JP2549127B2 - Topical drug for suppressing melanin production - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial field of application] The present invention relates to an external preparation for suppressing melanin production, which is incorporated into a cosmetic base or an ointment and has a whitening effect and a sunburn preventing effect. The present invention relates to a melanin production-inhibiting topical drug capable of achieving the above-mentioned additive effects by using kojic acid or its ester in combination with a specific crude drug.

[Conventional technology and problems]

It is known that kojic acid or its ester has a melanin production inhibitory action (JP-A-53-18739, JP-A-56-7776, JP-A-56-79616, (Kaisho 59-33207, etc.).

These kojic acids or their esters have the effect of suppressing the activity of tyrosinase, which is an enzyme that converts tyrosine to dopa and dopa to dopaquinone in the mechanism of melanin production, and as a result, suppresses the production of melanin.

In order to obtain a more effective melanin production inhibitory effect, the present inventors have synthesized various derivatives based on kojic acid or its ester and tried to prepare it with other drugs,
Surprisingly, it was found that the addition of crude drug suppresses the generation of melanin in a recurrent manner, and thus completed the present invention.

[Means for solving problems]

That is, the present invention relates to an external preparation for suppressing melanin production, which comprises kojic acid or its ester and a specific crude drug as active ingredients.

[Operation and Embodiment]

As described above, it is known that kojic acid or its ester has a melanin production inhibitory action, while,
It is also known that the herbs such as quince, toki, licorice, reishi, Kamala and mulberry bark have a whitening effect. However, surprisingly, when blending these different active ingredients, it is not the additive effect of adding the two effects at the end,
As will be described later, it is possible to obtain a cumulative effect that exceeds each effect. The mechanism of action is not clear, but it is considered that some delicate correlational action occurs in addition to the complementary action in which the other one complements a part that cannot be covered by one action.

One of the active ingredients of the present invention, kojic acid or its ester, has the general formula: (Wherein, R ¹ and R ² are the same or different and are a hydrogen atom or an acyl group having 3 to 20 carbon atoms).

As the ester, kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid monostearate, monoester such as kojic acid monocinnamoate or kojic acid monobenzoate, kojic acid dibutyrate, kojic acid dipalmitate, Diesters such as kojic acid distyalate or kojic acid dioleate are preferred. The monoester is preferably one in which the 5-hydroxyl group of kojic acid is esterified. When esterified, melanin production inhibitory action is equivalent to that of kojic acid, but stability against pH and light is improved.

The other active ingredient, a crude drug, is at least one selected from the group consisting of quince, toki, licorice, ganoderma, camara, and mulberry bark, and water, ethanol, propylene glycol, 1,3- It is used in a usual form such as a product extracted with a solvent such as butylene glycol or a mixed solution thereof, or a dried product thereof. In the case of licorice, in particular, it may be used in the form of liquiritin (licorice flavonoid), which is the active ingredient, in addition to the extract powder.

The external medicine of the present invention is an emulsion, lotion, liniment, ointment as well as cosmetics such as cream, lotion, pack, powder, etc. for the purpose of suppressing the production of melanin and preventing whitening or sunburn. Can be formulated into various external forms such as quasi-drugs such as agents, and the bases, excipients, stabilizers, pigments, fragrances, UV absorbers, antioxidants, preservatives, metals that are commonly used in each formulation You may mix | blend a blocking agent, an organic acid, etc. suitably.

The compounding ratio of kojic acid or its ester and crude drug varies depending on the combination, but is usually 1.0: 0.01 to 1.0: 10 by weight.
It is 0, preferably 1.0: 0.1 to 1.0: 10. The content of both active ingredients may vary depending on the form of use, purpose of use, method of use, dosage form, etc., but for example, in cosmetics, it is 0.01 to 20% (weight%, the same below), preferably 0.5 to 10%. In the case of agents, it is 0.01-10%, preferably 0.5% -5%.

Neither kojic acid, its ester, nor herbal medicines are harmless to the human body, and there is no problem even if they are used in combination.

Next, the external preparation for melanin production inhibition of the present invention will be explained based on Examples, but the present invention is not limited to such Examples.

Example 1 B-16 cultured cells derived from Caus scrotum were seeded in an Eagle MEM medium containing 10% fetal bovine serum to which kojic acid and crude drugs shown in Table 1 were added at the concentrations shown in the same table, and 37 ° C. 5,
After culturing for 5 days under the condition of% CO, the cells were dispersed with trypsin, centrifuged at 1,000 rpm for 5 minutes to collect the cells, and the blackness thereof was visually determined.

 The criteria for judgment are as follows.

-: Similar to the case where no melanin production inhibitor was added +: Slight whitening ++: Fair whitening +++: Almost whitening The results are shown in Table 1.

Example 2 A 2 × 2 cm site was provided on the inside of the upper right arm of the test participants (30 healthy male / female volunteers). Aluminum foil was set on the arm so that only the test site could be irradiated with ultraviolet rays, and two FL20S / BLB lamps and two FL20S / E-30 lamps from Toshiba Corp. were simultaneously installed at a distance of 10 cm and 0.8 × 10 ^-7 erg. /cm
It was irradiated three consecutive times in the ³ / times / day. Prior to irradiation, the test site was thoroughly washed with warm water. After the irradiation, the sample shown in Table 2 was applied to such a site three times a day (morning, noon and night). For the evaluation, the degree of pigmentation after 3 weeks was visually evaluated. The degree of improvement was evaluated in three grades of excellent, effective and ineffective.

 The results are shown in Table 2.

Parts by weight Kojic acid ester shown in Table 2 1.00 Crude drug shown in Table 2 1.00 (However, licorice extract powder and liquiritin 1.10) (A) Polyoxyethylene glycol monostearate (40E.O.) 2.00 Self-emulsifying monostearin Acid glycerin 5.00 Stearic acid 5.00 Behenyl alcohol 1.00 Liquid paraffin 1.00 parts by weight Glycerin trioctanoate 10.00 Preservative Suitable amount Fragrance (B) 1,3-butylene glycol 5.00 Purified water Residue (process) Kojic acid ester as a component belonging to (A) Was added and dissolved by heating (oil phase). Separately, a crude drug was added to the component belonging to the component (B) and dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, the mixture was emulsified with stirring, and then cooled to obtain a vanishing cream.

Next, representative prescription examples using the melanin production-suppressing drug of the present invention will be given, but the present invention is not limited to these.

(Lotion) Parts by weight Polyoxyethylene hydrogenated castor oil (60E.O.) 1.00 Ethanol 15.00 Citric acid 0.10 Sodium citrate 0.30 1,3-Butyleneglycrole 4.00 Kojic acid 1.00 Reishi ethanol extract 5.00 Preservative proper amount Fragrance Trace amount of purified water Residue (Production method) Each component was uniformly stirred, mixed and dissolved to give a lotion.

(Emulsion) parts by weight (A) Polyoxyethylene behenyl ether (20E.O.)
0.50 Polyoxyethylene Sobite Tetraoleate (60E.
O.) 1.00 Lipophilic glyceryl monostearate 1.00 Stearic acid 0.50 Behenyl alcohol 0.50 Avocado oil 1.00 Natural Vitamin E 0.02 Kojic acid monopalmitate 2.00 Preservative suitable amount Fragrance (B) 1,3-butylene glycol 5.00 Carboxyvinyl polymer 1.00 Sodium N-lauroyl-L-glutamate 0.50 Silica extract 1.00 Purified water Residue (Production method) The components belonging to (A) were dissolved by heating (oil phase), and the components belonging to (B) were dissolved by heating (aqueous phase). ). The aqueous phase was added to the oil phase, the mixture was stirred and emulsified, and then cooled to obtain an emulsion.

(Jelly-like pack) Weight part Citric acid 0.20 Propylene glycol 4.00 Concentrated glycerin 4.00 Ethanol 2.00 Carboxyvinyl polymer 1.00 Potassium carbonate 0.60 Kojic acid 0.50 Mulberry bark extract 3.00 Preservative A suitable amount Fragrance A minute amount of purified water Residue (production method) The mixture was stirred, mixed and dissolved to obtain a jelly-like pack.

(Cream pack) Parts by weight (A) Polyoxyethylene behenyl ether (20E.O.)
1.00 Polyoxyethylene Sobite Tetraoleate (40E.
O.) 2.00 Lipophilic type glyceryl monostearate 2.00 Behenyl alcohol 3.00 Squalane 25.00 Glycerin octanoate 10.00 Natural vitamin E 0.04 Monocinnamoate kojic acid 2.00 Preservative A suitable amount Fragrance (B) 1,3-butylene glycol 5.00 dl-pyrrolidone Sodium carboxylate 1.50 Citric acid 0.04 Liquiritin 0.05 Purified water Residue (Production method) The ingredients belonging to (A) were dissolved by heating (oil phase), and the ingredients belonging to (B) were separately dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, and the mixture was stirred and emulsified, and then cooled to obtain a creamy pack.

(Ointment) Part by weight (A) Polyoxyethylene sorbitan monostearate (60E.O.) 1.00 Polyoxyethylene sorbit tetraoleate (60E.O.)
O.) 1.50 Self-emulsifying glyceryl monostearate 1.50 Salix beeswax 2.00 Paraffin 2.00 Stearic acid 3.00 Behenyl alcohol 3.00 Shea butter 12.00 Liquid paraffin 5.00 parts by weight Natural vitamin E 0.04 Methyl polysiloxane 0.01 Kojic acid monobenzoate 3.00 Preservative Suitable amount Fragrance Fraction ( B) 1,3-butylene glycol 5.00 citric acid 0.30 dl-lauroyl-L-glutamate sodium 0.50 mulberry bark 50% ethanol extract 5.00 purified water Residue (process) Heat-dissolve the components belonging to (A) (oil phase) ), Separately, the components belonging to (B) were dissolved by heating (aqueous phase). The aqueous phase was added to the oil phase, and the mixture was emulsified with stirring, and then cooled to obtain an ointment.

(Whitening powder) Parts by weight Octyldodecyl myristate 1.0 Kojic acid 2.0 Kamala extract 0.5 Fragrance Maltitol Residue (Production method) Each component was uniformly stirred and mixed to obtain a whitening powder.

〔The invention's effect〕

According to the melanin production inhibiting external preparation of the present invention, by combining kojic acid or its ester with a specific crude drug, a contradictory melanin production inhibiting action is obtained, and a more remarkable whitening and sunburn preventing effect is obtained. Can be played.

Claims (1)

(57) [Claims] 1. A topical drug for suppressing melanin production, which comprises kojic acid or its ester and at least one selected from the group consisting of cinnamon bark, toki, licorice, reishi, camara and mulberry bark.