JPS6320205B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a whitening cosmetic, and more particularly to a whitening cosmetic containing at least one of pantethine or its acylated derivative. Conventionally, pantethine has been found to exist in the body together with pantetheine as a result of the in-vivo reaction of its precursor pantothenic acid, and is reduced to form pantetheine, a component of acetyl coenzyme and acetyl carrier protein, and is converted into carbohydrates. It is said to have a wide range of physiological actions, including being involved in direct injection, fatty acid decomposition, synthesis, etc. Pantethine has recently attracted attention for its pharmacological effects, and its effects on fat metabolism and prevention and repair effects on arteriosclerosis are currently being elucidated, but there have been no examples of its specific application in cosmetics yet. You can say that. On the other hand, ascorbic acid (derivatives), hydrogen peroxide, glutathione, colloidal sulfur, and various other natural products have long been known as substances that have been added to cosmetics for the purpose of achieving a whitening effect. is easily oxidized and unstable in systems containing a large amount of water, such as wet cosmetics, and tends to cause discoloration and odor. Due to the characteristics of hydrogen peroxide, it is difficult to say that it is sufficient in terms of storage and stability. Glutathione and colloidal sulfur are avoided in cosmetics because they emit a distinct odor. Furthermore, there are almost no natural products whose effects have been confirmed, and like the above-mentioned substances, their whitening effect on the skin is not fully satisfactory. Therefore, in view of the above situation, the present inventor conducted extensive research on pantethine and its acylated derivatives, and found that when these are blended into a cosmetic base and applied to the skin, even when a very small amount is blended, the precursor The present inventors have discovered that the substance pantothenic acid has a previously unknown effect, that is, a remarkable whitening effect based on tyrosinase activity inhibition and melanin pigment bleaching action, leading to the completion of the present invention. That is, the present invention is characterized in that pantethine represented by the following general formula () and/or pantethine acylated derivative represented by the general formula () is blended in an amount of 0.01 to 1% by weight based on the total cosmetic amount. Regarding whitening cosmetics, it is an object of the present invention to provide whitening cosmetics that have extremely excellent effects that cannot be obtained with the above-mentioned known whitening substances. General formula () General formula () (In the formula, at least one of R ₁ , R ₂ , R ₃ , and R ₄ is a linear or branched acyl group having 2 to 10 carbon atoms, unless all are hydrogen atoms or all acyl groups.) and the others represent hydrogen atoms.) The present invention will be described in detail below. Pantethine applied to the present invention is represented by the above general formula (), and is the so-called 2 of pantethine.
It is a substance produced by disulfide bonding between mercapto groups at the end of the molecule, and methods for obtaining it include, for example, Japanese Patent Publication No. 41-2896, Japanese Patent Publication No. 44-
There are various methods such as a synthesis method using pantothenic acid (salt) as a precursor as a starting material as seen in No. 3324, a method of isolating coenzyme A, and others. Similarly, the acylated pantethine derivative is represented by the general formula (), which can be easily obtained by a conventional acylation reaction of pantethine, such as the Syoshiten-Baumann reaction. Specific examples of pantethine acylated derivatives include monobutanoylpantethine, dipropioloylpantethine, dibutanoylpantethine, dicaproylpantethine, dipelargoylpantethine, tricapryloylpantethine, tri-2-ethylhexanoylpantethine, and tri-2-ethylhexanoylpantethine. Examples include those in which the acyl group in the general formula () has 2 to 10 carbon atoms, such as decanoylpantethine, and these are selected appropriately depending on the type of various cosmetic formulations, and are suitable for aqueous cosmetics such as lotions. If the acyl group has 2 to 6 carbon atoms
Preferably monobutanoyl pantethine, dipropioloyl pantethine, etc.; in the case of oil-based cosmetics such as cosmetic creams, those having 8 to 10 carbon atoms, preferably dipelargonoyl pantethine, tri-2-ethylhexanoyl pantethine, etc. . Next, a synthesis example of a pantethine acylated derivative applied to the present invention will be shown. Synthesis Example 1 Dibutanoylpantethine 11 g of pantethine and 4.5 g of triethylamine were dissolved in 50 ml of dimethylformamide (DMF), and under ice cooling, 30 ml of a tetrahydrofuran (THF) solution in which 5.5 g of butyric acid chloride was dissolved was added dropwise to react. After further reacting at room temperature for 2 hours, the solvent was removed and extracted with ethyl acetate. The extract was developed on a silica gel column and fractionated and purified using a gradient method (chloroform→chloroform:methinol=8:2) to obtain 7.8 g of dibutanoylpantethine in the form of a viscous liquid. Γ NMR (δ value) 2.9 (C H ₂ -S-S-C H ₂ ),
4.0 ( _COOCH2 )

[Formula] 7.3 (CON H ) Γ Elemental analysis value (as C ₃₀ H ₅₄ N ₄ O ₁₀ S ₂ ) Analysis value (%) C51.58, H8.01, N8.10 Calculated value (%) C51.85, H7.33, N8.06 Synthesis Example 2 Tri-2-ethylhexanoylpantethine Dissolve 22g of pantethine in 150ml of pyridine, cool on ice, and prepare 2-ethylhexanoyl chloride 22
100 ml of a benzene solution in which g was dissolved was added dropwise to cause a reaction. After further reacting at room temperature for 3 hours, the solvent was removed and extracted with ethyl acetate. The extract was developed on a silica gel column, fatty acids were eluted with n-hexane: ethyl ether = 1:1, and then fractionated and purified with n-hexane: ethanol = 85:15 to obtain a viscous liquid tri-2. -Ethylhexanoylpantethine
23.4g was obtained. Γ Elemental analysis value (as C ₄₆ H ₈₄ N ₄ O ₁₁ S ₂ ) Analysis value (%) C59.42, H8.92, N5.98 Calculated value (%) C59.20, H9.07, N6.00 pieces In the whitening cosmetic composition of the invention, the above-mentioned pantethine or pantethine acylated derivative is contained in an amount of 0.01 to 1% by weight, preferably 0.05 to 1% by weight, based on the total cosmetic composition.
It is blended within the range of. If the amount is less than 0.01% by weight, even if the whitening cosmetic is applied to the skin, the amount absorbed through the skin will not be the optimal amount to produce the whitening effect.On the other hand, if the amount is more than 1% by weight, the cosmetic Due to the compatibility with the base, for example, lotion systems may cause problems such as the formation of crusts, and although it varies from person to person, they tend to give an unnatural decolorizing effect due to excessive inhibition of tyrosinase activity (this tendency is particularly true for lotion systems). % by weight or more) and should therefore be avoided. When the above-mentioned pantethine and pantethine acylated derivatives are incorporated into a cosmetic base, they may be used alone or in combination, or with other reducing whitening substances, but pantethine itself is originally water-soluble. However, since it tends to impair chemical stability against oxidation, when used in actual systems, it is necessary to use it together with an antioxidant substance, or to use a pantethine acylated derivative, which is considerably more stable. Care should be taken when used in combination with
One of the important points of the present invention is that in order to fully exhibit the effects derived from pantethine, pantethine is derivatized and stabilized as described above. Next, in order to demonstrate how superior pantethine and pantethine acylated derivatives applied to the whitening cosmetics of the present invention are in terms of whitening effects, we investigated the tyrosinase activity inhibition effect, which is known as its mechanism. The test results are shown below. (Method) Harding-Passay
Using the enzyme tyrosinase extracted from mouse melanoma, its enzyme activity was expressed in Doperchrome.
The photometry method was used to measure absorbance at 475 nm. The test substances include pantethine according to the present invention, dibutanoylpantethine, which is one of the acylated derivatives of pantethine, calcium pantothenate, which is a precursor of pantethine, and disulfide bonds (--
An oxidized glutathione having an oxidized form of glutathione (S—S—) was used. A reaction solution obtained by incubating 5×10 ⁻⁵ mol of each sample with mouse liver homogenate was added to a tyrosinase inhibition system, and the inhibition rate was measured using liver homogenate alone as a control. The results are shown in Table 1.

[Table] As shown in the results in Table 1, calcium pantothenate, a precursor of pantethine, and oxidized glutathione, a disulfide compound,
Control liver homogenate alone and lag phase;
There was no or almost no change in the inhibition rate, and no direct inhibitory effect on tyrosinase was observed. On the other hand, pantethine and pantethine acylated derivatives according to the present invention inhibit tyrosinase activity by significantly delaying the induction period and significantly lowering the initial reaction rate, thereby inhibiting the production of intermediate doperchrome in the melanin production process. It has been demonstrated that it reduces Similarly, the skin whitening effect using the whitening cosmetic of the present invention,
We investigated its effectiveness in improving age spots and freckles, and compared it with conventional whitening cosmetics. The method of application was to select 30 women between the ages of 32 and 48 who suffer from dark skin, age spots, and freckles, and randomly divide them into three groups (10 women each).
The first group uses the whitening lotion of Example 1 described below, the second group uses the whitening lotion in which dibutanoyl pantethine in Example 1 is replaced with oxidized glutathione, and the third group uses Example 1. A control lotion with dibutanoyl pantethine removed (increased amount of water) was used three times a day in the morning, noon, and evening for three months. The subjects were asked to report their improvement status after three months. The results are shown in Table 2.

[Table] As detailed above, the present invention relates to a whitening cosmetic that effectively contains pantethine with excellent bioactivity and its acylated derivative.
It is far more effective at whitening the skin than skin whitening cosmetics containing glutathione, which has a similar mechanism of action in terms of inhibiting tisilonase activity and depigmenting melanin pigments, with whitening substances such as glutathione and colloidal sulfur. It can be used safely without any harmful effects. Next, examples of the whitening cosmetic composition of the present invention will be shown. The blending ratio is in parts by weight. Example 1 Whitening lotion ethanol 10.0 Propylene glycol 5.0 Polyoxyethylene (50) hydrogenated castor oil
0.5 Citric acid 0.015 Sodium citrate 0.1 Methylparaben 0.05 Dibutanoylpantethine 1.0 Fragrance 0.4 Water 83.0 Example 2 Whitening cosmetic oil Squalane 49.9 Castor oil 49.9 Tri-2-ethylhexanoylpantethine
0.3 Dibutylhydroxytoluene 0.01 Fragrance 0.3 Example 3 Whitening pack Polyvinyl alcohol 20.0 Ethanol 20.0 Dipropioloylpantethine 1.0 Glycerin 5.0 Fragrance 0.5 Water 53.5 Example 4 Two-layer type whitening lotion A Ethanol 1,3-butylene glycol 15.0 4.0 B Liquid paraffin Isopropyl tridecanoyl pantethine myristate 5.0 1.0 0.5 C Fragrance Methylparaben δ-Tocopherol Pantethine Water 0.4 0.1 0.1 0.5 74.4 Example 5 Whitening cream A Stearic acid Geirocetanol Lanolin Myristate Isopropyl squalane Olive oil Tri-2-ethyl hexa Noylpantethine monostearate polyoxyethylene sorbitan monostearate sorbitan 8.0 4.0 4.0 2.0 6.0 7.0 2.0 0.7 5.0 1.0 B Propylene glycol butyl paraben methyl paraben dibutyl hydroxytoluene Pantethine fragrance water 5.0 0.1 0.1 0.05 0.1 0.3 54.5 Example 6 whitening makeup Water Ethanol 7.0 Propylene Glycol 5.0 Polyoxyethylene (50) Hydrogenated Castor Oil
0.5 Citric acid 0.02 Sodium citrate 0.1 Methylparaben 0.05 δ-tocopherol 0.2 Pantethine 0.3 Fragrance 0.4 Water 87.0

Claims (1)

[Claims] 1. Pantethine represented by the general formula () and/or
Alternatively, a whitening cosmetic comprising a pantethine acylated derivative represented by the general formula () in an amount of 0.01 to 1% by weight based on the total cosmetic. General formula () General formula () (In the formula, at least one of R ₁ , R ₂ , R ₃ , and R ₄ is a linear or branched acyl group having 2 to 10 carbon atoms, unless all are hydrogen atoms or all acyl groups.) (Others represent hydrogen atoms.)