JPH0592916A - Medicine capable of suppressing melanogenesis for external use - Google Patents

Abstract

PURPOSE:To obtain a whitening medicine for external use, containing napththoresorcinol as an active ingredient, having excellent inhibitory action on tyrosinase activity and improved suppressing action on melanogenesis and capable of producing excellent whitening action. CONSTITUTION:A medicine for external use is obtained by blending 0.01-15.0%, preferably 0.1-10.0% compound expressed by the formula as an active ingredient with other ingredients. The above-mentioned compound is obtained by cyclizing ethylphenyl acetoacetate or heating 4-amino-2-naphthol-1-sulfonic acid with water. The medicine for external use is used as a skin cosmetic, such as toilet water, a cream, a milky lotion or a pack or a quasi-drug such as an ointment or a cataplasm.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for suppressing melanin production, and more particularly to an external preparation for suppressing melanin production containing naphthresorcinol as an active ingredient.

[0002]

2. Description of the Related Art Conventionally, as a quasi-drug intended for whitening cosmetics or whitening, a whitening external preparation containing various whitening agents has been known.

Vitamin C, cysteine, colloidal sulfur and the like have been tried as a whitening agent, but they are poor in stability and the effect as a whitening agent is extremely weak, and it is difficult to say that they are satisfactory whitening cosmetics. is there.

The present inventors have been researching external preparations such as whitening cosmetics and ointments for many years, and have already
Invented external preparations such as kojic acid, kojic acid derivatives, and cosmetics containing isokojic acid as a whitening component.
69, Japanese Patent Publication 60-9722, Japanese Patent Publication 61
No. 60801 and Japanese Patent Publication No. 62-59084.

Further, Japanese Patent Laid-Open No. 2-49715 discloses that
General formula

[0006]

[Chemical 1]

A whitening agent containing a resorcinol derivative represented by the formula (wherein R is a linear alkyl group having 2 to 12 carbon atoms in which one hydrogen atom may be substituted with a methyl group) as an active ingredient. It is disclosed.

[0008]

DISCLOSURE OF THE INVENTION The inventors of the present invention pursued a compound having an excellent melanin production-inhibiting effect in the course of continuing research on fair-whitening cosmetics, and as a result, naphthresorcinol produced excellent melanin production in B16 cells. Based on this finding, we succeeded in obtaining an excellent external preparation for suppressing melanin production, based on the finding that it has an inhibitory action and a tyrosinase activity inhibiting action.

[0009]

The present invention requires an external preparation for suppressing melanin production containing naphthresorcinol as an active ingredient.

Naphthoresorcinol, which is an active ingredient in the external preparation for suppressing melanin production of the present invention, has the formula:

[0011]

[Chemical 2]

It is a substance having a molecular weight of 160.16 and a melting point of 124 to 125 ° C., which is soluble in water, alcohols and ethers, and can be obtained by cyclizing ethylphenyl ester of acetoacetic acid. -Amino-2
It can also be obtained by heating naphthol-1-sulfonic acid with water.

The external preparation for suppressing melanin production of the present invention is mainly used as a skin cosmetic such as lotion, cream, milky lotion or pack, or as a quasi drug such as ointment or pack. The above-mentioned naphthresorcinol is blended together with an auxiliary agent in the base used for the external preparation.

The content of naphthresorcinol is 0.01 to 15.0% of the total amount of the external preparation, preferably 0.1 to 1.
It is 0.0%.

[0015]

BEST MODE FOR CARRYING OUT THE INVENTION A specific external preparation for suppressing melanin production using the naphthresorcinol of the present invention will be described.

Preparation Example of External Agent Preparation Example 1 (Toilet lotion) A moisturizing agent such as glycerin or propylene glycol, a skin nutrient, etc. are dissolved in purified water, and ethyl alcohol in which a preservative or a perfume is dissolved. The required amount of the above-mentioned naphthresorcinol is added to the cosmetic base prepared by mixing the above-mentioned at room temperature.

Preparation Example 2 (Cream) Prepared as the water phase part is purified water mixed with a humectant such as glycerin or sorbit, and the required amount of the above-mentioned naphthresorcinol is mixed therein.

As the oil phase part, solid oil components such as beeswax, paraffin, microphone crystallin wax, ceresin, higher fatty acid, and solidified oil, and liquid oil components such as squalane, liquid paraffin, various ester oils, preservatives, surfactants, etc. Prepare a mixture of the oily ingredients.

Next, the aqueous phase is gradually heated to about 80 ° C.
At this point, the oil phase portion heated to about the same temperature is added little by little and emulsified to give a cream.

Preparation Example 3 (Emulsion) As a water phase part, a predetermined amount of naphthresorcinol is added to a mixture obtained by adding a humectant such as glycerin and a pH adjusting agent of acid or alkali to purified water and heating and mixing.

As the oil phase portion, solid oil components such as beeswax and paraffin, semisolid oil components such as petrolatum and lanolin, liquid oil components such as squalane, liquid paraffin and various ester oils, and oil components such as preservatives and surfactants are added. Add and mix and heat to about 80 ° C.

Next, this oil phase part is added to the water phase part heated to a similar temperature to carry out preliminary emulsification, and a protective colloid agent such as carboxyvinyl polymer and carboxymethyl cellulose is added to this, and a homomixer is added. To evenly emulsify to form an emulsion.

Preparation Example 4 (pack) Purified water is swelled by adding a moisturizing agent such as glycerin, polyvinyl alcohol, a filming agent such as bee gum and the like, and if necessary, kaolin, talc, zinc oxide and the like are added. Powder is added, and ethyl alcohol in which flavors and preservatives are dissolved is further added and kneaded until a paste is formed. At any stage of the addition, the naphthresorcinol is mixed in a predetermined amount.

Preparation Example 5 (Ointment) A water phase part is prepared by adding a hydrophilic component such as naphthresorcinol, glycerin or a sorbit humectant to purified water.

The oil phase portion includes solid oil components such as beeswax, paraffin, microcrystalline wax, ceresin, higher fatty acids and hardened oil, semisolid oil components such as petrolatum, lanolin and glycerides, and squalane, liquid paraffin, various ester oils and the like. It is prepared by adding horse oil to liquid oil along with oil components such as preservatives and surfactants. Next, gently stir while warming the aqueous phase, and when it reaches about 80 ° C,
The oil phase portion heated to the same degree is gradually added to give an ointment.

As described above, the naphthresorcinol in the present invention is optionally blended with the base of the external preparation, but when the external preparation is composed of the oil phase and the water phase, the water phase part is always used. It is necessary to be blended with.

[0027]

EXAMPLES The present invention will be described based on examples below.

Example 1 (Cream) (wt%) 1 Polyethylene glycol monostearate (40 EO) 2.00 2 Self-emulsifying glyceryl monostearate 5.00 3 Stearic acid 5.00 4 Behenyl alcohol 1.00 5 Liquid paraffin 10.00 6 Glycerin trioctanoate 10.00 7 Naftresorcinol 4.00 8 Paraoxybenzoic acid ester 0.20 9 1,3-Butylene glycol 5.00 10 Disodium edetate 0.01 11 Purified water to 100 Manufacturing Method A 1 to 6 are heated and dissolved.

B 7 to 11 are heated and dissolved.

B is added to C A, emulsified, stirred, and cooled.

After cooling D C, it is filled in a container to be a product after inspection.

Dosage and Dose Appropriate amount is applied to the face.

Example 2 (Emulsion) (wt%) 1 Polyoxyethylene sorbitan monostearate (20 EO) 1.00 2 Polyoxyethylene sorbit tetraoleate (60 EO) 0.50 3 Lipophilic Type Glycerin monostearate 1.00 4 Stearic acid 0.50 5 Behenyl alcohol 0.50 6 Avocado oil 4.00 7 Glyceryl trioctanoate 4.00 8 Naphthoresorcinol 3.000 9 Paraoxybenzoate 0.20 10 1,3 -Butylene glycol 5.00 11 Xanthan gum 0.14 12 Disodium edetate 0.01 13 Purified water to 100 Manufacturing method A 1 to 7 are heated and dissolved.

B8 to 13 are heated and dissolved.

B is added to C A, emulsified, stirred, and cooled.

After cooling D C, it is filled in a container to be a product after inspection.

Dosage and Dose Appropriate amount is applied to the face.

Example 3 (lotion) (wt%) 1 polyoxyethylene hydrogenated castor oil (60 EO) 8.02 ethanol 15.00 3 naphthresorcinol 1.00 4 paraoxybenzoic acid ester 0.10 5 Citric acid 0.10 6 Sodium citrate 0.30 7 1,3-Butylene glycol 4.00 8 Disodium edetate 0.01 9 Purified water to 100 Manufacturing method A 1 to 9 are uniformly stirred and dissolved.

B A is filled in a container, and a product is obtained after the inspection.

Dosage and Dose Appropriate amount is applied to the face.

Example 4 (Cream pack) (% by weight) 1 Polyethylene glycol monostearate (40 EO) 2.00 2 Self-emulsifying glyceryl monostearate 5.00 3 Stearic acid 5.00 4 Behenyl alcohol 0. 50 5 Squalane 15.00 6 Cetyl octanoate 5.00 7 Naftresorcinol 5.00 8 Paraoxybenzoic acid ester 0.20 9 1,3-Butylene glycol 5.00 10 Disodium edetate 0.01 11 Purified water to 100 Manufacturing Method A 1 to 6 are heated and dissolved.

B7-11 are heated and dissolved.

B is added to C A, emulsified, stirred, and cooled.

After cooling D C, it is filled in a container to be a product after inspection.

Dosage and Dose Appropriate amount is applied to the face.

Example 5 (Ointment) (wt%) 1 Polyoxyethylene sorbitan monostearate (20 EO) 1.00 2 Polyoxyethylene sorbit tetraoleate (60 EO) 1.50 3 self Emulsified Glycerin Monostearate 1.50 4 White Beeswax 2.00 5 Paraffin 2.00 6 Stearic Acid 3.00 7 Behenyl Alcohol 3.00 8 Liquid Paraffin 5.00 9 Avocado Oil 12.00 10 Vitamin E 0.20 11 Naftresorcinol 10.00 12 Paraoxybenzoic acid ester 0.20 13 1,3-butylene glycol 5.00 14 Purified water -100 Manufacturing method A 1-10 is heated and melt | dissolved.

B11 to 14 are heated and dissolved.

B is added to C A, emulsified, stirred, and cooled.

After cooling D C, it is filled in a container to be a product after inspection.

Dosage and Dose Appropriate amount is applied to the face.

Example 6 (Emulsion) (wt%) 1 Polyoxyethylene sorbitan monostearate (20 EO) 1.00 2 Polyoxyethylene sorbit tetraoleate (60 EO) 0.50 3 Lipophilic Type Glycerin monostearate 1.00 4 Stearic acid 0.50 5 Behenyl alcohol 0.50 6 Avocado oil 4.00 7 Glyceryl trioctanoate 4.00 8 Naphthoresorcinol 3.000 9 Paraoxybenzoate 0.20 10 1,3 -Butylene glycol 5.00 11 Xanthan gum 0.14 12 Disodium edetate 0.01 13 Purified water to 100 Manufacturing method A 1 to 7 are heated and dissolved.

A part of B8 to 13 is heated and dissolved.

B is added to C A, the rest of 13 is added, and the mixture is emulsified, stirred, and cooled.

After cooling D C, it is filled in a container to be a product after inspection.

[Test Example] Evaluation of Melanin Production Inhibitory Effect of Naftresorcinol The tyrosinase activity inhibitory effect of naphthoresorcinol and melanin production inhibitory effect on cultured B16 cells were evaluated by the following methods.

(1) Tyrosinase activity inhibition test 100 mM phosphate buffer (pH 6.8) was added to B16 cells derived from mouse melanoma, and after homogenization, 30,000
The supernatant liquid centrifuged at 0 G was used as an enzyme solution. A 100 mM phosphate buffer (pH 6.8) is used as a buffer, and the tyrosinase activity inhibitory effect is measured by the following measuring method.

A sample solution containing 100 μl of the above enzyme solution, a buffer solution, and naphthresorcinol at a predetermined concentration is added.

After 2 minutes, 10 mM dopa solution 333
Add μl, incubate at 37 ° C., 475 nm
The absorbance was measured.

As a control, a kojic acid solution was used, and as a control, 100 μl of enzyme solution, 333 μl of 10 mM dopa solution, and 100 mM phosphate buffer solution (pH 6.
8) With the addition of 567 μl, the change in absorbance with time was measured by the same measurement. The results are shown in Table 1.

[0060]

[Table 1]

As is clear from the above results, naphthresorcinol, which is the active ingredient of the present invention, has a tyrosinase activity effect which is about 8 times higher than that of control kojic acid when compared at a 50% inhibitory concentration.

(2) Culture B16 Mouse Melanoma Cell Melanin Production Inhibition Test Naftresorcinol was added to the concentration shown in Table 2 10
Mouse melanoma-derived B16 cultured cells were seeded in an Eagle MEM medium containing 15% fetal bovine serum and incubated at 37 ° C., 5% CO ₂
After culturing for 5 days under the conditions, the cells were dispersed with trypsin, centrifuged at 1,000 rpm for 5 minutes to collect the cells, and the degree of blackness was visually determined. The results are shown in Table 2.

The criteria for judgment are as follows.

-Similar to that without addition of sample (control) + Slightly whitening ++ Fairly whitening +++ Almost whitening

[0065]

[Table 2]

As is clear from the above results, naphthresorcinol, which is the active ingredient of the present invention, shows the same degree of cell whiteness at an evaluation concentration of about 1/16 of that of kojic acid as a control.

[0067]

INDUSTRIAL APPLICABILITY According to the present invention, there is provided an external preparation for suppressing melanin production, which comprises as an active ingredient a compound which is soluble in water, alcohol and ether and has an excellent activity for suppressing melanin production and an activity for inhibiting tyrosinase activity.

Claims (1)

[Claims] 1. An external preparation for suppressing melanin production, which comprises naphthresorcinol as an active ingredient.