JPH09188608A - Grey hair preventive agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain grey hair preventive agent excellent in grey hair remedying effect through preventing grey hair development by activating hair follicle's pigment cells and promoting melanogeneticity. SOLUTION: This grey hair preventive agent is a chromone derivative (salt) of formula I (R<1> is H, an alkyl, carboxyl, a group of formula II or COOR<9> ; R<2> is H, an acyl or carboxyl; R<3> is H, hydroxyl, etc.; R<4> is H, hydroxyl, etc.; R<7> and R<8> are each H, an alkyl, etc.; R<9> is a 1-15C alkyl, alkenyl, etc.) (e.g. 7-methoxychromone). It is preferable that this derivative be formulated at 0.05-5wt.% in a grey hair preventive agent composition either singly or in the form of combination of two or more kinds thereof.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an anti-hair graying agent capable of activating pigment cells in hair follicles and promoting melanin production to prevent / improve gray hair.

[0002]

2. Description of the Related Art Gray hair is one of physiological aging phenomena.
It is known to be caused by various changes in hair matrix pigment cells, but the mechanism of its development remains unknown. Therefore, the prevention and improvement of gray hair has hitherto mainly been a symptomatic treatment, and for example, a hair dye has been used from the viewpoint of beauty. However, none of these is a fundamental countermeasure, and there has been a demand for the development of an anti-hair graying agent that essentially prevents / improves the occurrence of gray hair itself.

In response to such a demand, some proposals have been made, for example, those containing a specific nucleic acid-related substance as an active ingredient (Japanese Patent Laid-Open Nos. 62-45527 and 63-1835).
No. 18, No. 63-301810, No. 64-25712
And JP-A-1-316308 and 2-157221.
No. 4-112817, No. 4-124122, No. 4-360836, No. 5-58845, No. 6-48
925), and those containing a peptide hormone or cell growth factor as an active ingredient (JP-A-1-207225,
No. 1-207226, No. 5-43424, No. 5-2
Nos. 13720, 5-213721, etc.) and those containing other substances as active ingredients (JP-A-60-17470).
No. 5, No. 61-165310, No. 62-63509
Nos. 62-63510 and 64-79107) and the like. However, they have not been practically sufficiently satisfactory in terms of efficacy, stability of active ingredients, safety and the like.

[0004]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide an anti-hair graying agent which is excellent in the effect of preventing and improving the occurrence of gray hair and also in safety.

[0005]

[Means for Solving the Problems] Under such circumstances, the present inventor has conducted diligent studies, and as a result, a specific chromone derivative activates pigment cells in the hair follicle part to increase melanin production, thereby causing white hair. The present invention has been completed by finding out that it is excellent in the effect of preventing and improving the occurrence of.

That is, the present invention provides the following general formula (1):

[0007]

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[Wherein R ¹ is a hydrogen atom, an alkyl group, a carboxyl group, COOR ⁹ (R ⁹ is a linear or branched alkyl or alkenyl group having 1 to 15 carbon atoms) or the following formula (2)

[0009]

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[0010] (R ⁷ and R ⁸ are a hydrogen atom, an alkylene group or -CH ₂ CH ₂ OCH ₂ CH _2, or R ⁷ and R ⁸ represent an alkyl group together - to form a) a, R ² Is a hydrogen atom, an acyl group or a carboxyl group, R ³ is a hydrogen atom,
A hydroxyl group, a lower alkoxyl group, a carboxymethyloxy group or a lower alkoxycarbonylmethyloxy group, R ⁴ is a hydrogen atom, a hydroxyl group, OR ⁶ (R ⁶
Represents the same meaning as above), a lower acyloxy group, a carboxymethyloxy group, a lower alkoxycarbonylmethyloxy group or an aralkyloxy group, and R ⁵ represents a hydrogen atom, a hydroxyl group, an alkyl group or a lower alkoxyl group]. It is intended to provide an anti-hair graying agent containing the represented chromone derivative or a salt thereof as an active ingredient.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Regarding the relationship between chromone derivatives and pigment cells, 3-hydroxychromone compounds have a tyrosinase activity inhibitory action (JP-A-55-111).
No. 410, 55-143908) and specific chromone derivatives have excellent melanin production-suppressing and pigmentation-improving effects on the skin (JP-A-5-30181).
No. 3) is known, but a specific chromone derivative has a strong activating effect on pigment cells in the hair follicle part, and increases melanin production, thereby preventing remarkable gray hair.
It is not known that the improvement effect is exhibited, which is a new finding by the present inventors.

In the general formula (1), the alkyl group represented by R ¹ has 1 to 15 carbon atoms, specifically, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group. , T-butyl group, octyl group, undecyl group and the like. Examples of the alkyl group having 1 to 15 carbon atoms for R ⁶ include those similar to R ^1, and examples of the alkenyl group include vinyl group, allyl group, crotyl group, α-pentenyl group and the like. Examples of the alkyl group represented by R ⁷ and R ⁸ include those similar to R ¹ .
The alkylene group formed by R ⁷ and R ⁸ is preferably a linear alkylene group having 4 to 5 carbon atoms.

Examples of the acyl group represented by R ² include those having 1 to 5 carbon atoms, specifically, formyl group, acetyl group, propionyl group, butyryl group and the like. Examples of the lower alkoxyl group represented by R ³ include those having 1 to 5 carbon atoms, such as a methoxyl group, an ethoxyl group and a propoxyl group. Examples of the lower alkoxycarbonylmethyloxy group represented by R ³ include a C _1-5 alkyloxycarbonylmethyloxy group, and specific examples thereof include an ethoxycarbonylmethyloxy group and an ethoxycarbonylmethyloxy group. The lower acyloxy group represented by R ⁴ includes those having 1 to 5 carbon atoms, specifically, acetyloxy group, propanoyloxy group and the like, and the lower alkoxycarbonylmethyloxy group has 1 to 5 carbon atoms. Examples thereof include methoxycarbonylmethyloxy group and ethoxycarbonylmethyloxy group. As the lower alkoxycarbonylmethyl group represented by R ⁴ include the same as R ^3. Examples of the aralkyloxy group represented by R ⁴ include phenyl-C _1-5 alkyloxy group and naphthyl-C.
_Examples thereof include a _1-5 alkyloxy group and the like, and specific examples include a benzyloxy group and a naphthylmethyloxy group.
Examples of the alkyl group of R ⁵ are the same as those of R ^1, and examples of the lower alkoxyl group are the same as those of R ³ .

Examples of salts of the chromone derivative (1) include alkali metal salts, alkaline earth metal salts, and acid addition salts such as hydrochlorides and sulfates.

Examples of the chromone derivative (1) used in the present invention include 7-methoxychromone and 7-methoxychromone.
Hydroxychromone, 5-methoxychromone, 5,7-
Dihydroxychromone, 5-hydroxychromone, 3-
Acetyl-5,7-dihydroxy-2-methylchromone, 5,7-dihydroxy-2-methylchromone, 5-
Hydroxy-2-methylchromone, 3-acetyl-5-
Hydroxy-2-methylchromone, 7-carboxymethyloxychromone, 7-ethoxycarbonylmethyloxychromone, 7- (3,7-dimethylocta-2,6-
Dienyloxy) chromone, 3-formyl-5-hydroxychromone, 5-hydroxychromone-3-carboxylic acid, 5-methoxychromone-2-carboxylic acid n-undecyl ester, chromone-2-carboxylic acid n-pentyl ester, 7 -Methoxychromone-2-carboxylic acid n-
Pentyl ester, 5-methoxychromone-2-carboxylic acid n-pentyl ester, chromone-2-carboxylic acid methyl ester, 5-hydroxychromone-2-carboxylic acid n-undecyl ester, 5-methoxychromone-
2-carboxylic acid methyl ester, 7- (3-methyl-2
-Butenyloxy) chromone, 7-methoxychromone-
2-carboxylic acid, 5-hydroxy-7-methoxy-2-
Methylchromone, potassium 7-methoxychromone-2-carboxylic acid, 7-methoxychromone-2-carboxylic acid ethyl ester, chromone-2-carboxylic acid, 5-methoxychromone-2-carboxylic acid, 5,7-dimethoxychromone, 3 -Acetyl-2-methylchromone, 5-hydroxychromone-2-carboxylic acid, 7-carboxymethyloxy-5-hydroxy-2-methylchromone, 7-ethoxycarbonylmethyloxy-5-hydroxy-2-methylchromone, 3 -Acetyl-5-hydroxy-7-methoxy-2-methylchromone, 7-butyloxychromone, 7- (3-methylbutyloxy) chromone, 7-
(2-Ethylhexyloxy) chromone, 7-methoxychromone-2-carboxylic acid-n-undecyl, 5,7-
Bis (ethoxycarbonylmethyloxy) -2-methylchromone, 3,7-diacetyl-5-hydroxy-2-
Methylchromone, 8-methyl-7- (1-naphthylmethyloxy) -2-morpholinochromone, 2- (N, N-
Diethylamino) -7-ethoxychromone, 5-hydroxy-7-methoxy-2-methylchromone, 7-hydroxy-2-methylchromone and the like are mentioned as preferable ones.

Particularly preferred compounds are 5-hydroxychromone, 7-hydroxychromone, 7-methoxychromone, 5,7-dihydroxychromone, 5,7-dihydroxy-2-methylchromone and 3-formyl-5-hydroxy. Chromone, 5-methoxychromone-2-carboxylic acid n-undecyl ester, 3-acetyl-5-hydroxy-2-methylchromone, 7- (3-methyl-2-
Butenyloxy) chromone, 5-hydroxy-7-methoxy-2-methylchromone, 7-methoxychromone-2
-Carboxylic acid, chromone-2-carboxylic acid n-pentyl ester, 5-methoxychromone, chromone-2-carboxylic acid, 3,7-diacetyl-5-hydroxy-2-methylchromone, 8-methyl-7- (1 -Naphthylmethyloxy) -2-morpholinochromone, 2- (N, N-diethylamino) -7-ethoxychromone, 5-hydroxy-7-methoxy-2-methylchromone, 7-hydroxy-2-methylchromone and the like. be able to.

The chromone derivative (1) can be obtained by the method described in the literature (Suzuki, Analytical Chemistry, 17, 1284 (1968), Limaye, J., Indi.
an CS, 12, 788 (1935), Bheemasankara, RECUEL., 8
3, 1122 (1964), Chem. Ber., 104, 348 (1971), Indian
JC, 23B, 1036 (1984), Nohara & Eda, Tetrahedro
n, 30, 3553 (1979), JP-A-47-5377, etc.)
Or according to the method.

The anti-hair graying agent of the present invention may contain one kind of the above-mentioned chromone derivative (1) alone or in combination of two or more kinds.
10% by weight is preferable, and 0.05 to 5% by weight
Is particularly preferred.

The anti-hair graying agent of the present invention is preferably used as an external preparation for pharmaceuticals, quasi drugs, cosmetics and the like,
For example, cream, lotion, emulsion, ointment, gel, hair tonic, hair liquid, liniment, hair rinse,
It can be formulated into various forms such as hair shampoo, hair treatment, hair conditioner, aerosol and mousse. As the base, a wide variety of liquid and solid raw materials which are acceptable for hair application can be used. At that time, various known additives such as antiseptics, fragrances, stabilizers, colorants, ultraviolet absorbers, antioxidants, moisturizers, thickeners and the like can be added if necessary.

The topical anti-hair graying agent of the present invention can be applied topically to a site where gray hair is generated, to improve the gray hair generated at that site, and also to prevent the occurrence of gray hair. The amount of the anti-hair graying agent of the present invention to be used varies depending on the content of the active ingredient, but for example, in the case of a cream-shaped or ointment-shaped preparation, it is 1 to ²⁰ mg per cm ^{2 of} the skin surface, and in the case of a liquid preparation, it is also 1 to 10 mg. Is preferred.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 Hair follicle tissue was aseptically isolated from the back of a chinchilla mouse (tyrosinase-positive albino, exhibiting a grayish white hair color) around 10 days of age, and Dulbecco's MEM containing 10% fetal calf serum. A certain amount was immersed in the medium. The chromone derivative shown in Table 1 (final concentration 100 μM) and a predetermined concentration of radioactive melanin precursor were added thereto, and the mixture was incubated at 37 ° C. for 3 days. After culturing, the hair follicle tissue was washed and dissolved, and the amount of radioactive melanin precursor incorporated into the tissue was measured. The results were expressed as relative values, with the value when the chromone derivative was not added as 100 (Table 1).

[0023]

[Table 1]

Example 2 Chinchilla mice around the age of 10 weeks of age were removed from the dorsal hair to induce anagen hair at the same site, and a hair tonic having the composition shown in Table 2 was once a day (0. (1 ml / dose) It was continuously applied for 1 month, and the darkness of body hair at the applied part was visually judged according to the following criteria. The test was carried out in 7 groups of 8 to 10 animals / group, and the results were represented by the average value of each group (Table 2).

(Criteria) 3: Strongly darkened 2: Slightly darkened 1: Slightly darkened 0: Almost darkened

[0026]

[Table 2]

Example 3 21 males (39 to 51 years old) with white hair, 3 by 7
The hair tonic product of the composition shown in Table 3 is divided into groups, and one product of each group and a comparative product are separately applied on the right and left sides of each person's head, so that they are used twice a day for 3 months. The hair at the application site was compared before and after the test. The white hair improving effect of the product of the present invention with respect to the comparative product was visually judged according to the following criteria. The results were represented by the average value of each group (Table 3).

(Criteria) 3: Strongly improved 2: Slightly improved 1: Slightly improved 0: Almost no improvement

[0029]

[Table 3]

No particular abnormality was observed in the skin condition during and after the use of the anti-hair graying agent of the present invention for 3 months.

[0031]

EFFECTS OF THE INVENTION The anti-hair graying agent of the present invention has a strong activating effect on pigment cells in the hair follicle part, and exerts a remarkable effect of preventing and improving gray hair by increasing melanin production. is there.

Front Page Continuation (72) Inventor Takashi Hori 2606 Akabane, Kaicho, Haga-gun, Tochigi Prefecture Kao Stock Company Research Institute (72) Yoshinori Nishizawa 2606 Akabane, Kai-cho, Haga-gun, Tochigi Research Center Kao Corporation

Claims (1)

[Claims] 1. The following general formula (1): [In the formula, R ¹ is a hydrogen atom, an alkyl group, a carboxyl group, COOR ⁹ (R ⁹ is a linear or branched alkyl group or alkenyl group having 1 to 15 carbon atoms) or the formula (2) (R ⁷ and R ⁸ represent a hydrogen atom, an alkyl group, or R 7
⁷ and R ⁸ together form an alkylene group or -CH ₂ CH ₂ O
CH ₂ CH ₂ — is formed, R ² is a hydrogen atom, an acyl group or a carboxyl group, R ³ is a hydrogen atom, a hydroxyl group, a lower alkoxyl group, a carboxymethyloxy group or a lower alkoxycarbonylmethyloxy group, R ⁴ is a hydrogen atom, a hydroxyl group, OR ⁶ (R ⁶ has the same meaning as above), a lower acyloxy group, a carboxymethyloxy group, a lower alkoxycarbonylmethyloxy group or an aralkyloxy group, and R ⁵ is a hydrogen atom. , A hydroxyl group, an alkyl group or a lower alkoxyl group], or an anti-hair graying agent comprising a salt thereof as an active ingredient.