JP2000302642A - Melanin formation suppressive agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a melanin formation suppressive agent which emits fine fragrance and not only masks the bad smell of a substrate used but also exerts strong melanin production suppressive effect without giving adverse drug reactions, or the like, even to the skin and scalp by including a specific compound. SOLUTION: This melanin formation suppressive agent is obtained by including at least one of compounds represented by formulae I to IV (A is O, S or CH2; R1 to R9 are each H, OH, formyl, a 1-6C acyl, or the like). As the above compound, 5-methyl-2(3H)-furanone, 2-buten-4-olide, 2-hydroxymethyl furan, 2,5-dimethyl-4-hydroxy-3(2H)-furanone, 2-formyl furan, 3-formyl furan, methyl α-furyl ketone, furfuryl acetate, 2-hydroxy-3-methyl-2-cyclopenten-1-one, or the like, may preferably be used, for example, in a compounding proportion of about 0.00001-10 wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a melanin production inhibitor.

[0002]

2. Description of the Related Art It is known that melanin deposition in skin is due to the deposition of melanin in melanocytes, which are melanin producing cells, and the transfer of melanin from dendrites of melanocytes to epidermal keratinocytes [ American Scientists, 7th
0, page 136, 1982]. In general, pigmentation of the skin in spots, freckles, sunburn, and the like is considered to be caused by melanin-producing cells existing in the skin excessively producing melanin pigment.

[0003] Conventionally, a search for a substance that suppresses the production of melanin pigment has been widely conducted for the purpose of developing a whitening agent for preventing or treating the deposition of melanin pigment.

[0004] Substances that suppress the production of melanin by melanin-producing cells include hydroquinone, kojic acid, arbutin [Fragrance Journal
), Extra Edition, No. 14, p. 127, 1995
Year], Pantolacton (JP-A-7-126148), L-
Ascorbic acid-sulfuric acid [Fragrance Journal (F
ragrance Journal), September, p. 30, p. 1997
Year], 4-nonanolide, 4-heptanolide (Japanese Unexamined Patent Publication No.
No. 169625) is known.

[0005] It is known that tyrosinase is involved in the melanin production pathway, and a search for substances that inhibit the activity of tyrosinase has been conducted. Examples of such tyrosinase activity inhibitors include vitamin C (Yutaka Mishima et al., Basic Dermatology, page 258, Asakura Shoten, 1973), kojic acid (Nikkei Sangyo Shimbun, May 24, 1988) , Arbutin (Kenichi Tomita, Proceedings of the 20th FJ Seminar, page 21, Fragrance Journal, March 14, 1990), Lucinol (Nikkan Kogyo Shimbun, October 9, 1998), etc. ing.

[0006]

However, these conventional whitening ingredients have poor stability in the formulation system, and have problems of stability such as coloring and off-odor due to decomposition and chemical change. , While having a strong whitening effect,
There is a problem in terms of safety such as causing irreversible vitiligo rash.

As described above, conventionally used whitening ingredients are not truly practically satisfactory in any of effect, stability and safety, and have sufficient stability. The development of melanin production inhibitors has been desired.

[0008] The present inventors have set out to solve the above-mentioned problems.
Conventionally, it has been used stably in various forms of cosmetics, has a favorable fragrance itself, has the effect of masking offensive odor of those base materials, and further reports any side effects on the skin and scalp. By using fragrance substances which have not been used, they have found that they show an extremely high melanin production inhibitory action, and thus completed the present invention.

An object of the present invention is to provide a melanin production inhibitor which has a favorable aroma, masks the malodor of the base material used, has no side effects on the skin and scalp, and has an extremely high melanin production inhibitory action. To provide.

[0010]

The melanin production inhibitor of the present invention has the general formula (1)

[0011]

Embedded image Wherein A is O ₂ , S ₂ , CH ₂ , R ₁ -R ₉ are a hydrogen atom, a hydroxyl group, a formyl group, a C 1-6 acyl group, a C 1-6 acyloxy group, a carbon number 2 to 6 alkoxycarbonyl groups, or a hydroxyl group, an acyloxy group having 1 to 6 carbon atoms which may be substituted by a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms which may be substituted by a hydroxyl group, or a hydroxyl group may be substituted A hydrocarbon group having 1 to 9 carbon atoms which may be substituted by a group selected from alkenyloxy groups having 2 to 5 carbon atoms. ] It is a melanin production inhibitor characterized by containing at least one compound represented by these.

A preferred melanin production inhibitor of the present invention is represented by the following general formula (2):

[0013]

Embedded image[Wherein A is O, S, CH_Two, R₁, R_TwoIs a hydrogen source
Child, methyl group, R_ThreeIs a hydroxyl group, R_Four~ R_FiveHas 1 to 1 carbon atoms
An alkyl group of 3, R₆, R₈Is a hydrogen atom, R₇, R ₉Is
Hydrogen atom, formyl group, acyl group having 1 to 3 carbon atoms, carbon
Acyloxy group having 1 to 3 atoms, alkoxy having 2 to 4 carbon atoms
Carbonyl group or hydroxyl group, acyl having 1 to 3 carbon atoms
1 carbon atom which may be substituted by a group selected from oxy groups
To 6 hydrocarbon groups. ] The compound represented by
Both are melanin production inhibitors containing one.

Further, in the present invention, the compound represented by the above general formula (1) or (2) is a compound represented by the formula: 5-methyl-2 (3H) -furanone, 2-butene-4-olide, 2-hydroxymethyl Furan, 2,5-dimethyl-4-hydroxy-3 (2H)-
Furanone, 2-formylfuran, 3-formylfuran,
Methyl α-furyl ketone, furfuryl acetate, 2-hydroxy-3-methyl-2-cyclopenten-1-one, 2-hydroxy-3,5-dimethyl-2-cyclopentene-1
-One, 2,5-dimethyl-4-hydroxy-3 (2H) -thiophenone, 2-hydroxy-3-ethyl-2-cyclopentene-1-
On, tetronic acid or 2,3-pentanedione is preferred.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION The melanin production inhibitor of the present invention comprises:
General formula (1)

[0016]

Embedded image Wherein A is O ₂ , S ₂ , CH ₂ , R ₁ -R ₉ are a hydrogen atom, a hydroxyl group, a formyl group, a C 1-6 acyl group, a C 1-6 acyloxy group, a carbon number 2 to 6 alkoxycarbonyl groups, or a hydroxyl group, an acyloxy group having 1 to 6 carbon atoms which may be substituted by a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms which may be substituted by a hydroxyl group, or a hydroxyl group may be substituted A hydrocarbon group having 1 to 9 carbon atoms which may be substituted by a group selected from alkenyloxy groups having 2 to 5 carbon atoms. ] At least one compound represented by the formula:

Although it has been reported that some of the compounds used in the present invention can be used as fragrances, it has never been known that they have a melanin production inhibitory action.

In the general formula (1), among the groups represented by R _{1 to} R ₉ , the unsubstituted hydrocarbon group having 1 to 9 carbon atoms may be either saturated or unsaturated. Often,
It may be linear, branched or cyclic. More preferably, it is a linear or branched alkyl group, alkenyl group or alkynyl group having 1 to 3 carbon atoms (here, there may be a plurality of double bonds and triple bonds). Preferred specific examples of these groups include a methyl group, an ethyl group, an n-propyl group and an isopropyl group as an alkyl group; an allyl group and a 2-hexenyl group as an alkenyl group; and a 2,4-hexadiynyl group as an alkadienyl group. Is mentioned.

These hydrocarbon groups are substituted with a hydroxyl group, a formyl group, an acyl group having 1 to 6 carbon atoms, an acyloxy group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 2 to 6 carbon atoms, or a hydroxyl group or a hydroxyl group. A group selected from an alkoxy group having 1 to 5 carbon atoms and an alkenyloxy group having 2 to 5 carbon atoms which may be substituted by a hydroxyl group may be substituted. Here, as an acyl group having 1 to 6 carbon atoms, Includes an acetyl group, a butyryl group, a valeryl group, a malonyl group, and the like.
Examples of the acyloxy group having 2 to 6 carbon atoms include an acetoxy group, a butyryloxy group, and a valeryloxy group. Examples of the alkoxycarbonyl group having 2 to 6 carbon atoms include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group,
And a pentyloxycarbonyl group. Examples of the alkoxy group having 1 to 5 carbon atoms which may be substituted by a hydroxyl group include a methoxy group, a propoxy group, an isopropoxy group, a butoxy group, and a 2-hydroxyethoxy group. Examples of the alkenyloxy group which may be substituted by a hydroxyl group having 2 to 5 carbon atoms include an allyloxy group and a pentenyloxy group.

These R₁~ R₉Of which R₁, R_TwoWhen
A hydrogen atom, a methyl group; R_ThreeIs a hydroxyl group; R_Four~ R
_FiveIs an alkyl group having 1 to 3 carbon atoms; R₆, R₈Is hydrogen field
Child; R ₇, R₉Is a hydrogen atom, a formyl group, and has 1 to 3 carbon atoms.
Acyl group having 1 to 3 carbon atoms, acyloxy group having 1 to 3 carbon atoms, 2 carbon atoms
To 4 alkoxycarbonyl groups, or a hydroxyl group, carbon
A group selected from the acyloxy groups of formulas 1 to 3 is substituted
Particularly preferred are hydrocarbon groups having 1 to 6 carbon atoms.

Specific examples of the compound represented by the general formula (1) include 5-methyl-2 (3H) -furanone, 2-butene-4-olide, 2-hydroxymethylfuran, and 2,5-dimethyl-4. -Hydroxy-3 (2H) -furanone, 2-formylfuran, 3-formylfuran, methyl α-furyl ketone, furfuryl acetate, 2-hydroxy-3-methyl-2-cyclopenten-1-one, 2-hydroxy-3 , 5-Dimethyl-2-cyclopentene-1-, 2,5-one-dimethyl-4-hydroxy
-3 (2H) -thiophenone, 2-hydroxy-3-ethyl-2-cyclopenten-1-one, tetronic acid, 2,3-pentanedione, and the like. These may be used alone or in combination of two or more. They can be used in combination.

These compounds can be purchased from commercial products and used, but can also be synthesized according to known methods.

The compound represented by the general formula (1) of the present invention exhibits an excellent melanin production inhibitory effect as described below.

The melanin production inhibitor of the present invention contains a compound represented by the general formula (1) as an active ingredient. The compounding ratio of the compound represented by the general formula (1) is 0.00001% The content is preferably set to 10% by weight to 10% by weight (hereinafter simply referred to as “%”), more preferably 0.0001 to 5%.

Further, the melanin production inhibitor of the present invention includes, in addition to the compound represented by the general formula (1), various optional components used in ordinary cosmetics, quasi-drugs, pharmaceuticals, etc., such as oils and fats , Surfactants, alcohols, fatty acids, preservatives, bactericides, thickeners, antioxidants, pigments, fragrances, water-soluble polymers, ultraviolet absorbers, chelating agents, pH adjusters, buffers, purified water Other components can be appropriately blended.

Further, by adding various ultraviolet absorbing substances, the effect of preventing sunburn can be improved.

The melanin production inhibitor of the present invention can be used as a medicament, a quasi-drug, or a medicinal product by blending the above-mentioned active ingredient and other ingredients as required for various purposes.
Can be adjusted as cosmetics. Specifically, lotions, emulsions, creams, packs, skin cleansers, haptics, plasters, pastes, ointments, essences,
Gels, shampoos, rinses, powders, foundations, lotions, facial cleansers, hair tonics, hair tonics, bath preparations and the like can be prepared. In this case, as the other components, in addition to the above-described components, components conventionally used for such applications can be appropriately selected and blended.

Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these Examples.

[0029]

[Examples] (Example 1, Comparative Example) (Test method) 1.5 ml, 1.5 M phosphate buffer (potassium dihydrogen phosphate: manufactured by Kanto Chemical Co., Ltd., potassium phosphate: manufactured by Wako Pure Chemical Industries, Ltd.) 0.3 ml of mM tyrosine (manufactured by Tokyo Kasei Kogyo Co., Ltd.) and 0.5 ml of activator were added and stirred.
0.2 ml of a 1: 2 dilution was added. Stir until the solution is clear, and add 0.3 mg / ml mushroom tyrosinase (Sig
After adding 0.3 ml (manufactured by ma), the mixture was quickly stirred, and then incubated at 37 ° C. for 1 hour in a shaking thermostat. 1 hour later, UV
Wavelength 64 using a spectrophotometer (JASCO: UVIDEC-610C)
The amount of melanin produced was determined by measuring the absorbance at 0 nm. A sample to which 0.3 ml of buffer was added instead of tyrosinase was measured for each sample and used as a blank. As a control, ethanol was added instead of the above sample solution, and the measurement was performed in the same manner as a control.

(Calculation formula) Melanin suppression effect (%) = (A− (C−B)) / A × 100 (however, A: absorbance of control, B: absorbance of blank, C: absorbance of sample) It is shown in Table 1.

[0031]

[Table 1] Further, instead of the fragrance substance of the present invention shown in Table 1, each compound (sample) shown in Table 2 as a comparative example was similarly carried out. Table 2 shows the results.

[0032]

[Table 2] As is clear from the results shown in Table 1, the production of melanin was suppressed in the solution to which the fragrance substance of the present invention was added.
Furthermore, as shown in Table 2, the inhibitory effect was higher than that of a known melanin production inhibitor.

(Example 2) (Test method) 1.5 ml of 0.01 M phosphate buffer (potassium dihydrogen phosphate: manufactured by Kanto Chemical Co., Ltd., potassium phosphate: manufactured by Wako Pure Chemical Industries, Ltd.), 1.5 mM tyrosine (Tokyo, Japan) Add 0.3 ml of activator and 0.3 ml of activator and stir, add 0.2 ml of 5-methyl-2 (3H) -furanone diluted with ethanol and add 5-methyl-2 (3H) -furanone. Those with different concentrations were adjusted. These were stirred until the solution became clear, and 0.3 mg / ml mushroom tyrosinase (Sigma
After adding 0.3 ml, the mixture was quickly stirred and incubated at 37 ° C. for 1 hour in a shaking thermostat. One hour later, use a UV spectrophotometer (JASCO: UVIDEC-610C) to obtain a wavelength of 640.
The absorbance at nm was measured. A sample to which 0.3 ml of buffer was added instead of tyrosinase was measured and used as a blank. As a control, ethanol was added instead of the above-mentioned sample solution, and the same measurement was carried out and used as a control. The same operation was performed for 2,5-dimethyl-4-hydroxy-3 (2H) -thiophenone. Kojic acid, a known melanin production inhibitor, was also measured for comparison.

(Calculation formula) Melanin suppression effect (%) = (A− (C−B)) / A × 100 (where A: absorbance of control, B: absorbance of blank, C: absorbance of sample) 1 (the ordinate represents the melanin production inhibition rate, and the abscissa represents the logarithm of the molar concentration of the sample).

FIG. 1 shows the concentration at which 50% of melanin production is inhibited (hereinafter referred to as IC ₅₀ ).

[0036]

[Table 3] As is clear from the results shown in Table 1, the production of melanin was suppressed in the solution containing the compound of the present invention. Further, as shown in Table 2, the inhibitory effect was higher than the conventionally used substances.

[0037]

According to the present invention, it has a favorable scent,
It is possible to obtain a melanin production inhibitor that masks the bad smell of the base material used and has an extremely high melanin production inhibitory action without side effects on the skin and scalp.

[Brief description of the drawings]

FIG. 1 is a graph showing the melanin production inhibition rate (the vertical axis represents the melanin production inhibition rate and the horizontal axis represents the logarithm of the molar concentration of the sample).

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Nobuhiko Ito 1573-4 Funagata, Noda City, Chiba Pref. F term (reference) 4C083 AB052 AB282 AC102 AC211 AC582 AC841 AC842 AC861 EE01 EE10 EE16 4C206 AA01 AA02 CB21 MA01 MA04 MA83 ZA89

Claims (3)

[Claims] 1. A compound of the general formula (1) Wherein A is O ₂ , S ₂ , CH ₂ , R ₁ -R ₉ are a hydrogen atom, a hydroxyl group, a formyl group, a C 1-6 acyl group, a C 1-6 acyloxy group, a carbon number 2 to 6 alkoxycarbonyl groups, or a hydroxyl group, an acyloxy group having 1 to 6 carbon atoms which may be substituted by a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms which may be substituted by a hydroxyl group, or a hydroxyl group may be substituted It represents a hydrocarbon group having 1 to 9 carbon atoms which may be substituted by a group selected from alkenyloxy groups having 2 to 5 carbon atoms. ] A melanin production inhibitor comprising at least one compound represented by the formula: 2. A compound of the general formula (2)[Wherein A is O, S, CH_Two, R₁, R_TwoIs hydrogen field
Child, methyl group, R_ThreeIs a hydroxyl group, R_Four~ R_FiveHas 1 to 1 carbon atoms
An alkyl group of 3, R₆, R₈Is a hydrogen atom, R₇, R ₉Is
Hydrogen atom, formyl group, acyl group having 1 to 3 carbon atoms, carbon
Acyloxy group having 1 to 3 atoms, alkoxy having 2 to 4 carbon atoms
Carbonyl group or hydroxyl group, acyl having 1 to 3 carbon atoms
1 carbon atom which may be substituted by a group selected from oxy groups
To 6 hydrocarbon groups. ] The compound represented by
Inhibition of melanin production characterized by containing at least one
Agent. 3. The compound represented by the general formula (1):
5-methyl-2 (3H) -furanone, 2-butene-4-olide, 2-hydroxymethylfuran, 2,5-dimethyl-4-hydroxy
-3 (2H) -furanone, 2-formylfuran, 3-formyl
Furan, methyl α-furyl ketone, furfuryl acetate, 2-hydroxy-3-methyl-2-cyclopentene-1-
On, 2-hydroxy-3,5-dimethyl-2-cyclopenten-1-one, 2,5-dimethyl-4-hydroxy-3 (2H) -thiophenone, 2-hydroxy-3-ethyl-2-cyclopentene
The melanin production inhibitor according to claim 1, which is 1-one, tetronic acid or 2,3-pentanedione.