JPH05194177A - External agent for skin - Google Patents

Abstract

PURPOSE:To provide an external agent for skin, exhibiting excellent effect for preventing and improving the chromatosis by the melanogenesis suppressing action and having high safety. CONSTITUTION:The objective agent contains a liquid extracted from Genipa americana or its dried product as an active component and the amount of the component is preferably 0.01-10wt.%. The agent exhibits melanogenesis- suppressing action on chromocyte and has excellent pigmentation-ameliorating effect, skin-beautifying effect and high safety.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an external preparation for skin, more specifically, it is effective for the prevention and treatment of skin pigmentation, and its effect can be remarkably enhanced when used in combination with various active ingredients. It is intended to provide an external preparation.

[0002]

2. Description of the Related Art Skin pigmentation after spots, freckles and sunburn is a marked increase in melanin production due to activation of pigment cells (melanocytes) present in the skin.
It is one of the worries of the skin of the middle-aged and elderly. External skin preparations containing ascorbic acid, hydrogen peroxide, glutathione, colloidal sulfur and the like are known for the purpose of preventing and improving these skin pigment troubles.

[0003]

However, regarding the prevention and improvement of skin pigmentation, ascorbic acids are easily oxidized and unstable in a system containing a lot of water such as a water-containing cosmetic, which causes discoloration. .. Further, hydrogen peroxide water has problems in storage stability and safety, and glutathione and colloidal sulfur emit a remarkable off-flavor, so that their use in products is restricted. Further, hydroquinone, catechol and the like have problems in safety such as skin irritation and allergenicity, and at present, satisfactory ones have not yet been obtained. The present invention has been made in view of the above circumstances, preventing skin pigmentation, not only exerts an excellent effect for improvement, but also has no harmful effect on the skin and can be safely used for external use on the skin. The challenge was to provide the agent.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems, and as a result, have excellent melanin production in an extract or a crude product of a crude extract extracted or crudely purified from a specific crude drug. The present invention was completed based on the finding that it has a suppressing effect.

[0005] That is, the present invention is a
a Americana L. Rubiaceae plant) is extracted with an organic solvent or a mixed solution of an organic solvent and water, and the obtained extract or a dried product thereof is blended, which is a skin external preparation. The above-mentioned extract or its dry product is mixed in a proportion of 0.01 to 1 in terms of dry product.
It relates to 0% by weight of the external preparation for skin.

The present invention will be described in detail below.

The wit applied to the present invention is a plant of the family Rubiaceae and has a scientific name of Genipa Americana L. This plant is mainly from Latin America, and is especially suitable from Peru and Brazil. The fruit is shaped like a lemon and is used in soft drinks. However, no dried fruit of this plant was used for the prevention or treatment of skin pigmentation disease, which is the first confirmation by the present inventors.

Next, the organic solvent used in the present invention means
Methanol, ethanol, n-propanol, n-butanol, ethyl acetate, acetone, chloroform, dichloroethane, dibromoethane, diethyl ether, ethyl methyl ether, n-hexane, benzene, toluene,
Examples thereof include xylene, but are not limited thereto. At the time of extraction, one kind or a mixture of two or more kinds of these solvents is used.

As a method for extracting the active ingredient from the wit with an organic solvent, ordinary cold soaking or hot soaking is suitable.

In addition to the above-mentioned extract or its dried product, the external preparation for skin of the present invention includes various components generally used in pharmaceuticals, cosmetics, etc., that is, an aqueous component, an oil component, a powder component, and a surfactant. A moisturizing agent, a coloring agent, a fragrance, an antiseptic agent, or an antioxidant, an ultraviolet blocking agent, a chelating agent, an anti-inflammatory agent, and a whitening ingredient other than the present extract or its dried product may be added.

Further, the dosage form of the present invention is arbitrary and may be any as long as it has been conventionally used for this type of external preparation for skin, for example, ointment, cream, emulsion, lotion, pack, bath preparation and the like. Can be mentioned.

[0012]

EXAMPLES Next, production examples of an extract obtained by extracting from the wit applied to the external preparation for skin of the present invention or a dried product thereof will be shown.

<Production Example 1> (First Step) 500 g of weight was extracted with 5 L of a methanol solvent at room temperature for 7 days, the obtained extract was distilled off with an evaporator, and then concentrated to dryness with a vacuum pump. Then
50 g of concentrate was obtained. (Second step) 50 g of the concentrate obtained in the first step is added to 500 parts of water.
The operation of dissolving in mL and extracting with shaking with 500 mL of chloroform is repeated 5 times, and the fractions that transfer to the chloroform phase are combined in each time, and then the chloroform is distilled off to obtain 9 g of a dried product applicable to the present invention. Incidentally, in order to remove the dye contained in the dried product, silica gel column chromatography can be further performed.

<Production Example 2> (First Step) 500 g of wite was extracted with 5 L of a solvent of diethyl ether: ethanol = 1: 1 at room temperature for 7 days,
The solvent was distilled off from the obtained extract using an evaporator, and the mixture was concentrated to dryness with a vacuum pump to obtain 30 g of a dried product. (Second step) 5 g of the concentrate obtained in the first step is placed on a silica gel column and eluted with a solution of n-hexane: ethyl acetate = 7: 3, the eluate is distilled off, and the drying is applied to the present invention. 0.5 g of the product is obtained.

<Production Example 3> 500 g of wit was immersed in 5 L of an ethanol solvent and transferred to a Soxhlet extractor,
After heat extraction for a period of time, the obtained extract was evaporated using an evaporator and then concentrated to dryness with a vacuum pump.
10 g of dried product was obtained.

The mixing ratio of the extract or its dry product used in the external preparation for skin of the present invention is 0.
01 to 10% by weight is preferable. That is, when used in a skin external preparation such as a cosmetic for the purpose of preventing spots, freckles, and dark skin due to sunburn, 0.01% by weight or more is used as a drug for treating pigmentation. When used as a skin external preparation, 0.1% by weight or more is preferable as an effective amount. That is, if the content is less than 0.01% by weight, the object of the present invention cannot be achieved, and if it exceeds 10% by weight, it is difficult to expect the improvement of the effect commensurate with the increase.

Next, in order to confirm the usefulness of the present invention,
Perform various tests.

First, the melanin suppressing effect on pigment cells is tested. <Experimental Example 1> (Method) 3 in a plastic culture flask (75 cm ² ).
Eagle MEM medium 10 inoculated with 10 ⁴ mouse melanoma-derived cells B-16 and containing 10% fetal bovine serum 10
The cells were cultured in mL at 5% carbon dioxide at 37 ° C. Two
Day after the added obtained in Production Example 1 was dried product so that ^{1 × 10- 3% ~5 × 10-} 2% and (W / V) at a concentration in the medium, respectively. After 5 days, 15 mL of Eagle's MEM medium containing 10% fetal bovine serum and the dried product obtained in Production Example 1 were added, and the cells were further cultured for 2 days. After culturing, the medium is removed, the cells are washed with phosphate buffer, and trypsin and ED are then added.
It was peeled off using a TA-containing solution and collected by a high speed centrifuge. After washing the cells with phosphate buffer,
An aqueous solution of sodium hydroxide N was added and dissolved by heating. After cooling, chloroform was added and the mixture was centrifuged again. The supernatant thus obtained was measured for absorbance at 400 nm, and the amount of melanin was determined from a calibration curve prepared in advance using synthetic melanin. The amount of melanin was determined as the amount per 10 ⁶ cells.

(Result)

[Table 1] As is clear from the results of the suppression rate of melanin production in Table 1, the dried product from wit shows a remarkable melanin suppressing effect on pigment cells.

Next, the safety of the dried product obtained in Production Example 1 and the external preparation for skin mixed with the dried product is tested. Experimental Example 2 (a) Cumulative skin irritation (Method) The back of white guinea pigs (5 in each group) is shaved using an electric clipper and washed with an antiseptic solution. Dried one
%, 5%, 10% ethanol-water (1: 1) solution and 4 samples of the cream of Example 1 described below, 1 day per day
Each time, 50 mg / cm ^{2 was} applied, and the degree of irritation was visually measured daily.

(Result)

[Table 2] As is clear from the results of cumulative skin irritation in Table 2, the dried product of wit has no skin irritation at any concentration, and the external preparation for skin of the present invention has no skin irritation and is safe. ..

(B) Contact sensitization (Method) Using a healthy guinea pig having a body weight of 380 to 420 g, the method of Sato et al. (Contact Dermatitis, 7, 225)
(See 1981)). (Sample) Two samples of the dried product obtained in Production Example 1 and the external preparation for skin of the present invention (cream of Example 1) are used.

(Evaluation Criteria) Evaluation of contact sensitization is as follows.

[Table 3] Erythema and crust formation in

[Table 4] According to the edema formation score.

(Result)

[Table 5] As is clear from the results of contact sensitization in Table 5, no sensitization is observed in the dried product from wit and the external preparation for skin of the present invention.

Next, the effect of improving the pigmentation of the external preparation for the skin containing the dried product obtained in the above Production Example 1 will be tested. <Experimental Example 3> Skin pigmentation improving effect (Sample) Examples 1, 2, and 3 in which the dried product of the present invention was blended.
5 samples of the cream of No. 4 and the cream of Comparative Example 1 as a control product. (Method) Divide 100 female volunteers suffering from dark skin, spots and freckles into 5 groups with almost the same degree of pigmentation,
The above cream was continuously used for 3 months each.
Three months later, five beauty specialists evaluated the degree of the improvement effect on dark skin, spots, and freckles. Slightly effective when the above-mentioned improvement is recognized.

(Result)

[Table 6] As is clear from the results of the pigmentation improving effect in Table 6, it is understood that the external preparation for skin containing the dried product of the present invention has the pigmenting improving effect.

No side effects were observed in any of the creams during the test period, confirming that the external preparation for skin of the present invention is highly safe.

Examples of the present invention will be shown below, but the present invention is not limited thereto. The mixing ratio is parts by weight.

Example 1, 2, 3, 4 cream (prescription)

[Table 7]

(Manufacturing method) The components of (A) were combined and the temperature was adjusted to 80 ° C.
Heat to. The components of (B) are combined and heated to 80 ° C. All components of (A) are added to all components of (B) to emulsify with stirring, and then cooled.

Example 5 Emulsion (formulation) (A) Synthetic gallows 2.5 Cetanol 1.0 Squalane 4.0 Stearic acid 1.0 Polyethylene glycol monostearate (25EO) 2.2 Glycerin monostearate 0.5 Butyl Paraben 0.1 δ-Tocopherol 0.05 BHT 0.01 4- (1,1-Dimethylethyl) -4'-methoxydibenzoylmethane 0.5 Dried uit extract (Production Example 2) 1.0 (B) 1,3-Butylene glycol 3.0 Propylene glycol 7.0 Xanthan gum 0.1 Carboxyvinyl polymer 0.2 Potassium hydroxide 0.2 Purified water 76.64 (Production method) (A) and (B) respectively at 70 ° C. Dissolve with stirring. (A) is added to (B), preliminarily emulsified, homogenized with a homomixer, and after emulsification, cooled to 30 ° C. with stirring.

Example 6 Lotion (Formulation) (A) POE (20) Sorbitan monolaurate 1.5 POE (20) Lauryl ether 0.5 Ethanol 10.0 δ-Tocopherol 0.02 Weight extract dried product (Production) Example 3) 0.02 (B) Glycerin 5.0 Propylene glycol 4.0 Citric acid 0.15 Sodium citrate 0.1 Purified water 78.71 (Production method) (A) Dissolve. On the other hand, each component of (B) is also dissolved at room temperature and added to the component (A) to be solubilized.

Example 7 Ointment (Formulation) (A) Liquid paraffin 58.8 Vaseline 6.0 Polyoxyethylene sorbitan monostearate (20 EO) 6.0 Beeswax 3.0 Weight extract dried product (Production Example 1) ) 6.0 (B) Arbutin 0.2 Glycerin 10.0 Purified water 10.0 (Production method) (A) and (B) are dissolved with stirring at 70 ° C. (B) is added to (A) and emulsified. Cool to 30 ° C.

[0034]

INDUSTRIAL APPLICABILITY According to the present invention, the wit extract exerts a strong melanin production-inhibiting action on living pigment cells, and when it is blended in a base in a fixed ratio, it is remarkably excellent in whitening effect on the skin. Therefore, it can be used for the improvement and treatment of local spots such as spots, freckles, and dark skin due to sunburn, and systemic pigmentation diseases such as Addison's disease.
Moreover, since it has excellent safety, it can be used continuously for a long period of time.

Front page continuation (72) Inventor Takayuki Katagiri 27 Takashimadai, Kanagawa-ku, Kanagawa, Kanagawa 1 Pola Chemical Industry Co., Ltd. Yokohama Laboratory (72) Inventor Keiko Onuki 27, Takashimadai, Kanagawa-ku, Yokohama, Kanagawa Industrial Co., Ltd. Yokohama Research Laboratory (72) Inventor Hiroyuki Nakano 1 Takashimadai 27-1 Takashimadai, Kanagawa-ku, Yokohama, Kanagawa Pola Chemical Industry Co., Ltd. Yokohama Research Laboratory

Claims (2)

[Claims] 1. A skin characterized by being extracted with a weight (scientific name: Genipa Americana L. Rubiaceae) with an organic solvent or a mixed solution of an organic solvent and water, and incorporating the obtained extract or a dried product thereof. Topical agent. 2. The external preparation for skin according to claim 1, wherein the mixing ratio of the extract or the dried product thereof is 0.01 to 10% by weight based on the total amount of the dried product.