JP2007008900A - Hair growth promoter containing biflavones as active component - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To discover a component having direct effect on hair growth and develop an effective hair growth promoter. <P>SOLUTION: Biflavones such as sciadopitysin, ginkgetin, isoginkgetin, sequoiaflavone and bilobetin have hair growth promoting activity. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to the development of a hair restorer containing biflavones as active ingredients.

  Extracts extracted from ginkgo biloba are used as pharmaceuticals for the purpose of treating vascular dilation, increasing blood flow, preventing aging of the vascular system, particularly improving peripheral blood flow in the brain, and treating neurological disorders. Applications have also been developed as external preparations for skin (JP-A-4-321616 (Patent Document 1)) and cosmetics (JP-A-1-117816 (Technical Document 2)).

  Conventionally, herbal ingredients such as ginkgo biloba extract, assembly, chamomile and the like have been widely used as hair restorers. In particular, Ginkgo biloba extract is known to promote hair growth by promoting blood circulation of its components, terpenes and flavones. For example, Japanese Patent No. 26122012 (Patent Document 3) discloses that “Ginkgo biloba leaves are water-soluble. The hair growth and hair nourishing agent characterized by containing a ginkgo biloba extract extracted with an organic solvent or a water-containing water-soluble organic solvent.

  Further, “a cosmetic for hair characterized in that a ginkgo biloba extract having a total flavonoid content of 15 to 40% by weight and a total terpenoid content of 2 to 15% by weight is blended as a hair nourishing ingredient” No. 287531 (Technical Document 4)) is also disclosed.

  Furthermore, JP-A-9-59166 (Patent Document 5) describes that malonyl isoflavone glycoside is effective as a hair restorer.

  As described above, any of the hair-growth agents has a hair-growth effect by the blood circulation promoting action of terpenes or flavones in the ginkgo biloba extract, and does not directly have a hair-growth action.

In recent years, an increasing number of young women suffer from hair loss and thinning hair due to stress and rapid dieting, and the development of substances that are directly effective for hair growth is awaited.
JP-A-4-321616 JP-A 1-1117816 Japanese Patent No. 2612012 Japanese Patent Laid-Open No. 10-287531 JP-A-9-59166 JP 2005-104921 A

  Finding ingredients that are directly effective for hair growth and developing effective hair growth agents.

As a result of diligent efforts to solve the above-mentioned problems, the present inventors have found that biflavones have hair-growth activity and completed the present invention.
That is, the present invention
(1) Hair restorer containing biflavones as active ingredients,
(2) The biflavones are any one of Sciadopitysin, Ginkgetin, Isoginkgetin, Sequoiaflavone and Bilobetin or a mixture thereof (1) The hair restorer described,
(3) The present invention relates to a hair-restoring agent comprising a mixture of ginkgogetin and isoginkgetin or a chiadopiticin as an active ingredient.

  The present inventors have already developed a ginkgo biloba extract that does not contain salicylic acid derivatives that are harmful in contact with the skin, and that contains the active ingredient double flavones and organic acids in addition to the active ingredient of the conventional ginkgo biloba extract. (Japanese Patent Laid-Open No. 2005-104921 (Patent Document 6)).

  As a result of further experiments, the present inventors have found that biflavones and mixtures thereof in ginkgo biloba extract have a proliferative activity against human epidermal keratinocytes (HEKs), which are hair follicle epithelial cell-related cells. And having the effect of promoting the transition of the resting hair of C3H mice to the growth phase.

  Hair has a so-called hair cycle that circulates through the growth, regression, and rest periods. In normal hair, the growth period lasts 5 to 7 years, and after several months of regression and rest periods, hair loss occurs, and hair roots form and the hair enters the growth period.

  On the other hand, in the hair of many alopecia patients, it is known that the growth period is shortened to less than 2 years, the rest period is extremely extended, and the hair does not enter the growth period.

  This test product is effective as a therapeutic agent for alopecia and a prophylactic agent because it has the effect of shifting telogen hair to the growth phase.

That is, while the conventional hair restorer has an indirect effect, the hair restorer of the present invention is directly effective for hair growth and enables efficient hair growth.
Biflavones in the present invention are general formulas

で表される化合物群で、Ｒ_１は任意に水素(Ｈ)、メチル(ＣＨ_３)、アルキル、単糖類、多糖類を示し、Ｒ_２は水素(Ｈ)、ヒドロキシル(ＯＨ)、メトキシ(ＯＣＨ_３)、ＯＧｌ_ｃ(Ｇｌ_ｃ：単糖または多糖)を示す。またこれらを含むエキス、分画物も含まれる。

Wherein R ₁ is hydrogen (H), methyl (CH ₃ ), alkyl, monosaccharide, polysaccharide, and R ₂ is hydrogen (H), hydroxyl (OH), methoxy (OCH _{3), OGl c (Gl c} : show a monosaccharide or polysaccharide). Also included are extracts and fractions containing these.

  The main biflavones are Siadopitysin, Ginkgetin, Isoginkgetin, Sequoiaflavone, Bilobetin, and Amentoflavone. It is.

シアドピティシン(Sciadopitysin)

Sciadopitysin

ギンクゲチン(Ginkgetin)

Ginkgetin

イソギンクゲチン(Isoginkgetin)

Isoginkgetin

セコイアフラボン(Sequoiaflavone)

Sequoiaflavone

ビロベチン(Bilobetin)

Bilobetin

アメントフラボン(Amentoflavone)

Amentoflavone

  Biflavones are mainly contained in ginkgo biloba leaves, but are also contained in juniper plants, yew plants, flax genus plants and persimmon plants.

  In order to use the biflavones of the present invention as a hair-growth agent, according to conventional methods, for example, blended with various forms of base materials known as cosmetics for normal hair such as emulsions, creams, lotions, gels, aerosols, hair tonics, It can be a hair liquid, a hair lotion, a hair cream, or the like.

Needless to say, the hair restorer of the present invention can be blended with known additives such as oils such as petrolatum and olive oil, refreshing agents such as menthol, antibacterial agents, moisturizers, pigments and fragrances.
In the case of adults, it is preferable to apply about 1 to 2% of a preparation daily about 5 cc.

  Further, in the present invention, the hair growth agent has an effect of promoting hair growth / hair growth and preventing hair loss and dandruff / itch.

  The hair restorer of the present invention is directly effective for hair growth and enables efficient hair growth.

[Example 1] Purification of biflavones from ginkgo biloba extract After mixing 10.0 g of ginkgo biloba extract (manufactured by Ginkgo biloba industry) into 600 ml of methanol, the mixture was transferred to a separatory funnel and the mixture was washed with hexane (first time) 400ml, 200ml x 3 times for the second and subsequent times).

  After removing insolubles from the methanol layer by suction filtration, the filtrate was concentrated to obtain 8.73 g of a residue. This residue was fractionated with 200 ml of a solvent of chloroform: methanol = 9: 1 and 100 ml of water.

  The aqueous layer was extracted with a solvent of chloroform: methanol = 9: 1 (50 ml × 4 times), and all the obtained organic layers were combined. Sodium sulfate was added to dehydrate, filtered, and concentrated to obtain 0.39 g of extract.

  0.39 g of the extract obtained by the above method was subjected to silica gel column chromatography (ethyl acetate: hexane = 1: 1) to obtain 0.28 g of a biflavone mixture from which lipid components such as ginkgolic acid were removed. High-performance liquid chromatographic analysis revealed that this is a mixture of biflavones of Sciadopitysin, Ginkgetin, Isoginkgetin, Isobeckin, Bilobetin, and Amentoflavone. (Figure 1).

  This biflavone mixture was fractionated by silica gel thin layer chromatogram (ethyl acetate: hexane = 1: 1), and 5 fractions (Fr. 1:55 mg, Fr. 2: 102 mg, Fr. 3:34 mg, Fr. 4:20 mg, Fr. 5:35 mg).

  As a result of analysis by high performance liquid chromatography, Fr. 1 includes Sciadopitysin, and Fr. 2 contains Ginkgetin and Isoginkgetin in a ratio of about 1: 2, Fr. 3 contains Ginkgetin and Isoginkgetin in a ratio of about 1: 7. 4 was found to contain mainly bilobetin. Amentoflavone contained only a small amount and could not be separated, so a commercially available product was purchased (Fluka Chemical Co. Milwaukee, WI, USA).

[Example 2] Growth promoting activity of biflavones on human epidermal keratinocytes (HEKs)
Fr. 1 to Fr. 4 and Amentoflavone (Amentoflavone) were examined for their growth-promoting activity against human keratinocytes (HEKs). Human epidermal keratinocytes (HEKs) were cultured for 120 hours in the presence of each specimen after preculture. The number of cells was determined by a colorimetric method using WST1. Human epidermal keratinocytes (HEKs) are hair follicle epithelial cell-related cells, and substances that promote the proliferation of these cells can induce hair-growth activity.

  The sample concentration is Fr. 1 is cyanadopiticin (molecular weight: 580), Fr. 2 is ginkgotin (molecular weight: 566): isoginkgetin (molecular weight: 566) = 1: 2, Fr. 3 is Ginkgogetin: Isochinkugetin = 1: 7, Fr. 4 was calculated as virobetin (molecular weight: 553). The results are shown in FIG.

  Fr. 1 increased cell proliferation in a dose-dependent manner in the range of 0.1 μM to 50 μM. The highest activity was 170% at 50 μM. Fr. 2 and Fr. 3 also showed cell proliferation activity in the range of 0.1 μM to 50 μM. Fr. 2 showed the highest activity 138% at 0.1 μM. In the range of 0.1 μM to 50 μM, Fr. The activity was lower than 1. Fr. 4 is also Fr. The activity was the same as or slightly lower than 2 and 3. On the other hand, amentoflavone did not show cell proliferation effect at any concentration. At high concentrations (100 μM), Fr. Any of 1-4 showed cytotoxicity.

From the above results, it was suggested that as the number of methoxyl groups in biflavone increases, the growth promoting activity increases. That is, it was found that the most preferred biflavone for hair growth action is cyanadopiticin, followed by a mixture of ginkgetin and isoginkgetin.
The growth promoting activity rate in FIG.

  Table 1 shows the cell growth rate of the specimen when the cell growth rate of the control is 100%. Epidermal keratinocytes (HEK) were cultured for 120 hours in a medium containing each concentration of specimen. As a control, a medium containing no specimen was used. The cell growth rate is shown as an average value ± S.E.M (n = 6).

[Example 3] Mouse hair growth test 1% biflavone mixture (siadpiticin, ginkgogetin, isogingugetin, vilovetin, amentoflavone) was used as a test product, 1% ethanol was used as a control, and 1% minoxidil was used as a standard product (positive control). Using. Minoxidil is a highly effective hair growth agent approved by the Ministry of Health, Labor and Welfare as a pharmaceutical product. The 1% biflavone mixture as the test product was dissolved in ethanol.

  The back hair of C3H mice is known to have a time-synchronized cycle, and the back hair enters a resting state from 18-21 days and 47-95 days. Therefore, 200 μL each of these test products, control products, and standard products was shaved on the back of 7-week-old C3H / HeSlc male mice (Japan SLC, Shizuoka, Japan) whose hair cycle was at rest. It was applied once a day. The result of observing the skin on the back of the mouse on the 40th day after the start of the test is shown in FIG.

  FIG. 3-a is a photograph of the hair growth situation with the control product, FIG. 3-b is a photograph of the hair growth situation with the test product, and FIG. 3-c is a photograph of the hair growth situation with the standard product.

  The application of minoxidil, a positive standard, covered 99% of the back skin with hair. On the other hand, only 23% of the control product coated with ethanol was covered with hair. However, in the group to which this test product was applied, 95%, which was almost equivalent to the standard product, was covered with hair.

  These results indicate that the biflavone mixture has significant hair growth activity that induces hair growth.

The figure which shows the result of having analyzed the extract extracted from the ginkgo leaf by the high performance liquid chromatography. The figure which shows the proliferation promotion activity with respect to human epidermal keratinocytes (HEKs) of biflavones. The figure which shows the hair growth condition in the back | dorsal part of a mouse | mouth by the control | contrast goods (application | coating 1% ethanol). The figure which shows the hair growth condition in the back part of the mouse | mouth by this test article. The figure which shows the hair growth condition in the back | dorsal part of a mouse | mouth by a standard product (application | coating 1% minoxidil).

Claims (3)

  Hair restorer containing biflavones as active ingredients.   The hair growth according to claim 1, wherein the biflavones are any one of Sciadopitysin, Ginkgetin, Isoginkgetin, Sequoiaflavone and Bilobetin, or a mixture thereof. Agent.   A hair-growth agent comprising a mixture of ginkgetin and isoginkgetin or chiadopiticin as an active ingredient.

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