JP3140876B2 - Melanin production inhibitor and 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 a melanin production inhibitor and an external preparation for the skin, and more particularly to a medicament for inhibiting the production of melanin, which is a cause of skin pigmentation, and effective in preventing and treating skin pigmentation. It does not provide an external preparation.

[0002]

2. Description of the Related Art Skin spots, freckles and skin pigmentation after sunburn are the result of a marked increase in melanin production due to the activation of pigment cells (melanocytes) present in the skin. It has become one of.
Generally, melanin changes from tyrosine to dopa and dopa to dopaquinone by the action of the enzyme tyrosinase biosynthesized in pigment cells, and then converts intermediates such as 5,6-dihydroxyindophenol. It is supposed to be formed after passing through.

[0003] Therefore, in order to prevent or improve skin darkness, it is conceivable to inhibit the melanin production process or to bleach the already produced melanin in pale color. Various whitening components have been conventionally proposed based on such a concept. For example, as compounds that inhibit tyrosinase activity and suppress melanin production, colloidal sulfur and sulfur compounds typified by glutathione are exemplified. In addition, ascorbic acids, hydrogen peroxide, hydroquinone, catechol, and the like have been used as light-color bleaching of produced melanin.

[0004]

However, with respect to the prevention and improvement of skin pigmentation, ascorbic acids are easily oxidized and unstable in systems containing a large amount of water, such as hydrated cosmetics, and cause discoloration. . In addition, aqueous hydrogen peroxide has problems in storage stability and safety, and glutathione and colloidal sulfur emit a remarkable off-odor, so that their use in products is restricted. Further, hydroquinone, catechol and the like have problems in safety such as skin irritation and allergic property, and satisfactory ones have not yet been obtained.

The present invention has been made in view of the above circumstances, and provides a melanin production inhibitor and an external preparation for skin that has a sufficient effect of preventing and improving skin pigmentation and that can be used safely. Make things an issue.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, it has been found that an extract extracted from a flower of a specific crude drug or a dried product thereof is excellent in suppressing melanin production. The inventors have found that they have an effect, and based on this, completed the present invention.

[0007] That is, the present invention relates to an extract obtained by extracting from a flower of Achicium (Cichorium Intybus L.) asteraceae with water, a lower alcohol, a polyhydric alcohol, or a mixed solvent of these alcohols and water. Or a melanin production inhibitor comprising a dried product thereof, and at least one or more of the melanin production inhibitor is preferably contained in the base in an amount of 0.0
The present invention relates to an external preparation for skin characterized in that it is contained in an amount of from 0.01 to 10% by weight (in terms of dry matter).

Hereinafter, the present invention will be described in detail.

[0009] The melanin production inhibitor of the present invention can be obtained from water from the flower of athletic plant (Cichorium Intybus L.) of Asteraceae.
It consists of a lower alcohol, a polyhydric alcohol, or an extract obtained by extraction with a mixed solvent of these alcohols and water, or a dried product thereof.

[0010] Here, Aticolia used in the present invention is a kind of Asteraceae plant, which is also called Asteraceae, and its scientific name is Cichorium Intybus L. This plant is widely distributed from Europe to Siberia and North Africa, and is also native to South America. Roots are used as a substitute for coffee, folk medicines such as diuresis, tonic, stomach and blood purification, and whole plants are used for treatment of hepatitis.

Further, as an application to cosmetics, it has been reported that an extract of the aerial part (dry whole plant) of Aticoria has an effect of preventing aging (Japanese Patent Publication No. 2-500).
442). However, the examination by the present inventors has revealed that the above extract has no melanin production inhibitory effect and is difficult to apply to the prevention and treatment of skin pigmentation.

Next, in addition to water as the extraction solvent, methanol, ethanol, n-propanol, n-butanol and the like can be mentioned as the lower alcohol, and propylene glycol, glycerin, 1,1 as the polyhydric alcohol. Examples thereof include 3-butylene glycol, 1,4-butylene glycol, and 2,3-butylene glycol. Upon extraction, one or more of these solvents are used in combination.

[0013] The method of extracting the active ingredient from the flower of Aticoria with the above-mentioned solvent itself employs ordinary cold soaking or digestion. Hereinafter, a production example of a representative Aticoria flower extract or a dried product thereof will be described.

<Production Example 1> (First step) 1 kg of head flower of Aticoria was extracted with 1 liter of methanol at room temperature for 7 days, and the obtained extract was evaporated using an evaporator and concentrated by a vacuum pump. Dry to give 35 g of concentrate. (Second step) 35 g of the concentrate obtained in the first step was liquid-liquid distributed using 1 L of chloroform and 1 L of water using a separating funnel,
The aqueous phase is concentrated to dryness using an evaporator and a vacuum pump to obtain 7 g of a dried product.

<Production Example 2> (First step) 1 kg of head flower of Aticoria was extracted three times with 1 liter of ethanol at 60 ° C for 6 hours each, and the obtained extract was distilled off using an evaporator. Thereafter, the solution was concentrated to dryness with a vacuum pump to obtain 27 g of a concentrate. (Second step) 10 g is added to 27 g of the concentrate obtained in the first step.
After adding 0 ml of propylene glycol and sonicating for 15 minutes, the insoluble matter is removed using a centrifugal separator to obtain 65 ml of an Aticoria extract.

The external preparation for skin of the present invention preferably contains at least one melanin production inhibitor consisting of the above-mentioned flower extract of Aticoria or a dried product thereof, preferably in an amount of 0.001 to 10% by weight ( (In terms of dry matter). Of the skin external preparations, when used in skin external preparations such as cosmetics for preventing spots, freckles and darkness due to sunburn, 0.001% by weight or more, and treatment of pigmentation disease When used as an agent for the purpose of skin external preparation, 1% by weight or more is preferable as an effective amount.

That is, if the amount is less than 0.001% by weight, it is difficult to achieve the object of the present invention, and even if it exceeds 10% by weight, it is difficult to expect an effect corresponding to the increase.

In addition to the above-mentioned extract or its dried product, the skin external preparation of the present invention contains various components generally used in cosmetics, pharmaceuticals, etc., ie, an aqueous component, an oily component, a powder component, and a surfactant. In addition, agents such as humectants, coloring agents, fragrances, preservatives, or antioxidants, ultraviolet ray blocking agents, chelating agents, anti-inflammatory agents, whitening ingredients other than the present extract or a dried product thereof can be blended.

The dosage form of the external preparation for skin of the present invention is arbitrary,
Any of those usually used for pharmaceuticals, quasi-drugs, cosmetics and the like may be used, and examples thereof include dosage forms such as ointments, creams, emulsions, lotions, and packs.

Hereinafter, the present invention will be described in more detail with reference to various experimental examples conducted to evaluate the effectiveness of the flower extract of Aticoria or the dried product thereof according to the present invention.

<Experimental Example 1> Inhibition of melanin production on pigment cells 3 × 10 ⁴ mouse melanoma-derived cells B-16 were seeded in a plastic culture flask (75 cm ² ), and 10%
The cells were cultured in Eagle's MEM medium containing fetal calf serum at 37 ° C. under 5% carbon dioxide.

Two days later, the dried product obtained in the above Preparation Example 1 was used in a concentration of 1 × 10 ⁻⁴ % to 5 × 10 ⁻² % in the medium.
(W / V). On the other hand, as a comparative product, the dried product obtained by replacing the Aticoria flower with the whole plant dried product in Preparation Example 1 was extracted at a concentration of 5 × 1 in the medium.
The ^solution was added to a concentration of 0 ^-2 % (W / V), and the cells were further cultured for 4 days.

After completion of the culture, the medium was removed, and the cells were washed with an equilibrated phosphate buffered saline (PBS).
The cells were detached using the A-containing solution, and the cells were collected by a centrifuge. After the cells were washed with an equilibrated phosphate buffered saline solution, 1N sodium hydroxide was added to the precipitate to dissolve by heating. After cooling, chloroform was added, and the mixture was centrifuged again. The supernatant thus obtained was measured at an absorbance of 400 nm, and the amount of melanin was determined from a calibration curve previously prepared using synthetic melanin. The amount of melanin was determined as an amount per 10 ⁶ cells. Table 1 shows the results. In addition, the suppression rate in the table was obtained by the following equation.

Inhibition ratio (%) = (melanin content of control product−melanin content of test sample added product) × 100 / (melanin content of control product)

[0025]

[Table 1]

As is clear from the results in Table 1, the dried extract of Aticoria flower has a remarkable melanin production inhibitory effect on pigment cells at 0.001% or more as compared with the solvent control (control). On the other hand, it was demonstrated that the whole plant dry matter extract did not show any melanin production inhibitory action even at 0.05%.

<Experimental Example 2> Actual use test A comparative cream in which the cream of the present invention shown in Example 1 to be described later and the dry extract of Aticoria whole plant were used in place of the A. coli flower extract in Example 1 In addition, a control product cream replaced with the same amount of purified water in place of the Aticoria flower extract in Example 1 was used, and 60 female volunteers suffering from black and white, spots, and freckles were statistically equivalent to three groups. Each of them was continuously used for 3 months for a long period, and the improvement effect on pigmentation was evaluated by visual observation. Table 2 shows the results. In addition, the case where the effect more than a little improvement was recognized was made effective.

[0028]

[Table 2]

As is evident from the results in Table 2, it was proved that the product of the present invention to which the atchicholia flower extract was blended was clearly more effective than the comparative product and the control product. During the test period, no undesired reaction on the skin was observed at the sample application site, confirming that the safety was high.

Examples of the present invention will be described below, but the present invention is not limited to these examples. The mixing ratio is part by weight.

Example 1 Water-in-oil Cream (A) Squalane 12.0 Beeswax 2.0 Microcrystalline Wax 2.0 Glycerin (20EO) Pyroglutamic Acid Monopalmitate 5.0 4- (1,1-dimethylethyl) -4'-methoxydibenzoylmethane 0.5 γ-tocopherol 0.05 butylparaben 0.2 (B) malbit 8.0 1.3-butanediol 7.0 Aticoria flower extract (Production Example 1) 5.0 Purified water 58.25 (Production method) (A) is uniformly dissolved at 80 ° C, and separately dissolved at 80 ° C.
(A) is added to (A) while stirring with a homomixer and emulsified, and then cooled to 30 ° C.

Example 2 Oil-in-water Cream (A) POE (30) Cetyl Ether 2.0 Glycerin Monostearate 10.0 Liquid Paraffin 10.0 Vaseline 4.0 Cetanol 5.0 γ-Tocopherol 0.05 BHT 0 .01 2-Hydroxy-4-methoxybenzophenone 0.5 butylparaben 0.2 (B) Atikolia flower extract (Production Example 2) 10.0 Refined water 58.24 (Production method) Combine the components of (A) Heat to 80 ° C.
The components of (B) are combined and heated to 80 ° C. All the components of (A) are added to all the components of (B), and the mixture is emulsified with stirring, and then cooled.

Example 3 Emulsion (A) Synthetic gay wax 2.5 Cetanol 1.0 Squalane 4.0 Stearic acid 1.0 Polyethylene glycol monostearate (25EO) 2.2 Glycerin monostearate 0.5 Butylparaben 0. 1 γ-tocopherol 0.05 BHT 0.01 4- (1,1-dimethylethyl) -4′-methoxydibenzoylmethane 0.5 (B) 1,3-butylene glycol 3.0 propylene glycol 7.0 xanthan gum 0.1 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Atikoria flower extract (Production example 1) 1.0 Purified water 76.64 (Production method) While stirring (A) and (B) at 70 ° C, respectively. Dissolve. (A) is added to (B), preliminary emulsification is carried out, and the mixture is uniformly emulsified by a homomixer. After the emulsification, the mixture is cooled to 30 ° C. while stirring.

Example 4 Lotion (A) POE (20) sorbitan monolaurate 1.5 POE (20) lauryl ether 0.5 ethanol 10.0 γ-tocopherol 0.02 (B) glycerin 5.0 Extract (Production Example 2) 4.0 Sodium isoferrate 0.5 Citric acid 0.15 Sodium citrate 0.1 Purified water 78.23 (Production method) Combine the components of (A) and dissolve at room temperature I do. On the other hand, each component of (B) is also dissolved at room temperature, and is added to (A) formulation and solubilized.

Example 5 Packing Charge (A) Polyvinyl Alcohol 15.0 Purified Water 40.0 (B) Bisabolol 0.5 γ-Tocopherol 0.02 Ethanol 4.0 Aticoria Flower Extract (Production Example 2) 4.0 POE (8) Polyoxypropylene glycol (55) 3.0 Refined water 33.48 (Production method) (A) is dispersed and dissolved at room temperature. To this (B)
And dissolve uniformly.

[0036]

According to the present invention, it is possible to provide a melanin production inhibitor excellent in melanin production inhibitory action on living pigment cells, and a highly stable and safe melanin production inhibitor and an external preparation for skin. The topical skin preparation of the present invention can be used for preventing, improving, and treating local pigmentation such as spots, freckles, and sunburn, and systemic pigmentation such as Addison's disease. Moreover, it is excellent in safety and can be used continuously for a long time.

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Takayuki Katagiri 560 Paula-cho, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Prefecture Inside the Totsuka Research Laboratory (72) Koji Yokoyama 560 Paula-cho, Kashio-cho, Totsuka-ku, Yokohama-shi, Kanagawa Kasei Kogyo Co., Ltd., Totsuka Laboratory (72) Inventor Tadashi Suzuki Kanagawa Prefecture, Yokohama City, Totsuka-ku, Kashio-cho 560 Paula Kasei Kogyo Co., Ltd. (72) Inventor Tomomi Kato, Kanagawa Prefecture, Yokohama-shi Totsuka-ku, Kashio-cho, 560 Paula Kasei Kogyo Co., Ltd.Totsuka Research Laboratories (72) Inventor Norio Fujiwara Kanagawa Prefecture Yokohama City Totsuka-ku Kashio-cho 560 Paula Kasei Industry Co., Ltd. Totsuka Research Center (72) Inventor Hiroyuki Nakano Kanagawa Prefecture Yokohama-shi Totsuka-ku Kashiocho 560 Pola Chemical Industry Co., Ltd. Totsuka Laboratory (58) Fields surveyed (Int. Cl. ⁷ , DB name) A61K 35/78 A61K 7/00 A61K 7/48 A61P 17/00 BIOSIS (DIALOG) CA (STN) MEDLINE (STN)

Claims (3)

(57) [Claims] 1. An Asteraceae plant, Achikoria (Cichorium In)
tybus L.) A melanin production inhibitor comprising an extract obtained by extracting flowers, lower alcohols, polyhydric alcohols, or a mixed solvent of these alcohols and water from flowers, or a dried product thereof. 2. An external preparation for skin, wherein at least one or more of the melanin production inhibitors according to claim 1 is blended in a base. 3. The compounding amount of the melanin production inhibitor is 0.001 to 10% by weight (in terms of dry matter) of the whole.
2. The external preparation for skin according to item 1.