JP2000128741A - Hair papilla activator - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hair papilla activator, showing a hair-growing effect, e.g. acceleration of hair growth, by directly acting on the hair papillae. SOLUTION: This hair papilla activator contains, as the effective ingredient(s), one or more types of extracts from the plant(s) selected from the group consisting of those belonging to the genus Zizyphus of the family Rhamnaceae, the genus Entada of the family Leguminosae, the genus Thuja of the family Cupressaceae, and the genus Verbena of the family Verbenaceae.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a hair papilla activator. More specifically, the present invention relates to a hair nipple activating agent which contains a specific plant extract as an active ingredient and can exert a hair growth effect such as promotion of hair elongation by activating hair dermal papilla cells.

[0002]

2. Description of the Related Art In a modern society referred to as an aging society or a stressed society, there are more and more opportunities for head hair to be exposed to the risk of hair loss due to various causes. For this reason, various attempts have been made to provide a more excellent hair restorer.

[0003] By the way, even if hair is simply referred to as hair, it is composed of parts that play various roles, and it is conceivable that the hair growth component also has an action point in various parts of this hair.

[0004] In general, hair repeatedly grows and falls according to a so-called "hair cycle" consisting of a anagen, a catagen, and a telogen. One of the tissues that plays the most important role during the anagen phase of the hair cycle is the dermal papilla. The dermal papilla is located inside a slightly bulging portion called the hair bulb portion of the root of the hair root. Hair papilla cells act on hair follicle epithelial cells (cells that combine outer root sheath cells and matrix cells near the hair root) to promote their proliferation and play a central role in hair differentiation Is located. Therefore, it is considered that the hair-growing component that directly acts on the hair nipple has an excellent hair-growing action that can extend the anagen during the hair cycle or promote the transition from the telogen to the anagen. In addition, it is considered that it is possible to exhibit a hair growth inducing effect and a hair elongation promoting effect. Further, for example, by combining a hair-growing ingredient having an action point on the hair nipple with a hair-growing ingredient having another different action point, a hair restorer capable of exhibiting a synergistic hair-growing action at a plurality of different action points is produced. It is thought that it is also possible to do.

As described above, it is apparent that it is extremely useful to produce a hair restorer focusing on the specific structure of hair. However, the hair restoration agents provided so far have been developed by capturing only a relatively rough concept of hair loss, in other words, simply the phenomenon of hair loss inadvertently (for example, a bactericidal component, dandruff suppression, etc. in order to keep the scalp clean). Ingredients, moisturizing ingredients, etc.), and blood circulation promoters and 5α-reductase activity inhibitors that are thought to work on the entire hair have been reported, but have been developed by focusing on the point of action. Is not much.

As a major reason, it cannot be denied that a hair growth test method for simply testing the hair growth effect at these action points has not been sufficiently provided. In particular,
It is very difficult to establish a hair growth assay method for assaying the hair growth effect in the above-mentioned hair nipple, including the availability of the material.As a result, the hair growth agents provided so far have to focus only on the phenomenon as described above. I didn't get it.

[0007] The present inventors have already established a hair growth assay method capable of simply assaying the hair growth effect on hair papilla in vitro (Japanese Patent Application No. 9-49900). Therefore, using this hair growth assay method, a component that directly acts on the dermal papilla was found, and studies have been repeated to obtain a dermal papilla activator containing the active ingredient as an active ingredient.

[0008]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a hair papilla activator containing, as an active ingredient, a component which acts directly on the hair papilla.

[0009]

Means for Solving the Problems The present inventors have studied the components which directly act on the hair papilla in various substances using the hair growth assay method established by the present inventors. The inventors have found that the ability to activate the dermal papilla was recognized, and based on this, completed the present invention.

That is, the present invention relates to the buckthorn family (Rh
amnaceae) a plant belonging to the genus Zizyphus, a plant belonging to the leguminous family (Leguminosae), a modal genus (Entada), a plant belonging to the genus Cypress (Cupressaceae), the genus Thuja, a Verbenaceae family (Verbeaceae)
The present invention relates to a hair papilla activator comprising, as an active ingredient, an extract of one or more plants selected from the plants belonging to na).

The hair papilla activator of the present invention is particularly useful for the "hair papilla"
Focusing on the point of action, it is a hair-related drug containing as an active ingredient a component that has the effect of extending the anagen during the hair cycle and the action of promoting the transition from the telogen to the anagen, as a so-called individual-effect hair restorer It has the characteristics of

By using this hair papilla activator in combination with a hair restorer having other points of action, a synergistic effect can be achieved in specific alopecia.

That is, the hair papilla activator of the present invention has a use which is different from a general use of a hair restorer which has a loose hair growth effect.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

The hair papilla activator of the present invention is a plant belonging to the family Rhamnaceae, the genus Zizyphus, the plant belonging to the leguminous family (Leguminosae), the genus (Entada), the cypress family (Cupressaceae) or the genus Thuja. )
And an extract of one or more plants selected from plants belonging to the genus Verbenaceae or Verbena.

In the present invention, any plant belonging to the genus Jujube of the family Anthracidae can be used without particular limitation as long as it belongs to the genus. Among them, jujube (Zizyphus jujuba var. Jujuva) and jujube jujube (Zizyphus) jujuba var. spinosa) is particularly preferably used. Jujube is a deciduous small tree native to southern Europe and West Asia, and its drupes are known as edible and medicinal. The jujube is also found in southern Europe, eastern Asia
It is a deciduous small tree native to the southern dry zone, and its fruit is smaller than jujube.

As a plant belonging to the genus Modama of the legume family, any plant belonging to the genus can be used without any particular limitation. Among them, modama (Entada phaseoloide)
s) is particularly preferably used. Modama is an evergreen large climbing plant widely distributed in the tropics of Kyushu, Yakushima, Ryukyu Islands, Asia and Africa.

[0018] Plants belonging to the cypress family Black Bee include
Any plant belonging to the genus can be used without any particular limitation. Among them, Konotegashiwa (Thuja orie)
ntalis) is particularly preferably used. Konotegasiwa is an evergreen small tree native to northeastern China. Seeds, leaves, shoots and the like are medicated.

As the plants belonging to the genus Sperma, the genus Sperma, any plant belonging to the genus can be used without particular limitation.
enaofficinalis) are particularly preferably used. Versicolor is a perennial herb from Asia, Europe, and North Africa that is found in warm to tropical areas.

The plants belonging to each of the above genera can be used either as raw or dried, but are preferably used as a dry powder or a solvent extract from the viewpoints of usability, formulation and the like.

The extract of each of the above plants can be obtained by a conventional method. That is, it can be obtained by subjecting the above-mentioned plant as it is or after drying it as necessary, and then subjecting it to solvent extraction as it is or pulverized. In addition, as for the site of use of each of these plants, a plant derived from whole plant or any component thereof can be used as long as it contains an active ingredient exhibiting the effects of the present invention.

As the above-mentioned extraction solvent, any solvent can be used as long as it is a solvent usually used for plant extraction or the like. For example, hot water, methanol, ethanol, isopropanol,
Lower alcohols such as n-butanol, polyhydric alcohols such as propylene glycol and 1,3-butylene glycol, and hydrates of these alcohols, hydrocarbon solvents such as n-hexane and toluene, etc. They can be used in combination. Among them, lower alcohols such as methanol and ethanol are preferably used. When these lower alcohols are used, the resulting extract can be directly contained in the dermal papilla activator of the present invention, but may be contained after the extraction solvent is distilled off and, if necessary, dried.

The plant extract thus obtained is highly safe and has an excellent dermal papilla activating effect and a hair restoring effect.

The amount of the plant extract in the dermal papilla activator of the present invention can be appropriately selected depending on the dosage form of the dermal papilla activator, the method of application, and the like. The dry matter is preferably about 0.00001 to 10.0% by weight, more preferably about 0.01 to 1.0% by weight. If the amount is less than 0.00001% by weight, it is difficult to sufficiently activate the dermal papilla cells, which is the desired effect of the present invention. It is not possible to expect a corresponding increase in the effect, and it is not preferable from the viewpoint of formulation.

One or more of these extracts can be appropriately selected and used.

As described above, dermal papilla cells play a central role in hair differentiation, for example, by acting on hair follicle epithelial cells to promote their proliferation. The anagen in the hair cycle is the period during which hair differentiation is taking place, and the catagen and the telogen are periods in which this slows down and pauses. In other words, substances that activate the activity of hair papilla cells are thought to promote the differentiation of hair follicle epithelial cells into hair, prevent the transition to the catagen and telogen phases in the hair cycle, and prolong the anagen. . In addition, it is expected that stimulating the hair papilla cells will increase the hair papilla and form thick hair.

With respect to such a dermal papilla activating effect,
For example, it can be confirmed using an in vitro assay method (Japanese Patent Application No. 9-49900) using the proliferative activity of cultured dermal papilla cells as an index, which the present inventors have already found. The above plant extract used in the present invention was confirmed to activate hair papilla cells by this assay. Therefore, it is considered that the hair papilla activator of the present invention containing the above plant extract has an action of promoting the anagen during the hair cycle.

The hair papilla activator of the present invention can have a synergistic effect in specific alopecia by using it in combination with a hair restorer having another action point.

The dosage form of the dermal papilla activator of the present invention is not particularly limited as long as it can be applied to the outer skin, and can be appropriately selected from, for example, liquid, emulsion, ointment and the like. Specifically, for example, it can be in the form of a tonic, a hair cream, a mousse, a shampoo, a rinse, a cream, a milky lotion, a lotion, a pack, and the like, but is not limited to these.

The dermal papilla activator of the present invention may be used in general in cosmetics, quasi-drugs, pharmaceuticals and the like, if necessary, in addition to the above essential components, as long as the desired effects of the present invention are not impaired. Various oily or aqueous components used for humectants,
Thickeners, preservatives, antioxidants, fragrances, coloring agents, various chemicals and the like can be added.

[0031]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. In addition, the compounding amount is shown by weight% unless otherwise specified.

I. Cell proliferation test using cultured dermal papilla cells An in vitro cell proliferation test for evaluating the dermal papilla activating effect of each plant extract used as the dermal papilla activator of the present invention will be described.

(1) Collection of dermal papilla cells Adipose tissue was separated from the occipital skin (5 mm × 1.5 cm) of a 34-year-old man removed by orthopedic surgery.
The hair follicle was excised therefrom and the hair papilla cells were isolated from the hair bulb. The isolated hair papilla cells were transformed with 20% fetal bovine serum (FB).
The cells were cultured in a minimum essential medium (MEM) containing S) for 2 weeks (37 ° C., 5% CO ₂ ). When the outgrowth of the cells was confirmed from the hair papilla cells, the medium was replaced with MEM containing 10% FBS (MEM ⁺ 10% FBS), and the cells were cultured under the same conditions. Thereafter, the culture solution (M
(EM ⁺ 10% FBS) was exchanged to maintain the cells.

Subculture was performed 4 weeks after the start of the culture.
Thereafter, when the cells had proliferated sufficiently, the cells were passaged again, and this passage was repeated.

(2) Test method Using dermal papilla cells at the third passage, MEM ⁺ 10% FB
A cell suspension with a cell density of 10,000 cells / ml was prepared in S medium. 200 μl of this cell suspension was added to 96
Dispense into well microplates (ie, 2000
The cells were cultured at 37 ° C., 5% CO ₂ for 3 days to allow the cells to adhere. Then, as a control, the culture solution was replaced with serum-free MEM. The analyte system was 10 ^-5 % each of the extracts of the target substances, jujube, jujube jujube, modama, konotegasiwa, and black pine, and the extract of ginkgo.
The medium was replaced with serum-free MEM. Both control and test lines were cultured for an additional 4 days.

After completion of the culture, 20 μl of alamar blue (manufactured by BIOSOURSE) was added to each system, followed by further culturing for 8 hours, and the absorbance at 570 nm and 595 nm was measured with a microplate reader. According to the attached instruction manual, the reduction ratio of alamar blue was calculated from the measurement result of the absorbance. Since the reduction rate correlated with the cell number, the proliferation rates in the control and the test system were compared.

The extracts of the above plants were prepared in the following procedure.

That is, 500 g of dried matter of jujube, jujube jujube, modama, konotegasiwa, and black pine was added to
Each was immersed in 5 liters of 70% ethanol at room temperature for 3 days, the alcohol extract was separated, the solvent was distilled off, and finally dried to obtain each plant extract dried product. Each dried extract thus obtained was prepared in a 0.2% by weight solution with dimethyl sulfoxide (DMSO), and used after dilution.

The extract of Ginkgo biloba was known as a hair-growth component, and a commercially available product was used.

The results are shown in Table 1.

[0041]

[Table 1]

As is clear from the results in Table 1, it was confirmed that the plant extract contained in the hair papilla activator of the present invention had a significant effect of promoting the growth of cultured papilla cells in culture. On the other hand, this effect was not observed in the extract of Ginkgo biloba, and the point of action of the extract of Ginkgo biloba as a hair-growing component is considered to be a portion other than the hair papilla. This also suggests the utility of the hair papilla activator of the present invention, which acts particularly on the hair papilla.

II. Tricogram test In order to examine the hair growth effect as a result of activating the hair nipple by the hair nipple activator of the present invention, the following Examples 1 to 5, Comparative Example 1, and 70% ethanol as a control were used. A gram test was performed.

(Example 1) Hair tonic hair papilla activator (Blending components) Blending amount (% by weight) Dry matter extract of jujube jujube 0.00005 Ethanol 90.0 Sodium oleate 0.01 Dodecylbenzene sulfonic acid 0 .49 Hardened castor oil ethylene oxide (40 mol) adduct 0.5 Ion-exchanged water Residue (Preparation method) 500 g of Sunebusa jujube (dry matter) was immersed in 5 liters of 70% ethanol at room temperature for 3 days. Separation was performed, and the solvent was distilled off. Finally, the residue was dried to obtain a dried ethanol extract of a jujube jujube.
The dried ethanol extract of the jujube jujube thus obtained was mixed and stirred with each of the above components to prepare a hair tonic hair papilla activator.

Comparative Example 1 Comparative Example 1 was prepared by adding 0.1% by weight of dried pepper extract (Piper nigrum) in place of dried ethanol extract of juvenile jujube in Example 1. In addition, the dried ethanol extract of pepper is pepper (dried) 500
g in 5 liters of 70% ethanol at room temperature for 3 days, the alcohol extract was separated and the solvent was distilled off.
Obtained by drying.

Example 2 Hair Tonic Hair Nipple Activator A hair nipple activating agent of Example 1 was prepared by adding 10 (weight ratio) of ion-exchanged water to the hair nipple activating agent of Example 1.
And

(Example 3) O / W type emulsion liquid dermal papilla activator (compounding components) compounding amount (% by weight) (phase A) dry matter of jujube jujube methanol extract 1.0 polyoxyethylene (60 mol) Addition-hardened castor oil 2.0 Glycerin 10.0 Dipropylene glycol 10.0 1,3-butylene glycol 5.0 Polyethylene glycol 1500 5.0 (B phase) Cetyl isooctanoate 10.0 Squalane 5.0 Vaseline 2. 0 Propylparaben 2.0 (Phase C) Carboxyvinyl polymer 1% aqueous solution 30.0 Sodium hexametaphosphate 0.03 Ion exchange water 8.35 (D phase) Ion exchange water 4.5 (E phase) Potassium hydroxide 0. 12 Ion-exchanged water 5.0 (Preparation method) A-phase “Sanebut Jujube methanol extract dried product” In the manufacturing process of the pawl ethanol extract dried product used was prepared by immersing the Sanebutonatsume instead of ethanol methanol same concentration.

The phases A and B were each dissolved by heating at 60 ° C., mixed and homogenized to prepare a gel. Phase D was gradually added to this gel, and further dispersed with a homomixer. The C-phase and the E-phase were added thereto and dispersed with a homomixer to obtain an O / W type emulsion liquid nipple activator.

(Example 4) Creamy dermal papilla activator (Blending ingredients) Blending amount (% by weight) (Phase A) Liquid paraffin 5.0 cetostearyl alcohol 5.5 glyceryl monostearate 3.0 EO (20) Mol) -2-octyldodecyl ether 8.0 propylparaben 0.3 Perfume 0.1 (phase B) Dry matter extract of jujube jujube 5.0 Glycerin 8.0 Dipropylene glycol 20.0 Polyethylene glycol 4000 5.0 Dodecyl Sodium sulfate 0.1 Sodium hexametaphosphate 0.005 Ion-exchanged water Residue (Preparation method) As the “B-phase dried ethanol extract of jujuba jujube”, one prepared in the same manner as that used in Example 1 was used. The phases A and B were each dissolved by heating, mixed, and emulsified by a homomixer to obtain a creamy dermal papilla activator.

(Example 5) Lotion for activating the dermal papilla (Blending ingredients) Blending amount (% by weight) Dry matter extract of jujuba jujube 0.0005 Hardened castor oil ethylene oxide (40 mol) adduct 2.095% ethanol 55. 0 Ion-exchanged water residue (Production method) "Dried ethanol extract of jujube jujube"
Was used in the same manner as in Example 1. This was mixed with each of the above components to prepare a dermal papilla activator.

(Trichogram test method) The hair roots of the extracted hair before and after use of each sample were observed under a microscope, and the number of quiescent hair roots in the hair cycle was counted from the form of the hair roots. The hair growth effects of the samples were compared.

That is, the test sample and the control sample were applied to the scalp of 10 male subjects twice a day, 2 ml at a time, for 6 consecutive months, and one subject immediately before the application and immediately after the completion of the application for 6 months. 100 hairs were removed from each hair, each hair root was examined, and an actual use test was performed.
Table 2 shows the results.

The telogen hair root is a hair root in the telogen of the hair cycle, which is a hair root that has stopped growing.
It has been observed that those who report hair loss have a higher percentage of this telogen root than those who do not. That is, in this test, the higher the proportion of the telogen roots, the more the degree of hair loss is progressing.

[0054]

[Table 2]

As is evident from the results in Table 2, the hair papilla activator of the present invention containing the extract of jujube jujube was compared with Comparative Example 1 in which a large amount of the extract of pepper, which was confirmed to have a blood circulation promoting action, was added. It was also found that the hair growth effect was excellent.

(Examples 6 to 10) In the formulation of the dermal papilla activator of the present invention of Examples 1 to 5, instead of the extract of the jujube jujube, the alcohol of konotegashiwa prepared by the same process and the raw material weight as the jujube jujube ( (Ethyl alcohol or methyl alcohol) extract was added in the same amount as the same extract of the jujuba jujube to prepare the hair papilla activator of the present invention.

Using these samples of Examples 6 to 10, a tricogram test was performed in the same manner as described above. Table 3 shows the results
Shown in

(Example 11) In the formulation of the dermal papilla activator of the present invention in Example 1, an ethanol extract of Kumatsudura prepared by the same process and raw material weight as that of the jujube extract was used instead of the extract of jujube jujube. The hair papilla activator of the present invention was prepared by adding the same amount as the same extract of the jujube jujube.

Using the sample of Example 11, a tricogram test was performed in the same manner as described above. Table 3 shows the results.

(Example 12) In the formulation of the dermal papilla activator of the present invention of Example 1, an ethanol extract extract of Modama prepared by the same process and raw material weight as that of the Jujube jujube was used in place of the Jujube jujube extract. The hair papilla activator of the present invention was prepared by adding the same amount as the same extract of the jujube jujube.

A tricogram test was performed using the sample of Example 12 in the same manner as described above. Table 3 shows the results.

[0062]

[Table 3]

As is clear from the results in Table 3, Example 6
-10 to 10 (activator of the present invention having an extract of Aspergillus oryzae as an active ingredient), Example 11 (activator of the present invention having an extract of Aspergillus oryzae as an active ingredient), Example 12 (extraction of Modama) Activator of the present invention containing a substance as an active ingredient)
Were found to be significantly superior in their hair growth effect.

[0064]

As described in detail above, the present invention provides a hair papilla activator capable of activating hair papilla cells to exert a hair growth effect such as promotion of hair elongation.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 35/78 A61K 35/78 C (72) Inventor Masahiro Tajima 1050 Niiwacho, Kohoku-ku, Yokohama-shi, Kanagawa Stock Company F-term in Shiseido Daiichi Research Center (reference) 4C083 AA111 AA112 AB032 AB282 AC012 AC022 AC072 AC122 AC182 AC252 AC352 AC432 AC482 AC792 AD042 AD092 BB53 CC37 DD27 DD33 EE22 4C088 AB03 AB12 AB59 AC01 BA08 BA09 BA10 CA03 MA07 MA17 MA92

Claims (5)

[Claims] 1. A plant belonging to the family Rhamnaceae, the genus Zizyphus, the legume family (Leguminosae).
A plant belonging to the genus Modama (Entada), Cypress family (Cupressa)
ceae) a hair comprising an extract of one or more plants selected from plants belonging to the genus Thuja, plants belonging to the family Verbenaceae and Verbena, as active ingredients. Nipple activator. 2. The nipple activator according to claim 1, wherein the plant belonging to the genus Jujube of the buckthorn family is one or more of jujube (Zizyphusjujuba var. Jujuva) and jujube jujube (Zizyphus jujuba var. Spinosa). . 3. The hair papilla activator according to claim 1, wherein the plant belonging to the genus Modama of the legume family is Modama (Entada phaseoloides). 4. The hair papilla activator according to any one of claims 1 to 3, wherein the plant belonging to the cypress family belonging to the genus Knotweed is Thuja orientalis. 5. The hair papilla activator according to any one of claims 1 to 4, wherein the plant belonging to the genus Sperma in the family Spermataceae is Verbena officinalis.