KR101999539B1 - Composition for skin cell regeneration, anti-wrinkle, antioxidant, anti-imflamation, and skin whitening - Google Patents

Abstract

More particularly, the present invention relates to a composition for antioxidant, anti-inflammation and skin whitening. More particularly, the present invention relates to a composition for inhibiting free radical generation, inhibiting NO production, inhibiting anti-inflammatory effects and melanin synthesis And can be used as a pharmaceutical composition, an external preparation for skin, a cosmetic composition or a health food.

Description

TECHNICAL FIELD The present invention relates to a composition for antioxidant, anti-inflammation and skin whitening, and more particularly, to a composition for skin cell regeneration, anti-wrinkle, antioxidant, anti-imflamation,

The present invention relates to compositions for antioxidant, anti-inflammation and skin whitening.

Active oxygen introduced from the outside of the living body or generated in the living body causes many problems such as promoting aging of the living body or generating cancer. Therefore, the development and research of antioxidants that inhibit oxidation by active oxygen have been performed. Antioxidants are widely distributed in copper and plants. Many phenolic compounds, flavonoids, tocopherols, vitamin C and selenium are known in fruits and vegetables. However, the antioxidant substances present in nature can not be expected to have practically sufficient effects in skin application. Therefore, although synthetic antioxidants having excellent antioxidant ability and low cost are widely used, their use is restricted due to safety concerns such as human side effects.

In addition, inflammation is an immune response of a human body in response to a wound or disease, and oxidative stress such as ultraviolet rays, active oxygen, free radicals, etc. activate inflammatory factors and cause aging of various diseases and skin. The vasoactive polypeptide, kinin, plasmin and complement, have vasodilatory and contraction and chemotaxis effects, as well as lymphokines such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for inflammation. Arachidonic acid is metabolized through inflammatory mediators such as prostaglandin and lukotrienes via two pathways: cyclooxygenase or lipooxygenase, mediating a variety of inflammatory responses.

On the other hand, in order to eliminate inflammation, elimination of inflammation source, reduction of vital reaction and symptoms is called anti-inflammatory. To date, substances used for antiinflammatory purposes include nonsteroidal flufenamic acid, ibuprofen, benzydamine, indomethacin, prednisolone, , Dexamethasone, and the like. It is also known that allantoin, azene, hydrocortisone and the like are effective for antiinflammation. However, these materials are limited in their use due to safety of skin, .

Also, it is the constant desire of everyone to want to have a white, fine skin. It is genetically determined by the concentration and distribution of melanin in human skin, but is also influenced by environmental or physiological conditions such as sunlight, fatigue, and stress. Melanin is produced by a nonenzymatic oxidation reaction after tyrosine tyrosine, which is an amino acid, is converted to DOPA or dopaquinone by an enzyme called tyrosinase. Thus, the pathway through which melanin is made is known, but the mechanism by which melanin synthesis, the previous step in which tyrosinase acts, is not yet elucidated.

On the other hand, commonly known whitening ingredients include substances inhibiting tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, L-ascorbic acid and derivatives thereof, There are various plant extracts. By inhibiting the synthesis of melanin pigment, they can brighten the skin tone to realize skin whitening, and it is possible to improve skin hypercholesterolemia such as stain or freckles due to ultraviolet rays, hormones or heredity. However, when applied to skin, there is a problem that the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a practical effect can not be expected.

Therefore, it is strongly desired to develop a composition having antioxidant, antiinflammatory and whitening activity, which is more safe than a living body, has a stable active ingredient, and is more effective than a conventional antioxidant, antiinflammatory and whitening effect substance.

 Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974

Accordingly, the inventors of the present invention confirmed that Mogroside V inhibits melanin synthesis by inhibiting free radicals to inhibit antioxidative and nitric oxide (NO) production, thereby exhibiting an anti-inflammatory effect and exhibiting a whitening effect. .

Accordingly, it is an object of the present invention to provide antioxidant, anti-inflammatory or skin whitening applications of mogroside V.

As a means for solving the above problems, the present invention provides a pharmaceutical composition for antioxidant, anti-inflammation and skin whitening comprising a compound represented by the following general formula (1) as an active ingredient:

[Chemical Formula 1]

As another means for solving the above problems, the present invention provides an external preparation for skin for antioxidant, anti-inflammation and skin whitening comprising the compound of formula (1) as an active ingredient.

As another means for solving the above-mentioned problems, the present invention provides a cosmetic composition for antioxidant, anti-inflammation and skin whitening comprising the compound of Chemical Formula 1 as an active ingredient.

As another means for solving the above problems, the present invention provides a health food for antioxidant, anti-inflammation and skin whitening comprising the compound of Chemical Formula 1 as an active ingredient.

The mogroside V according to the present invention scavenges free radicals to exhibit an antioxidative effect, inhibits NO production involved in the inflammatory reaction, exerts excellent anti-inflammatory effect, inhibits melanin synthesis and exhibits a whitening effect, Can be used for food.

Hereinafter, the configuration of the present invention will be described in detail.

Antioxidant, anti-inflammatory and whitening ingredients have high antioxidative, anti-inflammatory and whitening activity at low concentration, excellent ability to permeate through the skin to be absorbed through skin, and antioxidative, anti-inflammatory and anti- It is preferable to have a low volatility so as to be able to stay for a sufficient time to exhibit a whitening effect, to stably maintain the active ingredient on the composition or the skin, to be easily formulated into medicines and cosmetics, and to be safe for the skin. However, the components satisfying all of the above-mentioned characteristics among the known components are not common. For example, some antioxidant, anti-inflammatory and whitening ingredients are excellent in antioxidant, anti-inflammatory and whitening activity even at a low concentration in an in vitro test, but they are difficult to be applied to real skin because of their ability to permeate through the skin. Other active ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some antioxidant, anti-inflammatory, and whitening ingredients may be degraded or transformed into other compounds when exposed to heat, light, or oxygen, and the effects may already be lost before application to the skin.

As can be seen in the following examples, Mogroside V exhibits remarkably excellent antioxidative, anti-inflammatory and whitening effects at a low concentration. Therefore, it is possible to provide medicines, cosmetics, and health food for antioxidation, anti- And the like.

Accordingly, the present invention provides a pharmaceutical composition for antioxidant, anti-inflammation and skin whitening comprising a compound represented by the following formula (1) as an active ingredient:

[Chemical Formula 1]

The compound name of the compound of Formula 1 is Mogroside V; Mogroside V; Momordica Extract; Momordica grosvenori swingle; -D-glucopyranosyl) -? - D-glucopyranosyloxy] -24- [2-O, 6-O-bis (? glucopyranosyloxy] cucurbit-5-ene-11.alpha., 25-diol; beta-D-glucopyranosyl) oxy) -11,25-dihydroxy-9-methyl (3beta, 9beta, 10alpha, 11alpha, 24R) -19-norlanost-5-ene-24-yl o-beta-D-glucopyranosyl- (1-2) -o - (beta-D-glucopyranosyl- (1-6)) -; Beta] -D-glucopyranosyl (1-6) -beta-D-glucopyranoside) -24-o- (beta-D-glucopyranosyl (1-2) 1-6)) - beta-D-glucopyranoside); It is called MomordicagrosvenoriSwingleP.E, also called Mogroside V.

The compound of formula (1) may be synthesized or a commercially available compound may be used.

The pharmaceutical composition for antioxidant, anti-inflammation and skin whitening of the present invention may include a pharmaceutically acceptable salt of the compound of formula (1).

The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid The organic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic 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.

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, known antioxidant, anti-inflammatory and skin whitening ingredients. The addition of additional antioxidants, anti-inflammatory and skin whitening ingredients may further enhance the antioxidant, anti-inflammatory and skin whitening effects 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 comprises an antioxidant component known in the art, such as tocopherol, selenium, vitamin C and a phenolic compound, as well as whitening components known in the art, such as kojic acid ), Arbutin and the like, a substance selected from the group consisting of hydroquinone, L-ascorbic acid and derivatives thereof and various plant extracts, And may further include two or more components. 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 .

In addition, the pharmaceutical composition for antioxidant, anti-inflammation and skin whitening of the present invention may further comprise a pharmaceutically acceptable carrier.

Pharmaceutically acceptable carriers may contain a variety of ingredients such as buffer, injectable sterile water, normal saline or phosphate buffered saline, sucrose, histidine, salts and polysorbates, and the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of oral and parenteral administration at the time of clinical administration. In the case of formulation, , An extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may be prepared by mixing the pharmaceutical composition of the present invention with at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like.

In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

In the present invention, the term 'antioxidative effect' refers to the action of free radicals or reactive oxygen species (ROS), which are highly reactive according to oxidative stress caused by intracellular metabolism or ultraviolet rays, Refers to inhibition of oxidation, and includes removal of free radical or reactive oxygen species, thereby reducing damage to the cells.

In the present invention, the term " anti-inflammatory effect " refers to suppression of inflammation, and the inflammation is one of defense reactions of biological tissue against a certain stimulus, and includes three kinds of tissue degeneration, circulatory disorder, Is a complex lesion. More specifically, inflammation is part of congenital immunity and, like in other animals, human congenital immunity recognizes a pattern of cell surfaces that are specifically present in a pathogen. Phagocytes recognize cells with such surfaces as non-magnetic and attack pathogens. If pathogens break through the physical barriers of the body, an inflammatory reaction occurs. Inflammation is a nonspecific defense that creates hostile environments for microorganisms entering the wound. In the inflammatory response, white blood cells that are responsible for the early stage of immune response, when wounded or infected, enter the body to express cytokines. Therefore, the expression level of intracellular cytokine is an index of activation of the inflammatory reaction. Examples of skin diseases associated with inflammation include atopic dermatitis, psoriasis, radiation, chemical substances, inflammatory diseases caused by burns, acid burns, vesicular dermatosis, visceral type diseases, itching due to allergies, seborrheic eczema, rose acne, Inflammatory hair loss such as pemphigus vulgaris, polymorphous exudative erythema, erythema nodosum, erythematosus, pharyngitis, alopecia areata, skin T-cell lymphoma, and the like.

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

The pharmaceutical composition of the present invention can provide the desired antioxidative, anti-inflammatory and whitening effects when an effective amount of the compound of Formula 1 is included. In the present invention, the term "effective amount" means an amount of a compound capable of inhibiting or alleviating oxidation of cells, inhibiting inflammation, or exhibiting a 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 dose 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 pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention can also be provided as a formulation of an antioxidant, anti-inflammatory and whitening dermatological external preparation containing 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 present invention can also provide formulations of antioxidant, anti-inflammatory and whitening cosmetic compositions containing the compound of Formula 1 as an active ingredient.

When the compound of Chemical Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Chemical Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation and a solubilized formulation. For example, creams, essences, cosmetic creams, sprays, gels, packs, sunscreens, make-up bases, liquids such as lotions such as lotion, facial lotion, body lotion, A powder, a cleansing lotion, a makeup removing agent such as a cleansing oil, a cleaning agent such as a cleansing foam, a soap, a body wash and the like.

The cosmetic composition may further contain, in addition to the compound of Formula 1, a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, , Ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics And may contain adjuvants commonly used in the cosmetics field, such as any of the other ingredients.

In the case of a wash-off type cosmetic such as a make-up removing agent, a detergent, etc. in which the active ingredient remains on the skin in a short period of time when the compound of formula (1) is produced into a cosmetic product, . On the other hand, in the case of leave-on type cosmetics, such as lotion, cream, essence, etc., in which the active ingredient remains on the skin for a long period of time, It may be included. In one embodiment of the present invention, although not limited thereto, the composition may contain 0.0001 wt% to 10 wt% (preferably 0.0001 wt% to 1 wt%) of the compound of Formula 1 based on the total weight of the composition . If the composition of the present invention contains less than 0.0001% by weight of the compound of formula 1, sufficient antioxidative, anti-inflammatory and whitening effects can not be expected. If the composition contains more than 10% by weight, Or to prevent skin safety problems.

The present invention also relates to antioxidant, anti-inflammatory and whitening health foods 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 food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, powdering or suspension, However, unlike general medicine, there is an advantage that there is no side effect that may occur when a drug is taken for a long time by using food as a raw material.

Since the health food of the present invention thus obtained can be taken on a daily basis, high antioxidative, anti-inflammatory and whitening effects 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 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). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. 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 foods to which the above substances can be added include dairy products including meats, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, gums, ice cream, soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and 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 composition 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 adjusters, stabilizers, preservatives, glycerin, , 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 composition of the present invention.

Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited to the following examples.

Reference Example  One: Mogroside  V ( Mogroside  V) Material information

[Chemical Formula 1]

Compound name: Mogroside Ⅴ; Mogroside V; Momordica Extract; Momordica grosvenori swingle; -D-glucopyranosyl) -? - D-glucopyranosyloxy] -24- [2-O, 6-O-bis (? glucopyranosyloxy] cucurbit-5-ene-11.alpha., 25-diol; beta-D-glucopyranosyl) oxy) -11,25-dihydroxy-9-methyl (3beta, 9beta, 10alpha, 11alpha, 24R) -19-norlanost-5-ene-24-yl o-beta-D-glucopyranosyl- (1-2) -o - (beta-D-glucopyranosyl- (1-6)) -; Beta] -D-glucopyranosyl (1-6) -beta-D-glucopyranoside) -24-o- (beta-D-glucopyranosyl (1-2) 1-6)) - beta-D-glucopyranoside); It is called MomordicagrosvenoriSwingleP.E, also called Mogroside V.

CAS No .: 88901-36-4

Where to buy: Tauto Biotech Co., Ltd.

Origin and Sources Plant: Momordica dried fruit of grosvenori swingle)

Example 1: Whitening effect - Confirmation of melanin formation inhibitory effect

The compound of Chemical Formula 1 was added to the culture of mouse melanoma cell (B-16 mouse melanoma cell) to test the whitening effect at the cellular level (Lotan R., Lotan D. Cancer Res . 40: 3345-3350, 1980 ). To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic. The compounds of formula (I) were added to the culture medium to give final concentrations of 1, 2.5, 5, 10 and 20 μg / mL. Arbutin, a control group, was added to the medium to a concentration of 200 μg / And cultured for 3 days. Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were incubated with 1 mL of sodium hydroxide solution (1N concentration), boiled for 10 minutes to dissolve melanin, and the absorbance was measured at 400 nm using a spectrophotometer to measure the amount of melanin produced. The amount of melanin was measured by an absorbance of 1 × 10 ⁶ cells per unit cell, and the amount of melanin produced relative to the control group was calculated as the inhibition rate (%). The results are summarized in Table 1. The experiment was repeated three times.

Inhibitory effect of melanin on cell-level sample Melanin production Inhibition rate (%) Control group (no addition) 0.078 - Control group 1: Arbutin (200 占 퐂 / mL) 0.044 44 The compound of formula (1) (20 / / mL) 0.023 71 Compound (1) (10 占 퐂 / mL) 0.039 50 The compound of formula 1 (5 / / mL 0.065 17 The compound of Formula 1 (2.5 占 퐂 / mL) - -

As can be seen from the results of Table 1, the compound of formula (I) has remarkably superior melanin production inhibitory effect on the melanoma cells of the rat cultured in comparison with the known whitening substance arbutin (Arbutin).

Example  2: Antioxidant effect - Free radical  Erasure rate

The free radical scavenging activity was measured to confirm the antioxidative activity of the compound of formula (1). Free radical scavenging activity was measured using DPPH. DPPH was purchased from Sigma Co. (Sigma Co., Ltd, USA) and used. First, a standard DPPH ethanol solution of 1.5 mM (0.06 mg / mL) was prepared. Then, ethanol was added to the ascorbic acid, which is an antioxidant, as a reference compound and the compound of formula (1), respectively, to prepare samples at concentrations of 50 μg / mL, 25 μg / mL, 12.5 μg / mL, 6.25 μg / mL and 3.125 μg / . Then, the sample and standard DPPH solution were added at the same ratio, stirred well, reacted at 37 ° C for 30 minutes, and absorbance was measured at 520 nm. At this time, ethanol was added instead of the sample to give a control group. The IC ₅₀ , half maximal inhibitory concentration (inhibition concentration), was determined for the free radical scavenging ability, and the results are shown in Table 2 below. IC ₅₀ is a common method of expressing free radical scavenging activity with the concentration of ascorbic acid and the compound of formula 1 required to remove 50% of the free radicals of the no-added control group.

Free radical scavenging rate (IC ₅₀ ) sample Free radical scavenging rate (占 퐂 / mL; ppm) Ascorbic acid 8 The compound of formula (1) 19

As shown in Table 2, the activity is lower than that of ascorbic acid (vitamin C), which is a strong antioxidant, but it has excellent antioxidative effect as a natural substance and exhibits stability and is suitable for use as an antioxidant-effective substance.

Example  3: Anti-inflammatory effect - NO  Production inhibitory effect

In order to confirm the anti-inflammatory effect and the skin trouble relieving effect of the compound of Chemical Formula 1, nitrite (NO) formation inhibition test was performed by the GRIESS method using RAW264.7 cell line (ATCC number: CRL-2278). Specifically, RAW264.7 cells, macrophages of mice, were subcultured several times, placed in 24-well plates so as to enter 3 × 10 ⁵ cells into each well, and cultured for 24 hours. Subsequently, the compound of Chemical Formula 1 was diluted with the concentrations shown in the following Table 3 and replaced with a cell culture medium containing the compound. In Table 3, 1% means the concentration obtained by dissolving 10 mg of the compound of the formula (1) per 1 mL of the medium, and 0.1%, 0.01% and 0.001% are the concentrations obtained by dissolving the compounds 1 mg, 0.1 mg and 0.01 mg, respectively. As a positive control, L-NMMA (L-NG-Monomethylarginine), which is a NO-production inhibitor, was treated together for 30 minutes. The treatment concentration was adjusted to 0.001% by adding 10 μg per 1 mL of the medium. In addition, LPS (Lipopolysaccharide) was treated with 1 ㎍ each as a stimulus source and cultured for 24 hours. 100 μl of the supernatant was transferred to a 96-well plate, and 100 μl of the GRIESS solution was added thereto at room temperature for 10 minutes. The absorbance at 540 nm was measured to determine the NO inhibitory effect of Compound 1, Respectively. The inhibition rate of NO production was determined based on the amount of NO produced in the experimental group treated with LPS alone.

NO generation inhibitory effect sample NO production inhibition rate (%) L-NMMA (positive control, 0.001%) 35.81 Compound (1) (0.001%) 5.03 The compound of formula (1) (0.01%) 25.83 Compound (1) (0.1%) 28.59 Compound (1) (1) 33.52

As shown in Table 3, when compared with L-NMMA, a typical anti-inflammatory substance, its activity is low, but it exhibits excellent anti-inflammatory activity as a natural substance and has an anti-inflammatory effect in whitening and wrinkle improvement A synergistic effect can be expected.

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

Compound of Formula 1 0.2 mg

Corn starch 100 mg

Lactose 100 mg

Stearic acid  Magnesium 2 mg

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

3. Preparation of capsules

Compound of Formula 1 0.2 mg

Corn starch 100 mg

Lactose 100 mg

Stearic acid  Magnesium 2 mg

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

Xylitol  0.5 g

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

Glucose 200 mg

Starch 600 mg

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)

As the following composition, the number of softening times containing the compound of formula (1) as an active ingredient was prepared according to a conventional method.

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%

PEG-12 nonyl phenyl ether 0.2 wt%

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 wt%

2. Manufacture of nutrition lotion (milk lotion)

As in the following composition, a nutritional lotion containing the compound of the formula (1) as an active ingredient was prepared by a conventional method.

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 wt%

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, as shown below.

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%

PEG-60 hardened castor oil 2.0 wt%

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 wt%

4. Manufacture of massage cream

A massage cream containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.

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%

PEG-60 hardened castor oil 2.0 wt%

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 wt%

5. Manufacture of pack

A pack containing the compound of formula (1) as an active ingredient was prepared according to a conventional method, as shown below.

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

PEG-12 nonyl phenyl ether 0.3 wt%

Polysorbate 60 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to  100 wt%

Formulation example  3: Topical  Produce

1. Manufacture of gel

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

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

PEG-60 hardened castor oil 0.5 wt%

Triethanolamine 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to  100 wt%

2. Manufacture of ointment

An ointment containing the compound of formula (I) as an active ingredient was prepared according to a conventional method, as shown below.

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%

PEG-60 hardened castor oil 2.0 wt%

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 wt%

3. Preparation of topical medicament (gel ointment)

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

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 wt%

4. Preparation of topical medicines (patches)

As the following composition, a patch containing a compound of the formula (1) as an active ingredient was prepared by a conventional method.

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 wt%

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 alfalted by a known method and dried, and the powder was prepared into a powder having a particle size of 60 mesh by a pulverizer. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried in a known manner, and were then ground to a powder having a particle size of 60 mesh. 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.

(10 parts by weight of black rice, 7 parts by weight of black sesame), the compound of formula (1) (0.1 part by weight), and the seeds (30 parts by weight of brown rice, 15 parts by weight of barley, 20 parts by weight of barley)

(0.5 part by weight),

Rhubarb (0.5 Weight portion )

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  All 900 mL

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring. Then, the solution thus prepared was filtered and sterilized in a sterilized 2L-container, Lt; RTI ID = 0.0 > health < / RTI >

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

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 (18)

delete delete delete delete delete delete delete delete delete delete delete delete A pharmaceutical composition for skin whitening comprising, as an active ingredient, a compound represented by the following formula (1) (Mogroside V, Mogroside V)
[Chemical Formula 1]

A skin external preparation for skin whitening comprising a compound represented by the following formula (Mogroside V, Mogroside V) as an active ingredient:
[Chemical Formula 1]

15. The method of claim 14,
Wherein the external preparation is a formulation of ointment, patch, gel, cream or spray.
A cosmetic composition for skin whitening comprising a compound represented by the following formula (1) (Mogroside V, Mogroside V) as an active ingredient:
[Chemical Formula 1]

17. The method of claim 16,
Cosmetics, essences, lotions, creams, packs, gels, powders, foundations or detergents.
Health food for skin whitening comprising a compound represented by the following formula (1) (Mogroside V, Mogroside V) as an active ingredient:
[Chemical Formula 1]