JPS5933207A - Whitening cosmetic - Google Patents

Abstract

PURPOSE:To provide a cosmetic effective to suppress the formation of melamine and free from undesirable side effect, by using a kojic acid derivative such as 2-cinnamoyloxymethyl-5-hydroxy-4H-pyran-4-one (new material), etc. as active component. CONSTITUTION:The objective cosmetic contains 0.01-1% of the compound of formula (R is benzoyloxy, cinnamoyloxy or phenoxy). The compound of formula exhibits remarkable effect to suppress the formation of melamine by the inhibition of the activity of tyrosinase existing in the human skin, and is used in cosmetics such as beauty wash, cream, milky lotion, pack, etc. The compound of formula wherein R is cinnamoyl or phenoxy is novel.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a skin-lightening cosmetic composition containing a Koji M derivative as an active ingredient and having an excellent skin-whitening effect.

And, 21-udic acid itself has a strong tyrosinase activity inhibitory ability.

The present inventors have previously invented a skin-lightening cosmetic containing kojic acid as an active ingredient by utilizing the tyrosinase activity inhibiting power of kojic acid. (Japanese Patent Publication No. 56-1 +51i! No. 1) Furthermore, he continued his research by synthesizing many kojic acid derivatives, examining their ability to inhibit tyrosinase activity, and making inventions for their use in skin-lightening cosmetics. (JP-A-5492632, JP-A-5FI-79616, 77272 SOJ, 7776
The present inventors further introduced various substituents into the hydroxymethyl group at the 2-position of the pyran nucleus, which is the mother nucleus of co-lysic acid derivatives, especially diI-usic acid. However, a kojic acid derivative to which benzoyloxy, cinnamoyloxy, or phenoquine groups are bonded has an extremely strong inhibitory effect on narodinase activity, and this compound is known as IL! It has been found that when formulated as 1'4, it exists in the human skin without causing any undesirable side effects on the human body. completed.

The present invention contains a compound having the general formula (in the formula, R represents 1. Fair skin makeup rate with anti-skin effect -1.

The compound having the general formula 1 in No. 11, which is the component J of the fairing cosmetic composition of the present invention, is 2-hendiyloxymethyl-
5-HilrI; j-N-4 II-pyran-4-one, 2-N-enyloxymethyl-5-hydroxy-411-bin-4-one, 2-phenoxymethyl-5-hy11 ″r-j-c411-pyran-4-one.

2-cinnamoyloxymethyl-5-hy10xymethyl-4II-pyran-4-one and 2-phenoxymethyl-5-hy1-roxy-411-pyran-4-one are new compounds unknown in the literature. It is a compound derived from kojic acid by the method shown in Production Example 2.3 below.

The cosmetics of the present invention are mainly skin cosmetics such as lotions, creams, milky lotions, and punctures.
Ten general formulas for cosmetic bases, auxiliary agents, etc. used are ¥1 to 5.
Compounds from 0.01 to I! In addition to J, you can make it an ICE benefit.

For example, in lotions, purified water dissolves humectants such as 4.1 glycerin, skin nourishing agents, etc., and contains 11 anti-rust agents,
In the production of general chemical liquid JL water, which involves dissolving spices, etc. in alcohol, mixing the two, and solubilizing them at room temperature,
A lotion is prepared by adding 0.01 to 1% of the compound having the general formula 1, which is the male component of the present invention, to the -R part.

In creams, hydrophilic ingredients such as glycerin, sorhino 1, and other humectants are added to purified water to form the aqueous phase.
Urawa part has micro-ci and paraffin.

Solid oils such as microcrystalline wax, sesame oil, higher fatty acids, hydrogenated oils, semi-solid oils such as wax, lanolin, glycerin, etc., and medicinal products such as squalane, liquid paraffin, and various types of Esterura. Preservatives in oil,
! i'i! Adjust by adding oil-based ingredients such as surfactants. The aqueous phase thus obtained is heated to 22A L, and while gently stirring, the Urawa part heated to the same temperature is gradually added and emulsified to form a cream. General cream - J9θ ) In the production process, a compound having the general formula 1, which is a JJ component of the present invention, is added to Urawa part in an amount of 0.01 to 1% to form a cream.

In the case of emulsions, humectants such as glycerin, acidic or alkaline pH adjusters, etc. are added to purified water, heated and mixed, and ethanol is added to form the aqueous phase, followed by beeswax.

Solid oils such as paraffin, semi-solid expanded oils such as vaseline and lanolin), liquid oils such as squalane, liquid paraffin, and various types of Esterura are mixed with oily components such as preservatives and surfactants.g45 Pre-emulsify by adding the Urawa part to the water phase, add a protective colloid such as carboxyvinyl polymer or carboxymethyl cellulose, and homogeneously emulsify with a pomo mixer. In the production of general milky lotion, 0.01 to 1% of a compound having general formula 1, which is the active ingredient of the present invention, is added to Urawa part.
Add to the aqueous phase to make an emulsion.

For the bag, add humectants such as glycerin, coating agents such as polyvinyl alcohol, and vegum to purified water to swell it, and if necessary, add powder such as kaolin, talc, and oxidized surface 113. In the general manufacturing of punctures, which involves adding ethanol in which preservatives, etc. are dissolved, and kneading the mixture until it becomes a paste I, the compound having the general formula 1, which is the active ingredient of the present invention, is added in an amount of 0.01 to 1%. 61,) in addition to the package.

Next, a production example of a compound having general formula 1, which is an active ingredient of the present invention, will be shown.

Production example 1 2-hendiyloxymethyl-5-hyde-10-4It
--Synthesis of pyran 4-one 2-1-benzene and kojic acid IG g (0,112
mol), 23-2 g of aluminum chloride was added and dissolved, and 1118 g (0,128 mol) of hendyl chloride was added dropwise while maintaining the liquid temperature below 5°C. After the reaction 11k was returned to room temperature, the reaction solution was heated to 5°C.
Pour into an aqueous hydrochloric acid solution while maintaining the following. IL! 'j L
shallow, solids with petroleum ether and water? ' and then recrystallized with ethanol to form 2-
5-Hydroxy-4II-pyran-4-oneka59.9
Gi, :, with a yield of 91i. This substance has a melting point of 17
3.5~+74.5°C 3-element analysis clay: Experimental value, C: 6
3.08%, II: 4.12%, calculated value as 0111006, C: 63.41%, II: 4.09
%.

Infrared absorption vector as shown in Figure 1.

Nuclear magnetic resonance spectrum 1 as shown in Figure 4.

Production example 2 2-syndi-moyloxymethyl-5-hydroxy-4
Synthesis of 11-pyran-4-one 16 g (0,112 mol) of kojic acid and 23.2 g of aluminum chloride were added to dil.
Cinnamoyl chloride 2 while keeping the temperature below 5℃
1.6 g (0,13T nil) are added dropwise. After the reaction solution was returned to room temperature, it was allowed to stand overnight, and then poured into an aqueous hydrochloric acid solution while maintaining the reaction solution at 5° C. or below. (”!+ then,
The solid was washed with petroleum ether and water and recrystallized with ethanol to give 17 g of 2-cinnamoyloxymethyl-5-hydroxy-4II-pyran-4-one (yield 48.
6%) is obtained. This substance has a melting point of 168.0-169
．． 7°C1 elemental analysis value: experimental value, C: 65.58%, I
I: 4.5.3%, CI! ; ll n, as Os! '=value, 0:66.18%, II; 4.
Feather% Aoi.

As shown in Figure 2 of the infrared absorption spectrum.

As shown in Figure 5 of the nuclear magnetic resonance spectrum.

Production Example 3 2-phenoxyzino-f-R 5-H-10xy 411-
Synthesis of pyran-4-one Roroporum 200rr+7+ and 2-1'J lomethyl 5-hil:'+', +xy411-pyran-4-
Add 28.9 g (0.18 mol) of 28.9 g (0.18 mol) of pyridinium paratoluenesulfonate, and heat at 30-40°C
So 10 francs 25.2g (0.36 mol) is 15
It takes a few minutes to drip.

After stirring the reaction solution at room temperature for 2 hours, the reaction solution was washed with a 2% aqueous solution of thorium carbonate, and then dehydrated with thorium sulfate.
Furanyloxy-4H-pyran-4-one is fU. Add this compound, Ilg (0.18 mol), and 1.24 g (0.21 mol) of sodium phenol to 140 ml of dimethylformamyl and heat at 85-90°C for over 30 minutes. Reaction completed 1 & 6 40mβ of N-hydrochloric acid was added, and the mixture was heated to remove dimethylformat and water.The residue was subjected to column chromatography.
5 g of II-pyran-4-one are obtained. This substance i
l+ Elemental analysis value: Experimental value, C; 65.68%, II:
4.594'6, d as C1x IT 1004
IW value, C: 66.05%, It: 4.61% Infrared absorption spectrum as shown in Figure 3.

Nuclear magnetism 11L1 Subek] Le As shown in Figure 6.

Examples of compounds having the general formula 1 which are self-effective ingredients of the present invention include 2-1-nzoyloxymethyl-5
-Hi1'lokidi-411-pyran-4-one (hereinafter abbreviated as compound 1), 2-cinnamo yloxymethyl-5
-Hydroxy-4II-pyran-4-one (hereinafter abbreviated as -1-compound 2), and 2-phenochiramenal-5-hi-10xy-4-pyran-4-one < LEJ, uncompound 3 The tyrosinase-inhibiting effect of (abbreviated as) is as follows.

Test method: In a test tube, add 2-benz, 4-nm-y-l, 5-h1, and 4-nm-y-l, which are the active ingredients of the fairing cosmetics of the present invention, to a test tube.
I-pyran-4-one (compound 1), 2-cinnamoyloxymethyl 5-hy10xy 411pyran-4-one (compound 2) and 2-phenoxymethyl-5-h]roxy 4 If pyran 4-one (compound 3) People 0
．． 01 p m o 77/'m/! and 0.05.
tl m o l! / m (concentration of ℃ solution 0.9
m 7! People 77 kills, in 14. Di! i l
I'Ii (M(, l I V; l i ne'
:;buffer5solution)1. Qrr to white 1°-tyrosine (1,66 mer rno 7!/
mj! ) is l, Qm/! Put, PII6.8.37
After incubating at ℃, add 800 LJ of tyrosinase to each test tube.
Incubate 1 again at 37°C,
η-Dopachrome (j1! Large absorption wave Pi 47
5 nm) was measured every minute. 7.
One batch was made in the same manner using water. Also, for comparison, kojic acid 0.2+urn.

The same operation was performed for β/rnn.

Test Results The test results from the above test were as shown in Table T. Based on this table, the degree of production of 1-Bacterium chloride with control and kojic acid for each compound is shown. Compound(
1), FIG. 8 is a diagram showing the degree of formation of 1·-bachrome of each compound (2), and FIG. 9 is compound (3).

Examples of fair skin cosmetics of the present invention are as follows.

Example 1 Lotion Compound 1 0.1% Glycerin 5.0 Propylene Glycol 5.0 Polyethylene Glycol 1500 2.0" Polyoxyconinalene Oleylether 2.0 Ethanol +5.0 Potassium Hydroxide 0.o3 〃Fragrance
Appropriate amount Preservative Purified water 70.7% Example 2゜Bac compound 2 0.3% Veegum 5.011 Skrawan 2.0 = Propylene glycol 5.0 = Zinc oxide
10.0 ~ Kaolin
IO,0〃Ethanol
5.0/l fragrance *'1 suitable m preservative 1! Wi! ! water fi2
．． 2% Example 3 Emulsion Compound 3 0.05% Squalane 5.0 Vaseline
2.0 Beeswax
0.5 Sorbitan sesquioleate 0.8 Polyoxyethylene oleyl ether 1.2 Propylene creel
5.0 horn ethanol
5. Oll carboquino-L", : monomer (19/6 water volume t&) 20.0 〃 Potassium hydroxide J, 0.1=
Fragrance, appropriate amount of preservatives and antioxidants! 1 Purified water 59.85% Example 4 Cream compound 4 0.15%
'n mouth ishi
6.
O7l cetanol 5.8
11 reduction lanolin 8.0=
Squalane 37.5/l
Fatty acid glycerin 4.0 ~ Lipophilic monoglycerate glycerin 2.0 Polyoxyethylene sorbicun monolaurate
2.011 Propylene glycol
5.0 Perfume Preservative Antioxidant Purified water 29.85%

[Brief explanation of the drawing]

FIG. 1 shows the infrared absorption spectrum of 2-benzo.1-oxydimethyl-5-hydroxy-4[1-pyran-4-one], which is the active ingredient of the present invention. (Nudizil) Figure 2 shows the infrared absorption spectrum of 2-cinnamoyloxymethyl-5-hydroxy-4I-pyran-4-one]
-L. (Nujol) Figure 3 shows the same 2 phenoxymethyl-5-hyroxy-
Infrared absorption spectrum of 4[■-pyran-4-one. (
Figure 4 shows the same, 2-benzoyloxymethyl-5-hy1
- Kuchikiji 411-pyran-4-one nuclear magnetic resonance spectrum. (100MII z,, DMS 0-CIJ
). Figure 5 shows the same 2-cinnamoyloxymethyl-5-hil°
Nuclear magnetic resonance spectra of roxy-411-pyran-4-one. (100MIIz,,DMSO-Q!g)
FIG. 6 is a nuclear magnetic resonance spectrum of 2-phenonidodimethyl-5-human 11xy-4II-pyran-4-one. (100M It z XCDCIt3) Figure 7 shows 2-hendiyloxymethyl 5-hydroxy 4
Dopamine of 11-pyran 4-one "Drawing showing one-person production, Figure 8 shows 2-cinnamoyloxymethyl-5-hyI
S Roxy 411 Pyran 4-one 1-vacr1
Figure 9 shows the formation of 2-phenoxymethyl-
FIG. 2 is a drawing showing the formation of 1°-bachrome from 5-hydroxy-4×1-pyran-4-one. Patent Applicant Sansho Pharmaceutical Co., Ltd. Agent Masu Tebori (2 idiots) No. 77 <V 8 Figure

Claims (1)

[Claims] (In the formula, 1 represents a hendiyloxy group, a cinnamoyloxy group, or a phenoxy group) as an active ingredient.