JP3242016B2 - Hair restoration cosmetics - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hair nourishing cosmetic having an excellent hair-growth effect, a hair loss-preventing effect, and an anti-dandruff effect.

[0002]

2. Description of the Related Art Conventionally, hair restoration cosmetics containing a scalp blood circulation promoting substance such as pepper tincture, assembly extract, Korean ginseng extract, nicotinic acid, methyl nicotinate and the like have been known. well known. However, these blood circulation promoting substances are disadvantageous in that they are highly irritating to the skin, have a limited amount, and have a short duration of blood circulation promotion. In addition, there is a problem that the hair nutrient component at a low concentration has a small amount of permeation into the skin and the effect is not sufficiently exhibited by itself. No substance has been found that is effective enough to exhibit effects such as hair growth, hair loss prevention and dandruff.

[0003] In recent years, the involvement of hormones in hair growth has been suggested. That, in the hair follicle, including the hair papilla, male hormone (testosterone) is, 5.alpha. by-reductase (delta ^4-3-keto steroid 5.alpha. oxidoreductase), is activated to active androgen (dihydrotestosterone) You. Furthermore, it binds to receptors and is taken up by the cell nucleus, transmitting information at the DNA level. This information controls the synthesis of enzymes involved in keratin synthesis, suppresses keratin synthesis in hair, reduces hair growth, and ultimately promotes hair loss. Therefore, in developing hair restorer,
Studies on inhibitors of the activity of 5α-reductase, an androgen-activating enzyme in the scalp and scalp, have attracted attention, but male pattern baldness is associated with poor circulation, decreased activity of hair matrix cells, and enlarged sebaceous glands. It is presumed that phenomena such as fibrosis of the scalp and the like are complicatedly involved. Therefore, at present, simply using an anti-androgen agent or the like as a hair-growth agent does not bring about the hair-growth effect.

As means for solving the above-mentioned problems, a hair growth agent containing a certain kind of carboxybetaine disclosed in JP-A-5-139936, and an acidic mucopolysaccharide and a hop extract described in JP-A-5-170625 are disclosed. Hair growth / hair restoration containing prickly pear cactus extract in JP-A-5-170627, JP-A-5-170627
-Hair growth and hair growth cosmetic containing sodium perborate and / or sodium percarbonate in JP-A-33627
Numerous hair-growing and hair-growing agents have been proposed, including a hair-growing agent containing a yoquinin extract in JP-A-8-12531, which promotes peripheral blood flow and activates hair matrix cells. Even if the substance is used alone, no remarkable hair-growth effect has been found, and the composition has not yet yielded a satisfactory result, and there is room for improvement in the hair-growth effect and the hair loss-preventing effect. there were.

[0005]

Means for Solving the Problems In view of such circumstances, the present inventors have proposed a substance having an action of improving androgen metabolism of the scalp, promoting peripheral blood flow and activating hair matrix cells.
As a result of intensive studies, curcumin, demethoxycurcumin, bisde, etc., obtained by fractionating from an extract of autumn turmeric (Curcuma longa) and / or spring turmeric (Curcuma aromatica), which has the ability to inhibit 5α-reductase activity. At least one or more substances selected from the group consisting of methoxycurcumin, and assembly extract, Korean ginseng extract, Duke extract, Pepper tincture, diisopropylamine dichloroacetate, γ-aminobutyric acid derivative,
Hair growth cosmetics containing at least one substance selected from the group consisting of hinokitiol, vitamin E derivatives, pantothenic acid derivatives, nicotinic acid derivatives, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, and tanzine extract, synergistic effect of each component As a result, the present inventors have found that excellent hair-growth and hair-growth effects, which are the objects of the present invention, have been developed, and have completed the present invention.

[0006] That is, the present invention provides a nutrient containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin represented by the following general formula (1) obtained by fractionating from an extract of autumn turmeric and / or spring turmeric. For hair cosmetics
And curcumin with Duke Extract or Tanjin Eki
Hair nourishing cosmetic, demethokiki characterized by blending
Siccurcumin, assembly extract, Korean carrot
, Duke extract, Pepper tincture, Diisopropyl
Luamine dichloroacetate, γ-aminobutyric acid, hinoki
Thiol, vitamin E nicotinate, pantothenic acid cal
Cium, nicotinic acid, methyl nicotinate, glycyrrhichi
Dipotassium, glycyrrhetinic acid and tanzine extract
At least one substance selected from the group consisting of
Bisdemethoxy, a hair nourishing cosmetic characterized by being blended
Curcumin and Duke Extract or Tanjin Extract
Hair restoration cosmetics characterized by being blended.

[0007]

Embedded image (In the above general formula, R ₁ is OCH ₃ , R ₂ is OCH _3
3 is curcumin, wherein R ₁ is OCH ₃ ,
R ₂ is a H is a demethoxycurcumin,
When R ₁ is H and R ₂ is H, bisdemethoxycurcumin is used. )

[0008]

DETAILED DESCRIPTION OF THE INVENTION Autumn turmeric is a ginger family (Zingri).
perennial plant belonging to C. berance), the rhizome of which is used as a hemostatic agent, flavor, curry powder, yellow dye, and a remedy for liver diseases. In addition, rhizome of spring turmeric of the same genus plant,
Like autumn turmeric, it is used for the above purposes. The turmeric extract used in the present invention is obtained by removing the rhizomes of autumn turmeric and / or spring turmeric from lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, and butanol, or hydrated lower alcohols, propylene glycol, and 1,3-butylene. Polyhydric alcohols such as glycols or water-containing polyhydric alcohols, acetone, methyl ethyl ketone, ethyl acetate, chloroform, n
-It is obtained by using an extraction method with an organic solvent such as hexane alone or in combination. Here, the turmeric extract refers to a turmeric extract which contains a small amount of the extraction solvent, and a dried product of the turmeric extract which is completely evaporated. Then, curcumin obtained by fractionation from the turmeric extract using column chromatography or the like, demethoxycurcumin, a crude fraction containing bisdemethoxycurcumin as a main component, or a crude fraction is recrystallized with a solvent. The purified fraction can be used in the present invention.

The specific amounts of curcumin, demethoxycurcumin and bisdemethoxycurcumin, which are contained in the turmeric extract and are not the main components in the turmeric extract, are determined according to the present invention. It is preferably 0.01 to 10.0% by weight (hereinafter abbreviated as wt%), more preferably 0.1% by weight, based on the total weight of the composition for hair restoration.
It is from 01% to 8.0% by weight. 0.01wt%
If the amount is less than the above, the intended effect of the present invention may not be sufficient. On the other hand, if the amount exceeds 10.0% by weight, the improvement of the effect corresponding to the increase may not be expected.

[0010] γ- amino butyric acid for use in the present invention is Ru known substances der.

Vitamin E used in the present inventionNicotinate
Is a known substanceYou.

[0012] calcium pantothenate used in the present invention Ru known substances der.

The nicotinic acid and nicotinic acid used in the present invention
Chill Ru Der known compounds.

The dicaliu glycyrrhizinate used in the present invention
Beam is Ru Der known compounds.

[0015] glycyrrhetinic acid used in the present invention is Ru known substances der.

The tanzine extract used in the present invention is obtained by drying the roots of tanjin (Salvia miltiorrhiza), a perennial plant belonging to the Labiatae family, by using a method described in JP-A-3-123720 by using a hydroalcohol or the like. Can be obtained by extraction.

[0017] Then, assembly extract according to the present invention, ginseng extract, Duke extract, capsicum tincture, diisopropylamine dichloroacetate, .gamma.-amino butyric acid, hinokitiol, vitamin E nicotinate,
Calcium pantothenate, nicotinic acid , methyl nicotinate
Le, glycyrrhizin dipotassium, glycyrrhetinic acid,
As a result of examining the range showing the hair-growth effect and the hair-leakage prevention effect, which are the objects of the present invention, the tanzine extract is preferably used in an amount of 0.001 to 20.0% by weight, more preferably 0.1 to 20.0% by weight, based on the total amount of the hair restoration cosmetic. 01 to 5.0 wt%.

The hair nourishing cosmetic composition of the present invention can be manufactured in a usual manner into a dosage form such as hair tonic, hair lotion, hair mousse, etc., which is directly applied to the scalp.
The hair restoration cosmetic of the present invention contains, as other components, dyes, fragrances, bactericides, preservatives, keratolytic agents, antiandrogens, antioxidants, and the like, as long as the object of the present invention is achieved. Can be blended.

Next, specific examples of the production of each of the fractions of glucumin, demethoxycurcumin, and bisdemethoxycurcumin, a method for confirming the chemical structure of each of the obtained fractions, and each fraction The content of the product will be described. Further, examples of hair-growth cosmetics containing the above components will be described.

[0020]

【Example】

(1) Production example of turmeric extract Extract 2 kg of autumn and spring turmeric mixed powder (imported from India) is accurately weighed, 10 times the amount of ethanol is added, leached for 4 hours with occasional shaking, and then filtered. did. This operation was repeated twice, and the filtrate was collected, concentrated to dryness under reduced pressure, and 129.40 g of a dried turmeric extract (yield: 6.47).
wt%).

(2) Preparation Example of Fractions of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin 8.9 g of the above dried turmeric extract was dried with silica gel column chromatography (Silica Ge, Merck).
160, 70-230 mesh, 8 cmI. D. ×
60 cm) and chloroform-methanol (40:
1 → 30: 1 → 20: 1 → 10: 1)
r. 1 to Fr. 6 fractions. Fr. 3 (2.4 g)
And silica gel column chromatography (Si
licaGel60, 70-230 mesh, 5cm
I. D. × 5 cm) and chloroform-methanol (50: 1 → 40: 1 → 30: 1 → 20: 1 → 10:
1) multi-stage elution, I to Fr. Fractionated into IV.
Fr. I (10 g) was recrystallized from ethyl acetate to obtain 270 mg of curcumin. II (0.4 g) and F
r. III (0.6 g) was recrystallized from chloroform-acetonitrile to obtain 180 mg of demethoxycurcumin and 270 mg of bisdemethoxycurcumin. The obtained compound was measured for ¹ H- and ¹³ C-NMR spectra, melting point, specific rotation, etc., and the literature values [Chem. Pharm.
Bull. 33. 1499-1502 (1985)] to confirm the structure and use it as a standard sample. .

(3) Determination of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin in Cured Extract of Autumn and Spring Turmeric Extract Approximately 50 mg of the dried product of turmeric extract was precisely weighed, and methanol was added to determine the total amount. To 50 ml. Further, accurately take 10 ml of the solution, add methanol to make the total volume exactly 50 ml, and use it as a sample solution. On the other hand, about 50 mg of curcumin, demethoxycurcumin and bisdemethoxycurcumin standard samples are precisely weighed, methanol is added to make the total volume exactly 50 ml, 2 ml thereof is accurately taken, and methanol is added to make the total volume exactly 100 ml. ,
Use each standard solution. The sample solution and the standard solution are injected into high performance liquid chromatography (HPLC), and the content is calculated from the peak heights of the obtained chromatogram using the following formula.

Curcumin, demethoxycurcumin and bisdemethoxycurcumin content (wt%) in the dried product of autumn and spring turmeric extracts = [weighed amount of standard sample (mg) /
Extracted amount of turmeric extract dry matter (mg)] x [sample peak height / standard sample peak height] x 10 HPLC conditions Column: Wakosil 115C18HG (4.6 mm ID x 250 mm) (manufactured by Wako Pure Chemical Industries, Ltd.) Phase: 50 wt% acetonitrile solution (0.1 wt%
Flow rate: 1.0 ml / min Column temperature: 40 ° C. Measurement wavelength: 420 nm Sample injection volume: 20 μl

As an example, Table 1 shows the results of measuring the components of autumn turmeric.

[0025]

[Table 1]

Hereinafter, the hair-growth cosmetic of the present invention will be described in detail based on Examples and Comparative Examples.

The 5α-reductase activity inhibition test, mouse hair growth promoting effect test method, human scalp hair growth promoting effect test method and practical test methods described in the Examples are shown below.

(1) Inhibition test of 5α-reductase activity (a) Enzyme source: SD rats (10-week-old, male) were sacrificed, the prostate was removed, and 0.3 volume of 0.25 M sucrose was added. 1M HEPES buffer (pH
Homogenized in 7.2). The obtained homogenate was subjected to centrifugation at 3000 rpm for 10 minutes to separate a nuclear fraction, and resuspended in the same volume of the above Hepes buffer to obtain an enzyme solution.

(B) Assay method: The microradioassay method was used for measuring 5α-reductase activity. Specifically, 1.5 nmol of (4- ¹⁴ C) -testosterone was added to 2 μl of a sample ethanol solution, and after evaporating the solvent, 10 μl of 50 mM dihydronicotinamide adenine dinucleotide phosphate (NADPH) and 60 μl of the above Hepes buffer were added. The solution was added, stirred, and pre-incubated at 37 ° C. for 5 minutes. The reaction was started by adding 30 μl of the enzyme solution. After incubating at 37 ° C for 60 minutes, the reaction was stopped by adding 0.4 ml of a chloroform: methanol (1: 2) solution, and the reaction was stopped at 3000 r.
After centrifugation at pm for 10 minutes, a sample for analysis was obtained.

(C) Analytical method: 50 μl of each analytical sample was subjected to the following two-step thin-layer chromatography (TLC;
Whatman LK6DF). According to this system, references [Clin. Endocrinol., MJ Thornton, I. Laing, K. Hamad
a, AGMessenger and VARandall, 39, 633-639, 199
As shown in [3], it is possible to analyze all androgen metabolites. 1) Dichloromethane: diethyl ether (70:10) 2) Chloroform: diethyl ether (90:10) After air-drying the TLC plate, use a radiochromatographic analyzer (Aloka JT601) to convert testosterone to 5α-dihydrotestosterone with 5α-reductase. Was measured. The 5α-reductase activity inhibition rate (%) was determined by the following formula and used as an index of the 5α-reductase activity inhibition ability.

[0031]

(Equation 1)

(2) Mouse Hair Growth Promotion Effect Test Method The back skin (2 cm × 4 cm) of a C3H mouse (8 weeks old, male, average weight 35 g) was cut with an electric clipper and a shaver, and from the next day, Examples and Comparative Examples were used. Each sample was applied twice a morning and evening twice to the skin of the test portion at 0.2 ml per animal for two weeks. A group of 10 animals was used for one sample. On the 14th day from the start of application, the skin of the test part of each sample was photographed with a video camera, the areas of the shaved part and the hair growth part were measured with an image analyzer, and the hair growth rate (%) was calculated by the following equation. . Hair growth rate (%) = (Area of hair growth part) / (Area of shaved part)
× 100 The hair growth effect was determined by comparing the average value of the hair growth rate of each group in the Examples or Comparative Examples by the average value of the control group (no application) as the degree of mouse hair growth promotion.

(3) Human scalp hair growth-promoting effect test method The hair at 5 cm above the ears of the heads of 10 test subjects with male pattern baldness was circularly shaped into 1 cm in diameter at two places on the left and right. Approximately 3 ml of each sample of Example and Comparative Example was applied to the left side of the test site twice daily in the morning and evening, and compared with the untreated right side. The effect was determined on the 28th day after the start of the test.
Twenty hairs at each of the left and right test sites were shaved, and the degree of promotion of human hair growth was evaluated using the value obtained by the following equation. Human hair growth promotion degree = (B) / (A) (A): Average value of length of 20 right-hand (untreated) hairs (B): Left-hand (coated with samples of Examples and Comparative Examples) 2
Average length of 0 lines

(4) Practical test method The effect of applying the composition to the heads of 20 test subjects who are male pattern baldness patients twice daily in the morning and evening for 6 consecutive months was evaluated. The test results show that for each item of hair growth effect, hair loss prevention effect, and dandruff prevention effect, “hair has become bristle or hair has increased,” “hair loss has decreased,” and “hair loss has decreased. And the number of respondents.

Examples 1 to 18 and Comparative Examples 1 to 19 (oily hair tonics) As shown in Tables 3 and 4 below, various hair growth promoting substances were blended in each of the oily compositions as shown in Tables 3 and 4 below. A hair tonic was prepared, and the tests (2), (3), and (4) were performed.
Was carried out. (B) Composition

[0036]

[Table 2]

(B) Preparation method In component (B) of Table 2 above, assembly extract, Korean ginseng extract, Duke extract, diisopropylamine dichloroacetate, γ-aminobutyric acid derivative, hinokitiol, vitamin E derivative, pantothenic acid derivative, nicotine The acid derivative, glycyrrhizic acid derivative, glycyrrhetinic acid derivative and the like are dissolved in the component (A), while red pepper tincture, turmeric extract, curcumin, demethoxycurcumin, bisdemethoxycurcumin, tangdin extract and the like are dissolved in the component (C). After the components (A) and (C) were uniformly dissolved, the components (A) and (C) were mixed, stirred and dispersed, and then filled in a container. At the time of use, the contents were uniformly shaken and used. In addition, the tanzine extract is obtained by adding 30 g of crushed dry root of tanzine to 90% ethanol containing water (200 m
After extraction under reflux in l), concentration under reduced pressure was carried out to obtain a dried residue 3.7.
A wt% tanzine extract (102 ml) was used.

(C) Characteristics Tables 3 and 4 show the results of various tests conducted on each oily hair tonic. In addition, the results of the above (1) 5α-reductase activity inhibition test were also described.

[0039]

[Table 3]

[0040]

[Table 4]

As shown in Table 3, Examples 1 to 18 which are hair-growth cosmetics according to the present invention are Comparative Examples 1 to 19 shown in Table 4.
Shows a higher hair growth promoting effect, and also shows a higher value due to a synergistic effect in the 5α-reductase activity inhibitory effect,
The object of the present invention can be achieved. In addition, in the case where the hair restoration cosmetics of any of the examples were used, inflammation and other symptoms considered to be side effects did not occur in mice and humans, and the hair restoration cosmetics according to the present invention had excellent safety. Was evident.

[0042]

Industrial Applicability As described above, the present invention provides a hair growth cosmetic which has excellent effects such as hair growth, hair loss prevention and dandruff, has an ability to inhibit 5α-reductase activity, and has low skin irritation. It is clear that.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-4-95032 (JP, A) JP-A-7-278003 (JP, A) JP-A-3-188013 (JP, A) JP-A 8- 48616 (JP, A) JP-A-10-139639 (JP, A) JP-A-7-238037 (JP, A) US Patent 5,554,608 (US, A) (58) Fields investigated (Int. Cl. ⁷ , DB) Name) A61K 7/06-7/135 CA (STN)

Claims (3)

(57) [Claims] 1. Curcumin obtained by fractionation from an extract of autumn turmeric (Curcuma longa) and / or spring turmeric (Curcumaaromatica), and Duke extract or tanzine
Hair restoration cosmetics characterized by incorporating an extract . 2. Demethoxycurcumin obtained by fractionation from an extract of autumn turmeric (Curcuma longa) and / or an extract of spring turmeric (Curcumaaromatica) ;
Korean carrot extract, Duke extract, Pepper citrus
G, diisopropylamine dichloroacetate, γ-a
Minobutyric acid, hinokitiol, vitamin E nicotinate,
Calcium pantothenate, nicotinic acid, methyl nicotinate
Le, dipotassium glycyrrhizinate, hair tonic cosmetics, which comprises blending at least one or more materials selected from the group consisting of glycyrrhetinic acid及<br/> beauty Tan Jin extract. 3. Turmeric (Curcuma longa) and / or
Fractionated from extract of spring turmeric (Curcumaaromatica)
Bisdemethoxycurcumin obtained with
And tanzine extract
Hair cosmetics.