JPH1179950A - Tyrosinase activity promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject promoter having tyrosinase activity promoting effect and useful as e.g. a gray hair preventive agent by formulating a saffron extract as active ingredient. SOLUTION: This tyrosinase activity promoter is obtained by formulating, as active ingredient, 0.001-10.0 (pref. 0.005-5.0) wt.% of a saffron extract (pref. a lower alcohol (e.g. methanol) extract).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a tyrosinase activity promoter in the technical field. More specifically, the present invention relates to a tyrosinase activity promoter that promotes the activity of tyrosinase, an enzyme deeply involved in the maintenance of black hair, by the action of saffron extract.

[0002]

2. Description of the Related Art Tyrosinase is an essential enzyme for the biosynthesis of tyrosine from "melanin", a black pigment widely distributed in human hair and mainly playing the role of absorbing excess light. is there. The action of this tyrosinase oxidizes tyrosine and then produces melanin via dopa and indolequinone. This melanin is involved in maintaining black hair in hair. That is, it is considered that if a means for promoting the activity of tyrosinase can be found, it is possible to artificially suppress the generation of gray hair in hair.

[0003] An anti-white hair agent can be obtained by screening an active substance with reference to the mechanism of gray hair development or, conversely, the mechanism of melanin pigment formation, or by randomly examining the white hair preventing action of various substances. The use of a wide variety of compounds as active ingredients has been studied. For example, those that improve the ability of melanocytes to produce cyclic AMP (see JP-A-4-124122) and those that activate the production of melanin in melanocytes (for example, JP-A-5-78222 and JP-A-7-285874).
And Japanese Unexamined Patent Application Publication No. 7-316026) and those which are said to exhibit both the hair-growth effect and the gray-hair preventing effect (see Japanese Patent Application Laid-Open Nos. 7-112789 and 7-126129).

[0004]

The problem to be solved by the present invention is to find a component that promotes the activity of tyrosinase, which plays a fundamental role in the production of melanin in hair, and to use this as an active ingredient. An object of the present invention is to provide a tyrosinase activity promoter that can be used as an inhibitor or the like.

[0005]

Means for Solving the Problems The present inventor has made intensive studies to solve this problem. As a result, they found that an extract from saffron had a desired tyrosinase activity promoting effect, and completed the present invention.

That is, the present invention provides a tyrosinase activity promoter comprising a saffron extract as an active ingredient. This tyrosinase activity promoter can be used as a gray hair inhibitor or the like.

[0007]

Embodiments of the present invention will be described below. The extract of saffron used as an active ingredient of the tyrosinase activity promoter of the present invention is an extract from saffron (Crocus sativus L.) belonging to the saffron genus Iridaceae, and contains bulbs, roots, leaves, stems, flowers, Styles and whole plants can be used as raw materials of this extract, and it is particularly preferable to use saffron extract using styles as this raw material as an active ingredient of the tyrosinase activity promoter of the present invention.

[0008] The saffron extract can be obtained by a method generally used for extracting a plant-derived extract. That is, it can be obtained by subjecting the above-mentioned raw material as it is or after drying it as necessary, and then subjecting it to solvent extraction as it is or pulverized. The solvent used at this time can be selected from commonly used solvents used when extracting plant components from plants, and is not particularly limited.

For example, hot water or water; lower alcohols such as methanol, ethanol, isopropanol and n-butanol; polyhydric alcohols such as propylene glycol and 1,3-butylene glycol; hydrates of these alcohols; n-hexane And a hydrocarbon solvent such as toluene, etc., but it is preferable to use a lower alcohol such as methanol or ethanol as the extraction solvent.
When using these lower alcohols as the extraction solvent,
The obtained extract can be directly blended as an active ingredient of the tyrosinase activity promoter of the present invention. However, the extraction solvent can be once distilled off and, if necessary, blended after drying.

[0010] In addition to blending the saffron extract obtained through such a step as an active ingredient of the tyrosinase activity promoter of the present invention, it is of course possible to blend a commercially available saffron extract [ Saffron extract BG (Maruzen Pharmaceutical), Saffron tincture (Ogi Pharmaceutical), Harbex saffron extract (Koei Kogyo), etc.].

The amount of such a saffron extract in the tyrosinase activity promoter of the present invention should be appropriately selected according to the specific embodiment of the tyrosinase activity promoter of the present invention, and is not particularly limited. . For example, when the tyrosinase activity promoter of the present invention is used as a “white hair inhibitor”, the saffron extract is generally blended in the range of 0.001% by weight or more and 10.0% by weight or less of the whole preparation. It is preferable to add 005% by weight or more and 5.0% by weight or less. If the amount is less than 0.001% by weight of the preparation, the desired effect of preventing gray hair is not sufficiently exhibited, and if the amount exceeds 10.0% by weight, a formulation problem is caused, which is not preferable.

[0012] Thus, by blending the saffron extract, the tyrosinase activity promoter of the present invention having the desired excellent tyrosinase activity promoting effect is provided. The tyrosinase activity promoter of the present invention can be used as an agent of various aspects that exhibits a desired effect by promoting tyrosinase activity.

[0013] As a typical embodiment of these, as described above, a "white hair preventing agent" is used to prevent or suppress the occurrence of gray hair.
Can be mentioned. This white hair inhibitor can exert an excellent white hair preventing effect.

The tyrosinase activity enhancer of the present invention comprises a general base component and a medicinal component which can be blended in a normal external preparation for the skin (including cosmetics for hair), depending on the mode of the specific agent. It can be blended as long as the desired effect in the embodiment is not impaired.

Specifically, diluents, surfactants, higher alcohols, oils, humectants, thickeners, solvents, usability improvers, preservatives, antioxidants, sequestering agents, ultraviolet protective agents, It can be formulated by appropriately using powder components, various chemicals, coloring agents, fragrances and the like according to the intended dosage form and form.

As the diluent, for example, water, ethanol,
Examples include isopropyl alcohol and glycols. Examples of the anionic surfactant include alkyl benzene sulfonate, polyoxyalkylene alkyl sulfate, alkyl sulfate, olefin sulfonate, alkyl phosphate, polyoxyalkylene alkyl ether phosphate, dialkyl sulfosuccinate. , Fatty acid salts and the like. Examples of the nonionic surfactant include polyoxyethylene alkyl ether,
Polyoxyethylene fatty acid ester, polyhydric alcohol fatty acid partial ester, polyoxyethylene polyhydric alcohol fatty acid partial ester, polyglycerin fatty acid ester,
Polyoxyethylene hydrogenated castor oil derivatives, fatty acid diethanolamide, and the like. Examples of the cationic surfactant include a tertiary aliphatic amine salt, an alkyltrimethylammonium halide, and a dialkyldimethylammonium halide. Examples of the amphoteric surfactant include amidobetaine type, imidazolinium betaine type, and sulfobetaine type amphoteric surfactants.

Examples of the higher alcohol include cetyl alcohol, stearyl alcohol, behenyl alcohol and the like. Examples of the oil component include higher fatty acids, solid paraffin, liquid paraffin, silicone oil, high molecular silicone and its derivatives, squalane, petrolatum, and ester oil. Examples of humectants include glycerin. Examples thereof include propylene glycol, 1,3-butylene glycol, dipropylene glycol, and sorbitol. Examples of the thickener include methylcellulose, hydroxyethylcellulose, carrageenan, carboxymethylcellulose, and cationized cellulose. Examples of the powder component include powder resins such as silica, nylon powder, and polyethylene powder.

Examples of various drugs include plant extracts such as assembly extracts and carrot extracts; vitamin B ₆
Vitamins such as vitamin E and its derivatives, biotin;
Nicotinic acid esters such as pantothenic acid and its derivatives, glycyrrhizic acid and its derivatives, benzyl nicotinate; amino acids such as serine and methionine; cepharanthin, capronium chloride, minoxidil, nicorandil,
Female hormones such as acetylcholine derivatives, cyclosporins, and estradiol.

Further, for example, antibacterial agents such as hinokitiol, hexachlorophen, benzalkonium chloride, undecylenic acid, trichlorocarbanilide, and bithionol; cooling agents such as menthol; salicylic acid, zinc and its derivatives, lactic acid and its alkyl esters, and the like. An active substance, an organic acid such as citric acid and the like can also be incorporated into the tyrosinase activity promoter of the present invention (these various drugs can be used as a mixture in which each is combined as necessary, of course). is there).

The dosage form of the tyrosinase activity promoter of the present invention is
Any kind of liquid, emulsion, ointment, etc. that can be applied to the skin or scalp may be used. In general, emollient lotion, emollient cream, moisture gel, lotion, hair tonic, hair liquid, sculpt treatment, hair cream, Aerosol mousse,
It can take the form of an aerosol spray, a hair gel, a spray mousse or the like. The specific form of the tyrosinase activity promoter of the present invention will be described later.

[0021]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples and the like, but the technical scope of the present invention should not be interpreted as being limited to these examples. Hereinafter, unless otherwise specified, the compounding amount is shown in% by weight.

[Preparation Example] Preparation of Saffron Extract 500 g of a saffron column was immersed in water at room temperature for one week, and the water in the extract was evaporated to obtain 8.6 g of a saffron extract. In the test examples and formulation examples described below, this extract was used as “saffron extract”.

[Test Example] Effect confirmation test The saffron extract obtained as described above was dissolved in dimethyl sulfoxide (DMSO) at 1%, and the solution was diluted to adjust the concentration. The following tests were performed using

(1) Cell culture method B16 melanoma cultured cells derived from a mouse were used. 3%
The cells were cultured in an Eagle MEM medium containing fetal bovine serum (FBS) at 37 ° C. in a CO ₂ incubator (5% CO ₂ ). After 24 hours of culturing, a test sample solution is added to a final concentration of 10 ^-3 to 10 ^-5 % by weight, and culturing is continued for further 3 days, and visual determination of the amount of melanin production and promotion of tyrosinase activity by the following method. The effect was measured.

(2) Judgment of visual perception of the amount of melanin Place a diffusion plate under the lid of a well plate, observe the amount of melanin in the cells with an inverted microscope, and in the case of a sample without the saffron extract (reference) And compared. Table 1 shows the results.

[0026]

[Table 1]

<Judgment Criteria> +: Black (melanin amount) ±: Slightly black (melanin amount) −: Standard (melanin amount)

From these results, it was revealed that the saffron extract visually promotes the production of melanin when its concentration is 10 ^-3 % by weight.

(3) Measurement of Tyrosinase Activity Before the measurement, the medium in the well was removed, and the well was washed twice with 100 μl of PBS. 45 μl of 1% Triton in each well
It was added to PBS containing X (trade name: manufactured by Rohm and Haas). The plate was vibrated for 1 minute to carefully destroy the cell membrane, and the absorbance at 475 nm was measured with a microplate reader, and this was taken as the absorbance at 0 minutes. Then, quickly 5 μl of 10 mM L-Dop
a. Add the solution and transfer to a 37 ° C. incubator,
The reaction was performed for 60 minutes.

After the reaction, the plate was shaken for 1 minute to
The absorbance at 0 minute (475 nm) was measured. The increase in the absorbance difference of the saffron extract relative to the absorbance difference between the time of 0 minute and the time of 60 minutes in the case of the sample (control) to which the saffron extract was not added was calculated as the promotion rate of tyrosinase activity (%).
And Table 2 shows the results.

[0031]

[Table 2]

Table 2 shows that the saffron extract promotes tyrosinase activity and is effective, for example, in preventing gray hair.

(4) Investigation on the effect of preventing human gray hair by cumulative application <Test method> As a test subject, each sample had 40 gray hairs.
Saffron extract [Lotion containing these derivatives and lotion without derivatives (control)] twice a day (morning, night) for 40 men and women between the ages of 60 to 60 by the half-head method The scalp was used separately, and the state of the application site was compared before and after the test, and the effect of preventing gray hair was examined. The ratio of preventing the generation of white hair while applying this lotion every day was determined by counting the number of white hairs per 1000 hairs at the top of the head before and 4 months after the start of application.

<Formulation of lotion> (Blending components) Blending amount (% by weight) Saffron extract 0.5 Polyvinylpyrrolidone / vinyl acetate copolymer 5.0 Preservatives proper amount Fragrance proper amount 0.5 Silicone derivative 0.5 Glycerin 2.0

Production Method A saffron extract, a polyvinylpyrrolidone / vinyl acetate copolymer, a preservative and a fragrance were added to ethyl alcohol and uniformly dissolved. The aqueous phase (purified water, silicone derivative, glycerin) previously dissolved therein was added thereto and dissolved.

<Judgment Criteria> ++ (Excellent effect): 50% or more of subjects whose number after application is less than 80% of the number of gray hair before application + (effective): Number of white hair before application On the other hand, 50% or more of the subjects had less than 90% of the number after application ± (slightly effective): 50% or more of the subjects had less than 100% of the number of gray hairs before the start of application-(ineffective) : Less than 50% of test subjects have less than 100% of the number of gray hairs before the start of application

The results of this test are shown in Table 3.

[Table 3]

From these results, it can be seen that in the saffron extract,
It became clear that the effect of preventing gray hair was observed.

Hereinafter, other formulation examples of the tyrosinase activity promoter of the present invention will be described as examples. In addition, when the tyrosinase activity promoter of the present invention of these examples was examined for the above-mentioned human gray hair prevention effect, all of the examples were evaluated as "effective" or "significantly effective".

Example 1 Hair Tonic (Blending Components) Blending Amount (% by Weight) (1) Hardened Castor Oil EO (40 mol) Adduct 2.0 (2) Saffron Extract 1.0 (3) 95% Ethanol 70.0 (4) Appropriate amount of flavor (5) Residual amount of purified water

After adding (1), (2) and (4) to the production method (3) and dissolving with stirring, (5) was added to obtain a hair tonic.

Example 2 Hair Tonic (Blending Components) Blending Amount (% by Weight) (1) Glycerin 2.0 (2) L-Menthol 0.1 (3) Saffron Extract 0.2 (4) 95% Ethanol 60.0 (5) Appropriate amount of fragrance (6) Residual amount of purified water

After adding (1), (2), (3) and (5) to the production method (4) and dissolving with stirring, (6) was added to obtain a hair tonic.

Example 3 Hair Tonic (Blending Component) Blending Amount (% by Weight) (1) Polyethylene Glycol 200 2.0 (2) L-Menthol 0.2 (3) Saffron Extract 0.01 (4) 95% ethanol 50.0 (5) Appropriate amount of perfume (6) Residual amount of purified water

(1), (2), (4) and (5) were added to the production method (3) and dissolved by stirring. Then, (6) was added to obtain a hair tonic.

Example 4 Hair Liquid (Components) Component (% by weight) (1) Polyoxypropyl butyl ether (40PO) 15.0 (2) Polyoxypropyl butyl ether phosphoric acid (40PO) 15.0 (3 ) Saffron extract 0.001 (4) 1,3-butylene glycol 5.0 (5) 95% ethanol 50.0 (6) Appropriate amount of flavor (7) Appropriate amount of pigment and edetic acid (8) Residual amount of purified water It was prepared in the same manner as in Production Example 1.

Example 5 Scalp Treatment (Components) Component (% by weight) (1) 1,3-propylene glycol 0.5 (2) Pentaerythritol tetra-2-ethylhexanate 1.2 (3) 95% ethanol 60.0 (4) saffron extract 1.0 (5) assembly extract 1.0 (6) perfume Appropriate amount (7) DME / LPG (95/5) as prepared as residual quantity preparation example 1 did.

Example 6 Hair Cream (Blending Components) Blending Amount (% by Weight) Phase A (1) Liquid Paraffin 5.0 (2) Cetostearyl Alcohol 5.5 (3) Vaseline 5.5 (4) Glyceryl Monostearate 3.0 (5) EO (20 mole addition) -2-octyldodecyl ether 3.0 (6) Vitamin E acetate 0.05 (7) Propyl paraben 0.3 (8) Fragrance 0.05 B phase (9) Saffron extract 0.5 (10) Glycerin 7.0 (11) Dipropylene glycol 20.0 (12) Polyethylene glycol 4000 5.0 (13) Sodium hexametaphosphate 0.005 (14) Remaining purified water

Method A The phase A was heated and melted and mixed, and the hot melt mixture of the phase B was added thereto and emulsified with a homomixer to obtain a hair cream.

Example 7 Hair Gel (Blending Component) Blending Amount (% by Weight) (1) Carboxyvinyl Polymer 0.7 (2) Polyvinylpyrrolidone 2.0 (3) Glycerin 4.0 (4) Saffron Extract 0 0.01 (5) sodium hydroxide qs (6) ethyl alcohol 20.0 (7) polyoxyethylene octyl dodecyl ether qs (8) flavor, edetic acid qs (9) purified water balance

The production method (1) was dispersed in (3) and a part of purified water. The other components were dissolved in the remaining purified water, and this was added to the above dispersion with stirring to obtain a hair gel.

Example 8 Hair Gel (Blending Components) Blending Amount (% by weight) (1) Carboxyvinyl polymer 0.5 (2) Glycerin 50.0 (3) Sodium hydroxide suitable amount (4) Ethyl alcohol 0 (5) saffron extract 0.001 (6) polyoxyethylene octyl dodecyl ether q.s. (8) perfume, edetate q.s. (9) was prepared as purified water Balance preparation example 7.

Example 9 Hair spray (stock solution formulation) Compounding amount (% by weight) (1) Acrylic resin alkanolamine salt (50%) 7.0 (2) Cetyl alcohol 0.1 (3) Silicone oil (methyl) (Phenylpolysiloxane) 0.3 (4) Ethyl alcohol 92.6 (5) Saffron extract 0.1 (6) Appropriate amount of perfume (filling formulation) (7) Stock solution 50.0 (8) Dimethyl ether 45.0 (9) ) LPG 5.0

The production methods (1), (2) and (3) were uniformly emulsified by a homomixer.
This was added to a solution of other components to prepare a stock solution. For filling, a can was filled with a stock solution, and after mounting a valve, gas was filled to obtain a hair spray.

[0055]

According to the present invention, a tyrosinase activity promoter excellent in efficacy and safety is provided. The tyrosinase activity promoter of the present invention is useful, for example, as a gray hair inhibitor.

Continued on the front page (72) Inventor Tsutomu Soma 2-12-1 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa Prefecture Inside of Shiseido 2nd Research Center Co., Ltd. (72) Yoshiki Moriya 1050 Nippa-cho, Kohoku-ku, Yokohama-shi, Kanagawa (72) Inventor Norio Kojima Shiseido Co., Ltd. 7-5-5 Ginza, Chuo-ku, Tokyo

Claims (2)

[Claims] 1. A tyrosinase activity promoter comprising a saffron extract as an active ingredient. 2. The tyrosinase activity promoter according to claim 1, wherein the tyrosinase activity promoter is a gray hair inhibitor.