KR101937433B1 - Composition for the preventing loss of hair and promoting growth of hair containing benzofuran derivative or pharmaceutically acceptable salts thereof as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for prevention of hair loss and a composition for promoting hair growth, which comprises a benzofuran derivative or a pharmaceutically acceptable salt thereof, and more particularly to a composition for prevention of hair loss and hair growth comprising a benzofuran derivative or a pharmaceutically acceptable salt thereof And a cosmetic composition for promoting hair growth, a pharmaceutical composition and a health functional food.
The 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol (IK-16) IK-16 of the present invention can be effectively used as an active ingredient of a cosmetic composition for preventing hair loss and promoting hair growth since it exhibits an effect of promoting proliferation and migration of cells and exhibiting a hair growth promoting effect in vivo have.

Description

[0001] The present invention relates to a composition for preventing hair loss and promoting hair growth, which comprises a benzofuran derivative or a pharmaceutically acceptable salt thereof,

The present invention relates to a composition for prevention of hair loss and a composition for promoting hair growth, which comprises a benzofuran derivative or a pharmaceutically acceptable salt thereof, and more particularly to a composition for prevention of hair loss and hair growth comprising a benzofuran derivative or a pharmaceutically acceptable salt thereof And a cosmetic composition for promoting hair growth, a pharmaceutical composition and a health functional food.

Human hair primarily acts as a defense function to protect the scalp from external stimuli such as ultraviolet rays and plays an aesthetic function expressing the external image of the individual. In modern society, however, hair loss is frequently caused by environmental factors such as environmental pollution, strong ultraviolet rays, stress, and hormonal imbalance. Unlike the past, which is confined to adult males, Therefore, the need for materials for prevention and treatment of these diseases has become urgent.

A hair follicle, which is a physiological organ in the body that produces hair, is involved in the process of growth, maintenance, and elimination of hair. Specifically, hair follicles are formed during the postnatal development and during the growth phase in which the hair is actively growing The hair growth cycle is divided into a catagen phase where the hair degenerates, a telogen phase which is maintained until the hair is removed, and an exogen phase where hair loss occurs. . Recently, interest in the activity of hair follicles has increased as hair loss has increased and demand for hair growth and hair growth promotion has increased. The activity of hair follicles is caused by dermal papilla cells, in particular, the proliferation and differentiation of dermal papilla cells are involved primarily in the progression of the hair growth cycle and hair formation. In the growth phase where the hair grows actively, the active growth and differentiation of the papillary cells occurs actively, the growth of the hair is stopped, and the cells are killed in the regenerator, the resting period and the hair removal period where the hair loss occurs.

Therefore, hair growth and hair loss are closely related to the proliferation and death of the dermal papilla cells. Therefore, prolonging the growth period or inhibiting apoptosis and shortening the period of regrowth, dormancy and hair loss by inducing proliferation of the dermal papilla cells will be a remedy It is attracting attention. Cell division and migration in the vicinity of the dermal papilla is closely related to the growth of the hair. In the growing phase, hair is newly generated from the dermal papilla. Cells are activated by various cytokines and hormones, Of the growth rate.

Representative drugs approved by the FDA as drugs that can promote hair growth and hair growth are minoxidil and finasteride. However, these drugs are accompanied by side effects such as hair growth of the whole body and deterioration of sexual function, and the specific mechanism of action of minoxidil is not clearly understood. Therefore, the hair follicle cell proliferation in the hair follicle and the expression of growth factors, while trying to develop a stable drug to human body.

Accordingly, the present inventors have made efforts to select a compound capable of promoting the proliferation and migration ability of dermal papilla cells and use it as an effective ingredient of an effective hair promoting composition. As a result, it has been found that a derivative of benzofuran, 6-methoxy- (4-methoxyphenyl) benzofuran-5-ol, IK-16) in the immortalized dermal papilla cells and the primary cultured The present inventors have completed the present invention by confirming that IK-16 can significantly exhibit the hair growth promoting effect in mice that exhibit an effect of promoting proliferation of dermal papilla cells and exhibit an effect of enhancing cell migration ability.

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Accordingly, the inventors of the present invention completed the present invention by confirming that among various compounds, IK-16 is a compound capable of increasing the proliferation and migration ability of dermal papilla cells and promoting hair growth in mice and the like.

Accordingly, an object of the present invention is to provide a cosmetic composition for preventing hair loss and promoting hair growth.

It is also an object of the present invention to provide a pharmaceutical composition for preventing hair loss and promoting hair growth.

Still another object of the present invention is to provide a health functional food for hair loss prevention and hair growth promotion.

In order to achieve the above object, the present invention provides a cosmetic composition for preventing hair loss and promoting hair growth, comprising a benzofuran derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient do.

[Chemical Formula 1]

.

.

Wherein R ₁ , R ₂ or R ₃ are each independently selected from H, hydroxy, C 1 -C 4 alkyl or methoxy.

The present invention also provides a pharmaceutical composition for preventing hair loss and promoting hair growth, which comprises the benzofuran derivative represented by the above formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention also provides a health functional food for preventing hair loss and promoting hair growth, comprising the benzofuran derivative represented by the above formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

In a preferred embodiment of the present invention, the benzofuran derivative is 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol having the structure of the following formula 4-methoxyphenyl) benzofuran-5-ol).

(2)

.

.

Accordingly, the present invention provides a composition for preventing hair loss and promoting hair growth comprising a benzofuran derivative or a pharmaceutically acceptable salt thereof as an active ingredient.

6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol, which is a derivative of the benzofuran of the present invention, IK -16) promotes the proliferation of immortalized dermal papilla cells and primary cultured dermal papilla cells, exhibits an effect of enhancing cell migration ability, and can significantly exhibit the hair growth promoting effect in hairless mice. Therefore, IK-16 of the present invention is effective as an active ingredient of a cosmetic composition for preventing hair loss and promoting hair growth, a quasi-drug, a pharmaceutical composition and a health functional food.

Figure 1 quantitatively demonstrates the effect of various novel compounds on promoting the development of the dermal papilla cell.
Figure 2 shows the morphology of the dermal papilla cells grown when the various new compounds were treated.
FIG. 3 is a graph showing the effect of stimulation of proliferation of IK-16 on the proliferation-promoting effect of immortalized dermal papilla cells (I-DPC) over time.
FIG. 4 is a graph showing the effect of promoting proliferation of IK-16 according to the concentration of IK-16 in promoting I-DPC proliferation.
FIG. 5 shows the morphology of the dermal papilla grown according to the treatment concentration of IK-16 in the I-DPC promoting effect of IK-16.
FIG. 6 is a graph showing the effect of accelerating the migration ability of IK-16 according to time, in the effect of promoting the I-DPC migration ability of IK-16.
FIG. 7 shows the observation of the migrated form of I-DPC according to the concentration of IK-16 in the I-DPC migration promoting effect of IK-16.
FIG. 8 is a graph showing the effect of accelerating the proliferation of IK-16 according to time, in the effect of accelerating the DPC proliferation of primary culture of IK-16.
Fig. 9 shows the effect of promoting proliferation of IK-16 according to the concentration of IK-16 in the primary culture-promoting effect of DPC proliferation.
FIG. 10 shows the morphology of the dermal papilla grown according to the treatment concentration of IK-16 in the DPC proliferation promoting effect of primary culturing of IK-16.
Fig. 11 shows the confirmation of the effect of accelerating hair growth in mice and the like when IK-16 was applied to skin by dermal application.
Fig. 12 shows confirmation of hair growth promoting effect in mice and the like when IK-16 was administered by subcutaneous injection.
Fig. 13 shows the increase in hair weight due to the promotion of hair growth when IK-16 was administered by subcutaneous injection.

Hereinafter, the present invention will be described in detail.

As described above, in addition to changes in hormone secretion, the demand for a cosmetic composition capable of preventing hair loss and promoting hair growth has been increased due to an increase in hair loss due to stress. However, among the compounds known to be safe for human body, effective hair loss prevention and hair growth There has not been much reported on the compounds that can be promoted.

6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol, which is a derivative of the benzofuran of the present invention, IK -16) promotes the proliferation of immortalized dermal papilla cells and primary cultured dermal papilla cells, exhibits an effect of enhancing cell migration ability, and can significantly exhibit the hair growth promoting effect in hairless mice. Therefore, IK-16 of the present invention is effective as an active ingredient of a cosmetic composition for preventing hair loss and promoting hair growth, a quasi-drug, a pharmaceutical composition and a health functional food.

Accordingly, the present invention provides a cosmetic composition for preventing hair loss and promoting hair growth, comprising a benzofuran derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

.

.

Wherein R ₁ , R ₂ or R ₃ are each independently selected from H, hydroxy, C 1 -C 4 alkyl or methoxy.

The "benzofuran derivative" of the present invention is a 6-methoxy-3- (4-methoxyphenyl) benzofuran derivative having a structure of the following formula (2) benzofuran-5-ol), but is not limited thereto:

(2)

.

.

In a specific example of the present invention, the present inventors selected compounds capable of promoting the proliferation of dermal papilla cells and increasing the ability to migrate cells, and found that 6-methoxy-3- (4-methoxyphenyl) benzofuran (IK-16) (Figs. 1 and 2).

In addition, the inventors of the present invention found that IK-16 inhibited significantly apoptotic dermal papilla cells (I-DPC) and primary cultured cells at a concentration of 1 to 10 μM (FIG. 3, FIG. 4, FIG. 5, FIG. 8, FIG. 9, and FIG. 10), and it was found that when treated with I-DPC, (Figs. 6 and 7).

In addition, the present inventors have found that IK-16 can exhibit a significant hair growth promoting effect in vivo. As a result, when applied to the back of hairless mice and administered by percutaneous absorption or subcutaneous injection, (Fig. 11, Fig. 12, and Fig. 13).

Thus, the 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol (IK-16) IK-16 of the present invention is useful as an active ingredient of a cosmetic composition for preventing hair loss and promoting hair growth since it exhibits an effect of promoting proliferation and migration of dermal papilla cells and exhibiting an effect of promoting hair growth in vivo Can be used.

When the compound of the formula (1) of the present invention is used as an active ingredient of the quasi-drug composition, the compound of the formula (1) which exhibits the effect of preventing hair loss and promoting hair growth can be directly added or used together with other quasi-drugs or quasi drugs , And can be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.

The composition for preventing hair loss and promoting hair growth of the present invention is not particularly limited in its formulation and may be variously formulated in the form of a quasi-drug known in the art to exhibit hair loss prevention and hair growth promoting effects. The formulated quasi-drugs include hair tonic, hair lotion, hair cream, hair spray, hair mousse, hair gel, hair conditioner, hair shampoo, hair rinse, hair pack, hair treatment, eyebrow hair removal agent, eyelash hair growth agent, Shampoos, pet rinse, hand cleaner, detergent soap, soap, disinfectant cleaner, wet tissue, mask, ointment, patch or filter filler, and all the quasi-drugs in the usual sense.

In addition, the composition for preventing hair loss and promoting hair growth in each formulation can be blended with other ingredients arbitrarily selected depending on the formulation of the other quasi-drugs, the purpose of use, and the like. The amount of the active ingredient to be mixed may be appropriately determined depending on the purpose of use, and may include, for example, customary adjuvants such as thickeners, stabilizers, solubilizers, vitamins, pigments and flavors, and carriers.

The content of the composition is preferably 0.0001 to 10% by weight based on the total weight of the composition. If it is more than 10% by weight, the color and stability of the composition are poor. When the composition is less than 0.0001% by weight, . The quasi-drug composition containing the compound of formula (I) of the present invention as an active ingredient has little toxicity and side effects to cells as confirmed by the treatment index, and thus can be usefully used as a quasi-drug product.

The present invention also provides a pharmaceutical composition for preventing hair loss and promoting hair growth, comprising a benzofuran derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:

[Chemical Formula 1]

.

.

The "benzofuran derivative" of the present invention is a 6-methoxy-3- (4-methoxyphenyl) benzofuran derivative having a structure of the following formula (2) benzofuran-5-ol), but is not limited thereto:

(2)

.

.

The compound of the present invention can be used in the form of a pharmaceutically acceptable salt. As the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include those derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxyalkanoates, Dioleate, aromatic acid, aliphatic and aromatic sulfonic acids. Such pharmaceutically innocuous salts include, but are not limited to, sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate chloride, bromide, Butyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, succinate, maleic anhydride, maleic anhydride, , Sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Methoxybenzoate, phthalate, terephthalate, benzene sulfonate, toluene sulfonate, chlorobenzene sulfide Propyl sulphonate, naphthalene-1-yne, xylenesulfonate, phenylsulfate, phenylbutyrate, citrate, lactate,? -Hydroxybutyrate, glycolate, maleate, Sulfonate, naphthalene-2-sulfonate or mandelate.

The acid addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving the compound of the formula (1) in an excess amount of an acid aqueous solution, and mixing the salt with a water-miscible organic solvent such as methanol, ethanol, Followed by precipitation using nitrile. By heating the same amount of the compound of formula (I) and an acid or alcohol in water, and then evaporating and drying the mixture, or by filtering the precipitated salt by suction filtration.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess amount of an alkali metal hydroxide or an alkaline earth metal hydroxide solution, filtering the insoluble compound salt, and evaporating and drying the filtrate. At this time, it is preferable for the metal salt to produce sodium, potassium or calcium salt. The corresponding silver salt is also obtained by reacting an alkali metal or alkaline earth metal salt with a suitable salt (such as silver nitrate).

The compound of formula (I) of the present invention includes not only pharmaceutically acceptable salts, but also all salts, hydrates and solvates which can be prepared by conventional methods.

The addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving the compound of Chemical Formula 1 in a water-miscible organic solvent such as acetone, methanol, ethanol, or acetonitrile, Or by adding an aqueous acid solution of an inorganic acid, followed by precipitation or crystallization. Subsequently, in this mixture, a solvent or an excess acid is evaporated and dried to obtain an additional salt, or the precipitated salt may be produced by suction filtration.

When the composition of the present invention is used as a medicine, the pharmaceutical composition containing the compound of the formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient can be formulated into various oral or parenteral dosage forms But the present invention is not limited thereto.

Examples of the formulations for oral administration include tablets, pills, light / soft capsules, liquids, suspensions, emulsions, syrups, granules and elixirs. These formulations may contain, in addition to the active ingredient, a diluent (e.g., lactose, dextrose, (E.g., silica, talc, stearic acid and magnesium or calcium salts thereof and / or polyethylene glycols), such as, for example, water, rosin, sucrose, mannitol, sorbitol, cellulose and / or glycine. The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine and may optionally contain additives such as starch, agar, alginic acid or its sodium salt A disintegrating or boiling mixture and / or an absorbent, a colorant, a flavoring agent, and a sweetening agent.

The pharmaceutical composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient can be administered parenterally, and parenteral administration can be carried out by subcutaneous injection, intravenous injection, intramuscular injection, As shown in FIG. In this case, in order to formulate the composition for parenteral administration, the compound of the formula (1) or a pharmaceutically acceptable salt thereof may be mixed with water or a stabilizer or a buffer to prepare a solution or suspension, . The compositions may contain sterilized and / or preservatives, stabilizers, wettable or emulsifying accelerators, adjuvants such as salts and / or buffers for the control of osmotic pressure, and other therapeutically useful substances, Or may be formulated according to the coating method.

The dose of the compound of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health condition, and disease severity. In general, when referring to an adult patient weighing 60 kg, And may be 0.01 to 500 mg / day, preferably 0.01 to 500 mg / day, and may be administered once or several times a day at regular intervals according to the judgment of a doctor or pharmacist.

The present invention also provides a health functional food for preventing hair loss and promoting hair growth, comprising a benzofuran derivative represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

.

.

The "benzofuran derivative" of the present invention is a 6-methoxy-3- (4-methoxyphenyl) benzofuran derivative having a structure of the following formula (2) benzofuran-5-ol), but is not limited thereto:

(2)

.

.

The food composition according to the present invention can be prepared in various forms according to a conventional method known in the art. Common foods include but are not limited to beverages (including alcoholic beverages), fruits and processed foods (eg, canned fruits, jam, maamalade, etc.), fish, meat and processed foods (Eg butter, chewing), edible vegetable oil, margarine (such as corn oil, etc.), breads and noodles (eg udon, buckwheat noodles, ramen noodles, spaghetti, macaroni, etc.), juice, various drinks, cookies, , Vegetable protein, retort food, frozen food, various kinds of seasonings (for example, soybean paste, soy sauce, sauce, etc.). The nutritional supplement may be prepared by adding the compound of formula (I) of the present invention to capsules, tablets, rings and the like. The health functional food is not limited to this. For example, the compound of formula (I) of the present invention itself may be prepared in the form of tea, juice, and drink to be liquefied, granulated, encapsulated And powdered. In order to use the compound of formula (I) of the present invention in the form of a food additive, it may be prepared in the form of powder or concentrate. In addition, the compound of formula (I) of the present invention may be mixed with a known active ingredient known to be effective in preventing hair loss and promoting hair growth to prepare a composition.

When the compound of the formula (1) of the present invention is used as a health drink, the health beverage composition may contain various flavors or natural carbohydrates as an additional ingredient like ordinary beverages. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose; Polysaccharides such as dextrin, cyclodextrin; Xylitol, sorbitol, erythritol, and the like. Sweeteners include natural sweeteners such as tau Martin and stevia extract; Synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

The compound of formula (I) of the present invention may be contained as an active ingredient of a health functional food for preventing hair loss and promoting hair growth, and the amount thereof is specifically limited to an amount effective for achieving hair loss prevention and imitation growth promoting effect However, it is preferably 0.01 to 100% by weight based on the total weight of the composition. The food composition of the present invention may be prepared by mixing together with the compound of formula (1) together with other active ingredients known to be effective in preventing hair loss and effect of stimulating growth.

In addition to the above, the health food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acid, protective colloid thickener, pH adjusting agent, Glycerin, an alcohol or a carbonating agent, and the like. In addition, the health food of the present invention may contain natural fruit juice, fruit juice drink, or pulp for the production of vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these examples are for illustrative purposes only and that the scope of the present invention is not construed as being limited by these examples.

Dairy cattle  Cells (dermal papilla cells, DPC ) Preparation and selection of new compounds with proliferation promoting effect

<1-1> DPC  Selection of compound having proliferation effect

Novel compounds were synthesized for use as the subject compounds of the present invention to produce a total of 20 synthetic compounds.

Then, a human-derived dermal papilla cell (I-DPC; donated by Professor Sung Young-Kwan of Kyungpook National University, College of Medicine, Shin, Seung-Hyun, et al.) Establishment and characterization of an immortalized human dermal papilla cell line. BMB reports 44.8 (2011): 512-516) were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS) and penicillin-streptomycin antibiotics for 3 days to prepare pelvic cell lines. On the third day of culturing, the cells cultured in the culture dish were transferred to a 96-well plate, and when the cells were attached to the well bottom, the respective synthetic compounds were treated in each well at a concentration of 10 μM and cultured for 48 hours . The culture was carried out in a constant temperature incubator at 37 ° C and 5% carbon dioxide. After completion of the incubation, the wells in which the cells were cultured were observed with a phase contrast microscope to confirm the morphology of the cells. Then, 10 μl of CCK-8 (Dojindo, Gaithersburg, MD) solution was added to each well and incubated for 3 hours , And absorbance was measured at 450 nm using a microplate reader. Then, the relative cell proliferation effect according to the added synthetic compound was compared as a percentage based on the cell proliferation rate of 100% in the untreated control group to which the synthetic compound was not added.

As a result, as shown in Figs. 1 and 2, it was confirmed that the dermal papilla cells were proliferated in an environment treated with the synthesized compound (Fig. 1), and in the well treated with Compound 16 (IK-16) Cell proliferation showed the highest level, indicating a level of about 120% as compared to the untreated control (Fig. 2).

<1-2> IK -16 Characterization of compounds

The structures of IK-16 compounds, which were confirmed to have the highest level of promoting the growth of papilla cells, were analyzed by NMR analysis.

As a result, NMR analysis results of the IK-16 compound were confirmed as follows: White solid; _{^{1 HNMR (400 MHz, CDCl 3}} ) δ7.63 (s, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.31 (s, 1H), 7.06 (s, 1H), 7.00 (d, J = 8.0 Hz, 2H), 5.55 (s, 1H), 3.97 (s, 3H), 3.86 (s, 3H).

Further, the IK-16 compound is a 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol having a structure represented by the following formula (2) 5-ol): &lt; / RTI &gt;

(2)

.

.

IK -16 of the compound Dairy cattle  Identification of cell proliferation promoting effect

Among the various compounds, it was confirmed that the promoting effect of IK-16 on the proliferation of the dermal papilla cells was the highest, so that the proliferation promoting effect was more specifically confirmed.

Specifically, the I-DPC cell line was prepared by culturing under the same conditions as in the above Example <1-1>, treated with IK-16 at a concentration of 1, 10 or 50 μM in a cell culture medium, Respectively. At 24, 48 and 72 hours after the initiation of the culture, the degree of saturation of the cells attached to the bottom of the well (phase object confluence,%) was confirmed. Forty-eight hours after the incubation, the wells were observed under a phase contrast microscope to confirm the morphology of the cells. Then, 10 μl of CCK-8 solution was added to each well and incubated for 3 hours, and the absorbance at 450 nm was measured using a microplate reader . Then, the relative cell proliferation effect according to the added synthetic compound was compared as a percentage based on the cell proliferation rate of 100% in the untreated control group to which the synthetic compound was not added.

As a result, as shown in FIG. 3 to FIG. 5, it was confirmed that IK-16 affects the proliferation of IK-16 in a concentration-dependent manner in promoting the proliferation of I-DPC and was treated at a concentration of 1 to 10 μM (Fig. 3 to Fig. 5). &Lt; tb &gt; &lt; TABLE &gt;

IK -16 of the compound Dairy cattle  cell Migration ability (cell migration) promotion effect

Since the migration of dermal papilla cells in hair growth is closely related, it has been confirmed whether the IK-16 compound of the present invention can promote the cell migration ability as well as the dermal papilla cell growth.

Specifically, the I-DPC cell line was inoculated in a 6-well plate containing DMEM medium supplemented with 10% fetal bovine serum (FBS) and penicillin-streptomycin antibiotic and incubated for 24 hours in a constant temperature incubator at 37 DEG C under 5% The cells were cultured, and the cells were asked to be on the plate. Then, the cells were washed twice with serum-free DMEM medium containing no FBS, wounded using a microtip, and then divided into two groups. Serum-free medium was added to the first group (control group), and serum-free medium containing IK-16 at a concentration of 1 or 10 μM was added to the second group (experimental group) for additional 16 hours. At 6, 12 and 16 hours after the initiation of the culture, the degree of cell migration was observed with a phase contrast microscope to confirm cell migration ability.

As a result, as shown in FIG. 6 and FIG. 7, the migration ability of I-DPC was influenced by the concentration-dependent effect of IK-16, and it was confirmed that the cell migration ability was promoted when IK-16 was treated with 1 to 10 μM (Figs. 6 and 7).

Primary culture Dairy cattle  In a cell IK -16 Promoting growth promotion effect

Since IK-16 has a significant proliferation promoting effect on dermal papilla cells, which are immortalized cells, it is possible to determine whether IK-16 can promote proliferation even in the case of dermal papilla cells isolated from tissues Respectively.

Specifically, primary dermal papilla cells (purchased from PromoCell, C12071) were cultured in the same manner as in Example <1-1>, and IK-16 compounds were added to the medium at a concentration of 1, 10 or 50 μM And then cultured for 72 hours in the same manner as in <Example 2> to confirm the proliferation effect of the dermal papilla cells.

As a result, as shown in FIG. 8 to FIG. 10, it was confirmed that IK-16 affects the proliferation of IK-16 in a concentration-dependent manner in promoting tissue-derived dermal papilla cell proliferation and treated with a concentration of 1 to 10 μM (Fig. 8 to Fig. 10). As shown in Fig.

In vivo IK Identification of effect of promoting hair growth by -16

It was confirmed that IK-16 promotes the proliferation and migration ability of the dermal papilla cells. Therefore, when applied in vivo, the hair cycle was induced from the dormant period to the anagen, and it was confirmed that it could exhibit the effect of promoting actual hair growth.

Specifically, male C57BL / 6N mice, 6 weeks of age, were purchased and tested for the negative control group and the IK-16 treatment group in order to confirm the hair promoting effect upon administration of IK-16. When the mouse was 8 weeks old, hair was removed from the mouse back plate using a mouse clipper to check the hair growth effect, and IK-16 was applied to the skin of the mouse once a day by vaseline treatment , The negative control group was applied with only Vaseline, which did not contain IK-16, and was bred for a total of 2 weeks.

In order to confirm the effect of promoting hair growth in the hypodermic injection of IK-16, PBS containing 100 μM IK-16 was subcutaneously injected into the hair dorsal rats on a daily basis for 2 weeks. After the end of the rearing period, the hair of the backing plate was removed with a mouse clipper, and the weight of the hair collected was measured and compared with the weight of the hair of the non-administration control group.

As a result, as shown in FIG. 11 to FIG. 13, hair cycle was induced by IK-16 when both IK-16 application and subcutaneous injection were induced. As a result, (Fig. 11 and Fig. 12). When the weight of the hair was measured, it was confirmed that the weight of hair was about twice that of the hair (Fig. 13), and it was confirmed that hair growth was promoted by IK-16 .

Claims (7)

delete 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol having the structure of the following formula (2) A cosmetic composition for preventing hair loss and promoting hair growth comprising an acceptable salt as an active ingredient:
(2)

.
The cosmetic composition according to claim 2, wherein the cosmetic composition is selected from the group consisting of hair tonic, hair lotion, hair cream, hair spray, hair mousse, hair gel, hair conditioner, hair shampoo, hair conditioner, hair pack, hair treatment, A cosmetic composition for preventing hair loss and promoting hair growth, characterized in that it is a formulation of a nutrient, a shampoo for a pet, or a rinse for a pet.
delete A method for preventing hair loss and promoting hair growth comprising 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol or a pharmaceutically acceptable salt thereof as an active ingredient having a structure represented by the following formula Pharmaceutical composition:
(2)

.
delete A method for preventing hair loss and promoting hair growth comprising 6-methoxy-3- (4-methoxyphenyl) benzofuran-5-ol or a pharmaceutically acceptable salt thereof as an active ingredient having a structure represented by the following formula Health functional foods:
(2)

.

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