KR102248956B1 - Composition for skin cell anti-inflammation or skin whitening - Google Patents

Abstract

The present invention relates to a composition for anti-inflammatory and skin whitening. Stevenleaf according to the present invention can be used as a pharmaceutical composition or a cosmetic composition by inhibiting the production of NO in the skin to exhibit an anti-inflammatory effect and a whitening effect by inhibiting melanin synthesis.

Description

Composition for skin cell anti-inflammation or skin whitening}

The present invention relates to a composition for anti-inflammatory and 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, and 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 and lukotriene, which are inflammatory mediators 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, indomethacin, etc. as non-steroids, and prednisolone as a steroidal system , Dexamethasone, and the like. In addition, allantoin, azene, hydrocortisone, etc. are known to have anti-inflammatory effects, but these substances are limited in use due to safety issues on the skin, or the effect is insignificant, so the effect of substantially reducing inflammation cannot be expected. There is this.

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 are plant extracts. 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 for the development of a component that is safe for the living body, has a stable active ingredient, and, above all, has an effect superior to a substance having anti-inflammatory and whitening effects.

Accordingly, the present inventors confirmed that Stevenleaf has an anti-inflammatory effect by inhibiting NO production in the skin, and exhibits a whitening effect by inhibiting melanin synthesis, and completed the present invention.

Accordingly, an object of the present invention is to provide an anti-inflammatory and 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 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 problem, the present invention

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

[Formula 1]

Stevenleaf according to the present invention has excellent anti-inflammatory effect by inhibiting NO generation involved in the inflammatory reaction of the skin, and exhibits a whitening effect by inhibiting melanin synthesis, so that it can be used in medicines and cosmetics.

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

In order to exert excellent effects when the anti-inflammatory and whitening ingredients are actually applied to the skin, they exhibit high-activity anti-inflammatory and whitening activity at low concentrations, have excellent ability to penetrate and absorb the skin, and are sufficient to exhibit anti-inflammatory and whitening effects. It is preferable that the volatility is low so that it can stay for a period of time, the active ingredient is stably maintained on the composition or the skin, it is easy to formulate into a medicine or cosmetics, and is safe for the skin. However, among known components, components that satisfy all of the above properties are not common. For example, some anti-inflammatory and whitening ingredients are excellent in anti-inflammatory and 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 and whitening ingredients may be decomposed or transformed into other compounds when exposed to heat, light, or oxygen, and their effect may disappear prior to application to the skin.

As can be seen in the following examples, Stevenleaf exhibits remarkably excellent anti-inflammatory and whitening effects at low concentrations, so it can be used as an active ingredient such as pharmaceuticals and cosmetics for anti-inflammatory and skin whitening.

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

[Formula 1]

The compound of Formula 1 may be used separately or synthesized from a plant extract, or a commercially available compound may be used.

The pharmaceutical composition for anti-inflammatory and skin whitening of the present invention may contain the compound of Formula 1 in the form of a glycoside, a non-glycoside, or a pharmaceutically acceptable salt of the compound of Formula 1.

The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid. , 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 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 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, 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 and skin whitening ingredients. If additional anti-inflammatory and skin whitening ingredients are included, the anti-inflammatory and skin whitening effects 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 and arbutin, hydroquinone, vitamin-C (L-Ascorbic acid) and 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% to 10% by weight based on the total weight of the composition, and the content range may be adjusted according to requirements such as skin safety and ease of formulation of the compound of Formula 1 .

In addition, the pharmaceutical composition for anti-inflammatory and 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, salt, and polysorbate.

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

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these 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 or lactose, gelatin, and the like.

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, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as humectants, sweeteners, fragrances, and preservatives may be included. .

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

In the present invention, the term "anti-inflammatory effect" refers to suppressing inflammation, and the inflammation is one of the defense responses of living tissues against a certain stimulus, and causes three kinds of tissue deterioration, circulatory disorders and effusion, and tissue proliferation. Refers to a complex lesion. 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 triggered by radiation, chemicals, burns, acid burns, bullous skin disease, lichen shape type disease, itching due to allergies, seborrheic eczema, rose acne, Pemphigus vulgaris, polymorphic exudative erythema, nodular erythema, balanitis, vulvitis, inflammatory hair loss such as alopecia areata, cutaneous T-cell lymphoma, and the like, but are not limited thereto.

In the present invention, "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 inheritance.

The pharmaceutical composition of the present invention can provide a desirable 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" means an amount of a compound capable of suppressing inflammation of the skin 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, and 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.

The pharmaceutical composition of the present invention may be used alone or in combination with other methods to achieve the intended use.

The present invention can also be provided in a formulation of an anti-inflammatory and 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, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, Commonly used in ionic or nonionic emulsifiers, fillers, sequestering 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. 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 in a formulation for external application for skin, it is not limited thereto, but may have 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 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 prepared by containing the compound of Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation and a solubilized formulation. For example, a lotion such as a flexible lotion or a nutrient lotion, an emulsion such as a facial lotion, a body lotion, a cream such as a nourishing cream, a moisturizing cream, an eye cream, an essence, a cosmetic ointment, a spray, a gel, a pack, a sunscreen, a makeup base, a liquid It may have a formulation such as a foundation such as a type, a solid type, or a spray type, a powder, a cleansing cream, a cleansing lotion, a makeup remover such as a cleansing oil, a cleansing foam, a soap, a body wash, and the like.

In addition, the cosmetic products include fatty substances, organic solvents, solubilizers, thickeners and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water in addition to the compound of Formula 1 , Ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, lipid vesicles or commonly used in cosmetics It may contain adjuvants commonly used in the cosmetic field, such as any other ingredients.

The compound of Formula 1 is a relatively high concentration of the compound of Formula 1 in the case of wash-off type cosmetics such as makeup removers and detergents 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, and essences, in which the active ingredient stays on the skin for a long period of time, a lower concentration of the compound of Formula 1 is used compared to the wash-off type cosmetics. It would be okay to include 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 and whitening effects cannot be expected, and when it contains more than 10% by weight, unwanted reactions such as allergy or skin There may be a safety problem, so this is to prevent this.

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: Stephen Lip ( Stevenleaf ) Substance information

[Formula 1]

(2R,3R,4S,5S,6R)-2-[[(10R,12S,14R)-17-[(2R)-2-[[(2S,3R,4R,5S,6R)-6-[ [(2S,3R,4S,5R)-4,5-dihydroxy-3-methoxy-2-oxanyl]oxymethyl]-3,4,5-trihydroxy-2-oxanyl]oxy]-6-methylhept-5-en -2-yl]-12-hydroxy-4,4,10,14-tetramethyl-1,2,3,5,6,7,8,9,11,12,13,15,16,17-tetrad

CAS No.: 80321-63-7

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

Example 1: Whitening effect - check the effect of reducing the total amount of melanin

The compound of Formula 1 was added to the culture medium 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, toxicity was evaluated for the melanoma cells of mice, and a non-toxic concentration was selected to perform whitening evaluation.

The compound of formula 1 was tested in the culture medium at a final concentration of 1 ppm, 2.5 ppm, 5 ppm, 10 ppm, and 20 ppm, and arbutin, a control, was added to the medium to be 200 ppm, respectively, to B-16 melanoma cells. Treated and 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) 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 amount of melanin production relative to the control group was calculated as an inhibition rate (%), and the results are summarized in Table 1. Also, the experiment was repeated 3 times.

The effect of reducing the total amount of melanin at the cellular level according to the concentration sample Melanin production (Abs.) Inhibition rate (%) Control (no addition) 0.234 - Control 1: Arbutin (200 ppm) 0.156 33.3 Compound of Formula 1 (20 ppm) 0.078 66.7 Compound of Formula 1 (10 ppm) 0.131 44 Compound of Formula 1 (5 ppm) 0.142 39.3

As can be seen from the results of Table 1, it can be seen that the compound of Formula 1 has a superior ability to inhibit melanin production with respect to the melanoma cells of cultured mice when compared to Arbutin, which is a previously known whitening material.

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

In order to confirm the anti-inflammatory effect and skin trouble alleviation effect of the compound of Formula 1, nitric oxide (NO) formation inhibition was conducted by the GRIESS method using 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 ^{3×10 5 cells in each well, and cultured for 24 hours.} Subsequently, the compound of Formula 1 was diluted to the concentration shown in Table 2 and replaced with a cell medium containing. 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 an stimulating source and incubated for 24 hours. I did. 100 μl of the supernatant was taken and transferred to a 96-well plate, and 100 μl of a grease 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 Compound 1, and the result Are shown in Table 2 below.

NO production inhibitory effect sample NO production inhibition rate (%) L-NMMA (positive control) 44.33 Compound of Formula 1 (0.001 %) 17.21 Compound of Formula 1 (0.01 %) 25.42 Compound of formula 1 (0.1%) 29.54 Compound of formula 1 (1%) 35.27

As can be seen from Table 2, the compound of Formula 1 has similar activity when compared to L-NMMA, a representative anti-inflammatory drug substance, and exhibits excellent activity as a natural substance, so that the anti-inflammatory effect is assisted in whitening or wrinkle improvement. It can be expected to have a synergistic effect by acting as an effective role.

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

Claims (4)

delete delete A pharmaceutical composition for skin whitening comprising a compound represented by the following Formula 1 as an active ingredient:
[Formula 1]

A cosmetic composition for skin whitening comprising a compound represented by the following Formula 1 as an active ingredient:
[Formula 1]