JPH0812552A - Skin external preparation - Google Patents

Abstract

PURPOSE:To obtain a skin external preparation composed of a Amor Seco extract, having suppressing action against melanin formation and inhibiting action against tyrosinase activity, excellent in fading effect for the pigmented skin, spots, freckles after sunburn, chloasma, etc., beautifying effect and safety and useful for a beautifying ointment and cream, etc. CONSTITUTION:This skin external preparation is composed of preferably 0.005-20.0wt.%, especially preferably 0.01-10.0wt.%, of an extract of Amor Seco (Biden andicola HBK). Further, Amor Seco is a plant grown in a dry grassland, a pastureland, etc., in South America, especially in Andes district. The extract is obtained e.g. by immersing leaves, stems, fruits, etc., or a total plant of Amor Seco in an extraction solvent such as ethanol or subjecting them to reflux extraction under heating with the solvent followed by filtration, concentration, etc.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to Amor Seco (Amo)
The present invention relates to a skin external preparation effective for preventing and improving pigmentation, spots, freckles, melasma, etc. after sunburn by suppressing the formation of melanin by incorporating an extract of r Seco).

[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 melanocytes (melanocytes) between the epidermis and dermis,
The generated melanin diffuses into adjacent cells by the osmotic effect. 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 is converted to black melanin via the red and colorless pigments by the enzymatic or non-enzymatic oxidation action is the melanin pigment formation process. Therefore, suppressing the action of tyrosinase, which is the first step of the reaction, is important for suppressing melanin production.

[0003]

However, compounds that suppress the tyrosinase action, except for hydroquinone, have very slow onset of their effects, so that the effect of improving skin pigmentation is not sufficient. On the other hand, although hydroquinone is recognized as having an effect, its use is generally restricted because of its sensitizing properties. Therefore, in order to improve its safety, attempts have been made to use higher fatty acid monoesters or alkyl monoethers (JP-A-58-154507), but 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.

[0004]

[Means for Solving the Problems] Therefore, as a result of investigating the melanin production inhibitory effect of various substances as a solution to these problems, the present inventors have found that Amor Seco (scientific name: Biden andicola HBK) The present inventors have found that the extract of Escherichia coli has a melanin production inhibitory action and a tyrosinase inhibitory action, and completed the present invention. There has been no report on the melanin production inhibitory action of the extract of Amor Seco, etc., and its application to a whitening agent has not been known at all. The present inventors have completed the present invention based on the above findings.

That is, the present invention is based on Amor Seco (Am
or Seco, scientific name: Biden andicola HBK). The external preparation of the present invention is preferably a whitening skin external preparation.

The structure of the present invention will be described in detail below. Amor Sec used in the present invention
o) is a plant that grows in South America, especially in dry grasslands such as the Andes, and grass. The extract used in the present invention is obtained by immersing or heating and refluxing the whole amor / seco whole plant such as leaves and stems or fruits, and then filtering and concentrating. The extraction solvent used in the present invention may be any solvent as long as it is a solvent usually used for extraction, in particular, alcohols such as methanol and ethanol, hydrous alcohols,
Organic solvents such as acetone and acetic acid ethyl ester can be used alone or in combination.

The amount of the amor-seco extract in the present invention is 0.005 to 2 as a dry product in the total amount of the external preparation.
It is 0.0% by weight, preferably 0.01 to 10.0% by weight. If it is less than 0.005% by weight, the effect of the present invention is not sufficiently exhibited, and if it exceeds 20.0% by weight, formulation is difficult, which is not preferable. Further, even if it is blended in an amount of 10.0% by weight or more, the effect is not so much improved.

In addition to the above-mentioned essential components, the external preparation for skin of the present invention is a component that is usually used in external preparations for skin such as cosmetics and pharmaceuticals, for example, other whitening agents, moisturizers, antioxidants and oily components. , UV absorber, surfactant, thickener,
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 preparation for skin of the present invention may be any ointment, cream, emulsion, lotion, pack, bath agent or the like as long as it is a conventional external preparation for skin, and its form is not particularly limited.

[0011]

Next, the present invention will be described in more detail by way of 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 Results 1. Sample Preparation 50 g of Amor Seco stem and branch was immersed in ethanol at room temperature for 1 week and the extract was concentrated to obtain 4.9 g of ethanol extract. This extract was dissolved in DMSO at a concentration of 1%, the solution was diluted to adjust the concentration, and the following experiment was conducted 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 cultured in an Eagle MEM medium containing C. in a CO ₂ 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 well plate, observe the intracellular melanin amount with an inverted microscope, and compare it with the sample (reference) to which the amor-seco extract was not added . 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. Further, in the table, "toxic" means that it is cytotoxic.

<Judgment Criteria> ◯: White (amount of melanin) Δ: Slightly white (amount of melanin) ×: Reference (amount of melanin)

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
(Rohm and Haas product name, surfactant) containing PBS is added. Shake the plate for 1 minute, break the cell membrane well, and use a microplate reader for 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 tyrosinase activity inhibition rate (%) is the decrease in the absorbance difference of the sample added with the Amor Seco extract relative to the absorbance difference at 0 minutes and 60 minutes in the case of the sample (control) to which the Amor Seco extract is not added. And Table 1 shows the results. 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, "toxic" means that cytotoxicity was observed, and "-" means that no significant difference was observed within a risk rate of 5% as compared with the control.

[0017]

[Table 1] ─────────────────────────────────── Test Melanin production Visual evaluation Tyrosinase activity inhibition rate ( %) ──────── ──────────────────────── concentration (wt%) 10 ^-5 10 ^-4 10 ^-3 10 ^{- 2} 10 ^-5 10 ^-4 10 ^-3 10 ^-2 ─────────────────────────────────── Amor ・Seco extract × × × ○ − − 27 55 Kaigai extract × × × × − − − − 55 ───────────────────────────── ───────

5. Whitening test [Test method] 40 subjects exposed to sunlight in summer for 4 hours (2 hours per day for 2 days) each sample from 5 days after the day of sun exposure to the skin of the upper arm inner skin Was applied once each morning and evening for 4 weeks. The panel was divided into 8 groups, and 5 groups were prepared, and the tests were conducted according to the formulations shown below. (Alcohol phase) 95% Ethyl alcohol 55.0% by weight Polyoxyethylene (25 mol) hydrogenated castor oil ether 2.0 Antioxidant / preservative proper amount Fragrance proper amount drug (listed in Table 2) (water phase) glycerin 5.0 Sodium hexametaphosphate Suitable amount Ion-exchanged water Residue <Production method> An aqueous phase and an alcohol phase are prepared, respectively, and then both are mixed and solubilized.

[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
In the case of less than 80% Δ: Remarkable and effective proportion of subjects is 30% to
When less than 50% x: When the ratio of markedly effective or effective among the subjects 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.

[0021]

[Table 2] ────────────────────────── Drug compounding amount (% by weight) Effect ────────── ──────────────── Additive- × Hydroquinone 1.0 △ Amor / Seco extract 0.1 ○ Amor / Seco extract 1.0 ○ Amor / Seco extract 10. 0 ◎ ──────────────────────────

The Amor Seco extract shown in Table 2 was obtained by heating and reducing whole grass of Amor Seco 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 amor-seco extract can prevent excessive deposition of melanin pigment and prevent darkening. Admitted.

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 Amor-secomethanol extract 0.01 Caustic potassium 0.2 Sodium bisulfite 0.01 Preservative Suitable amount Perfume Suitable amount Ion-exchanged water Residual (production method) Dissolve propylene glycol, amor-secomethanol extract and caustic potash in ion-exchanged water, heat and keep 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. After that, homogenize with a homomixer,
Cool to 30 ° C while stirring well.

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 Glycerine monostearate 2.0 Propylene glycol 5.0 Amor-secoethanol extract 0.05 Sodium hydrogen sulfite 0.03 Ethylparaben 0.3 Fragrance suitable amount Ion-exchanged water Residue (production method) Propylene in ion-exchanged water Add glycol,
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 soap powder 0.1 borax 0.2 amor / secoacetone extract 0.05 amor / secoethanol extract 0.05 sodium bisulfite 0.03 ethylparaben 0.3 perfume proper amount ion-exchanged water residual (production method) ion-exchange Soap powder and borax are added to water, dissolved by heating 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.

Example 4 Emulsion (formulation) Stearic acid 2.5 wt% Cetyl alcohol 1.5 Vaseline 5.0 Liquid paraffin 10.0 Polyoxyethylene (10 mol) monooleate 2.0 Polyethylene glycol 1500 3. 0 triethanolamine 1.0 carboxyvinyl polymer 0.05 (trade name: Carbopol 941, BFGoodrich Chemical company) Amor-secoacetic acid ethyl ester extract 0.01 sodium bisulfite 0.01 ethylparaben 0.3 perfume proper amount ion Exchanged water Residue (production method) A carboxyvinyl polymer is dissolved in a small amount of ion exchanged water (phase A). Polyethylene glycol 1500 and triethanolamine were added to the remaining ion-exchanged water, and the mixture was heated and dissolved and maintained at 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 for preliminary emulsification, the phase A is added and the mixture is homogenized with a homomixer, and after emulsification, the mixture is cooled to 30 ° C. while being well stirred.

Example 5 Emulsion (Formulation) Microcrystalline wax 1.0% by weight Beeswax 2.0 Lanolin 20.0 Liquid paraffin 10.0 Squalane 5.0 Sorbitan sesquioleate 4.0 Polyoxyethylene (20 mol) ) Sorbitan monooleate 1.0 Propylene glycol 7.0 Amor-secoacetone extract 10.0 Sodium hydrogen sulfite 0.01 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 kept at 70 ° C. (oil phase). While stirring the oil phase, the aqueous phase is gradually added to this and the mixture is uniformly emulsified with a homomixer. After emulsification, cool to 30 ° C while stirring well.

Example 6 Jelly (formulation) 95% ethyl alcohol 10.0 wt% dipropylene glycol 15.0 polyoxyethylene (50 mol) oleyl alcohol ether 2.0 carboxyvinyl polymer 1.0 (trade name: Carbopol 940, BFGoodrich Chemical company) Caustic soda 0.15 L-Arginine 0.1 Amor Seco 50% ethanol aqueous solution extract 7.0 2-Hydroxy-4-methoxybenzophenone sulfonate sodium 0.05 Ethylenediaminetetraacetate-3 sodium-2 Water 0.05 Methylparaben 0.2 Perfume Appropriate amount Ion-exchanged water Residue (production method) Carbopol 940 is uniformly dissolved in ion-exchanged water, while Amor Seco 50% in 95% ethanol
An aqueous ethanol solution extract and polyoxyethylene (50 mol) oleyl alcohol ether are dissolved and added to the aqueous phase. Next, after adding other ingredients, caustic soda,
Thicken by neutralizing with L-arginine.

Example 7 Beauty Serum (Formulation) (Phase A) Ethyl Alcohol (95%) 10.0% by Weight Polyoxyethylene (20 mol) Octyldodecanol 1.0 Pantotenyl Ethyl Ether 0.1 Amor Secomethanol Extract 1.5 Methylparaben 0.15 (Phase B) Potassium hydroxide 0.1 (Phase C) Glycerin 5.0 Dipropylene glycol 10.0 Sodium bisulfite 0.03 Carboxyvinyl polymer 0.2 (trade name: Carbo Pole 940, BFGoodrich Chemical company) Purified water Residue (production method) Phases A and C are uniformly dissolved, and A is added to phase C
Add phase and solubilize. Next, phase B is added and then filling is performed.

Example 8 Pack (formulation) (Phase A) 5.0% by weight dipropylene glycol Polyoxyethylene (60 mol) hydrogenated castor oil 5.0 (Phase B) Amor-secomethanol extract 0.01 Olive oil 5 0.0 Tocopherol acetate 0.2 Ethylparaben 0.2 Perfume 0.2 (Phase C) Sodium hydrogen sulfite 0.03 Polyvinyl alcohol 13.0 (Saponification degree 90, degree of polymerization 2,000) Ethanol 7.0 Purified water Residue (Manufacturing method) Phase A, phase B, and phase C are uniformly dissolved,
Phase B is added to the phase to solubilize it. Next, this is added to phase C and then filled.

Example 9 Solid Foundation (Formulation) Talc 43.1 wt% Kaolin 15.0 Sericite 10.0 Zinc white 7.0 Titanium dioxide 3.8 Yellow iron oxide 2.9 Black iron oxide 0.2 Squalane 8 0.0 isostearic acid 4.0 POE sorbitan monooleate 3.0 isocetyl octoate 2.0 amor / secoethanol extract 1.0 preservative appropriate amount perfume appropriate amount (manufacturing process) Talc to black iron oxide powder components are sufficient with a blender After mixing, an oily component of squalane to isocetyl octoate, an amor / secoethanol extract, an antiseptic and a fragrance are added and kneaded well, then filled into a container and molded.

Example 10 Emulsion type foundation (cream type) (Formulation) (Powder part) Titanium dioxide 10.3% by weight Sericite 5.4 Kaolin 3.0 Yellow iron oxide 0.8 Bengala 0.3 Black iron oxide 0.2 (Oil phase) Decamethylcyclopentasiloxane 11.5 Liquid paraffin 4.5 Polyoxyethylene-modified dimethylpolysiloxane 4.0 (Aqueous phase) Purified water 50.0 1,3-Butylene glycol 4.5 Amole -Secoethanol extract 1.5 Sorbitan sesquioleate 3.0 Preservative proper amount Perfume proper amount (Production method) After stirring the aqueous phase by heating, the powder portion thoroughly mixed and pulverized is added and treated with a homomixer. Further, the heated and mixed oil phase is added and subjected to a homomixer treatment, and then a fragrance is added with stirring and cooled to room temperature.

[0034]

Industrial Applicability As described above, the external preparation for skin of the present invention has a melanin production inhibitory action and a tyrosinase activity inhibitory action, and it causes lightening of pigmentation, stains, freckles, melasma etc. after sunburn. It is an external preparation for skin that has excellent whitening effect and safety.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication location A61K 35/78 ADA 8217-4C AED T 8217-4C (72) Inventor Masako Naganuma Kohoku, Yokohama, Kanagawa Prefecture Shibaido Daiichi Research Center, Inc. 1050 Shinba-cho, Ku (72) Minor Fukuda Minoru Fukuda, Shibaido Daiichi Research Center 1050, Shinba-cho, Kohoku-ku, Yokohama-shi, Kanagawa

Claims (3)

[Claims] 1. Amor Seco,
Scientific name: Biden andicola HBK) external preparation for skin, characterized by being blended. 2. The content of the extract of Amor Seco is 0.
The external preparation for skin according to claim 1, which is 005 to 20.0% by weight. 3. The external preparation for skin according to claim 1, which is an external preparation for whitening skin.