JP2000201650A - Hair-restoring food and oral hair-restoring agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a hair-restoring food scarcely giving a side effect, excellent in safety and in hair restorability, and useful as an oral hair-restoring agent, etc., by adding proanthocyanidin as an active ingredient. SOLUTION: This hair-restoring food contains proanthocyanidin, a plant extract containing the proanthocyanidin as a main ingredient, or the purified product of the plant extract. The content of the proanthocyanidin is 0.1-50%, preferably 1-20%. The plant is a plant belonging to the genus Vitis, Malus, Hordeum, Cocos, Theobroma, Pinus, Phaseolus or Arachis. A hair-restoring food or an oral hair-restoring agent is preferably prepared by adding the alcohol fermentation product of a plant extract containing the proanthocyanidin or the purified product of the alcohol fermentation product as an active ingredient. The proanthocyanidin is preferably taken at a daily dose of 100-2,000 mg for an adult.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair restorer and an oral hair restorer containing proanthocyanidin as an active ingredient and for the purpose of growing hair.

[0002]

2. Description of the Related Art Proanthocyanidins are substances which are widely present in the plant kingdom and are known to have strong antioxidant activity. The present inventors have revealed that proanthocyanidins exhibit hair growth activity by external use. (WO96 / 00
561). However, it is not known that the substance exerts a hair growth activity orally.

[0003] Japanese Patent Application Laid-Open Nos. 8-205818 and 9-2 relate to health foods and pharmaceuticals containing procyanidin.
91039, etc., but no hair growth food or hair growth oral pharmaceutical containing proanthocyanidin is known. Hair restorer containing grape component is disclosed in Japanese Patent Application Laid-Open No. 56-6860.
6, JP-A-6-172129 and JP-A-7-6984
3, all of which are external preparations manufactured by a specific method, and the active ingredient is not specified.

A hair restorer containing an apple-derived component is disclosed in
No. 81337, but no oral hair growth action is known. A hair restorer containing barley components, which relates to volatile components derived from malt (Japanese Patent Laid-Open No. 8-3)
4709) is known, and Japanese Patent Application Laid-Open No. 8-81337
, But all are external preparations, and no active ingredient is specified.

A hair restorer containing oyster leaf components is disclosed in
Although it is described in 329518, it is an external preparation and the active ingredient is not specified. Also, hair growth foods containing seaweed, oyster leaves and kelp are disclosed in
No. 6, the active ingredient is not specified, and the oral hair growth effect of proanthocyanidin is not known.

[0006] Hair restorers are known which contain the distilled components of compositions containing wine (AU-A-32774 / 89),
The oral hair-growth effect of proanthocyanidins contained in grapes and red wine is not known. An anti-alopecia food and drink and an anti-alopecia agent containing an oolong tea extract are known (JP-A-9-309840), but the active ingredient has not been specified.

[0007]

An object of the present invention is to provide a hair growth food and an oral hair growth agent containing proanthocyanidin as an active ingredient.

[0008]

Means for Solving the Problems The inventors of the present invention have searched for a substance having a hair-growth effect by oral ingestion, and as a result of repeated research,
Strong hair growth activity was found in proanthocyanidins. The present invention relates to a hair growth food and an oral hair growth agent characterized by containing proanthocyanidin as an active ingredient.

[0009] The present invention also relates to a hair growth food and an oral hair growth agent containing, as an active ingredient, a plant extract containing proanthocyanidin as a main component or a purified product thereof. As the plant, plants such as grape genus, apple genus, barley genus, coconut genus, cacao genus, pine genus, kidney bean, and peanut genus are preferable. In addition, the present invention provides a hair growth food and an oral hair growth agent containing, as an active ingredient, an alcohol fermentation product of a plant extract containing proanthocyanidin or a purified product thereof.

[0010] The plants are preferably plants of the genus Grape, Apple, Barley and the like.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Proanthocyanidins are a group of compounds obtained by polymerizing a flavan-3-ol derivative represented by the following formula (I) as a constitutional unit.

[0012]

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(Wherein R ¹ and R ² are the same or different and represent hydrogen or a hydroxyl group) Specific examples of the flavan-3-ol derivative represented by the formula (I) include catechin, epicatechin, gallocatechin,
Epigallocatechin, afzeletin, epiafuzeletin and the like, and all of these optical isomers are included,
Proanthocyanidins containing epicatechin or catechin as a constitutional unit are more preferably used in the present invention.

The binding mode of the flavan-3-ol derivative represented by the formula (I) may be in any manner. For example, as a dimer in which two flavan-3-ol derivatives are polymerized, the following formula (I) II)

[0015]

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(Wherein R ³ and R ⁴ are the same or different and represent hydrogen or a hydroxyl group, and R ¹ and R ² have the same meanings as described above), Examples of the above polymers include those in which the bonding modes are the same or different. The proanthocyanidin used in the present invention may be a dimer or more of a flavan-3-ol derivative, but is preferably a dimer to a dimer, more preferably a dimer to a pentamer, and still more preferably a dimer to a pentamer.
It is a trimer. Examples of the dimer of the flavan-3-ol derivative include a combination of epicatechin and catechin such as epicatechin- (4β → 8) -catechin, and epicatechin-
(4β → 6) -epicatechin, epicatechin- (4β →
8) dimer of epicatechin such as -epicatechin, and dimer of catechin such as catechin- (4α → 8) -catechin. Examples of the trimer of flavan-3-ol derivative include epimer dimer. Catechin- (4β → 8) -epicatechin- (4β → 8) -epicatechin, epicatechin- (4β
Epicatechin trimers such as → 8) -epicatechin- (4β → 6) -epicatechin; catechin trimers such as catechin- (4α → 8) -catechin- (4α → 8) -catechin; Catechin- (4β → 8) -epicatechin- (4
Mixed trimers of epicatechin and catechin, such as β → 8) -catechin, can be mentioned.

The proanthocyanidins of the present invention also include compounds obtained by adding sugars such as gallic acid, glucose, and rhamnose to these proanthocyanidins. Proanthocyanidins include grape, apple, barley,
Oyster, coconut, cocoa, pine, kidney beans,
Grapes, apples, barley, etc. belonging to peanuts, etc.
Oysters, palms, cacao, pine, adzuki beans, peanuts, etc., are obtained by extraction and purification, and fermented products of these extracts, for example, wine, apple cider, beer, etc.
It can also be obtained by purifying them.

Extraction and purification from plants can be performed by the following known methods. After collecting the fruits, seeds, leaves, stems, roots, rhizomes, etc. of the raw materials of the plant at an appropriate time,
It is used as it is or is usually subjected to a drying step such as air drying to obtain an extraction raw material. When proanthocyanidins are extracted from the dried plants described above, a known method [Chemical and Pharmaceutical Britain (Chemical & Ph.
armaceutical Bulletin), 38 : 3218, 1990 and Id., 4
0 : 889-898, 1992]. That is, after pulverizing or shredding the raw material, extraction is performed using a solvent. As the extraction solvent, a hydrophilic or lipophilic solvent such as water, alcohols such as ethanol, methanol, and isopropyl alcohol; ketones such as acetone and methyl ethyl ketone; and esters such as methyl acetate and ethyl acetate; Can be used as The extraction temperature is usually 0 to 100 ° C, preferably 5 to 100 ° C.
５０50 ° C.

The extraction time is about 1 hour to about 10 days, and the amount of the solvent is usually 1 to 30 times, preferably 5 to 10 times the weight of the dry raw material. The extraction operation may be performed by stirring or immersion. The extraction operation may be repeated two or three times as necessary. The method of purifying proanthocyanidin from the extract obtained by removing the insoluble residue from the crude extract obtained by the above operation by filtration or centrifugation, or the squeezed liquid or sap of a plant (purification method A) is a known crude drug separation method. Any purification method may be used, but two-phase solvent partitioning, column chromatography,
It is preferable to use preparative high performance liquid chromatography alone or in combination. For example, as a two-phase solvent partitioning method, a method of extracting and removing oil-soluble components and dyes from the above-mentioned extract with n-hexane, petroleum ether, etc. To recover the proanthocyanidin into the solvent phase. As a column chromatography method, Amberlite IR-120 is used as a carrier.
B, ion-exchange column chromatography using Amberlite IRA-402, etc., as a carrier, normal-phase silica gel, reverse-phase silica gel, Diaion HP-20,
Examples include adsorption column chromatography using Sepabeads SP-207 and the like, gel filtration using Sephadex LH-20 and the like as carriers, and these can be used alone or in combination and repeated. Examples of the preparative high performance liquid chromatography method include a method using a reverse phase column using octadecyl silica or the like, a method using a normal phase column using silica gel or the like, and the like.

By the above purification method, proanthocyanidins can be obtained as a result of removing water-soluble ionic substances such as salts, nonionic substances such as saccharides and polysaccharides, oils, dyes, and the like from the crude extract. As a method for producing proanthocyanidins by a synthesis method, a method for producing a dimer of epicatechin or catechin is disclosed in Journal of the Chemical Society, Parkin Transaction I.
Chemical Society: Perkin TransactionsI): 1535-154
3, 1983, and can be synthesized according to the method described in the literature or a method analogous thereto.

An alcohol fermentation product of a plant extract containing proanthocyanidin can be obtained by the following known method. That is, in the case of a single fermentation type fermented liquor such as wine and apple liquor, fruit juice is produced by alcohol fermentation with yeast. For example, in the production of red wine from grape juice, grape fruit is crushed, an antioxidant is added, and then 2-5% of sake brewer is added, followed by main fermentation for 7-10 days. Then, it is squeezed to remove the pericarp and sediment, transferred to an oven with a fermentation stopper, and post-fermented at about 10 ° C. to a residual sugar of 0.2% or less. Precipitates such as tartar, tannin, protein, etc. are produced and stored and aged for several years. In the case of a double fermentation type fermented liquor such as beer, cereal starch is used as a raw material, saccharification with amylase is performed first, and then alcohol fermentation is performed. For example, in the production of beer using barley as a main raw material, wort is made from malt and water, and yeast is added for fermentation. Main fermentation is carried out at 7-10 ° C for 10 days, transferred to a storage tank and post-fermented at 0-2 ° C for 60 days. After completion of the post-fermentation, filtration or heat sterilization is performed to obtain a desired fermentation product.

As a method for purifying proanthocyanidin from the above-mentioned alcoholic fermentation product, the same method as exemplified in the above-mentioned purification method A can be mentioned. By the above purification method, proanthocyanidins can be obtained as a result of removing water-soluble ionic substances such as salts, nonionic substances such as saccharides and polysaccharides, oils, pigments and the like from alcoholic fermentation products.

When proanthocyanidins are used as the active ingredient of the present invention, one or more proanthocyanidins may be mixed. Specific examples include grape seed extract proanthocyanidin, red wine extract purified product, apple-derived proanthocyanidin, pine-derived proanthocyanidin, purified proanthocyanidin oligomer, and the like.

Next, the effects of the hair growth food or the oral hair growth agent of the present invention will be specifically described by test examples.

Test Example 1 Effect on Hair Growth in Mice Ogawa et al.'S method [The Journal of Dermatology]
(The Journal of Dermatology), 10 : 45-54, 1983], and a test of the hair growth effect in mice was performed.

9 weeks old C3H / H in the rest period of the hair cycle
After carefully shaving the back hair of eSlc male mice (4 to 5 mice per group) with an electric clipper and an electric shaver, the proanthocyanidin samples obtained in Reference Examples 1 and 2 were fed to a powder feed for breeding (CE-2, Japan). In addition to the above, a hair growth test was conducted with free intake. To the control group, only a powder feed for breeding (CE-2, manufactured by CLEA Japan) was given freely.

The skin on the back of the mouse on the 18th day after the start of the test was sampled and photographed, and then the percentage of the area of the hair growth part to the total area of the back skin was measured using an image analysis processor (Avionics, Spica II). Was determined, and the value obtained by subtracting the value of the hair growth rate of the control group from the value of the hair growth rate of the test drug group was defined as an increased hair growth area ratio (%). Table 1 shows the test samples, test concentrations and test results.

[0028]

[Table 1]

As shown in Table 1, the proanthocyanidin-containing hair growth food and the oral hair growth agent of the present invention showed a remarkable mouse hair growth promoting effect. The food of the present invention contains proanthocyanidin in an amount of 0.1% in food ingredients, particularly food ingredients which are essentially free of proanthocyanidins.
Proanthocyanidin is added in the form of a pure product, a purified product, a roughly purified product, etc. so as to contain at least 01%, preferably 0.1 to 50%, more preferably 1 to 20%, and a general food production method is used. Thus, it can be processed and manufactured.

The hair growth food of the present invention may be in the form of tablets,
Capsules, powders, pills, jellies, beverages, frozen foods, powdered foods, sheet foods, bottled foods, canned foods, retort foods, etc., as well as natural liquid foods, semi-digestive nutrition foods, component nutrition foods, etc. It can be added in the form of processing, etc., and can be added with general raw materials used in foods, for example, proteins, sugars, fats, trace elements, vitamins, emulsifiers, fragrances, and the like.

The types of foods include juices, soft drinks, teas, lactic acid beverages, fermented milk, frozen desserts, dairy products (butter, cheese, yogurt, processed milk, skim milk, etc.), and meat products (ham, sausage) , Hamburgers, etc.), fish paste products (kamaboko, bamboo rings, fried tomatoes, etc.), egg products (dashi rolls, egg tofu, etc.), confectionery (cookies, jelly, snacks, etc.), breads, noodles, pickles, smoked products, dried fish , Tsukudani, salted goods, soups, seasonings and the like.

The form of the oral hair restorer of the present invention includes tablets, capsules, powders, pills, powders, fine granules, granules,
Syrups, troches and the like can be mentioned. Proanthocyanidin pure product, purified product, crude product, etc. may be administered as it is, but tablets, capsules, powders, pills, powders, fine granules, granules together with pharmacologically acceptable excipients. Agent,
They may be administered in the form of syrups, troches and the like. As excipients, sorbitol, lactose, glucose, sugars such as lactose, dextrin, starch, calcium carbonate, inorganic substances such as calcium sulfate, crystalline cellulose, distilled water, sesame oil, corn oil, olive oil, cottonseed oil, etc.
Any commonly used one can be used. In formulating, additives such as a binder, a lubricant, a dispersant, a suspending agent, an emulsifier, a diluent, a buffer, an antioxidant, and a bacteriostatic agent can also be used.

The proanthocyanidin content in the oral hair restorer is 0.01% or more, preferably 0.1 to 50%, more preferably 1 to 20%. The oral dose of proanthocyanidin varies depending on the symptoms of the disease, the age of the patient, and the like.
000 mg, preferably 100-2000 mg, more preferably 200-500 mg.

[0034]

EXAMPLE Reference Example 1 Purification method of proanthocyanidin B-2 [epicatechin- (4β → 8) -epicatechin] from apple juice A diamond prepared by equilibrating 5280 kg of apple juice (4 times concentrated solution) with water. Column (60cmφ × 88.5cm: 250L) packed with Ion HP-20 resin (Mitsubishi Chemical Corporation)
And washed with 1000 L of demineralized water and 500 L of 15% (V / V) methanol. Next, the target substance was eluted with 500 L of 45% (V / V) methanol. The eluate was dried to obtain 9450 g of a dried product.

1465 g of the dried product was 25% (V /
V) A column packed with Sephadex LH-20 (manufactured by Pharmacia) dissolved in methanol and equilibrated with 25% methanol (18 cmφ × 39.3 cm: 10 L volume).
And 20 L of 25% (V / V) methanol, 20 L
After sequentially washing the column with 50% (V / V) methanol of L, the target substance was eluted with 20 L of 75% (V / V) methanol, and the eluate was dried to obtain 233 g of a dried product.

After dissolving 116 g of the dried product in deionized water, the solution was subjected to preparative high performance liquid chromatography (150 mmφ ×
1000 mm: ODS column, methanol / 0.000
(1% aqueous acetic acid solution = 12/88). Thus, 16.5 g of proanthocyanidin B-2 (purity of 94% or more) was obtained. Reference Example-2 Purification method of proanthocyanidin from red wine 30 L of purified water was added to 16.2 L of red wine, and a column (100 mmφ × 400 mm: 3 L) filled with Diaion HP-20 resin (manufactured by Mitsubishi Kasei Corporation) equilibrated with water. volume)
And 6 L of demineralized water and 6 L of 20% (V / V)
The column was washed with methanol and then 1.5 L of 40% (V / V) methanol. Next, 40% of 4.5 L (V
/ V) methanol and 3 L of 60% (V / V) methanol sequentially eluted the desired product.

The eluate was concentrated and freeze-dried to obtain about 20 g.
(A mixture of various proanthocyanidins, purity of 90% or more, catechin: epicatechin = 1: 6.2, average degree of polymerization of 3.5) was obtained.

Example 1 Beverage The proanthocyanidin obtained in Reference Example 2 was blended in the following composition, and purified water was added to bring the total amount to 1000.
The beverage was prepared in ml. Red wine refined proanthocyanidin (Reference Example 2) 1.0 g Sodium benzoate 1.0 g Fructose 10.0 g Flavoring appropriate amount Pigment appropriate amount

Example 2 Tablets The proanthocyanidins obtained in Reference Example 1 were blended in the following composition and tableted with a single-shot tableting machine to produce tablets having a diameter of 7 mm and a weight of 250 mg. . Proanthocyanidin B-2 (Reference Example 1) 10.0 g Lactose 90.0 g Dried corn starch 2.0 g Talc 1.8 g Calcium stearate 0.2 g

[0040]

Industrial Applicability According to the present invention, a safe and effective hair growth food and an oral hair growth agent containing proanthocyanidin as an active ingredient can be provided.

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Claims (16)

[Claims] A hair-growing food containing proanthocyanidin as an active ingredient. 2. A hair growth food containing a plant extract containing proanthocyanidin as a main component or a purified product thereof as an active ingredient. 3. The hair growth food according to claim 2, wherein the plant is a grape, apple, barley, coconut, cacao, pine, kidney bean or peanut plant. 4. A hair-growing food comprising, as an active ingredient, an alcohol fermentation product of a plant extract containing proanthocyanidin or a purified product thereof. 5. The hair growth food according to claim 4, wherein the plant is a grape, apple or barley plant. 6. A proanthocyanidin content of 0.1 to 5
The hair growth food according to any one of claims 1 to 5, which is 0%. 7. A proanthocyanidin content of 1 to 20%
The hair growth food according to any one of claims 1 to 5, wherein 8. The hair growth food according to claim 1, wherein the daily intake of proanthocyanidin for an adult is 100 to 2000 mg. 9. An oral hair restorer containing proanthocyanidin as an active ingredient. 10. An oral hair restorer containing a plant extract containing proanthocyanidin as a main component or a purified product thereof as an active ingredient. 11. The oral hair restorer according to claim 10, wherein the plant is a grape, apple, barley, coconut, cacao, pine, kidney bean or peanut plant. 12. An oral hair restorer containing, as an active ingredient, an alcohol fermentation product of a plant extract containing proanthocyanidin or a purified product thereof. 13. The oral hair restorer according to claim 10, wherein the plant is a grape, apple or barley plant. 14. A proanthocyanidin content of 0.1 to
The oral hair restorer according to claims 9 to 13, which is 50%. 15. A proanthocyanidin content of 1 to 20.
%. The oral hair restorer according to claims 9 to 13. 16. The daily intake of proanthocyanidin for an adult is 100 to 2000 mg.
3. The oral hair restorer according to 3.