KR20220014372A - Composition for inhibiting sebum secretion comprising ellagic acid extract as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for inhibiting excessive sebum secretion comprising ellagic acid as an active ingredient. More specifically, it relates to a cosmetic composition, a pharmaceutical composition, and a food composition comprising ellagic acid, which can effectively control excessive sebum secretion by inhibiting the differentiation of sebum cells, as an active ingredient.
The composition according to the present invention exhibits an effect of effectively inhibiting sebum secretion by inhibiting sebum cell proliferation and lipid synthesis by inhibiting the differentiation of sebum cells while having excellent human safety due to no skin irritation and cytotoxicity. It can be usefully used as an active ingredient in a cosmetic composition for inhibiting secretion, a pharmaceutical composition for preventing, treating or improving sebum-related diseases, and a food composition.

Description

Composition for inhibiting sebum secretion comprising ellagic acid extract as an active ingredient

The present invention relates to a composition for inhibiting sebum secretion comprising ellagic acid as an active ingredient. More specifically, it relates to a cosmetic composition, a pharmaceutical composition, and a food composition containing ellagic acid, which can effectively control excessive sebum secretion by inhibiting the differentiation of sebum cells, as an active ingredient.

In modern society, the skin is the most external part, and when trouble occurs, it causes aesthetic and psychological stress along with changes in appearance. In particular, due to westernized eating habits, lifestyle, and fine dust, skin troubles are on the rise. Heavy metals such as mercury, lead, and aluminum exist in fine dust, and these particles are very small and go deep into the pores and mix with sebum, causing acne or worsening the condition. In addition, due to the abnormal climate where the temperature is gradually rising, the secretion of sebum and sweat in the hair follicles becomes more vigorous, which causes skin diseases related to the secretion of sebum. As such, representative skin diseases caused by abnormal sebum secretion include folliculitis or seborrheic dermatitis, which are chronic inflammatory diseases of the sebaceous glands that cause comedones, papules, pustules, cysts, and nodules.

The sebaceous glands that secrete sebum exist in a high density on the face side, are connected to the isthmus of the hair follicles, and together with the hair follicles are called sebaceous gland units. The outermost layer of the sebaceous gland is the peripheral zone (PZ), which is composed of one cell, and presebaceous cells that only proliferate without differentiation are located. Sebum cells are located. Sebum cells differentiate from PZ to MZ, and finally, in the innermost necrotic zone (NZ), the nucleus and membrane of the differentiated sebum cells are decomposed to secrete sebum (Clayton RW et al., Br J Dermatol). ., 181(4):677-690, 2019). Sebum is composed of triglyceride, wax esters, squalene, cholesterol esters, and cholesterol, and free fatty acids produced by the decomposition of triglycerides by bacteria are It plays an important role in pathogenesis. Factors affecting sebum secretion include sex hormone androgen, vitamin A derivative retinoid, and nuclear hormone receptor, peroxisome proliferator-activated receptorγ (PPARγ), which regulates the expression of lipogenic genes. , it is known that Wnt (Wingless-type) signaling, which plays an important role in embryonic development and tissue homeostasis, and insulin and insulin-related growth factor-1 are involved. Insulin and insulin-related growth factor-1 activate the PI3K/Akt and MAPK mechanisms, increase the expression of mTORC1 (mammalian target of rapamycin complex 1), pass through SREBP-1 (sterol regulatory element binding protein 1), and finally lipid synthesis. Activate it.

Seborrheic dermatitis is eczema caused by abnormal secretion of sebum. It occurs in areas where the activity of the sebaceous glands is increased, and the incidence is high within 3 months of life and between 40 and 70 years of age. There is no gender difference in infants, but in adults, it is more common in men and is known to be associated with oily skin. Seborrheic skin is a skin type that has increased continuously since 2006, and exhibits symptoms accompanied by redness, tight skin, and dead skin cells due to excessive sebum secretion. Seborrheic dermatitis appearing on the scalp is called seborrheic dermatitis and is also known to aggravate hair loss. Seborrheic scalpitis is a disease that occurs frequently during the changing seasons, and if the symptoms of itchy scalp are left unattended, it can progress to seborrheic scalpitis. Seborrheic dermatitis is more common in people with acne prone faces.

Ellagic acid (ellagic acid) is a heterocyclic compound and is a component that exists in the form of ellagitannin, a precursor, in plants. It is known to be present in fruits such as grapes, strawberries, raspberries, pomegranates, walnuts, nuts, and green tea. Ellagic acid, a vegetable phenol, suppresses the destruction of skin collagen and inflammation by UV rays, and has antioxidant, antiviral, anti-mutagenic, and anticancer functions. In addition, the effects of fat cell growth, delay of aging, and prevention of hair loss are known.

Regarding the efficacy of ellagic acid, Korean Patent No. 10-1068763 discloses a composition containing ellagic acid having an effect of inhibiting skin aging by ultraviolet rays, and Korean Patent No. 10-1091641 discloses a method for separating ellagic acid and The anti-wrinkle effect and the whitening effect are disclosed. Also, Korean Patent Registration No. 10-1135285 discloses the efficacy of inhibiting hair loss by inhibiting apoptosis of keratinocytes of ellagic acid or a derivative thereof.

According to non-patent literature, ellagic acid has anticancer effects through various cancer cell proliferation inhibition, metastasis, and apoptosis (Nutrients. 2018 Nov; 10(11): 1756), and ellagic acid contained in bokbunja fruit is AMPK (AMP- The effect of regulating active protein kinase), SREBP-2 (sterol regulatory element binding protein 2) and cholesterol metabolism has also been disclosed (Nutrients. 2020 Mar; 12(3): 610). In addition, there are results showing antioxidant and anti-inflammatory effects in the liver and brain of rats (Sci Rep. 2018; 8: 1465), but the suppression effect of ellagic acid on sebum secretion has not been revealed yet.

Accordingly, the present inventors conducted a study to find a natural material capable of inhibiting the differentiation of sebum cells, and thus completed the present invention by discovering that ellagic acid can effectively inhibit sebum secretion.

Republic of Korea Patent Registration No. 10-1068763 (2011.09.28. Announcement) Republic of Korea Patent Registration No. 10-1091641 (2011.12.08. Announcement) Republic of Korea Patent Registration No. 10-1135285 (2012.04.12. Announcement)

Nutrients. 2018 Nov; 10(11): 1756. Nutrients. 2020 Mar; 12(3): 610. Sci Rep. 2018; 8: 1465.

It is an object of the present invention to provide a cosmetic composition for suppressing or improving sebum secretion, in particular, excessive sebum secretion, comprising ellagic acid as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating sebum-related diseases, comprising ellagic acid as an active ingredient.

Another object of the present invention is to provide a food composition for preventing or improving sebum-related diseases, comprising ellagic acid as an active ingredient.

In order to achieve the above object, the present invention provides a cosmetic composition for suppressing or improving sebum secretion, in particular, excessive sebum secretion, comprising ellagic acid as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for preventing or treating sebum-related diseases, comprising ellagic acid as an active ingredient.

In addition, the present invention provides a food composition for preventing or improving sebum-related diseases, comprising ellagic acid as an active ingredient.

The composition for inhibiting sebum secretion containing ellagic acid as an active ingredient of the present invention has excellent human safety due to no skin irritation and cytotoxicity, while improving or treating seborrheic dermatitis caused by excessive sebum secretion by inhibiting the differentiation of sebum cells It can be usefully used as an active ingredient in a cosmetic composition for, a pharmaceutical composition for preventing, treating or improving sebum-related diseases, and a food composition.

1 is a graph showing the effect of inhibiting sebum secretion by inhibiting sebum cell differentiation according to the present invention. Specifically, a microscopic photograph (left) showing the degree of inhibition of differentiation of sebum cells and numerically analyzing the inhibition of sebum secretion. It is the graph shown (right).

The present invention relates to a composition for inhibiting sebum secretion comprising ellagic acid or a salt thereof as an active ingredient. More specifically, it relates to a cosmetic composition, a pharmaceutical composition, and a food composition comprising ellagic acid or a salt thereof as an active ingredient, wherein the composition has excellent human safety due to no skin irritation and cytotoxicity, and effectively inhibits the differentiation of sebum cells By doing so, it is possible to effectively inhibit excessive sebum secretion and prevent, treat, and improve seborrheic dermatitis caused by excessive sebum secretion.

Ellagic acid of the present invention is a heterocyclic compound and is a component present in the form of ellagitannin, a precursor, in a plant.

The ellagic acid of the present invention may be in the form of a pharmaceutically, cosmetically and/or food-acceptable salt or a form that becomes ellagic acid in the body (eg, a prodrug). Such salts include acid addition salts formed with free acids or metal salts formed with bases that are pharmaceutically, cosmetically and/or food acceptable. The free acid may be an inorganic acid or an organic acid. Examples of the inorganic acid include hydrochloric acid, sulfuric acid, hydrobromic acid, sulfurous acid or phosphoric acid. Examples of the organic acid may include citric acid, acetic acid, maleic acid, humic acid, gluconic acid, methanesulfonic acid, and the like. The metal salt includes an alkali metal salt or an alkaline earth metal salt, and sodium, potassium or calcium salt may be usefully used.

In the present invention, the effect of inhibiting excessive sebum secretion and preventing, improving, and treating seborrheic dermatitis caused by excessive skin secretion can be achieved by inhibiting the differentiation of sebum cells by ellagic acid.

In one specific embodiment, in order to confirm the inhibitory effect of ellagic acid on excessive sebum branching, the differentiation ability of sebum cells, that is, the degree of sebum production of sebum cells, was analyzed. It was found that the inhibition was excellent (Fig. 1).

In one aspect, the present invention provides a cosmetic composition for suppressing or improving excessive sebum secretion, comprising ellagic acid or a cosmetically acceptable salt thereof as an active ingredient.

As used herein, the term "sebum" refers to secretions from the sebaceous glands in the skin, which play a role in maintaining moisture in the skin and preventing the invasion of microorganisms in the skin including the scalp and face, but cause acne after puberty. In particular, in the case of women in their twenties or later, excessive secretion of sebum causes many cosmetic problems, such as oiliness of the skin, lifting of makeup, and enlarged pores. In addition, it is known that excessive secretion of sebum affects the occurrence of seborrheic dermatitis and the like.

The cosmetic composition comprising ellagic acid or a cosmetically acceptable salt thereof of the present invention can be used for the purpose of suppressing and improving excessive sebum secretion, and the cosmetic composition is generally applied to the face, scalp or back area with a lot of sebum secretion. It may be applied to any region where the sebaceous glands are developed without being limited only to the above region.

In the present invention, the ingredients included in the "cosmetic composition" may include ingredients commonly used in cosmetic compositions in addition to the active ingredient as an active ingredient, for example, antioxidants, stabilizers, solubilizers, vitamins, pigments and customary adjuvants such as perfumes, and carriers. The cosmetic composition of the present invention may be prepared in any formulation conventionally prepared in the art, for example, solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing , oil, powder foundation, emulsion foundation, wax foundation, pack, massage cream, spray, etc., but is not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray, or a powder.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component. can

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component, for example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-butylglycol oil, glycerol fatty ester, polyethylene glycol or fatty acid ester of sorbitan.

When the formulation of the present invention is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Adult cellulose, aluminum metahydroxide, bentonite, agar or tracanth may be used.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additional chlorofluorohydrocarbon, propane /may contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a surfactant-containing cleansing agent, aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, fatty acid amide ether as carrier components Sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester may be used.

When the cosmetic composition of the present invention is a soap, a surfactant-containing cleansing formulation, or a surfactant-free cleansing formulation, it may be applied to the skin and then wiped off, removed, or washed off with water. As a specific example, the soap is liquid soap, powder soap, solid soap, and oil soap, the surfactant-containing cleansing formulation is a cleansing foam, cleansing water, cleansing towel, and cleansing pack, and the surfactant-free cleansing formulation is a cleansing cream , cleansing lotion, cleansing water, and cleansing gel, but not limited thereto.

The content of ellagic acid or a cosmetically acceptable salt thereof contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, based on the total weight of the composition. %, more preferably 0.001 to 10% by weight.

In another aspect, the present invention provides a pharmaceutical composition for preventing or treating sebum-related diseases, comprising ellagic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

The effect of inhibiting excessive sebum secretion of the ellagic acid or a pharmaceutically acceptable salt thereof is as described above.

The sebum-related disease refers to seborrheic dermatitis caused by excessive sebum secretion. The seborrheic dermatitis may refer to any disease caused by excessive sebum secretion, such as seborrheic scalpitis, folliculitis, and seborrheic eczema.

As used herein, the term "pharmaceutical composition" refers to one prepared for the purpose of preventing or treating a disease, and each may be formulated in various forms according to a conventional method and used. For example, it can be formulated in oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, and diluents or excipients such as lubricants, wetting agents, flavoring agents, emulsifying agents, suspending agents, preservatives, surfactants, etc. It can be formulated and used as a parenteral formulation using In addition, it can be formulated and used in the form of external preparations, suppositories, external preparations for skin, and sterile injection solutions. Specifically, the composition of the present invention can be used by a method such as direct application or dispersion on the face, scalp, or back area that generally produces a lot of sebum. The composition of the present invention is not limited to the above site, and can be applied to any site where the sebaceous gland is developed.

In addition, according to each formulation, it can be prepared by further including a carrier known in the art, such as a pharmaceutically acceptable carrier, such as a buffer, an analgesic agent, a solubilizer, an isotonic agent, a stabilizer, a base, and the like.

As used herein, the term "pharmaceutically acceptable carrier" may refer to a carrier or diluent that does not inhibit the biological activity and properties of the injected active ingredient without stimulating the organism. The type of carrier usable in the present invention is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and the like. These may be used alone or in mixture of two or more. The carrier may be a non-naturally occurring carrier.

The composition of the present invention can be administered in a pharmaceutically effective amount. The pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and not to cause side effects, and the effective dose level is determined by the patient's health condition, disease type, severity, The activity of the drug, the sensitivity to the drug, the administration method, administration time, administration route and excretion rate, treatment period, factors including drugs used in combination or concurrently, and other factors well known in the medical field may be determined according to factors. Specifically, it is generally 0.01 mg to 5000 mg per 1 kg of body weight of the administered subject, and may be administered in divided doses once or several times a day at regular time intervals according to the judgment of a doctor or pharmacist, but is not limited thereto.

The content of ellagic acid or a pharmaceutically acceptable salt thereof contained in the composition is not particularly limited thereto, but is 0.00001 to 100% by weight, preferably 0.0001 to 15% by weight, more preferably 0.001 to 15% by weight, based on the total weight of the composition. %, more preferably 0.001 to 10% by weight.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with other active pharmaceutically active compounds exhibiting the effect of preventing or improving diseases related to excessive sebum secretion or forming an appropriate group.

The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without causing side effects, and can be easily determined by those skilled in the art.

In the present invention, the term "administration" means introducing the pharmaceutical composition of the present invention to an individual by any suitable method, and the administration route of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. It can be administered through

The method of administration of the pharmaceutical composition according to the present invention is not particularly limited, and may follow a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered by oral administration or parenteral administration. Specifically, the composition of the present invention can be used by a method such as directly applying or dispersing to all areas where the sebaceous glands are developed, such as the face, scalp, and back areas that generally produce a lot of sebum.

The pharmaceutical composition according to the present invention may be prepared in various dosage forms depending on the desired administration method.

The administration frequency of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times by dividing the dose.

As another aspect, the present invention provides a method for preventing or treating sebum-related diseases, comprising administering to an individual a pharmaceutical composition comprising ellagic acid or a pharmaceutically acceptable salt thereof.

The effect of inhibiting excessive sebum secretion of the ellagic acid or a pharmaceutically acceptable salt thereof and a sebum-related disease are as described above.

As used herein, the term "individual" may refer to any animal, including humans, that has or is likely to develop a sebum-related disease. The animal may be a mammal, such as a cow, a horse, a sheep, a pig, a goat, a camel, an antelope, a dog, or a cat, in need of treatment for symptoms similar to those of a human as well as humans, but is not limited thereto.

Specifically, the prevention or treatment method of the present invention may include administering the composition in a pharmaceutically effective amount to an individual who has or is at risk of developing a sebum-related disease. The method of administration is the same as described above.

The prevention may refer to any act of inhibiting or delaying the onset of sebum-related diseases by administering the composition for suppressing excessive sebum secretion according to the present invention to an individual.

In addition, the treatment may refer to any act of administering the composition of the present invention to a subject suspected of having a sebum-related disease so that the symptoms of the sebum-related disease are improved or beneficial.

The pharmaceutical composition comprising the ellagic acid or a pharmaceutically acceptable salt thereof is as described above.

For administration, the composition of the present invention may include a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredients described above. The carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

A suitable dosage of the composition of the present invention may vary depending on the patient's condition and weight, the degree of disease, drug form, and time, but may be appropriately selected by those skilled in the art. Specifically, the dosage of the ellagic acid may be 50 to 500 mg/Kg.

As another aspect, the present invention provides a food composition for preventing or improving sebum-related diseases, comprising ellagic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

The effect of inhibiting excessive sebum secretion of the ellagic acid or a pharmaceutically acceptable salt thereof and a sebum-related disease are as described above.

When the composition of the present invention is used as a food additive, the ellagic acid or a pharmaceutically acceptable salt thereof may be added as it is, or it may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment), and may further include a food pharmaceutically acceptable food supplement additive. Since the composition of the present invention uses a material derived from a natural product as an active ingredient, there is no problem in terms of stability, so there is no great limitation on the mixing amount.

The food composition of the present invention may include all foods in a conventional sense, and may be used interchangeably with terms known in the art, such as functional food and health functional food.

As used herein, the term "functional food" refers to food manufactured and processed using raw materials or ingredients useful for the human body according to Health Functional Food Act No. 6727, and "functionality" refers to the structure of the human body. And it means ingestion for the purpose of obtaining useful effects for health purposes such as regulating nutrients for function or physiological action.

In addition, the term "health functional food" as used in the present invention refers to a food manufactured and processed using a specific ingredient as a raw material or by extracting, concentrating, refining, or mixing a specific ingredient contained in the food raw material for the purpose of health supplementation, It refers to a food designed and processed to sufficiently exert biological control functions such as biological defense, regulation of biological rhythm, prevention and recovery of disease, etc., by the above ingredients, and the composition for health food is used for prevention of diseases and prevention of diseases. It can perform functions related to recovery, etc.

There is no limitation on the type of food in which the composition of the present invention can be used for suppressing excessive sebum secretion and preventing and improving sebum-related diseases. In addition, the composition comprising ellagic acid or a salt thereof of the present invention as an active ingredient can be prepared by mixing known additives with other suitable auxiliary ingredients that may be contained in food according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and There are vitamin complexes and the like, and it can be prepared by adding ellagic acid or a salt thereof according to the present invention as a main component to juice, tea, jelly, juice, and the like.

In addition, foods that can be applied to the present invention include, for example, special nutritional foods (eg, formula milk, infant food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramen, noodles, etc.), health supplements , Seasoned foods (eg soy sauce, soybean paste, red pepper paste, mixed soy sauce, etc.), sauces, sweets (eg snacks), dairy products (eg fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.) ), beverages (eg, fruit, vegetable beverages, soy milk, fermented beverages, etc.), and natural seasonings (eg, ramen soup, etc.).

When the health functional food composition of the present invention is used in the form of a beverage, it may contain various sweetening agents, flavoring agents, or natural carbohydrates as additional ingredients, as in a conventional beverage. In addition to the above, the health functional food composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin , alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage.

Hereinafter, examples and the like will be described in detail to help the understanding of the present invention. However, the embodiments according to the present invention may be modified in various other forms, and the scope of the present invention should not be construed as being limited to the following examples. The embodiments of the present invention are provided to more completely explain the present invention to those of ordinary skill in the art.

Example 1: In vitro ( in vitro ) of ellagic acid to measure the sebum secretion inhibitory effect

To find out what effect ellagic acid has on sebum secretion, the sebum secretion inhibitory ability of sebum cells was measured.

Specifically, human sebum cells, sebocytes (Celprogen), were cultured in a complete medium containing serum and then inoculated into a coated 24-well plate (1×10 ⁴ cells). / well), 5% concentration of CO ₂ In an incubator, 37 ° C., incubated for 24 hours. After dissolving ellagic acid in DMEM medium containing 1% FBS, each well incubated with palmitic acid was treated and cultured again for 48 hours. After 48 hours, the cell culture supernatant was removed, washed once with PBS, and treated with 4% formaldehyde for 10 minutes. After washing 3 times with PBS, 10 μg/ml of Nile Red was mixed with PBS at a ratio of 1:100 and treated, and left at room temperature for 15 minutes. After washing 3 times with PBS, nuclear staining was performed with Dapi. After washing 3 times again, the degree of staining was checked under a microscope. The photograph obtained with a microscope was analyzed with Image J, and the values are shown in FIG. 1 .

As shown in FIG. 1 , compared to the sebum production increased by palmitic acid, ellagic acid exhibited about 70% of sebum production inhibitory ability at 50 ppm.

Example 2: Safety confirmation test for human skin of ellagic acid

In order to confirm whether the ellagic acid according to the present invention is safe for human skin, a skin safety verification experiment was performed. For this purpose, a cumulative skin irritation test was conducted.

Nutrient creams containing 0.1%, 0.5% and 1% of ellagic acid, respectively, were prepared. Specifically, the aqueous phase purified water, triethanolamine, and propylene glycol were heated to 70° C. and dissolved, and then beeswax, liquid paraffin, oily components, emulsifiers and preservatives were heated to 70° C. and the dissolved solution was added to emulsify. After the emulsification was completed, the solution was cooled to 45° C., and 0.1%, 0.5% and 1% of ellagic acid were added and dispersed, respectively, and then cooled to 30°C. As the content of the ellagic acid extract was increased to 0.1%, 0.5%, and 1%, the content of liquid paraffin was reduced to 9.91%, 9.51% and 9.01%, respectively, to prepare a nourishing cream.

Using the nutritional cream prepared as described above, 30 healthy adults were subjected to a total of 9 cumulative patches on the upper forearm every other day for 24 hours to determine whether ellagic acid stimulates the skin.

As the patching method, a Finn chamber (Epitest Ltd, Finland) was used. After 15 μl of each of the above external preparations for skin was dripped into the chamber, patching was performed. The degree of the reaction shown on the skin each time was scored using the following [Equation 2], and the results are shown in Table 1 below.

[Equation 1]

Average reactivity = [[(response index × reactivity)/ (total number of subjects × highest score (4 points))] × 100] ÷ number of tests (9 times)

In the reactivity, ± 1 point, + 2 points, and ++ 4 points are given, and when the average reactivity is less than 3, it is judged as a safe composition.

test substance Number of subjects who responded average
reactivity 1 week 2 weeks 3 weeks Primary Secondary tertiary 4th 5th 6th 7th 8th 9th ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ ± + ++ control
(Squalene) One - - 0 - - - - - - - - - - - - - - - - - - - - - - - 0.09 ellagic acid
(0.1%)
[Test group 1] 0 - - 0 - - - - - - - - - - - - - - - - - - - - - - - 0.00 ellagic acid
(0.5%) [Test group 2] 0 - - 0 - - - - - - - - - - - - - - - - - - - - - - - 0.00 ellagic acid
(One%)
[Test group 3] 0 - - 0 - - - - - - - - - - - - - - - - - - - - - - - 0.00

As shown in Table 1, the number of persons corresponding to ±, + and ++ in test groups 1, 2, and 3 was 0, and the average response was also 0.00. Since the test result showed an average reactivity of 3 or less, the ellagic acid extract according to the present invention was determined to be a safe material for human skin that does not show a distinct cumulative stimulation pattern.

The composition of the present invention may be prepared as a formulation example as follows, but is not limited thereto.

Formulation Example 1: Cosmetic formulation

Formulation Example 1-1: Softening lotion

As shown in Table 2 below, a softening lotion containing ellagic acid as an active ingredient was prepared according to a conventional method.

ingredient weight% ellagic acid 0.01 glycerin 3.0 butylene glycol 2.0 propylene glycol 2.0 carboxyvinyl polymer 0.1 ethanol 10.0 triethanolamine 0.1 Preservatives, trace colors, trace fragrances and trace purified water 82.79 sum 100.0

Formulation Example 1-2: Nutrient lotion

Nutrient lotion containing ellagic acid as an active ingredient was prepared according to a conventional method as shown in Table 3 below.

ingredient weight% ellagic acid 0.01 beeswax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 5.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 3.0 butylene glycol 3.0 propylene glycol 3.0 carboxyvinyl polymer 0.1 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 69.69 sum 100.0

Formulation Example 1-3: Nourishing Cream

As shown in Table 4 below, a nutritional cream containing ellagic acid as an active ingredient was prepared according to a conventional method.

ingredient weight% ellagic acid 0.01 beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 liquid paraffin 10.0 squalane 5.0 Caprylic/Capric Triglycerides 5.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 56.79 sum 100.0

Formulation Example 1-4: Massage Cream

As shown in Table 5 below, a nutritional cream containing ellagic acid as an active ingredient was prepared according to a conventional method.

ingredient weight% ellagic acid 0.01 beeswax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.8 liquid paraffin 40.0 squalane 5.0 Caprylic/Capric Triglycerides 4.0 glycerin 5.0 butylene glycol 3.0 propylene glycol 3.0 triethanolamine 0.2 Preservatives, micro pigments, micro fragrances and micro-purified water 27.49 sum 100.0

Formulation Example 1-5: Pack

As shown in Table 6 below, a pack containing ellagic acid as an active ingredient was prepared according to a conventional method.

ingredient weight% ellagic acid 0.01 polyvinyl alcohol 13.0 Sodium Carboxymethylcellulose 0.2 allantoin 0.1 ethanol 5.0 nonylphenyl ether 0.3 Preservatives, micro pigments, micro fragrances and micro-purified water 81.39 sum 100.0

Formulation Example 2: Pharmaceutical Formulation

Formulation Example 2-1: Preparation of powder

ingredient content (g) ellagic acid 2 lactose One

The above ingredients were mixed and filled in an airtight cloth to prepare a powder.

Formulation Example 2-2: Preparation of tablets

ingredient Content (mg) ellagic acid 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the above ingredients, tablets were prepared by tableting according to a conventional manufacturing method of tablets.

Formulation Example 2-3: Preparation of capsules

ingredient Content (mg) ellagic acid 100 corn starch 100 lactose 100 Magnesium Stearate 2

After mixing the above ingredients, the capsules were prepared by filling in gelatin capsules according to a conventional manufacturing method of capsules.

Formulation Example 2-4: Preparation of gel

ingredient weight% ellagic acid 1.00 Butylene Glycol 2.00 glycerin 1.00 Disodium EDIT 0.02 PEG-60 Hydrogenated Castor Oil 1.00 Cocamidopropyl Betaine 4.00 Lauryl Glucoside 6.00 Polysorbate 20 1.00 Sodium Benzoate 0.40 caprylic glycol 0.20 sodium lactate 0.50 Hydroxyethyl Cellulose 0.7 Purified water 82.18 sum 100.0

After mixing the above ingredients, a gel containing ellagic acid as an active ingredient was prepared according to a conventional method.

Formulation Example 2-5: Preparation of ointment

ingredient weight% ellagic acid 1.0 diethanolamine 1.5 polyvinylptolidone 5.0 propylene glycol 30.0 Purified water 62.5 sum 100.0

Claims (4)

A cosmetic composition for inhibiting or improving sebum secretion comprising ellagic acid or a cosmetically acceptable salt thereof as an active ingredient.
The cosmetic composition of claim 1, wherein the cosmetic composition is composed of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray. A cosmetic composition for suppressing or improving excessive sebum secretion, which has a formulation selected from the group.
A pharmaceutical composition for preventing or treating seborrheic dermatitis comprising ellagic acid or a pharmaceutically acceptable salt thereof as an active ingredient.
A food composition for preventing or improving seborrheic dermatitis comprising ellagic acid or a pharmaceutically acceptable salt thereof as an active ingredient.

Images