JPH11116446A - External preparation for head - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an external preparation having hair restoring action such as depilation-preventing effect or trichogenous effect and capable of using as hair tonic and a trichogenous agent by including 5-aminolevulinic acid (derivative) as an active ingredient. SOLUTION: This external preparation is obtained by including 5- aminolevulinic acid (derivative), preferably in an amount of >=0.001 wt.% and <=10.0 wt.%, more preferably >=0.01 wt.% and <=5.0 wt.% as an active ingredient. 5-Aminolevulinic acid is called as δ-aminolevulinic acid and is a sort of amino acid represented by the formula HOOC-(CH2 )2 (CO)-CH2 -NH2 . 5- Aminolevulinic acid is widely distributed in various kinds of organisms and usually biosynthesized from succinylCoA and glycine by 5-aminolevulinic acid synthetase. 5-Aminolevulinic acid is known as intermediate for biosynthesis of porphyrin. 5-Aminolevulinic acid is produced by chemical synthesis method, biological fermentation method or enzymatic method.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for a head which is particularly suitable as a hair restorer or a hair growth promoter. More specifically, by using 5-aminolevulinic acid as an active ingredient, an external preparation for a head mainly used for the head, which has characteristics useful as a hair growth promoter and a hair growth promoter such as an excellent hair growth promoting effect. It is an invention concerning.

[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. In response to this, various attempts have been made to provide an external preparation for the head such as a hair restorer having various medicinal effects such as a superior hair restorer. For example, the main effects of the hair nourishing agent on hair include a hair growth inducing effect (hair growth promoting effect, growth period inducing effect), an effect of thickening hair, a hair growth period extending effect, and 5α.
-Reductase inhibitory effect, blood circulation promoting effect, bactericidal effect, dandruff preventing effect, moisturizing effect, antioxidant effect and the like.

[0003] However, despite various attempts as described above, conventional hair restorations do not always have sufficient hair restoration effects such as hair loss prevention and hair growth effects. This is probably due to various causes of hair loss and the very complex mechanism of hair growth. Therefore, it is desired to provide an external preparation for a head that can be applied to various uses in order to widely cope with such a complicated mechanism of hair.

[0004]

An object of the present invention is to further find a specific component having a favorable effect as an active component of a preparation for external use on the head such as a hair growth promoting effect, and to incorporate a specific component thereof as an active component. An object of the present invention is to provide an external preparation to improve the above situation.

[0005]

Means for Solving the Problems The present inventor has already known that a search for a component useful as an active component of an external preparation for hair has a hair-growth effect such as a hair loss preventing effect and a hair growth promoting effect. In order to achieve the above-mentioned object, the present invention was studied. As a result, it has been surprisingly found that 5-aminolevulinic acid and its derivatives have an excellent hair growth-promoting action, and that 5-aminolevulinic acids are extremely useful as an active ingredient of an external preparation for head use. I found it.

That is, the present invention provides an external preparation for a head comprising 5-aminolevulinic acid and / or a 5-aminolevulinic acid derivative as an active ingredient. The external preparation for the head according to the present invention is preferably used, for example, in a mode as a hair restorer or a hair growth promoter.

In the present invention, “external preparation for head” means almost all external preparations used for the head.
It is an external preparation that can take aspects such as hair restoration and hair growth promoter.
Further, in the present invention, the “hair growth promoting agent” is an external preparation for hair whose primary purpose is to directly exert a hair growth promoting effect of particularly promoting the hair growth action of the head.

[0008] On the other hand, the "hair nourishing agent" not only includes the concept of "hair growth promoting agent", but also various functions useful for other hair, specifically, the hair growth described above. Induces hair growth, thickens hair, prolongs hair growth period, inhibits 5α-reductase, promotes blood circulation, kills bacteria, prevents dandruff, moisturizes, antioxidant, and cures hair. It is meant broadly for external preparations for hair.

In the present invention, “5-aminolevulinic acid and / or 5-aminolevulinic acid derivative” (also referred to as “5-aminolevulinic acid throughout the present specification”) refers to “5-aminolevulinic acid” or “5-aminolevulinic acid”. The term “aminolevulinic acid derivative” includes, of course, “salts of 5-aminolevulinic acid” and “salts of 5-aminolevulinic acid derivatives”. Specific embodiments of this salt will be described later.

[0010]

Embodiments of the present invention will be described below. As described above, the external preparation for head of the present invention comprises 5-
It is an external preparation for the head containing aminolevulinic acid and / or a derivative thereof as an active ingredient.

5-Aminolevulinic acid is also referred to as δ-aminolevulinic acid and is a kind of amino acid represented by the formula HOOC- (CH ₂ ) ₂ (CO) —CH ₂ —NH ₂ (hereinafter also referred to as 5-ALA). ). This 5-aminolevulinic acid is widely distributed in various organisms, and is usually biosynthesized from succinyl-CoA and glycine by 5-aminolevulinic acid synthetase. This 5-aminolevulinic acid is known as an intermediate in porphyrin biosynthesis.

5-Aminolevulinic acid can be produced by a known method such as a chemical synthesis method, a microbial fermentation method or an enzymatic method and used as an active ingredient of the external preparation for head use of the present invention. In the case where 5-aminolevulinic acid is produced by a microorganism or an enzymatic production method and used in the present invention, the crudely purified 5-aminolevulinic acid obtained by these production methods is also used in human bodies. As long as it does not contain harmful substances, it can be incorporated into the external preparation for head of the present invention without separation and purification.

[0013] 5-Aminolevulinic acid is a herbicide (Table 1).
61-502814), insecticides (JP-A-2-138201), and plant growth regulators (Patent No. 2613136) are known to be useful as active ingredients. However, in the field of skin external preparations such as cosmetics, they are blended in cosmetics and the like as a means of protecting against light such as ultraviolet rays.
No. 7-10750), and there is no report on the hair growth promoting effect observed in the present invention.

Representative examples of the 5-aminolevulinic acid derivative which can be blended as an active ingredient of the external preparation for the head of the present invention include esters of 5-aminolevulinic acid and N-acyl-5-aminolevulinic acid. it can.

As an embodiment of the 5-aminolevulinic acid ester, for example, a linear, branched or cyclic alkyl ester having 1 to 24 carbon atoms which may have a substituent, preferably, for example, a methyl group, an ethyl group, an isopropyl group, n-hexyl, cyclohexyl, n-heptyl, n-octyl, n-nonyl, n-dodecyl, n-hexadecyl, benzyl, phenethyl, 3-phenylpropyl, hydroxyethyl, ethoxy Examples thereof include 5-aminolevulinic acid ester having an ethyl group or the like as an ester residue. Examples of the substituent which these alkyl groups may have include a hydroxy group, an alkoxy group, a phenyl group, a benzyl group, and a hydroxymethyl group.

As the N-acyl-5-aminolevulinic acid, a compound in which the amino group of 5-aminolevulinic acid is acylated with, for example, an alkanoyl group having 1 to 24 carbon atoms, an aromatic acyl group, a benzyloxycarbonyl group or the like is used. No. More specifically, preferred embodiments of the N-acyl group include, for example, an acetyl group, an n-pentanoyl group, an n-hexanoyl group, an n-nonanoyl group, a benzoyl group, and a benzyloxycarbonyl group.

These esters of 5-aminolevulinic acid and N-acyl-5-aminolevulinic acid can be produced by a generally known chemical synthesis method described in, for example, JP-A-4-9360. In addition, the crude product containing the target product obtained in the production process is also included in the external preparation for head of the present invention without separation and purification unless these crude products contain substances harmful to the human body. Can be blended.

Of the 5-aminolevulinic acid derivatives, 5-
Some of the compounds selected from esters of aminolevulinic acid and N-acyl-5-aminolevulinic acid include herbicides (Japanese Patent Application Laid-Open No. 4-9360) and plant growth regulators (Japanese Patent Application No. 5-05075).
It is known to be useful as
There is no report on the hair growth promoting effect of aminolevulinic acid derivatives.

Examples of the salts of these 5-aminolevulinic acids include various pharmaceutically acceptable salts.
The salts are not particularly limited as long as they are not harmful to the human body, and include, for example, inorganic salts, organic acid salts, alkali metal salts, alkaline earth metal salts, ammonium and alkylammonium salts.

More specifically, for example, hydrochloride, phosphate, nitrate, acetate, sulfate, propionate, butyrate, valerate, citrate, fumarate, maleate, malate Salt, hydrobromide, hydroiodide, succinate, oxalate, lactate, tartrate, glycolate,
Examples include acid addition salts such as methanesulfonate and toluenesulfonate, and metal salts such as sodium, potassium and calcium salts.

The amount of 5-aminolevulinic acid in the external preparation for the head of the present invention can be appropriately selected according to the form of the external preparation, the method of application, and the like, and should not be limited uniformly. However, it is generally 0.001% by weight or more and 10.0% by weight or less, preferably 0.01% by weight or more and 5.0% by weight or less of the external preparation. If the amount is less than 0.001% by weight of the preparation for external use, the desired effect of the present invention, such as the hair growth promoting action, is not sufficiently exhibited. This is not preferable because it becomes difficult.

[0022] As described above, an external preparation for a head which can be suitably used as a hair restorer or a hair growth promoting agent which exhibits an excellent hair growth promoting action by blending 5-aminolevulinic acid as an active ingredient. Is provided. In the external preparation for a head of the present invention, generally known components can be combined and compounded depending on the specific mode (for example, a hair restorer and a hair growth promoter).

For example, higher unsaturated fatty acids, solid paraffin, liquid paraffin, silicone oil, squalane, glyceryl monooleate, olive oil, higher alcohols and other oils; glycerin, hyaluronic acid, propylene glycol, maltitol, atelocollagen, sodium lactate, etc. Humectants; thickeners such as quince, carboxyvinyl polymer and xanthan gum; nicotinamide;
Benzyl nicotinate, vitamin E acetate, assembly extract, carpronium chloride, minoxidil, nicorandil, cyclosporine derivative, acetylcholine derivative, etc .; amino acids such as serine, methionine, arginine;
Vitamins such as vitamin B ₆ , vitamin E (or a derivative thereof), biotin, pantothenic acid (or a derivative thereof); nicotinic acid esters such as nicotinic acid, methyl nicotinate, and tocopherol nicotinate; skin function enhancers such as cepharanthin A female hormone agent such as estradiol; an anti-inflammatory agent such as glycyrrhetinic acid (or a derivative thereof); an antibacterial agent such as hinokitiol, hexachlorophen, benzalkonium chloride, bithionol; a refreshing agent such as menthol; , Lactic acid (or its alkyl ester) and the like; and organic acids such as citric acid and the like.

In the case where the external preparation for a head of the present invention takes a form as a hair growth promoting agent, for example, a component which is known to contribute to the promotion of hair growth is particularly selected. , As an active ingredient.

When the external preparation for a head of the present invention takes the form of a "hair restorer" more widely, not only the hair growth promoting component but also other hair restorer components are selected and blended. It is possible to characterize it as a hair restorer (of course, even in the case of taking a mode as a hair growth promoter, these hair restorer components can be blended as needed).

The external preparation for the head of the present invention can take any form as long as it can be applied to the scalp, such as liquid, emulsion, ointment and the like. In general, hair tonic, hair liquid , Sculpting treatment, hair cream, aerosol mousse, aerosol spray, hair gel, spray mousse, shampoo, rinse and the like. Specific formulations of the external preparation for head use of the present invention are exemplified in Examples.

[0027]

EXAMPLES Next, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. In addition, the compounding amount is weight% unless otherwise specified. The hair growth effect test and the results will be described in order.

[Hair growth test] Sample preparation 5-aminolevulinic acid (5-ALA) 0.1%, 0.2%, 0.5%, 1.0%
% And 2.0% were dissolved in a 75% ethanol solution to obtain Samples 1 to 5. Sample 6 was obtained by dissolving 1.0% of 5-aminolevulinic acid methyl ester (5-ALA-ME) in a 75% ethanol solution.

2. Hair growth test method and results The hair growth test was performed on the liquid samples 1 to 5 of the present invention (see Table 1) using a 75% ethanol suspension of 0.1% croton oil as a positive control sample. That is, C3H / HeNCrJ mice in the telogen of the hair cycle are used as experimental animals, and the method of Ogawa et al. [Normal and Abnormal, Epidermal, Differentiation (Normal)
and Abnormal Epidermal Differentiation), M.P. Se
iji and I. A. Bernstein, pp. 159-170, 1982, University of Tokyo Press].

That is, each group consisted of 10 mice, each of which was composed of test samples 1 to 6 and a control sample (75% of 0.1% croton oil).
Divided into 5 groups for ethanol suspension and), the back of the mouse was shaved with a clipper, and each sample was taken once a day.
Each 0.1 ml was applied. Twenty-four days later, the hair regeneration area was measured. The result was represented by the average value of the reproduction area. These are shown in Table 1.

[0031]

[Table 1]

<Evaluation criteria> Effective: Hair regeneration area is 40% or more Weak effect: Hair regeneration area is 5% or more and less than 40% No effect: Hair regeneration area is less than 5%

From Table 1, it is found that 5-aminolevulinic acid and 5
-Aminolevulinic acid methyl ester showed an excellent hair growth effect in a mouse hair growth test. The effect of 5-aminolevulinic acid was not improved at a concentration of 1.0% or more. From this result, it is clear that the cosmetic of the present invention containing 5-aminolevulinic acid or 5-aminolevulinic acid ester has an excellent hair-growth effect, and these are suitable for hair-growth use and hair-growth promotion use. It was found to be an external preparation for the head.

Examples of various formulations of the external preparation for head use according to the present invention will be described below as examples. In addition, any of these external preparations for the head can be used for both aspects of the hair growth agent and the hair growth promoter. Then, when the above-mentioned hair growth test was performed on these head external preparations of the present invention, the head external preparations of the present invention of any of the formulations had a hair regeneration area of 40% or more, and were judged to be “effective”. It was done.

[0035] Example 1 emulsion Ingredients weight (A phase) of 5-aminolevulinic acid 0.5 Polyoxyethylene (60 moles) added hardened castor oil 2.0 Glycerin 10.0 Dipropylene glycol 10.0 1, 3-butylene glycol 5.0 polyethylene glycol 1500 5.0 (phase B) cetyl isooctanoate 10.0 squalane 5.0 petrolatum 2.0 propylparaben 2.0 (phase C) 1% aqueous solution of carboxyvinyl polymer 30.0 Sodium hexametaphosphate 0.03 Ion-exchanged water 7.85 (D-phase) Ion-exchanged water 5.4 (E-phase) Kaseikari 0.12 Ion-exchanged water 5.0

(Manufacturing method) The phases A and B are each heated and dissolved at 60 ° C., mixed and treated with a homomixer to form a gel. Phase D was gradually added to this and dispersed with a homomixer. Next, the dissolved C phase was added thereto, and finally the dissolved E phase was added and emulsified by a homomixer to obtain an O / W emulsion.

Example 2 Cream Ingredient Ingredient Amount (Phase A) Liquid Paraffin 5.0 Cetostearyl Alcohol 5.5 Glyceryl Monostearate 3.0 EO (20 mol) -2-Octyldodecyl Ether 8.0 Propyl Paraben 0.3 Fragrance 0.1 (Phase B) 5-Aminolevulinic acid 2.0 Glycerin 8.0 Dipropylene glycol 20.0 Polyethylene glycol 4000 5.0 Sodium dodecyl sulfate 0.1 Sodium hexametaphosphate 0.005 Deionized water 42.995

(Production method) The phases A and B were each dissolved by heating, mixed, and emulsified by a homomixer to obtain a cream.

[0039] Example 3 Hair tonic Ingredients amount of 5-aminolevulinic acid 1.0 stearyl dimethyl amine oxide 0.5 Hydrogenated Castor Oil oxide (40 mol) adduct 1.0 95% Ethanol 54.0 Ion exchanged water Remaining amount

(Production method) Ion-exchanged water was added to 95% ethanol, hydrogenated castor oil ethylene oxide (40 mol) adduct and stearyl dimethylamine oxide were added, and the dried extract was added. I got

[0041] Example 4 0.1 95% hair tonic Ingredient weight Glycerin 5.0 L-menthol 0.1 ALA ethanol 60.0 Perfume 0.5 Ion exchanged water Balance

(Production method) Glycerin, L-menthol, flavor and dried extract were added to 95% ethanol, and the mixture was dissolved by stirring, and then ion-exchanged water was added.

Example 5 Hair Tonic Ingredients Component Amount N-cocolauryl-β-aminopropionate sodium 0.2 5-aminolevulinic acid 5.0 Sodium dodecylbenzenesulfonate 0.5 Hardened castor oil ethylene oxide (40 mol) Additive 1.0 95% ethanol 70.0 Deionized water balance

(Production method) Ion-exchanged water was added to 95% ethanol, hydrogenated castor oil ethylene oxide (40 mol) adduct, stearyldimethylamine oxide and sodium N-cocolauryl-β-aminopropionate were added, and the extract was added. The dried product was added and dissolved by stirring to obtain a hair tonic.

[0045] Example 6 Shampoo Ingredient weight cocoyl methyl taurate, sodium 2.0 Polyoxyethylene (8 mol) oleyl alcohol 2.0 Lauric acid diethanolamide 4.0 Ethylene glycol fatty acid ester 1.0 Glycerin 0.2 Menthol 0.1 5-Aminolevulinic acid 0.2 Perfume Appropriate amount Propylene glycol 2.0 Deionized water balance

(Manufacturing method) Ion-exchanged water was heated to 70 ° C., and other components were added and uniformly dissolved. Then, the system was cooled to obtain a shampoo.

Example 7 Rinse Component Ingredients Stearyl Trimethylammonium Chloride 0.7 Silicone Oil 3.0 Stearyl Alcohol 1.0 Polyoxyethylene (10 mol) Oleyl Alcohol Ether 1.0 Glycerin 5.0 5-Aminolevulin Acid 0.01 Preservative qs Ultraviolet absorber qs Deionized water balance

(Production method) Stearyltrimethylammonium chloride and glycerin were added to ion-exchanged water,
And an aqueous phase was prepared. On the other hand, other components were mixed, melted by heating, and kept at 70 ° C. to prepare an oil phase. The oil phase was added to the aqueous phase, emulsified with a homomixer, and cooled with stirring to obtain a rinse.

[0049]

According to the present invention, there is provided an external preparation for a head which is suitable for use as a hair restorer or a hair growth promoter having an excellent hair growth promoting effect.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Masahiro Tajima 1050 Nippacho, Kohoku-ku, Yokohama, Kanagawa Prefecture Inside Shiseido First Research Center Co., Ltd. (72) Inventor Yoshiharu Tsuji 1050 Nippacho, Kohoku-ku, Yokohama-shi, Kanagawa Inside Shiseido Daiichi Research Center Co., Ltd. (72) Inventor Kiyoshi Takahashi 1-1-1, Shibaura, Minato-ku, Tokyo Inside Cosmo Research Institute, Inc. (72) Inventor Toru Tanaka 1134-2 Gongendo, Satte City, Saitama (72) Inventor Koji Hotta 1134-2 Gongendo, Satte City, Saitama Pref. Cosmo Research Institute R & D Center

Claims (3)

[Claims] An external preparation for the head comprising 5-aminolevulinic acid and / or a 5-aminolevulinic acid derivative as an active ingredient. 2. The external preparation for a head according to claim 1, wherein the external preparation for a head is a hair restorer. 3. The external preparation for a head according to claim 1, wherein the external preparation for a head is a hair growth promoter.