KR102248955B1 - Composition for anti-imflammation, or skin whitening - Google Patents

Abstract

The present invention relates to a composition for anti-inflammatory or skin whitening.
Epimedin A1 according to the present invention can be used as a pharmaceutical composition, an external preparation for skin, a cosmetic composition or a health food by showing an anti-inflammatory effect by inhibiting the production of nitrogen oxide (NO), and a whitening effect by reducing the total amount of melanin.

Description

Composition for anti-imflammation, or skin whitening}

The present invention relates to a composition for anti-inflammatory or skin whitening.

Inflammation is the body's immune response in response to wounds or diseases, and oxidative stress such as ultraviolet rays, free radicals, etc. activates inflammatory factors, causing various diseases and aging of the skin. Vasoactive polypeptides such as kinin, plasmin, or complement act as 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 prostaglandin or lukotriene, an inflammatory mediator, through two pathways of cyclooxygenase or lipooxygenase, mediating various inflammatory reactions.

On the other hand, in order to eliminate inflammation, it is called an anti-inflammatory agent that acts to remove inflammatory sources, reduce biological reactions, and symptoms. Substances used for anti-inflammatory purposes to date include flufenamic acid, ibuprofen, benzydamine, or indomethacin as non-steroids, and prednisolone as a steroid system. Or dexamethasone. In addition, allantoin, azene, hydrocortisone, etc., are known to have anti-inflammatory effects [Patent Document 1], but these substances have limited amounts of use due to safety issues on the skin, or are insignificant, so that they substantially relieve inflammation. There is a problem that cannot be expected.

Also, it is a common desire to have white and fair skin. The color or brightness of the skin 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 solar ultraviolet rays, fatigue or stress. Melanin is produced through a non-enzymatic oxidation reaction after being sequentially converted into dopa and dopaquinone by an enzyme called tyrosinase acting as a catalyst on tyrosine, a kind of amino acid. As such, the pathway by which melanin is produced is known, but the cause of the triggering of tyrosinase in the mechanism that induces melanin synthesis is still not elucidated in detail.

Meanwhile, as a commonly known whitening component, substances that inhibit tyrosinase enzyme activity such as Kojic acid or arbutin, hydroquinone, vitamin C (L-Ascorbic acid), or derivatives thereof, and various There is a plant extract [Patent Document 2]. By inhibiting the synthesis of melanin pigments, they can not only realize skin whitening by brightening skin tone, but also improve skin hyperpigmentation such as spots and freckles caused by ultraviolet rays, hormones or genetics. However, when applied to the skin, there is a problem in that the amount of use 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, there is an urgent need to develop a component having an anti-inflammatory or whitening activity that is safe for the living body, has a stable active ingredient, and, above all, is superior to a substance having an anti-inflammatory or whitening effect.

Korean Patent Registration No. 1060634 Korean Patent Publication No. 2004-0049999

Accordingly, the present inventors confirmed that epimedin A1 exhibits an anti-inflammatory effect by inhibiting the production of nitric oxide (NO), and the total amount of melanin significantly decreased to show a whitening effect, and the present invention was completed.

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

[Formula 1]

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

It provides an anti-inflammatory or skin whitening cosmetic composition comprising a compound represented by the following Formula 1 as an active ingredient.

[Formula 1]

Epimedin A1 according to the present invention has an excellent anti-inflammatory effect by inhibiting the production of nitric oxide (NO) involved in the inflammatory reaction, and has a whitening effect by remarkably reducing the total amount of melanin. Can be used.

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

In order for an anti-inflammatory or whitening component to exhibit an excellent effect when applied to the actual skin, it is preferable that it exhibits high activity anti-inflammatory or whitening activity at a low concentration, and has excellent ability to penetrate and absorb the skin. In addition, it is preferable that the volatility is low so that it can stay for a sufficient time to exhibit anti-inflammatory or whitening effect, the active ingredient is stably maintained on the composition or the skin, it is easy to formulate into a medicine or cosmetic, and is safe for the skin. However, among the known components, it is not common to find a component that satisfies all of the above properties. For example, some anti-inflammatory or whitening ingredients have excellent anti-inflammatory or whitening activity even at low concentrations when tested in vitro, but their ability to penetrate and absorb through the skin is poor, making it difficult to apply to actual skin. Other active ingredients have low hydrophilic properties, making it difficult to formulate them as pharmaceuticals or cosmetics. In addition, some anti-inflammatory or whitening ingredients may be decomposed or transformed into other compounds when exposed to heat, light, or oxygen, and their effect may disappear before being applied to the skin.

As can be seen in the following examples, Epimedin A1 exhibits an inhibitory effect on the production of nitric oxide at a low concentration, so it can be used as an active ingredient such as pharmaceuticals, cosmetics or health foods for anti-inflammatory or skin whitening.

Accordingly, the present invention provides a pharmaceutical composition for anti-inflammatory or skin whitening comprising a compound represented by the following Formula 1 as an active ingredient.

[Formula 1]

The compound of Formula 1 is referred to as epimedin A1, and may include all possible isomers.

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

The pharmaceutical composition for anti-inflammatory or skin whitening of the present invention may contain 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 or inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, 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, Benzenesulfonic acid, p-toluenesulfonic acid, or methanesulfonic acid-based salts. Inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid-based salts. Preferably, it may be in the form of hydrochloride or acetate, and more preferably in the form of hydrochloride.

The above-mentioned acid addition salt is a) directly mixing the compound of Formula 1 and an acid, b) dissolving and mixing one of them in a solvent or aqueous solvent, or c) adding the compound of Formula 1 to a solvent or dropping It is prepared by a general salt preparation method by placing them in an acid in a solvent and mixing them.

In addition to the above, additional salts are possible: gaba salt, gabapentin salt, pregabalin salt, nicotinic acid salt, adipate salt, hemimalonic acid salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt or And aspartate.

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 function. For example, it may contain known anti-inflammatory or skin whitening ingredients. If additional anti-inflammatory or skin whitening ingredients are included, the anti-inflammatory or skin whitening effect of the composition of the present invention may be further enhanced. When the above ingredients are added, skin safety, ease of formulation, and stability of active ingredients can be considered in combination with use. In one embodiment of the present invention, the composition is a whitening component known in the art, a substance that inhibits tyrosinase enzyme activity such as kojic acid or arbutin, hydroquinone, vitamin-C (L-Ascorbic acid), derivatives thereof, and one or more components selected from the group consisting of various plant extracts may be further included. Additional ingredients may be included in an amount of 0.0001% by weight or more and 10% by weight or less based on the total weight of the composition. For example, 0.0001% by weight or more and 1% by weight or more, 0.0001% by weight or more and 0.1% by weight or less, 0.0001% by weight or more and 0.001% by weight or less, 0.001% by weight or more and 10% by weight or less, 0.001% by weight or more and 1 It may be less than or equal to 0.001% by weight and less than or equal to 0.1% by weight, from less than or equal to 0.01% by weight to less than or equal to 10% by weight, and less than or equal to 0.01% by weight and less than or equal to 1% by weight. The content range may be adjusted according to requirements such as skin safety and ease of formulation of the compound of Formula 1.

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

The pharmaceutically acceptable carrier may contain various components such as a buffer solution, sterile water for injection, general saline or phosphate buffered saline, sucrose, histidine, or polysorbate.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered in the form of a general pharmaceutical formulation, for example, in various oral or parenteral formulations during clinical administration. , Extenders, binders, wetting agents, disintegrants, or surfactants, such as diluents or excipients.

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

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

Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, or suppositories. As the non-aqueous solvent or suspension solvent, vegetable oils such as propylene glycol, polyethylene glycol, or olive oil; Injectable esters such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper or glycerogelatin may be used.

In the present invention, the term "anti-inflammatory effect" refers to suppressing inflammation. Inflammation is one of the defense responses of biological tissues to certain stimuli, and refers to a complex lesion that causes tissue deterioration, circulatory disorders, exudation and tissue proliferation. More specifically, inflammation is part of innate immunity, and, as in other animals, innate immunity in humans recognizes patterns on the cell surface that are specific to pathogens. Phagocytes recognize cells with such surfaces as non-magnetic and attack pathogens. If pathogens break through the body's physical barriers, an inflammatory reaction occurs. The inflammatory reaction is a non-specific defense action that creates a hostile environment for microorganisms invading the wound. In the inflammatory reaction, when a wound or an external infectious agent enters the body, the white blood cells responsible for the initial stage immune response flock to express cytokines. Therefore, the amount of expression of cytokines in cells becomes an indicator of activation of the inflammatory response. Examples of skin diseases related to inflammation include atopic dermatitis, psoriasis, erythematous disease caused by radiation, chemical substances, or burns; Itching due to acid burns, bullous skin disease, lichen planus disease or allergies; Inflammatory hair loss such as seborrheic eczema, rose acne, pemphigus vulgaris, polymorphic exudative erythema, nodular erythema, balanitis, vulvitis or alopecia areata; Cutaneous T-cell lymphoma and the like, but are not limited thereto.

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

When the pharmaceutical composition of the present invention contains an effective amount of the compound of Formula 1, it can provide a desirable anti-inflammatory or whitening effect. In the present invention, "effective amount" means an amount of a compound capable of suppressing damaged 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, the method in which the compound is applied to the skin, or the time it stays on the skin. For example, when the composition is commercialized as a pharmaceutical product, it may contain the compound of Formula 1 at a higher concentration than when it is commercialized as a cosmetic product 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, based on the amount of the compound of Formula 1, and 1 to It can be administered 6 times.

The pharmaceutical composition of the present invention may be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, or methods using biological response modifiers.

The present invention may also be provided in a formulation of an anti-inflammatory or whitening skin external preparation comprising the compound of Formula 1 as an active ingredient.

When the compound of Formula 1 is used for external skin, additionally fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants , Water, ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic activators, lipophilic activators or lipid vesicles, etc. It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in the dermatology field. In addition, the above ingredients may be introduced in an amount 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, but may be a formulation such as an ointment, patch, gel, cream, or spray.

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

When the compound of Formula 1 is used as a cosmetic, a cosmetic prepared by containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation or a solubilized formulation. For example, a lotion such as a flexible lotion or a nutritional lotion; Emulsions such as facial lotion or body lotion; Creams such as nourishing cream, moisturizing cream, or eye cream; essence; Cosmetic ointment; spray; Gel; pack; Sunscreen; Makeup base; Foundations such as liquid type, solid type or spray type; powder; Makeup removers such as cleansing cream, cleansing lotion, and cleansing oil; It may have a formulation such as a detergent such as a cleansing foam, soap, and body wash.

In addition, the cosmetics are fatty substances, organic solvents, solubilizers, thickeners, gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water in addition to the compounds of Formula 1 , Ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic activators, lipophilic activators or lipid vesicles, etc. It may contain adjuvants used as.

The compound of Formula 1 is a relatively high concentration of the compound of Formula 1 in the case of a wash-off type cosmetic such as a makeup remover or detergent in which the active ingredient stays on the skin within a short period of time when it is commercialized as a cosmetic. Could be included. On the other hand, in the case of leave-on-type cosmetics such as lotions, emulsions, creams, or essences in which the active ingredient stays on the skin for a long period of time, the compound of Formula 1 is contained in a lower concentration than the wash-off type cosmetics. It would be okay to do it. Although not limited thereto, in one embodiment of the present invention, the composition comprises 0.0001% by weight to 10% by weight (preferably 0.0001% by weight to 1% by weight) of the compound of Formula 1 based on the total weight of the composition. I can. When the composition of the present invention contains less than 0.0001% by weight of the compound of Formula 1, sufficient anti-inflammatory or whitening effect cannot be expected, and when it contains more than 10% by weight, unwanted reactions such as allergies or skin There may be a safety problem, so this is to prevent this.

The present invention also relates to an anti-inflammatory or whitening health food comprising the compound of Formula 1.

In the present specification, the term'health food' refers to food prepared by adding the compound of Formula 1 to food materials such as beverages, teas, spices, gums, confectionery, or encapsulating, powdering, suspension, etc. It means bringing about a specific effect, but unlike general drugs, it has the advantage of having no side effects that may occur when taking drugs for a long time by using food as a raw material.

Since the health food of the present invention obtained in this way can be consumed on a daily basis, a high anti-inflammatory or whitening effect can be expected, and it 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 may be used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment). In general, when preparing food or beverage, 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 based on the raw material. However, when ingested for a long time for health and hygiene purposes, the content below the above range may be included, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, There are alcoholic beverages or vitamin complexes, and all health foods in the usual sense are included.

The health beverage composition of the present invention may contain various flavoring agents or natural carbohydrates as an additional component, like a conventional beverage. The natural carbohydrates described above include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, and erythritol. Sweeteners include natural sweeteners such as taumatin and stevia extract; 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, 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, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, It may contain glycerin, alcohol, or a carbonating agent. In addition, the health food of the present invention may contain flesh for the manufacture of natural fruit juice, fruit juice beverage, or vegetable beverage. These ingredients may be used independently or in combination. Although the proportion of these additives is not very important, it 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 One: Epimedine A1( Epimedin A1) Substance information

[Formula 1]

3-[(6-deoxy-3-O-beta-D-glucopyranosyl-alpha-L-mannopyranosyl)oxy]-7-(beta-D-glucopyranosyloxy)-5-hydroxy- 2-(4-methoxyphenyl)-8-(3-methyl-2-buten-1-yl)-4H-1-benzopyran-4-one; Hexanedraside F

CAS No.: 140147-77-9

Where to buy: Sichuan Hongjie Import&Export CO., LTD

Example 1: Effect of reducing the total amount of melanin

The whitening effect was confirmed by measuring the total amount of melanin at the cell level by adding it to the culture medium of mouse melanoma cells (B-16 mouse melanoma cells) (Lotan R., Lotan D. Cancer) Res . 40:3345-3350, 1980). Before the experiment, toxicity was evaluated for the melanoma cells of mice, and a non-toxic concentration was selected to perform whitening evaluation.

The final concentration of the compound of Formula 1 was 5 ppm, 10 ppm, and 20 ppm in the culture medium, and arbutin, a control, was added to the medium so that it became 200 ppm, and each treated with B-16 melanoma cells was cultured for 3 days.

Thereafter, the cells were treated with trypsin, removed 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) 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 a method expressed in terms of absorbance per unit cell count (10 6} cells), and the total amount of melanin relative to the control was calculated as an inhibition rate (%), and the results are summarized in Table 1. The experiment was repeated 3 times.

The effect of reducing the total amount of melanin at the cellular level according to the concentration sample Total amount of melanin Inhibition rate (%) Control (no addition) 0.234 - Control 1: Arbutin (200 ppm) 0.156 33.3 Compound of Formula 1 (20 ppm) 0.068 75.6 Compound of Formula 1 (10 ppm) 0.122 46.6 Compound of Formula 1 (5 ppm) 0.136 41.5

As can be seen from the results of Table 1, the compound of Formula 1 significantly decreases the total amount of melanin in the melanoma cells of the mice cultured even at a small concentration compared to arbutin (200 ppm), which is known as a whitening material. I could see that I could.

Example 2: anti-inflammatory effect- NO Production inhibitory effect

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

Specifically, RAW264.7 cells, which are mouse macrophages, were subcultured several times, placed in a 24-well plate so as to enter each ^{of 3×10 5 cells in each well, and cultured for 24 hours.} Subsequently, a cell medium containing the compound of Formula 1 diluted to a concentration of 1% (10 mg/ml), 0.1% (1 mg/ml), 0.01% (0.1 mg/ml), and 0.001% (0.01 mg/ml) Replaced with. At this time, 0.001% of the NO-production inhibitor L-NMMA (L-NG-Monomethylarginine) was treated together as a positive control and incubated for 30 minutes, and 1 μg of LPS (Lipopolysaccharide) was treated as a stimulating source and incubated for 24 hours. I did. 100 μl of the supernatant was taken and transferred to a 96-well plate, 100 μl of the GRIESS solution was added each to react at room temperature for 10 minutes, and the absorbance at 540 nm was measured to determine the NO inhibitory effect of the compound of Formula 1, and the result It is shown in Table 2 below.

NO production inhibitory effect sample NO production inhibition rate (%) L-NMMA (positive control, 0.001%) 44.33 Compound 1 (0.001 %) 17.51 Compound 1 (0.01%) 23.25 Compound 1 (0.1%) 28.74 Compound 1 (1%) 34.72

As can be seen from Table 2, the compound of Formula 1 has low activity when compared to L-NMMA, which is a representative anti-inflammatory drug, but exhibits excellent activity as a natural substance, so that the anti-inflammatory effect is auxiliary in whitening or wrinkle improvement. It acts as a role and can expect a synergistic effect.

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 an airtight cloth to prepare a powder.

2. Preparation of tablets

0.2 mg of the compound of formula 1

Corn starch 100mg

100mg lactose

Stearic acid 2 mg of magnesium

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

3. Manufacture of capsules

0.2 mg of the compound of formula 1

Corn starch 100mg

100mg lactose

Stearic acid 2 mg of magnesium

After mixing the above ingredients, a gelatin capsule was filled according to a conventional capsule preparation method to prepare a capsule formulation.

4. Preparation of pills

0.003 g of compound of formula 1

1.5 g lactose

1 g glycerin

Xylitol 0.5 g

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

5. Preparation of granules

2 mg of compound of formula 1

50 mg of soybean extract

200 mg of glucose

Starch 600 mg

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

Formulation example 2: manufacture of cosmetics

1. Manufacture of flexible lotion (skin lotion)

As shown in the following composition, a flexible lotion 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

1.0% by weight of beta-1,3-glucan

2.0% by weight of butylene glycol

2.0% by weight of propylene glycol

0.1% by weight of carboxyvinyl polymer

PG-12 nonylphenyl ether 0.2% by weight

Polysorbate 80 0.4% by weight

Ethanol 10.0% by weight

0.1% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

2. Manufacture of nutrient cosmetic water (milk lotion)

As shown in the following composition, nutrient cosmetic water 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

1.0% by weight of beta-1,3-glucan

Beeswax 4.0% by weight

1.5% by weight of polysorbate 60

1.5% by weight of sorbitansquioleate

0.5% by weight of liquid paraffin

Caprylic/Capric Triglyceride 5.0% by weight

3.0% by weight of glycerin

3.0% by weight of butylene glycol

Propylene glycol 3.0% by weight

0.1% by weight of carboxyvinyl polymer

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

3. Manufacture of nourishing 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 the compound of formula 1

5.0% by weight of beta-1,3-glucan

10.0 wt% beeswax

1.5% by weight of polysorbate 60

Sebum 60 hydrogenated castor oil 2.0% by weight

0.5% by weight of sorbitansquioleate

Liquid paraffin 10.0% by weight

5.0% by weight of squalane

Caprylic/Capric Triglyceride 5.0% by weight

5.0% by weight of glycerin

3.0% by weight of butylene glycol

Propylene glycol 3.0% by weight

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

4. Manufacturing 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 the compound of formula 1

Beta-1,3-glucan 3.0% by weight

10.0 wt% beeswax

1.5% by weight of polysorbate 60

Sebum 60 hydrogenated castor oil 2.0% by weight

0.8% by weight of sorbitansquioleate

Liquid paraffin 40.0% by weight

5.0% by weight of squalane

Caprylic/Capric Triglyceride 4.0% by weight

5.0% by weight of glycerin

3.0% by weight of butylene glycol

Propylene glycol 3.0% by weight

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

5. Manufacture of the 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 the compound of formula 1

1.0% by weight of beta-1,3-glucan

13.0% by weight of polyvinyl alcohol

Sodium carboxymethylcellulose 0.2% by weight

5.0% by weight of glycerin

0.1% by weight of allantoin

Ethanol 6.0% by weight

PG-12 nonylphenyl ether 0.3% by weight

Polysorbate 60 0.3% by weight

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

Formulation example 3: External skin Produce

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 the compound of formula 1

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

Sodium ethylenediamine acetate 0.05% by weight

5.0% by weight of glycerin

0.3% by weight of carboxyvinyl polymer

Ethanol 5.0% by weight

PEG-60 hydrogenated castor oil 0.5% by weight

0.3% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 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 the compound of formula 1

Beta-1,3-glucan 10.0% by weight

10.0 wt% beeswax

5.0% by weight of polysorbate 60

PEG 60 hydrogenated castor oil 2.0% by weight

0.5% by weight of sorbitansquioleate

Vaseline 5.0% by weight

Liquid paraffin 10.0% by weight

5.0% by weight of squalane

Shea butter 3.0% by weight

Caprylic/Capric Triglyceride 5.0% by weight

Glycerin 10.0% by weight

10.2% by weight of propylene glycol

0.2% by weight of triethanolamine

0.05% by weight of preservative

0.05% by weight of pigment

Perfume 0.05% by weight

Purified water to 100% by weight

3. Preparation of drugs for topical administration (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 the compound of formula 1

Beta-1,3-glucan 10.0% by weight

1.5% by weight of polyacrylic acid (Carbopol 940)

5.0% by weight of isopropanol

25.0% by weight of hexylene glycol

1.7% by weight of triethanolamine

Deionized water to 100% by weight

4. Preparation of drugs (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 the compound of formula 1

3.0% by weight of beta-1,3-glucan

Hexylene glycol 20.0% by weight

0.7% by weight of diethylamine

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)

2.5% by weight viscous paraffin oil

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

Polyethylene glycol 400 3.0% by weight

Deionized water to 100% by weight

Formulation example 4: manufacture of food

Foods containing the compound of Formula 1 of the present invention were prepared as follows.

1. Manufacture of flour food

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

2. Manufacture 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 Seonsik

Brown rice, barley, glutinous rice, and adlay were gelatinized and dried by a known method, and then roasted, 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 roasted, and then prepared into a powder having a particle size of 60 mesh with a grinder. The dried product obtained by concentrating the compound of Formula 1 under reduced pressure in a vacuum concentrator, spraying, and drying with a hot air dryer was pulverized with a grinder to a particle size of 60 mesh to obtain a dry powder.

The grains, seeds, and dry powder of the compound of Formula 1 were mixed in the following ratio based on 100 parts by weight of the mixed powder.

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

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

A compound of formula 1 (0.1 parts by weight),

Ganoderma lucidum (0.5 parts by weight),

Rehmannia (0.5 Parts by weight )

Formulation example 5: preparation of beverages

1. Manufacture of health drinks

0.1 mg of the compound of formula 1

Citric acid 1000 mg

100 g oligosaccharides

2 g of plum concentrate

1 g taurine

Purified water By total 900 mL

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

The composition ratio is composed of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences, such as the class of demand, the country of demand, and the purpose of use.

2. Manufacture of vegetable juice

Vegetable juice for health promotion was prepared by adding 1 g of the compound of Formula 1 of the present invention to 1,000 mL of tomato or carrot juice.

3. Manufacture of fruit juice

Fruit juice for health promotion was prepared by adding 1 g of the compound of Formula 1 to 1,000 mL of apple or grape juice.

Claims (4)

delete delete A pharmaceutical composition for skin whitening comprising the synthesized compound of Formula 1 as an active ingredient:
[Formula 1]

A cosmetic composition for skin whitening comprising the synthesized compound of Formula 1 as an active ingredient:
[Formula 1]