KR102114894B1 - Composition for antioxidant, anti-imflamation, and skin whitening - Google Patents

Abstract

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

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 outside the body, or generated in the body, causes many problems such as promoting aging of the body or generating cancer. Therefore, many researches and developments have been made on antioxidants that inhibit oxidation by free radicals. Antioxidants are widely distributed in animals and plants, and many phenolic compounds, flavonoids, tocopherols, vitamin C, and selenium are known in fruits and vegetables. However, the antioxidants present in nature cannot be expected to have a substantially sufficient effect when applied to the skin. Accordingly, although synthetic antioxidants having excellent antioxidant power and low cost are frequently used, their use is limited due to safety concerns such as human side effects.

In addition, inflammation is an immune response of the human body that responds to wounds and diseases, and oxidative stress, such as ultraviolet rays, free radicals, and free radicals, activates inflammatory factors, causing various diseases and skin aging. Vascularly active polypeptides, such as kinin, plasmin, and complement, act to expand and contract blood vessels and chemotaxis, and other lymphokas, such as interleukin-6 (IL-6) Phosphorus and arachidonic acid are responsible for the inflammatory response. Arachidonic acid is metabolized to prostaglandin and leukotriene, which are inflammatory mediators, through two pathways: cyclooxygenase or lipooxygenase.

On the other hand, in order to eliminate inflammation, the action of reducing the inflammatory source, reducing biological reactions and symptoms is called anti-inflammatory. Materials that have been used for anti-inflammatory purposes to date include non-steroidal drugs such as flufenamic acid, ibuprofen, benzydamine, and indomethacin, 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 limitations in the amount of use due to safety problems for the skin, or the effect is insignificant, so that the effect of alleviating inflammation cannot be expected. There is this.

In addition, it is a constant desire of everyone to have a white skin. It is genetically determined according to the concentration and distribution of melanin in a person's skin, but is also affected by environmental or physiological conditions such as sun UV rays, fatigue, and stress. Melanin is produced by undergoing a non-enzymatic oxidation reaction after tyrosinase, an amino acid tyrosine, is converted to dopa (DOPA) or dopaquinone. The pathway by which melanin is produced is known, but the mechanism by which tyrosinase acts as a precursor for melanin synthesis is 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 kinds thereof There are plant extracts. By inhibiting the synthesis of melanin pigments, they can not only realize skin whitening by brightening the skin tone, but also improve skin hyperpigmentation, such as ultraviolet rays, hormones, or freckles caused by genetics. However, when applied to the skin, there is a problem in 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 cannot be expected.

Therefore, it is urgently desired to develop a component having an antioxidant, anti-inflammatory and whitening activity that is safe for a living body, has an active ingredient that is stable, and above all, has a superior effect than a substance having an existing antioxidant, anti-inflammatory, and whitening effect.

Thus, the present inventors have confirmed that the Tosenndanin (Toosendanin) by free radical scavenging to have an anti-inflammatory effect by inhibiting the antioxidant effect and NO production, and inhibiting melanin synthesis to show a whitening effect and completed the present invention.

Accordingly, an object of the present invention is to provide a composition for antioxidant, anti-inflammatory and skin whitening comprising a 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 an anti-oxidation, anti-inflammatory and skin external preparation for skin whitening comprising the 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 an antioxidant, anti-inflammatory and skin whitening cosmetic composition 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 health food for antioxidant, anti-inflammatory and skin whitening comprising the compound represented by the formula (1) as an active ingredient.

[Formula 1]

Toosendanin according to the present invention exhibits an antioxidant effect by scavenging free radicals, suppresses NO production involved in an inflammatory reaction, has excellent anti-inflammatory effect, inhibits melanin synthesis, and exhibits a whitening effect, thereby exhibiting a whitening effect. Can be used for health food.

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

In order for the antioxidant, anti-inflammatory, and whitening components to exhibit excellent effects when applied to actual skin, it exhibits high-activity antioxidant, anti-inflammatory, and whitening activities at low concentrations, and has excellent ability to penetrate and absorb skin, and has antioxidant, anti-inflammatory, and It is preferable that the volatility is low, the active ingredient is stably maintained on the composition or the skin, it is easy to formulate it into medicine or cosmetics, and it is also safe for the skin so that it can stay for a sufficient time to exhibit a whitening effect. However, few known components satisfy all of the above properties. For example, some antioxidant, anti-inflammatory, and whitening components have excellent antioxidant, anti-inflammatory, and whitening activity even at low concentrations in vitro experiments, but their ability to penetrate and absorb the skin is difficult to apply to actual skin. Other active ingredients have low hydrophilicity, making them difficult to formulate into medicine or cosmetics. In addition, some antioxidant, anti-inflammatory, and whitening ingredients, when exposed to heat, light, or oxygen, the active ingredient is decomposed or transformed into another compound, and the effect may be lost before being applied to the skin.

As can be seen in the examples below, Tosenndanin exhibits excellent anti-oxidant, anti-inflammatory and whitening effects at low concentrations, so it is effective for anti-oxidation, anti-inflammatory and skin whitening medicines, cosmetics, health foods, etc. Can be used as an ingredient.

Therefore, the present invention therefore provides a pharmaceutical composition for antioxidant, anti-inflammatory and skin whitening comprising the 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, also known as tucene It is called Toosendanin.

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

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 above.

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 is, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, 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, aminooxy acetic acid , 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. Preferably it may be in the form of a hydrochloride or acetate, and more preferably in the form of a hydrochloride.

The above-mentioned acid addition salts are either 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-containing solvent, or c) solvent or submerging the compound of Formula 1 It is prepared by the general salt preparation method of placing them in an acid in a solvent and mixing them.

Apart from the above, possible salt forms include gaba salt, gabapentin salt, pregabalin salt, nicotinate salt, adipate salt, hemimalonate salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, And aspartates.

In addition, when the compound of Formula 1 of the present invention is used as a pharmaceutical, 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 whitening ingredients. The inclusion of additional antioxidant, anti-inflammatory and skin whitening components will further enhance the antioxidant, anti-inflammatory and skin whitening effects of the compositions of the present invention. When adding the above components, skin safety, ease of formulation, and stability of active ingredients according to the combined use may be considered. In one embodiment of the 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, koji acid (Kojic acid), arbutin (Arbutin) Adds one or two or more components selected from the group consisting of substances that inhibit tyrosinase enzyme activity such as), hydroquinone, vitamin-C (L-Ascorbic acid) and their derivatives and various plant extracts It can contain as. The additional component may be included in an amount of 0.0001% to 10% by weight based on the total composition weight, and the content range may be adjusted according to requirements such as skin safety and ease in formulating the compound of Formula 1 .

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

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

The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered in various forms of a general pharmaceutical preparation, for example, oral and parenteral when administered clinically. , Can be prepared using diluents or excipients, such as extenders, binders, wetting agents, disintegrating agents, surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These 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 stearate talc are also used. Liquid preparations for oral use include suspensions, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, may be included.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents, suspension solvents include propylene glycol (Propylene glycol), polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, and glycerogelatin may be used.

In the present invention, the term 'antioxidant effect' refers to a cell by a free radical or reactive oxygen species (ROS), which is highly reactive according to oxidative stress due to intracellular metabolism or ultraviolet rays. Refers to inhibiting oxidation, and includes removing free radicals or free radical species, thereby reducing cell damage.

In the present invention, the term 'anti-inflammatory effect' refers to suppressing inflammation, and the inflammation is one of biological tissues' defense responses to certain stimuli, and is associated with three types of tissue degeneration, circulatory disorder and exudation, and tissue proliferation. Complex lesions. More specifically, inflammation is part of innate immunity, and as in other animals, innate immunity in humans recognizes patterns on cell surfaces that are specifically present in pathogens. Phagocytes recognize cells with such a surface as non-magnetic and attack pathogens. If pathogens break through the body's physical barrier, an inflammatory reaction occurs. Inflammatory reactions are non-specific protective actions that create a hostile environment against microorganisms that have entered the wound. In an inflammatory reaction, when a wound or an external infectious agent enters the body, white blood cells that are in charge of the initial stage of immune reactions flock to express cytokines. Therefore, the amount of cytokine expression in the cells is an indicator of activation of the inflammatory response. Examples of skin diseases associated with inflammation include atopic dermatitis, psoriasis, radiation, chemicals, erythematous diseases triggered by burns, acid burns, blistering skin diseases, thyroid-like diseases, itching due to allergies, seborrheic eczema, rose acne, Inflammatory hair loss such as vulgar erythema, polymorphic exudative erythema, nodular erythema, laryngitis, vulvitis, alopecia areata, skin T-cell lymphoma, but is not limited thereto.

In the present invention, the term “whitening effect” refers to not only brightening the skin tone by inhibiting the synthesis of melanin pigments, but also improving skin hyperpigmentation, such as ultraviolet rays, hormones, or freckles caused by genetics.

The pharmaceutical composition of the present invention can provide a desirable antioxidant effect, anti-inflammatory effect, and whitening effect when an effective amount of the compound of Formula 1 is included. In the present invention, the term 'effective amount' refers to an amount of a compound capable of inhibiting or alleviating oxidation of cells, suppressing inflammation, and 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, the method in which the compound is applied to the skin, and the length of time it remains on the skin. For example, when the composition is commercialized as a pharmaceutical product, the compound of Formula 1 may be included at a higher concentration than when commercialized as a cosmetic product that is applied to skin on a daily basis. Therefore, the daily dosage is 0.1 to 100 mg / kg, preferably 30 to 80 mg / kg, more preferably 50 to 60 mg / kg, and 1 to 1 day, based on the amount of the compound of Formula 1 It can be administered 6 times.

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

The present invention may also provide a formulation for external application for skin for anti-oxidation, 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, fatty substances, organic solvents, solubilizers, thickeners and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants , Water, ionic or nonionic emulsifiers, fillers, metal ion blockers and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or external preparations for skin It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as. In addition, the ingredients may be introduced in an amount commonly used in the field of skin science.

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 ointment, patch, gel, cream or spray.

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

When the compound of Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsifying formulation and a solubilizing formulation. For example, lotion such as soft lotion or nutrition lotion, emulsion such as facial lotion, body lotion, cream such as nutrition cream, moisture cream, eye cream, essence, cosmetic ointment, spray, gel, pack, sunscreen, makeup base, liquid It may have a formulation such as foundation type, solid type or spray type, powder, cleansing cream, cleansing lotion, makeup remover such as cleansing oil, cleansing agent such as cleansing foam, soap, body wash, and the like.

In addition, the cosmetic is a fat substance, an organic solvent, a solubilizer, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, and water in addition to the compound of Formula 1 , Ionic or nonionic emulsifiers, fillers, metal ion blockers and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or commonly used in cosmetics It may contain adjuvants commonly used in the cosmetic field, such as any other ingredient.

The compound of Formula 1 is a relatively high concentration of the compound of Formula 1 in the case of wash-off cosmetics such as makeup removers, detergents, etc., in which the active ingredient stays on the skin within a short period of time when it is commercialized as a cosmetic. It may contain. On the other hand, in the case of a leave-on type cosmetics such as lotion, emulsion, cream, essence, etc., in which the active ingredient stays on the skin for a long period of time, the compound of Formula 1 has a lower concentration than the wash-off type cosmetics. You may include it. Without being 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 composition weight. Can be. When the composition of the present invention contains less than 0.0001% by weight of the compound of Formula 1, sufficient antioxidant, anti-inflammatory and whitening effects cannot be expected, and when it exceeds 10% by weight, unwanted reactions such as allergies occur. Or, there is a problem with the safety of the skin.

The present invention also relates to a health food for antioxidant, anti-inflammatory and whitening comprising the compound of Formula 1.

In the present specification, the term 'healthy food' refers to foods prepared by adding the compound of Formula 1 to food materials such as beverages, teas, spices, gums, confectionery, or by encapsulation, powdering, suspension, etc. It means that it has a certain specific effect, but it has the advantage of not having side effects that can occur when taking the drug for a long time using food as a raw material, unlike ordinary drugs.

Since the health food of the present invention obtained in this way 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 suitably used according to a conventional method. The mixing amount of the active ingredient can be appropriately determined according to its purpose of use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, with respect to the raw materials in the production of a food or beverage. However, in the case of long-term intake for health and hygiene purposes or for health control, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range. .

There are no particular restrictions on the type of food. Examples of foods to which the above substances can be added are meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, dairy products including gums, ice cream, various soups, beverages, teas, drinks, Alcoholic beverages and vitamin complexes, and all of the health foods in the ordinary sense.

The health drink composition of the present invention may contain various flavoring agents, natural carbohydrates, and the like as additional ingredients, like a conventional beverage. The aforementioned natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetener, natural sweeteners such as taumatin and stevia extract, and synthetic sweeteners such as saccharin and aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g per 100 mL of the composition of the present invention, preferably about 0.02 to 0.03 g.

In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols , Carbonic acid used in carbonated beverages, and the like. In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice beverages and vegetable beverages. These ingredients may be used independently or in combination. The proportion of these additives is not critical, but is generally selected from 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 examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are 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 Origin: Melia azedarach L., Melia Toosendanin Sieb. et Zucc

Example 1: whitening effect - check the inhibitory effect of melanin production

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

Prior to the experiment, whitening evaluation was performed by selecting the non-toxic concentration by evaluating the toxicity of the melanoma cells of the mouse.

The compounds of Formula 1 were tested in the culture solution so that the final concentrations were 5 ug / ml, 10 ug / ml, and 20 ug / ml, and the control arbutin was added to the medium to be 200 ug / ml and treated with B-16 melanoma cells, respectively. Cultured for 3 days.

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

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

Inhibition effect of melanin production at cell level according to concentration sample Melanin production Inhibition rate (%) Control (no additives) 0.085 - Control 1: Arbutin (200ug / 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 (5ug / ml) 0.070 18

As can be seen from the results in Table 1, it can be seen that the compound of Formula 1 has superior melanin production inhibitory ability to the cultured rat melanoma cells compared to the known whitening substance Arbutin.

Example 2: Antioxidant effect-free radical scavenging rate

Free radical scavenging activity was measured to confirm the antioxidant activity of Toosendanin. Free radical scavenging activity was measured using DPPH. DPPH was purchased and used by Sigma Co., Ltd. (USA). First, a standard DPPH ethanol solution of 1.5 mM (0.06 mg / ml) was made. Then, ethanol was added to ascorbic acid, an antioxidant, as a compound of Formula 1 and a reference material 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 at the same rate, stirred well, reacted at 37 ° C for 30 minutes, and absorbance was measured at 520 nm. At this time, instead of the sample, ethanol was added as a control. The free radical scavenging activity was obtained by obtaining the IC ₅₀ , which is a half maximal inhibitory concentration (inhibition median), 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 a compound of formula 1 and ascorbic acid required to remove 50% of free radicals of 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 a low activity compared to a representative strong antioxidant, ascorbic acid (Vitamin C), but is a natural substance and is stable with excellent levels of antioxidant effect and is suitable for use as an antioxidant efficacy substance. Can be seen.

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 Formula 1, an experiment for inhibiting nitric oxide (NO) formation was performed by the GRIESS method using the 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 cultured for 24 hours. Subsequently, the compound of Formula 1 was diluted to the concentration shown in Table 3 and replaced with a cell medium containing it. The concentration refers to the concentration of the compound of Formula 1 in the medium used for evaluation, 1% = 10 mg / ml, 0.1% = 1 mg / ml, 0.01 = 0.1 mg / ml, 0.001 = 0.01 mg / ml It means On the other hand, the NO-producing inhibitor L-NMMA (L-NG-Monomethylarginine) was treated together as a positive control and incubated for 30 minutes, and LPS (Lipopolysaccharide) as a stimulus was treated with 1 μg for incubation 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, and the mixture was reacted for 10 minutes at room temperature, and absorbance at 540 nm was measured. The NO inhibitory effect of the compound of Formula 1 compared to the negative control group treated only with LPS and NO inhibitor was not shown, and the results are shown in Table 3 below.

NO production suppression 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 has a low activity when compared to the representative anti-inflammatory substance NMMA, but exhibits excellent activity as a natural substance, so the anti-inflammatory effect acts as a secondary role in improving whitening and wrinkles, thus synergistic effect. Can be expected.

Formulation Example 1: Preparation of pharmaceutical preparation

1. Preparation of powder

0.001 g of compound of formula 1

1 g of lactose

A powder was prepared by mixing the above components and filling the gas-tight fabric.

2. Preparation of tablets

0.2 mg of compound of formula 1

Corn starch 100mg

Lactose 100mg

Magnesium stearate 2mg

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

3. Preparation of capsules

0.2 mg of compound of formula 1

Corn starch 100mg

Lactose 100mg

Magnesium stearate 2mg

After mixing the above components, the capsules were prepared by filling the gelatin capsules according to a conventional capsule preparation method.

4. Preparation of pills

0.003 g of compound of formula 1

1.5 g lactose

Glycerin 1 g

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 50 mg

Glucose 200 mg

Starch 600 mg

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

Formulation Example 2: Preparation of cosmetics

1. Manufacture of flexible cosmetic (skin lotion)

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

0.1% by weight of 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%

PG-12 nonylphenyl ether 0.2 wt%

Polysorbate 80 0.4 wt%

Ethanol 10.0% by weight

Triethanolamine 0.1 wt%

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

2. Preparation of nutrient makeup (milk lotion)

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

0.1% by weight of compound of formula 1

Beta-1,3-glucan 1.0 wt%

Wax 4.0% by weight

Polysorbate 60 1.5 wt%

Sorbitan sesquioleate 1.5 wt%

Liquid paraffin 0.5 wt%

Caprylic / Capric Triglyceride 5.0 wt%

Glycerin 3.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Carboxyvinyl polymer 0.1 wt%

Triethanolamine 0.2% by weight

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

3. Preparation of nutrition cream

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

0.2% by weight of compound of formula 1

Beta-1,3-glucan 5.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

PAGE 60 Cured Castor Oil 2.0 wt%

Solbitan sesquioleate 0.5 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Caprylic / Capric Triglyceride 5.0 wt%

Glycerin 5.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Triethanolamine 0.2% by weight

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

4. Preparation of massage cream

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

0.1% by weight of compound of formula 1

Beta-1,3-glucan 3.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

PAGE 60 Cured Castor Oil 2.0 wt%

Solbitan sesquioleate 0.8 wt%

Liquid paraffin 40.0 wt%

Squalane 5.0 wt%

Caprylic / Capric Triglyceride 4.0 wt%

Glycerin 5.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Triethanolamine 0.2% by weight

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

5. Manufacture of pack

As shown 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% by weight of compound of formula 1

Beta-1,3-glucan 1.0 wt%

Polyvinyl alcohol 13.0 wt%

Sodium carboxymethyl cellulose 0.2 wt%

Glycerin 5.0 wt%

Allantoin 0.1 wt%

Ethanol 6.0% by weight

PG-12 Nonylphenyl ether 0.3 wt%

Polysorbate 60 0.3 wt%

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

Formulation Example 3: Preparation of external preparation for skin

1. Preparation of gel

As shown 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 compound of formula 1

Beta-1,3-glucan 0.1 wt%

Sodium ethylenediamine acetate 0.05 wt%

Glycerin 5.0 wt%

Carboxyvinyl polymer 0.3 wt%

Ethanol 5.0 wt%

AGE-60 Cured castor oil 0.5% by weight

Triethanolamine 0.3 wt%

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

2. Preparation of ointment

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%

Wax 10.0 wt%

Polysorbate 60 5.0 wt%

PAGE 60 Cured Castor Oil 2.0 wt%

Solbitan sesquioleate 0.5 wt%

Vaseline 5.0 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Shea butter 3.0 wt%

Caprylic / Capric Triglyceride 5.0 wt%

Glycerin 10.0 wt%

Propylene glycol 10.2 wt%

Triethanolamine 0.2 wt%

Preservative 0.05 wt%

Pigment 0.05 wt%

Fragrance 0.05% by weight

Purified water to 100% by weight

3. Preparation of topical medication (gel ointment)

As shown in the following composition, a gel 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%

Polyacrylic acid (Carbopol 940) 1.5 wt%

Isopropanol 5.0 wt%

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100% by weight

4. Preparation of pharmaceuticals (patches) for topical administration

As shown 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%

Polyacrylic acid (Carbopol 934P) 1.0 wt%

Sodium sulfite 0.1 wt%

Polyoxyethylene lauryl ether (E.O = 9) 1.0 wt%

Polyhydroxyethylene cetyl stearyl ether (Cetomacrogol 1000) 1.0 wt%

2.5% by weight of viscous paraffin oil

Caprylic acid ester / capric acid ester (Cetiol LC) 2.5 wt%

Polyethylene glycol 400 3.0 wt%

Deionized water to 100% by weight

Formulation Example 4: Preparation of food

Foods comprising the compound of Formula 1 of the present invention were 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 wheat flour, and bread, cake, cookie, cracker and noodles were prepared using this mixture to prepare healthy food.

2. Manufacturing of dairy products

0.2 parts 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

The brown rice, barley, glutinous rice, and yulmu were alpha-polished in a known manner to distribute the dried one, and then prepared into a powder having a particle size of 60 mesh with a grinder. Black soybeans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, and then distributed into a powder having a particle size of 60 mesh with a grinder. The compound of Formula 1 was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray or hot air dryer was pulverized to a particle size of 60 mesh to obtain a dry powder.

The dry powders of the above-mentioned grains, seeds, and compounds of Formula 1 were blended with 100 parts by weight of the mixed powder to prepare them.

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

Compound of formula 1 (0.1 parts by weight),

Territory (0.5 parts by weight),

Ground sulfur (0.5 parts by weight)

Formulation Example 5: Preparation of beverage

1. Preparation of health drinks

0.1 mg of compound of formula 1

Citric acid 1000 mg

Oligosaccharide 100 g

2 g of plum concentrate

Taurine 1 g

900 mL total by adding purified water

After mixing the above ingredients according to a conventional health drink manufacturing method, and stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered, obtained in a sterilized 2L-container, sealed and sterilized, then refrigerated and then viewed. It was used to prepare the health drink composition of the invention.

Although the above composition ratio is a mixture of components suitable for a relatively preferred beverage in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, country of demand, and usage.

2. Preparation of vegetable juice

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

3. Production of fruit juice

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

Claims (6)

Antioxidant cosmetic composition comprising the compound represented by Formula 1 as an active ingredient:
[Formula 1]

According to claim 1,
Cosmetic composition which is a formulation of lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
Antioxidant health food comprising a compound represented by the following formula (1) as an active ingredient:
[Formula 1]

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