KR102215168B1 - Composition for skin whitening containing acetic acid 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester - Google Patents

Abstract

The present invention relates to a composition for whitening containing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid, and more specifically, 16-hydroxy-octadeca-9,17 -Diene-12,14-diynyl ester shows remarkably excellent whitening effect by using acetic acid, especially in a composition that improves pigmentation symptoms such as spots and freckles or dullness of the skin, and makes the skin look even and bright. About.

Description

Composition for skin whitening containing acetic acid 16-hydroxy-octadeca-9,17-diene-12 (16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester) ,14-diynyl ester}

The present invention relates to a composition for whitening containing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid, and more specifically, 16-hydroxy-octadeca-9,17 -Diene-12,14-diynyl ester shows remarkably excellent whitening effect by using acetic acid, especially in a composition that improves pigmentation symptoms such as spots and freckles or dullness of the skin, and makes the skin look even and bright. About.

Human skin color is determined by several factors such as the activity of melanocytes that make melanin pigments, the distribution of blood vessels, the thickness of the skin, and the presence or absence of pigments inside and outside the body such as carotenoids and bilirubin. In particular, melanin, a black pigment produced by the action of various enzymes such as tyrosinase, is the most important factor in melanocytes. The formation of melanin pigment is influenced by genetic factors, physiological factors related to hormone secretion, stress, and environmental factors such as ultraviolet irradiation. Melanin exists in the skin and plays an important role in protecting the body from ultraviolet rays, but it is known to play a major role in promoting pigmentation and skin aging due to overproduction of melanin, as well as inducing skin cancer. Ascorbic acid, kojic adcid, arbutin, and hydroquinone have been previously used to treat or alleviate skin pigmentation symptoms and excessive melanin pigmentation caused by exposure to UV rays. , Glutathione or derivatives thereof, and substances with tyrosinase inhibitory activity have been used in cosmetics or pharmaceuticals. These have insufficient whitening effect, safety issues for the skin, and formulations when incorporated into cosmetics. Its use is limited due to stability issues and the like.

On the other hand, in recent years, as a kind of component separated from natural materials, there is increasing interest in components extracted from ginseng, especially polyyne components. Among them, it has been found that panaxinol, panaxidol, panaxtriol, and the like, as polyacetylene components, have cytotoxicity against cancer cells and thus have anticancer effects. However, studies on the polyacetylene component are still insignificant, and in particular, notable research results have been reported on the efficacy exhibited in relation to improving skin conditions other than the anticancer effect.

Korean Patent Application Publication No. 10-2012-0083943 (published on July 27, 2012)

Accordingly, the inventors of the present invention were studying to find a material that exhibits excellent skin whitening effect, etc., while 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid can provide excellent skin whitening effect. It was found that the irritation to the skin was small, and the present invention was completed.

Accordingly, an object of the present invention is to provide a composition exhibiting excellent skin whitening effect by using 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid.

In order to achieve the above object, the present invention is a skin whitening agent containing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid, which is a compound represented by the following formula (1) as an active ingredient. It provides a composition for external application or a pharmaceutical composition.

The composition of the present invention provides excellent skin whitening effect by containing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid to reduce pigmentation symptoms such as spots and freckles, and It improves dullness and makes the skin look even and bright.

The composition of the present invention comprises 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid (acetic acid 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester) Contained as an active ingredient, it provides excellent skin whitening effect.

16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid used in the present invention is a compound having the structure of the following formula (1), has a molecular weight of 316, and (Z)-16 Also known as -hydroxy-9,17-octadecadiene-12,14-diynyl acetate ((Z)-16-hydroxy-9,17-octadecadiene-12,14-diynyl acetate).

[Formula 1]

The composition according to the present invention contains 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid in an amount of 0.001 to 50% by weight, preferably 0.01 to 30% by weight, based on the total weight of the composition. Preferably, it may be contained in an amount of 0.1 to 10% by weight. If the content of the 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid is less than 0.001% by weight, the efficacy and effect of the component is weak, and if it exceeds 50% by weight, skin safety Or because there is a problem in the formulation.

The composition of the present invention may be formulated as a composition for external application for skin, in particular, a cosmetic composition, and may be formulated containing a cosmetically or dermatologically acceptable medium or base. In addition, the composition of the present invention may be provided in any formulation suitable for topical application, for example, a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oil phase, suspension, solid, gel, powder, It may be provided in the form of a paste, foam or aerosol composition. Specifically, the composition of the present invention may be provided in the form of a cream, skin, lotion, powder, ointment, spray or conceal stick. Compositions of such formulations can be prepared according to conventional methods in the art.

In addition, the composition according to the present invention may contain other ingredients that can give synergistic effect to the main effect, preferably within a range that does not impair the main effect in addition to the above-described substances. In addition, the composition according to the present invention may further include a moisturizing agent, an emollient agent, an ultraviolet absorber, a preservative, a sterilizing agent, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, a cooling agent or a limiting agent. The blending amount of the ingredients can be easily selected by a person skilled in the art within a range that does not impair the object and effect of the present invention, and the blending amount may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight, based on the total weight of the composition. .

In addition, the composition of the present invention can be formulated as a pharmaceutical composition. When the composition according to the present invention is applied to pharmaceuticals, it can be formulated as an oral or parenteral dosage form in a solid, semi-solid or liquid form by adding an inorganic or organic carrier commercially available to the active ingredient used in the present invention. , The pharmaceutical composition according to the present invention may be administered orally, parenteral, rectal, topical, transdermal, intravenous, intramuscular, intraperitoneal, subcutaneous, and the like.

Formulations for oral administration include tablets, pills, granules, capsules, powders, fine granules, powders, emulsions, syrups, pellets, and the like. In addition, the formulation for parenteral administration may include injections, drops, ointments, lotions, sprays, suspensions, emulsions, and suppositories. The composition according to the present invention can be easily formulated as an active ingredient by conducting it according to a commercial method, and in this case, surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffers, suspensions, and other commonly used auxiliary agents can be appropriately used. have.

The dosage of the active ingredient of the pharmaceutical composition of the present invention will vary depending on the age, sex, weight, pathological condition and severity of the subject to be administered, the route of administration, or the judgment of the prescriber. Determination of an appropriate dose based on these factors is within the level of those skilled in the art, and its daily dose is, for example, 0.1 mg/kg/day to 100 mg/kg/day, more specifically 5 mg/kg/day to 50 mg/kg. /It can be work, but is not limited thereto.

Hereinafter, the present invention will be described in more detail through examples. These examples are for illustrative purposes only, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not construed as being limited by these examples.

[Reference Example 1]

16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid for testing the efficacy of the composition of the present invention was purchased and used from Cosvision (Korea).

[Test Example 1] Tyrosinase inhibitory effect

The tyrosinase enzyme was extracted from Mushroom and was used by SIGMA. First, the substrate tyrosine is dissolved in distilled water to make a solution of 0.3 mg/ml, and the solution is added to a test tube by 1.0 ml. Then, 1.0 ml of potassium-phosphate buffer (0.1 mol concentration, pH 6.8) and 0.7 ml of distilled water are added thereto. Added.

Add 0.2 ml of a sample solution prepared by mixing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid of Reference Example 1 in an ethanol solution at an appropriate concentration into the reaction solution, and then in a 37°C thermostat Reacted for 10 minutes. At this time, as a negative control (no addition), only 0.2 ml of the solvent was added instead of the sample solution, and ascorbic acid was used as a positive control. To this reaction solution, 0.1 ml of a 2500 unit/ml tyrosinase solution was added and reacted again in a 37°C incubator for 10 minutes. The test tube containing the reaction solution was put in ice water to stop the reaction, and the absorbance at a wavelength of 475 nm was measured with a photoelectric spectrometer, and the results are shown in Table 1 below. Each tyrosinase inhibitory effect was calculated by Equation 1 below.

Test substance Tyrosinase inhibition rate (%) Control (no addition) 0 Ascorbic acid 52 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 36

From the results of Table 1, it can be seen that the 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid used in the present invention has excellent tyrosinase inhibition.

[Test Example 2] Inhibitory effect of melanin production using B16/F10 melanoma cells

The B16/F10 melanoma used in this test example is a mouse-derived cell line, and is a cancer cell resulting from malignantization of cells secreting a black pigment called melanin. The degree of reduction in melanin production was evaluated by treating the test substance during artificial culture of these cells. The B16/F10 melanoma used in this test example was sold and used from the Korea Cell Line Bank (KCLB No: 8008).

Measurement of the inhibitory effect of melanin biosynthesis of B16/F10 melanoma was performed as follows. DMEM (fetal bovine serum) containing 10% FBS (fetal bovine serum) for about 24 hours at 37°C, 5% CO ₂ incubator (MCO-20AIC, Sanyo) by dispensing B16/F10 melanoma into a 6-well plate at 5×10 ⁵ /well. Dulbecco's Modified Eagle's Medium). As a test substance, 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid of Reference Example 1 was added at 0.1% by weight to a fresh DMEM medium without FBS, followed by 72 hours. After treatment with trypsin-EDTA and centrifugation to separate cells, melanin was lysed at 95° C. using 1N NaOH containing DMSO. Absorbance was measured at 405 nm using an ELISA reader (DIbiotech, Korea). Cells to which no test substance was added were used as a control, and the degree of inhibition of melanogenesis of each test substance was measured by comparing it with the melanin content in the control group. The melanin production inhibition rate was calculated according to Equation 2 and the results are shown in Table 2.

Test substance Melanogenesis inhibition rate (%) Control (no addition) 0 Kojisan 53 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 36

From the results of Table 2, it can be seen that the 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid used in the present invention has excellent inhibition of melanogenesis.

[Formulation Example 1 and Comparative Formulation Example 1]

A nutrient cream was prepared by a conventional method according to the composition in Table 3 below (unit: wt%).

Ingredients Formulation Example 1 Comparative Formulation Example 1 Purified water To 100 To 100 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.1 - Hydrogenated vegetable oil 1.50 1.50 Stearic acid 0.60 0.60 Glycerol stearate 1.00 1.00 Stearyl alcohol 2.00 2.00 Polyglyceryl-10 Pentastearate & Behenyl Alcohol & Sodium Stearoyl Lactylate 1.00 1.00 Arachidyl Behenyl Alcohol & Arachidyl Glucoside 1.00 1.00 Cetearyl Alcohol & Cetearyl Glucoside 2.00 2.00 PEG-100 stearate & glycerol oleate & propylene glycol 1.50 1.50 Caprylic/Carlic Triglyceride 11.00 11.00 Cyclomedicone 6.00 6.00 Preservatives, incense Appropriate amount Appropriate amount Triethanol amine 0.1 0.1

[Test Example 3] Skin tone improvement effect

In order to examine the skin tone improvement effect of 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid, 20 subjects were divided into 2 groups each of 10 subjects, and the above Formulation Example 1 was given to the subjects of each group. And Comparative Formulation Example 1 was each used (applied once in the evening/day, for a total of 1 week), and then the degree of skin tone improvement was evaluated using a Facial Stage DM-3 (Moritex, Japan) device. The skin tone improvement rate was determined by obtaining the skin brightness and color change values from the skin brightness and color measurement values, and the average value of the results was calculated and shown in Table 4 below. The larger the brightness and color change values, the better the skin tone.

Test substance Skin tone improvement rate (%) brightness Color Formulation Example 1 13 12 Comparative Formulation Example 1 10 9

Looking at the results in Table 4, Comparative Formulation Example 1 that does not contain 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid did not show significant skin tone improvement effect, whereas 16- Formulation Example 1 containing hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid as an active ingredient, it can be seen that skin tone after use is significantly improved than before use.

[Formulation Example 1] Lotion

To prepare a lotion according to a conventional method with the composition shown in Table 5 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 2.0 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PEG 12 nonylphenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 2] Nourishing Cream

To prepare a nourishing cream according to a conventional method with the composition shown in Table 6 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 2.0 Polysorbate 60 1.5 Solbitansesuquioleate 0.5 PEG 60 hydrogenated castor oil 2.0 Floating paraffin 10.0 Squalane 5.0 Caprylic/Capractriglyceride 5.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 3] Massage Cream

A massage cream was prepared according to a conventional method with the composition shown in Table 7 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 1.0 Beeswax 10.0 Polysorbate 60 1.5 PEG 60 hydrogenated castor oil 2.0 Sorbitansquioleate 0.8 Floating paraffin 40.0 Squalane 5.0 Caprylic/Capric Triglyceride 4.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 4] Pack

A pack was prepared according to a conventional method with the composition shown in Table 8 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 1.0 Polyvinyl alcohol 13.0 Sodium carboxymethyl cellulose 0.2 glycerin 5.0 Allantoin 0.1 ethanol 6.0 PEG 12 nonylphenyl ether 0.3 Polysorbate 60 0.3 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 5] Gel

A gel was prepared according to a conventional method with the composition shown in Table 9 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.5 Sodium ethylenediamine acetate 0.05 glycerin 5.0 Carboxyvinyl polymer 0.3 ethanol 5.0 PEG 60 hydrogenated castor oil 0.5 Triethanolamine 0.3 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 6] Ointment

An ointment was prepared by a conventional method with the composition shown in Table 10 below.

Content (% by weight) 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.1 glycerin 8.0 Butylene glycol 4.0 Floating paraffin 15.0 Beta glucan 7.0 Carbomer 0.1 Caprylic/Capric Triglyceride 3.0 Squalane 1.0 Cetearyl glucoside 1.5 Sorbitan Stearate 0.4 Cetearyl alcohol 1.0 Beeswax 4.0 Preservatives, colors, flavors Appropriate amount Purified water Balance

[Formulation Example 7] Soft Capsule

16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.0025 g, vitamin C 0.0025 g, palm oil 2 mg, hydrogenated palm oil 8 mg, sulfur wax 4 mg and lecithin 6 mg were mixed in the usual way. Accordingly, 400 mg per capsule was filled to prepare a soft capsule.

[Formulation Example 8] Tablet

16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.0025g, vitamin C 0.0025g, glucose 100mg, starch 96mg and magnesium stearate 4mg were mixed and 30% ethanol was added 40mg After forming the granules, they were dried at 60° C. and then tableted into tablets using a tablet press.

[Formulation Example 9] Granules

After mixing 150 mg of 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid, 150 mg of vitamin C, 100 mg of glucose, and 600 mg of starch, and adding 100 mg of 30% ethanol to form granules, , Dried at 60° C. to form granules and then filled in a cloth. The final weight of the contents was 1 g.

[Formulation Example 10] Drinks

16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid 0.0025 g, vitamin C 0.0025 g, glucose 10 g, citric acid 2 g, and purified water 187.8 g were mixed and filled into a bottle. The final volume of the contents was 200 ml.

As described above, specific parts of the present invention have been described in detail, and it is obvious that these specific techniques are only preferred embodiments for those of ordinary skill in the art, and the scope of the present invention is not limited thereby. something to do. Therefore, it will be said that the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims (4)

A composition for external application for skin for whitening containing 16-hydroxy-octadeca-9,17-diene-12,14-diynyl ester acetic acid represented by the following formula (1) as an active ingredient.
[Formula 1]

The composition for external application for skin according to claim 1, wherein the active ingredient is contained in an amount of 0.001 to 50% by weight based on the total weight of the composition. The composition for external application for skin according to claim 1, wherein the composition is for improving complexion and skin tone. The composition for external application for skin according to claim 1, wherein the composition is a cosmetic composition.