JP3527406B2 - Skin whitening external preparation - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an eggplant (Solanaceae)
Jurbeba Pates, a plant of the genus Solanum
( Jurubeba paiz , Scientific name : Solanum paniculatum ) By adding an extract, it suppresses the production of melanin and is effective for preventing and improving pigmentation, spots, freckles, chloasma , etc. after sunburn. .

[0002]

BACKGROUND OF THE INVENTION Although there are some unclear points about the mechanism of skin spots and the like, in general, melanin pigments are formed due to hormonal abnormalities and irritation of ultraviolet rays from the sun, and this is the skin. It is thought to be abnormally deposited inside.

This melanin pigment, which causes skin coloring, is produced in melanin-producing granules (melanosomes) in the melanocytes (melanocytes) between the epidermis and the dermis, and the produced melanin is osmotic to adjacent cells. Spread to. The biochemical reaction in this melanocyte is presumed to be as follows.

That is, the process in which tyrosine, which is an essential amino acid, becomes dopaquinone by the action of the enzyme tyrosinase, and this changes to black melanin through the red or colorless pigment by the enzymatic or non-enzymatic oxidation action is the process of melanin pigment formation. is there.

Therefore, suppressing the action of tyrosinase, which is the first step of the reaction, is important for suppressing melanin production.

[0006]

However, the compounds that suppress the action of tyrosinase, except for hydroquinone, exhibit their effects very slowly, so that the effect of improving skin pigmentation is not sufficient.

On the other hand, although hydroquinone has been confirmed to be effective, its use is generally limited because of its sensitizing property. Therefore, in order to improve its safety, attempts have been made to obtain higher fatty acid monoesters or alkyl monoethers (JP-A-58-154507). However, the esters are decomposed by a hydrolase in the body. Therefore, it is not always safe, and ethers have not been sufficiently satisfactory in terms of safety.

[0008] Accordingly, the present inventors have results of examining the wide variety of melanin production inhibitory effect for substances In order to solve these problems, eggplant (Solanaceae) family Solanum (Solanum) of plants of the genus Jurubeba-Paitsu (jurubeba p
It was found that the aiz , scientific name : Solanum paniculatum ) extract has a melanin production inhibitory action and a tyrosinase inhibitory action, and has completed the present invention.

Solanum (Solanaceae)
) Regarding the report on the extract of the genus plant, an example which has been used as an external preparation for skin for improving acne skin has been reported (JP-A-56-1).
54500), there is a melanin production inhibitory action,
No application to whitening agents is known. The present inventors have completed the present invention based on the above findings.

An object of the present invention is to provide a skin-care external preparation for whitening, which has excellent melanin production inhibitory action and tyrosinase inhibitory action and is highly safe.

[0011]

[Means for Solving the Problems] That is, the present invention provides a juvenile plant of the genus Solanum of the family Solanaceae.
Rubeba-Paitsu (jurubeba paiz, scientific name: Solanum panic
ulatum ) is an external preparation for whitening skin, which is characterized by containing an extract.

[0012]

Further, in the present invention, the compounding amount of the extract of the plant of the genus Solanum of the family Solanaceae is 0.0
The above external whitening skin preparation is characterized by being 005 to 10.0% by weight.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The constitution of the present invention will be described in detail below.

As a plant of the genus Solanum of the family Solanaceae used in the present invention, jurubeba paiz (scientific name: Solanum paniculatum) is preferable. This is a plant that grows especially on Brazilian dry grasslands and pastures.

[0016] Solanum (Solanaceae)
) Jurubeba-Paitsu (jurubeba paiz of plants of the genus, Manabu
Name : Solanum paniculatum ) melanin production inhibitory action and tyrosinase inhibitory action are the effects first discovered by the present inventor, and their application to whitening agents and whitening skin external preparations is not known at all.

The extract used in the present invention is a branch, root, leaf, stem including rhizome, fruit, flower or the like of the above plant, or
After soaking or heating under reflux the whole plant with extraction solvent,
Obtained by filtration and concentration. The extraction solvent used in the present invention is not particularly limited as long as it is a solvent used for extraction, and examples thereof include alcohols such as methanol and ethanol, hydrous alcohols, acetone, and organic solvents such as ethyl acetate. Alternatively, it is preferable to use them in combination.

[0018] eggplant (Solanaceae) in the present invention Department of Solanum (Solanum) of plants of the genus Jurubeba-Paitsu (jurube
ba paiz , scientific name : Solanum paniculatum ) The compounding quantity of the extract is 0.0005-10.
It is 0% by weight, preferably 0.01 to 5.0% by weight.
If it is less than 0.0005% by weight, the effect of the present invention is not sufficiently exhibited, and if it exceeds 10.0% by weight, formulation is difficult, which is not preferable. Further, even if it is blended in an amount of 5.0% by weight or more, the effect is not significantly improved.

In addition to the above essential components, the external whitening agent for skin whitening of the present invention also contains components that are usually used in external skin externalizing agents such as cosmetics and pharmaceuticals, such as other whitening agents and moisturizers.
Antioxidants, oily components, UV absorbers, surfactants, thickeners, alcohols, powder components, coloring materials, aqueous components, water,
Various skin nutrients and the like can be appropriately blended as necessary.

In addition, sequestering agents such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extraction Substance, glabridin, hot water extract of fruits of fire thorns, various crude drugs, tocopherol acetate,
Drugs such as glycyrrhizic acid and its derivatives or salts thereof, vitamin C, magnesium ascorbate phosphate,
Other whitening agents such as ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, mannose,
Sugars such as sucrose and trehalose can also be appropriately added.

The external whitening agent for whitening of the present invention includes, for example, ointments, creams, emulsions, lotions, packs, bath agents and the like.
Any conventional skin external preparation may be used,
The dosage form is not particularly limited.

[0022]

The present invention will be described in more detail with reference to Examples. The present invention is not limited to this. The blending amount is% by weight. Prior to Examples, test methods and results of the melanin suppressing effect, tyrosinase activity inhibiting effect and whitening effect of the plant extract of the present invention will be described.

"Test Method and Result" 1. Sample preparation Root part of jurubeba paiz 100
g was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 1.6 g of an ethanol extract. This extract is D
The solution was dissolved in MSO at 1%, the solution was diluted to adjust the concentration, and the following experiment was carried out using this.

2. Cell culture method B16 melanoma cultured cells derived from mouse were used. 1
0% FBS and theophylline (0.09 mg / ml)
The cells were cultivated in an Eagle MEM medium containing C. in a CO2 incubator (95% air, 5% carbon dioxide) at 37 ° C. After 24 hours of culturing, the sample solution was added so as to have a final concentration (concentration of extracted dry matter) of 10 ^-2 to 10 ^-5 % by weight, culturing was continued for another 3 days, and the melanin production amount was visually sensed by the following method. The determination and the tyrosinase activity inhibitory effect were measured.

3. Visual measurement of melanin amount Place a diffusion plate on the lid of the plate of the well, observe the intracellular melanin amount with an inverted microscope, and check the sample (reference) without adding the extract of Solanaceae plants. Compared to the case. The results are shown in "Table 1". In addition, as a reference example, the same test as above was carried out on an extract of Kaigai (Lamiaceae, Odorikosou Subfamily), which is already known to have an action of suppressing melanin production. The results are also shown in "Table 1".

<Judgment Criteria> ◯: White compared to the reference (less melanin amount compared to the reference) Δ: Slightly white compared to the reference (slightly smaller melanin amount compared to the reference) ×: With reference About the same

4. Measurement of tyrosinase activity Before the measurement, the medium in the wells is removed, and the wells are washed twice with 100 μl of PBS. 45 μl of 1% Triton-X in each well
PBS containing (trade name of Rohm and Haas, surfactant) is added. Shake the plate for 1 minute to break the cell membrane well, then use a microplate reader to 475n
The absorbance at m was measured and this was taken as the absorbance at 0 minutes. Then, 5 μl of 10 mM L-DOPA solution was quickly added, and the mixture was transferred to an incubator at 37 ° C. and reacted for 60 minutes. The plate was shaken for 1 minute, and the absorbance (475 nm) at 60 minutes was measured. The ratio of the difference in absorbance of the plant extract-added sample to the difference in absorbance at 0 minutes and 60 minutes in the case of the sample to which the plant extract was not added (control) was defined as the tyrosinase activity rate (%). The results are shown in "Table 1". Further, as a reference example, the same test as above was carried out on an ethanol extract of mussel, which is already known to have a tyrosinase activity inhibitory action. The results are also shown in "Table 1". In the table, −
Means that no significant difference was observed within 5% of the risk rate as compared with the control. The blank column means that the test was not conducted because the tyrosinase activity inhibitory action was observed at a lower concentration.

[0028]

[Table 1] ---------------------------------------------- -------------------------- Test Melanin production Visual evaluation Tyrosinase activity rate (%) ------------ -------------------------------------------------- ---------- Concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^-2 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ----------- -------------------------------------------------- ----------- Jurbeba Pates × ○ 90 106 Extract Keigai Extract × × × × − − − 55 ------------------- -------------------------------------------------- ---

5. Whitening effect test [Test method] 40 subjects exposed to artificial sunlight (UV-A + UV-B) for 30 minutes (10 minutes a day for 3 days) were exposed to sunlight on the upper arm skin After 5 days, each sample was applied once a morning and evening for 4 weeks. The panel is divided into 8 groups,
The test was conducted with 5 groups and the formulation shown below. (Alcohol phase) 95% Ethyl alcohol 55.0% by weight Polyoxyethylene (25 mol) Hardened castor oil ether 2.0 Antioxidant / preservative Appropriate amount Perfume Appropriate amount Drug (listed in Table 2) (Water phase) Glycerin 5.0 Sodium hexametaphosphate Suitable amount Ion-exchanged water Residual <Production method> Prepare an aqueous phase and an alcohol phase, respectively, and then mix and solubilize them.

[Evaluation Method] The lightening effect after use was judged based on the following judgment criteria. <Judgment Criteria> ⊚: When the rate of marked efficacy and efficacy among subjects is 80% or more ◯: The rate of marked efficacy and efficacy among subjects is 50% to
If less than 80% Δ: 30% to 30% of subjects show excellent efficacy
When less than 50% x: when the proportion of subjects showing marked efficacy and efficacy is less than 30%

Samples having the blending composition described in the above test method were prepared and the whitening effect was compared using the agents shown in Table 2.
The results are shown in "Table 2".

[0032]

[Table 2] -------------------------------------------------- ---------       Compounding amount (% by weight) Effectiveness -------------------------------------------------- ---------   No additive − ×   Hydroquinone 1.0 △   Jurbeba pine extract 0.1 ○   Jurbeba pine extract 1.0 ○   Jurbeba Pates Extract 5.0 ◎ -------------------------------------------------- ---------

The extract of Jurbeba pine of Table 2 is obtained by heating and reducing the root of Jurbeba pine in ethanol, filtering and concentrating and drying.

As is clear from [Table 2], the effect after exposure to sunlight is that the addition of the extract of Jurbeba pine prevents the deposition of excess melanin pigment and prevents darkening. Was confirmed.

Examples of the external whitening agent for whitening of the present invention are shown below. The Jurbeba pine extract is obtained by heating and reducing the root in each extraction solvent, filtering and concentrating and drying.

Example 1 Cream (Formulation) Stearic acid 5.0% by weight Stearyl alcohol 4.0 Isopropyl myristate 18.0 Glycerin monostearate 3.0 Propylene glycol 10.0 Jurbeba piezmethanol extract 01 Caustic potash 0.2 Preservative A proper amount Fragrance A proper amount Ion-exchanged water Residual (manufacturing method) Propylene glycol, Jurbeba pine methanol extract and caustic potash were added to ion-exchanged water and dissolved, and heated and kept at 70 ° C (water phase). The other ingredients are mixed, heated and melted and maintained 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 cause the reaction. Then, it is uniformly emulsified with a homomixer and cooled to 30 ° C. with thorough stirring.

Example 2 Cream (Formulation) Stearic acid 2.0% by weight Stearyl alcohol 7.0 Hydrogenated lanolin 2.0 Squalane 5.0 2-Octyldodecyl alcohol 6.0 Polyoxyethylene (25 mol) cetyl alcohol ether 3.0 Glycerin monostearate ester 2.0 Propylene glycol 5.0 Jurbeba piets ethanol extract 0.05 Ethylparaben 0.3 Perfume proper amount Ion-exchanged water Residual (production method) Add propylene glycol to ion-exchanged water,
Heat to maintain 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is added to the aqueous phase to carry out preliminary emulsification, and the mixture is uniformly emulsified with a homomixer and then cooled to 30 ° C. with thorough stirring.

Example 3 Cream (formulation) Solid paraffin 5.0% by weight Beeswax 10.0 Vaseline 15.0 Liquid paraffin 41.0 Glycerin monostearate 2.0 Polyoxyethylene (20 mol) sorbitan monolaurate 2 0.0 Soap powder 0.1 2-Ethylhexyl paramethoxycinnamate 1.5 Borax 0.2 Jurbeba pine acetone extract 0.05 Jurbeba pine ethanol extract 0.05 Ethyl paraben 0.3 Perfume proper amount Ion-exchanged water residue ( Manufacturing method) Soap powder and borax are added to ion-exchanged water, and the mixture is heated and melted and kept at 70 ° C (aqueous phase). The other ingredients are mixed, heated and melted and maintained at 70 ° C. (oil phase). The oil phase is stirred into the water phase and gradually added to carry out the reaction. After the reaction is completed, the mixture is uniformly emulsified with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. with thorough stirring.

[0039]

[0040]

[0041]

Example 4 Beauty essence (Production Method) Phases A and C are uniformly dissolved, and phase A is added to phase C to solubilize it. Next, phase B is added and then filling is performed.

Example 5 Pack (Production Method) Phases A, B, and C are uniformly dissolved, and phase B is added to phase A to solubilize it. Next, this is added to phase C and then filled.

Example 6 Solid Foundation (Manufacturing method) Powder components of talc to black iron oxide are thoroughly mixed with a blender, and then an oily component of squalane to isocetyl octoate, an extract of julbeba pies ethanol, an antiseptic and a fragrance are added, and the mixture is well kneaded, and then added to a container. Fill and mold.

Example 7 Emulsion type foundation (cream type) (Manufacturing method) The aqueous phase is heated and stirred, and then the powder portion that has been sufficiently mixed and pulverized is added and subjected to a homomixer treatment. Further, the heated and mixed oil phase is added, and the mixture is treated with a homomixer. Then, the fragrance is added with stirring and the mixture is cooled to room temperature.

[0046]

Industrial Applicability As described above, the whitening skin external preparation of the present invention has a melanin production inhibitory action and a tyrosinase activity inhibitory action, and is effective in treating pigmentation, stains, freckles, melasma, etc. after sunburn. It has excellent effects in lightening and whitening, and also in safety.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification symbol FI A61P 17/16 A61P 17/16 // A61P 43/00 111 43/00 111 (72) Inventor Masako Naganuma Kohoku Ward, Yokohama City, Kanagawa Prefecture Shibaido Daiichi Research Center Co., Ltd. 1050, Shinba Town (72) Inventor Masahiro Ota 1050 Shibaido Daiichi Research Center Co., Ltd., Kohoku Ward, Yokohama City, Kanagawa Prefecture (56) Reference JP-A-5-201846 (JP , A) JP-A-8-12565 (JP, A) JP-A-8-99858 (JP, A) JP-A-5-320062 (JP, A) JP-A-7-25741 (JP, A) (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K ^7/ 00-7/50 A61K 35/78

Claims (2)

(57) [Claims] 1. A solanum of the family Solanaceae
m) Jurubeba-Paitsu of a plant belonging to the genus (jurubeba paiz, Manabu
Name : Solanum paniculatum ) An external preparation for whitening skin, which contains an extract. 2. The Solanaceae family Solanu
m) The amount of the extract of the genus plant is 0.0005 to 10.0
The whitening skin external preparation according to claim 1, wherein the external preparation is white.