JP6177638B2 - Skin external preparation for whitening - Google Patents

Description

  The present invention relates to an external preparation for skin comprising a compound salt having a specific structure. Preferably, since it contains acesulfame potassium salt as a compound salt and has a whitening effect, it relates to a skin external preparation used for whitening.

  Various functions are required for external preparations for skin, and new substances and new methods have been studied and developed. As one of them, the components for external preparation for skin used for whitening are required to be the same as or higher than those of conventionally known active ingredients, or have higher safety.

  By the way, acesulfame potassium is known as one of artificial sweeteners and is a substance having a sweetness that is said to be 200 times that of sucrose (sucrose). Several decades have passed since this substance was discovered as a sweetener, and it is a substance that has been designated as a food additive in Japan and has been confirmed to be safe, with use standards and ingredient standards established. This acesulfame potassium is, for example, as shown in Patent Documents 1 and 2, etc., sweeteners utilizing a synergistic effect with other ingredients in confectionery, sweeteners for improving the taste of oral liquid, It has been widely studied and used in practice as a sweetening ingredient.

Patent No. 4889846 Japanese Patent No. 5211777

  An object of this invention is to provide the novel skin external preparation component. In particular, ingredients that are used in whitening applications and have been widely confirmed to be safe for oral administration are used.

  As a result of searching for ingredients used for the topical skin preparation, the present inventor has found that the following components exhibit an effective function as a topical skin preparation, and have reached the present invention.

That is, the present invention relates to the following inventions.
<1> A skin external preparation for whitening comprising a compound salt represented by the formula (1).

In the formula (1), R is an alkyl group, and M ⁺ is a cation of the compound salt represented by the formula (1).
<2> The skin external preparation for whitening according to the above <1>, comprising an acesulfame salt represented by the formula (2) wherein R is a methyl group in the formula (1).

<3> The skin external preparation for whitening according to <2>, wherein the acesulfame salt is acesulfame potassium.

  An object of the present invention is to provide a novel skin external preparation ingredient and to provide a skin external preparation containing the ingredient. The skin external preparation provided by the present invention has an excellent whitening effect, and further expands the range of design of conventional skin external preparations.

  DESCRIPTION OF EMBODIMENTS Embodiments of the present invention will be described in detail below. However, the description of the constituent elements described below is an example (representative example) of an embodiment of the present invention. It is not limited to the contents.

  The present invention relates to a skin external preparation comprising a compound salt represented by the formula (1). This external preparation for skin exhibits excellent melanin production inhibitory action and the like, and is suitable for, for example, whitening use.

In the formula (1), R is an alkyl group, and M ⁺ is a cation of the compound salt represented by the formula (1). Here, referring to the carbon number of R, it is preferably 1 to 5 carbon atoms, and more preferably 1 to 3 carbon atoms. Among these, a methyl group having 1 carbon is preferable.

  The kind of the salt of the compound salt of the present invention is not particularly limited, and examples thereof include salts such as ammonium salts and amino acid salts in addition to alkali metal salts such as sodium salts and potassium salts. Among these, alkali metal salts are preferable from the viewpoint of dissociation of ions and solubility as compound salts.

  6-methyl-1,2,3-oxathiazin-4 (3H) -one-2,2-dioxide, which is an example of the compound represented by the formula (1), is represented by the following formula: It is. This compound is an oxathiadinone dioxide derivative obtained by reacting diketene and sulfamic acid and reacting this with sulfur trioxide to form an acesulfame ring and then neutralizing it. Here, acesulfame potassium preferably used in the present invention can be obtained by neutralization with potassium hydroxide.

[Acesulfame salt]
The external skin preparation of the present invention preferably contains an acesulfame salt in which R in the formula (1) is a methyl group. The system name of acesulfame is 6-methyl-1,2,3-oxathiazin-4 (3H) -one-2,2-dioxide, and a salt thereof is used in the present invention. A typical acesulfame salt is shown in Formula (2). In particular, acesulfame potassium (a compound salt represented by the following formula (3)), which is a potassium salt that has been confirmed to be safe in food applications, is preferably used.

  The skin external preparation of this invention is provided with the form of the formulation containing the compound salt represented by said Formula (1) which is an active ingredient of this invention. Here, the form of the preparation can be provided for external use, and the external preparation for skin is generally used by selecting an acceptable base and directly applying it to the affected area. In this case, in addition to homogeneous preparations represented by lotions and essences, general emulsification systems such as O / W and W / O types represented by creams and emulsions, W / O / W, O / W / O-type special multi-layer emulsions, other types such as pastes, ointments and tinctures, sprays such as aerosols and sprays, patch types such as poultices and plasters, etc. The basic base is also used in combination with other components and is not particularly limited.

  In particular, acesulfame potassium, which is a representative compound salt of the present invention, dissolves well in water, alcohols and polyhydric alcohols, and therefore is used in cosmetics such as creams and emulsions (O / W and W / O) and lotions and essences. The mold can be blended almost without problems.

  In these present inventions, the amount of acesulfame salt used is in the case of cosmetics such as creams, lotions, emulsions, packs, lotions, essences, etc., and in the case of use as a dosage form such as sheet masks, poultices, plasters, etc. In any case, it is blended in the range of 0.001 to 25% by weight, preferably 0.01 to 15% by weight, more preferably 0.1 to 12% by weight based on the whole preparation. When the blending amount is small, the whitening effect may not be sufficiently exhibited. Further, even if it exceeds 25% by weight, there is no particular difference in effect from the case of less than that, and the preparation as a preparation may be restricted from the viewpoints of solubility and compatibility with other bases and the like.

  In the present invention, various known active ingredients that are usually used, for example, kojic acid, quercetin, glutathione, hydroquinone known as a whitening agent, and derivatives thereof, condensed tannins, caffeic acid, ellagic acid, etc. Phenolic compounds, peripheral vasodilators such as vitamin E, vitamin E nicotinate, nicotinic acid, nicotinic acid amide, various kinds of vitamins such as benzyl nicotinate, ginger tincture, chili pepper tincture, anti-inflammatory agents such as corticosteroids, ε -Various compounds such as aminocaproic acid, lysozyme chloride, glycyrrhizin, allantoin, and other extracts derived from animals, plants and microorganisms such as placenta extract, licorice extract, purple root extract, lactic acid bacteria culture extract, etc. Appropriately added according to the purpose of the application within a range that does not impair It is possible to use Te.

  Furthermore, in addition to these known active ingredients, the skin external preparation of the present invention, in addition to base components such as fats and oils, as well as known moisturizers, antiseptics, antioxidants, chelating agents, pH adjustments as necessary Various additives such as an agent, a fragrance, and a colorant can be used in combination as long as the effects of the present invention are not impaired.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to a following example, unless the summary is changed.

<Test Example 1> Cell test "Examples 1-4, Comparative Example 1, Reference Example 1"
As Examples 1 to 4, acesulfame potassium of acesulfame salt in which R is a methyl group and M is potassium in the compound represented by formula (1), which is one of the active ingredients of the external preparation for skin of the present invention, Using, the following melanin production inhibitory action was confirmed. Moreover, in order to confirm the difference of the presence or absence of an acesulfame salt, the test which does not add an acesulfame salt as a comparative example 1 was done. Further, as Reference Example 1, a test using kojic acid known to have an extremely high whitening effect was performed.

<Melanin production inhibitory action>
a) Test method The medium used was a MEM (Eagle's Minimum Essential Medium) medium supplemented with 10% FBS (fetal bovine serum), and the cells were B16 mouse melanoma cell F10 strain. A plastic petri dish (φ100 mm Falcon3003) was seeded with 0.5 × 10 ⁵ cells / mL and cultured for 24 hours.
After culturing for 24 hours, an aqueous solution of the sample was added in the amount shown in Table 1. After the sample was added, the medium was changed on the second day of culture, and the cells were cultured for 5 days at 5% CO ₂ and 37 ° C. After completion of the culture, cells grown on the bottom of the petri dish are collected with a cell scraper, suspended in PBS (Phosphate buffered saline), placed in a transparent centrifuge tube, centrifuged at 1,000 rpm for 2 minutes, and the resulting cell pellet The color tone was visually determined according to the following criteria.

・ Criteria-: Black (equivalent to control)
±: Black gray (slightly whiter than control)
+: Gray (equivalent to 2.5 mmol / L kojic acid)
++: White (whiter than kojic acid 2.5 mmol / L)

b) Test results Table 1 shows the determination results. Since acesulfame potassium did not show cytotoxicity at a concentration of 20 mmol / L, a decrease in cell growth rate was not observed. Thus, acesulfame potassium exhibited a melanin production inhibitory effect equivalent to a concentration of kojic acid of 2.5 mmol / L.

<Test Example 2> Human ultraviolet irradiation test "Example 5"
As Example 5, the pigmentation inhibitory effect by ultraviolet irradiation was evaluated for 10 human subjects.

<Inhibition of human ultraviolet irradiation pigmentation>
a) Test Method a-1) Preparation of Formulation As a test drug, a cream having the following formulation was prepared and used for the test.
・ Acesulfame potassium formulation (A)
The compounding components having the concentrations described in the following Formulation Example 1 were mixed by a conventional method for preparing a skin external preparation to obtain an acesulfame potassium compounded preparation (A).
[Formulation Example 1] (wt%)
Acesulfame potassium 10.00
1,3-butylene glycol 7.00
P-Hydroxybenzoate 0.30
Behenyl alcohol 5.00
Hardened oil 3.00
Stearic acid 2.40
Palmitic acid 2.00
Liquid paraffin 7.00
Octyldodecanol 4.00
Silicon oil 0.50
Polyoxyethylene behenyl ether 3.50
Glycerol monostearate 1.50
Polyoxyethylene hydrogenated castor oil 0.30
Purified water balance

・ Placebo preparation (B)
From the above acesulfame potassium-containing preparation (A), acesulfame potassium was removed and replaced with purified water to obtain a placebo preparation (B).

a-2) Application of test drug The test was conducted on 10 healthy subjects, and two 1.3 cm × 1.3 cm ultraviolet irradiation sites were provided on the inner side of the upper arm, and the test drug was applied.
The drug application was started 5 hours before the ultraviolet irradiation, and the drug was applied five times a day on the ultraviolet irradiation day and three times a day from the next day after the ultraviolet irradiation. Ultraviolet irradiation was performed for 3 consecutive days using a UVA + UVB lamp (FL20SE, FL20BLB) so as to be 1 MED per day (about 40 to 70 mJ / cm ² ).

a-3) Method for confirming whitening effect The degree of pigmentation was determined before, 7 days, 14 days and 21 days before the start of the test, and the whitening effect was examined by a comparison method between a 10% acesulfame potassium-containing preparation and a placebo preparation. The determination is made according to the following visual criteria (shown in Tables 2 and 3), and the skin color brightness (L value) is measured using a color difference meter (manufactured by Konica Minolta) as an objective index of pigmentation, and then irradiated with ultraviolet rays. The lightness of each observation day was subtracted from the previous lightness to obtain a ΔL value.

b) Test results Table 4 shows the test results. As is apparent from Table 4, a certain effect was observed in at least 8 out of 10 people. That is, it was confirmed that the preparation containing 10% acesulfame potassium has an effect of improving pigmentation. Here, subjects 3 and 6 are invalid, but they are relatively invalid compared to other subjects in the sense that the difference from the placebo test is small and it is difficult to judge the evaluation results, and the lightness indicated by the ΔL value is higher than that of the placebo. Can also be confirmed. During the test period, no skin irritation reaction was observed at the test drug application site of the subject, indicating that the product of the present invention is safe even in the form of the preparation.

[Prescription Example 2] Lotion (wt%)
Acesulfame potassium 3.00
Allantoin 0.50
Ethanol 15.00
Citric acid 0.10
P-Hydroxybenzoate 0.30
1,3-butylene glycol 4.00
Purified water balance Acesulfame potassium, which is one of the compound salts of the present invention, can be stably formulated even when used in a lotion as in Formulation Example 2, and the effect of the present invention is achieved at this concentration. To do.

[Prescription Example 3] Essence (wt%)
Acesulfame potassium 1.00
Dipotassium glycyrrhizinate 0.10
Sodium hyaluronate 5.00
Glycerin 2.00
P-Hydroxybenzoate 0.30
1% carboxyvinyl polymer aqueous solution 2.00
Edetate disodium 0.03
Purified water balance Acesulfame potassium which is one of the compound salts of the present invention can be stably formulated even when used in the essence as in Formulation Example 3, and the effect of the present invention is achieved at this concentration. .

[Formulation Example 4] Cream pack (wt%)
Acesulfame potassium 0.50
Dipotassium glycyrrhizinate 0.20
Polyethylene glycol 1500 5.00
Stearic acid diethanolamide 5.00
Stearic acid 5.00
Myristic acid 5.00
Coconut oil 15.00
Natural vitamin E 0.04
P-Hydroxybenzoate 0.30
dl-Pyrrolidonecarboxylate solution 5.00
Edetate disodium calcium 0.01
Purified water balance Acesulfame potassium, which is one of the compound salts of the present invention, can be stably formulated even when used in a cream pack as in Formulation Example 4, and the effect of the present invention is achieved at this concentration. To do.

[Prescription Example 5] Emulsion (wt%)
Acesulfame potassium 0.10
Octyldodecanol 3.00
Polyoxyethylene oleyl ether (20E.O.) 1.00
Stearic acid 0.50
Shea Butter 1.00
Avocado oil 4.00
P-Hydroxybenzoate 0.30
Xanthan gum 0.15
Natural vitamin E 0.01
Purified water balance Acesulfame potassium, which is one of the compound salts of the present invention, can be stably formulated even when used in the emulsion as in Formulation Example 5, and achieve the effects of the present invention at this concentration. .

  The present invention provides a compound salt used as an external preparation for skin. The external preparation for skin containing this compound salt is particularly useful because it has a whitening effect and the like.

Claims (3)

A skin whitening external preparation for whitening comprising a compound salt represented by the formula (1).
In the formula (1), R is an alkyl group, and M ⁺ is a cation of the compound salt represented by the formula (1). The whitening skin external preparation of Claim 1 containing the acesulfame salt represented by Formula (2) whose R is a methyl group in Formula (1).
The skin external preparation for whitening according to claim 2, wherein the acesulfame salt is acesulfame potassium.