WO2017196048A1 - Externally applied composition for alleviating skin wrinkles, containing extract of fermented wheat germ product as active ingredient - Google Patents

Abstract

The present application relates to an externally applied composition for preventing, alleviating, or treating skin wrinkles, containing, as an active ingredient, a compound of chemical formula 1, or a fermented wheat germ product or an extract thereof.

Description

External preparation for skin wrinkle improvement containing extract of wheat germ fermentation as an active ingredient

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

In general, skin wrinkles are known to be produced by various factors such as the moisture content of the skin, the content of collagen, and the ability to act on the external environment. Among the above, collagen is known to have the greatest effect on the formation of skin wrinkles. have.

Collagen is mostly present in the dermal layer of the skin and accounts for about 70-80% of the total dry weight of the skin, supporting most of the extracellular matrix. However, biosynthesis of collagen is reduced by internal factors such as decrease of cellular activity due to natural aging, and the decomposition of collagen is accelerated by the increase of stress caused by harmful environment and external factors such as sun rays, and the skin substrate is destroyed. Wrinkles are created. Therefore, much research has been conducted on active ingredients that can prevent and improve such phenomena.

Elastase present in human neutrophil granulocytes is an enzyme that degrades elastin, a substrate protein important for maintaining skin elasticity in the dermis, and also has collagen-degrading activity. When Elastase is properly expressed and activated, it is involved in wound recovery, but when overexpressed or activated, elastin loses elasticity by decomposing elastin in the skin. Therefore, elastase inhibitors have an effect of improving skin wrinkles, and ursolic acid is used as an elastase inhibitor.

On the other hand, an external preparation composition for improving skin wrinkles containing Jeonho extract or parsley extract (Korean Patent No. 0507292), an external preparation composition for improving wrinkles containing natural extracts such as rhubarb, sandalwood and sandalwood (Korea Patent No. 1220903) In addition to studies on natural products such as external skin composition containing scleroglucan (Korean Patent Publication No. 2010-0043923), as well as an aqueous dispersion of a film-forming polymer composed of polyurethane and acrylic polymer dispersed in water Research on synthetic polymers, such as the composition for external preparations for skin (Korean Patent No. 1101363), has also been made. However, there has not been developed a skin external preparation composition for improving wrinkles derived from natural products that is satisfactory to consumers in terms of stability and wrinkle improvement.

The present inventors have made efforts to develop an external composition for improving wrinkles by fermenting natural materials, and as a result, the extract of wheat germ fermentation and 2,6-dimethoxybenzoquinone (2,6-DMBQ: 2,6-Dimethoxybenzoquinone) While excellent in safety, while inhibiting collagen and elastin degradation while increasing collagen biosynthesis, when applied to the skin it was confirmed that the effect of improving skin wrinkles (for example, wrinkles on the eyes) was completed.

It is an object of the present invention to provide a cosmetic composition for preventing or improving skin wrinkles containing a compound of Formula 1, or wheat germ fermentation product or extract thereof.

[Formula 1]

It is another object of the present invention to provide a pharmaceutical composition for preventing or treating skin wrinkles containing the compound of Formula 1, or wheat germ fermentation product or extract thereof.

Another object of the present invention to provide a quasi-drug composition for preventing or improving skin wrinkles containing the compound of Formula 1, or wheat germ fermentation or extracts thereof.

Another object of the present invention is to provide a method of preventing, ameliorating or treating skin wrinkles, comprising administering the compound of Formula 1, or wheat germ fermentation product or extract thereof, or a composition of the present invention to a subject in need thereof. To provide.

The compositions herein are non-toxic, promote procollagen biosynthesis, inhibit collagenase and elastase expression by ultraviolet light, and have the effect of reducing dermal density and skin wrinkle depth to prevent, improve or It can be used for therapeutic purposes.

1 shows a calibration curve using 2,6-DMBQ, a compound of Formula 1 of the present application, and then converts the area of the peak using a calibration curve to extract 2,6-in the extract of a wheat germ fermentation product according to an embodiment of the present application. It is the result of converting DMBQ content.

Figure 2 is a graph showing the results of performing the cytotoxicity test on the NHDF cells of the extract of wheat germ fermentation (CJ) according to an embodiment of the present application.

Figure 3 is the result of measuring the cytotoxicity to 2,6-DMBQ human skin fibroblasts.

4A and 4B are graphs showing the type 1 procollagen biosynthesis of extracts of wheat germ fermentation (FIG. 4A) and 2,6-DMBQ (FIG. 4B) according to an embodiment of the present disclosure.

Figures 5a and 5b is a graph comparing the inhibitory activity of MMP-1 production by ultraviolet irradiation of the extract of the wheat germ fermentation (FIG. 5a) and 2,6-DMBQ (Fig. 5b) according to an embodiment of the present application.

Figure 6 is a graph comparing the inhibition of the elastase activity of the extract of wheat germ fermentation according to an embodiment of the present application.

7 is a diagram illustrating wrinkle parameters R1 and R3 in the case of measuring the wrinkles around the eyes.

8a to 8f is a view comparing the extract containing product (CJD cream) and the negative control product (control cream) of wheat germ fermentation according to an embodiment of the present application. FIG. 8A is a graph showing changes in wrinkles around the eye area of each time point, and FIG. 8B is a graph illustrating the increase / decrease rate of wrinkles around the eyes according to the use of the product by time point, and FIG. FIG. 8D is a graph showing changes in skin dermal density by time point, and FIG. 8E is a graph showing increase and decrease of dermal density according to product use at each time point, and FIG. 8F is a photograph showing changes in dermal density of individuals according to product use. to be.

9A to 9F are diagrams comparing the extract-containing product (CJD cream) and the positive control product (ADE cream: adenosine containing) of the wheat germ fermentation according to an embodiment of the present application. FIG. 9A is a graph showing changes in wrinkles around the eyes, and FIG. 9B is a graph illustrating increases and decreases in the wrinkles around the eyes according to the use of products by time, and FIG. 9C is a photograph illustrating changes in the wrinkles of the eyes according to the use of products. FIG. 9D is a graph showing changes in skin dermal density by time point, and FIG. 9E is a graph showing increase and decrease of dermal density according to product use at each time point, and FIG. 9F is a photograph showing changes in dermal density of an individual according to product use. to be.

As one embodiment for achieving the above object, the present application provides a cosmetic composition for preventing or improving skin wrinkles comprising a compound represented by the following formula (1), or wheat germ fermentation or extracts thereof.

Compounds that may be included as an active ingredient in the cosmetic composition of the present application may be represented by the following formula (1).

[Formula 1]

Compound represented by Formula 1 of the present application is a compound named 2,6-dimethoxybenzoquinone (2,6-DMBQ: 2,6-Dimethoxybenzoquinone), a chemical or biological synthesis, or purchased commercially Can be used. Alternatively, it can be obtained by separating from natural products (eg, plants, etc.) known to contain the compounds of the present application. However, it is not particularly limited thereto. Herein, it was confirmed that the compound represented by Chemical Formula 1 included in the wheat germ fermentation product or its extract has the effect of preventing or improving skin wrinkles.

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, the effect of improving the wrinkles of wheat germ is not known.

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 wheat germ fermentation herein may comprise a compound of Formula 1 herein.

In addition, wheat germ fermentation of the present application may be obtained by inoculating microorganisms in wheat germ or a medium containing the same and then cultured. 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 Dekkera anomala , Streptomyces olivochromogenes , or Streptomyces griseus , but examples of skin folds for purposes herein It is not limited to this as long as it can exhibit room or improvement effect. 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.) but may be a microorganism, but is not limited thereto so long as it can have an effect of preventing or improving skin wrinkles. 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 can exhibit the effect of preventing or improving skin wrinkles.

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.

Without being particularly limited thereto, the extract of wheat germ fermentation herein may comprise a compound of Formula 1 herein.

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 wheat germ fermentation by any method as long as it has an effect of preventing, improving or treating wrinkles. Cold extraction method to extract at room temperature to 25 ℃, heat extraction method to be extracted by heating to 40 to 100 ℃, ultrasonic extraction method by applying ultrasonic waves, reflux extraction method using a reflux cooler and the like can be used. 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 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 0.1 μg / ml to 200 μg / ml. Specifically, the wheat germ fermentation product or the extract thereof may be 0.1 μg / ml to 150 μg / ml, 0.1 μg / ml to 100 μg / ml, 0.1 μg / ml to 70 μg / ml, 0.1 μg / ml To 50 μg / ml, 0.5 μg / ml to 200 μg / ml, 0.5 μg / ml to 150 μg / ml, 0.5 μg / ml to 100 μg / ml, 0.5 μg / ml to 70 μg / ml, 0.5 μg / ml To 50 μg / ml, 0.8 μg / ml to 200 μg / ml, 0.8 μg / ml to 150 μg / ml, 0.8 μg / ml to 100 μg / ml, 0.8 μg / ml to 70 μg / ml, 0.8 μg / ml To 50 μg / ml, 1 μg / ml to 200 μg / ml, 1 μg / ml to 150 μg / ml, 1 μg / ml to 100 μg / ml, 1 μg / ml to 70 μg / ml, 1 μg / ml To 50 μg / ml, 5 μg / ml to 200 μg / ml, 5 μg / ml to 150 μg / ml, 5 μg / ml to 100 μg / ml, 5 μg / ml to 70 μg / ml, 5 μg / ml To 50 μg / ml, 8 μg / ml to 200 μg / ml, 8 μg / ml to 150 μg / ml, 8 μg / ml to 100 μg / ml, 8 μg / ml to 70 μg / ml, 8 μg / ml To 50 μg / ml, 10 μg / ml to 200 μg / ml, 10 μg / ml to 150 μg / ml, 10 μg / ml to 1 00 μg / ml, 10 μg / ml to 70 μg / ml or 10 μg / ml to 50 μg / ml.

In addition, the compound represented by Formula 1 of the present application may be used in 0.00001% to 0.1% by weight relative to the total weight of the composition, specifically 0.0001% to 0.07% by weight, 0.0001% to 0.05% by weight, 0.0001% by weight To 0.3 wt%, 0.0001 wt% to 0.02 wt%, 0.0001 wt% to 0.01 wt%, 0.0005 wt% to 0.1 wt%, 0.0005 wt% to 0.07 wt%, 0.0005 wt% to 0.05 wt%, 0.0005 wt% to 0.03 Wt%, 0.0005 wt% to 0.02 wt%, 0.0005 wt% to 0.01 wt%, 0.001 wt% to 0.1 wt%, 0.001 wt% to 0.07 wt%, 0.001 wt% to 0.05 wt%, 0.001 wt% to 0.03 wt% , 0.001 wt% to 0.02 wt%, 0.001 wt% to 0.01 wt%, 0.005 wt% to 0.1 wt%, 0.005 wt% to 0.07 wt%, 0.005 wt% to 0.05 wt%, 0.005 wt% to 0.03 wt%, 0.005 % By weight to 0.02% by weight, 0.005% by weight to 0.01% by weight or 0.007% by weight It may be included in% by weight.

In addition, the compound represented by Formula 1 of the present application may be included in 0.1 ng / ml to 1250 ng / ml in the composition of the present application. Specifically wheat germ fermentation herein or extract thereof is 0.1 ng / ml to 1000 ng / ml, 0.1 ng / ml to 500 ng / ml, 0.1 ng / ml to 200 ng / ml, 0.1 ng / ml To 120 ng / ml, 0.1 ng / ml to 90 ng / ml, 0.1 ng / ml to 60 ng / ml, 0.1 ng / ml to 30 ng / ml, 1 ng / ml to 1250 ng / ml, 1 ng / ml To 1000 ng / ml, 1 ng / ml to 500 ng / ml, 1 ng / ml to 200 ng / ml, 1 ng / ml to 120 ng / ml, 1 ng / ml to 90 ng / ml, 1 ng / ml To 60 ng / ml, 1 ng / ml to 30 ng / ml, 1 ng / ml to 1250 ng / ml, 1 ng / ml to 1000 ng / ml, 1 ng / ml to 500 ng / ml, 1 ng / ml To 200 ng / ml, 1 ng / ml to 120 ng / ml, 1 ng / ml to 90 ng / ml, 1 ng / ml to 60 ng / ml, 1 ng / ml to 30 ng / ml, 5 ng / ml To 1250 ng / ml, 5 ng / ml to 1000 ng / ml, 5 ng / ml to 500 ng / ml, 5 ng / ml to 200 ng / ml, 5 ng / ml to 120 ng / ml, 5 ng / ml To 90 ng / ml, 5 ng / ml to 60 ng / ml, 5 ng / ml to 30 ng / ml, 10 ng / ml to 1250 ng / ml, 10 ng / ml to 1000 ng / ml, 10 ng / ml To 500 ng / ml, 10 ng / ml to 200 ng / ml, 10 ng / ml to 120 ng / ml, 10 ng / ml to 90 ng / ml, 10 ng / ml to 60 ng / ml, 10 ng / ml to 30 ng / ml, 15 ng / ml to 1250 ng / ml, 15 ng / ml to 1000 ng / ml, 15 ng / ml to 500 ng / ml, 15 ng / ml to 200 ng / ml, 15 ng / ml to 120 ng / ml, 15 ng / ml to 90 ng / ml, 15 ng / ml to 60 ng / ml, 15 ng / ml to 30 ng / ml, 30 ng / ml to 1250 ng / ml, 30 ng / ml to 1000 ng / ml, 30 ng / ml to 500 ng / ml, 30 ng / ml to 200 ng / ml, 30 ng / ml to 120 ng / ml, 30 ng / ml to 90 ng / ml, 30 ng / ml to 60 ng / ml, 60 ng / ml to 1250 ng / ml, 60 ng / ml to 1000 ng / ml, 60 ng / ml to 500 ng / ml, 60 ng / ml to 200 ng / ml, 60 ng / ml to 120 ng / ml or 60 ng / It may be included in ml to 90 ng / ml.

As used herein, the term “wrinkle” refers to a fine line caused by skin decay and may be caused by a gene, a decrease in collagen present in skin dermis, an external environment, and the like. The wrinkles may include skin aging or skin elasticity reduction. The skin aging refers to the type and intangible changes that appear on the skin with age, as well as endogenous aging (natural aging) that occurs with everyone without special environmental factors, as well as stress, ultraviolet rays, smoking, drug use, etc. It may include all of the exogenous aging that occurs as a cause. Photoaging in the exogenous aging refers to a phenomenon in which skin damage occurs, such as decreased elasticity and moisture of the skin and wrinkles upon repeated or prolonged exposure to ultraviolet rays of sunlight. Specifically, the photoaging may refer to an actinic elastosis symptom that causes degeneration or deposition of elastic fibers, thermal insulation of collagen fibers, and the like.

Wrinkles of the present application may be wrinkles that occur on the face, neck, etc. of the eyes, the forehead, forehead, and the like, and specifically, may be wrinkles around the eyes.

According to one embodiment of the present disclosure, the compositions of the present disclosure may promote procollagen biosynthesis, inhibit collagenase (MMP-1) expression by ultraviolet radiation, inhibit elastase activity and / or increase skin dermal density. have.

As used herein, the term "prevention" means any action by which a composition according to the present invention inhibits or delays the occurrence of wrinkles.

As used herein, the term "improvement" means any action that at least reduces the parameters associated with the condition of wrinkles, such as the extent of wrinkles. In particular, the improvement herein may be a decrease in the depth of the wrinkles, an increase in the dermal density and / or a decrease in the number of wrinkles in a given area.

The cosmetic compositions herein are selected from 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 in a form that is provided.

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 the cosmetically acceptable carrier include saline, sterile water, buffered saline, dextrose solution, maltodextrin solution, glycerol, 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 It includes all, or the form of the mask sheet pack, but is not particularly limited thereto.

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 preventing or treating skin wrinkles containing a compound of formula (1), or wheat germ fermentation or extract thereof.

[Formula 1]

In the pharmaceutical composition of the present application, the compound of Formula 1, wheat germ, fermented wheat germ, extract of wheat germ fermentation, skin wrinkles and prevention are all described above.

As used herein, the term "treatment" means any action that causes the composition to improve or benefit from the appearance of skin wrinkles. Specifically, it may be a decrease in the depth of wrinkles, increase in the dermal density, decrease in the number of wrinkles in a certain area and / or removal of wrinkles.

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 anti-wrinkle or therapeutic activity and properties of the pharmaceutical compositions of the present application. 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 used herein, the term "administration" means introducing a given substance into a subject in any suitable manner and can be administered via any general route by which the compositions 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 may be administered parenterally, and more specifically, it may be applied in a manner of applying 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 quasi-drug composition for preventing or improving skin wrinkles containing a compound of Formula 1, or wheat germ fermentation or extract thereof.

In the quasi-drug composition of the present application, all of the above-mentioned compounds apply to the compound of Formula 1, wheat germ, wheat germ fermentation, extract of wheat germ fermentation, skin wrinkle, prevention and improvement.

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 extract of the compound of formula 1, wheat germ fermentation or wheat germ fermentation herein is used as a quasi-drug additive, the extract of the compound of formula 1, wheat germ fermentation or wheat germ fermentation of the present application is added as is or other quasi-drug or quasi-drug components It can be used together, and can be suitably used according to a conventional method.

As another aspect to achieve the object of the present application, skin wrinkles comprising administering a compound of formula (1), wheat germ fermentation or extract thereof, or a composition of the present invention to a subject in need thereof Provide a method of preventing, ameliorating or treating.

In the method for preventing, improving or treating skin wrinkles herein, the compound of formula 1, wheat germ, fermentation of wheat germ, extract of wheat germ fermentation, skin wrinkle, prevention, improvement, treatment and administration of the present invention are described above. One bar applies to all.

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 Fermented product  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'.

Production Example  2: Wheat germ Fermented product  Component Analysis of Extracts

Analysis of the components of the extract of wheat germ fermentation by high performance liquid chromatography (HPLC) revealed that 2,6-dimethoxybenzoquinone (2,6-DMBQ: 2,6-Dimethoxybenzoquinone) was contained and its content was wheat germ. The freeze-dried 700ppm of the extract of the fermentation product. The DMBQ content is dilution of commercial 2,6-DMBQ (Sigma-Aldrich) by concentration using chloroform, and then draw the calibration curve with the peak area analyzed by HPLC, and then the calibration curve for the peak area of DMBQ in the extract of wheat germ fermentation Calculated by using (FIG. 1).

2,6-DMBQ in the following Experimental Examples and Examples was purchased from Sigma-Aldrich.

Experimental Example 1 : Cell viability assay

The cytotoxicity in NHDF cells was measured for the extract (CJ) of wheat germ fermentation of Preparation Example 1. Specifically, NHDF cells were dispensed in 96-well plates at 6 × 10 ³ cells / well, followed by Fibroblast Basal Medium, FBM containing 0.1% Insulin, 0.1% rhFGF, 0.1% gentamicin, 2% FBS. Lonza, CC-3131) medium and maintained at 37 ℃ incubated for 24 hours in an incubator containing 5% carbon dioxide. After incubation for 12 hours, after starvation, the fermented wheat germ extract of Experimental Example 1 and the FBM medium without the supplement (supplement), respectively, were added and cultured for 24 hours. . Then, to measure the viability of the cells, the WST-1 (water-soluble tetrazolium salt-1, Roche) reaction solution was diluted 1/10 in FBM medium without additives, and 100 μl of each well was treated for 1 hour. After the reaction, the absorbance at 450 nm was measured. The relative cell viability of the case where the NHDF cells were treated with only the FBM medium except for the sample (control), when the extract (CJ) of the wheat germ fermented product of Preparation Example 1 (test) was expressed as a percentage.

As a result, it was confirmed that the sample does not show any cytotoxicity at 200 μg / ml or less (FIG. 2). Accordingly, in the subsequent in vitro experiments, the concentration of the sample was set to 50 μg / ml or less.

In addition, cytotoxicity of human dermal fibroblasts (HDF) of 2,6-DMBQ (Sigma-Aldrich) was measured. Specifically, HDF cells were cultured in DMEM with 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin added to ⁶ × 10 ⁵ cells / well. The cells were cultured in a 5% CO ₂ incubator using a 100 mm cell culture dish, and the cells that reached confluence were kept passaged using Trypsin-EDTA. Thereafter, 2 × 10 ³ cells / well concentration of HDF cells in 96 well cell culture plates were incubated for 24 hours with DMEM (Thermo) culture added with 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin, followed by 2, 6-DMBQ was treated. The 2,6-DMBQ treatment is prepared by diluting 2,6-DMBQ in water, diluting the stock by 1/2 for each concentration, and final concentration (0.3125) in DMEM (serum free, P / S 1%) medium. μg / ml, 0.625 μg / ml and 1.25 μg / ml) were diluted to remove all of the previous cultures, followed by incubation for 48 hours. After incubation, the cells were replaced with DMEM (serum free, P / S 1%) medium containing 10% of EZ-CYTOX (EZ-1000, Daeil lab service, Korea), and the absorbance was measured at 450 nm using a plate reader. The cell viability was determined.

As a result, it was confirmed that no cytotoxicity was observed at all concentrations of 1.25 μg / ml or less (FIG. 3).

Effect of DMBQ on Survival of HDF Cells

Concentration (μg / ml)	Cell survival rate (%)		Statistical analysis (p-value)
	Average	Standard Deviation
Control	100.0	2.5	-
0.3125	107.9	7.0	0.179
0.625	105.3	1.7	0.045
1.25	110.8	4.7	0.037

Experimental Example  2: evaluation of wrinkle improvement efficacy

2-1: Type 1 Procollagen  Biosynthesis Promotion Experiment

NHDF cells were aliquoted into 1 × 10 ⁴ cells / well in 48-well plates and incubated for 24 hours in the same FBM medium as in Experimental Example 1. Thereafter, the medium was removed, and the cells were starved for 24 hours, and then the extracts of wheat germ fermentation of Preparation Example 1 and 2,6-DMBQ were diluted in FBM (except additives), respectively, by concentration (wheat flour fermented product). Extracts: 1 μg / ml, 10 μg / ml, 50 μg / ml; 2,6-DMBQ: 15 ng / ml, 30 ng / ml, 60 ng / ml and 120 ng / ml) Time incubation. Thereafter, cultured cells were harvested and the amount of procollagen was measured using a procollagen type I c-peptide (PIP) EIA kit (TAKARA, MK101). On the other hand, the cells attached to the bottom was washed with PBS, lysed with 1N NaOH (lysis), and the total protein amount was measured to calculate the amount of procollagen synthesis per protein.

As a result, it was confirmed that the extract of wheat germ fermentation increased the production of procollagen in a concentration-dependent manner (FIG. 4A). In addition, 2,6-DMBQ promoted procollagen expression at a statistically significant level in the concentration range of 15 ng / ml to 120 ng / ml, and concentration-dependent behavior in the concentration range of 15 ng / ml to 30 ng / ml. It was confirmed that there was a very good procollagen expression promoting ability similar to the positive control by promoting up to the level of 188.53 ± 9.23% when treated with 30 ng / ml (Table 2, Figure 4b, Paired t-test: * p <0.05, ** p <0.01, *** p <0.001).

Concentration (ng / ml)	Type 1 Procollagen Expression (%)		Statistical analysis (p-value)
	Average	Standard Deviation
Control	100.0	11.6	-
15	172.4	2.6	0.0063
30	188.5	9.2	0.0006
60	177.8	5.3	0.0025
120	161.9	15.0	0.0057
TGF-β (5 ng / ml)	203.8	5.9	0.009

2-2: Collagenase ( MMP -1) expression inhibition experiment

Among the various mechanisms in which wrinkles are formed, the expression of collagenase (MMP-1, Matrix metalloproteinase-1), a collagen degrading enzyme expressed by ultraviolet light, was measured by using an immuno ELISA assay to evaluate the wrinkle improvement efficacy of the sample. .

Specifically, NHDF cells were dispensed into 24-well plates at 2 × 10 ⁴ cells / well and then incubated for 24 hours in the same medium as Experimental Example 1. After 24 hours, the medium was discarded and washed with DPBS, and then UV-B 40 mJ / cm 2 was irradiated by adding 200 µl of DPBS. Thereafter, the extracts (CJ) of the wheat germ fermentation product of Preparation Example 1, the same concentrations as in Experimental Example 2-1, were treated to the cells and incubated for 24 hours. Subsequently, the culture medium was taken and the amount of MMP-1 was measured by a human whole MMP-1 ELISA kit (R & D system, DY901), and the measured amount of MMP-1 was corrected by the total protein amount.

In the case of 2,6-DMBQ treatment, the MMP-1 amount was measured in the same manner except that UV-B irradiation was performed at 15 mJ / cm ² , and retinoic acid was used as a positive control.

As a result, the treatment of wheat germ extract (CJ) in the control group (+) in which MMP-1 expression was increased according to UVB irradiation showed a tendency of MMP-1 to decrease significantly in a concentration-dependent manner (FIG. 5A).

In addition, the treatment of 2,6-DMBQ showed a significant level of MMP-1 inhibitory effect in the concentration range of 15 to 120 ng / ml, and showed a concentration-dependent pattern, which was highest compared to the negative control at 120 ng / ml. It was confirmed that the inhibition by 68% (Table 3, Figure 5b).

Concentration (ng / ml)	MMP-1 expression rate (% of control)		Statistical analysis (p-value)	% Inhibition of expression
	Average	Standard Deviation
non-UV	61.8	6.0	-	-
Control	100.0	10.3	-	0.0
15	92.5	16.6	0.5	19.7
30	89.5	14.8	0.4	27.4
60	83.2	9.8	0.1	44.1
120	73.7	6.6	0.0	68.7
Retinolic Acid (200 ng / ml)	63.7	9.9	0.0	95.0

2-3: elastase ( elastase Inhibition experiment

Inhibition of Elastase and N-STANA (N-succinyl- (Ala) 3-p-nitroanilide) Reaction with Elastase to Confirm that Extract of Wheat Germ Fermentation and 2,6-DMBQ Inhibit Elastase Activity The degree was evaluated. First, 0.2M Tris-HCl (pH 8.0) containing 0.1% triton X-100 was added to NHDF cells, which are skin fibroblasts, and homogenized by an ultrasonic mill. The supernatant obtained by centrifugation at 3,000 rpm for 20 minutes was used as a sample for confirming the elastase activity.

After 200 μg / ml of the sample, 0.2M Tris-HCl buffer and the extract (CJ) of the wheat germ fermentation product of Preparation Example 1, respectively, were mixed by concentration, 50 mM N-STANA was added thereto, and cultured at 37 ° C., and then at 405 nm. Absorbance was measured. Thereafter, the degree of inhibition of elastase activity was calculated relative to the negative control (labeled with '-') that was not treated with the extract of wheat germ fermentation. As a positive control, phosphoramidon (phosphoramidon, 10 mM, indicated as '+'), which is known as an elastase inhibitor, was used.

As a result, it was confirmed that the extract (50 ㎍ / ml) of the wheat germ fermentation inhibited the elastase activity at about 62% compared to the negative control and at the same time showed the same level of effect on the positive control (FIG. 6).

Example 1 Preparation of Cosmetics Containing Extract of Wheat Germ Fermentation

1-1 Preparation of Cosmetic Cream

Like the composition (% by weight) disclosed in Table 4, 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: Improve wrinkles of makeup cream Clinical Evaluation of Efficacy

1-2-1: Experiment Outline

Wrinkle improvement effect of the cosmetic cream prepared in Example 1-1 (hereinafter referred to as 'CJD cream'), a negative control (cream containing the same amount of purified water instead of the extract of wheat germ fermentation in the composition of Table 4, below) Clinical evaluation by comparing with a control cream) or a positive control (a cream containing 0.04% of adenosine, an ingredient for wrinkle improvement functional notification, instead of an extract of wheat germ fermentation, hereinafter referred to as an ADE cream) Was performed. The subjects were 20 Korean females aged 30-55 years who had eye wrinkles (Gross Hearing Skin Care Center SOP 3).

First, the control cream and the area to be applied with the ADE cream and the CJD cream are allocated through block randomization and used for 12 weeks, and then before use (0 week), after 4 weeks, after 8 weeks, and after 12 weeks. At the time point, visual evaluation, instrumental measurements (photographing, skin wrinkles, dermal density) and safety evaluation were performed to evaluate the effectiveness of the cream containing the extract of wheat germ fermentation on the improvement of wrinkles of human skin. Specific sample information and method of use are summarized in Table 5 and Table 6 below.

The subjects were to wash their face at each time of evaluation, and then stabilize the skin for 20 minutes in a space maintained under constant temperature and humidity conditions (22 ± 2 ℃, 50 ± 5%) without air movement and direct sunlight. Participated. Measurement and evaluation procedures are summarized in Table 7 below.

The instrument was measured for dermal density of right and left cheeks of clinical evaluation chiefs before and after 4 weeks of use, 4 weeks, 8 weeks, and 12 weeks of use. It was.

1-2-2: Evaluation of Control Cream

Replica measurement

Skin-Visiometer® SV600 (Courage + Khazaka GmbH, Germany) is a device that measures the improvement of skin wrinkles by analyzing the intensity of light generated by the light emitted from an artificial light source passing through a silicon material. It was put into an analysis kit and analyzed by Imagemeter software of Visiometer. As R1 and R3 values decrease, skin wrinkles are improved and depth of wrinkles is lowered. The unit is an arbitrary unit (AU). As shown in FIG. 7, the wrinkle parameter (R-parameter) R1 represents the distance between the highest point and the lowest point of the profile in terms of skin roughness, and R3 represents the profile in average roughness. Is successively averaged into five lengths, and then the arithmetic average of the R1 values in each region.

As a result, as shown in Table 8, CJD cream showed statistically significant decrease in R1 and R3 compared to before use at all time points (after 4 weeks, 8 weeks, and 12 weeks) after using the product. Appeared excellent.

As a result of comparison between the groups, skin roughness (R1) value and average roughness (R3) value after 8 weeks of cream use were statistically significant in the CJD cream use group compared to the control cream use group as shown in Table 9 and FIGS. 8A to 8C. Decreased.

Dermal Density Measurement

DermaScanC®USB is a high-resolution 20MHz ultrasound imaging device that uses ultrasound waves to reflect echoes of different densities to produce echoes of varying sizes, allowing imaging of changes in the skin and dermal layer changes due to collagen fiber reflectance. The magnitude of the echo is synthesized by the computer and expressed in color to create a two-dimensional image. In this study, the subjects measured the dermal density of the left and right cheeks (the area where the tip of the nose and the side of the nose meet) using DermaScanC®USB. Density values were analyzed in the captured images.

Compared to before cream use, the CJD cream use group had a statistically significant increase (improvement) in the dermis density at 12 weeks after product use (Table 10 and FIGS. 8D-8F).

In comparison between the groups, at 12 weeks after the use of the product, the CJD cream had a statistically significant increase (improvement) in the dermal density (Control 11) compared to the control cream use group (Table 11 and FIGS.

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 clinical subjects (Table 12).

The results of the evaluation were analyzed statistically using SPSS® Package Program version 22. The normality of the measured values before using the test product was tested by the Sapiro-wilks test. Comparisons before and after use of the product are performed using the Repeated Measures ANOVA if the measured values meet the normal distribution, and the nonparametric methods (Krusckal-Wallis and Mann-Whitney U test) if the measured values do not meet the normal distribution. Significance was verified. The comparison between groups was performed using Repeated Measures ANOVA in consideration of the interdependence (interaction) of the results that were repeatedly measured in the same subject, and the significance level was set to p <0.05. . Survey evaluation was analyzed using frequency analysis.

According to the results of the clinical evaluation, skin adverse reactions could not be observed in all clinical evaluation subjects, CJD cream showed a significant wrinkle improvement effect compared to the control cream.

1-2-3: Evaluation of ADE Cream

Replica measurement

Measurement was performed in the same manner as the method for measuring the wrinkles of eyes 1-2-2. As a result, the skin roughness (R1) and the average roughness (R3) were statistically significantly decreased (improved) at 8 weeks after the use of the CJD cream, and after 12 weeks (p <0.05) ( Table 13 and Figures 9A-9C). This improvement was superior to the ADE cream.

The change of R-parameters according to the time points between the groups is shown in Table 14, and the wheat germ fermentation extract is a natural extract, but the adenosine containing ADE obtained through chemical purification process (resin adsorption, ammonia, ethanol elution, etc.) after microbial fermentation It was found to have the same level of effect as the cream.

Dermal Density Measurement

It measured by the same method as the dermal density measurement method of 1-2-2. As a result, the CJD cream showed a statistically significant increase (improvement) in the thickness of the dermis at 12 weeks after the use of the product, and an increase in the density at 8 and 12 weeks after the use of the product (p <0.05) (Table < 15 and FIGS. 9D-9F). This improvement was similar or higher than that of ADE cream.

The skin dermal density change of each time point between the groups is shown in Table 16. As described above, the wheat germ fermentation extract is a natural extract but has an equivalent effect to the ADE cream containing adenosine, which has undergone chemical purification. Could.

Safety evaluation

At 4 weeks, 8 weeks, and 12 weeks after the use of the test product (CJD cream and ADE cream), the skin condition of the clinical subjects was observed, and the skin condition for subjective and objective stimulus was confirmed through question and answer with the subjects. Were recorded and evaluated. As a result, no skin abnormalities were observed in all clinical subjects (Table 17).

According to the results of the clinical evaluation, skin adverse reactions could not be observed in all clinical subjects, and CJD cream showed the same wrinkle improvement effect as ADE cream.

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 (13)

1. A cosmetic composition for preventing or improving skin wrinkles containing a compound of Formula 1, or wheat germ fermentation product or extract thereof.

   [Formula 1]

   
2. The method of claim 1,

   The wheat germ fermentation product or extract thereof comprises the compound of Formula 1, cosmetic composition for preventing or improving skin wrinkles.
3. The method of claim 1,

   The wheat germ fermentation product is obtained by inoculating wheat germ or a medium containing the yeast and then cultured, cosmetic composition for preventing or improving skin wrinkles.
4. The method of claim 3,

   The yeast is Saccharomyces cerevisiae (Saccharomyces cerevisiae), a cosmetic composition for preventing or improving skin wrinkles.
5. The method of claim 3,

   The culture is carried out at 20 ℃ to 40 ℃ for 12 hours to 60 hours, skin wrinkle prevention or improvement cosmetic composition.
6. The method of claim 1,

   The wheat germ fermented product or extract thereof is contained in 0.001% to 10% by weight of the total cosmetic composition, cosmetic composition for preventing or improving skin wrinkles.
7. The method of claim 1,

   The composition is a cosmetic composition for preventing or improving skin wrinkles to promote procollagen biosynthesis.
8. The method of claim 1,

   Wherein the composition is to inhibit the collagenase (MMP-1) expression by ultraviolet rays, skin wrinkle prevention or improvement cosmetic composition.
9. The method of claim 1,

   The composition is to suppress the elastase activity, cosmetic composition for preventing or improving skin wrinkles.
10. The method of claim 1,

    The composition is to increase the skin dermal density, cosmetic composition for preventing or improving skin wrinkles.
11. A pharmaceutical composition for preventing or treating skin wrinkles containing the compound of Formula 1, or wheat germ fermentation product or extract thereof.

    [Formula 1]

    
12. A quasi-drug composition for preventing or improving skin wrinkles containing the compound of Formula 1, or wheat germ fermentation product or extract thereof.

    [Formula 1]

    .

    
13.  A method of preventing, ameliorating or treating skin wrinkles, comprising administering to a subject in need thereof a compound of Formula 1, or wheat germ fermentation product or extract thereof, or a composition comprising the same.

    [Formula 1]

    

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