JPH0959169A - Melanogenesis inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject inhibitor comprising the extracted essence of CHOUTOUKOU (a hook attached to the main axis of Uncaria rhynchophylla Miq. or Uncaria sinensis) as an active ingredient having inhibitory effect on melanogenesis, excellent beautifying effect, preventing and treating effect on stain/freckles caused by suntan, etc., useful as a cosmetic having high safety. SOLUTION: This melanogenesis inhibitor comprises the extracted essence of CHOUTOUKOU [a hook attached to the main axis of Uncaria rhynchophlla Miq. or Uncaria sinensis of (Rubiaceae)] as an active ingredient. The extraction, for example, is preferably carried out by extracting 30-150g of CHOUTOUKOU prepared by grinding after drying with 1l of ethanol under heating at 70 deg.C for 3 hours under reflux. The amount of CHOUTOUKOU is 0.005-0.1wt.% calculated as the dry weight of the extracted essence based on the whole amount of a skin preparation for external use.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a melanin production inhibitor containing an extract of Ginkgo biloba as an active ingredient. The melanin production inhibitor is useful as a whitening cosmetic, a skin anti-aging agent, and the like.

[0002]

2. Description of the Related Art Pigmentation of spots and freckles is one of the skin aging phenomena. The cause has not yet been completely elucidated, but one of the causes is that ultraviolet rays from sunlight or the like activate melanocytes that produce melanin, resulting in excessive production of melanin. It is considered. From such a viewpoint, as a therapeutic agent or a preventive agent for spots and freckles, in addition to an ultraviolet absorber, a reducing agent such as ascorbic acid or a hydroquinone derivative, a tyrosinase inhibitor such as kojic acid or linoleic acid (for example, JP-A- 63-284
See Japanese Patent Laid-Open No. 109-85907. ),
Whitening agents containing catechol glycosides as a main component (see, for example, JP-A No. 4-1115), whitening agents containing flavonoids as a main component (see, for example, JP-A-55-92305). , And a whitening agent whose main ingredient is isoferulic acid (
See, for example, JP-A-62-10312. ), A whitening agent containing azelaic acid as a main component (see, for example, JP-A-61-853).
See Publication 07. ), Etc. have been developed. On the other hand, the butterfly is Uncaria.
rhynchophylla Miq.) or stag beetle (Uncaria sin
Ensis) (Rubiaceae) is a hook attached to the main axis of the indole-type alkaloid, rhync
Containing hophylline and isorhynchophylline, it is used as an analgesic / spasmodic agent for convulsions due to high fever, pediatric antrum, etc. Moreover, Chotoko has a blood pressure lowering effect and is also effective for headache due to high blood pressure, dizziness, numbness, etc. (Natural Drug Dictionary, Takuo Okuda, Hirokawa Shoten). However, it is not known to those skilled in the art at present that the extract of Ginkgo biloba has a melanin production inhibitory action and that it contains a melanin production inhibitor as an active ingredient to produce a whitening agent.

[0003]

The above-mentioned whitening agents of the prior art listed above are not sufficiently effective, and
Nowadays when the market interest in prevention and treatment of freckles is very high, development of a whitening agent having a stronger melanin production inhibitory effect is desired. Therefore, an object of the present invention is to provide a melanin production inhibitor having a stronger melanin production inhibitory action.

[0004]

Means for Solving the Problems As a result of continuing the search for a melanin production inhibitory substance capable of solving the above-mentioned problems, the extract of Ginkgo biloba extract is a compound having a remarkable melanin production inhibitory action. It was discovered that the present invention was completed and the present invention was completed. That is, according to the present invention,
Provided is a melanin production inhibitor containing an extract of Ginkgo biloba as an active ingredient. The melanin production inhibitor according to the present invention can also be used in the form of an external preparation for the skin for the purpose of preventing and treating the occurrence of spots, freckles, dark skin, etc. due to sunburn and pigmentation. The buttercup extract of the present invention is a) 30 to 150 g of dried and crushed buttercup, 1 liter of ethanol is added, heated to 70 ° C., and refluxed for 3 hours. B) 30) dried and crushed
An extract obtained by adding 1 liter of a mixed solvent of ethanol / water to room temperature to 50 ° C with occasional agitation to 150 g of Ginkgo biloba and squeezing separation; c) 30 to 150 g of crushed and dried butterflies To Toko, add 1 liter of methanol, heat to 70 ° C, and reflux for 3 hours.
Digested methanol extract; d) Extracts with diethyl ether, acetone, ethyl acetate, hexane, etc .; e) 30 g to 150 g of dried and crushed Gypsophila
Add liters of water, heat to 70 ° C., and digest with water for 3 hours at reflux, etc. In some cases, the extraction solvent may be further distilled off with an evaporator for the purpose of adjusting the concentration of the thus-prepared extract, and the concentration-enhanced or powdered active ingredient may be directly mixed with the formulation. .

When the melanin production inhibitor according to the present invention is applied, the compounding amount of the extract of Ginkgo biloba is not particularly limited, but the dry weight of the extract is preferably 0.0001 per the total weight of the external preparation for skin. ~ 1% by weight
, More preferably 0.005 to 0.1% by weight. If this blending amount is less than 0.0001% by weight, the purpose of preventing or treating pigmentation may not be sufficiently achieved, and if the blending amount exceeds 1% by weight, it is as described below. When preparing into a different dosage form, the preparation may be difficult in terms of solubility, dispersibility and the like. The melanin production inhibitor according to the present invention can be prepared into a dosage form such as an ointment, a cream, an emulsion, a pack and a lotion by a known method. In addition, the types of constituent components that can be used in the preparation of these dosage forms, the blending amount,
Etc. can be appropriately determined by a person skilled in the art according to a common practice. The types, blending amounts, etc. of these constituents should not be limited by the following examples, and are any types, blending amounts, etc. known to be capable of preparing the intended dosage form. be able to. In addition, these skin external preparations,
In the preparation of drugs, etc., conventional melanin production inhibitors,
An ultraviolet absorber, an ultraviolet scatterer, an anti-inflammatory agent, etc. may be combined together.

[0006]

The present invention will be further described by the following examples, but the scope of the present invention should not be limited by these examples.

Example 1 and Example 1'and Comparative Example 1
Beauty 2 First, the results of experiments assessing the effect on melanogenesis inhibitory effect of extract of butterfly Uncariae is a component of the melanin production inhibitor of the present invention. Toukou Kanae Co., Ltd.Kanai Tokichi Shoten Co., Ltd.
Obtained from 9-11). The obtained butterfly was from China, and was cut several centimeters above and below, centered around the key-like spines on the stem in August-September, and dried in the sun.
To 30 g of butterfly, add 240 ml of ethanol,
Heated to 70 ° C. and digested at reflux for 3 hours and filtered to give an ethanol extract solution, which was used in Example 1. Also, add 30 g of butterflies to 100
Add ml water, heat to 70 ° C. and reflux for 3
Digested for hours and filtered to give a water extract solution, which was used in Example 1 '. HM3KO cell whitening effect The cells used in the experiment for evaluating the cell whitening effect are human skin-derived melanoma cell line HM3KO. This cell line
Derived from mice that have been used extensively in experiments of this kind
Like the B16 melanoma cell line, it has the property of producing a large amount of melanin in its cells under normal conditions, and is suitable as a cell to be used in this test. In addition, the use of human skin-derived cell lines in this experiment can be more suitable as a drug evaluation method considering application to the human body. HM3KO cells were placed in a 10 cm diameter culture dish at 1 x 10 ⁵
Cells were seeded at a density of 4 cells / dish and cultured for 24 hours at 37 ° C. using Dulbecco's modified Eagle medium containing 10% fetal bovine serum. After that, the extract of Ginkgo biloba extract has a concentration of 0.0001-0.
It was added to be 01% and cultured for 6 days. After culturing, the cells are collected, a cell pellet is prepared by centrifugation, and the color tone is visually evaluated by the following four-step evaluation method: +++: Remarkable whitening is observed ++: Sufficient whitening is recognized +: Slight whitening is observed ±: Evaluation is made by measuring the whitening degree in the absence of whitening.

On the other hand, as Comparative Examples 1 and 2, hydroquinone monobenzyl ether (see JP-A-61-227516), which is known to have a melanin production-inhibiting effect, and kojic acid (JP-A-61-227516). No. 63-2770619).
Compared with. The results are shown in Table 1.

Table 1 ────────────────────────────────── Example 1 Example 1 ′ Comparative Example 1 Comparative Example 2 Gypsophila Gypsophila Hydroquinone Concentration (%) Extract Extract Water Extract Extract Monobenzyl Ekojic Acid Ether ─────────────────────────────── ──── 0.0001 + + ± ± 0.0005 ＋＋ ＋ ＋ ＋ ± 0.001 ＋＋＋ ＋＋＋＋＋ ± 0.01 ＋ ───────────────────────────── ───── As can be seen from Table 1, the extract of Ginkgo biloba has a stronger whitening effect than hydroquinone monobenzyl ether and kojic acid.

Example 2 and Comparative Example 3 PUVA Treatment Induces in Colored Guinea Pig A-1
Inhibition test of pigmentation As described above, the extract of Ginkgo biloba exhibits a whitening effect on cultured cells (HM3KO) in vitro, but whether it shows the same effect in an in vivo test using experimental animals. The following test was carried out in order to investigate whether or not Colored guinea pigs used in this test
A-1 is a hybrid of the English-colored guinea pig JY-8 and the Hartley albino guinea pig, which has cinnamon-colored hair and is capable of inducing pigmentation by ultraviolet rays. A 48-week-old male A-1 dorsal coat was shaved with a clipper and a shaver, and then a site for causing pigmentation was divided into 2 × 2 cm squares. At this site, 30 ppm of 8-methoxypsoralen (8-Methoxyps
After applying 50 μl of oralen), the mixture was allowed to stand for 30 minutes, and the site was irradiated with long-wavelength UV-A at an energy dose of 10 J / cm ² . Immediately after irradiation, 100 μl of an ethanol solution of 0.5% Gypsophila communis extract was applied to the test site immediately after irradiation, and this application was performed twice a day for 40 consecutive days, and the degree of pigmentation was measured by ACI Japan. TI
Densitometric analysis by AS was used to compare with controls applied only ethanol. As a result, it was observed that the area to which the extract of Ginkgo biloba extract was applied had a markedly reduced degree of pigmentation compared to the control.

The following Table 2 shows the results of evaluating the degree of pigmentation in five grades [1] to [5] in the order of weak pigmentation. Since the lightness of the skin differs between the individual animals used, the lightness was not evaluated by the absolute value of lightness, but was relatively evaluated for each animal. Where grade [1]
Is the lightness (A ₁ ) of the skin in which no pigmentation is induced, that is to say that it is not exposed to UV light and is of the grade [5]
Refers to the lightness (A ₅ ) of the skin with the highest degree of pigmentation exposed to UV light without any drug applied, and the grades [2] to [4] are respectively those of the grade [1] above. The brightness (A ₂ ~ A that internally divides the difference between the brightness and the brightness of the grade [5] into 3 levels
₄ ). A ₂ = A ₁ + (A ₅ -A ₁ ) × 1/4 A ₃ = A ₁ + (A ₅ -A ₁ ) × 2/4 A ₄ = A ₁ + (A ₅ -A ₁ ) × 3 It is / 4.

[0012] In this test, no side effects such as inflammatory hypersensitivity reaction, eg, erythema, were observed at the site coated with the extract of Ginkgo biloba extract. It was confirmed that the extract can effectively suppress the production of melanin within a range that does not exhibit side effects. Table 2 Example 2 Comparative Example 3 Individual number Butterfly extract extract Ethanol only, control 1 4 5 2 3 5 3 2 5 4 3 5 5 3 4 6 3 4

Examples of the melanin production inhibitor according to the present invention will be described in Examples 3 to 7 below. Example 3 (Ointment 1) Ingredients By Weight A Chotox extract 0.001 White petrolatum 25 Stearyl alcohol 22 B Propylene glycol 12 Sodium lauryl sulphate 1.5 Preservative / antioxidant Adequate amount Perfume Appropriate amount Purified water Remaining amount ────── ──────────────────── Dissolve all ingredients belonging to 100 A in a hot water bath (oil phase), and separately
The components belonging to B are dissolved by heating (aqueous phase). Add the aqueous phase to the resulting oil phase, stir to emulsify and cool,
Ointment 1 was obtained.

Example 4 (Ointment 2) Ingredients by Weight A Chotoko Extract Extract 0.05 White Vaseline 40 Cetanol 15 Sorbitan Sesquioleate 5 B Lauromacrogol 0.5 B Preservative / Antioxidant Proper amount Perfume Proper amount Purified water Remaining amount ── ──────────────────────── All ingredients belonging to 100 A are dissolved in a hot water bath (oil phase), and separately
The components belonging to B are dissolved by heating (aqueous phase). Add the aqueous phase to the resulting oil phase, stir to emulsify and cool,
Ointment 2 was obtained.

Example 5 (milky lotion) Ingredients by weight A Agar beetle extract 0.5 Silicone KF56 2 Isopropyl myristate 3 POE (20) POP (4) Cetyl ether 1 B Glycerin 3 Hibiswako 105 0.2 Ethanol 5 Antiseptic / antioxidant Agent Appropriate amount Fragrance Appropriate amount Purified water Remaining amount ────────────────────────────────────────────────────────────── total amount 100] total 100
Then, A was added to B and emulsified uniformly to obtain an emulsion.

Example 6 (packing agent) Ingredients by weight Butterfly extract extract 0.1 Ethanol 10 Glycerin 5 Dipropylene glycol 5 Polyethylene glycol 4000 1 Polyvinyl alcohol 10 Vinyl acetate resin emulsion 13 Titanium oxide 12 Olive oil 3 Squalene 0.5 Preservative / antioxidant Agent Appropriate amount Perfume Appropriate amount Purified water Remaining amount ────────────────────────── Total amount 100 All the above ingredients were uniformly dissolved to obtain a pack. .

Example 6 (Toilet lotion) Ingredients by weight Butterfly extract Extract 0.5 Glycerin 41,3 Butylene glycol 4 Ethanol 7 POE (20) Oleyl alcohol 0.5 Preservative / antioxidant Proper amount Fragrance Proper amount Purified water Remaining amount ── ──────────────────────── Total amount 100 Glycerin and 1,3-butylene glycol were dissolved in purified water to obtain an aqueous solution. On the other hand, separately, ethanol, an extract of Ginkgo biloba and POE (20) oleyl alcohol were mixed. This mixture was added to the above aqueous solution, dissolved,
Then, it was filtered to obtain a lotion.

[0018]

Industrial Applicability As described above, the present invention can provide a novel and effective melanin production inhibitor, and a cosmetic composition containing them has an excellent whitening effect and a sunburn effect. It has a preventive and therapeutic effect on spots and freckles and is highly safe.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location A61K 7/48 A61K 7/48

Claims (2)

[Claims] 1. A melanin production inhibitor which contains an extract of Ginkgo biloba (Hanto Hou) as an active ingredient. 2. The melanin production inhibitor according to claim 1, which is in the form of a skin external preparation.