JP2008247784A - Hair papilla cell growth promoter and hair-restoring or growing agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hair papilla cell growth promoter exhibiting excellent effect on prophylaxis and improvement of hair-removing or hair-thinning symptom and having excellent effect for growing hair papilla cell and high safety equal or superior to those of minoxidil acknowledged as a medicine. <P>SOLUTION: This hair-restoring and growing agent having excellent hair-restoring and growing effect and high safety is produced by compounding an extract of Sargassum ringgoldianum which is a seaweed belonging to the genus Sargassum, family Sargassaceae, order Fucales, and having excellent hair papilla cell growth promoting activity. Further, the use of the extract of Sargassum ringgoldianum in combination with a blood flow accelerator synergistically improves the excellent hair restoring and growing effect and the alopecia preventing effect to provide a hair-restoring and growing agent exhibiting hair-restoring and growing effect having improved effect and high safety. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to a hair papilla cell growth promoter characterized by containing an extract of green grass (scientific name: Sargassum ringgoldianum), and a hair nourishing and hair-loss-promoting and hair-loss preventing effect comprising the same. Regarding hair growth. Further, the present invention relates to a hair nourishing and hair restorer that has a sufficient effect by using a combination of oberum extract and a blood circulation promoter.

AGA (male pattern baldness) is a condition in which the hair unique to adult men is thinned. It is seen by more than 12.6 million people nationwide, and 8 million men care about it, of which some kind of care was taken There are statistics that there are 6.5 million people. In recent years, alopecia has become one of the problems faced by many people. In addition to the epidemic hair loss, alopecia due to congenital constitution, hair loss due to stress accompanying the complex social structure, or alopecia due to side effects of drugs has increased. I am doing. Although various explanations have been given for the cause of hair loss, there are still many unclear points about the details of the onset mechanism. A typical example of the mechanism of hair loss onset is sebum secretion from the sebum line, which is mixed with scalp stains and sebum leakage, which clogs the pores and causes hair root nutrition and circulation disorders. Sebum sequela, hormone theory that male hormones (testosterone) are overproduced, and that the hormonal imbalance occurs in the parietal region that was previously governed by the balance of male and female sex hormones, or genetic or nutritional There are various theories such as However, neither can be a definitive cause.

As an active ingredient of these hair loss preventing agents, hair growth agents or hair nourishing agents, blood circulation promoters such as hinokitiol or menthol; amino acids such as methionine; minoxidil (2,4-diamino-6-piperidinopyrimidine- 3-oxide), vasodilators such as acetylcholine derivatives; anti-inflammatory agents such as purple root extract; female hormones such as estradiol; skin function enhancers such as cephalanthin; 5α-reductase inhibitors; vitamin B ₆ Vitamin agents such as anti-androgenic agents; or phthalide derivatives such as 4-hydroxy-3-heptylphthalide (Patent Document 1) are known. Since these drugs may cause skin irritation in some cases, the amount of blending is limited, and sufficient effects such as hair growth, hair loss prevention and dandruff prevention are not sufficient, and various problems remain. Is the current situation. In addition, these actions secondarily activate hair-related cells, and in order to develop more effective hair-restoring / hair-growth materials, hair-restoring / hair-growth materials that directly activate hair-related cells are not available. It is requested.

Among the hair-related cells, a hair nourishing / hair growth agent that directly acts on the hair papilla cells responsible for the hair growth mechanism and significantly promotes the growth of the cells is desired. So far, what activates hair papilla cells has been disclosed. That is, citrus peel-derived peptides (see Patent Document 2), extracts such as ogi, auren, and kashu (see Patent Document 3) Amblet seed essential oil purified fraction (see Patent Document 4), ammonium compounds, calcium compounds, magnesium Compound, L-glutamic acid or a salt thereof, L-serine, PCA (pyrrolidonecarboxylic acid) or a salt thereof, an extract of Chlorella vulgaris, a fruit extract of Citrus junos, a fruit of Ages (Rosa multiflora) Ginkgo (Ginkgo) extract
biloba) leaf extract (see Patent Document 5), minoxidil (Non-Patent Document 1), etc., promoting the growth of hair papilla cells, button pi extract, litchi extract (see Patent Document 6), Aogiaceae Fusen Akamegashi genus plant extract (see patent document 7), Asteraceae feline genus plant extract (see patent document 8), Euphorbiaceae genus plant extract (see patent document 9), Aloe, Arnica, Ogon, Cuckon And the like having an action of activating the hair papilla, such as an extract of the genus Lumeaceae (see Patent Document 11) and the like (see Patent Document 10).
On the other hand, Obermok (scientific name: Sargassum
ringgoldianum) extract is disclosed to have a testosterone-5α-reductase inhibitory effect (see Patent Document 12), but experimental data that it has a hair-restoring / hair-growth effect is not disclosed or even suggested. In other words, it was not known at all that the extract of Psyllium has a dermal papilla cell growth-promoting effect and has a hair-growth / hair growth effect in mice and humans, which will be described later.

By the way, the dermal papilla cell proliferation promoter can be effectively used in regenerative medicine. Induction of hair follicles by transplantation of hair papilla has been clarified by experiments using buccal papilla such as rats. For example, Oliver et al.'S experiment showed that the hair follicle regenerates by re-implanting the dermal papilla directly under the upper half left after cutting off the lower half of the hair follicle. It is nothing but the fact that hair follicle stem cells (epithelial stem cells) in the bulge region are differentiated into hair follicles by differentiation signals of hair papilla cells. After that, Jahoda et al. Demonstrated that hair follicles were also formed by cultured rat hair papilla cells. At this time, the culture technology for human hair papilla cells had already been established. We anticipate the realization of hair follicle regenerative treatment using hair. Certainly, if human hair papilla cells can be cultured while maintaining the ability to induce hair follicles, hair regeneration is achieved by collecting hair papilla cells from a small number of hair follicles, culturing them in large quantities, and then transplanting them into the lash part. There is a possibility of treatment. As shown above, testosterone-5α-reductase inhibitors and hair papilla cell proliferation promoters have different application ranges.
Furthermore, it will be explained that not all components having testosterone-5α-reductase inhibitory effect have the effect of promoting hair papillary cell proliferation. It can be seen from Table 1 that the peony extract has a testosterone-5α-reductase inhibitory effect (see Patent Document 12). From Table 2, it can be seen that there is no effect on proliferation of hair papilla cells.
JP-A-3-135907 JP-A-9-202716 JP-A-9-208431 JP 2005-213143 A JP 2006-282597 A JP-A-10-226628 Japanese Patent Laid-Open No. 11-1416 Japanese Patent Laid-Open No. 11-12134 Japanese Patent Laid-Open No. 11-124317 JP-A-11-240823 JP 2000-128741 A JP 7-278003 A JP 58-88307 A Journalof Dermatological Science (2004) 34, 91-98

An object of the present invention is to provide a hair nourishing and hair restorer that directly acts on hair papilla cells that are responsible for the mechanism of hair growth and promotes the growth of the cells.
Up to now, when 1.0 μM (0.3 ppm) minoxidil is used as a hair nourishing and hair restoring agent that directly acts on hair papilla cells and promotes the growth of the cells, the effect of proliferation of hair papilla cells with a control ratio of 200% Has been reported (Non-patent Document 1).
Minoxidil was originally used as an oral antihypertensive agent, but was developed with a focus on the hair-growth effect as a side effect. (See Patent Document 13). Currently, hair restorers formulated with minoxidil are sold in the market as pharmaceuticals having a hair restoring effect. However, although minoxidil has an excellent effect as a hair restorer, it has safety problems such as palpitations due to continuous use and appearance of side effects such as slight skin irritation, and the blending amount is limited. Accordingly, an object of the present invention is to provide a dermal papilla cell proliferation promoter having an excellent proliferation effect of dermal papilla cells equivalent to or better than minoxidil recognized as a pharmaceutical product, and further promote the proliferation of dermal papilla cells. It is to provide a hair nourishing and hair restorer that has a synergistic effect on hair restoration / hair growth and hair loss prevention by using an agent and a blood circulation promoting composition in combination.

As a result of intensive studies to achieve the above object, the present inventors have found that the seaweed of the genus H.
ringgoldianum) extract was found to have excellent hair papilla cell proliferation activity, and the present invention was completed. In addition, the composition containing the monkey extract and the blood circulation promoter described later synergistically provides a better hair restoration / hair growth and hair loss prevention effect than the single use of the monkey extract, The present inventors have found that it has high safety over a long period of time and have completed the present invention.

According to the present invention, it is possible to provide a hair nourishing / hair restoring agent that exhibits an excellent effect, a hair nourishing / hair restoring agent, and a hair papillary cell proliferating agent that has an excellent effect.

Hereinafter, embodiments of the present invention will be described.
The leaf extract used in the present invention is dried at room temperature or under warming after drying all parts of the seaweed (Sargassum ringgoldianum), which is a seaweed of the genus Hondaraceae, It can be obtained by extracting with a solvent or using an extraction device such as a Soxhlet extractor.

Examples of the solvent used in the present invention include water and / or an organic solvent, and an organic solvent is particularly preferable. Specific examples of the organic solvent include polyhydric alcohols such as glycerin, polyethylene glycol, and propylene glycol, a mixed solution of these polyhydric alcohols and water (preferably 5 to 30% aqueous solution); an anionic surfactant aqueous solution. , Nonionic surfactant aqueous solution, amphoteric surfactant; alcohols such as methanol, ethanol, butanol; mixed solution of these alcohols and water (10-99.5%, preferably 20-90% aqueous solution); hexane, Hydrocarbons such as benzene, toluene, xylene and petroleum ether; Halogenated hydrocarbons such as chloroform, dichloromethane and 1,2-dichloroethane; Ethers such as diethyl ether and tetrahydrofuran; Esters such as ethyl acetate and isopropyl myristate Liquid paraffin, soybean oil, sesame Various mineral oils and the like, animal oils, vegetable oils, and the like and mixtures thereof.

Next, a specific example of an extraction method for obtaining a plant extract from a plant body is illustrated below. These methods may be appropriately selected depending on the purpose and application. For the purposes of the present invention, the method of Example 1) or Example 7) is preferred. For example, when ethanol, water, hydrous ethanol or the like is used as an extraction solvent, the concentration can be adjusted by appropriately adding ethanol, water or the like without completely distilling off the solvent. Further, impurities can be generated at room temperature or lower, which can be used after being removed by filtration or the like.
Example 1): A method of pulverizing a dried plant of oberomoku, followed by extraction with water, anhydrous or hydrous ethanol solvent, and distilling off the solvent.
Example 2) After pulverizing the dried green grass, it was extracted with water, anhydrous or hydrous ethanol solvent, and the resulting extract was selected from activated carbon, polyamide resin, polystyrene resin such as HP-20, and polyethylene methacrylate resin for decolorization etc. The method of processing by 1 type, or 2 or more types.
Example 3) After pulverizing the dried green grass, it was extracted with a solvent such as anhydrous or hydrous lower alcohol, and then the extract was subjected to liquid-liquid extraction using hydrous lower alcohol and hydrocarbons. A method of distilling off the solvent from the transferred hydrocarbon phase.
Example 4) After pulverizing the dried green grass, it was extracted with a solvent such as anhydrous or hydrous lower alcohol, and then the extract was subjected to liquid-liquid extraction using water and a solvent immiscible with water such as ethyl acetate, Further, the solvent is distilled off from the organic phase or the aqueous phase.
Example 5) A method of subjecting the aqueous phase obtained in Examples 3 and 4 to liquid-liquid extraction using butanol and water and further distilling off the solvent from the butanol phase.
Example 6) In Example 4 and Example 5, before or after performing liquid-liquid extraction, the extract is one or more selected from activated carbon, polyamide resin, polystyrene resin such as HP-20, and polyethylene methacrylate resin. How to handle with.
Example 7) After pulverizing the dried green moth, it was extracted with a suitable solvent, and then the extraction phase was treated with one or more selected from activated carbon, polyamide resin, polystyrene methacrylate resin such as HP-20, and the like. A method of adsorbing the components, then extracting the active components with methanol, ethanol, acetone, or a mixture thereof with water, and distilling off the solvent.

The extract can be used as it is as an active ingredient of the hair nourishing and hair restorer of the present invention. However, the extract is further subjected to an appropriate separation means such as gel filtration or silica gel column chromatography, or reverse phase or normal phase. A fraction having high activity can be fractionated by high performance liquid chromatography.

Thus, it is preferable to use the obermoku extract obtained by dissolving in a solvent such as water or water-lower alcohol. It is preferable that the oberomoku extract is blended in the hair nourishing / hair growth material of the present invention in a dry weight of 0.0001 to 5% by weight (hereinafter simply referred to as “%”).

As the blood circulation promoter used in the present invention, synthetic or natural components, d, 1-α-tocopherol acetate, L-menthol, biotin, nicotinic acid and derivatives thereof, hinokitiol, assembly extract, garlic extract, Ginseng extract, clove extract, toki extract, river cucumber extract, chimpi extract, thin leaf extract, ginkgo biloba extract, capsicum tincture, etc., among these, d, l-acetate α-tocopherol, assembly extract, L-menthol, ginseng extract, nicotinic acid and its derivatives are particularly preferred. The blood circulation promoter is preferably used after being dissolved in a solvent such as water or water-lower alcohol.

The blood circulation promoter is preferably added in an amount of 0.001 to 5% in the hair nourishing and hair restoring agent of the present invention.

In addition to the essential components described above, the hair nourishment / hair growth material of the present invention is an oily base used in normal cosmetics, quasi-drugs, pharmaceuticals, etc., as long as the effects of the present invention are not impaired. , Emollients, gelling agents, various emulsifiers, fragrances, antioxidants such as parahydroxybenzoic acid esters, coloring agents such as dyes, cooling agents such as menthol, fungicides, and wetting agents such as propylene glycol. Can do.

Further, the hair nourishing and hair restorer of the present invention is a hair tonic, hair cream, hair liquid prepared by blending an extract extracted from the active ingredient with water and / or an organic solvent, or the various active ingredients. It can be applied to cosmetics such as hair gel, hair blow, hair mousse, hair lotion, pomade, hair shampoo, hair rinse, and emulsion. The cosmetic can be applied in various cosmetic shapes such as solution, sol, gel, emulsion, ointment, oil, wax and spray. Further, the hair nourishing and hair restorer of the present invention can be used in combination with other known hair nourishing and hair restoring agents.

Hereinafter, the present invention will be described in more detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.

<Example 1>
Add 121Og of 95% ethanol to 121g of dried seaweed Oobamoku (chopped), extract at room temperature for 5 days, and filter through filter paper. Thereafter, the filtrate is recovered (concentration 0.1% wt / v solid). The filtrate was distilled under reduced pressure, dried and dissolved in 95% ethanol to obtain 381 g of a 95% ethanol solution. Filter through filter paper to obtain the extract.

(1) Hair papilla cell culture method Hair papilla cells were cultured using normal human hair papilla cells CS-ABI-3047 (Dainippon Pharmaceutical Co., Ltd.). The culture medium is CS-C medium kit CS-4Z0-500 (10% FBS, including growth factor),
CS-C serum-free medium kit CS-SF-4Z0-500S (with or without growth factors) was used.

(2) Method 1 for measuring cell proliferation rate of dermal papilla cells
4 passages, pDL9 hair papilla cells are seeded in 96 wells at 3.5 × 10 ³ , then cultured in the above CS-C medium for 1 day, the supernatant medium is discarded, and CS-C serum-free medium (containing growth factors) The sample prepared at each concentration was added and the WST assay was performed after 50 hrs to evaluate the cell proliferation rate. The results are shown in Table 2.

(3) Method 2 for measuring cell proliferation rate of dermal papilla cells
Passage 7, pDL16 papilla cells are seeded at 4 × 10 ^{3 in} 96 wells, then cultured in the above CS-C medium for 2 days, the supernatant medium is discarded, and CS-C serum-free medium (without growth factors) The sample prepared above was exchanged and added to each concentration. After 73 hrs, the WST assay was performed to evaluate the cell proliferation rate. The results are shown in Table 3.

A study was conducted on the effect of promoting the growth of dermal papilla cells using the extract of Oberomoku. To the human hair dermal papilla cell culture system, the moss extract was added to a concentration of 15 ppm, 10 ppm, 1 ppm, and 0.3 ppm, respectively, and the cell growth rate of human hair dermal papilla cells after 50 hours was determined by WST assay. did. The experimental results are shown in Table 2. In addition, to the human hair dermal papilla cell culture system, the lobster extract was added to a concentration of 10 ppm, and the cell proliferation rate of human hair dermal papilla cells after 73 hrs was quantified by WST assay. The experimental results are shown in Table 3. As can be seen from Tables 2 and 3, the lobster extract was excellent in the cell growth promoting effect of hair papilla cells, and the same effect was confirmed as compared with minoxidil. (The results in Tables 2 and 3 show the average value and standard deviation of the results of three experiments)

The hair nourishing and hair restoring compositions of Examples 1 to 8 and Comparative Examples 1 to 4 shown in Table 5 were prepared according to conventional methods. The back of C3H mice (5 per group) in the resting period is shaved, and the hair restoration and hair restoration shown in Table 5 are applied once a day (100 μl), and the regenerated hair area 16 days after shaving. The ratio (regenerated hair area / shaved area) and the regenerated hair length ratio (regenerated hair length / pre-shaved hair length) were measured based on the scoring criteria shown in Table 4. The results are also shown in Table 5.

As is clear from the results shown in Table 5, it can be seen that Examples 1 to 8 show remarkable hair regeneration compared to Comparative Examples 2 to 4. Furthermore, it can be seen that the combined composition of the bark extract of Examples 1 to 7 and the blood circulation promoter shows the same level of hair regeneration as that of Comparative Product 1, which is known to have an excellent hair growth effect. . As described in paragraph 0008, Comparative Example 1 has excellent effects as a hair restorer, but has side effects such as palpitations due to continuous use and slight skin irritation, and has a safety problem. is doing. However, in the present invention, even if the test of Paragraph 0037 was performed, there were no panelists that caused abnormalities in hair, skin and physical condition, and high safety was exhibited.

The following examples illustrate the present invention in more detail, but the present invention is not limited thereto.

Hereinafter, the human hair growth effect of the present invention will be described in detail. In order to confirm the effect of the present invention, the following experiment was conducted.

[Hair nourishing / hair growth effect test]
Nineteen men (age 30-59 years old) who suffer from thin hair were subjects, and the hair-growth tonic shown in Table 8 was used twice a day for 1 month on the head. The feeling of use after one month was performed by subject's sensory evaluation, and the results are shown in Table 10.

Evaluation of the hair-growth / hair-growth effect of the above-mentioned hair-growth tonic revealed that it had been used continuously for only one month, from the effect of preventing hair removal, the effect of irritating the hair, and the effect of reducing the baldness. After one month, about 50% of the subjects clearly felt the effect of hair restoration / hair growth. This hair growth tonic was found to have a sufficient hair growth effect.

It was proved in the above examples that the hair preparations and hair washing agents such as shampoos, conditioners, tonics, and essences of the present invention have excellent hair nourishing and hair restoration effects. In each example, the fact that no abnormalities were found in the panelists in hair, skin, physical condition, etc. during and after use indicates high safety.

The hair restoration / hair-growth composition containing the extract of the mosquito, which is a seaweed of the genus Hondamataceae of the present invention, has an excellent hair-growth / hair-growth effect and high safety, so it is widely applied to hair-growth / hair-growth agents. I can expect.

Claims (4)

  A dermal papilla cell growth promoter characterized by containing an extract of Obermok as an active ingredient.   A hair nourishing / hair-growth composition characterized by containing an extract of Obermoku as an active ingredient.   A hair nourishing / hair-growth composition characterized by containing an oberomoku extract and a blood circulation promoter. The blood circulation promoter is one selected from d, l-α-tocopherol acetate, L-menthol, nicotinic acid and its derivatives, assembly extract, ginseng extract, chimpi extract, ginkgo biloba extract, red pepper tincture or The hair nourishing and hair restoring material according to claim 3, wherein there are two or more kinds.