavone glycoside to the (B) 6-benzylaminopurine is preferably 1: 100000 to 1000: 1, and 1: 1000000 to 10: 1. 1 is more preferable, and 1: 1000000 to 1: 1 is more preferable. Within this range, an excellent effect of promoting the proliferation of keratinocytes can be obtained.

  The skin surface is covered with the epidermis, and the cells mainly constituting the epidermis are cells called epidermal keratinocytes. Epidermal keratinocytes are widely used as materials for dermatological research and at the same time as models for hair science research. This is because hair is an appendage of the skin and a part of the skin in terms of dermatology. The hair restorer composition of the present invention promotes the growth of epidermal keratinocytes and also promotes the growth of keratinocytes in the hair, thereby forming a thick hair root and promoting hair growth and at the same time preventing hair loss. it can.

  The hair restorer composition of the present invention comprises (A) soybean isoflavone glycoside and (B) 6-benzylaminopurine, and when applied directly to the scalp, the hair cycle changes from the growth phase to the resting phase. By suppressing the transition and further extending the growth period, an even more excellent hair loss prevention effect is exhibited together with a stronger hair growth effect. In order to further enhance such a synergistic effect, the hair restorer composition of the present invention contains (A) soybean isoflavone glycoside and (B) 6-benzylaminopurine as necessary or according to the purpose of use. Arbitrary components other than can be contained within a range not impairing the object and effects of the present invention.

  The optional component is not particularly limited and may be appropriately selected depending on the intended purpose. For example, water, ethanol, nonionic surfactant, amphoteric surfactant or other surfactant, celluloses, vegetable oil , Ester oils, keratolytic agents, polymer resins, ultraviolet absorbers, vitamins, vasodilators, cell activators, amino acids, anti-inflammatory agents, skin function enhancers, colorants, fragrances, and the like.

Examples of the water include purified water, distilled water, ion exchange water, pure water, ultrapure water, and deep sea water.
Examples of the celluloses include hydroxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the like.
Examples of the nonionic surfactant include sorbitan fatty acid esters (sorbitan monolaurate, sorbitan monooleate, etc.), polyoxyethylene hydrogenated castor oil, polyoxyethylene hydrogenated castor oil mono or isostearate, glycerin fatty acid ester, Polyglycerin fatty acid ester (monomyristic acid decaglycerin, monomyristic acid pentaglycerin), etc. are mentioned.
Examples of the esters include polyhydric alcohol fatty acid esters (polyhydric alcohol fatty acid esters such as glycerin tri-2-ethylhexanoate and trimethylolpropanoic acid triisostearate).
Examples of the vegetable oil include eucalyptus oil, safflower oil, evening primrose oil, jojoba oil, and the like.
Examples of the ester oil include unsaturated fatty acid alkyl esters (such as ethyl oleate and isopropyl linoleate), methyl myristate, and isopropyl myristate.
Examples of the keratolytic agent include salicylic acid and resorcin.
Examples of the polymer resin include amphoteric polymers, cationic polymers, anionic polymers, and nonionic polymers.
Examples of the ultraviolet absorber include octyl methoxycinnamate (Neoheliopan AV), oxybenzone, urocanic acid, and the like.
Examples of the vitamins include vitamin A, vitamin B, vitamin C, vitamin E, tocopherol acetate, and the like.
Examples of the vasodilator include carpronium chloride, minoxidil, cephalanthin and the like.
Examples of the cell activator include pentadecanoic acid glyceride, coleus extract, ginseng extract, and adenosine.
Examples of the amino acids include glutamic acid, methionine, serine, glycine, cystine, and threonine.
Examples of the anti-inflammatory agent include β-glycyrrhetinic acid, dipotassium glycyrrhizinate, rosemary extract, perilla extract, and the like.
Examples of the skin function enhancer include D-pantenol, pantothenyl ethyl ether, and the like.

-Application-
The hair restorer composition of the present invention is used for hair tonics, hair creams, hair liquids, shampoos, pomades, rinses, etc. in the form of uniform solutions, lotions, gels and the like according to conventional methods. Moreover, it can be used as an external preparation having a hair growth effect.

-Form-
The hair restorer composition of the present invention can take the form of an aerosol composition, in which case, in addition to the above components, lower alcohols such as n-propyl alcohol or isopropyl alcohol; butane, propane, isobutane, liquefaction Combustible gas such as petroleum gas and dimethyl ether; compressed gas such as nitrogen gas, oxygen gas, carbon dioxide gas and nitrous oxide gas can be contained.

  The hair-growth composition of the present invention comprises a soybean isoflavone glycoside as component (A) and 6-benzylaminopurine as component (B), and when applied directly to the scalp, the hair cells have a synergistic effect. It is possible to promote the growth of the hair, improve the thick and firm hair, and exhibit the effect of preventing hair loss.

  Examples of the present invention will be described below, but the present invention is not limited to these examples.

<Method of measuring epidermal keratinocyte proliferation activity>
The proliferation activity of epidermal keratinocytes was measured as follows.
As normal human epidermal keratinocytes, a primary culture frozen product derived from a 24-year-old woman (manufactured by Cascade Biologics, NHEK (B)) was used. Moreover, Humedia KG2 (made by Kurashiki Boseki Co., Ltd.) was used for the culture medium. It seed | inoculated so that it might become 4400cells / well to 24 hole plate (made by Sumitomo Bakelite Co., Ltd.), and this was used for culture | cultivation at 37 degreeC under 5% carbon dioxide gas and saturated water vapor | steam. After culturing for 24 hours, the culture solution was aspirated, fresh Humdia KG2 was added, the evaluation substance was added, and the cells were further cultured for 48 hours. After culturing, Alamar Blue (manufactured by Invitrogen) was added to a concentration of 10%, and fluorescence (excitation 544 nm, measurement 590 nm) was measured, and this was used as an initial measurement value. Fluorescence (excitation 544 nm, measurement 590 nm) was measured again after 3 hours of incubation at 37 ° C. in 5% carbon dioxide gas and saturated water vapor, and the difference between the measured value and the initial value was defined as Alamar Blue activity. The Alamar Blue activity of each evaluation extract when the Alamar Blue activity when ethanol was used instead of the evaluation extract was taken as 100% was defined as the epidermal keratinocyte proliferation activity.

(Experimental example 1)
-Evaluation of cell proliferation activity of epidermal keratinocytes-
Prepare Humedia KG2 medium containing 10 ng / mL of any one of daidzin, genistin, malonyl daidzin, malonylgenistin, and 6-benzylaminopurine (50 μg of soybean isoflavone glycoside or 6 mL of ethanol with 10 mL of ethanol). A solution diluted 50-fold with ethanol was used as a stock solution, and then a stock solution of 1/100 of the volume of the Humedia KG2 medium was added to the Humedia KG2 medium) Thus, the cell proliferation activity of epidermal keratinocytes was evaluated.
As a comparison, a Humedia KG2 medium containing 5 ng / mL of any one of daidzin, genistin, malonyl daidzin, and malonylgenistin and 5 ng / mL 6-benzylaminopurine was prepared. That is, a solution obtained by dissolving 50 μg of soybean isoflavone glycoside or 6-benzylaminopurine in 10 mL of ethanol and then diluting 50 times with ethanol was used as a stock solution. Thereafter, a soy isoflavone glycoside stock solution of 1/200 of the amount of the Humedia KG2 medium and a stock solution of 6-benzylaminopurine of 1/200 of the volume were prepared in the Humedia KG2 medium.
The cell growth activity of epidermal keratinocytes was evaluated using these prepared media. As a control, the cell proliferation activity of epidermis keratinocytes was also evaluated for a control prepared by adding ethanol to 1/100 of the volume of the Humedia KG2 medium, and the cells at the time of each sample addition when the proliferation activity of this control was taken as 1. The proliferation activity is shown in FIG. 1 as proliferation activity ratio (proliferation activity ratio = cell proliferation activity at the time of sample addition / cell proliferation activity at the time of addition of ethanol (control)).

  From the results shown in FIG. 1, malonyl daidzin and malonylgenistin have 3.7-fold and 3.8-fold proliferation activities, respectively, and malonylated isoflavone glycosides as described in JP-A-9-59166. Physiological activity of the body was observed. Daidine and genistin were also found to have 1.5-fold and 1.6-fold proliferative activity, respectively, but when combined with 6-benzylaminopurine, the proliferative activity was 12.3 times and 10.8 times active, respectively. The synergistic effect by using soybean isoflavone glycoside and 6-benzylaminopurine together was recognized. Moreover, although the malonylated isoflavone glycoside also increased proliferation activity by using together with 6-benzylamino purine, there was no significant difference compared with the case where each was added independently.

(Experimental example 2)
-Epidermal keratinocyte proliferation activity when the molar ratio of daidzin and 6-benzylaminopurine is changed-
A Humdia KG2 medium containing 10 ng / mL of total amount of daidzin and 6-benzylaminopurine and a molar ratio of daidzin and 6-benzylaminopurine adjusted from 0: 1 to 1: 0 was prepared.
Next, the epidermal keratinocyte proliferation activity was evaluated by the same method as the measurement of the epidermis keratinocyte proliferation activity. The results are shown in FIG.
As is clear from the results in FIG. 2, a high epidermal keratinocyte proliferation promoting activity was observed by adding both in combination rather than adding daidzin and 6-benzylaminopurine alone. The epidermal keratinocyte proliferation-promoting effect was observed when the molar ratio of daidzin: 6-benzylaminopurine was 1: 1000000 to 10,000: 1, and particularly high epidermal keratinocyte proliferation activity was observed. Was the case where the molar ratio of daidzin: 6-benzylaminopurine was 1: 100000-1: 1.

(Experimental example 3)
-Epidermal keratinocyte proliferation activity when changing the molar ratio of genistin and 6-benzylaminopurine-
A Humedia KG2 medium containing genistin and 6-benzylaminopurine in a total amount of 10 ng / mL and a molar ratio of daidzin and 6-benzylaminopurine adjusted from 0: 1 to 1: 0 was prepared.
Next, the epidermal keratinocyte proliferation activity was evaluated by the same method as the measurement of the epidermis keratinocyte proliferation activity. The results are shown in FIG.
As is clear from the results of FIG. 3, a higher epidermal keratinocyte proliferation activity was observed by adding both genistin and 6-benzylaminopurine in combination than by adding them alone. The epidermal keratinocyte proliferation promoting effect was observed when the molar ratio of genistin: 6-benzylaminopurine was 1: 1000000 to 10: 1, and particularly high epidermal keratinocyte proliferation activity was observed. The molar ratio of genistin: 6-benzylaminopurine was 1: 100000-1: 1.

(Experimental example 4)
-Test for confirming the effect of promoting gene expression by 6-benzylaminopurine and daidzin-
Epidermis keratinocytes were seeded in a 24-well plate at 3,000 cells / cm ^2, and Humedia KG2 (manufactured by Kurashiki Boseki Co., Ltd.) was dispensed as a medium at 0.5 mL per well. The cells were cultured at 37 ° C. under 5% carbon dioxide gas and saturated water vapor. The next day, (a) 6-benzylaminopurine 1 μg / mL, (b) daidzin 1 μg / mL, or (c) daidin 500 ng / mL and 6-benzylaminopurine 500 ng / mL [molar ratio (Daidin: 6-benzylamino Purine) = 1: 1.8] concentration solution was prepared using ethanol.
These were added to Humedia KG medium at 1 / 100th of the medium amount (final concentrations in the medium were (a) daidzin 10 ng / mL, (b) genistin 10 ng / mL, (c) daidzin 5 ng / mL, and genistin 5 ng / mL). After culturing the epidermal keratinocytes in these media for 20 hours, mRNA was extracted. For extraction and purification of mRNA, QIA shredder (manufactured by QIAGEN) and RNeasy Mini (manufactured by QIAGEN) were used. Based on the purified mRNA, cDNA was synthesized using RTase (manufactured by TOYOBO).
Based on the synthesized cDNA, PCR reaction using ExTaq HS (TaKaRa) (incubation at 94 ° C for 5 minutes, followed by 30 cycles of amplification reaction (94 ° C for 30 seconds, primer melting temperature for 60 seconds) 60 seconds) at 72 ° C.). Using this reaction solution, electrophoresis on a 1% agarose gel was performed, and the gene expression of female hormone receptors β (ER-β), BMP-2, and GAPDH (control) was compared. The results are shown in FIG.
From the results shown in FIG. 4, it was found that the gene expression of female hormone receptor β and BMP-2 synergistically increased when both daidzin and 6-benzylaminopurine were added to the cells.

-Synergistic effect of the combination of 6-benzylaminopurine and daidzin or genistin-
So far, the applicant of the present application has reported that BMP-2 has a cell growth promoting effect on hair follicle keratinocytes (see Journal of Dermatological Science (2004) 36, 25-32). It has also been reported that the gene expression of BMP-2 is promoted by female hormone receptor β (Basic Aging Society 29, 25 (2005), FRAGRANCE JOURNAL, December 2005), female hormone receptor β. Have been shown to promote hair follicle growth via BMP-2.
However, as shown in Experimental Example 4, it is a new finding that the gene expression of female hormone receptor β is synergistically promoted by using soybean isoflavone glycoside and 6-benzylaminopurine in combination. It is considered that the effect of promoting the proliferation of epidermal keratinocytes shown in Experimental Examples 1 to 3 was observed in response to the promotion of BMP-2 gene expression.
Therefore, the hair restorer composition comprising (A) soy isoflavone glycoside and (B) 6-benzylaminopurine has a thick and firm hair against thinning hair and hair loss caused by a decrease in female hormones. The effect of improving and preventing hair loss can be exhibited.

(Examples 1-9 and Comparative Examples 1-5)
-Preparation of hair restorer composition-
Each hair restorer composition was prepared by a conventional method with the composition shown in Table 1 below. In addition, a compounding unit is the mass% and the whole quantity is 100 mass%.
About each obtained hair restorer composition, the clinical test result about the therapeutic effect with respect to androgenetic alopecia was performed as follows. The results are shown in Table 1.

<Clinical test method for diffuse alopecia>
104 female volunteers with diffuse alopecia were targeted and randomly assigned as 8 per group to a total of 13 groups of test drug group and control group.
In the test, an appropriate amount was applied from the forehead to the top of the head twice a day in the morning and at night. The administration period was 4 months.
At the end of the test (4 months), the hair was washed, and the non-woven fabric was covered in duplicate to collect the hair that fell out during the hair washing. The number of collected hairs was measured and compared with the number of hairs lost during hair washing at the start of the test. Hair washing was performed once a day for 3 consecutive days, and the average value of the number of 3 hair loss was used for determination, and the change in the number of hair loss was measured by the following formula.
In addition, at the end of the test, the degree of improvement in hair findings (change in hair quality) compared to before the start of the test, with reference to photographic findings, the following five-level evaluation (significant improvement, moderate improvement, mild improvement, unchanged, (Deterioration).

[Criteria]
-Change in the number of hair loss-
The change in the number of missing hairs at the end of the test when the number of missing hairs at the start of the test was taken as 100% was calculated ((number of missing hairs at the end of the test / number of missing hairs at the start of the test) × 100).
“Improved”: The number of hair loss at the end of the test is less than 90% of the initial value “Invariant”: The number of hair loss at the end of the test is within 90% to 110% of the initial value “Deteriorated”: The number of hair loss at the end of the test is the initial value 111% or more of hair-Changes in hair quality-
"Significantly improved": 5 points (those with soft hair almost disappeared and normalized)
"Moderate improvement": 4 points (those with softened hairs)
"Mild improvement": 3 points (slightly softened hair)
“No change”: 2 points (no change in hair quality)
"Deterioration": 1 point (thickened hair)

* Daijin (manufactured by Fujicco Co., Ltd., solid content purity 99% or more, molecular weight = 416.38)
* Genistin (manufactured by Fujicco Corporation, solid content purity 99% or more, molecular weight = 432.38)
* 6-Benzylaminopurine (Sansho Pharmaceutical Co., Ltd., molecular weight = 225.26)
* Polyethylene glycol # 300 (manufactured by Lion Corporation)
* POE (30) POP (6) -decyl tetradecyl ether (manufactured by Nikko Chemical Co., Ltd.)
(* 1): In Example 4 and Comparative Example 4, 0.1% by mass of flavosterone SE is contained. Flavosterone SE is a soybean extract manufactured by Ichimaru Falcos Co., Ltd., which contains 0.1% by mass of daidzin and 0.02% by mass of genistin.
(* 2): The molar ratio is a value rounded to one decimal place.

From the results of Table 1, Examples 1 to 9 containing a predetermined amount of active ingredients [component (A) and component (B)] within the scope of the present invention were all excellent in hair loss prevention effect and hair quality improvement effect. It was found to show characteristics. Further, even when a soybean extract containing these soybean isoflavone glycosides (flavosterone SE (manufactured by Ichimaru Falcos)) is used (Example 4), even if it is not a purified product of soybean isoflavone glycosides such as daidzin and genistin. It was found to be excellent in preventive effect and hair quality improving effect. Moreover, Examples 1-6 were found to be particularly preferable because they were more effective than Examples 7-8. Moreover, as a compounding quantity to a hair restorer composition, (A) component is 0.000002 mass%-4 mass% as seen in Examples 1-8, (B) component is 0.02 mass%- An excellent effect was confirmed when the content was 2% by mass. Among them, when the component (A) is 0.000002% by mass to 0.2% by mass, the excellent effect is confirmed when the component (B) is 0.1% by mass to 0.5% by mass. It turned out that it is especially preferable as a compounding quantity to an agent composition.
On the other hand, it was found that none of Comparative Examples 1 to 5 outside the scope of the present invention exhibited excellent characteristics. When Comparative Example 1 does not contain both the (A) component and the (B) component, Comparative Examples 2 to 4 contain only the (A) component, and Comparative Example 5 contains only the (B) component. In these cases, it has been found that the effects of hair growth and hair loss prevention, which are the effects of the present invention, cannot be exhibited.

Next, specific blending examples in which the hair-restoring agent composition of the present invention showing excellent properties in hair removal preventing effect and hair growth weight are applied to actual products are shown below. In addition, the hair restorer composition of the following combination example was prepared according to the usual method of each dosage form according to each composition.
About the hair-restoring agent composition (hair growth agent, hair-growth spray, hair-growth tonic, hair-growth hair lotion) of various dosage forms of the following combination examples 1-5, the hair-growth effect is carried out similarly to the said Examples 1-9 and Comparative Examples 1-5. As a result, all showed the same excellent effects as in Examples 1 to 9 in terms of the hair removal preventing effect and the hair growth weight.

(Formulation Example 1)
-Hair restorer-
・ Flavosterone SE *: 0.1% by mass (A) component ・ 6-Benzylaminopurine: 0.5% by mass (B) component ・ Coleus forskori root extract and purified extract: 3.0 mass %
Palm oil fatty acid sorbitan: 1.0% by mass
・ Sucrose myristic acid ester: 0.5% by mass
・ Lauryldimethylaminoacetic acid betaine: 0.5% by mass
・ Concentrated glycerin: 0.8% by mass
・ Nomyristate decaglycerin: 0.3% by mass
Biotin: 0.002% by mass
・ Succinic acid: 0.3% by mass
DL-α-tocopherol acetate: 0.1% by mass
-Fragrance: 0.5% by mass
・ 95% ethanol: 50% by mass
-Purified water: Remainder * Flavosterone SE is a soybean extract manufactured by Ichimaru Falcos Co., Ltd., which contains 0.1% by mass of daidzin and 0.02% by mass of genistin.
Molar ratio [component (A): component (B)] = 1: 7947 (molar ratio indicates a value rounded to one decimal place)

(Formulation Example 2)
-Hair growth spray-
-Daidine: 0.0001% by mass (A) component-6-Benzylaminopurine: 0.1% by mass (B) component-Coleus / Forskori root extract: 1.0% by mass
Amphoteric polymer (N-methacryloylethyl-N, N-dimethylammonium / α-N-methylcarboxybetaine / alkyl methacrylate copolymer): 0.2% by mass
-Ethyl oleate: 1.0% by mass
・ Succinic acid: 0.3% by mass
・ Sucrose laurate: 0.5% by mass
・ Lauryldimethylaminoacetic acid betaine: 0.5% by mass
・ Concentrated glycerin: 0.8% by mass
・ Decaglycerin monomyristic acid: 0.3% by mass
・ L-menthol: 0.1% by mass
・ DL-α-tocopherol acetate: 0.1% by mass
-Fragrance: 0.5% by mass
・ 95% ethanol: 50% by mass
・ Purified water: remainder-filling liquid for dilution-
-Stock solution: 80% by mass
・ LPG: 20% by mass
Molar ratio [component (A): component (B)] = 1: 1919 (molar ratio indicates a value rounded to one decimal place)

(Formulation Example 3)
-Hair growth tonic-
Genistin: 0.00001% by mass (A) component 6-benzylaminopurine: 0.05% by mass (B) component POE (8 mol) oleyl ether: 1.5% by mass
・ Glycerin: 3.0% by mass
・ L-menthol: 0.1% by mass
-Hinokitiol: 0.3% by mass
・ Methylparapen: 0.1% by mass
-Fragrance: 0.3% by mass
・ 95% ethanol: 50% by mass
-Purified water: remainder Molar ratio [(A) component: (B) component] = 1: 9242 (Molar ratio indicates a value rounded to one decimal place)

(Formulation Example 4)
-Hair growth hair lotion-
・ Daidin: 0.001 mass% (A) component ・ 6-Benzylaminopurine: 0.5 mass% (B) component ・ Natural vitamin E: 0.5 mass%
・ Sucrose myristic acid ester: 0.5% by mass
-POE (40) hydrogenated castor oil: 0.5 mass%
Propylene glycol: 0.5% by mass
・ Citric acid: 0.1% by mass
・ L-menthol: 0.1% by mass
・ Fragrance: appropriate amount ・ 95% ethanol: 50% by mass
Purified water: balance Molar ratio [(A) component: (B) component] = 1: 9597 (Molar ratio indicates a value rounded to one decimal place)

(Formulation Example 5)
-Hair growth tonic-
Genistine: 0.001% by mass (A) component 6-benzylaminopurine: 0.5% by mass (B) component Nicotinamide: 0.1% by mass
・ Piroctone olamine: 0.05% by mass
Β-glycyrrhetinic acid: 0.01% by mass
Melissa extract: 3.0% by mass
-POE (2 mol) oleyl ether: 0.5 mass%
-Polyethylene glycol 400: 2.0% by mass
・ L-menthol: 0.1% by mass
-Hinokitiol: 0.3% by mass
-Fragrance: 0.3% by mass
・ 95% ethanol: 50% by mass
-Purified water: remainder Molar ratio [(A) component: (B) component] = 1: 9242 (Molar ratio indicates a value rounded to one decimal place)

  The hair restorer composition of the present invention has excellent epidermal keratinocyte proliferation promoting effect and BMP-2 gene expression promoting effect, and is particularly effective for hair defects caused by rapid female hormone reduction in women. For example, it is widely used in hair tonics, hair creams, hair liquids, shampoos, pomades, rinses, external preparations and the like having a hair-growth effect.

FIG. 1 is a graph showing the results of evaluating the proliferation activity of epidermal keratinocytes in Experimental Example 1. FIG. 2 is a graph showing the results of evaluating the proliferation activity of epidermal keratinocytes when the molar ratio of daidzin and 6-benzylaminopurine in Experimental Example 2 was changed. FIG. 3 is a graph showing the results of evaluating the proliferation activity of epidermal keratinocytes when the molar ratio of genistin and 6-benzylaminopurine in Experimental Example 3 was changed. FIG. 4 is a graph showing the results of evaluating the gene expression promoting effects of female hormone receptor β and BMP-2 by 6-benzylaminopurine and daidzin in Experimental Example 4.

Claims (4)

And soybean isoflavone glycoside, Ri name contains a 6-benzylaminopurine,
The soy isoflavone glycoside and (A), the molar ratio of the 6-benzylaminopurine (B) (A: B) of 1: 1,000,000 to 1,000: 1 der Rukoto hair restorer composition characterized.   The hair restorer composition according to claim 1, wherein the soybean isoflavone glycoside is at least one of daidzin and genistin. The hair restorer according to any one of claims 1 to 2, wherein the molar ratio (A: B) of soybean isoflavone glycoside (A) to 6-benzylaminopurine (B) is 1: 1000000-10: 1. Composition. The blending amount of (A) soybean isoflavone glycoside is 0.000002 mass% to 4 mass%, and the blending amount of (B) 6-benzylaminopurine is 0.02 mass% to 2 mass%. To 4. The hair restorer composition according to any one of items 1 to 3.