KR20190114940A - Composition for antioxidant, anti-imflamation, and skin whitening - Google Patents

Abstract

The present invention relates to a composition for antioxidant, anti-inflammation, and skin whitening. Toosendanin according to the present exhibits an antioxidant effect by inhibiting free radical production, an anti-inflammatory effect by inhibiting NO production, and a skin whitening effect by inhibiting melanin synthesis, thereby being able to be used as a pharmaceutical composition, an external skin preparation, a cosmetic composition or health food.

Description

Composition for antioxidant, anti-imflamation, and skin whitening}

The present invention relates to a composition for antioxidant, anti-inflammatory 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 developing cancer. Therefore, many researches and developments on antioxidants that inhibit oxidation by active oxygen have been made. Antioxidants are widely distributed in copper and plant systems, and many phenolic compounds, flavonoids, tocopherols, vitamin C, and selenium are known in fruits and vegetables. However, the antioxidants present in nature are not expected to have a substantial enough effect on skin application. Therefore, many synthetic antioxidants having excellent antioxidant power and low cost are used, but their use is limited due to safety concerns such as human side effects.

In addition, inflammation is an immune response of the human body in response to a wound or disease, and oxidative stress such as ultraviolet rays, free radicals, and free radicals activates inflammatory factors to cause various diseases and aging of the skin. Vascular activating polypeptides such as kinin, plasmin, and complement act on vasodilation, contraction and chemotaxis, and other lymphokines such as interleukin-6 (IL-6). Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized to inflammatory mediators, prostaglandin and leukotriene, through two pathways, cyclooxygenase or lipooxygenase, to mediate various inflammatory reactions.

On the other hand, the anti-inflammatory agent that acts to remove the inflammatory source, reduce the biological response and symptoms to eliminate inflammation. Materials used for anti-inflammatory purposes to date are nonsteroidal flufenamic acid, ibuprofen, benzydamine, indomethacin, and indonethacin, and prednisolone as a steroid system. , Dexamethasone, and the like. In addition, allantoin, azene, hydrocortisone, etc. are known to be effective in anti-inflammatory, but these substances have a limited amount of use as a matter of safety to the skin, or a problem that can not be expected to substantially reduce the effect of the inflammation. There is this.

Also, to have white and fair skin is everyone's constant desire. 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 sun ultraviolet rays, fatigue and stress. Melanin is a type of amino acid tyrosine (tyrosine) acts as an enzyme called tyrosinase (tyrosinase) is converted into dopa (DOPA), dopaquinone (dopaquinone) is produced through a non-enzymatic oxidation reaction. The pathway by which melanin is produced is known, but the mechanisms that induce melanin synthesis, the previous stages of tyrosinase action, are still unknown.

Meanwhile, as a general known whitening component, substances that inhibit tyrosinase enzyme activity such as kojic acid and arbutin, hydroquinone, vitamin-C (L-Ascorbic acid) and derivatives thereof and various There is a plant extract. By inhibiting the synthesis of melanin pigments, they not only brighten the skin tone to realize skin whitening, but also improve skin hyperpigmentation such as blemishes and freckles due to ultraviolet rays, hormones or heredity. However, when the skin is applied, there are limitations on the amount of use due to safety problems such as irritation and redness, or there is a problem in that a substantial effect cannot be expected due to a slight effect.

Therefore, there is an urgent need for the development of components that are safe for the living body, stable in active ingredients, and most of all, have antioxidant, anti-inflammatory and whitening activities that are superior to conventional antioxidant, anti-inflammatory and whitening agents.

Accordingly, the present inventors have confirmed that Tusendinin (Toosendanin) by scavenging free radicals to inhibit the antioxidant effect, NO production, has an anti-inflammatory effect and inhibits melanin synthesis to show a whitening effect, to complete the present invention.

Accordingly, an object of the present invention to provide an antioxidant, anti-inflammatory and skin whitening composition comprising the compound represented by the following formula (1) as an active ingredient:

[Formula 1]

As a means for solving the above problems, the present invention

It provides a pharmaceutical composition for antioxidant, anti-inflammatory and skin whitening comprising a compound represented by the formula (1) as an active ingredient.

 [Formula 1]

As another means for solving the above problems, the present invention

It provides a skin external preparation for antioxidant, anti-inflammatory and skin whitening comprising a compound represented by the following formula (1) as an active ingredient.

[Formula 1]

As another means for solving the above problems, the present invention

It provides a cosmetic composition for antioxidant, anti-inflammatory and skin whitening comprising a compound represented by the formula (1) as an active ingredient.

[Formula 1]

As another means for solving the above problems, the present invention

It provides an antioxidant, anti-inflammatory and skin whitening health food comprising the compound represented by the following formula (1) as an active ingredient.

[Formula 1]

Tusendinin (Toosendanin) according to the present invention exhibits an antioxidant effect by scavenging free radicals, exhibits an anti-inflammatory effect by inhibiting NO production involved in an inflammatory reaction, and exhibits a whitening effect by inhibiting melanin synthesis. Can be used for health foods.

EMBODIMENT OF THE INVENTION Hereinafter, the structure of this invention is demonstrated concretely.

Antioxidant, anti-inflammatory and whitening ingredients have high activity of anti-oxidation, anti-inflammatory and whitening activity at low concentration, and have excellent ability to penetrate and absorb the skin. It is desirable to have low volatility so as to stay for a sufficient time to have a whitening effect, to keep the active ingredient stable on the composition or the skin, to be easily formulated into medicine or cosmetics, and to be safe for the skin. However, among the known components, components that satisfy all of the above properties are rare. For example, some antioxidant, anti-inflammatory and whitening ingredients have excellent antioxidant, anti-inflammatory and whitening activity even at low concentrations in vitro, but their ability to penetrate and absorb the skin makes them difficult to apply to real skin. Other active ingredients are less hydrophilic and difficult to formulate in medicine or cosmetics. In addition, some antioxidant, anti-inflammatory and whitening ingredients may be decomposed or transformed into other compounds when exposed to heat, light, or oxygen, and the effects are already lost before application to the skin.

As can be seen in the following examples, Tusendinin (Toosendanin) exhibits an excellent antioxidant, anti-inflammatory and whitening effect at low concentrations, so it is effective for medicines, cosmetics, health foods, etc. for antioxidant, anti-inflammatory and skin whitening. Can be used as a component.

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

[Formula 1]

The compound name of the compound of Formula 1 is 28-Deacetylsendanin; Chuanliansu; (1S, 3R, 4aR, 6R, 6aS, 6bS, 7aR, 9R, 9aR, 10R, 11aR, 11bS, 14R) -9- (furan-3-yl) -1,6,14-trihydroxy-4,6a, 9a-trimethyl-11-oxotetradecahydro-1H-4,11b- (methanooxymethano) naphtho [1 ', 2': 6,7] indeno [1,7a-b] oxirene-3,10-diyl diacetate; (1S, 4R, 4aR, 6R, 6aS, 6bS, 7aR, 9R, 9aR, 10R, 11aR, 11bS, 14S) -9- (furan-3-yl) -1,6,14-trihydroxy-4,6a, 9a-trimethyl-11-oxotetradecahydro-1H-4,11b- (methanooxymethano) naphtho [1 ', 2': 6,7] indeno [1,7a-b] oxirene-3,10-diyl diacetate. It is called Toosendanin.

The compound of Formula 1 may be synthesized or used a commercially available compound.

The pharmaceutical composition for antioxidant, anti-inflammatory 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 or trifluoroacetic acid. , 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, dichloroacetic acid, aminooxyacetic acid And benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid salts and inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid salts. It may preferably be in the form of hydrochloride or acetate, more preferably in the form of hydrochloride.

The above-mentioned acid addition salts may be a) directly mixing the compound of formula 1 and an acid, b) dissolving and mixing one of them in a solvent or a hydrous solvent, or c) solvent or submerging the compound of formula 1 It is prepared by a general salt preparation method which is placed in an acid in a solvent and mixed with them.

In addition to the above, salts that can be additionally salted are Gabar salt, Gabapentin salt, Pregabalin salt, Nicotinate, Adipate salt, Hemimalonate, Cysteine salt, Acetylcysteine salt, Methionine salt, Arginine salt, Lysine salt, Ornithine salt, Aspartate.

In addition, when using the compound of Formula 1 of the present invention as a medicine, it may further contain one or more active ingredients exhibiting the same or similar functions. For example, it may contain known antioxidant, anti-inflammatory and skin lightening ingredients. The inclusion of additional antioxidant, anti-inflammatory and skin whitening ingredients will further enhance the antioxidant, anti-inflammatory and skin whitening effects of the compositions of the present invention. When the ingredient is added, skin safety, ease of formulation, and stability of the active ingredients may be considered. In one embodiment of the present invention, the composition is an antioxidant component known in the art, tocopherol, selenium, vitamin C and phenolic compounds, as a whitening component known in the art, Kojic acid, Arbutin (Arbutin Added one or two or more components selected from the group consisting of substances that inhibit enzymatic activity such as tyrosinase, hydroquinone, vitamin-C (L-Ascorbic acid) and derivatives thereof and various plant extracts It can be included as. Additional ingredients may be included from 0.0001% to 10% by weight relative to the total composition weight, and the content range may be adjusted according to requirements such as skin safety, ease of formulating the compound of Formula 1, and the like. .

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

Pharmaceutically acceptable carriers may contain various components such as buffers, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, salts, polysorbates and the like.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered in the form of a general pharmaceutical preparation, for example, in various dosage forms, orally and parenterally, during clinical administration. , Diluents or excipients such as extenders, binders, wetting agents, disintegrants, surfactants and the like.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin and the like.

In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral use include suspensions, solutions, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents.

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

In the present invention, the 'antioxidative effect' refers to a cell caused by free radicals or reactive oxygen species (ROS) that are highly reactive due to oxidative stress caused by intracellular metabolism or ultraviolet light. Refers to the inhibition of oxidation, including the removal of free radicals or reactive oxygen species, thereby reducing damage to cells.

In the present invention, the "anti-inflammatory effect" refers to inhibiting inflammation, which is one of the defense responses of biological tissues to a certain stimulus, which involves three kinds of tissue degeneration, circulatory disorder and exudation, and tissue proliferation. Refers to complex lesions. More specifically, inflammation is part of innate immunity and, as in other animals, human innate immunity recognizes patterns of cell surfaces that are specific to pathogens. Phagocytes recognize cells with such surfaces as nonmagnetic devices and attack pathogens. If the pathogen breaks through the body's physical barrier, an inflammatory reaction occurs. Inflammatory reactions are nonspecific defenses that create a hostile environment against invading microbes. In inflammatory reactions, when wounded or an external infectious agent enters the body, white blood cells in the early stages of immune response rush to express cytokines. Therefore, the expression level of cytokines in cells is an indicator of inflammatory response activation. Examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, radiation, chemicals, burns, etc., erythematous disease, acid burns, bullous skin disease, mammary gland-type diseases, allergic itching, seborrheic eczema, rose acne, Vulgaris, polymorphic exudative erythema, nodular erythema, glansitis, vulvitis, inflammatory hair loss such as alopecia areata, cutaneous T-cell lymphoma, and the like.

In the present invention, the term "whitening effect" means not only brightening skin tone by inhibiting the synthesis of melanin pigments, but also improving skin hyperpigmentation such as blemishes and freckles due to ultraviolet rays, hormones or heredity.

The pharmaceutical composition of the present invention may provide desirable antioxidant, 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 the oxidation of a cell, inhibiting inflammation, or exhibiting a whitening effect. The effective amount of the compound of formula 1 included 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, the time it stays on the skin, and the like. For example, when the composition is manufactured as a medicine, it may include the compound of Formula 1 in a higher concentration than when manufactured as a cosmetic that is routinely applied to the skin. Therefore, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, 1 to 1 day, based on the amount of the compound of Formula 1 It may be administered six times.

The pharmaceutical compositions of the present invention may be used alone or in combination with other methods for achieving the use.

The present invention can also be provided in the formulation of an external preparation for antioxidant, anti-inflammatory and whitening 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 is further added to fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants. Common in water, ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for the skin It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as. The ingredients may also be introduced in amounts generally used in the field of dermatology.

When the compound of Formula 1 is provided as an external preparation for skin, it is not limited thereto, and may have a formulation such as an ointment, a patch, a gel, a cream, or a spray.

The present invention can also be provided in the formulation of the antioxidant, anti-inflammatory and whitening cosmetics containing the compound of Formula 1 as an active ingredient.

When the compound of Formula 1 is used as a cosmetic, the cosmetic prepared by containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsion formulation and solubilized formulation. For example, lotions such as flexible lotions or nourishing lotions, emulsions such as facial lotions, body lotions, creams such as nourishing creams, moisture creams, eye creams, essences, cosmetic ointments, sprays, gels, packs, sunscreens, makeup bases, liquids Formulations such as foundations, powders, cleansing creams, cleansing lotions, makeup removers such as cleansing oils, cleansing foams, soaps, body washes and the like.

In addition, the cosmetics are in addition to the compound of Formula 1, fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water Commonly used in ionic or nonionic emulsifiers, fillers, metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics It may contain adjuvants conventionally used in the cosmetic field, such as any other ingredient.

The compound of Formula 1 may be a relatively high concentration of the compound of Formula 1 in the case of a wash-off type cosmetic such as a make-up remover, a detergent, etc., in which the active ingredient stays on the skin within a short time when it is commercialized. It may include. On the other hand, in the case of a leave-on type cosmetic such as a lotion, an emulsion, a cream, an essence, etc., in which the active ingredient stays on the skin for a long time, the compound of Chemical Formula 1 has a lower concentration than the wash-off type cosmetic. It may be included. Although not limited thereto, in one embodiment of the present invention, the composition may include the compound of Formula 1 in an amount of 0.0001% to 10% by weight (preferably 0.0001% to 1% by weight) based on the total weight of the composition. Can be. When the composition of the present invention comprises less than 0.0001% by weight of the compound of Formula 1 can not expect sufficient antioxidant, anti-inflammatory and whitening effect, when containing more than 10% by weight unwanted reactions, such as allergies occur In order to prevent this problem, there may be a problem with skin safety.

The present invention also relates to an antioxidant, anti-inflammatory and whitening health food comprising the compound of formula (1).

In the present specification, 'health food' is a food prepared by adding the compound of Formula 1 to food materials such as beverages, teas, spices, gums, confectionery, or the like, encapsulated, powdered, suspensions, and the like when ingested It means to bring a certain effect, but unlike the general medicine has the advantage that there are no side effects that can occur when taking a long-term use of the drug as a raw material.

Since the health food of the present invention thus obtained can be consumed on a daily basis, high antioxidant, anti-inflammatory and whitening effects can be expected, which is very useful.

When the compound of Formula 1 is used as a food additive, the compound of Formula 1 may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixed amount of the active ingredient can be suitably determined according to the purpose of use (prevention, health or therapeutic treatment). Generally, in the preparation of food or beverages, the composition of the present invention is added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight based on the raw materials. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .

There is no particular limitation on the kind of food. Examples of the food to which the substance may be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. Natural carbohydrates described above are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of said 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 includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the health food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice drink and vegetable drink. These components can 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 by way of examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Reference Example 1: Toosendanin Substance Information

28-Deacetylsendanin; Chuanliansu; (1S, 3R, 4aR, 6R, 6aS, 6bS, 7aR, 9R, 9aR, 10R, 11aR, 11bS, 14R) -9- (furan-3-yl) -1,6,14-trihydroxy-4,6a, 9a-trimethyl-11-oxotetradecahydro-1H-4,11b- (methanooxymethano) naphtho [1 ', 2': 6,7] indeno [1,7a-b] oxirene-3,10-diyl diacetate; (1S, 4R, 4aR, 6R, 6aS, 6bS, 7aR, 9R, 9aR, 10R, 11aR, 11bS, 14S) -9- (furan-3-yl) -1,6,14-trihydroxy-4,6a, 9a-trimethyl-11-oxotetradecahydro-1H-4,11b- (methanooxymethano) naphtha [1 ', 2': 6,7] indeno [1,7a-b] oxirene-3, 10-diyl diacetate

CAS No .: 58812-37-6

Molecular Formula: C ₃₀ H ₃₈ O ₁₁

Molecular Weight: 574.62

Where to buy: Tauto Biotech Co., Ltd.

Plant of interest: Melia azedarach L., Melia Toosendanin Sieb. et Zucc

Example 1: whitening effect - confirm melanin production inhibitory effect

The compound of formula 1 was added to the culture solution of mouse melanoma cells (B-16 mouse melanoma cells) to test the whitening effect at the cellular level. (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980).

Before the experiment, rat melanoma cells were assessed for toxicity, and non-toxic concentrations were selected for whitening evaluation.

The compound of formula 1 was tested in a final concentration of 5ug / ml, 10ug / ml, 20ug / ml in the culture medium, Arbutin as a control was added to the medium to 200ug / ml treated with B-16 melanoma cells, respectively Incubated for 3 days.

Thereafter, the cells were trypsin-treated and removed from the culture vessel and centrifuged to extract melanin. The detached cells were added with 1 ml of sodium hydroxide solution (1 N concentration), boiled for 10 minutes to dissolve the melanin, and the absorbance was measured at 400 nanometers (nm) using a spectrophotometer to measure the amount of melanin produced.

The melanin amount was measured by the absorbance of the unit cell number (10 ⁶ cells), the relative melanin production relative to the control group was calculated as the inhibition rate (%) and the results are summarized in Table 1. In addition, the experiment was repeated three times.

Inhibitory effect of melanin production at the cellular level sample Melanin production % Inhibition Control group (no addition) 0.085 - Control 1: Arbutin (200 ug / ml) 0.046 46 Compound of Formula 1 (20ug / ml) 0.021 75 Compound of Formula 1 (10ug / ml) 0.046 46 Compound of Formula 1 (5 ug / ml) 0.070 18

As can be seen from the results of Table 1, the compound of Formula 1 has a superior melanin production inhibitory ability against the cultured mouse melanoma cells compared with the known whitening material Arbutin (Arbutin).

Example 2 Antioxidant Effect-Free Radical Scavenging Rate

Free radical scavenging activity was measured to confirm the antioxidant activity of tusendanin. Free radical scavenging activity was measured using DPPH. DPPH was purchased from Sigma Co., Ltd, USA. First, a 1.5 mM (0.06 mg / ml) standard DPPH ethanol solution was made. In addition, ethanol was added to the ascorbic acid, an antioxidant, as a compound of Formula 1 and a reference material, 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 / ml. . Then, the sample and the standard DPPH solution were added in the same ratio, stirred well, and then reacted at 37 ° C. for 30 minutes, and the absorbance was measured at 520 nm. At this time, ethanol was added instead of the sample as a control. The free radical scavenging ability was obtained from IC ₅₀ , which is a half maximal inhibitory concentration, and the results are shown in Table 2 below. IC ₅₀ is a general method of expressing free radical scavenging ability as a concentration of ascorbic acid and a compound of formula (1) required to remove 50% of free radicals from an additive-free control group.

Free radical scavenging rate (IC ₅₀ ) sample Free radical scavenging rate (ug / ml; ppm) Ascorbic acid 9 Compound of Formula 1 16

As shown in Table 2, the compound of Formula 1 has lower activity than ascorbic acid (Vitamin C), which is a representative strong antioxidant, but is stable as it is a natural substance with an excellent level of antioxidant effect and suitable for use as an antioxidant potency material. It can be seen.

Example 3: anti-inflammatory effect-NO production inhibitory effect

In order to confirm the anti-inflammatory effect and skin trouble alleviating effect of the compound of Formula 1, the nitric oxide (NO) formation inhibitory experiment was conducted by GRIESS method using RAW264.7 cell line (ATCC number: CRL-2278).

Specifically, RAW264.7 cells, which are macrophages of mice, were passaged several times, placed in a 24-well plate to enter 3 × 10 ⁵ cells in one well, and then cultured for 24 hours. Subsequently, the compound of formula 1 was diluted and replaced with the cell medium containing the concentration shown in Table 3 below. The concentration refers to the concentration of the compound of formula 1 dissolved in the medium used for the evaluation, 1% = 10 mg / ml, 0.1% = 1 mg / ml, 0.01 = 0.1 mg / ml, 0.001 = 0.01 mg / ml Means. Meanwhile, L-NMMA (L-NG-Monomethylarginine), a NO-producing inhibitor, was treated together as a positive control and incubated for 30 minutes, and treated with 1 μg of LPS (Lipopolysaccharide) as a stimulus and incubated for 24 hours. 100 μl of the supernatant was taken and transferred to a 96-well plate, 100 μl of the GRIESS solution was added thereto, reacted at room temperature for 10 minutes, and the absorbance at 540 nm was measured. Determining the NO inhibitory effect of the compound of formula 1 compared to the negative control treated with LPS only, no inhibitor was shown in Table 3 below.

NO production inhibitory effect sample NO production inhibition rate (%) L-NMMA (positive control, 0.001%) 24.25 Compound of Formula 1 (0.001%) 12.87 Compound of Formula 1 (0.01%) 21.91 Compound of Formula 1 (0.1%) 30.07 Compound of Formula 1 (1%) 32.28

As shown in Table 3, the compound of formula 1 is lower than the representative anti-inflammatory material NMMA, but the activity is low, but shows excellent activity as a natural material, so the anti-inflammatory effect acts as a secondary role in the improvement of whitening and wrinkles synergistic effect You can expect.

Formulation Example 1 Preparation of Pharmaceutical Formulation

1. Preparation of powder

0.001 g of compound of Formula 1

1g lactose

The above ingredients were mixed and filled in airtight cloth to prepare a powder.

2. Preparation of Tablets

0.2 mg of compound of Formula 1

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

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

3. Preparation of Capsule

0.2 mg of compound of Formula 1

Corn Starch 100mg

Lactose 100mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

4. Manufacture of rings

0.003 g of compound of Formula 1

Lactose 1.5 g

1 g of glycerin

Xylitol 0.5 g

After mixing the above components, it was prepared to be 4 g per ring according to a conventional method.

5. Preparation of Granules

2 mg of compound of formula 1

Soybean Extract 50mg

Glucose 200 mg

Starch 600 mg

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules, and then filled in fabric.

Formulation Example 2: Preparation of Cosmetics

1. Preparation of Soft Cosmetics (Skin Lotion)

Like the following composition, a flexible longevity containing the compound of formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Butylene Glycol 2.0 wt%

Propylene Glycol 2.0 wt%

Carboxy vinyl polymer 0.1 wt%

Fiji-12 nonylphenyl ether 0.2% by weight

Polysorbate 80 0.4 wt%

Ethanol 10.0 wt%

0.1% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

2. Preparation of Nutrients (Milk Lotion)

As shown in the following composition, nutrient longevity containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Beeswax 4.0 wt%

Polysorbate60 1.5 wt%

Sorbanthesquioleate 1.5 wt%

0.5% by weight of liquid paraffin

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 3.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

Carboxy vinyl polymer 0.1 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

3. Preparation of nutrition cream

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

0.2 wt% of a compound of Formula 1

Beta-1,3-Glucan 5.0 wt%

Beeswax 10.0 wt%

Polysorbate60 1.5 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

0.5 wt% sorbitan sesquioleate

10.0% by weight of liquid paraffin

Squalane 5.0 wt%

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 5.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

4. Preparation of Massage Cream

As in the following composition, a massage cream containing a compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 3.0 wt%

Beeswax 10.0 wt%

Polysorbate60 1.5 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

Sorbanthesquioleate 0.8 wt%

40.0% by weight of liquid paraffin

Squalane 5.0 wt%

Caprylic / Capric Triglyceride 4.0 wt%

Glycerin 5.0 wt%

Butylene Glycol 3.0 wt%

Propylene Glycol 3.0 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

5. Manufacture of pack

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

0.2 wt% of a compound of Formula 1

Beta-1,3-Glucan 1.0 wt%

Polyvinyl Alcohol 13.0 wt%

Sodium Carboxymethyl Cellulose 0.2% by weight

Glycerin 5.0 wt%

Allantoin 0.1 wt%

Ethanol 6.0 wt%

0.3% by weight of sebum-12 nonylphenyl ether

Polysorbate 60 0.3 wt%

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

Formulation Example 3: Preparation of external skin preparation

1. Preparation of Gel

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

0.1 wt% of a compound of Formula 1

Beta-1,3-Glucan 0.1 wt%

0.05% by weight of ethylenediamine sodium acetate

Glycerin 5.0 wt%

Carboxy vinyl polymer 0.3 wt%

Ethanol 5.0 wt%

Fiji-60 Cured Castor Oil 0.5 wt%

0.3% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

2. Manufacture of ointments

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

0.5% by weight of compound of formula 1

Beta-1,3-Glucan 10.0 wt%

Beeswax 10.0 wt%

Polysorbate 60 5.0 wt%

Sebum 60 Cured Castor Oil 2.0 wt%

Sorbitan sesquioleate 0.5 wt%

Vaseline 5.0 wt%

10.0% by weight of liquid paraffin

Squalane 5.0 wt%

Shea Butter 3.0 wt%

Caprylic / Capric Triglycerides 5.0 wt%

Glycerin 10.0 wt%

Propylene Glycol 10.2 wt%

0.2% by weight of triethanolamine

0.05 wt% preservative

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100% by weight

3. Preparation of Topical Drug (Gel Ointment)

As the following composition, a gel ointment comprising the compound of formula 1 as an active ingredient was prepared according to a conventional method.

0.5% by weight of compound of formula 1

Beta-1,3-Glucan 10.0 wt%

1.5% by weight of polyacrylic acid (Carbopol 940)

Isopropanol 5.0 wt%

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100% by weight

4. Preparation of medicament (patch) for topical administration

As in the following composition, a patch containing the compound of Formula 1 as an active ingredient was prepared according to a conventional method.

0.5% by weight of 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)

Sodium sulfite 0.1 wt%

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

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

Viscous paraffin oil 2.5% by weight

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

Polyethylene glycol 400 3.0 wt%

Deionized water to 100% by weight

Formulation Example 4 Preparation of Food

Food containing the compound of formula 1 of the present invention was prepared as follows.

1. Preparation of flour food

0.05 to 1.0 parts by weight of the compound of Formula 1 was added to the flour, and using the mixture to prepare bread, cake, cookies, crackers and noodles to prepare a health food.

2. Manufacturing of Dairy Products

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

3. Manufacture of wire

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh. Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then roasted to prepare a powder having a particle size of 60 mesh. The compound of Chemical Formula 1 was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray and a hot air dryer was pulverized with a particle size of 60 mesh to obtain a dry powder.

The dry powder of the grains, seeds and the compound of Formula 1 prepared in the above was prepared by blending at 100 parts by weight of the mixed powder in the following ratio.

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

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

Compound of formula 1 (0.1 parts by weight),

Ganoderma lucidum (0.5 parts by weight),

Foxglove (0.5 part by weight)

Formulation Example 5 Preparation of Beverage

1. Manufacture of health drinks

0.1 mg of compound of Formula 1

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 mL of purified water

After mixing the above components according to the conventional healthy beverage manufacturing method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained by sterilization in a sterilized 2L-container, sealed sterilization and refrigerated It was used to prepare a healthy beverage composition of the invention.

Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and intended use.

2. Preparation of Vegetable Juice

1 g of the compound of Chemical Formula 1 of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice for health promotion.

3. Preparation 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 pharmaceutical composition for antioxidant comprising the compound represented by the following Formula 1 as an active ingredient:
[Formula 1]

Skin external preparation for antioxidant containing the compound represented by the following formula 1 as an active ingredient:
[Formula 1]

The method of claim 2,
The external preparation is an external preparation for skin in the form of an ointment, patch, gel, cream or spray.
An antioxidant cosmetic composition comprising the compound represented by the following Formula 1 as an active ingredient:
[Formula 1]

The method of claim 4, wherein
Cosmetic composition in the form of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
Health food for antioxidant containing a compound represented by the following formula 1 as an active ingredient:
[Formula 1]