WO2017196049A1 - Externally applied composition for skin whitening, containing extract of fermented wheat germ product as active ingredient - Google Patents

Abstract

The present application relates to an externally applied composition for skin whitening or to a composition, externally applied to the skin, for preventing, alleviating, or treating skin hyperpigmentation disorders, both compositions containing, as an active ingredient, a fermented wheat germ product or an extract thereof.

Description

External preparation composition for skin whitening containing extract of wheat germ fermentation as an active ingredient

The present application relates to an external preparation composition for skin whitening containing an extract of wheat germ fermentation as an active ingredient.

Skin exposed to ultraviolet rays protects the body from ultraviolet rays by synthesizing melanin pigment in melanocytes. Melanin pigment, whose synthesis is temporarily increased by stimulation of ultraviolet rays, migrates and accumulates in the surrounding keratinocytes. As the synthesis and accumulation of melanin pigment increases, pigmentation occurs on the skin and becomes black. In order to inhibit such pigmentation, a method of inhibiting the synthesis or inhibiting the synthesis of tyrosinase, a melanogenesis enzyme, has been proposed to reduce the production of melanin.

Known whitening ingredients include arbutin, kojic acid, azelaic acid, aloesin, 4-butylresosocin, resveratrol, ceramide, sphingosine-1-phosphate, sph, which inhibit tyrosinase enzyme activity. Substances such as polyphosphorylcholine, hydroquinone (Korean Patent Publication No. 2016-0014271), vitamin-C (L-ascorbic acid) and derivatives thereof, and extracts derived from green tea leaves (Korean Patent Publication No. 2015-0025540) Etc.

However, when applied to the skin, there is a problem in that the amount of usage is limited due to problems of skin safety, such as irritation and redness, or the practical effect is insignificant. In particular, hydroquinone also follows the problem of safety due to the compounds added to counteract its irritation.

Therefore, there is a demand for the development of a whitening component that is safer in vivo and superior in ability to inhibit melanin synthesis than existing materials.

The present inventors earnestly endeavored to develop an excellent external composition for skin whitening, the extract of wheat germ fermented product was confirmed that the excellent effect of inhibiting melanin synthesis while excellent safety and whitening effect was completed.

It is an object of the present invention to provide a cosmetic composition for skin whitening containing wheat germ fermentation or extracts thereof.

Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of dermatological pigmentation disease containing wheat germ fermentation or extracts thereof.

It is yet another object of the present invention to provide a method for preventing or treating a dermatological pigmentation disease comprising administering a wheat germ fermentation product or an extract thereof, or a pharmaceutical composition of the present invention to a subject in need thereof.

Still another object of the present application is to provide a quasi-drug composition for skin whitening containing a wheat germ fermentation product or an extract thereof.

Another object of the present disclosure is to provide a method for whitening skin, comprising administering a wheat germ fermentation product or extract thereof, or a composition of the present invention to a subject in need thereof.

The composition of the present invention is not only toxic and stable, but also has the effect of inhibiting tyrosinase activity, inhibiting melanin synthesis, and improving pigmentation, thereby preventing, improving or preventing external use of skin whitening or hyperpigmentation diseases. It can be used as a therapeutic external preparation.

Figure 1 is a graph showing the results of the cytotoxicity test for the melan-a (Melan-a) cells of the extract (expressed as CJ) wheat germ fermentation according to an embodiment of the present application.

Figure 2 is a graph showing the degree of inhibition of tyrosinase activity of the extract (CJ) wheat germ fermentation according to an embodiment of the present application.

Figure 3 is a graph showing the degree of inhibition of melanin synthesis of the extract (CJ) of wheat germ fermentation according to an embodiment of the present application.

Figure 4 is a graph comparing the visual evaluation change of the skin color according to the use of the product of the extract containing wheat germ fermentation product (CJD cream) and the negative control product (control cream) according to an embodiment of the present application.

Figure 5 is a graph comparing the increase and decrease rate of the skin melanin index (M.I.) according to the use of the product of the extract containing wheat germ fermentation product (CJD cream) and the negative control product (control cream) according to an embodiment of the present application.

As one aspect for achieving the object of the present application, the present application provides a cosmetic composition for skin whitening comprising wheat germ fermentation or extracts thereof.

As used herein, the term "wheat germ" means the seed of wheat. It is a nutritious embryo of wheat kernels (wheat kernel) that is removed from the process of processing whole wheat flour, which takes about 2 to 3% of the whole wheat grain. Wheat germ is known to be rich in vitamin E (tocopherol), which is known to be an antioxidant vitamin to date, and recent studies have shown that natural substances extracted from fermented wheat germ restore the damaged immune function of the human body. However, there is no known skin whitening effect of wheat germ.

Wheat germs herein may include, but are not limited to, dried, milled, concentrate and mixtures thereof.

As used herein, the term "fermentation" refers to any activity or process, including enzymatic or metabolic degradation of organic material with microorganisms.

As used herein, the term "wheat embryo fermentation" means the result of enzymatic or metabolic degradation of wheat germ with a microorganism.

The fermentation product of wheat germ may be obtained by inoculating microorganisms into wheat germ or a medium including the same and then culturing the same. Specifically, the microorganism may be at least one selected from the group consisting of yeast, lactic acid bacteria, bacteria and fungi.

The yeast is for example Saccharomyces cerevisiae ( Saccharomyces cerevisiae ), Saccharomyces ellipsoideus ( S. ellipsoideus ), Saccharomyces correaus ( S. coreanus ), Saccharomyces Carlsbergensis ( S. carlsbergensis), Saccharomyces access to my Paz Astoria Augustine (S. pastorianus), Saccharomyces access to my lactis (S. lactis), Saccharomyces access to my ruksi (S. rouxii), to access Shijo Saccharomyces pombe Mai (Schizosaccharomyces pombe ), Zygosaccharomyces major , Hansenula anomala , Brettanomyces bruxellensis , B. custersianus , Decera cyano do (Dekkera anomala), Streptomyces up balk our jeneseu (Streptomyces olivochromogenes), or Streptomyces draw three-house (S. griseus), but the purpose can be skin whitening effect of the present application A no longer be limited, which can be represented. For example, the yeast may be Saccharomyces cerevisiae.

The lactic acid bacteria are for example Bifidobacterium sp.), Lactobacillus sp., Lactococcus sp., Pediococcus sp., Streptococcus. sp, or Leuconostoc sp.) may be a microorganism, but the present invention is not limited thereto so long as it can exhibit a skin whitening effect. For example, the lactic acid bacteria are Bifidobacterium bifidum ( B. bifidum ), Bifidobacterium breve ( B. breve ), Bifidobacterium long gum ( B. longum ), Bifidobacterium animalis ( B. animalis ), Bifidobacterium lactis ( B. lactis ), Lactobacillus ashdophyllus ( L. acidophilus ), Lactobacillus casei ( L. casei ), Lactobacillus gaseri ( L. gasseri ), Lactobacillus del brew L. delbrueckii spp., L. bulgaricus , L. helveticus , L. helveticus , L. fermentum , L. paracasei L. paracasei , Lactobacillus tarum plan (L. plantarum), Lactobacillus flow Terry (L. reuteri), Lactobacillus Caucasus ramno (L. rhamnosus), raised bariwooseu Lactobacillus (L. salivarius), Lactococcus lactis (L. lactis) , Peddie Oh Celebi jiae Caucus (P. cerevisiae), Peddie Oh Caucus kids CD Rock City (P. acidilactici), Streptococcus lactis (S. lactis), Streptococcus thermostat Phillies (S. thermophiles), Streptococcus Crescent Morris (S. cremoris), or the current mail center Stock Pocono Roy Rhodes (L. mesenteroides) Can be. Herein, lactic acid bacteria may be used in the same sense as lactic acid bacteria.

In addition, the fungus used in the fermentation may include, but is not limited to, mushrooms, for example, shiitake mushrooms, oyster mushrooms, enoki mushrooms, matsutake mushrooms, mushroom mushrooms, tree mushrooms, roe deer mushrooms, It may be a Ganoderma lucidum mushroom, or a situation mushroom, but is not limited thereto as long as it may exhibit a skin lightening effect for the purpose of the present application.

The inoculation amount, the culture temperature, the culture humidity, and the incubation time of the microorganisms used to prepare the wheat germ fermentation product of the present application may be appropriately selected by those skilled in the art in consideration of the types of microorganisms used for the fermentation. As a non-limiting example, the culture of the present application may be carried out for 12 to 60 hours at a temperature of 20 ℃ to 40 ℃. Specifically, the culture of the present application is 25 ℃ to 35 ℃, 28 ℃ to 32 ℃ or 30 ℃ temperature and / or 12 hours to 50 hours, 20 hours to 50 hours, 30 hours to 50 hours, 35 hours to 45 hours, 38 It can be carried out for hours to 42 hours or 40 hours.

As used herein, the term “extract of wheat germ fermentation” refers to a material that has removed microorganisms from wheat germ fermentation.

Removal herein may include any method as long as it is a method for removing microorganisms (eg, yeast cells) contained in the microbial fermentation known in the art. Specifically, the extract of the wheat germ fermentation of the present application may be a supernatant obtained by centrifuging the wheat germ fermentation of the present application. More specifically, the centrifugation is revolution per minute of 6,000 rpm to 10,000 rpm, 7000 rpm to 9000 rpm, 7500 rpm to 8500 rpm, 7800 rpm to 8200 rpm or 8000 rpm and / or 5 minutes to 120 minutes. Minutes, 5 minutes to 90 minutes, 5 minutes to 60 minutes, 5 minutes to 40 minutes, 5 minutes to 30 minutes, 10 minutes to 120 minutes, 10 minutes to 90 minutes, 10 minutes to 60 minutes, 10 minutes to 40 minutes, 10 minutes to 30 minutes, 15 minutes to 120 minutes, 15 minutes to 90 minutes, 15 minutes to 60 minutes, 15 minutes to 40 minutes, 15 minutes to 30 minutes, 15 minutes to 25 minutes or 20 minutes.

Extracts of wheat germ fermentation herein include extracts of all formulations that can be formed using extracts such as extracts of the wheat germ fermentation herein and their dilutions, concentrates, dry matters, crudes, tablets or mixtures thereof. Specifically, the extract of the wheat germ fermentation of the present application may be a dry matter, more specifically, may be a freeze-dried product.

In addition, the extract of the wheat germ fermentation of the present application can be obtained from the wheat germ fermentation by any method as long as it has a skin whitening effect or a prevention, improvement or treatment effect of skin hyperpigmentation disease, non-limiting example wheat germ fermentation Immersion of water in a solvent, cold extraction extracted at room temperature of 10 to 25 ℃, heating extraction to be heated to 40 to 100 ℃ extraction, ultrasonic extraction by applying ultrasonic waves, reflux extraction method using a reflux condenser Can be. These methods may be performed alone or in combination of two or more methods.

The type of extraction solvent used for the extraction herein is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent of the present application from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane, ethyl acetate, chloroform, dichloromethane and mixed solvents thereof A solvent selected may be mentioned, and specifically, the extraction solvent of the present application may be hot water.

The extract herein may be one comprising a fraction thereof. As used herein, the term "fraction" refers to the result obtained by performing fractionation to separate a particular component or group of components from a mixture comprising a variety of different components.

The fractionation method for obtaining a fraction of the present application is not particularly limited and may be performed according to a method conventionally used in the art. Solvent fractionation by treatment of various solvents, ultrafiltration fractionation through passage of ultrafiltration membranes with constant molecular weight cut-off values, and various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) Chromatography), and combinations thereof.

The type of fractional solvent used to obtain the fractions herein is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of fractional solvents herein include polar solvents such as water, alcohols; And nonpolar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of one or more.

Wheat germ fermentation herein or the extract thereof may be used in 0.001% to 10% by weight relative to the total weight of the composition of the present application, specifically 0.01% to 7% by weight, 0.01% to 5% by weight, 0.01% by weight % To 3%, 0.01% to 2%, 0.01% to 1%, 0.05% to 10%, 0.05% to 7%, 0.05% to 5%, 0.05% to 3 wt%, 0.05 wt% to 2 wt%, 0.05 wt% to 1 wt%, 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt% %, 0.1 wt% to 2 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%, 0.8 wt% to 10 wt%, 0.8 wt% to 7 wt%, 0.8 wt% to 5 wt%, 0.8 wt% to 3 in %, 0.8 wt% to 2 wt%, 0.8 wt% may be included as to 1% or 1% by weight.

Wheat germ fermentation herein or extract thereof may be included in the composition of the present application from 0.1 μg / ml to 100 μg / ml. Specifically, the wheat germ fermentation product or the extract thereof may be 0.1 μg / ml to 70 μg / ml, 0.1 μg / ml to 50 μg / ml, 0.5 μg / ml to 70 μg / ml, 0.5 μg / ml To 50 μg / ml, 0.8 μg / ml to 70 μg / ml, 0.8 μg / ml to 50 μg / ml, 1 μg / ml to 70 μg / ml, 1 μg / ml to 50 μg / ml, 5 μg / ml To 70 μg / ml, 5 μg / ml to 50 μg / ml, 8 μg / ml to 70 μg / ml, 8 μg / ml to 50 μg / ml, 10 μg / ml to 70 μg / ml or 10 μg / ml To 50 μg / ml.

According to one embodiment of the present disclosure, the composition of the present disclosure may inhibit tyrosinase activity and / or inhibit melanin synthesis.

The cosmetic compositions herein are in the group consisting of solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, sprays, and packs It may be formulated and provided in the form of choice.

Cosmetic compositions herein may further comprise a cosmetically acceptable carrier.

The kind of the cosmetically acceptable carrier of the present application is not particularly limited as long as it does not impair the activity and properties of the cosmetic composition of the present application, any carriers commonly used in the art and cosmetically acceptable may be used. Non-limiting examples of such cosmetically acceptable carriers include saline, sterile water, buffered saline, dextrose solution, maltodextrin solution, glycerol and ethanol, and the like. These may be used alone or in combination of two or more thereof. The cosmetically acceptable carrier of the present disclosure may include a non-naturally occuring carrier.

The cosmetically acceptable carriers herein vary depending on the formulation of the cosmetic composition.

When the formulation of the cosmetic composition of the present application is a paste, cream or gel, the carrier component is animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide and the like. May be used, but is not limited thereto.

When the formulation of the cosmetic composition of the present application is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, etc. may be used as the carrier component, and in particular, in the case of a spray, additionally chlorofluoro Propellants such as, but not limited to, hydrohydrocarbons, propane / butane or dimethyl ether.

When the formulation of the cosmetic composition of the present application is a solution or emulsion, a solvent, a solubilizer or an emulsifier may be used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzo Ate, propylene glycol, 1,3-butylglycol oil and the like can be used, and in particular, cottonseed oil, peanut oil, corn seed oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or sorbitan Fatty acid esters may be used, but are not limited thereto.

When the formulation of the cosmetic composition of the present application is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester , Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant may be used, but is not limited thereto.

When the formulation of the cosmetic composition of the present application is a soap, as the carrier component, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, aliphatic alcohols, vegetable oils, glycerol, sugars and the like It may be used, but is not limited thereto.

When the formulation of the cosmetic composition of the present application is a pack, a peel-off pack containing polyvinyl alcohol or the like, a wash-off pack containing pigments such as kaolin, talc, zinc oxide, or titanium dioxide in the general emulsion cosmetic Or mask sheet packs, and the like.

The cosmetic composition of the present application may further include components included in conventional skin external preparation components such as water, surfactants, humectants, lower alcohols, chelating agents, fungicides, antioxidants, preservatives, pigments and flavorings.

As another aspect for achieving the object of the present application, the present application provides a pharmaceutical composition for the prevention or treatment of dermatological pigmentation disease containing wheat germ fermentation or extract thereof.

In the pharmaceutical composition of the present application, all the above-mentioned for wheat germ, wheat germ fermentation and extract thereof is applied. As used herein, the term "dermal hyperpigmentation disease" refers to a disease having an excessive pigmentation on the skin, and specifically, the dermal hyperpigmentation disease may be blemishes, freckles, blemishes or melanoma.

As used herein, the term "prevention" refers to any action by which a composition herein inhibits or delays the occurrence of blemishes, freckles, blemishes or melanoma, etc., which are symptoms of dermatologically pigmented diseases.

As used herein, the term "treatment" means any action that causes the pharmaceutical composition of the present application to improve or benefit from blemishes, freckles, blemishes, or melanoma, etc., which are symptoms of dermatological pigmentation disease.

Herein, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier.

As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier or diluent that does not irritate an organism and does not inhibit the prophylactic or therapeutic activity and properties of dermal hyperpigmentation disease symptoms of the composition. Acceptable pharmaceutical carriers in compositions formulated as liquid solutions are sterile and physiologically compatible, including saline, sterile water, Ringer's solution, buffered saline, albumin injectable solutions, dextrose solution, maltodextrin solution, glycerol, ethanol And one or more of these components may be used in combination, and other conventional additives such as antioxidants, buffers, bacteriostatic agents may be added as necessary.

In addition, the pharmaceutically acceptable carrier herein may include an unnatural carrier.

The pharmaceutical compositions herein may be administered in single or multiple amounts in pharmaceutically effective amounts.

As used herein, the term “pharmaceutically effective amount” means an amount sufficient to prevent or treat a disease at a reasonable benefit / risk ratio applicable to medical prophylaxis or treatment, and an effective dose level refers to the severity of the disease, the activity of the drug. , Factors including the body weight, health, sex of the patient, sensitivity to the drug of the patient, time of administration of the composition used herein, route of administration and rate of release, duration of treatment, drugs used in combination with or concurrently with the composition of the invention used and others It may be determined according to factors well known in the medical field.

As another aspect to achieve the object of the present application, the present application provides for the prevention or treatment of dermatological hyperpigmentation disease comprising administering wheat germ fermentation, extract thereof, or pharmaceutical composition of the present invention to a subject in need thereof Provide a method.

In the method of preventing or treating dermatologically pigmented disease of the present application, wheat germ, wheat germ fermented product, extract of wheat germ fermentation, and dermatological pigmented disease, prevention and treatment are as described above.

As used herein, the term "administration" means introducing a given substance into an individual in any suitable manner and can be administered via any general route by which a composition herein can reach a target in vivo. The route of administration of the compositions herein is not particularly limited but may be oral or parenteral. Specifically, it can be administered parenterally, and more specifically, it can be applied in a manner that is applied to the skin (ie, transdermal administration). Specifically, the administration of the present application may be performed once to four times, two to three times or twice a day. In addition, the administration herein may be carried out for a period of at least 4 weeks, at least 8 weeks, 4 to 12 weeks or 8 to 12 weeks.

As another aspect to achieve the object of the present application, the present application provides a qualitative composition for skin whitening containing wheat germ fermentation or extracts thereof.

Extracts of wheat germ, wheat germ fermentation, and wheat germ fermentation in the quasi-drug composition of the present application are as described above.

As used herein, the term "quasi drug" refers to articles that are less effective than drugs among those used for the purpose of diagnosing, treating, ameliorating, alleviating, treating, or preventing a disease in humans or animals. According to the quasi-drug product, the drug is used for the purpose of medicine, and it includes a product used for the treatment or prevention of diseases of humans and animals, and a product having a slight or no direct action on the human body.

The quasi-drug composition of the present application may be prepared in a form selected from the group consisting of body cleanser, foam, soap, mask, ointment, cream, lotion, essence and spray, but is not limited thereto.

When the wheat germ fermentation product or its extract is used as an quasi-drug additive, the wheat germ fermentation product or its extract can be added as it is or used together with other quasi-drug or quasi-drug components, and can be appropriately used according to a conventional method. .

As another aspect to achieve the object of the present application, the present application provides a method for whitening skin, comprising administering wheat germ fermentation, extract thereof, or composition of the present invention to a subject in need thereof. .

In the method for whitening the skin of the present application, wheat germ, wheat germ fermentation product, extract of wheat germ fermentation product, composition and administration of the present application are as described above.

Wheat germ fermentation herein, extracts thereof, or compositions herein may be administered to an individual in need thereof in an effective amount.

 The level of effective dose can be determined by one skilled in the art based on conventional common knowledge to the extent that the desired skin lightening effect is exhibited.

Hereinafter, the present application will be described in more detail in the following examples. However, these examples are only to aid the understanding of the present application, and the present application is not limited thereto.

Production Example  One: Wheat germ fermentation  Extract manufacturer

50 g of wheat germ (CJ CheilJedang) and 500 g of water were added to the flask, mixed well, and sterilized at 121 ° C. for 15 minutes and cooled. Then, 5% (2.5 g) of dry yeast [bread yeast (Saccharomyces cerevisiae), Angel Yeast] was inoculated, fermented at 30 ° C. for 40 hours, and then 20 minutes at 8000 rpm. The supernatant was taken by centrifugation. The supernatant was lyophilized and recovered to prepare an extract of wheat germ fermentation.

In this embodiment, the extract of the wheat germ fermentation was named 'CJ'.

Experimental Example 1 : Cell viability assay

Cytotoxicity against extract (CJ) of wheat germ fermentation of Preparation Example 1 was measured in melan-a cells.

Specifically, melan-a cells were dispensed at 5 × 10 ⁴ cells / well in 96-well plates, then 10% fetal bovine serum (FBS), 50 U / ml penicillin, 50 μg / ml streptomycin, 200 nM pobol 12 in RPMI 1640 medium. -Incubated for 24 hours at 37 ℃, 10% C0 ₂ medium with the addition of myristate 13-acetate (phobol 12-myristate 13-acetate, PMA). After incubation for 12 hours after starvation, the fermented wheat germ extract of Experimental Example 1 and the supplement (supplement) RPMI 1640 medium (control) were added to each concentration, and cultured for 24 hours. It was. Then, in order to measure the survival rate of the cells, WST-1 (water-soluble tetrazolium salt-1, Roche) reaction solution was diluted 1/10 in RPMI 1640 medium without additives and treated with 100 μl of each well. After reacting for a time, absorbance was measured at 450 nm. Then, the relative cell viability of the case where the melan-a cells were treated only with RPMI 1640 except for the additive (control), when the extract (CJ) of the wheat germ fermentation product of Preparation Example 1 was treated (test).

As a result, it was confirmed that when treated with 100 μg / ml or less of the extract of wheat germ fermentation, no cytotoxicity was observed (FIG. 1). Therefore, in the following Examples and Experimental Examples, the concentration of the extract of wheat germ fermentation was set to 50 μg / ml or less.

Experimental Example  2: whitening efficacy evaluation

2-1: Tyrosinase ( tyrosinase ) Confirm activity inhibition

220 μl of 0.1 M phosphate buffer solution, 20 μl of HBSS (Hanks' Balanced Salt solution, Sigma-Aldrich) dilution of the extract of the wheat germ fermentation of Preparation Example 1, and 20 μl of mushroom tyrosinase solution (1500 U / mL) After the addition, 40 μl of 1.5 mM tyrosine solution was added to prepare a sample solution. The reaction was carried out at 37 ° C. for 10 to 15 minutes, and the absorbance was measured at 490 nm using an ELISA reader. As the blank sample solution, 0.1M phosphate buffer solution (pH 6.5) was used in place of the HBSS dilution solution of the extract of wheat germ fermentation product in the sample solution. Thereafter, the activity inhibition rate was calculated as in Equation 1 below.

[Equation 1]

a: absorbance after reaction of blank sample liquid

b: absorbance after the reaction of the sample liquid

a ', b': absorbance measured by replacing buffer with tyrosinase

As a result, the extract of wheat germ fermentation (CJ) was found to be a potent enzyme similar to that of the positive control (arbutin, 1 mM, '+' in the figure) at concentrations of 10 μg / ml and 50 μg / ml. It was shown to have inhibitory activity (FIG. 2).

2-2: Confirmation of melanin synthesis inhibition

Melan-a cells were aliquoted into 24-well plates to be 3x10 ⁴ cells / well, and then cultured in RPMI 1640 medium for 24 hours in a cell incubator so that the cells adhere well to the plates, Embryonic fermentation extracts (CJ) were dissolved in RPMI 1640 medium and added twice per 3 days over 6 days at different concentrations (1 μg / ml, 10 μg / ml, 50 μg / ml). After dissolving the cells in cell lysis buffer (Bio-rad), the supernatant was separated by centrifugation at 17000 rpm for 30 minutes to quantify the protein (BCA method), and added 1N NaOH at 405 nm. The absorbance was measured to calculate the melanin amount relative to the measured protein amount.

As a result, the melanin synthesis inhibitory activity of the extract of the wheat germ fermentation was particularly excellent at a concentration of 10 ㎍ / ml or more, this activity is shown in the group treated with arbutin (1 mM) (positive control, '+' in the figure) ) Better than Figure 3).

Example  One: Wheat germ Fermented product  Containing extract Cosmetic  Whitening efficacy evaluation

1-1. Cosmetic cream manufacturers

Like the composition (wt%) disclosed in Table 1 below, a cosmetic cream containing an extract of wheat germ fermentation of Preparation Example 1 as an active ingredient was prepared according to a conventional method.

1-2. Whitening cream Clinical Evaluation of Efficacy

1-2-1. Experiment Outline

Skin whitening effect of the cosmetic cream (hereinafter referred to as 'CJD cream') prepared in Example 1-1, a cream containing the same amount of purified water instead of the extract of wheat germ fermentation in the composition of Table 1, below The clinical evaluation was performed by comparing each with 'control cream'. The subjects were 22 Korean women aged 30 to 55 years with dark skin color and pigmentation.

First, the control cream and the CJD cream are allocated to the area to be applied for 12 weeks through block randomization, and then visually observed before (0 week), 4 weeks after use, 8 weeks after, and 12 weeks after use. Evaluation, instrumentation (skin melanin index measurement) and safety evaluation were conducted to evaluate the effectiveness of the cream containing the extract of wheat germ fermentation on the whitening of human skin. Specific sample information and method of use are summarized in Table 2 below.

The subjects were to wash their face at each evaluation point, and then stabilize the skin for 20 minutes in a space maintained at constant temperature and humidity conditions (22 ± 2 ℃, 50 ± 5%) without air movement and direct sunlight. Participated. Measurement and evaluation procedures are summarized in Table 3 below.

1-2-2. Visual evaluation of skin color

Visual evaluation of skin color (including pigmentation) was carried out by two investigators evaluated in the 0-9 steps based on the visual evaluation criteria as shown in Table 4.

As a result, as shown in Table 5, the skin color visual evaluation score of the CJD cream group was statistically significantly decreased at 8 weeks after using the product, and the effect of brightening (whitening) of the skin color was clearly observed (p). <0.05).

On the other hand, as a result of comparison between the groups, as shown in Table 6 and Figure 4, after 8 weeks of using the cream CJD cream skin color visual evaluation score significantly reduced compared to the control cream using group, the whitening effect of the CJD cream Excellent (p <0.05).

1-2-3. Melanin index measurement

The skin melanin index (up to 8 weeks) and skin color of the right and left cheeks of the subjects were measured before (0 week), 4, 8, and 12 weeks of use.

Mexameter® MPA580 (C + K, Germany) is an instrument that measures the amount of melanin and hemoglobin, the main determinants of skin color, using the absorption principle. Melanin index is measured by the absorption in two different wavelength regions. The erythema index is measured as the skin absorption in the wavelength region, which excludes the absorption peak of hemoglobin and the interference of other pigments such as bilirubin. The skin absorption rate of each wavelength region is digitized and displayed as Melanin Index (M.I) and Erythema Index (E.I). In this test, the test site (cheek, pigmentation site) was repeatedly measured three times for each evaluation time point, and the average value of melinin index was analyzed.

Compared to before using the product, the CJD cream use group had a statistically significant decrease (improvement) of skin melanin index (M> I) at the cheek and pigmentation areas at 4 and 8 weeks after using the product (FIG. 5). . On the other hand, the control cream use group showed a statistically significant decrease (improvement) of melanin index (M.I) only in the cheek area only after 8 weeks of use. Table 7 summarizes the melanin index change by time.

On the other hand, as a result of comparison between the groups, the skin melanin index (M.I) of the CJD cream decreased significantly (improvement) at 4 weeks after the product use compared to the control cream use group. Table 8 below shows comparative data between groups of skin melanin index changes by time.

6-2-4. Safety evaluation

At 4 weeks, 8 weeks, and 12 weeks after the use of the test product (CJD cream and control cream), the skin condition of the clinical subject was observed, and the skin condition for subjective and objective stimulation was confirmed through question and answer with the subject. It was recorded and evaluated. As a result, no skin abnormalities were observed in all subjects (Table 9).

From the above description, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. In this regard, the examples described above are illustrative in all respects and should be understood as not limiting. The scope of the present application should be construed that all changes or modifications derived from the meaning and scope of the claims and the equivalent concepts described below rather than the detailed description are included in the scope of the present application.

Claims (12)

1. Cosmetic composition for skin whitening containing wheat germ fermented product or extract thereof.
2. The method of claim 1,

   The wheat germ fermented product is obtained by inoculating wheat germ or a medium containing the same after incubating yeast, cosmetic composition for skin whitening.
3. The method of claim 2,

   The yeast is Saccharomyces cerevisiae (Saccharomyces cerevisiae), the cosmetic composition for skin whitening.
4. The method of claim 1,

   The culturing is carried out for 12 hours to 60 hours at a temperature of 20 ℃ to 40 ℃, cosmetic composition for skin whitening.
5. The method of claim 1,

   The wheat germ fermentation product or extract thereof is contained in 0.001% to 10% by weight of the total cosmetic composition, cosmetic composition for skin whitening.
6. The method of claim 1,

   The composition is to inhibit the tyrosinase (tyrosinase) activity, cosmetic composition for skin whitening.
7. The method of claim 1,

   The composition is to inhibit melanin synthesis, cosmetic composition for skin whitening.
8. Pharmaceutical composition for the prevention or treatment of dermatological pigmentation disease containing wheat germ fermented product or extract thereof.
9. The method of claim 8,

   The dermal hyperpigmentation disease is a blemish, freckles, blemishes or melanoma, the pharmaceutical composition for the prevention or treatment of dermal hyperpigmentation disease.
10. A quasi-drug composition for skin whitening containing wheat germ fermentation or extracts thereof.
11. A method for preventing or treating a dermatologically pigmented disease comprising administering a wheat germ fermentation product or extract thereof, or a pharmaceutical composition comprising the same to a subject in need thereof.
12. A method for whitening skin, comprising administering a wheat germ fermentation product or extract thereof, or a composition comprising the same to a subject in need thereof.

Images