KR20040073459A - Melanogenesis inhibitors and whitening agents comprising ergosterol derivatives and compositions containing ergosterol derivatives - Google Patents

Abstract

An object of the present invention is to provide a substance which is effective for the prevention, improvement and treatment of pigmentation of skin such as whitening of sunburned skin after ultraviolet irradiation, blotch, freckles and blemishes caused by sunburn, and a composition containing the same. do.

Means employed to solve the problem are melanin production inhibitors and whitening agents made of ergosterol derivatives. Moreover, it is a melanin production inhibitor and a whitening agent containing the said ergosterol derivative. Moreover, it is a composition for melanin production suppression and the whitening composition containing the said ergosterol derivative. Moreover, it is a cosmetics, a medicine, a skin external preparation, a melanin suppression food, and a whitening food containing the said ergosterol derivative. Moreover, it is the said composition containing a whitening agent component other than the said ergosterol derivative and the said ergosterol derivative, cosmetics, medicine, external skin agent, melanin production inhibitory food, and whitening food.

According to the present invention, compositions such as cosmetics, medicines, external skin preparations and foods having a novel melanin production inhibitor, a whitening agent and a melanin production inhibitory action and a whitening action are obtained.

Description

MELANOGENESIS INHIBITORS AND WHITENING AGENTS COMPRISING ERGOSTEROL DERIVATIVES AND COMPOSITIONS CONTAINING ERGOSTEROL DERIVATIVES}

Pigmentation of skin such as blotch, freckles, and blemishes caused by the sun occurs with age, and it is difficult to increase or disappear with age, which is a problem for middle-aged and elderly people. Although the mechanism for the development of these pigmentation is not clear yet, melanin pigment is produced in melanogenesis granules called melanosomes in melanocytes present in epidermal cells by burning in the sun by sunlight (especially ultraviolet rays). It is thought that the resulting melanin pigment is caused by diffusion into adjacent cells.

There is a strong demand for development of a substance capable of recovering such pigmentation to a normal skin color, and many substances have been commercialized. For example, L-ascorbic acid, kojic acid, hydroquinone, and the like are known.

However, L-ascorbic acid has difficulty in stability, and kojic acid is once recognized for its effect, but its effect is weak. On the other hand, although hydroquinone is once recognized for its effects, it has irritation and allergy, there is a problem in safety, and there is a problem in blending as a drug. Therefore, it is a present situation that the substance which has sufficient pigmentation prevention and improvement effect is not known yet.

Although the compound according to the present invention is a known substance, it has an effect of inhibiting melanin production and is not known to have a skin whitening effect (for example, Koji Ohta, Yasunori Yaoita and Masao Kikuchi), Natural Medicines (Natural Medicines) (Japan), 1996, Vol. 50, No. 5, p. 366.).

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and an object thereof is a substance effective for whitening of sunburned skin after ultraviolet irradiation, and for preventing, improving and treating pigmentation of skin such as sunburn, freckle, freckles, and blemishes. And it is providing the composition containing this.

The present invention relates to melanin production inhibitors and whitening agents consisting of ergosterol derivatives and compositions containing ergosterol derivatives, in particular cosmetics, medicine, external skin preparations and foods. More specifically, the production of melanin in melanocytes can be suppressed to prevent, improve and treat whitening of sunburned skin after ultraviolet irradiation and pigmentation of skin such as sunburn, freckle, freckles and blemishes. Melanogenesis inhibitors, whitening agents, and compositions, in particular cosmetics, medicine, external application for skin, food.

MEANS TO SOLVE THE PROBLEM As a result of earnestly researching in order to solve the said subject, the inventors discovered that the ergosterol derivative which has a specific structure has a strong melanin production inhibitory effect and the whitening effect, and the said subject is solved, and in order to complete this invention, Reached.

That is, this invention is the following formula (1)

It is a melanin production inhibitor and a whitening agent which consist of an ergosterol derivative represented by this.

Moreover, this invention is a melanin production inhibitor and a whitening agent containing the ergosterol derivative represented by said Formula (1).

Moreover, this invention is a composition for inhibiting melanin production and the composition for whitening containing the ergosterol derivative represented by said Formula (1).

Moreover, this invention is the cosmetics containing the ergosterol derivative represented by said Formula (1), This cosmetics may be for melanin production suppression and whitening use.

In addition, the present invention is a medicament containing the ergosterol derivative represented by the formula (1), which may be for inhibiting melanin production and for whitening.

In addition, the present invention is a skin external preparation containing the ergosterol derivative represented by the formula (1), the skin external preparation may be for inhibiting melanin production and for whitening.

In addition, the present invention is a food for inhibiting melanin production and a food for whitening containing the ergosterol derivative represented by the formula (1).

Moreover, in this invention, cosmetics, such as melanin production inhibitory composition, the composition for whitening, the melanin production inhibitory, whitening, etc. containing the ergosterol derivative represented by said Formula (1), for melanin production inhibitory, and whitening In compositions such as pharmaceuticals such as melanin production inhibitors, skin external preparations such as whitening agents, food products for melanin production inhibitors, and foods for whitening, the composition may further contain a whitening agent component other than the ergosterol derivative represented by the formula (1). have. By the combination of the whitening agent component and the ergosterol derivative represented by the formula (1), the melanin production inhibitory effect and the whitening effect can be synergistically improved.

EMBODIMENT OF THE INVENTION Hereinafter, embodiment of this invention is described in detail.

Formula (1) used in the present invention

An ergosterol derivative (hereinafter, simply referred to as an ergosterol derivative) is a known substance and can be isolated from, for example, fungi. All fungi containing an ergosterol derivative can be used for production of an ergosterol derivative, but it is preferable to use, for example, chlorophyllum molybdites. Moreover, it is also possible to prepare by chemical synthesis. Isolation of the ergosterol derivative from the fungus containing the ergosterol derivative can be performed as follows. That is, the extraction solution obtained by pulverizing a partial part of the fruiting body of the fungus or the mycelium, spores, etc., preferably immersed in the extraction solvent or heated to reflux in the extraction solvent, and further removing the insolubles by filtration, centrifugation or the like After concentration, if desired, it is isolated by known separation and purification means.

The solvent used for extraction should just be a solvent normally used for extraction of fungi, plants, etc., for example, alcohols, such as methanol and ethanol, organic solvents, such as acetone and ethyl acetate, and water can be used individually or in combination. . The extraction method may be any conventional method, and in general, the extraction temperature is in the range of 0 to 100 ° C, preferably 40 to 70 ° C, and the extraction time is 1 to 168 hours, preferably 24 to 72 hours. . Isolation from an extraction solution can be performed by chromatography, such as reverse phase chromatography, a gel filtration column chromatography, a liquid chromatography, for example.

Below, the specific example of production of an ergosterol derivative is given.

Purification Example (Isolation from Fungi)

After cultivating the fruiting body of cultivated Oshiro Caracastake, it was immersed in methanol, and extraction was performed at 40 degreeC for 72 hours. Subsequently, the insoluble matters were removed by filtration, and the obtained extraction solution was concentrated, and then purified by reverse phase chromatography. The structure of the purified product was determined by mass spectrometry gas chromatography and NMR. This compound was (22E, 24R) -5a, 8a-epidioxyergosta-6,9,22-triene shown in the said Formula (1), and was a derivative of ergosterol.

The ergosterol derivative of the present invention has a melanin production inhibitory action and a whitening action as described below. Therefore, it can be used as a melanin production inhibitor and a whitening agent. It is also applicable to melanin production inhibitors and whitening agents containing ergosterol derivatives. These melanogenesis inhibitors and whitening agents inhibit melanin production in melanocytes and prevent, improve whitening of sunburned skin after UV irradiation, and pigmentation of skin such as sunburn, freckle, freckles and blemishes. It can be cured. In addition, as a composition, a composition for inhibiting melanin production and a whitening composition containing an ergosterol derivative, and also a cosmetic, medicine, external skin agent and melanin production in the cosmetic, pharmaceutical and food fields containing an ergosterol derivative It can be applied to food for suppression, food for whitening and the like. The cosmetics, medicines, and external skin preparations are preferably used as melanin production inhibitory and whitening agents having the function of the ergosterol derivatives. The composition is a composition for the prevention and treatment of symptoms related to the melanin production inhibitory and whitening.

The composition of the present invention may take the form of oral (content) or parenteral (external). In the case of oral use, the composition of this invention can be prepared, for example in the form of a medicine or food. In the case of parenteral use, it can be prepared in the form of cosmetics, quasi-drugs, medicines, skin external preparations and the like.

In the formulation of the ergosterol derivative to the composition of the present invention, a pure product of the ergosterol derivative is blended, but may be blended in the form of extracts or extracts of plants, fungi and the like containing the ergosterol derivative.

In the present invention, a composition containing the above ergosterol derivative, that is, a composition for inhibiting melanin production, a composition for whitening, a composition for inhibiting melanin production, a cosmetic such as for whitening, a drug for inhibiting melanin production, a whitening agent, and a melanin production Compositions such as skin external preparations for suppression and whitening, foods for inhibiting melanin production, and foods for whitening may further contain a whitening agent component (hereinafter also simply referred to as a whitening component) other than the ergosterol derivative. By using a combination of a sterol derivative and a whitening agent component, the melanin production inhibitory effect and the whitening effect can be synergistically improved.

As said whitening agent component, it does not specifically limit, For example, ascorbic acid, its derivative (s), and salts thereof (for example, ascorbic acid, ascorbic acid 2-glucoside, ascorbic acid phosphate ester magnesium salt, Sodium ascorbate, stearic acid ascorbyl, palmitic acid ascorbyl, dipalmitic acid ascorbyl, tetraisopalmitate ascorbyl, magnesium ascorbate, chitosan ascorbate, ascorbyl methyl silanol pectinate , Ascorbic acid polypeptide, diazelate ascorbyl, ascorbic acid polyphosphate ester, ascorbic acid polyoxyethylene derivative, ricinolic acid ascorbyl, ascorbic acid-2-sulfate ester sodium salt, etc.), hydroquinone and Derivatives and salts thereof (e.g. arbutin), cysteines and derivatives and salts thereof (e.g. L-cysteine, N, N'-diacetyl Cystinedimethyl, etc.), placenta extract, kojic acid and its derivatives, rucinol, errac acid and its derivatives, glucosamine and its derivatives, azeline and its derivatives, hydroxycinnamic acid and its derivatives, glutathione, plant extracts (camomile extract, arnica Extract, Ogon Extract, Cheongung Extract, Mulberry Leaf Extract, Psycho Extract, Windproof Herb Extract, Mugwort Wind Extract, Gymnema Extract, Basswood Extract, Peach Leaf Extract, Red Ginseng Extract, Chew Extract, Touki Extract, Yulmu Rice Extract , Persimmon Leaf Extract, Rhubarb Extract, Peony Extract, Hamamelis Extract, Horse Chestnut Extract, Red Pepper Herb Extract, Clown Extract, Licorice Extract, Capillary Extract, Cinnamon Extract, Mountain Head Extract, Ibukitoranoo (Plygonum bistorta) Linn) extract, red ginseng extract, sanjay extract, lily extract, hop extract, brier extract, etc.), Glab Dean, there may be mentioned Gras Brenner, François Come Tin, isopropyl leak Come Augustine, hydrophobic licorice flavonoid, Ricoh chalcone A, such as placenta extract. 1 type (s) or 2 or more types are arbitrarily selected and can be mix | blended with the whitening agent component. As for the compounding quantity (content) of the whitening agent component at the time of mix | blending the whitening agent component, 0.01 to 10 weight% is preferable in the said composition whole quantity, More preferably, it is 0.01 to 5 weight%. In addition, in the case of an extract, it is the quantity converted into the dry weight which removed the solvent from the extract.

Hereinafter, the specific composition of the present invention containing the ergosterol derivative will be described in more detail by use.

The cosmetics which are the first use of the present invention are, for example, medicaments such as ointments, solutions, creams, emulsions, lotions, lotions, gels, essences (cosmetics), foundations, pack masks, rouge, sticks, bathing agents and the like. Applicable in a wide range including extraneous goods.

In addition, the formulations of cosmetics, solution, solubilizing, emulsifying, powder, powder dispersion, emulsion, gel, ointment, aerosol, water-oil two-layer, water-oil- three-layer, etc. Formulations may be employed.

As for the compounding quantity of the ergosterol derivative to the cosmetics of this invention, 0.001-20 weight% is preferable in cosmetics whole quantity, More preferably, it is 0.01-16 weight%, More preferably, it is 0.1-12 weight%. Most preferred is 1 to 10% by weight. The cosmetic of the present invention has a melanin production inhibitory effect and a whitening effect, and thus is used as a melanin production inhibitory cosmetic and a whitening cosmetic. Moreover, since the cosmetics of this invention can be preferably applied especially to the use as a skin external preparation, it is used as a skin external preparation for melanin production suppression, and a whitening skin external preparation.

The pharmaceutical of the second use of the present invention can be adopted by any method of oral administration, parenteral administration, and can be in the form of a pharmaceutical formulation suitable for each. Examples of pharmaceutical preparations include liquid preparations such as liquids, syrups, injections, inhalants, and emulsions, tablets, powders, granules, capsules, solid preparations such as inhalants, and external skin preparations such as ointments and suppositories. External preparations; and the like.

As for the compounding quantity of the ergosterol derivative in a pharmaceutical agent, 0.001-30 weight% is preferable in the pharmaceutical whole quantity. More preferably, it is 0.01 to 20 weight%, Most preferably, it is 0.1 to 10 weight%. The dosage is appropriately changed based on the age and weight of the patient, the route of application, the progression of the disease, and the treatment being performed in parallel, but is not particularly limited, but is generally about 4 to 10 ml per day, Although administration can be carried out once per day or divided into 2-3 times, it is not limited to this. Since the medicine of this invention has a melanin production inhibitory effect and a whitening effect, it is used as a melanin production inhibitory medicine and a whitening medicine. In addition, the medicament of the present invention can be suitably applied to the use as a skin external preparation, and is therefore used as a skin external preparation for melanin production inhibition and a whitening skin external preparation.

The food of the third use of the present invention is useful as a so-called health functional food, and is widely applicable, for example, to beverages such as sweets and soft drinks, vegetables or fruit products, meat products, seasonings and the like. The form is a powder, a solid product, a solution, or the like. The compounding quantity of an ergosterol derivative in foodstuff can be changed suitably according to the objective, product form, etc. Generally, in the case of solutions, such as a drink, it is 0.001-10 mg in 30 ml, Preferably it is 0.1-5 mg, More preferably, it is 0.15-1 mg. Moreover, in the case of powder solid products, such as a tablet, it is 0.001-10 mg in 300 mg, for example, Preferably it is 0.01-5 mg, More preferably, it is 0.1-1 mg. Since the food of this invention has a melanin production inhibitory effect and a whitening effect, it is used as a melanin production inhibitory food and a whitening food.

In addition to the ergosterol derivatives described above, other ingredients usually used in cosmetics, medicines, external skin preparations, foods, and the like can be blended into the compositions such as cosmetics, medicines, and foods of the present invention within the range not impairing the effects of the present invention.

For example, cosmetics include oils, powders, surfactants, moisturizers, thickeners, lower alcohols, coatings, ultraviolet absorbers, metal ion sequestrants, organic amines, pH adjusters, active ingredients, sugars, preservatives, vitamins, antioxidants, Fragrance, water, etc. are mentioned.

Examples of the oil include jojoba oil, olive oil, avocado oil, castor oil, palm oil, tallow, hydrogenated oil, natural oils and derivatives thereof such as liquid lanolin, lead such as carnauba wax, beeswax and lanolin, liquid paraffin, micro crystalline wax , Hydrocarbons such as squalene and petrolatum, higher fatty acids such as stearic acid, higher alcohols such as cetyl alcohol and stearyl alcohol, glycerin monostearic acid ester, glyceryl triglycerate, glycerin monooleate, myristic acid isopropyl, Esters such as diisostearyl malic acid, glycerin di2-heptyl undecanoate, trimethylolpropane tri-ethylhexyl trimetholpropane, trimethyl tripropanolate, di2-ethylhexyl sebacic acid, peppermint oil, rose oil, sheet Essential oils, such as a normal, dimethyl polysiloxane, and silicone oils, such as a decamethyl cyclopentasiloxane, etc. are mentioned. Although the compounding quantity of an oil component is suitably selected according to the form, formulation, etc. of cosmetics, Usually, it can be 0.1-95 weight% in cosmetics whole quantity.

Examples of the powder include talc, mica, kaolin, silica, galvanized, mica titanium, titanium oxide, iron oxide, nylon powder, and the like.

Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene hardened castor oil, polyoxyethylene sorbitol fatty acid ester, polyoxyalkylene-modified polysiloxane, and the like. Nonionic surfactants, anionic surfactants such as sodium palmitate, cationic surfactants such as stearyltrimethylammonium chloride, and amphoteric surfactants such as betaine, amidebetaine, sulfobetaine, and imidazolinium. Can be.

Examples of the moisturizing agent include glycerin, 1,3-butylene glycol, polyethylene glycol, dipropylene glycol, sorbitol, and the like.

Examples of the thickener include water-soluble polymers such as carboxyvinyl polymer, carboxymethyl cellulose and polyvinyl alcohol, and clay minerals such as bentonite.

Examples of ultraviolet absorbers include paraamino benzoic acid (abbreviated as PABA), glyceryl PABA, ethyldihydroxypropyl PABA, octylmethoxycinnamate, 2-ethoxyethyl-p-methoxycinnamate, 2,4- Dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4-methylbenzophenone, 2-hydroxy-4-methoxy-4-methylbenzophenonesul Fonates, urokanoic acid ethyl esters, 2-phenyl-5-methylbenzokizazole, 4-methoxy-4-t-butyldibenzoylmethane, paramethoxycinnamic acid ethylhexyl, and the like.

As an example of a metal ion blocking agent, tetrasodium edetic acid, citric acid, etc. are mentioned. Examples of the lower alcohols include ethanol and the like. Examples of the organic amines include monoethanolamine, triethanolamine, and the like. As an example of a pH adjuster, buffers, such as a lactic-sodium lactate and a citric acid-sodium citrate, are mentioned.

Examples of the active ingredient include pantothenyl ethyl ether, glycidyl acid salt, and the like. Examples of the vitamins include vitamin E or derivatives thereof. Examples of the antioxidant include tocopherols, dibutylhydroxytoluene, propyl gallate, and the like.

Examples of the saccharides include erythritol, sucrose, hyaluronic acid and the like. As an example of a preservative, ethyl paraben, butyl paraben, sodium benzoate, etc. are mentioned. In addition, it can also select and mix | blend among the components which can be mix | blended with the medicine and food mentioned later.

Next, as a medicament, various additives such as excipients, stabilizers, moisturizers, emulsifiers, absorption accelerators, pH adjusters, surfactants, diluents, and carriers can be blended. Specific examples of these additives include starch, sugars such as lactose, cellulose derivatives such as magnesium sulfate, talc, gelatin, hydroxypropyl cellulose, vegetable oils such as soybean oil, sesame oil, animal oils or synthetic oils, rubber, physiological Water such as saline, alcohols such as ethanol, 1,3-butylene glycol, polyalkylene glycol, and the like. In addition, it can also select and mix | blend among the components which can be mix | blended with the said cosmetics and the foodstuff mentioned later.

Next, as the food, various additives such as sweeteners, acidulants, preservatives, flavoring agents, coloring agents, excipients, stabilizers, moisturizers, emulsifiers, absorption accelerators, pH adjusters, surfactants, diluents, carriers, and the like can be blended. Specific examples of these additives include mushroom extracts, ginseng extracts, ginger extracts, various food extracting solutions such as honey, liquid foods, sugars, cyclic oligosaccharides, reduced maltose, trehalose, lactose, sucrose fatty acid esters, and the like. Can be mentioned. In addition, it can also select and mix | blend among the components which can be mix | blended with the said cosmetics and medicine.

The said composition of this invention can mix 1 type (s) or 2 or more types of the essential component of this invention and the said arbitrary compounding components, and can be prepared in arbitrary forms and formulations by a conventional method.

The present invention will be described in detail with reference to the following Examples. In the compounding quantity of a composition, it is weight% which is not specifically described.

Example 1 Melanin Production Inhibition Effect

[Melanin Production Inhibition in B16 Melanomeric Cells]

Melanogenesis-inhibiting action is a solution obtained by diluting the ergosterol derivative purified in the above purification example using B16 10F7 melanomer cells, which are mouse-derived melanocytes (obtained from Akita Prefecture Food Research Institute). Was evaluated by observing the production of melanin by acting on the cells. B-16 cells were washed with PBS to remove 70% confluent cells, trypsin was removed, and the cells were centrifuged by centrifugation (800 rpm) with the addition of trypsin and an equivalent amount of serum (E-MEM + 10% FBS). , 5min). The cell number was counted and adjusted to about 10 ⁴ cells / ml (E-MEM + 10% FBS). The dilution of the ergosterol derivative solution was injected by dividing 20 μL of sterile PBS into the cell culture plate (for adherent cells), taking 20 μL of the ergosterol derivative solution and diluting it to 4 times (the final concentration in the culture solution was 100 μg / mL to 0.0012 μg / mL). ). As a control, arbutin (final concentration of 140 µg / mL to 0.22 µg / mL in the culture solution) and methanol were similarly diluted.

The cell suspension was divided into 80 μL and injected into the plate containing this diluent. In addition, 72 hours of incubation at 37 ℃, CO ₂ incubator, and observed the melanin production of the by microscopy, cells. In addition, when melanin was produced, the melanin production amount was evaluated by removing the medium, dissolving melanin with 300 μL of 1N and NaOH, and measuring ultraviolet absorption at 470 nm. The value which reacted methanol which was a solvent was made into 100%, the dose change of ergosterol derivative and arbutin was carried out, and the density | concentration which shows melanin synthesis inhibition at the lowest concentration was calculated | required. The results are shown in Table 1.

Arbutin Ergosterol derivatives Minimum inhibitory concentration 0.88 μg / mL 0.5 μg / mL

As can be seen from Table 1, the ergosterol derivative exhibits the same melanogenesis inhibitory effect (whitening effect) as that of melanin production inhibitor Arbutin on melanomer B16 cells, and it is clear that it is useful as a melanin inhibitor and a whitening agent.

In the case of the ergosterol derivative, black micrographs of B-16 cells similar to those of arbutin were also inhibited by micrographs, and it was confirmed that they had excellent melanin production inhibitory effect and whitening effect.

EXAMPLES 2-3 AND COMPARATIVE EXAMPLES 1-2 Measurement of the whitening effect

Ingredient compounding amount (% by weight)

(Alcoholic)

Ethyl alcohol 25.0

Polyoxyethylene (25 mol) cured castor oil 2.0

Appropriate amount of antioxidant

Preservative

Fragrance

Test compound (listed in Table 2) Amount listed in Table 2

(Awards)

Glycerin 5.0

Sodium hexametaphosphate

Ion Exchange Water Residue

(Manufacturing method) After preparing the water phase and alcohol phase in the prescription of the said composition, respectively, both were mixed and solubilized and the composition (lotion) was obtained.

(Test Methods)

Twenty panelists were exposed to four hours of sunlight over two days, from 11 am to 1 pm in summer. The exposed panelist skin was applied to the inner skin of the upper arm, and the composition (lotion) was applied once in the morning and evening for five weeks from five days after the day of exposure to sunlight.

(Assessment Methods)

The test results after use were evaluated according to the following criteria.

(Criteria)

Low effect: Pigmentation became almost inconspicuous.

Effectiveness: Pigmentation became very thin.

Somewhat effective: Pigmentation thinned.

Invalid: no change.

(Judgment)

(Double-circle): More than 16 of the panelists showed more than effective effect.

(Circle): 11-15 of panelists showed more than effective effect.

(Triangle | delta): 6-10 of the panelists showed more than effective effect.

X: Five or less panelists showed more than effective effect.

The evaluation results are shown in Table 2.

Test compound Compounding amount (% by weight) effect Example 2 Ergosterol derivatives 0.2 ○ Example 3 Ergosterol derivatives 1.0 ◎ Comparative Example 1 No addition - × Comparative Example 2 Hydroquinone 1.0 △

As is apparent from Table 2, the composition (lotion) containing the ergosterol derivative prevented the deposition of melanin pigment, inhibiting melanin production and whitening. On the other hand, in the case where the test compound was not added (Comparative Example 1), and hydroquinone was added (Comparative Example 2), no effect was observed.

EXAMPLES 4-7, COMPARATIVE EXAMPLES 3-4 Measurement of the whitening effect

The emulsion component of the following component and compounding quantity was manufactured by the conventional method. In addition, the component names and the compounding quantity of the whitening agent component used together with the compounding quantity of an ergosterol derivative are described in Table 3.

Ingredient compounding amount (% by weight)

Monostearic Acid Polyethyleneglycol 2.0

Glyceryl Monostearate 5.0

Behenyl Alcohol 5.5

Squalane 8.0

Glyceryl trioctanoate 8.0

Glycerin 5.0

Citric Acid 0.1

Sodium Citrate 0.9

Paraben 0.2

Purified water residual

Ergosterol Derivatives Table 3

Whitening Ingredients (Listed in Table 3) Amounts listed in Table 3

(Combination Amount (wt%)) Example Comparative example 4 5 6 7 3 4 Ergosterol derivatives 0.01 0.005 0.005 0.01 - - Ascorbic acid 2-glucoside 0.02 0.01 - - 0.02 - Ascorbic acid phosphate ester magnesium salt - - 0.01 - - 0.02

(Test Methods)

Clearly, 30 healthy ordinary volunteers with blemishes and freckles were divided into 6 groups of 5 people, and the compositions of Examples 4-7 and Comparative Examples 3-4 were applied twice a day in the morning and before bedtime. Then, color photographs were taken after the start of the test and 4 weeks in the state of no makeup, and the state of the color compared with the start of the test was visually determined.

(result)

The determination results are shown in Table 4. Table 4 shows the number of people corresponding to each judgment item by the judgment.

Judgment item Example Comparative example 4 5 6 7 3 4 It was surely pale in comparison with the start date 5 people 4 people 3 people 3 people 0 people 0 people Slightly pale compared to start date 0 some 1 person 2 people 2 people 2 people 2 people No change or thicker 0 people 0 people 0 people 0 people 3 people 3 people

As can be seen from Table 4, by combining the ergosterol derivatives with ascorbic acid 2-glucoside or ascorbic acid phosphate ester magnesium salt, the whitening effect of the ergosterol derivative, that is, the melanin production inhibitory effect is synergistically improved. have.

Hereinafter, the Example of this invention which prepared the composition of various prescriptions by the conventional method is shown. In addition, the melanin production inhibitory effect and the whitening effect were excellent in any Example.

Example 8 Cream

Ingredient compounding amount (% by weight)

Stearic Acid 6.0

Glycerine Monostearic Acid Ester 2.0

Polyoxyethylene (20 mol) sorbitan monostearic acid ester 2.0

1,3-butylene glycol 10.0

Ergosterol Derivatives 5.0

Isopropyl myristate 12.0

Squalene 5.0

Floating Paraffin 3.0

Vitamin E 0.05

Sodium hydrogen sulfite

Preservative

Fragrance

Ion Exchange Water Residue

Example 9 Latex

Ingredient compounding amount (% by weight)

Stearyl Alcohol 2.0

Squalene 5.0

Liquid Lanolin 3.0

Trioctanoic acid trimetholpropane 2.0

Glyceryl trioctanoate 5.0

Glycerin Monooleate 2.0

Polyoxyethylene (20 mol) sorbitan monooleic acid ester 1.0

Vitamin C 0.1

Preservative

Ergosterol Derivatives 8.0

Paraamino benzoic acid 0.1

Fragrance

Sodium hydrogen sulfite

Glycerin 5.0

Carboxy Vinyl Polymer 0.2

Triethanolamine 1.0

Purified water residual

Example 10 Gel

Ingredient compounding amount (% by weight)

Dipropylene Glycol 10.0

PEG1500 5.0

Carboxy Vinyl Polymer 1.0

Ethyl alcohol 2.0

Polyoxyethylene (50 mol) oleyl ether 2.0

Potassium Hydroxide 0.15

Ergosterol derivative 1.0

Sodium 2-hydroxy-4-methoxybenzophenonesulfonic acid 0.05

Preservative

EDTA, 3Na appropriate amount

Fragrance

Ion Exchange Water Residue

Example 11 Gel

Ingredient compounding amount (% by weight)

Dipropylene Glycol 10.0

PEG1500 5.0

Carboxy Vinyl Polymer 1.0

Ethyl alcohol 2.0

Polyoxyethylene (50 mol) oleyl ether 2.0

Potassium Hydroxide 0.15

Ergosterol derivative 1.0

Ascorbic acid 2-glycoside 0.01

Sodium 2-hydroxy-4-methoxybenzophenonesulfonic acid 0.05

Preservative

EDTA, 3Na appropriate amount

Fragrance

Ion Exchange Water Residue

Example 12 Essence

Ingredient compounding amount (% by weight)

Glycerin 5.0

Dipropylene Glycol 10.0

Ethanol 10.0

Carboxy Vinyl Polymer 0.2

Sodium Hyaluronate 0.5

Potassium Hydroxide 0.1

Polyoxyethylene (20 mol) sorbitan monooleic acid ester 0.5

Polyoxyethylene (20 mol) octyldodecyl ether 1.0

Olive oil 0.15

Vitamin E Acetate 0.1

Ergosterol derivative 3.0

Sodium hydrogen sulfite

Preservative

EDTA, 3Na appropriate amount

Fragrance

Purified water residual

Example 13 Pack

Ingredient compounding amount (% by weight)

Polyvinyl acetate emulsion 15.0

Polyvinyl Alcohol 10.0

Dipropylene Glycol 5.0

Sorbitol 5.0

Tocopherol Acetate 0.2

Olive Oil 1.0

Squalene 3.0

Polyoxyethylene (20 mol) sorbitan monooleic acid ester 1.5

Titanium oxide 5.0

Talc 10.0

Ethanol 7.0

Ergosterol derivative 3.0

Preservative

Fragrance

Purified water residual

Example 14 Cosmetic Water

Ingredient compounding amount (% by weight)

1,3-butylene glycol 6.0

Glycerin 5.0

Sodium Hyaluronate 0.3

Polyoxyethylene (20 mol) sorbitan monostearic acid ester 1.5

Polyoxyethylene (20 mol) octyldodecyl ether 0.5

Ethanol 15.0

Ergosterol Derivatives 4.0

Preservative

Fragrance

Purified water residual

Example 15 Cosmetics

Ingredient compounding amount (% by weight)

1,3-butylene glycol 6.0

Glycerin 5.0

Sodium Hyaluronate 0.3

Polyoxyethylene (20 mol) sorbitan monostearic acid ester 1.5

Polyoxyethylene (20 mol) octyldodecyl ether 0.5

Ethanol 15.0

Ergosterol Derivatives 4.0

Ascorbic Acid 2-Glucoside 0.05

Ascorbic acid-2-sulphate ester sodium salt 0.05

Preservative

Fragrance

Purified water residual

Example 16 Ointment

Ingredient compounding amount (% by weight)

Polyoxyethylene (30 mol) hardened castor oil 2.0

Glyceryl Monostearate 10.0

Squalane 10.0

Vaseline 40.0

Cetanol 6.0

Ergosterol Derivatives 5.0

1,3-butylene glycol 10.0

Ion Exchange Water Residue

Preservative

Fragrance

Example 17 Ointment

Ingredient compounding amount (% by weight)

Polyoxyethylene (30 mol) hardened castor oil 2.0

Glyceryl Monostearate 10.0

Squalane 10.0

Vaseline 40.0

Cetanol 6.0

Ergosterol Derivatives 5.0

Ascorbic acid 2-glycoside 0.003

Camomile Extract (Dry Weight) 0.002

1,3-butylene glycol 10.0

Ion Exchange Water Residue

Preservative

Fragrance

Example 18 Foundation

Ingredient compounding amount (% by weight)

Talc 3.0

Titanium Oxide 5.0

Bengara 0.5

Iron Oxide 1.5

Iron Oxide 0.1

Bentonite 0.5

Polyoxyethylene (20 mol) sorbitan monostearic acid ester 1.0

Triethanolamine 1.0

Glycerin 5.0

Propylene Glycol 5.0

Stearic Acid 2.0

Glycerin Monostearate 10.0

Floating paraffin 10.0

Dimethylpolysiloxane 5.0

Polyoxyalkylene Modified Polysiloxane 3.0

Ergosterol derivative 3.0

Purified water residual

Preservative

Fragrance

Example 19 Health Drink

Ingredient compounding quantity (in 30mL)

Ergosterol derivative 0.085 mg

Ginseng Extract 50mg

Cordyceps Sinensis Extract 100mg

Ginger Extract 300mg

Honey 150mg

Cyclic oligosaccharide 300mg

Sweetener

Appropriate amount of acidulant

Preservative

Fragrance

Water residual

Example 20 Health Drink

Ingredient compounding quantity (in 30mL)

Ergosterol derivative 0.085 mg

Vitamin C 1000mg

Ginseng Extract 50mg

Cordyceps Sinensis Extract 100mg

Ginger Extract 300mg

Honey 150mg

Cyclic oligosaccharide 300mg

Sweetener

Appropriate amount of acidulant

Preservative

Fragrance

Water residual

Example 21 Health Drink

Ingredient compounding quantity (in 30mL)

Ergosterol derivative 0.5mg

Ginseng Extract 50mg

Cordyceps Sinensis Extract 100mg

Ginger Extract 300mg

Honey 150mg

Cyclic oligosaccharide 300mg

Sweetener

Appropriate amount of acidulant

Preservative

Fragrance

Water residual

Example 22 Health Food Tablets

Ingredient compounding amount (in 300mg)

Ergosterol derivative 0.025mg

Reduced maltose 87.8mg

Trehalose 41.2mg

Lactose 16.5mg

Sucrose Fatty Acid Ester 6.2mg

Dextrin 148.275mg

Example 23 Health Food Tablets

Ingredient compounding amount (in 300mg)

Ergosterol derivative 0.025mg

Vitamin C 100mg

Reduced maltose 87.8mg

Trehalose 41.2mg

Lactose 16.5mg

Sucrose Fatty Acid Ester 6.2mg

Dextrin 48.275mg

Example 24 Health Food Tablets

Ingredient compounding amount (in 300mg)

Ergosterol derivative 0.025mg

L-cysteine 40mg

Reduced maltose 87.8mg

Trehalose 41.2mg

Lactose 16.5mg

Sucrose Fatty Acid Ester 6.2mg

Dextrin 108.275mg

Example 25 Health Food Tablets

Ingredient compounding amount (in 300mg)

Ergosterol derivative 0.5mg

Reduced maltose 87.8mg

Trehalose 41.2mg

Lactose 16.5mg

Sucrose Fatty Acid Ester 6.2mg

Dextrin 147.8mg

As described above, according to the present invention, a novel melanin production inhibitor, a whitening agent, and a composition having a melanin production inhibitory effect and a whitening effect are obtained. In addition, it has a melanin production inhibitory effect and a whitening effect, and has an excellent effect on the whitening of sunburned skin after UV irradiation, and the prevention, improvement and treatment of pigmentation of skin such as sunburned mushrooms, freckles, and blemishes. , Medicines, external preparations for skin, foods are obtained. In addition, the composition of the present invention can synergistically improve the melanin production inhibitory effect and the whitening effect by combining a whitening agent component together with an ergosterol derivative.

Claims (18)

Equation (1) below Melanin inhibitor which consists of an ergosterol derivative represented by these. The whitening agent which consists of an ergosterol derivative represented by Formula (1). Melanin production inhibitor containing an ergosterol derivative represented by Formula (1). A whitening agent containing the ergosterol derivative represented by Formula (1). Melanin production suppression composition containing the ergosterol derivative represented by Formula (1). A composition for whitening containing an ergosterol derivative represented by formula (1). Cosmetics containing ergosterol derivative represented by Formula (1). The cosmetic according to claim 7, which is for inhibiting melanin production. The cosmetic according to claim 7, which is for whitening. A medicament containing an ergosterol derivative represented by formula (1). The pharmaceutical according to claim 10, which is for inhibiting melanin production. The medicament according to claim 10, which is for whitening. A skin external preparation containing an ergosterol derivative represented by formula (1). The external preparation for skin according to claim 13, which is for inhibiting melanin production. The external preparation for skin according to claim 13, which is for whitening. A food product for inhibiting melanin production containing an ergosterol derivative represented by formula (1). A whitening food containing an ergosterol derivative represented by Formula (1). The composition, cosmetic, medicine, external skin preparation or food according to any one of claims 5 to 17, further comprising a whitening agent component other than the ergosterol derivative represented by the formula (1).