JP2928414B2 - External preparation for skin - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external preparation for skin, and more particularly, to an external preparation for skin which is effective in preventing and treating skin pigmentation and, in particular, has improved stability.

[0002]

2. Description of the Related Art Spots and freckles and pigmentation after tanning are caused by the remarkable enhancement of melanin production due to the activation of pigment cells existing in the skin. I have. Generally, melanin is converted from tyrosine to dopa and dopa to dopaquinone by the action of the enzyme tyrosinase biosynthesized in pigment cells, and then formed via an intermediate such as 5,6-dihydroxyindole. .

[0003] Therefore, in order to prevent or improve the color darkness, it is necessary to inhibit the production during the melanin production process or to bleach the existing melanin in a light color. Based on this, various whitening components have been proposed. For example, sulfur compounds typified by glutathione are used for inhibiting tyrosinase activity, and hydrogen peroxide, hydroquinone, vitamin C and the like have been used for pale bleaching.

[0004] However, these conventional components have extremely poor stability in the formulation system and cause coloration and off-odor due to decomposition,
In terms of effect and efficacy, it was still insufficient at the cellular or biological level. Hydroquinone has a strong fairness effect, but has a problem in safety, such as causing irreversible vitiligo and rash. Under such circumstances, the present inventors have searched for a substance having good safety and stability and an excellent effect of improving skin pigmentation, and as a result, have found that arbutin satisfies this condition. (JP-A-60-16906).

[Problems to be solved by the invention]

However, subsequent studies have revealed that arbutin gradually becomes colored when stored for a long period of time under severe conditions such as heat and light in a prescription system. (Japanese Patent Application Laid-Open (JP-A) No. 61-21010) has also been proposed, but although this method has a stabilizing effect on heat, it does not have much effect on light and is still satisfactory. There is no situation to be.

[0006] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide an external preparation for skin having improved stability while improving the effect of arbutin on skin pigmentation. And

[0007]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that pantethein-
The inventors have found that S-sulfonic acid or a salt thereof exhibits an excellent effect of stabilizing arbutin in a formulation system, and based on this, completed the present invention.

That is, the present invention is an external preparation for skin characterized by containing arbutin and pantethein-S-sulfonic acid or a salt thereof. In a preferred embodiment, the content of arbutin is based on the whole base. 0.1-5% by weight
And an external preparation for skin wherein the content ratio by weight of arbutin and pantethein-S-sulfonic acid or a salt thereof is 1: 0.1 or more.

Hereinafter, the present invention will be described in detail.

The arbutin used in the present invention is a hydroquinone in which D-glucose is β-linked, that is, hydroquinone-β-glucopyranoside. This arbutin is naturally found in awaurushi (Arctostaphylos uva-u
rsi (L.) Sprengel) leaves and cowberry (Vaccinium vitis-id
aea L.var minus Loddig) is contained in leaves at a rate of 4-7.5%, and its properties are colorless needles, mp 142 ° C.
It is soluble in water and has the property of being decomposed with a mineral acid or β-glucosidase to give hydroquinone and glucose.

In the present invention, arbutin is contained in the external preparation for skin at a ratio of 0.1 to 5% by weight. Among them, 0.1% by weight when used in an external preparation such as a cosmetic for the purpose of preventing spots, freckles and darkness due to sunburn.
As described above, 1% by weight or more is contained as an effective amount when used in an external preparation as a drug for treating pigmentation disease. If the content is less than 0.1% by weight, the effect of improving skin pigmentation is not sufficient, and if it exceeds 5% by weight, it may be unfavorable from the viewpoint of skin safety.

On the other hand, an essential component similarly applied to the present invention is pantethein-S-sulfonic acid (hereinafter abbreviated as PSS) or a salt thereof. PSS is represented by the following general formula (I)
Which is naturally present in carrots, is known as a factor that promotes the growth of Bifidobacterium, and is also known to have a whitening effect itself.

HOCH ₂ C (CH ₃ ) ₂ CH (OH) CONHCH ₂ CH ₂ CONHCH ₂ CH ₂ SSO ₃ H (I)

The PSS can be used in the form of a salt as well as the free acid. Examples of the salt include a wide range of organic acid salts and inorganic acid salts, and alkali metal salts and alkaline earth metal salts are preferred.

In the present invention, the above-mentioned PSS or a salt thereof is 1: 0.1 or more, preferably 1: 0.1 to 1:10, more preferably 1: 0.5 to 1 in weight ratio to arbutin.
They are used together in the range of 1: 5. If the weight ratio of PSS or a salt thereof to arbutin is less than 0.1, the stabilizing effect is insufficient, which is not preferable.

In addition to the above-mentioned arbutin and PSS or a salt thereof, the skin external preparation of the present invention contains various components generally used in cosmetics and pharmaceuticals, such as aqueous components, powder components, surfactants, humectants, and the like. Thickeners, preservatives, ultraviolet absorbers, coloring agents, drugs, fragrances, and the like can be added. Of course, these must be used within a quantitative and qualitative range that does not impair the effects of the present invention. Further, the dosage form of the external preparation for skin of the present invention is arbitrary, and any dosage form conventionally used for this type of external preparation for skin may be used, for example, ointment, cream, emulsion, lotion and the like.

[0017]

Next, the present invention will be described in more detail with reference to examples. The present invention is not limited by this. In addition, the compounding amount is weight%.

Example 1 Lotion (alcohol phase) 95% ethanol 25 Polyoxyethylene (60) hydrogenated castor oil 2 Preservatives Appropriate amount Fragrance Appropriate amount (aqueous phase) Arbutin 1 PSS calcium salt 0.2 Glycerin 5 Ion exchange Water residue (Method) Solubilize after adjusting aqueous phase and alcohol phase.

Example 2 Cream Stearic acid 5 Stearyl alcohol 4 Butyl stearate 5 Glycerin monostearate 2 Propylene glycol 10 Arbutin 3 PSS potassium salt 5 Caustic potash 0.2 Preservative proper amount Perfume proper amount Ion-exchanged water residue ( Production method) Arbutin, PSS potassium salt, propylene glycol, and potassium hydroxide are added to ion-exchanged water, dissolved, heated and maintained at 70 ° C (aqueous phase). The other components are mixed, melted by heating and kept at 70 ° C. (oil phase). The oil phase is gradually added to the water phase, and after the addition is completed, the temperature is maintained for a while to allow the reaction to proceed. Thereafter, the mixture is uniformly emulsified with a homomixer and cooled to 30 ° C. while stirring well.

Example 3 Emulsion Stearic acid 2.5 Cetyl alcohol 1.5 Vaseline 5 Liquid paraffin 10 Polyoxyethylene (10) monooleate 2 Polyethylene glycol 1500 3 Triethanolamine 1 Arbutin 5 PSS sodium salt 10 Ion exchange Water Perfume Appropriate amount Preservatives Appropriate amount (Preparation method) Add arbutin, PSS sodium salt, polyethylene glycol, and triethanolamine to ion-exchanged water, dissolve by heating and maintain at 70 ° C (aqueous phase). The other components are mixed, dissolved by heating and kept at 70 ° C (oil phase).
Add oil phase to water phase, pre-emulsify, homogenize uniformly with homomixer, and after emulsification, stir to 30 ° C.
Cooling.

Example 4 Water Absorbing Ointment Vaseline 40 Stearyl Alcohol 18 Mokurou 20 Polyoxyethylene (10) Monooleate 0.25 Glycerin Monostearate 0.25 Arbutin 5 PSS Calcium Salt 2 Ion-exchanged Water Residue ) Arbutin and PSS calcium salt are added to ion-exchanged water and kept at 70 ° C. (aqueous phase). Other components at 70 ° C
To dissolve (oil phase). The oil phase is added to the water phase, and the mixture is uniformly emulsified by a homomixer and then cooled.

(Comparative Experiment) The light stability of the cosmetic obtained according to the present invention was compared with that of a conventional cosmetic and that of a comparative cosmetic.

<Discoloration test>

Samples (a) Lotion of Example 1 of the present invention (a) Conventional lotion in which PSS calcium salt was removed (increased amount of water) from the lotion of Example 1 of the present invention (c) The present invention A comparative lotion in which the PSS calcium salt in the lotion of Example 1 was replaced with tocopherol acetate.

Experimental Method 10 g of each sample was separately weighed into a 20 ml screw tube, and three samples were prepared for each sample.
This was irradiated with a xenon lamp light at 25 ° C. for 16 hours. Xenon lamp is Shimadzu Xenon Tester XF-6
Using the 0S type, the amount of light energy received at the sample surface at a lamp output of 5 KW is about 1200 μW / mm ² / sec.
Its wavelength is close to that of sunlight. Next, the color depth of each sample after light irradiation was measured by the Gardner method, and the degree of discoloration was examined by comparing with the non-light-irradiated sample. The average value of each of the three samples is shown in Table 1. The numerical values in the table are Gardner numbers, and the larger the numerical value, the deeper the coloring.

[0026]

[Table 1]

As shown in the results in Table 1, the cosmetics of the present invention are remarkably suppressed in coloring and at a level that does not cause any practical problem, whereas the cosmetics of the conventional product and the comparative product are considerably large. It was proved that the coloring was advanced and the commercial value was lost.

<Residual rate test>

Sample The same product as the one used in the discoloration test (A) and the conventional product
(A) and a comparative product (C) were used.

Experimental Method For each sample (non-irradiated product and light-irradiated product, 3 samples per sample), 1 g of each sample was added to methanol to make 10 ml as a sample for HPLC, and arbutin was analyzed by high performance liquid chromatography. And the residual ratio was determined by the following formula, and shown in Table 2 as an average value of three samples. A higher residual ratio of arbutin indicates better stability.

[0031]

(Equation 1)

[0032]

[Table 2]

As shown in the results in Table 2, in the cosmetic of the present invention, arbutin is stabilized, and a sufficient amount remains under the conditions of receiving light such as sunlight or fluorescent light. It was proved that the effect of improving skin pigmentation could be sufficiently exhibited.

[0034]

According to the present invention, the use of arbutin in combination with PSS or a salt thereof provides an external preparation for skin having excellent stability without discoloration or decomposition over time and an excellent effect of improving skin pigmentation. Can be provided. Furthermore, PS
The whitening effect originally possessed by S or a salt thereof can also be used.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 9/06 A61K 9/06 G

Claims (3)

(57) [Claims] An external preparation for skin, comprising arbutin and pantethein-S-sulfonic acid or a salt thereof. 2. The external preparation for skin according to claim 1, wherein the content of arbutin is 0.1 to 5% by weight based on the whole base. 3. The external preparation for skin according to claim 1, wherein the content ratio by weight of arbutin to pantethein-S-sulfonic acid or a salt thereof is 1: 0.1 or more.