KR20160066729A - COMPOSITION FOR SKIN WHITENING CONTAINING (2S)-1-O-7(Z),10(Z),13(Z)-HEXADECATRIENOYL-3-O-β-D-GALACTOPYRANOSYL-SN-GLYCEROL - Google Patents

Abstract

The present invention relates to a whitening composition containing (2S)-1-O-7(Z),10(Z),13(Z)-hexadecatrienoyl-3-O-beta-D-galactopyranosyl-sn-glycerol and, more specifically, to a composition which shows a significantly excellent whitening effect by using (2S)-1-O-7(Z),10(Z),13(Z)-hexadecatrienoyl-3-O-beta-D-galactopyranosyl-sn-glycerol, improves skin pigmentation or deadness of a skin such as chloasmas and freckles, and can evenly and brightly show skin tone.

Description

Skin whitening products containing (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-0-? -D-galactopyranosyl-sn- (Z) -hexadecatrienoyl-3-O-beta-D-galactopyranosyl-sn-glycerol}

The present invention relates to a process for the preparation of a composition containing (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-0-? -D- galactopyranosyl- (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-β-D-gal Glycopyrrolopyranosyl-sn-glycerol. The present invention relates to a composition which improves pigmentation symptoms such as spots and freckles or dullness of the skin, and makes the skin color uniform and bright.

Human skin color is determined by various factors such as the activity of melanocyte making melanocyte, the distribution of blood vessels, the thickness of skin, and the presence or absence of pigment inside and outside the body, such as carotenoids and bilirubin. The most important factor is melanin, a melanin produced by various enzymes such as tyrosinase in melanocytes. The formation of melanin pigment is affected by environmental factors such as genetic factors, hormonal secretion, physiological factors such as stress, and ultraviolet irradiation. Melanin is present in the skin and protects the body from ultraviolet rays, but it is known that melanin is overproduced, thereby promoting pigmentation and aging of the skin and leading to skin cancer induction. (Ascorbic acid, kojic adcid, arbutin, hudroquinone) have been previously used to treat or relieve excessive melanin pigmentation caused by skin pigmentation abnormalities and ultraviolet exposure. Glutathione or a derivative thereof and a substance having inhibitory activity against tyrosinase have been used in cosmetics or medicines in combination with insufficient whitening effect, safety to the skin, Its use is restricted due to stability problems and so on.

On the other hand, (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O- beta -D- galactopyranosyl- (BJ et al., Glycosyl glycerides from hydrophobic Panax ginseng inhibited NO production in LPS-stimulated RAW264.7 cells, Journal of Ginseng Research (2014), doi: 10.1016 / j.jgr.2014.10.005), the efficacy of the above compounds in relation to the improvement of skin condition is not yet known in detail.

Korean Patent Laid-Open No. 10-2012-0083943 (published on July 27, 2012)

Cha BJ et al., Glycosyl glycerides from hydrophobic Panax ginseng inhibited NO production in LPS-stimulated RAW 264.7 cells, Journal of Ginseng Research (2014), doi: 10.1016 / j.jr.2014.10.005

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O (Z), and the like. -β-D-galactopyranosyl-sn-glycerol can provide a superior skin-whitening effect, while the stimulation to the skin is small, thereby completing the present invention.

Therefore, the present invention relates to the use of (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyle-3-0-β-D- galactopyranosyl- To provide a composition exhibiting excellent skin whitening effect.

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3- (2-methylphenyl) O-beta-D-galactopyranosyl-sn-glycerol as an active ingredient, or a pharmaceutical composition thereof.

The composition of the present invention is a composition comprising (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O- To provide an excellent skin whitening effect to reduce pigmentation symptoms such as spots and freckles, to improve skin dullness, and to make skin color uniform and bright.

The composition of the present invention is a composition comprising (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O- (Z) -hexadecatrienoyl-3-O-β-D-galactopyranosyl-sn-glycerol) as an active ingredient, Effect.

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol Is a compound having a structure represented by the following formula (1) and having a molecular weight of 486.

[Chemical Formula 1]

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol Glycosyl glycerides extracted from ginseng (Cha BJ et al., Glycosyl glycerides from hydrophobic Panax ginseng inhibited NO production in LPS-stimulated RAW 264.7 cells, Journal of Ginseng Research (2014), doi: 10.1016 / j.jgr.2014.10.005), but the present invention is not limited thereto. May be extracted from plants, synthesized according to methods known in the art, and commercially available ones may be used.

The composition according to the present invention comprises (2S) -1-0-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-0- Glycerol may be contained in an amount of 0.001 to 50% by weight, preferably 0.01 to 30% by weight, more preferably 0.1 to 10% by weight, based on the total weight of the composition. When the content of (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-0- 硫 -D-galactopyranosyl- If the content is less than 10% by weight, the effect and effect of the above-mentioned ingredients are insufficient. If the content is more than 50% by weight, skin safety or shape problems may occur.

The composition of the present invention may be formulated as an external preparation for skin, in particular as 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 form suitable for topical application, for example, as a solution, an emulsion obtained by dispersing an oil phase in water phase, an emulsion obtained by dispersing water phase in water phase, a suspension, a solid, a gel, Pastes, foams, or aerosol compositions. Specifically, the composition of the present invention may be provided in the form of a cream, a skin, a lotion, a powder, an ointment, a spray or a cone stick. Compositions of such formulations may be prepared according to conventional methods in the art.

In addition, the composition according to the present invention may contain, in addition to the above-mentioned substances, other ingredients which can give a synergistic effect to the main effect, to the extent that the main effect is not impaired. The composition according to the present invention may further comprise a humectant, an emollient, an ultraviolet absorber, an antiseptic, a bactericide, an antioxidant, a pH adjuster, an organic or inorganic pigment, a perfume, a cold agent or a limiting agent. The compounding amount of the above components can be easily selected by a person skilled in the art within the range not impairing the object and effect of the present invention, and the amount thereof may be from 0.01 to 5% by weight, specifically from 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 medicines, it may be formulated into oral, parenteral or parenteral dosage forms in solid, semi-solid or liquid form by adding an inorganic or organic carrier compatible with the active ingredient used in the present invention , The pharmaceutical composition according to the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.

Examples of the formulations for oral administration include tablets, pills, granules, capsules, powders, fine granules, powders, emulsions, syrups and pellets. In addition, the formulations for parenteral administration include injections, drops, ointments, lotions, sprays, suspensions, emulsions, suppositories, and the like. The composition according to the present invention can be easily formulated into an active ingredient by carrying out the composition according to a conventional method. In this case, a surfactant, excipient, coloring agent, spice, preservative, stabilizer, buffer, suspending agent, have.

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

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for illustrating the present invention and that the scope of the present invention is not construed as being limited by these embodiments.

Reference Example 1 Synthesis of (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-β-D- galactopyranosyl- Preparation of

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O- beta -D-galactopyran for the experiment of the efficacy of the composition of the present invention The noxyl-sn-glycerol has been reported in the prior art (Cha BJ et al., Glycosyl glycerides from hydrophobic Panax ginseng inhibited NO production in LPS-stimulated RAW 264.7 cells, Journal of Ginseng Research (2014), doi: 10.1016 / j.jgr.2014.10.005).

Test Example 1: Effect of tyrosinase inhibition

The tyrosinase enzyme was extracted from Mushroom and was obtained from Sigma. First, the substrate, tyrosine, is dissolved in distilled water to make a 0.3 mg / ml solution. The solution is put into a test tube in an amount of 1.0 ml. Then, 1.0 ml of potassium phosphate buffer solution (0.1 mol concentration, pH 6.8) and 0.7 ml of distilled water .

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O- beta -D-galactopyranosyl-sn-glycerol Was mixed with the ethanol solution at a suitable concentration, and 0.2 ml of the prepared sample solution was added to the reaction solution, which was then reacted for 10 minutes in a 37 ° C thermostat. As a negative control, 0.2 ml of a solvent was used instead of the sample solution, and ascorbic acid was used as a positive control. 0.1 ml of tyrosinase solution of 2500 units / ml was added to the reaction solution, followed by reaction at 37 ° C for 10 minutes. The reaction tube was immersed in ice water to quench the reaction, and the absorbance at 475 nm was measured with a photoelectron spectrometer. The results are shown in Table 1 below. Each tyrosinase inhibitory effect was calculated by the following equation (1).

Test substance Inhibition rate of tyrosinase (%) Control group (no addition) 0 Ascorbic acid 52 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 37

(Z), 10 (Z), 13 (Z) -hexadecatriethnoyl-3-O-β-D-gal It can be confirmed that the inhibition rate of tyrosinase of lactopyranosyl-sn-glycerol is excellent.

[Test Example 2] Inhibitory effect on melanin formation by B16 / F10 melanoma cells

The B16 / F10 melanoma used in this test example is a mouse-derived cell line, and is a cancer cell caused by malignant cell which secretes a melanin pigment called melanin. During the artificial incubation of these cells, the test material was treated to compare the degree of decrease in melanin production. The B16 / F10 melanoma used in this test was purchased from Korean Cell Line Bank (KCLB No: 8008).

Melanin biosynthesis inhibitory effect of B16 / F10 melanoma was measured as follows. B16 / F10 melanoma cells were seeded in a 6-well plate at 5 × 10 ⁵ cells / well and cultured in DMEM containing 10% FBS (fetal bovine serum) for 24 hours in a 5% CO ₂ incubator (MCO-20AIC, Dulbecco ' s Modified Eagle ' s Medium). (Z), 10 (Z), and 13 (Z) -hexadecatrienoyl-3-O-beta-D-glucopyranoside of Reference Example 1, D-galactopyranosyl-sn-glycerol was added in an amount of 0.1% by weight and aged for 72 hours. After treatment with trypsin-EDTA, the cells were separated by centrifugation, and melanin was dissolved at 95 ° C in 1N NaOH containing DMSO. Absorbance was measured at 405 nm using an ELISA reader (DIbiotech, Korea). Cells to which the test substance was not added were used as a control group, and the melanin formation inhibition degree of each test substance was measured by comparing with the melanin content in the control group. The inhibition rate of melanin production was calculated according to Equation (2), and the results are shown in Table 2.

Test substance Melanin inhibition rate (%) Control group (no addition) 0 Kojic acid 53 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 38

(Z), 10 (Z), and 13 (Z) -hexadecatriethnoyl-3-O-β-D-gal It can be confirmed that the inhibitory rate of melanin formation of lactofuranosyl-sn-glycerol is excellent.

[Formulation Example 1 and Comparative Formulation Example 1]

Nutritive creams were prepared in a conventional manner according to the composition of Table 3 below (unit: wt%).

Compounding ingredient Formulation Example 1 Comparative Formulation Example 1 Purified water To 100 To 100 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.1 - Vegetable hydrogenated oil 1.50 1.50 Stearic acid 0.60 0.60 Glycerol stearate 1.00 1.00 Stearyl alcohol 2.00 2.00 Polyglyceryl-10pentastearate and behenyl alcohol and sodium stearoyl lactylate 1.00 1.00 Arachidyl behenyl alcohol and arachidyl glucoside 1.00 1.00 Cetylaryl Alcohol and Cetearyl Glucoside 2.00 2.00 PEG-100 Stearate & Glycerololate & Propylene Glycol 1.50 1.50 Caprylic / carboxy triglyceride 11.00 11.00 Cyclomedicone 6.00 6.00 Preservative, incense Suitable amount Suitable amount Triethanolamine 0.1 0.1

[Test Example 3] Skin tone improvement effect

(2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-β-D-galactopyranosyl- Twenty subjects were divided into two groups by 10 persons, and subjects of each group were subjected to the above-mentioned Formulation Example 1 and Comparative Formulation Example 1 (once a day / once a day for a total of one week), and Facial Stage DM -3 (Moritex, Japan). The skin tone improvement rate was determined by determining the brightness and color change values of the skin from the lightness and color measurement values of the skin, and the average value of the results was obtained. The larger the value of brightness and color change, the better the skin tone.

Test substance Skin tone improvement rate (%) brightness Color Formulation Example 1 14 12 Comparative Formulation Example 1 10 9

The results in Table 4 show that the (2S) -1-O-7 (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-β-D- galactopyranosyl- (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-glycerol-free Comparative Formulation Example 1 showed no significant skin tone improving effect, It can be confirmed that Formulation Example 1 containing 3-O-? -D-galactopyranosyl-sn-glycerol as an active ingredient has much improved skin tone after use than before use.

[Formulation Example 1] Lotion

Lotions are prepared according to a conventional method with the composition shown in Table 5 below.

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 2.0 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 PEG 12 nonyl phenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 2] Nourishing cream

Nutrition cream is prepared according to the conventional method with the composition shown in Table 6 below.

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 2.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 PEG 60 hardened castor oil 2.0 Liquid paraffin 10.0 Squalane 5.0 Caprylic / caproic triglyceride 5.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 3] Massage cream

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

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 1.0 Wax 10.0 Polysorbate 60 1.5 PEG 60 hardened castor oil 2.0 Sorbitan sesquioleate 0.8 Liquid 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 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 4] Pack

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

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 1.0 Polyvinyl alcohol 13.0 Sodium carboxymethylcellulose 0.2 glycerin 5.0 Allantoin 0.1 ethanol 6.0 PEG 12 nonyl phenyl ether 0.3 Polysorbate 60 0.3 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 5] Gel

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

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.5 Ethylenediamine sodium acetate 0.05 glycerin 5.0 Carboxyvinyl polymer 0.3 ethanol 5.0 PEG 60 hardened castor oil 0.5 Triethanolamine 0.3 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 6] Ointment

Ointments were prepared in a conventional manner with the compositions shown in Table 10 below.

Content (% by weight) (Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.1 glycerin 8.0 Butylene glycol 4.0 Liquid 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 Wax 4.0 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 7] Soft capsule

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.0025 g, vitamin C , Palm oil 2 mg, palm kernel oil 8 mg, yellow pearl 4 mg, and lecithin 6 mg were mixed, and 400 mg per capsule was filled according to a conventional method to prepare a soft capsule.

[Formulation Example 8] Tablets

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.0025 g, vitamin C 0.0025 g of glucose, 100 mg of starch, 96 mg of starch and 4 mg of magnesium stearate were mixed and 40 mg of 30% ethanol was added to form granules. The granules were dried at 60 ° C and tableted by tabletting using a tablet machine.

[Formulation Example 9]

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol, 150 mg of vitamin C , 100 mg of glucose, and 600 mg of starch were mixed and 100 mg of 30% ethanol was added to form granules. The granules were then dried at 60 ° C to form granules, which were then filled in a capsule. The final weight of the contents was 1 g.

[Formulation Example 10]

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn-glycerol 0.0025 g, vitamin C 0.005 g of glucose, 10 g of glucose, 2 g of citric acid and 187.8 g of purified water were mixed and filled in a bottle. The final volume of the contents was adjusted to 200 ml.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. something to do. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (4)

(Z), 10 (Z), 13 (Z) -hexadecatrienoyl-3-O-? -D-galactopyranosyl-sn- A composition for external application for skin for whitening comprising glycerol as an active ingredient.
[Chemical 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 color and skin tone. The composition for external application for skin according to claim 1, wherein the composition is a cosmetic composition.