KR101931978B1 - Composition for enhancing whitening - Google Patents

Abstract

The present invention relates to a whitening composition.
More specifically, lindenenol according to the present invention inhibits the production of melanin to exhibit a whitening effect, and also has no cytotoxicity, and thus can be used as a pharmaceutical or cosmetic composition or as a health food.

Description

Composition for enhancing whitening [

The present invention relates to a whitening composition.

Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known. Such collagen is reduced by aging and photo aging caused by ultraviolet irradiation, and it is known that it is closely related to elasticity of skin. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.

In the prior art, there have been products that incorporate collagen into cosmetics from the skin moisturizing effect of collagen, but these cosmetics apply collagen to the skin surface, and since the collagen, which is a polymer, can not be expected to be moisturized by transdermal absorption, Can not be said.

On the other hand, there have been known effective ingredients exhibiting an effect of promoting collagen synthesis and promoting elasticity. For example, retinoic acid, transforming growth factor (TGF) [non-patent document 1], animal placenta-derived protein [Patent document 1], betulinic acid [Patent document 2], chlorella extract [ Patent Documents 3 and 4] are known as collagen synthesis promoting substances. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and redness when applied to the skin, or have insufficient effect, so that the effect of improving the skin function by promoting the collagen synthesis of the skin can not be expected. Therefore, there is a desperate need to develop a composition that is safe in living body, stable in its effective component, and most effective in improving elasticity, which is more effective than conventional collagen synthesis promoting substances.

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

On the other hand, commonly known whitening ingredients include substances inhibiting the activity of tyrosinase enzymes such as kojic acid and arbutin, hydroquinone, vitamin C (L-Ascorbic acid) There are plant extracts. By inhibiting the synthesis of melanin pigment, they can brighten the skin tone to realize skin whitening, and it is possible to improve skin hypercholesterolemia such as stain or freckles due to ultraviolet rays, hormones or heredity. However, as with the collagen synthesis promoting materials, there is a problem in that when the skin is applied, the use amount is limited due to safety problems such as irritation and redness, or the effect is insignificant, so that a substantial effect can not be expected. Therefore, it is urgently required to develop a whitening ingredient which is safe in the living body, stable in its effective ingredient and, above all, excellent in the ability to inhibit melanin synthesis.

[Prior Art]

[Patent Literature]

Japan Patent No. 8-231370

Japan Patent No. 8-208424

Japan Patent No. 9-40523

Japan Patent No. 10-36283

[Non-Patent Document]

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

Thus, the present inventors confirmed that lindenenol has a whitening effect and completed the present invention.

Accordingly, an object of the present invention is to provide a whitening composition containing lindenenol as an active ingredient.

As means for solving the above problems,

There is provided a pharmaceutical composition for whitening comprising a compound represented by the following formula (1).

[Chemical Formula 1]

As another means for solving the above problems,

There is provided a whitening external preparation for skin comprising the compound of formula (1).

As another means for solving the above problems, the present invention provides a whitening cosmetic composition comprising the compound of formula (1).

As another means for solving the above problems, the present invention provides a health food for whitening comprising the compound of formula (1).

The lindenenol according to the present invention exhibits a whitening effect and is also cytotoxic and can be used in medicines, cosmetics or health food without side effects.

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

In order to exert an excellent effect when the whitening component is applied to the actual skin, it exhibits a highly active skin whitening activity at a low concentration, has excellent ability to permeate and absorb the skin, has a low volatility so as to be able to stay for a sufficient time to exhibit a whitening effect , It is preferable that the active ingredient remains stable on the composition or on the skin, is easy to be formulated into medicines or cosmetics, and is safe for the skin. However, among the components for improving the skin whitening effect, there are not many components that satisfy all of the above characteristics. For example, some skin whitening ingredients have excellent skin whitening activity even at low concentrations in vitro, but they are not able to be absorbed through the skin and applied to actual skin. Other skin whitening ingredients have low hydrophilicity and are difficult to formulate into medicines or cosmetics. In addition, some of the whitening agents may decompose or transform into other compounds when exposed to heat, light, or oxygen, which may have already eliminated the whitening effect prior to application to the skin.

As can be seen in the following examples, lindenenol exhibits excellent effects at low concentrations, and thus can be used as an effective ingredient for medicines, cosmetics or health food for skin whitening.

Accordingly, the present invention provides a pharmaceutical composition for skin whitening comprising a compound represented by the following formula (1), an external preparation for skin or a cosmetic composition or a health food:

[Chemical Formula 1]

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

As a specific example according to the present invention, the present invention provides a pharmaceutical composition for skin whitening comprising the compound of formula (1).

The pharmaceutical composition for skin whitening of the present invention may comprise a pharmaceutically acceptable salt of the compound of formula (1).

The pharmaceutically acceptable salt of the compound of Formula 1 may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid The organic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydrochloric acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, hydrobromic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, , Benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and the inorganic acid includes, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

In addition to the above, additionally saltable forms include, but are not limited to, the salts of gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, Aspartate and the like.

When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, a known skin whitening component may be included. The addition of additional whitening ingredients may further enhance the whitening effect of the compositions of the present invention. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use. In one embodiment of the invention, the composition comprises retinoic acid, TGF, proteins from animal placenta, betulinic acid and chlorella extract, whitening ingredients known in the art, as wrinkle and elasticity improving ingredients known in the art, (Hydroquinone), vitamin C (L-ascorbic acid), derivatives thereof, and various plant extracts, which are effective to inhibit tyrosinase enzyme activity such as kojic acid and arbutin One or more components may be further included. The added skin whitening ingredient may be contained in an amount of 0.0001% by weight to 10% by weight with respect to the weight of the whole composition, and the content range may be set in accordance with requirements such as collagen synthesis promoting activity, skin safety, . ≪ / RTI >

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

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

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

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

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

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

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

The pharmaceutical composition of the present invention can provide a desired whitening effect when an effective amount of the compound of Formula 1 is included. In the present invention, the term "effective amount" means the amount of a compound capable of producing new collagen and exhibiting a whitening effect. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a medicament for dermatological treatment based on wrinkle formation, reduction in elasticity, spots, freckles, and the like, when it is commercialized as a cosmetic product that is routinely applied to skin, The compound of the formula (1) may be contained at a higher concentration than that of the compound of the formula (1). Accordingly, 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) Can be administered 6 times

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

As a specific example according to the present invention, the present invention provides a skin external preparation for skin whitening comprising the compound of formula (1).

When the compound of Formula 1 is provided as an external preparation for skin, it may have a formulation such as, but not limited to, ointments, patches, gels, creams or sprays.

In one embodiment of the present invention, but not limited thereto, the composition may comprise from 0.0001% to 10%, more specifically from 0.001% to 1% by weight of the compound of Formula 1, have. If the composition of the present invention contains less than 0.0001% by weight of the compound of the formula 1, sufficient skin whitening effect can not be expected. If the composition contains more than 10% by weight of the compound of the present invention, an undesired reaction such as allergy or skin safety To prevent this, there is a problem.

When the compound of Formula 1 is used as an external preparation for skin, it may further contain at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickening and gelling agents, softening agents, antioxidants, suspending agents, stabilizers, foaming agents, A preservative, a vitamin, a blocking agent, a wetting agent, a necessary oil, a dye, a pigment, a hydrophilic or lipophilic active agent, a lipid vesicle or a skin external preparation for a skin, such as an active agent, water, ionic or nonionic emulsifier, filler, sequestering agent and chelating agent And may contain adjuvants conventionally used in the field of dermatology, such as any other ingredient commonly used. The components can also be introduced in amounts commonly used in the field of dermatology.

As a specific example according to the present invention, the present invention provides a whitening cosmetic composition comprising the compound of formula (1).

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

In addition, the cosmetic composition may further include auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments or fragrances commonly used in cosmetic compositions, in addition to the compounds of formula (1). For example, it is also possible to use other additives such as fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, In the cosmetology field, such as metal ion sequestrants and chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics And may contain auxiliary agents used.

In the case of a wash-off type cosmetic such as a make-up remover, a detergent, etc., in which the active ingredient remains on the skin in a short period of time when the cosmetic product is commercialized, the compound of formula (1) It will be possible. On the other hand, in the case of leave-on type cosmetics such as lotion, cream, essence and the like in which the active ingredient remains on the skin for a long period of time, a lower concentration of lindenenol than that of the wash- It may be included. In one embodiment of the present invention, but not limited thereto, the composition may comprise from 0.0001% to 10%, more specifically from 0.001% to 1% by weight of the compound of Formula 1, have. When the composition of the present invention contains less than 0.0001 wt% of the compound of the present invention, a sufficient whitening effect can not be expected. When the composition of the present invention is contained in an amount exceeding 10 wt%, undesired reactions such as allergy occur, To prevent this.

The present invention also relates to a skin whitening health food comprising the compound of formula (1).

The term 'health food' as used herein means a food prepared by adding the compound of formula (1) to food materials such as beverage, tea, spice, gum and confectionery, or by encapsulation, powdering or suspension, But it has the advantage that there are no side effects that can occur when a drug is used for a long period of time using a food as a raw material.

Since the health food of the present invention thus obtained can be ingested on a daily basis, a high skin whitening effect can be expected, which is very useful.

When the compound of Chemical Formula 1 is used as a food additive, the compound of Chemical Formula 1 may be added as it is or may be used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). In one embodiment of the present invention, the health food contains 0.0001 wt% to 10 wt%, more specifically 0.001 wt% to 1 wt% of the compound of Formula 1 based on the total composition weight . However, in the case of long-term consumption intended for health and hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range .

There is no particular limitation on the kind of the food. Examples of the food to which the above substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health drink of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Or sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of sweeteners include natural sweeteners such as tau Martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the health drink of the present invention.

In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like.

In addition, the health food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health food of the present invention.

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

< Reference Example  1> (1)  Compound information

Linderene, Lindeneol, Lindenenol, (4R) -4,4a.alpha., 5,5a.alpha., 6.6a.alpha., 6b.beta.-Octahydro-3.beta.- (4R) -3,6bβ-Dimethyl-5-methylene-4,4aa, 5,5aa, 6,6aa, 6b, 7-octahydrocyclopropa [2,3] indeno [5,6- b] furan-4a-ol

CAS No. : 26146-27-0

Origin: Dactylicapnos scandens

Example 1: Whitening effect test

Confirmation of inhibition of melanin formation

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

To evaluate the toxicity of melanoma cells in rats before the experiment, whitening evaluation was performed by selecting a concentration that is not toxic.

The compound of Chemical Formula 1 was added to the culture medium to a final concentration of 0.01 ug / ml, 0.1 ug / ml, 1 ug / ml and 10 ug / ml, and the control group, arbutin, Melanoma cells and cultured for 3 days.

Cells were then trypsinized, detached from the culture, centrifuged, and extracted with melanin. The removed cells were melted with 1 ml of sodium hydroxide solution (1N concentration), boiled for 10 minutes, melanin was dissolved, and the amount of melanin produced by measuring the absorbance at 400 nanometers (nm) was measured using a spectrophotometer.

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

Inhibitory effect of melanin on cell-level sample Melanin production Inhibition rate (%) Control group (no addition) 0.065 ± 0.002 - Control 1: Arbutin (200 mg / ml) 0.033 0.001 49% The compound of Formula 1 (0.01 mg / ml) 0.059 ± 0.003 10% The compound of Formula 1 (0.1 mg / ml) 0.051 0.002 21% The compound of formula (1) (1 mg / ml) 0.036 ± 0.001 44% The compound of formula (1) (10 mg / ml) 0.010 ± 0.001 85%

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

Formulation example  1: Preparation of pharmaceutical preparations

1. Manufacturing of powder

0.001 g of the compound of formula (1)

Lactose 1g

The above components were mixed and packed in airtight bags to prepare powders.

2. Preparation of tablets

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

Stearic acid  Magnesium 2 mg

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

3. Preparation of capsules

0.2 mg of the compound of formula (1)

100 mg of corn starch

100 mg of milk

Stearic acid  Magnesium 2 mg

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

4. Manufacture of rings

0.003 g of the compound of formula (1)

Lactose 1.5 g

Glycerin 1 g

Xylitol  0.5 g

After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.

5. Manufacture of granules

2 mg of the compound of formula (1)

Soybean extract 50 mg

200 mg of glucose

600 mg of starch

After mixing the above components, 100 mg of 30% ethanol was added and dried at 60 캜 to form granules, which were then filled in a capsule.

Formulation example  2: Manufacture of cosmetics

1. Manufacture of softening longevity (skin lotion)

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

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Butylene glycol 2.0 wt%

Propylene glycol 2.0 wt%

Carboxyvinyl polymer 0.1 wt%

0.2% by weight of phage-12 nonylphenyl ether

Polysorbate 80 0.4 wt%

Ethanol 10.0 wt%

0.1% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of nutrition lotion (milk lotion)

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

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

4.0 wt%

Polysorbate 60 1.5 wt%

1.5% by weight of sorbitan sesquioleate

0.5% by weight liquid paraffin

Caprylic / capric triglyceride 5.0 wt%

Glycerin 3.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

Carboxyvinyl polymer 0.1 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Manufacture of nutritional cream

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

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 5.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

4. Manufacture of massage cream

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

0.1% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.8% by weight of sorbitan sesquioleate

Liquid paraffin 40.0 wt%

Squalane 5.0 wt%

Caprylic / capric triglyceride 4.0 wt%

Glycerin 5.0 wt%

3.0% by weight of butylene glycol

3.0% by weight of propylene glycol

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

5. Manufacture of pack

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

0.2% by weight of the compound of formula (1)

Beta-1,3-glucan 1.0 wt%

Polyvinyl alcohol 13.0 wt%

0.2% by weight of sodium carboxymethylcellulose,

Glycerin 5.0 wt%

Allantoin 0.1 wt%

6.0% by weight of ethanol

0.3% by weight of phage-12 nonylphenyl ether

Polysorbate 60 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

Formulation example  3: Topical  Produce

1. Manufacture of gel

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

0.1% by weight of the compound of formula (1)

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

0.05% by weight of sodium ethylenediaminetetraacetate

Glycerin 5.0 wt%

Carboxyvinyl polymer 0.3 wt%

5.0% by weight of ethanol

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

Triethanolamine 0.3 wt%

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

2. Manufacture of ointment

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

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

Wax 10.0 wt%

Polysorbate 60 5.0 wt%

&Lt; tb &gt; &lt; tb &gt; &lt; tb &gt;

0.5% by weight of sorbitan sesquioleate

Vaseline 5.0 wt%

Liquid paraffin 10.0 wt%

Squalane 5.0 wt%

SHARE BUTTER 3.0 wt%

Caprylic / capric triglyceride 5.0 wt%

Glycerin 10.0 wt%

Propylene glycol 10.2 wt%

0.2% by weight triethanolamine

Preservative 0.05 wt%

0.05% by weight of pigment

0.05% by weight fragrance

Purified water to 100%

3. Preparation of topical medicament (gel ointment)

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

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 10.0 wt%

1.5% by weight of polyacrylic acid (Carbopol 940)

5.0% by weight of isopropanol

Hexylene glycol 25.0 wt%

Triethanolamine 1.7 wt%

Deionized water to 100%

4. Preparation of topical medicines (patches)

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

0.5% by weight of the compound of formula (1)

Beta-1,3-glucan 3.0 wt%

Hexylene glycol 20.0 wt%

Diethylamine 0.7 wt%

1.0% by weight of polyacrylic acid (Carbopol 934P)

0.1% by weight of sodium sulfite

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

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

Viscous paraffin oil 2.5 wt%

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

Polyethylene glycol 400 3.0 wt%

Deionized water to 100%

Formulation example  4: Manufacturing of food

Foods containing the compound of formula (I) of the present invention were prepared as follows.

1. Manufacture of Flour Food

0.05 to 1.0 part by weight of the compound of Formula 1 was added to wheat flour, and a bread, a cake, a cookie, a cracker and a noodle were prepared using the mixture to prepare a health food.

2. Manufacture of dairy products

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

3. Manufacturing of wire

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer. The compound of Formula 1 was concentrated under reduced pressure in a vacuum concentrator, sprayed, and dried with a hot-air drier, and the resulting dried product was pulverized to a size of 60 mesh with a pulverizer to obtain a dried powder.

The grains, seeds, and dry powder of the compound of formula (1) prepared above were blended in the following proportions relative to 100 parts by weight of the mixed powder.

(30 parts by weight of brown rice, 15 parts by weight of yulmu, 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)

(1) (0.1 part by weight),

(0.5 part by weight),

Rhubarb (0.5 Weight portion )

Formulation example  5: Manufacture of beverages

1. Manufacture of health drinks

0.1 mg of the compound of formula (1)

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water  All 900 mL

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

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

2. Manufacture of vegetable juice

1 g of the compound of formula (I) of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice for health promotion.

3. Manufacture of fruit juice

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

Claims (10)

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

The method according to claim 1,
Wherein the compound represented by Formula 1 is contained in an amount of 0.0001 to 10% by weight based on the total weight of the composition.
An external preparation for whitening skin comprising a compound represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

The method according to claim 3,
Wherein the external preparation is a formulation of ointment, patch, gel, cream or spray.
The method according to claim 3,
Wherein the compound represented by Formula 1 is contained in an amount of 0.0001 to 10% by weight based on the total amount of the external preparation for skin.
A cosmetic composition for whitening comprising a compound represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

The method of claim 6,
Wherein the cosmetic composition is a formulation of a lotion, essence, lotion, cream, pack, gel, powder, foundation or detergent.
The method of claim 6,
Wherein the compound represented by the following formula (1) is contained in an amount of 0.0001 to 10% by weight relative to the total composition.
A whitening health functional food comprising a compound represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

The method of claim 9,
Wherein the compound represented by the following general formula (1) is contained in an amount of 0.0001 to 10% by weight relative to the total health functional food.