KR101574765B1 - Cosmetic or pharmaceutical composition for skin whitening comprising saikosaponin D - Google Patents

Abstract

The present provides a composition for skin whitening containing saikosaponin D or pharmaceutically acceptable salt thereof as an active ingredient. Especially, the present invention provides cosmetics, a pharmaceutical composition, or health food. The cosmetics, the pharmaceutical composition, and the health food of the present invention are safe on the human body due to little side effects, and show excellent skin whitening effects as well.

Description

(Cosmetic or pharmaceutical composition for skin whitening comprising saikosaponin D)

The present invention relates to a cosmetic or pharmaceutical composition having a skin whitening effect. The present invention also relates to an excellent skin whitening cosmetic or pharmaceutical composition without cytotoxicity.

It is a common desire to have white skin. It is a well-known fact that the skin color of a person is determined by the concentration and distribution of melanin in the skin. The concentration and distribution of melanin is not only genetically determined, but also influenced by environmental or physiological conditions such as fatigue, stress, and ultraviolet light. Melanin is produced by a nonenzymatic oxidation reaction in which tyrosine, an amino acid, is catalyzed by an enzyme called tyrosinase, which is subsequently converted to dopa (DOA) and dopaquinone.

On the other hand, known whitening ingredients include substances such as arbutin and kojic acid which inhibit tyrosinase enzyme activity, hydroquinone, vitamin C (L-ascorbic acid) and derivatives thereof, And various plant extracts. These substances decreased the total amount of melanin pigment in vitro, and showed skin whitening as well as improvement of skin hypercholesterolemia such as spots and freckles. However, when they are applied to the skin, there is a limitation in the use amount due to safety problems such as irritation and redness, or there is a problem that the effect is insignificant so that a substantial effect can not be expected. Therefore, it is urgently required to develop a whitening ingredient which is safe in the living body, stable in its active ingredient, and which, among other things, has a better ability to reduce the total amount of melanin than the existing substances.

Accordingly, the present invention is to provide such a useful use of a new active ingredient, that is, an active ingredient, which solves the above problems and has few side effects and is safe for human body and has excellent skin whitening effect.

In other words, a problem to be solved by the present invention is to provide a composition comprising the active ingredient having excellent efficacy as an active ingredient.

In order to solve the above problems, the present invention provides a skin whitening composition, preferably a cosmetic composition, a pharmaceutical composition or a health food, comprising saikosaponin D or a pharmaceutically acceptable salt thereof as an active ingredient .

That is, the present invention provides a new use for skin whitening of psychosaponin D or a pharmaceutically acceptable salt thereof.

The inventors of the present invention have found that psycho saponin D has no cytotoxicity and not only decreases the total amount of melanin but also inhibits tyrosinase enzyme activity and exhibits a whitening effect, thus completing the present invention.

In the present invention, the 'whitening effect' refers to not only brightening the skin tone by reducing the total amount of melanin pigment but also improving skin hypercholesterolemia due to ultraviolet rays, hormones or heredity, such as spots or freckles.

In order to solve the above-mentioned problems and to achieve the object of the present invention, the present invention provides a composition comprising a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof. Specifically, there is provided a pharmaceutical composition, a cosmetic composition or a health food for skin whitening comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof.

[Chemical Formula 1]

The compound represented by the above formula (1) is named saikosaponin D.

The present invention is not particularly limited to the method for obtaining Saikosaponin D, and may be chemically synthesized by a method known in the art, or a commercially available material may be used.

The "pharmaceutically acceptable salt" of the present invention may be an acid addition salt formed using an organic acid or inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, But are not limited to, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, Acetic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.

The pharmaceutically acceptable salts may also include base addition salts, such as, but not limited to salts of sodium, potassium, calcium, ammonium, or magnesium.

The psychosaponin D of the present invention may exist in unsolvated form as well as solvated form including form of hydrate, ethanol, and the like. The psycho saponin D of the present invention may exist in a crystalline or amorphous form, and all such physical forms are included within the scope of the present invention.

The cosmetic composition for skin whitening according to the present invention can be used as a skin whitening cosmetic composition in the form of a solution, a ointment for external use, a cream, a foam, a nutrition lotion, a softening water, a pack, But may be formulated as a suspension, emulsion, paste, gel, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation, patch, But is not limited thereto.

In addition, the cosmetic composition of the present invention may further comprise at least one cosmetically acceptable carrier incorporated in a cosmetic composition for general skin, and examples thereof include oil, water, a surfactant, a moisturizer, a lower alcohol, A thickening agent, a chelating agent, a coloring matter, an antiseptic, a perfume, and the like may be appropriately compounded, but the present invention is not limited thereto.

The cosmetically acceptable carrier to be contained in the cosmetic composition of the present invention varies depending on the formulations. When the formulation of the present invention is an ointment, a paste, a cream or a gel, the carrier component may be an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide Mixtures of these may be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or a mixture thereof may be used as the carrier component, Propellants such as fluorohydrocarbons, propane / butane or dimethyl ether.

When the formulation of the present invention is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, -Butyl glycol oil, and in particular fatty acid esters of cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is a soap, alkali metal salts of fatty acids, fatty acid hemiesters, fatty acid protein hydrolizates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like are used as carrier components .

The present invention also provides a skin whitening method comprising the step of applying a compound represented by the following formula (1) to the skin of an individual. The subject includes, without limitation, mammals including rats, livestock, humans, and the like.

According to another embodiment of the present invention, there is provided a pharmaceutical composition for skin whitening comprising the compound of Chemical Formula 1 as an active ingredient.

The composition comprising the compound of the present invention may be various oral or parenteral formulations, but may preferably be a parenteral agent. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, and emulsions. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.

The present invention can also provide a formulation for external skin preparation for skin whitening effect comprising the compound of Formula 1 as an active ingredient.

When the compound of formula (1) is used as an external preparation for skin, it may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.

When the compound of Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, ointments, patches, gels, creams or sprays.

The pharmaceutical composition of the present invention is particularly preferably used as a parenteral preparation. For example, the external preparation for skin may be a pharmaceutically acceptable base such as vaseline or stearyl alcohol; Suitable pharmaceutically acceptable surfactants such as polysorbate, sorbitan sesquioleate, and the like; A suitable pharmaceutically acceptable humectant such as glycerin; A suitable pharmaceutically acceptable solvent; And a conventional external preparation for skin preparation in which a flavoring agent, a coloring agent, a stabilizer, a tackifier and the like are homogeneously mixed.

When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, a known skin whitening component may be included. The addition of an additional skin whitening ingredient may further enhance the skin whitening effect of the composition of the present invention. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the present invention, the composition is a whitening ingredient known in the art and includes a substance inhibiting tyrosinase enzyme activity such as kojic acid, arbutin, etc., hydroquinone, vitamin C (L-Ascorbic acid), and the like. The additional component may be included in an amount of 0.0001 to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety, ease of formulation of the compound of Formula 1 .

The pharmaceutical composition of the present invention can provide a desired skin whitening effect when an effective amount of the compound of Formula 1 is included. In the present invention, the term "effective amount" means the amount of a compound capable of exhibiting a skin whitening effect.

An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a pharmaceutical product, the compound of Formula 1 may be contained at a higher concentration than that of a cosmetic product that is routinely applied to skin. Accordingly, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, based on the amount of the compound of formula (1) 6 times a day.

The present invention also relates to a skin whitening health food comprising the compound of formula (1).

The term "health food" as used herein means a food prepared by adding the compound of formula (1) to a food material such as beverage, tea, spice, gum or confection or a capsule, powder or suspension, Unlike general medicines, it has the advantage that it does not have side effects that can occur when a drug is taken for a long time by using the food as a raw material.

Since the health food of the present invention thus obtained can be taken for a long time on a daily basis, a high skin whitening effect can be expected, which is very useful.

When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 may be added as it is or may be used together with other food or food ingredients, and the ingredients and mixing methods may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). In one embodiment of the present invention, the health food contains 0.0001 wt% to 10 wt%, more specifically 0.001 wt% to 1 wt% of the compound of Formula 1 based on the total composition weight . However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .

There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health drink of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Or sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of sweeteners include natural sweeteners such as tau Martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the health drink of the present invention.

In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like.

In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention.

According to an embodiment of the present invention, the cosmetic composition, the pharmaceutical composition and the health food may contain 0.0001% to 10% by weight, more specifically 0.001% to 1% by weight, As shown in FIG. When the composition of the present invention contains less than 0.0001% by weight of the compound of the formula 1, sufficient skin whitening effect may not be expected. If the composition contains more than 10% by weight of the compound of the present invention, This is to prevent safety problems.

The composition containing psycho saponin D of the present invention or a pharmaceutically acceptable salt thereof exhibits a skin whitening effect.

The composition containing the psycho saponin D of the present invention or a pharmaceutically acceptable salt thereof can be used as safe and excellent cosmetic ingredients and pharmaceutical ingredients.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.

< Reference Example  1> Information on the compound of formula (1)

[Chemical Formula 1]

(3β, 16α-16,23-Dihydroxy-13,28-epoxyolean-11-en-3-yl 3-O- (6-deoxy-β-D-glucopyranosyl) -β-D-galactopyranoside

CAS No. : 20874-52-6

Where to buy: Sigma Aldrich

Example  1: Non-toxic to cells

The compound of formula (1) was added to the culture medium of human normal human melanocyte (NHM) to test the whitening effect at the cellular level.

The compound of formula (1) was added to the culture medium to a final concentration of 0.1 μg / ml, 0.5 μg / ml, and 1.0 μg / ml, and the cells were treated with NHM cells for 6 days. Cells were then treated with CCK-8 for 4 hours and cell viability was measured by absorbance at 450 nm using a spectrophotometer.

The cell viability was measured by the absorbance of 10 ⁶ cells per unit cell, and the survival rate relative to the control group was calculated as a percentage (%). The results are summarized in Table 1. The experiment was repeated three times.

Cytotoxicity (number of repeats = 3) according to the concentration of the compound of formula (1)

sample Absorbance Survival rate (%) Control group (no addition) 0.638 + 0.100 - The compound of the formula (1) (0.1 g / ml) 0.611 + 0.069 96% The compound of formula (1) (0.5 g / ml) 0.588 + 0.018 92% The compound of Formula 1 (1.0 占 퐂 / ml) 0.573 + 0.116 90%

As shown in the results of Table 1, the compound of Formula 1 showed 90% NHM cell viability up to 1.0 μg / ml and was found to be harmless to cells.

Example  2: Confirming the effect of decreasing total melanin

The compound of formula (1) was added to the culture medium of human normal human melanocyte (NHM) to test the whitening effect at the cellular level.

To evaluate the toxicity of normal melanocyte cells in the pre - experiment, whitening evaluation was performed by selecting the concentration without toxicity.

The compound of Chemical Formula 1 was added to the medium to a final concentration of 0.1 μg / ml, 0.2 μg / ml, 0.5 μg / ml and 1.0 μg / ml, and the control group, arbutin, NHM cells and cultured for 6 days.

Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 100 ul of 1N sodium hydroxide solution containing 10% DMSO for 20 minutes to dissolve the melanin, and the amount of melanin produced by the absorbance at 400 nm was measured using a spectrophotometer.

The amount of melanin was measured by an absorbance of 10 ⁶ cells per unit cell, and the total amount of melanin relative to the control group was calculated as a percentage (%). The results are summarized in Table 2. The experiment was repeated three times.

Reduction effect of total amount of melanin of compound of formula (1) (number of repeats = 3)

sample Total amount of melanin Decrease (%) Control group (no addition) 32.0 ± 0.28 - Control group 1: Arbutin (500 / / ml) 15.7 ± 0.23 51% The compound of the formula (1) (0.1 g / ml) 29.0 + - 0.76 9% The compound of formula (1) (0.2 g / ml) 25.1 ± 0.36 22% The compound of formula (1) (0.5 g / ml) 17.3 ± 0.29 46% The compound of Formula 1 (1.0 占 퐂 / ml) 11.8 ± 0.85 63%

As can be seen from the results in Table 2, the compound of formula (I) has excellent melanin total reducing ability for NHM cells cultured than arbutin, which is a known whitening substance.

That is, it was confirmed that the compound of the formula (1) reduced the total amount of melanin even though the amount of the compound of the formula (1) was much smaller than that of arbutin.

From the above results, it can be seen that the compound of Chemical Formula 1 is suitable for skin whitening application.

Example  3: Tyrosinase  Identification of enzyme inhibitory effect

The compound of formula (1) was added to the culture medium of human normal human melanocyte (NHM) to test the whitening effect at the cellular level.

To evaluate the toxicity of normal melanocyte cells in the pre - experiment, whitening evaluation was performed by selecting the concentration without toxicity.

The compound of Chemical Formula 1 was added to the medium to a final concentration of 0.1 μg / ml, 0.2 μg / ml, 0.5 μg / ml and 1.0 μg / ml, and the control group, arbutin, NHM cells and cultured for 6 days.

Then, the cells were trypsinized, removed from the culture vessel, centrifuged, and extracted with 0.1 M phosphate buffer containing 1% Triton X-100 and 0.1 mM PMSF. 50 μl of the extracted protein was incubated with 50 μl of 1 mM DOPA diluted in 0.1 M phosphate buffer for 1 hour at 37 ° C. and the degree of tyrosinase enzyme activity was measured by absorbance at 475 nm using a spectrophotometer.

The tyrosinase enzyme activity was measured by the absorbance of 10 ⁶ cells per unit cell, and the relative enzyme activity relative to the control group was calculated as a percentage (%). The results are summarized in Table 3. The experiment was repeated three times.

Inhibitory effect of the compound of formula (I) on tyrosinase enzyme activity

sample Tyrosinase enzyme activity Inhibition rate (%) Control group (no addition) 0.370 ± 0.003 Control group 1: Arbutin (500 / / ml) 0.218 + 0.014 41% The compound of the formula (1) (0.1 g / ml) 0.333 + 0.012 10% The compound of formula (1) (0.2 g / ml) 0.292 ± 0.007 21% The compound of formula (1) (0.5 g / ml) 0.246 + 0.022 34% The compound of Formula 1 (1.0 占 퐂 / ml) 0.146 + 0.016 61%

As can be seen from the results in Table 3, the compound of formula (I) has excellent tyrosinase enzyme activity inhibitory activity on NHM cells cultured than arbutin, which is a known whitening substance.

That is, it was confirmed that the compound of formula (1) inhibited tyrosinase enzyme activity even though the amount of compound of formula (1) was much smaller than that of arbutin.

From the above results, it can be seen that the compound of Chemical Formula 1 is suitable for skin whitening application.

Example  4: Psycho saponin  D and the effect of reducing total melanin levels in other compounds with similar chemical structure

In order to confirm that the compound of Chemical Formula 1 has an excellent whitening effect as compared with other compounds having a chemical structure similar to that of Chemical Formula 1, the total amount of melanin was decreased for saikosaponin C and saikosaponin B2 Respectively.

Psychosaponin C and Psychosaponin B2 were represented by Formulas (2) and (3), respectively.

(2)

(3)

The compounds of formulas (1), (2) and (3) were added to the culture medium of human normal melanocytes (NHM) to test the whitening effect at the cellular level.

To evaluate the toxicity of normal melanocyte cells in the pre - experiment, whitening evaluation was performed by selecting the concentration without toxicity.

Compounds of formulas 1, 2, and 3 were added to the culture medium to a final concentration of 1.0 μg / ml. Arbutin, a control group, was added to the culture medium to a concentration of 500 μg / ml and NHM cells were cultured for 6 days.

Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 100 ul of 1N sodium hydroxide solution containing 10% DMSO for 20 minutes to dissolve the melanin, and the amount of melanin produced by the absorbance at 400 nm was measured using a spectrophotometer.

The amount of melanin was measured by an absorbance of 10 ⁶ cells per unit cell, and the total amount of melanin relative to the control group was calculated as a percentage (%). The results are summarized in Table 4. The experiment was repeated three times.

Reduction effect of the total amount of melanin of the compounds of formulas (1), (2) and (3)

sample Total amount of melanin Decrease (%) Control group (no addition) 32.0 ± 0.28 - Control group 1: Arbutin (500 / / ml) 15.7 ± 0.23 51% The compound of Formula 1 (1.0 占 퐂 / ml) 11.8 ± 0.85 63% The compound of Formula 2 (1.0 [mu] g / ml) 30.9 ± 0.85 3% The compound of Formula 3 (1.0 g / ml) 29.3 ± 0.44 8%

As can be seen from the results in Table 4, the compounds of formulas (2) and (3) show that the total amount of melanin is decreased significantly for the NHM cells cultured at the same concentration than the compound of formula (1).

That is, even a compound of the psychosaponin family having a structure similar to that of the compound of the formula (1) does not have the same or similar effect.

Formulation example  1: Preparation of pharmaceutical preparations

1. Manufacturing of powder

0.001 g of the compound of formula (1)

Lactose 1g

The above components were mixed and packed in airtight bags to prepare powders.

2. Preparation of tablets

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

2 mg of magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

3. Preparation of capsules

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

2 mg of magnesium stearate

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

4. Manufacture of rings

0.003 g of the compound of formula (1)

Lactose 1.5 g

Glycerin 1 g

0.5 g of xylitol

After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.

5. Manufacture of granules

2 mg of the compound of formula (1)

Soybean extract 50 mg

200 mg of glucose

600 mg of starch

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 캜 to form granules, which were then filled in a capsule.

Formulation example  2: Manufacture of cosmetics

1. Manufacture of softening longevity (skin lotion)

The softening water containing the compound of formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Butylene glycol 2.0 wt%

Propylene glycol 2.0 wt%

Carboxyvinyl polymer 0.1 wt%

0.2% by weight of phage-12 nonylphenyl ether

Polysorbate 80 0.4 wt%

Ethanol 10.0 wt%

0.1% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of nutrition lotion (milk lotion)

A nutritional lotion comprising the compound of the formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

4.0 wt%

Polysorbate 60 1.5 wt%

1.5% by weight of sorbitan sesquioleate

0.5% by weight liquid paraffin

Caprylic / capric triglyceride 5.0 wt%

Glycerin 3.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

Carboxyvinyl polymer 0.1 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Manufacture of nutritional cream

A nutritional cream containing the compound of formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 5.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

4. Manufacture of massage cream

A massage cream containing the compound of formula (I) as an active ingredient was prepared by a conventional method such as the following composition.

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.8% by weight of sorbitan sesquioleate

Liquid paraffin 40.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 4.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

5. Manufacture of pack

A pack containing the compound of formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Polyvinyl alcohol 13.0 wt%

0.2% by weight of sodium carboxymethylcellulose,

Glycerin 5.0 wt%

Allantoin 0.1 wt%

6.0% by weight of ethanol

0.3% by weight of phage-12 nonylphenyl ether

Polysorbate 60 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

Formulation example  3: Topical  Produce

1. Manufacture of gel

A gel containing the compound of formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.1% by weight of the compound of formula (1)

0.1% by weight of beta-1,3-glucan

0.05% by weight of sodium ethylenediaminetetraacetate

Glycerin 5.0 wt%

Carboxyvinyl polymer 0.3 wt%

5.0% by weight of ethanol

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

Triethanolamine 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of ointment

Ointment containing the compound of formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

Wax 10.0 wt%

Polysorbate 60 5.0 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Vaseline 5.0 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

SHARE BUTTER 3.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 10.0 wt%

Propylene glycol 10.2 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Preparation of topical medicament (gel ointment)

A gel ointment agent containing the compound of formula (1) as an active ingredient was prepared according to a conventional method as the following composition.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

1.5% by weight of polyacrylic acid (Carbopol 940)

5.0% by weight of isopropanol

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100%

4. Preparation of topical medicines (patches)

A patch containing a compound of the formula (1) as an active ingredient was prepared according to a conventional method such as the following composition.

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Hexylene glycol 20.0 wt%

Diethylamine 0.7 wt%

1.0% by weight of polyacrylic acid (Carbopol 934P)

0.1% by weight of sodium sulfite

1.0% by weight of polyoxyethylene lauryl ether (E.O. = 9)

1.0% by weight of polyhydroxyethylene cetyl stearyl ether (Cetomacrogol 1000)

Viscous paraffin oil 2.5 wt%

2.5% by weight of caprylic acid ester / capric acid ester (Cetiol LC)

Polyethylene glycol 400 3.0 wt%

Deionized water to 100%

Formulation example  4: Manufacturing of food

Foods containing the compound of formula (I) of the present invention were prepared as follows.

1. Manufacture of Flour Food

0.05 to 1.0 part by weight of the compound of Formula 1 was added to wheat flour, and a bread, a cake, a cookie, a cracker and a noodle were prepared using the mixture to prepare a health food.

2. Manufacture of dairy products

0.2 part by weight of the compound of Formula 1 was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

3. Manufacturing of wire

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer. The compound of Formula 1 was concentrated under reduced pressure in a vacuum concentrator, sprayed, and dried with a hot-air drier, and the resulting dried product was pulverized to a size of 60 mesh with a pulverizer to obtain a dried powder.

The grains, seeds, and dry powder of the compound of formula (1) prepared above were blended in the following proportions relative to 100 parts by weight of the mixed powder.

(30 parts by weight of brown rice, 15 parts by weight of yulmu, 20 parts by weight of barley)

Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)

(1) (0.1 part by weight),

(0.5 part by weight),

(0.5 parts by weight)

Formulation example  5: Manufacture of beverages

1. Manufacture of health drinks

0.1 mg of the compound of formula (1)

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to the flask to obtain a total of 900 mL

The above ingredients were mixed according to a conventional health drink manufacturing method and stirred and heated at 85 캜 for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 L-container, and then refrigerated, and then used in the preparation of the health beverage composition of the present invention.

The composition ratio is an example in which a composition suitable for a relatively desirable beverage is mixed in a desirable ratio. The composition ratio may be arbitrarily changed according to local, national and cultural preferences such as demand stratum, demanding country, use purpose, and demand.

2. Manufacture of vegetable juice

1 g of the compound of formula (I) of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice for health promotion.

3. Manufacture of fruit juice

1 g of the compound of formula (1) was added to 1,000 mL of apple or grape juice to prepare fruit juice for health promotion.

Claims (6)

A cosmetic composition for skin whitening comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The composition of claim 1, wherein the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition. A pharmaceutical composition for skin whitening comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The composition according to claim 3, wherein the compound represented by Formula 1 or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition. 1. A skin whitening health food comprising a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.
[Chemical Formula 1]

The health food according to claim 5, wherein the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.