JPH07157494A - New isoflavone glycoside and cosmetic containing the same - Google Patents

Abstract

PURPOSE:To obtain the subject compound which is a new isoflavone glycoside having an excellent whitening effect on the skin and an excellent preventive and therapeutic effect on a spot or a ephelis caused by sunburn, etc., and useful as a cosmetic material for cream, emulsion, lotion, etc. CONSTITUTION:A new isoflavone glycoside (e.g. 6''-O-apiosylpuerarin-4'-O- glycoside) represented by the formula (R<1> is apiosyl, glucosyl or H; R<2> is H or OH; R<3> is H or glucosyl), having an excellent whitening effect on the skin and an excellent preventive and therapeutic effect on a spot or a freckle caused by sunburn, etc., and useful as a raw material for a cream-, ointment-, emulsion-, lotion-, solution-, gel-, pack- or stick-shaped cosmetic. This compound is obtained by extracting an extract from tapioca roots with 20% aqueous ethanol, treating the resultant extract with an adsorption resin column, eluting it with methanol and purifying the eluted fraction by the medium-pressure reverse phase chromatography.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel isoflavone glycoside having an excellent skin whitening effect and an effect of preventing spots and freckles caused by sunburn, and a cosmetic containing the same.

[0002]

2. Description of the Related Art It is generally considered that blemishes and freckles on the skin are generally activated by the stimulation of ultraviolet rays, hormonal abnormalities, etc., and the melanin pigment biosynthesized there is deposited on the skin. Conventionally, as a method for treating such spots and freckles, melanin inhibitors such as ascorbic acids, hydroquinone derivatives, kojic acids, and placenta extract have been used, but when these substances are used alone, they produce melanin. The inhibitory effect was weak, and when blended in cosmetics and the like, a sufficient whitening effect could not be exhibited.

[0003]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a substance having an excellent whitening effect on the skin and capable of effectively preventing and treating spots and freckles, and a cosmetic containing the same.

[0004]

In view of such circumstances, the present inventors have earnestly studied to develop a cosmetic having an excellent whitening effect, and as a result, a novel compound represented by the following general formula (1). It was found that isoflavone glycosides suppress the production of melanin, prevent pigmentation, and exhibit an excellent whitening effect,
Further, they have found that the combination of this with a known whitening agent such as ascorbic acid synergistically enhances the whitening effect, and completed the present invention.

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

[0006]

[Chemical 2]

Of the isoflavone glycoside represented by the formula: wherein R ¹ represents an apiosyl group, a glucosyl group or a hydrogen atom, R ² represents a hydrogen atom or a hydroxyl group, and R ³ represents a hydrogen atom or a glucosyl group. A first invention, a second invention of a cosmetic composition containing the same, and a second invention of a cosmetic composition containing the same and one or more selected from ascorbic acids, hydroquinone derivatives, kojic acids and placenta extracts. It provides the third invention.

The isoflavone glycoside of the present invention is represented by the above general formula (1). Of these, 6 ″-
O-apiosylpuerarin-4'-O-glucoside,
6 ″ -O-glucosyl puerarin, 3′-hydroxypuerarin-4′-O-glucoside, and 6 ″ -O-apiosyl-3′-hydroxypuerarin are preferable for use in cosmetics because of their high whitening effect.

The isoflavone glycoside (1) of the present invention can be obtained, for example, by a method such as fractionation from Kuzukon extract by chromatography.

That is, dried kudzu roots are crushed and an extract is obtained using water, alcohol such as ethanol, hydrophilic organic solvent such as acetone, or a mixed solution thereof. The residue obtained by removing the solvent from the obtained extract is hexane, petroleum ether, diethyl ether, chloroform, methyl ethyl ketone, ethyl acetate, acetone, isopropyl alcohol, methanol, at least one solvent selected from ethanol as an elution solvent, DIAION HP-2
0, column chromatography using a porous polymer such as TSKGEL HW-40, Sephadex such as Sephadex LH-20, polyamide, cellulose, reverse phase silica gel, silica gel, etc. as a carrier,
The above isoflavone glycoside can be obtained by subjecting it to preparative HPLC and preparative thin layer chromatography.

The cosmetic of the present invention contains the above-mentioned isoflavone glycoside (1), and the amount of this is 0.00001 to 2.5% by weight based on the total weight of the cosmetic. In particular, 0.0001 to 1% by weight (hereinafter, simply referred to as "%") is preferable for whitening effect.

The cosmetic of the present invention comprises, together with the isoflavone glycoside (1), one or two selected from ascorbic acids, hydroquinone derivatives, kojic acids and placenta extracts.
Blending more than one species can enhance the whitening effect synergistically.

Examples of the ascorbic acid used in the present invention include L-ascorbic acid, L-ascorbic acid phosphoric acid ester, L-ascorbic acid sulfuric acid ester and metal salts thereof, such as sodium salt, potassium salt, magnesium salt, calcium salt, Aluminum salts and the like can be mentioned as preferable ones, but the present invention is not limited thereto.

As the hydroquinone derivative, there are condensates of hydroquinone and sugar, condensates of alkylated hydroquinone and sugar, and preferred examples include arbutin and the like. Examples of kojic acids include kojic acid, monoesters and diesters of kojic acid, such as butyrate of kojic acid, palmitate of kojic acid, stearate of kojic acid, and oleate of kojic acid, but are not limited thereto. Absent.

Examples of the placenta extract include water-soluble components of placenta of animals such as cows and pigs, and commercially available water-soluble placenta extract may be used.

When one or more of these whitening agents such as ascorbic acid are blended in the cosmetic of the present invention, the blending amount is 0.01 to 30%, particularly 0.1 to 5% of the cosmetic. Preferably. That is, if it is less than 0.01%, it is difficult to obtain a synergistic effect with the isoflavone glycoside (1), and if it exceeds 30%, storage stability and usability as cosmetics are remarkably deteriorated, which is not preferable.

Further, the cosmetic of the present invention may be appropriately blended with various optional components used in ordinary cosmetics, quasi drugs, pharmaceuticals, etc. other than the above-mentioned essential components, within a range that does not impair the effects of the present invention. You can Such optional components include
For example, purified water, ethanol, oily substances, moisturizers, thickeners, preservatives, emulsifiers, medicinal ingredients, powders, ultraviolet absorbers,
Examples thereof include dyes, fragrances, emulsion stabilizers and pH adjusters. Specifically, as the oil component, liquid paraffin,
Vaseline, paraffin wax, squalane, beeswax, carnauba wax, olive oil, lanolin, higher alcohols, fatty acids, synthetic ester oils of higher alcohols and fatty acids, silicone oils, and the like, and moisturizing agents include sorbitol, xylitol, glycerin, maltitol,
Propylene glycol, 1,3-butylene glycol,
1,4-butylene glycol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, polyoxypropylene fatty acid ester, polyethylene glycol and the like can be mentioned. As the thickener, carboxyvinyl polymer, carboxymethylcellulose, polyvinyl alcohol, carrageenan, gelatin and the like can be mentioned. Water-soluble polymer, sodium chloride,
Examples include electrolytes such as potassium chloride, preservatives such as urea, methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, and the like, emulsifiers such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, Nonionic surfactants such as polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitol fatty acid ester, and the like, and powders Is talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc flower, mica,
Examples thereof include titanium mica, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, iron oxide and ultramarine. The cosmetic of the present invention is preferably acidic to neutral (pH 7 or less) for stability of the system. The pH adjuster used here is lactic acid-sodium lactate, citric acid-
Examples include buffering agents such as sodium citrate.

The cosmetic material of the present invention can be manufactured by a conventional method. Further, the cosmetics to which the present invention is applied are not limited to general skin cosmetics, but include quasi-drugs,
It includes external medicines, and its dosage form can be arbitrarily selected according to its purpose, and is in the form of cream, ointment, emulsion, lotion, solution, gel, pack, stick. And so on.

[0019]

The isoflavone glycoside (1) of the present invention is
It has an excellent skin whitening effect and a preventive and therapeutic effect on spots and freckles due to sunburn and the like, and this effect is synergistically enhanced by the combined use of ascorbic acid and the like.
Therefore, the cosmetics containing them show an excellent whitening effect.

[0020]

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

Example 1 Production of isoflavone glycoside: Kuzukogen (powder) 100 g
Was extracted with 1 liter of 20% ethanol water at room temperature, filtered and concentrated to obtain a crude extract (39.8 g). This was dissolved in 0.5 liter of water and then partitioned three times with an equal amount of ethyl acetate, and the obtained aqueous layer was subjected to DIAION HP-20 column chromatography. After washing with water, 20% methanol elution zone (fraction A 1.2 g), 40% methanol elution zone (fraction B)
2.8 g) was obtained. Fraction B was subjected to medium pressure reverse phase chromatography (Merck Rover column RP-18 sizeB, methanol / water system) to obtain a 20% methanol fraction (fraction B-2).
0) and a 30% methanol fraction (fraction B-30) were obtained.
Fraction B-20 was further analyzed by HPLC (JAIGEL ODS
10 μm 10 × 250 mm, 0.3% acetic acid water: acetonitrile = 9: 1, flow rate 9 ml / min, detection UV254 nm) to obtain 15.2 mg of 3′-hydroxypuerarin-4′-O-glucoside. Similarly, fraction B-30 was analyzed by HPLC.
(3% acetic acid water: acetonitrile = 88: 12),
6 "-O-apiosylpuerarin-4'-O-glucoside 12.2 mg, 6" -O-glucosylpuerarin 1
8.0 mg and 6 ″ -O-apiosyl-3′-hydroxypuerarin of 8.2 mg were obtained. The results of instrumental analysis are shown below.

6 "-O-apiosylpuerarin-4'-
O-Glucoside FAB-MS (M + H) ⁺ 711 ¹ H-NMR δ (DMSO-d ₆ ) TMS; 4.77 (d, J = 2.8Hz, 1H), 4.80
(d-like, 1H), 4.92 (d, J = 7.0Hz, 1H), 7.00 (d, J = 8.8Hz, 1
H), 7.08 (d, J = 8.7Hz, 2H), 7.52 (d, J = 8.7Hz, 2H), 7.94 (d, J
= 8.8Hz, 1H), 8.40 (s, 1H). ¹³ C-NMR δ (DMSO-d ₆ ) TMS; 60.7, 62.9, 68.3, 69.7,
70.5, 70.7, 73.2, 73.2, 73.4, 75.7, 76.6, 77.0, 78.
6,78.7, 80.0, 100.3, 102.4, 109.0, 112.5, 115.0, 11
5.9, 116.8, 116.7, 122.8, 125.5, 126.3, 129.9, 153.
1, 156.1, 157.1, 161.1, 174.8.

6 "-O-glucosylpuerarin FAB-MS (M + H) ⁺ 579 ¹ H-NMR δ (DMSO-d ₆ ) TMS; 4.14 (d, J = 7.4Hz, 1H), 4.80
(d, J = 9.8Hz, 1H), 6.80 (d, J = 8.6Hz, 2H), 6.99 (d, J = 8.8Hz,
1H), 7.40 (d, J = 8.6Hz, 2H), 7.94 (d, J = 8.8Hz, 1H), 8.34 (s,
1H). ¹³ C-NMR δ (DMSO-d ₆ ) TMS; 60.7, 69.0, 69.7, 70.1,
70.4, 73.1,73.2, 76.3, 76.5, 78.2, 79.8, 102.8,10
9.0, 112.1, 114.9, 115.9, 116.6, 116.7, 122.4, 123.
0, 126.4, 130.0, 152.7, 156.1, 156.8, 160.9, 175.1.

3'-hydroxypuerarin-4'-O-
Glucoside FAB-MS (M + H) ⁺ 595 ¹ H-NMR δ (DMSO-d ₆ ) TMS; 4.73 (d, J = 7.1Hz, 1H), 4.80
(d, J = 9.8Hz, 1H), 6.92 (dd, J = 2.0Hz, 8.6Hz, 1H), 6.98 (d, J =
8.9Hz, 1H), 7.08 (d, J = 2.0Hz, 1H), 7.14 (d, J = 8.6Hz, 1H),
7.93 (d, J = 8.8Hz, 1H), 8.37 (s, 1H). ¹³ C-NMR δ (DMSO-d ₆ ) TMS; 60.8, 61.4, 69.8, 70.5,
70.7, 73.3, 73.5, 75.9, 77.2, 78.8, 81.8, 102.4, 11
2.7, 115.1, 115.3, 116.5, 116.7, 119.8, 122.8, 126.
2, 126.8, 145.1, 146.4, 153.1, 155.2, 161.3, 174.7.

6 "-O-apiosyl-3'-hydroxypuerarin FAB-MS (M + H) ⁺ 565 ¹ H-NMR δ (DMSO-d ₆ + D ₂ O) TMS; 4.83 (d, J = 3.2Hz , 1H), 4.8
7 (d-like, 1H), 6.82 (d-like, 1H), 6.87 (d-like, 1H), 7.02
(br.s, 1H), 7.04 (d, J = 8.9Hz, 1H), 7.99 (d, J = 8.9Hz, 1H), 8.
27 (s, 1H). ¹³ C-NMR δ (DMSO-d ₆ + D ₂ O) TMS; 63.5, 68.8, 70.8, 71.
4, 73.8, 74.0, 76.4, 78.9, 79.3, 80.5, 109.5, 112.
8,115.8, 116.2, 117.1, 117.5, 120.9,123.7, 124.0,
127.3, 145.2, 145.6, 153.6, 156.9, 161.6, 176.2.

Example 2 A cream (pH 6.0) containing a whitening agent and an isoflavone glycoside in the composition shown in Tables 3 and 4 was prepared according to the composition of Table 2, and the following test was conducted for the whitening effect by continuous application thereof. Investigated by. The results are shown in Table 5.

(Whitening Effect Test on UV-B Induced Pigment Spots) 20 subjects to be examined were irradiated with UV rays in the UV-B region at twice the minimum erythema dose once a day for 2 days to induce the induction. The whitening effect obtained by continuously applying the sample to the tested spots twice a day for one month was examined. The evaluation was performed using a color difference meter (CMS-1200 manufactured by Murakami Color Co., Ltd.), the L ^* value was calculated from the obtained Munsell value, and the ΔΔL ^* value representing the recovery was used. The ΔΔL ^* value was defined as follows. Sample application test site and the sample uncoated test site L ^* value of each L _O of the sample application immediately before, as L _O ', each of the sites in the L ^* values after each successive coating 1 month L _1, L _1' ΔΔL ^* is expressed by the following formula.

[0028]

## EQU1 ## ΔΔL ^* = (L ₁ −L _O ) − (L ₁ '−L _O ')

The evaluation is shown by the average value of the evaluation points of the 20 test subjects in Table 1 below.

[0030]

[Table 1]

[0031]

[Table 2]

[0032]

[Table 3]

[0033]

[Table 4]

[0034]

[Table 5]

Continuation of front page (51) Int.Cl. ⁶ Identification code Office reference number FI Technical display area A61K 7/00 K X 7/48

Claims (3)

[Claims] 1. The following general formula (1): (In the formula, R ¹ represents an apiosyl group, a glucosyl group or a hydrogen atom, R ² represents a hydrogen atom or a hydroxyl group, and R ³ represents a hydrogen atom or a glucosyl group). 2. A cosmetic containing the isoflavone derivative according to claim 1. 3. One or two selected from ascorbic acids, hydroquinone derivatives, kojic acids and placenta extracts.
A cosmetic containing at least one species and the isoflavone derivative according to claim 1.