JP3131105B2 - Hair restoration / hair restoration - 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 growth / hair restoration material, and more particularly, to a hair growth / growth material excellent in hair shaft elongation promoting effect and hair growth effect.

[0002]

2. Description of the Related Art
Synthetic drugs or natural product extracts having various effects are used in pharmaceuticals or cosmeceuticals for the purpose of hair growth and hair growth, but none of these can provide sufficient effects with the addition of small amounts. On the other hand, a large amount of the natural product extract gives an unpleasant irritating feeling at the site of application when added in a large amount, and when used continuously, dermatitis occurs or the extract cannot be blended in a large amount due to the color and smell of the extract Some of them have such a drawback.

[0003] Further, the above-mentioned hair growth and hair growth products do not directly act on the differentiation and proliferation of the hair matrix, but rely on an indirect action through normalization of the condition of the scalp, Enough hair nourishment for human hair
It did not show a hair growth effect.

[0004] Therefore, by directly acting on the differentiation and proliferation of hair mother cells, excellent hair-growth and hair-growth effects and an effect of preventing hair loss are exhibited, and the hair-growth and hair-growth are highly safe for a long period of time.
The development of hair growth materials has been desired.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies in view of the above circumstances, and as a result, the flavanol compound represented by the following general formula (1) directly acts on the differentiation and proliferation of hair mother cells. The present inventors have found that the present invention has excellent hair-growth and hair-growth effects and has high safety for a long period of time, and has completed the present invention.

That is, the present invention provides a compound represented by the general formula (1)

[0007]

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(Wherein R ¹ represents an alkyl group, R ² and R ³ represent a hydrogen atom, an alkyl group which may have a substituent, an alkoxyl group which may have a substituent, a hydroxyl group, (Showing a cyano group or a halogen atom).

[0009] In the above formula (1), which represents the flavanonol derivative (1) used as an active ingredient in the hair restoration and hair restoration of the present invention, the alkyl group represented by R ¹ may be a straight-chain or a straight-chain having 1 to 12 carbon atoms. A branched alkyl group is preferable, a linear or branched alkyl group having 1 to 8 carbon atoms is more preferable, a linear or branched alkyl group having 1 to 5 carbon atoms is further preferable, and a methyl group and an ethyl group are particularly preferable.

The optionally substituted alkyl group represented by R ² and R ³ includes a carbon atom which may be substituted by 1 to 3 groups selected from a halogen atom, a hydroxyl group and an amino group. include straight-chain or branched-chain alkyl group having from 1 to 12, of which 1-3 carbon atoms, which may halogen atom substituted 1-12 (more preferably C _1-8, more preferably C The linear or branched alkyl group of _1-5 ) is preferred. Examples of the alkyl group which may have a substituent include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a tert-butyl group, an n-pentyl group, and a trifluoromethyl group. And the like. Examples of the alkoxyl group which may have a substituent include an alkoxyl group having 1 to 12 carbon atoms and 1 carbon atom which may be substituted by a group selected from a hydroxyl group.
To 12 alkoxyl groups.
1 to 12 carbon atoms which may be substituted by alkoxyl to
Is preferable, and an alkoxyl group having 1 to 6 carbon atoms which may be substituted by an alkoxyl group having 1 to 6 carbon atoms is particularly preferable. Examples of the alkoxyl group which may have such a substituent include a methoxy group, an ethoxy group, and n
-A propoxy group, an isopropoxy group, an n-butoxy group,
Examples thereof include an n-pentyloxy group, a methoxymethoxy group, a 2-ethoxyethoxy group, and a 2-methoxyethoxy group. Examples of the halogen atom include a fluorine atom, a bromine atom, a chlorine atom and an iodine atom.

The flavanonol derivative (1) has a plurality of stereoisomers due to the presence of asymmetric carbon atoms at the 2- and 3-positions. In the present invention, both of these stereoisomers and mixtures thereof are used. be able to. As for the stereoisomer, the relationship between the 2-position aromatic ring and the 3-position hydroxyl group is described as a trans form or a cis form.

The flavanonol derivative (1) can be produced, for example, according to the following reaction formula.

[0013]

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[0014] (wherein, R ^2a and R ^3a represents a hydrogen atom, an optionally substituted alkyl group, optionally alkoxyl group which may have a substituent, a cyano group or a halogen atom, R ¹ Is the same as above)

That is, the benzaldehydes (3) are reacted with the o-hydroxyacylbenzenes (2) to obtain flavanones (4), which are then reacted with an oxidizing agent to give the flavanonols (1-a). Manufactured.

First, the reaction between o-hydroxyacylbenzenes (2) and benzaldehydes (3) proceeds by, for example, heating and stirring with acetic acid and pyrrolidine in an alcohol. Alternatively, the mixture may be heated and stirred in aqueous dimethylformamide in the presence of a base such as sodium hydroxide.

The reaction between the flavanones (4) and the oxidizing agent is as follows:
For example, it is preferable to carry out the reaction in an aqueous alcohol in the presence of a base such as sodium hydroxide. As the oxidizing agent, it is preferable to use a peracid such as hydrogen peroxide and perbenzoic acid.

In the general formula (1), R ² and / or R ³
Is a hydroxyl group, for example, can be produced by hydrolyzing a compound in which R ^2a and / or R ^{3a in the} above formula (1-a) is an alkoxyalkoxy group. The hydrolysis reaction proceeds, for example, by heating and stirring a methoxymethoxy group with 3N hydrochloric acid in alcohol.

The compound of the general formula (1) wherein R ² and / or R ³ is an alkoxy group can also be produced according to the above reaction formula, but a compound wherein R ² and / or R ³ is a hydroxyl group is used. It can also be produced by O-alkylation. The O-alkylation proceeds by reacting a base such as potassium carbonate and an alkyl halide in a polar solvent such as dimethylformamide.

The flavanonol derivative (1) thus obtained directly acts on the differentiation and proliferation of hair cells, has the effect of promoting hair shaft elongation, and has a strong hair-growth effect. It can be used as an active ingredient of the ingredient, and its compounding amount in the hair growth / hair restoration is preferably 0.0001 to 10% by weight, particularly preferably 0.001 to 3% by weight.

The flavanonol derivative (1) may be used alone, but for the purpose of further enhancing the hair growth effect, a blood circulation promoting agent, an antibacterial agent, a keratolytic agent, an antiseborrheic agent, a local stimulant, an anti-inflammatory agent, a moisturizing agent Agents, antiandrogens, hair follicle activators and the like. These do not act directly on the hair but have a different mechanism from the flavanolol derivative (1), so that the combined use exerts a stronger hair-growth effect. For example, blood circulation enhancers promote nutrient supply to hair matrix and transport of metabolites from hair matrix, and antimicrobial agents suppress bacterial action on scalp,
Each indirectly promotes hair growth.

Among these components, blood circulation promoters include acetylcholine, syrup extract, carrot extract, ginkgo extract, carpronium chloride, diphenhydramine hydrochloride, γ-oryzanol, circretin, cromakalim, cepharanthin, nicorandil, vitamin E, vitamin E nicotinate And the like, pinacidyl, minoxidil, phthalides, kina extract, shobu root extract, spruce extract, this drug extract, yuzu extract and the like. Among them, acetylcholine, assembly extract, carrot extract, ginkgo extract, vitamin E and its derivatives, cepharanthin, minoxidil, carpronium chloride, diphenhydramine hydrochloride, γ-oryzanol, circretin, cromakalim, cepharanthin, nicorandil, pinacidil, minoxidil, phthalides, kina extract , Shobu root extract, spruce extract,
This drug extract and yuzu extract are preferable, and particularly, assembly extract, carrot extract, ginkgo extract, vitamin E and its derivatives, cepharanthin, minoxidil, carpronium chloride, and phthalides are preferable.

Examples of the antibacterial agent include isopropylmethylphenol, benzalkonium chloride, octopirox, photosensitive dye 101, photosensitive dye 201, chlorhexidine, salicylic acid, zinc pyrithione, potassium sorbate, biosol, hinokitiol, and phenol. Examples of the topical stimulant include camphor, l-menthol, nonylate vanillylamide, tincture tincture,
Examples include Dutch mustard extract, cantaris tincture, salamander extract, peppermint oil, wasabi radish extract and the like.
Of these, octopirox, benzalkonium chloride,
Zinc pyrithione, salicylic acid and isopropylmethylphenol are preferred.

Examples of the keratolytic agent include aspirin and the like. Antiseborrheic agents include sulfur, thioxolone, banside, polysorbates, lecithin, cashew extract and the like.

Examples of the anti-inflammatory agent include azulene, guaiazulene, antihistamines (such as diphenhydramine), hydrocortisone acetate, prednisolone, ougon extract, chamomile extract, sagebrush extract, fennel extract, kyonin extract, gardenia extract, kumazasa extract, gentian extract, Free extract, hawthorn extract, birch extract, Yarrow extract,
Gentle oil extract, Tonin extract, peach leaf extract, loquat leaf extract and the like.

Examples of the humectant include hypericum, soluble collagen, glycerin, chondroitin sulfate, tuberose polysaccharide, cordyceps, trisaccharide, urea, biohyaluronic acid, hyaluronic acid, vitamin C calcium phosphate, sodium pyrrolidone carboxylate, propylene Glycol, prolonged life extract,
Barley extract, orange extract, seaweed extract, cucumber extract, burdock extract, shiitake extract, syrup extract, duke extract, loquat extract, grape leaf extract, prune extract, loofah extract, Maikai extract,
Mini Sasanishiki, lily extract, apple extract and the like can be mentioned.

Examples of the antiandrogen include ethinyl estradiol, chlormadinone acetate and the like.

As the hair follicle activator, N-acetyl-L-
Methionine, disodium adenosine triphosphate, potassium aspartate, photosensitive dye 301, pentadecanoic acid glyceride, netacanal, ethyl pantothenate, panthenol, biotin, mononitroguaiacol sodium, yeast extract, pearl protein extract, daisy extract, chik Ginseng, garlic components, placenta extract, royal jelly extract and the like.

The active ingredients other than the flavanonole derivative (1) are preferably used alone or as a mixture of two or more, and are preferably used after being dissolved in water or a solvent such as water-lower alcohol. These components are contained in the hair growth and restoration product of the present invention in an amount of 0.001 to 5 from the viewpoint of a synergistic effect with the flavanonol derivative (1) and a feeling of irritation to the scalp.
% By weight, particularly 0.01 to 3% by weight.

The dosage form of the hair-growing / hair-growing agent of the present invention is mainly composed of a liquid and is typically a lotion, but may be a cream or a gel. It is particularly preferable that the liquid preparation further contain carbon dioxide gas. Carbon dioxide gas is known to be present as CO ₂ molecules when the solution in which it is dissolved has an acidic pH, and exhibit a vasodilatory effect. Therefore,
The liquidity of the hair restorer / hair restorer of the present invention containing carbon dioxide is pH 7
Hereinafter, it is particularly preferable to adjust the pH to 4.5 to 6.5. It should be noted that the pH of the hair-growing / hair-growing agent is further increased by injecting carbon dioxide gas into the hair-growing / hair-growing material, and the final pH may be adjusted to fall within the above range. As the pH adjuster, for example, organic acids such as citric acid, tartaric acid, and lactic acid or salts thereof, or phosphoric acid or salts thereof are suitably used.

In order to incorporate carbon dioxide into the hair-growing / hair-growing agent of the present invention, other components except carbon dioxide are put into a pressure-resistant container, and high-pressure carbon dioxide is sealed therein. A method of adding a component that generates carbon dioxide gas containing carbonate and adding a pH adjusting agent to the mixture to generate carbon dioxide gas and sealing immediately, or a method of sealing by placing dry ice pellets in a container, etc. Although it is adopted, a method of sealing high-pressure carbon dioxide gas is particularly preferable.

At this time, a part of the carbon dioxide gas is dissolved and blended in the hair growth and fostering material of the present invention, and a part thereof is present as a gas in the container. In the present invention, it is important that the carbon dioxide gas is dissolved and compounded in the hair growth and hair growth material, and the compounding amount is preferably a carbon dioxide gas concentration of 60 ppm or more. Cannot be obtained. The amount of carbon dioxide gas can be adjusted by adjusting the amount of carbon dioxide gas injected (press-fitted). In general, the pressure in the vessel is 35 ° C. and 1.2 to 8 kg / cm ^2.
(Gauge pressure).

In addition to the above-mentioned components, the hair-growing / hair-growing agent of the present invention may contain, if necessary, an oily base, a gelling agent, and various oils used in ordinary cosmetics as long as the effects of the present invention are not impaired. Emulsifiers, fragrances, antioxidants such as parahydroxybenzoic acid esters, and coloring agents such as dyes can be added and blended.

The hair-growing / hair-growing agent of the present invention can be produced by subjecting the above essential components and optional components to operations such as mixing according to a conventional method.

[0035]

EFFECT OF THE INVENTION The hair-growing / hair-growing agent of the present invention has excellent hair-growth and
It has a hair growth and hair loss prevention effect and has high safety for a long period of time.

[0036]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Synthesis Example 1 trans-3,4'-dimethylflavanonol: 2'-hydroxypropiophenone (15.0) under a nitrogen atmosphere
g, 0.10 mol), 4-methylbenzaldehyde (1
3.2 g, 0.11 mol), piperidine (20.0 ml,
0.20 mol) and acetic acid (10.0 ml, 0.17 mol)
Was stirred at reflux for 18 hours in ethanol (100 ml). After evaporating the solvent, water (300 ml) was added to obtain crude crystals, which were recrystallized from hexane: ethyl acetate to give trans-3,4'-dimethylflavanone (23.5 g, 93.
(3 mmol, 93%). Trans-3,4'-dimethylflavanone (2.52 g, 10.0 mol) and sodium hydroxide (3.20 g, 80.0 mmol) in a mixed solvent of ethanol (20 ml) and water (60 ml) 30% hydrogen peroxide Water (6.80 g, 60.0 mol) was added dropwise and stirred at 40 ° C. After 72 hours, water (100 ml) was added and the mixture was cooled with ice. The precipitate was collected by filtration to obtain a crude crystal. Silica gel column chromatography (SiO ₂ 300 g, hexane: ethyl acetate)
Then, recrystallized from hexane: ethyl acetate to give trans-
3,4'-dimethylflavanonol (1.61 g, 6.
(0 mmol, 60%).

Colorless fine crystals mp. 104.9-10
5.4 ° C IR (KBr, cm ^-1 ) 3492, 2996, 1694, 1612, 1468,
1310, 1274, 1178, 1014, 966, 7
70. ¹ H-NMR (CDCl ₃ , δ ppm) 1.19 (s, 3H), 2.39 (s, 3H), 3.7
2 (s, 1H), 5.26 (s, 1H), 7.10
(D, 2H, J = 8.1 Hz), 7.12 to 7.22
(M, 2H), 7.48 (d, 2H, J = 8.1H)
z), 7.53-7.61 (m, 1H), 7.94 (d
d, 1H, J = 8.1, 1.6 Hz).

Using the corresponding aldehyde, the same reaction as in Synthesis Example 1 was carried out to obtain the following compounds of Synthesis Examples 2 to 12.

Synthesis Example 2 trans-4'-ethyl-3-methylflavanonol: colorless fine crystals mp. 130.5 to 131.3 ° C IR (KBr, cm ^-1 ) 3484, 1692, 1610, 1466, 1308,
1234,1018. ¹ H-NMR (CDCl ₃ , δ ppm) 1.21 (s, 3H), 1.27 (t, 3H, J = 7.
6 Hz), 2.70 (q, 2H, J = 7.6 Hz),
3.74 (bs, 1H), 5.27 (s, 1H), 7.
08 to 7.15 (m, 2H), 7.27 (d, 2H, J
= 8.1 Hz), 7.50 (d, 2H, J = 8.1H)
z), 7.50-7.62 (m, 1H), 7.94 (d
d, 1H, J = 8.1, 1.8 Hz).

Synthesis Example 3 cis-4'-butyl-3-methylflavanonol: colorless fine crystals mp. 112.7-113.3 ° C IR (KBr, cm ^-1 ) 3536, 2956, 2872, 1688, 1612,
1466, 1296, 1234, 766. ¹ H-NMR (CDCl ₃ , δ ppm) 0.91 (t, 3H, J = 7.2 Hz), 1.23 to
1.42 (m, 2H), 1.49 to 1.64 (m, 5
H), 2.58 (t, 2H, J = 7.4 Hz), 2.9
9 (s, 1H), 5.31 (s, 1H), 7.01-
7.11 (m, 2H), 7.11 (d, 2H, J = 8.
2 Hz), 7.25 (d, 2H, J = 8.2 Hz),
7.50 to 7.58 (m, 1H), 7.89 (dd, 1
H, J = 7.8, 1.7 Hz).

Synthesis Example 4 trans-4'-butyl-3-methylflavanonol: colorless fine crystals mp. 88.5-89.3 ° C. IR (KBr, cm ⁻¹ ) 3476, 2960, 2860, 1684, 1610,
1470, 1312, 1234, 1014, 758. ¹ H-NMR (CDCl ₃ , δ ppm) 0.94 (t, 3H, J = 7.2 Hz), 1.21
(S, 3H), 1.29 to 1.47 (m, 2H), 1.
52 to 1.70 (m, 2H), 2.65 (t, 2H, J
= 7.9 Hz), 3.74 (s, 1H), 5.27
(S, 1H), 7.07 to 7.15 (m, 2H), 7.
25 (d, 2H, J = 8.0 Hz), 7.49 (d, 2
H, J = 8.0 Hz), 7.52 to 7.61 (m, 1
H), 7.94 (dd, 1H, J = 8.0, 1.8H)
z).

Synthesis Example 5 trans-3-methyl-4'-methoxyflavanonol: colorless fine crystals mp. 119.3-119.8 ° C IR (KBr, cm ^-1 ) 3480, 2988, 2940, 2868, 2844,
1690, 1610, 1518, 1470, 1312
1252, 1228, 1180, 1030, 1014
908,776. ¹ H-NMR (CDCl ₃ , δ ppm) 1.20 (s, 3H), 3.74 (s, 1H), 3.8
5 (s, 3H), 5.24 (s, 1H), 6.97
(D, 2H, J = 8.9 Hz), 7.05-7.15
(M, 2H), 7.52 (d, 2H, J = 8.9H)
z), 7.54-7.62 (m, 1H), 7.94 (d
d, 1H, J = 8.3, 1.7 Hz).

Synthesis Example 6 trans-4'-propoxy-3-methylflavanonol: colorless fine crystals mp. 137.2-138.1 ° C IR (KBr, cm ^-1 ) 3496, 2964, 2880, 1692, 1616,
1466, 1250, 1236, 1182, 752. ¹ H-NMR (CDCl ₃ , δ ppm) 1.05 (t, 3H, J = 7.5 Hz), 1.20
(S, 3H), 1.20 to 1.56 (m, 2H), 3.
72 (s, 1H), 3.96 (t, 2H, J = 6.6H)
z), 5.24 (s, 1H), 6.96 (d, 2H, J
= 8.8 Hz), 7.02 to 7.15 (m, 2H),
7.49 (d, 2H, J = 8.8 Hz), 7.52-
7.61 (m, 1H), 7.93 (dd, 1H, J =
8.0, 1.7 Hz).

Synthesis Example 7 trans-4'-chloro-3-methylflavanonol: colorless fine crystals mp. 112.1 to 112.6 ° C IR (KBr, cm ^-1 ) 3492, 2988, 2896, 1692, 1610,
1496, 1470, 1306, 1230, 1182
1014,966,758. ¹ H-NMR (CDCl ₃ , δ ppm) 1.16 (s, 3H), 3.79 (s, 1H), 5.2
7 (s, 1H), 7.09 to 7.18 (m, 2H),
7.41 (d, 2H, J = 8.6 Hz), 7.53-
7.63 (m, 3H), 7.94 (dd, 1H, J =
8.8, 1.5 Hz).

Synthesis Example 8 trans-3′-chloro-3-methylflavanonol: colorless fine crystals mp. 102.9-103.3 ° C IR (KBr, cm ^-1 ) 3460, 1696, 1610, 1466, 1306,
1124, 1022, 798, 758, 704. ¹ H-NMR (CDCl ₃ , δ ppm) 1.18 (s, 3H), 3.81 (s, 1H), 5.2
6 (s, 1H), 7.09 to 7.18 (m, 2H),
7.35 to 7.64 (m, 5H), 7.94 (dd, 1
H, J = 7.8, 1.9 Hz).

Synthesis Example 9 trans-2'-chloro-3-methylflavanonol: colorless fine crystals mp. 171.6-172.6 ° C IR (KBr, cm ^-1 ) 3468, 3080, 2992, 2940, 1684,
1606, 1476, 1468, 1306, 1230,
1150, 1098, 1016, 760, 736. ¹ H-NMR (CDCl ₃ , δ ppm) 1.32 (s, 3H), 3.62 (s, 1H), 5.8
9 (s, 1H), 7.05 to 7.18 (m, 2H),
7.34 to 7.61 (m, 4H), 7.78 to 7.81
(M, 1H), 7.97 (dd, 1H, J = 7.8,
1.8 Hz).

Synthesis Example 10 trans-4'-cyano-3-methylflavanonol: colorless fine crystals mp. 194.5-195.1 ° C IR (KBr, cm ^-1 ) 3484, 3316, 1690, 1662, 1610,
1476, 1308, 1232, 756. ¹ H-NMR (CDCl ₃ , δ ppm) 1.17 (s, 3H), 3.84 (s, 1H), 5.3
5 (s, 1H), 7.10 to 7.18 (m, 2H),
7.56 to 7.65 (m, 1H), 7.71 (d, 2
H, J = 8.4 Hz), 7.89 (d, 2H, J = 8.
4 Hz), 7.95 (dd, 1H, J = 7.8, 1.8)
Hz).

Synthesis Example 11 trans-4'-trifluoromethyl-3-methylflavanonol: colorless fine crystals mp. 122.8-123.5 ° C IR (KBr, cm ^-1 ) 3496, 2992, 2904, 1694, 1610,
1470, 1332, 1110, 760. ¹ H-NMR (CDCl ₃ , δ ppm) 1.16 (s, 3H), 3.84 (s, 1H), 5.3
5 (s, 1H), 7.10 to 7.19 (m, 2H),
7.56 to 7.65 (m, 1H), 7.69 (d, 2
H, J = 8.7 Hz), 7.75 (d, 2H, J = 8.
7 Hz), 7.96 (dd, 1H, J = 8.8, 1.5
Hz).

Synthesis Example 12 trans-3 ', 4'-dimethoxy-3-methylflavanonol: colorless fine crystals mp. 102.1 to 102.7 ° C. IR (KBr, cm ⁻¹ ) 3480, 2980, 2876, 2848.1696,
1610, 1520, 1470, 1224, 1140,
1024. ¹ H-NMR (CDCl ₃ , δ ppm) 1.22 (s, 3H), 3.75 (s, 1H), 3.9
2 (s, 3H), 3.94 (s, 3H), 5.24
(S, 1H), 6.94 (d, 1H, J = 8.2H)
z), 7.09-7.19 (m, 4H), 7.54-
7.62 (m, 1H), 7.94 (dd, 1H, J =
8.0, 1.6 Hz).

Synthesis Example 13 trans-6-chloro-3-methylflavanonol: p
-Chlorophenol (20.0 g, 156 mmol), pyridine (14.8 g, 187 mmol) and toluene (150
ml) to the mixture of propionyl chloride (17.3 g, 1
(87 mmol) was added dropwise and stirred at room temperature for 1 hour. Water (15
0 ml), and the mixture was separated. The organic layer was concentrated and distilled under reduced pressure (b).
p. 73-76 ° C / 0.2 mmHg) and propionic acid-p
-Chlorophenyl ester (25.6 g, 138 mmol,
89%). Next, a mixture of propionic acid-p-chlorophenyl ester (20.0 g, 108 mmol) and anhydrous aluminum chloride (27.5 g, 206 mmol) was stirred at a bath temperature of 180 ° C. for 15 minutes. After cooling on ice, 1N hydrochloric acid (400
ml) and extracted with methylene chloride. After evaporating the solvent from the extract, recrystallization from hexane gave 5-chloro-2.
-Hydroxyphenyl ethyl ketone (16.7 g, 91
mmol, 84%). Next, the reaction was carried out in the same manner as in Synthesis Example 1 using 5-chloro-2-hydroxyphenylethyl ketone to obtain trans-6-chloro-3-methylflavanonol.

Colorless fine crystals mp. 92.0-92.5
° C IR (KBr, cm ^-1 ) 3480, 1698, 1604, 1472, 1172,
1022. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.03 (s, 3H), 5.43 (s, 1H), 5.8
9 (s, 1H), 7.22 (d, 1H, J = 8.8H)
z), 7.39-7.52 (m, 5H), 7.68 (d
d, 1H, J = 8.8, 2.7 Hz), 7.77 (d,
1H, J = 2.7 Hz).

The same reaction as in Synthesis Examples 1 and 13 was carried out using the corresponding raw materials to obtain compounds of Synthesis Examples 14 to 22.

Synthesis Example 14 cis-3,6-dimethylflavanonol: colorless fine crystals mp. 112.5-113.5 ° C IR (KBr, cm ^-1 ) 3448, 1680, 1622, 1496, 1300,
1124, 1146, 1018, 758, 696. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.07 (s, 3H), 2.31 (s, 3H), 5.2
5 (s, 1H), 5.89 (s, 1H), 6.96
(D, 1H, J = 8.4 Hz), 7.37 to 7.43
(M, 4H), 7.53-7.58 (m, 2H), 7.
62 (d, 1H, J = 1.7 Hz).

Synthesis Example 15 trans-3,6-dimethylflavanonol: colorless fine crystals mp. 145.5 to 146.5 ° C IR (KBr, cm ^-1 ) 3468, 1684, 1618, 1492, 1298,
1124, 1148, 1128. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.01 (s, 3H), 2.32 (s, 3H), 5.3
2 (s, 1H), 5.73 (s, 1H), 7.05
(D, 1H, J = 8.4 Hz), 7.38 to 7.52
(M, 6H), 7.63 (d, 1H, J = 1.8H
z).

Synthesis Example 16 cis-7-chloro-3-methylflavanonol: colorless fine crystals mp. 95.0-96.0 ° C IR (KBr, cm ^-1 ) 3460, 1688, 1602, 1430, 1218,
1016, 742, 696. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.06 (s, 3H), 5.40 (s, 1H), 6.0
3 (s, 1H), 7.18 (dd, 1H, J = 8.3,
1.8 Hz), 7.24 (d, 1H, J = 1.8H)
z), 7.39-7.58 (m, 5H), 7.84.
(D, 1H, J = 8.3 Hz).

Synthesis Example 17 trans-7-chloro-3-methylflavanonol: colorless fine crystals mp. 65.5-67.5 ° C IR (KBr, cm ^-1 ) 3480, 1690, 1604, 1430, 1218,
1020. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.03 (s, 3H), 5.44 (s, 1H), 5.8
5 (s, 1H), 7.22 (dd, 1H, J = 8.4,
1.9 Hz), 7.31 (d, 1H, J = 1.9H)
z), 7.38-7.51 (m, 5H), 7.84.
(D, 1H, J = 8.4 Hz).

Synthesis Example 18 trans-3,7-dimethylflavanonol: colorless fine crystals mp. 92.0-92.5 ° C IR (KBr, cm ^-1 ) 3468, 1684, 1618, 1494, 1456,
1248, 1154, 1120, 1028, 744, 6
98. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.00 (s, 3H), 2.35 (s, 3H), 5.3
3 (s, 1H), 5.71 (s, 1H), 6.97
(S, 1H), 6.98 (d, 1H, J = 8.5H)
z), 7.37-7.52 (m, 5H), 7.72
(D, 1H, J = 8.5 Hz).

Synthesis Example 19 trans-3-ethylflavanonol: colorless fine crystals mp. 100.2-100.7 ° C IR (KBr, cm ^-1 ) 3488, 2972, 2940, 2880, 1692,
1620, 1468, 1328, 1276, 1224
1024, 766, 700. ¹ H-NMR (CDCl ₃ , δ ppm) 0.66 (t, 3H, J = 7.5 Hz), 1.45
1.94 (m, 2H), 3.92 (s, 1H), 5.3
6 (s, 1H), 7.08 to 7.15 (m, 2H),
7.37 to 7.63 (m, 6H), 7.92 (dd, 1
H, J = 8.1, 1.7 Hz).

Synthesis Example 20 trans-3-octylflavanonol: yellow oil IR (neat, cm ^-1 ) 3496, 3040, 2982, 2860, 1694,
1612, 1470, 1324, 1296, 1226
1014, 756, 696. ¹ H-NMR (CDCl ₃ , δ ppm) 0.81 (t, 3H, J = 7.3 Hz), 1.10
1.88 (m, 14H), 3.93 (s, 1H), 5.
32 (s, 1H), 7.03 to 7.16 (m, 2H),
7.35 to 7.66 (m, 6H), 7.91 (dd, 1
H, J = 8.0, 1.8 Hz).

Synthesis Example 21 trans-8-chloro-3-methylflavanonol: colorless fine crystals mp. 86.7-87.9 ° C IR (KBr, cm ^-1 ) 3464, 1704, 1602, 1472, 1446,
1248, 1136, 1022. ¹ H-NMR (CDCl ₃ , δ ppm) 1.18 (m, 3H), 3.75 (s, 1H), 5.3
7 (s, 1H), 7.03 to 7.11 (m, 1H),
7.40 to 7.50 (m, 3H), 7.62 to 7.68
(M, 3H), 7.86 (dd, 1H, J = 7.9,
1.6 Hz).

Synthesis Example 22 trans-3,7,4'-trimethylflavanonol: yellow oil IR (neat, cm ^-1 ) 3496, 3016, 2988, 2928, 2872,
1690, 1620, 1456, 1238, 1186
1154, 1040, 818, 752. ¹ H-NMR (CDCl ₃ , δ ppm) 1.17 (s, 3H), 2.39 (s, 3H), 2.4
0 (s, 3H), 3.74 (s, 1H), 5.23
(S, 1H), 6.91 to 6.95 (m, 2H), 7.
24 (d, 2H, J = 8.1 Hz), 7.47 (d, 2
H, J = 8.1 Hz), 7.82 (d, 1H, J = 8.
4 Hz).

Synthesis Example 23 trans-7-methoxymethoxy-3-methylflavanonol: 2 ', 4'-dihydroxypropiophenone (46.5 g, 0.28 mol) in methylene chloride (500
ml) solution with N, N-diisopropylethylamine (4
0.1 g, 0.31 mol), and chloromethyl methyl ether (25.0 g, 0.31 mol) was added under ice-cooling.
It was added dropwise in 0 minutes. The mixture was gradually returned to room temperature and stirred for 1 hour.
After adding water (300 ml) and separating the layers, the organic layer was concentrated and chromatographed on silica gel (700 g of SiO ₂ , hexane: ethyl acetate) to give 2′-hydroxy-4 ′-(methoxymethoxy) propiophenone (52.5 g). , 0.25mol
, 89%). Next, 2'-hydroxy-4'-
The same reaction as in Synthesis Example 1 was carried out using (methoxymethoxy) propiophenone and the corresponding aldehyde to obtain trans-7-methoxymethoxy-3-methylflavanonol.

Colorless fine crystals mp. 104.0-10
6.4 ° C. IR (KBr, cm ⁻¹ ) 3464, 3092, 2964, 1686, 1612,
1450, 1252, 1150, 1104, 1072
1014, 766, 730. ¹ H-NMR (CDCl ₃ , δ ppm) 1.18 (s, 3H), 3.50 (s, 3H), 3.8
0 (s, 1H), 5.24 (s, 2H), 5.28
(S, 1H), 6.70 to 6.80 (m, 2H), 7.
40 to 7.65 (m, 5H), 7.88 (d, 1H, J
= 8.6 Hz).

Synthesis Example 24 trans-7-methoxymethoxy-3,4'-dimethylflavanonol: 2'-hydroxy- obtained in Synthesis Example 23
Using 4 '-(methoxymethoxy) propiophenone and the corresponding aldehyde, the same reaction as in Synthesis Example 1 was performed to obtain the target compound.

Colorless fine crystals mp. 139.9-14
0.7 ° C. IR (KBr, cm ⁻¹ ) 3480, 2980, 2924, 1684, 1610,
1454, 1252, 1142, 1000. ¹ H-NMR (CDCl ₃ , δ ppm) 1.17 (s, 3H), 2.39 (s, 3H), 3.4
9 (s, 3H), 3.75 (s, 1H), 5.23
(S, 3H), 6.72-6.79 (m, 2H), 7.
23 (d, 2H, J = 8.2 Hz), 7.46 (d, 2
H, J = 8.2 Hz), 7.87 (d, 1H, J = 8.
6 Hz).

Synthesis Example 25 Trans-4'-methoxymethoxy-3-methylflavanonol: The same reaction as in Synthesis Example 23 was carried out using 4'-hydroxybenzaldehyde to obtain 4'-methoxymethoxy-benzaldehyde. The same reaction as in Example 1 was performed to synthesize the target compound.

Colorless fine crystals mp. 100.5-10
1.2 ° C IR (KBr, cm ⁻¹ ) 3476, 2952, 1690, 1612, 1516,
1468,1308,1232,1152,986,7
52. ¹ H-NMR (CDCl ₃ , δ ppm) 1.20 (s, 3H), 3.50 (s, 3H), 3.7
4 (s, 1H), 5.23 (d, 2H, J = 1.9H)
z), 5.25 (s, 1H), 7.07-7.15
(M, 4H), 7.45 to 7.61 (m, 3H), 7.
94 (dd, 1H, J = 7.8, 2.0 Hz).

Synthesis Example 26 trans-7-hydroxy-3-methylflavanonol: 7-methoxymethoxy-3-methylflavanonol (1.57 g, 5.0 mmol) and 4.3 N hydrochloric acid (28 ml)
Was stirred at 50 ° C. for 1 hour in ethanol (10 ml).
After evaporating the solvent, the residue was extracted with ethyl acetate, and the solid obtained by silica gel column chromatography (SiO ₂ 150 g, hexane: ethyl acetate) was recrystallized to obtain trans-7-hydroxy-3-methylflavanonol (1.13 g). , 4.2mm
ol, 84%).

Colorless fine crystals mp. 169.3-16
9.8 ° C. IR (KBr, cm ⁻¹ ) 3396, 1682, 1606, 1470, 1372,
1278, 1244, 1104, 1026, 854, 7
58,728. ¹ H-NMR (CDCl ₃ + DMSO-d ₆ , δpp
m) 1.15 (s, 3H), 3.93 (s, 1H), 5.2
4 (s, 1H), 6.51 (d, 1H, J = 2.2H
z), 6.62 (dd, 1H, J = 2.2, 8.7H)
z), 7.35-7.60 (m, 5H), 7.80
(D, 1H, J = 8.7 Hz), 9.90 (bs, 1
H).

Trans-4'-methoxymethoxy-3-
The same reaction as in Synthesis Example 26 was carried out using methylflavanonol or trans-7-methoxymethoxy-3,4'-dimethylflavanonol, and compounds of Synthesis Examples 27 and 28 were synthesized.

Synthesis Example 27 trans-4'-hydroxy-3-methylflavanonol: colorless fine crystals mp. 155.2 to 155.7 ° C IR (KBr, cm ^-1 ) 3524, 3444, 2932, 1690, 1614,
1520, 1470, 1228, 758. ¹ H-NMR (DMSO-d ₆ , δ ppm) 1.03 (s, 3H), 5.24 (s, 1H), 5.6
6 (bs, 1H), 6.78 (d, 2H, J = 8.6H)
z), 7.08-7.17 (m, 2H), 7.27
(D, 2H, J = 8.6 Hz), 7.57 to 7.65
(M, 1H), 7.81 (dd, 1H, J = 7.8,
1.4 Hz), 9.49 (bs, 1H).

Synthesis Example 28 trans-7-hydroxy-3,4'-dimethylflavanonol: colorless fine crystals mp. 222.0-222.4 ° C IR (KBr, cm ^-1 ) 3436, 1674, 1622, 1462, 1276,
1114. ¹ H-NMR (DMSO-d ₆ , δ ppm) 0.97 (s, 3H), 2.33 (s, 3H), 5.2
2 (s, 1H), 5.52 (s, 1H), 6.34
(D, 1H, J = 2.2 Hz), 6.57 (dd, 1
H, J = 8.7, 2.2 Hz), 7.20 (d, 2H,
J = 8.1 Hz), 7.35 (d, 2H, J = 8.1H)
z), 7.68 (d, 1H, J = 8.7 Hz).

Synthesis Example 29 trans-7-methoxy-3-methylflavanonol:
Trans-7-hydroxy-3-methylflavanonol (0.54 g, 2.0 mmol) and potassium carbonate (0.41 g)
g, 3.0 mmol) in acetone (20 ml), and then iodomethane (0.57 g, 4.0 mmol).
Stirred at C for 1 hour. And extracted with ethyl acetate, silica gel column chromatography (SiO ₂ 70 g, hexane: ethyl acetate) to obtain a trans-7-methoxy-3-methyl flava Roh Nord (0.57g, 2.0mmol, 100%) .

Colorless oil IR (neat, cm ^-1 ) 3840, 3068, 3040, 2984, 2940,
2844, 1684, 1440, 1260, 1098,
1026,838,724,698. ¹ H-NMR (CDCl ₃ , δ ppm) 1.17 (s, 3H), 3.83 (s, 1H), 3.8
6 (s, 3H), 5.29 (s, 1H), 6.54
(D, 1H, J = 2.3 Hz), 6.68 (dd, 1
H, J = 8.9, 2.4 Hz), 7.38 to 7.61.
(M, 5H), 7.87 (d, 1H, J = 8.9H)
z).

Synthesis Example 30 Trans-7-hydroxy-3,4'-dimethylflavanonol was used to carry out the same reaction as in Synthesis Example 5 to obtain trans-7-methoxy-3,4'-dimethylflavanonol. Was.

Colorless fine crystals mp. 117.4-11
8.2 ° C. IR (KBr, cm ⁻¹ ) 3460, 2972, 2928, 1680, 1610,
1448, 1262, 1096, 1024. ¹ H-NMR (CDCl ₃ , δ ppm) 1.17 (s, 3H), 2.39 (s, 3H), 3.7
7 (s, 1H), 3.86 (s, 3H), 5.24
(S, 1H), 6.53 (d, 1H, J = 2.3H
z), 6.67 (dd, 1H, J = 8.9, 2.3H)
z), 7.24 (d, 2H, J = 8.2 Hz), 7.4
6 (d, 2H, J = 8.2 Hz), 7.86 (d, 1
H, J = 8.9 Hz).

Example 1 A hair follicle organ of a newborn SD rat was surgically removed. A phosphate buffer solution for maintaining humidity was put on the outer peripheral portion of an organ culture dish (Falcon 3037), and the obtained hair follicles (5 pieces / dish) were arranged on a triangular grit placed on an inner dish. Flavanonol derivative (1) was added to the medium (RPMI 1640) to a final concentration of 0.1 nM,
The cells were cultured at 31 ° C. in a gas phase of 0% O ₂ and 5% CO ₂ , and daily hair growth was observed. Table 1 shows the results. The degree of hair elongation in Table 1 is a relative value on the third day of culture when the culture solution alone (no addition group) was set to 100. As is clear from Table 1, the remarkable hair shaft elongation-promoting effect was observed in the flavanonol derivative (1) of the present invention.

[0079]

[Table 1]

Example 2 The back hair of a 7-week-old C3H mouse (♂) at rest was shaved over 2 × 4 cm ² using an electric clipper and an electric razor so as not to damage the skin. These mice were grouped into 20 mice, and the shaved site was coated with the flavanonol derivative (1) (0.05%) dissolved in 70% ethanol once a day at 20 μl / day. In order to observe the state of hair regeneration, a photograph of the shaved site was taken at a fixed magnification, and a regenerated hair area ratio (regenerated hair area / shaved area) was produced using an image analyzer to determine hair growth activity. . In addition, the case where only the solvent (70% ethanol) was applied was used as a control product. Table 2 shows the hair growth activity (%) on day 20 after the start of sample application. As is clear from the results shown in Table 2 below, superior and remarkable promotion of hair growth was observed in the group to which the present flavanonol derivative (1) was applied compared to the group to which the control product was applied. In addition, the mice to which the flavanol compound of the present invention was applied were all healthy and had no effect on the skin.

[0081]

[Table 2]

Example 3 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B carpronium chloride 1.0 sodium dodecyl sulfate 0.12 dodecylmethyl Amine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 4 Hair restorer

(Table 4) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B ginseng extract 1.0 sodium dodecyl sulfate 0.12 dodecyl Methylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 5 Hair Tonic

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 minoxidil 1.0 polyoxyethylene hydrogenated castor oil 0.8 gingerbread tincture 1.0 isopropylmethylphenol 0.05 ethanol 55 2.0 B Glycerin 2.0 1-Menthol 0.06 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 6 Hair Tonic

Table 6 (% by weight) A trans-3,7-dimethylflavanonol 0.05 cepharanthin 0.02 polyoxyethylene hydrogenated castor oil 0.8 gingerbread 1.0 isopropylmethylphenol 0.05 ethanol 55. 0 B Glycerin 2.0 1-menthol 0.25 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 7 Hair cream

(Weight%) A Liquid paraffin 10.0 Squalane 7.0 Jojoba oil 3.0 Solid paraffin 3.0 Polyoxyethylene cetyl ether 2.0 Sorbitan sesquioleate 1.0 Potassium hydroxide 0.1 B Trans-3,4'-dimethylflavanonol 0.05 pepper tincture 0.05 glycerin 3.0 ethylparaben 0.1 purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 8 Hair Treatment

Table 8 (% by weight) A Avocado oil 5.0 Squalane 5.0 Liquid paraffin 10.0 Stearic acid 3.0 Glycerin monostearate 3.0 Lanolin alcohol 5.0 B Trans-3,7-dimethylflavano Knol 0.05 Assembly extract 1.0 1,3-butylene glycol 5.0 Triethanolamine 1.0 Methyl paraben 0.2 Purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred uniformly, emulsified and then cooled to obtain a hair treatment.

Example 9 Hair shampoo

(Table 9) A trans-3,4'-dimethylflavanonol 0.05 Vitamin E 0.05 lauric acid diethanolamide 2.0 lauric acid 0.5 Cationic polymer (Polymer JR400 manufactured by Union Carbide Co., Ltd.) ) 0.3 polyoxyethylene lauryl ether 20.0 B fragrance 0.2 citric acid 1.5 methyl paraben 0.1 purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, a uniformly dissolved component belonging to B was gradually added to produce a hair shampoo.

Example 10 Hair rinse

(% By weight) A trans-3,7-dimethylflavanonol 0.05 cetanol 3.0 propylene glycol 2.0 liquid paraffin 0.5 hydroxyethyl cellulose (HEC Daicel SE-850) 0.5 B glycyrrhetin Glyceryl acid 0.1 Stearyl trimethyl ammonium chloride 1.0 Methyl paraben 0.1 Citric acid qs Perfume 0.2 Purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, a uniformly dissolved component belonging to B was gradually added to produce a hair rinse.

Example 11 Aerosol

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 benzyl nicotinate 0.01 vitamin E acetate 0.05 cetanol 1.2 propylene glycol 4.0 ethanol 8.0 purified water Appropriate amount B Liquefied petroleum gas (propellant) 4.0

The components belonging to A were uniformly mixed and placed in a container, and B was filled into the container by a conventional method to produce an aerosol.

Example 12 Hair Foam

(Wt%) A trans-3,7-dimethylflavanonol 0.05 hinokitiol 0.1 cetanol 1.2 propylene glycol 2.0 dimethyl silicone oil 2.0 polyoxyethylene hydrogenated castor oil 2.5 Liquid paraffin 1.0 Polyvinyl pyrrolidone 0.5 Methyl paraben 0.2 Ethanol 10.0 Purified water Amount B Liquid petroleum gas (propellant) 4.0

The components belonging to A were uniformly mixed and placed in a container, and B was filled into the container by a conventional method to produce a hair foam.

Example 13 Hair restorer

(% By weight) A trans-3,4′-dimethylflavanonol 0.05 glyceride pentadecanoate 1.0 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B sodium dodecyl sulfate 0.12 dodecyl Methylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 14 Hair restoration

(Wt%) A trans-3,7-dimethylflavanonol 0.05 ethyl pantothenate 1.0 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B sodium dodecyl sulfate 0.12 dodecylmethyl Amine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 15 Hair Tonic

Table 15 (% by weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B biotin 1.0 glycerin 2.0 l-menthol 0.25 lactic acid qs purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 16 Hair Tonic

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B ginseng extract 1.0 glycerin 2.0 l-menthol 0.25 lactic acid qs purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 17 Aerosol

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 thixin ginseng 0.01 vitamin E acetate 0.05 cetanol 1.2 propylene glycol 4.0 ethanol 8.0 purified water Appropriate amount B Liquefied petroleum gas (propellant) 4.0

The components belonging to A were uniformly mixed and placed in a container, and B was filled into the container by a conventional method to produce an aerosol.

Example 18 Hair restoration

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B dipotassium glycyrrhizinate 0.1 sodium dodecyl sulfate 0.12 dodecylmethyl Amine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 19 Hair Tonic

(% By weight) A trans-3,4′-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 gingerbread tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B glycyrrhetin Acid 0.1 Glycerin 2.0 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 20 Hair cream

(% By weight) A trans-3,7-dimethylflavanonol 0.05 liquid paraffin 10.0 squalane 7.0 jojoba oil 3.0 solid paraffin 3.0 polyoxyethylene cetyl ether 2.0 sorbitan Sesquioleate 1.0 Potassium hydroxide 0.1 B Chamomile extract 1.0 Glycerin 3.0 Ethyl paraben 0.1 Purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 21 Hair Treatment

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 avocado oil 5.0 squalane 5.0 liquid paraffin 10.0 stearic acid 3.0 glycerin monostearate 3.0 lanolin Alcohol 5.0 B Peach extract 1.0 1,3-butylene glycol 5.0 Triethanolamine 1.0 Methyl paraben 0.2 Purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred uniformly, emulsified and then cooled to obtain a hair treatment.

Example 22 Hair shampoo

(% By weight) A trans-3,7-dimethylflavanonol 0.05 lauric acid diethanolamide 2.0 lauric acid 0.5 Cationic polymer (Polymer JR400 manufactured by Union Carbide) 0.3 Polyoxy Ethylene lauryl ether 20.0 B 1-menthol 0.25 Fragrance 0.2 Citric acid 1.5 Methyl paraben 0.1 Purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, a uniformly dissolved component belonging to B was gradually added to produce a hair shampoo.

Example 23 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B benzalkonium chloride 0.1 sodium dodecyl sulfate 0.12 Dodecylmethylamine oxide 0.18 isopropyl alcohol 15.0 benzyl alcohol 15.0 glycerin 2.0 purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 24 Hair Tonic

Table 24 (% by weight) A trans-3,7-dimethylflavanonol 0.05 Octopirox 0.05 Polyoxyethylene hydrogenated castor oil 0.8 Showa tincture 1.0 Isopropylmethylphenol 0.05 Ethanol 55.0 B Glycerin 2.0 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 25 Hair cream

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 liquid paraffin 10.0 squalane 7.0 jojoba oil 3.0 solid paraffin 3.0 polyoxyethylene cetyl ether 2.0 Sorbitan sesquioleate 1.0 potassium hydroxide 0.1 B hinokitiol 0.1 glycerin 3.0 ethyl paraben 0.1 purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 26 Hair restoration

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B thioxolone 0.1 sodium dodecyl sulfate 0.12 dodecyl methylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 27 Hair Tonic

Table 27 (% by weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B hydrochloric acid Pyridoxine 0.1 Glycerin 2.0 Lactate qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 28 Hair cream

(% By weight) A trans-3,7-dimethylflavanonol 0.05 vitamin B ₆ 0.05 liquid paraffin 10.0 squalane 7.0 jojoba oil 3.0 solid paraffin 3.0 polyoxyethylene Cetyl ether 2.0 sorbitan sesquioleate 1.0 potassium hydroxide 0.1 B glycerin 3.0 ethyl paraben 0.1 purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 29 Hair shampoo

(Table 29) A trans-3,4'-dimethylflavanonol 0.05 sulfur 0.05 lauric acid diethanolamide 2.0 lauric acid 0.5 cationic polymer (Polymer JR400 manufactured by Union Carbide) 0.3 polyoxyethylene lauryl ether 20.0 B fragrance 0.2 citric acid 1.5 methyl paraben 0.1 purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, the uniformly dissolved components belonging to B were gradually added to obtain a hair shampoo.

Example 30 Hair rinse

(% By weight) A trans-3,7-dimethylflavanonol 0.05 cetanol 3.0 propylene glycol 2.0 liquid paraffin 0.5 hydroxyethyl cellulose (HEC Daicel SE-850) 0.5 B lecithin 1.0 Stearyl trimethyl ammonium chloride 1.0 Methyl paraben 0.1 Citric acid qs Perfume 0.2 Purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, a uniformly dissolved component belonging to B was gradually added to obtain a hair rinse.

Example 31 Hair restorer

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B Maikai extract 1.0 sodium dodecyl sulfate 0.12 dodecylmethyl Amine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 32 Hair Tonic

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B hyaluronic acid 1.0 Glycerin 2.0 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 33 Hair cream

Table 33 (% by weight) A trans-3,4'-dimethylflavanonol 0.05 liquid paraffin 10.0 squalane 7.0 jojoba oil 3.0 solid paraffin 3.0 polyoxyethylene cetyl ether 2.0 Sorbitan sesquioleate 1.0 Potassium hydroxide 0.1 B Cordyceps sinensis extract 1.0 Glycerin 3.0 Ethyl paraben 0.1 Purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 34 Hair shampoo

(% By weight) A trans-3,7-dimethylflavanonol 0.05 sulfur 0.05 lauric acid diethanolamide 2.0 lauric acid 0.5 cationic polymer (Polymer JR400 manufactured by Union Carbide) 0 0.3 Polyoxyethylene lauryl ether 20.0 B Duke extract 1.0 Fragrance 0.2 Citric acid 1.5 Methyl paraben 0.1 Purified water qs

The components belonging to A are uniformly stirred and dissolved.
Separately, a uniformly dissolved component belonging to B was gradually added to produce a hair shampoo.

Example 35 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B cantharis extract 1.0 sodium dodecyl sulfate 0.12 dodecyl Methylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 36 Hair Tonic

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 gingerbread tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B camphor 0 Glycerin 2.0 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 37 Hair cream

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 liquid paraffin 10.0 squalane 7.0 jojoba oil 3.0 solid paraffin 3.0 polyoxyethylene cetyl ether 2.0 Sorbitan sesquioleate 1.0 Potassium hydroxide 0.1 B Vanillyl amide nonylate 0.05 Glycerin 3.0 Ethyl paraben 0.1 Purified water qs

The components belonging to A are dissolved by heating. Separately, B
Is heated and dissolved. B was added to A, stirred and mixed uniformly, emulsified, and then cooled to obtain a hair cream.

Example 38 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 salicylic acid 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B sodium dodecyl sulfate 0.12 dodecylmethylamine Oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 39 Hair restorer

(% By weight) A trans-3,7-dimethylflavanonol 0.05 ethinylestradiol 0.1 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B sodium dodecyl sulfate 0.12 dodecylmethylamine Oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 40 Hair Tonic

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 oxendrone 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55 2.0 B Glycerin 2.0 l-Menthol 0.25 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 41 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 glyceride pentadecanoate 1.0 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B carpronium chloride 1.0 dodecyl sulfate Sodium 0.12 Dodecylmethylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 42 Hair restoration

(% By weight) A trans-3,7-dimethylflavanonol 0.05 minoxidil 1.0 pentadecanoic acid glyceride 1.0 chlormadinone acetate 0.1 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B sodium dodecyl sulfate 0.12 dodecyl methylamine oxide 0.18 isopropyl alcohol 15.0 benzyl alcohol 15.0 glycerin 2.0 purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 43 Hair restoration

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 glyceride pentadecanoate 1.0 oxendrone 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B carpronium chloride 1 0.0 Glycyrrhetinic acid 0.1 Maikai extract 1.0 Sodium dodecyl sulfate 0.12 Dodecylmethylamine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

Example 44 Hair Tonic

(% By weight) A trans-3,7-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ginger tincture 1.0 isopropylmethylphenol 0.05 ethanol 55.0 B assembly extract 1.0 Carrot extract 1.0 Dipotassium glycyrrhizinate 0.1 Canthari tincture 1.0 Glycerin 2.0 1-menthol 0.25 Lactic acid qs Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A and mixed uniformly with stirring to obtain a hair tonic.

Example 45 Hair restorer

(% By weight) A trans-3,4'-dimethylflavanonol 0.05 polyoxyethylene hydrogenated castor oil 0.8 ethanol 30.0 B hypericum extract 1.0 sodium dodecyl sulfate 0.12 dodecylmethyl Amine oxide 0.18 Isopropyl alcohol 15.0 Benzyl alcohol 15.0 Glycerin 2.0 Purified water qs

The components belonging to A are dissolved. Separately, the components belonging to B are dissolved. B was added to A, and the mixture was uniformly stirred and mixed to obtain a hair restorer.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Mitsuyuki Hotta 3167-2 Ujiie-machi, Shioya-gun, Tochigi Prefecture 201 Global Ujiie 201 (56) References JP-A-1-96126 (JP, A) JP-A-5-96 78347 (JP, A) JP-A-8-157466 (JP, A) JP-A-7-112916 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 7/00-7 / 50 CA (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A compound of the general formula (1) (Wherein R ¹ represents an alkyl group; R ² and R ³ represent a hydrogen atom, an alkyl group which may have a substituent, an alkoxyl group which may have a substituent, a hydroxyl group, a cyano group or A hair foster / hair restorer containing a flavanonol derivative represented by the following formula: 2. R ¹ is an alkyl group having 1 to 12 carbon atoms, R ² and R ³ are a hydrogen atom, an alkyl group having 1 to 12 carbon atoms which may be substituted by a halogen atom, and 1 to 12 carbon atoms. The hair restoration and hair restoration composition according to claim 1, wherein the alkoxyl group is an alkoxyl group having 1 to 12 carbon atoms, a hydroxyl group, a cyano group or a halogen atom which may be substituted.