KR20150125053A - Composition including 3-bromo-4,5-dihydroxybenzaldehyde for prevention of hair loss or for promoting hair growth - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing hair loss or promoting hair growth, including 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or salt thereof as an active ingredient. The composition including 3-bromo-4,5-dihydroxybenzaldehyde (BDB) is recognized to have efficacies of suppressing and preventing hair loss and promoting hair growth, and thus being able to be variously utilized in fields of pharmacy, cosmetics, beauty care, and so on.

Description

[0001] The present invention relates to a composition for preventing hair loss or promoting hair growth comprising 3-bromo-4,5-dihydroxybenzaldehyde as an active ingredient. }

The present invention relates to a composition for promoting hair loss prevention or hair growth comprising 3-bromo-4,5-dihydroxybenzaldehyde (BDB) compound and a salt thereof as an active ingredient .

The hair of the human body is about 100,000 to 150,000, and it is formed in "hair follicle". There is a nipple in the hair follicle, where small blood vessels are distributed to supply the nutrients needed to grow hair, and beside the papilla there is a bore hole that supplies the hair with shine oil. Hair follicles are composed of several different epithelial cells and dermal papilla cells (DPCs). DPCs are mesenchymally-derived fibroblasts located at the base of hair follicles and play an important role in hair growth. In particular, minoxidil has been reported to have proliferative and anti-apoptotic effects on DPCs. Similarly, several reports have shown an increase in hair growth through the proliferation of DPCs. Each hair has a different cycle and grows through anagen, catagen, and telogen, and then falls off. This cycle repeats over 3 to 6 years, with an average of 50 to 100 hairs dropping normally on a daily basis. In general, alopecia refers to an abnormal increase in the number of hair that has fallen due to a shortening of the percentage of growing hair and an increase in the number of retrogressive or resting hair among these cycles.

The causes of hair loss include male hypothyroidism, excess sebaceous glands, poor blood circulation, peroxidation, hypofunction of the scalp, genetic factors, aging, and stress. Testosterone, a type of male hormone, is activated by dihydrotestoserone (DHT) by an enzyme called 5α-reductase, which binds to a specific receptor and induces a protein that causes hair loss. . In addition, this mechanism causes excessive production of sebum, acne and seborrheic dermatitis, which can lead to hair loss with inflammation in the scalp. Alopecia is known to be caused by disease, malnutrition, aging, and hormonal imbalance. Although many studies have been conducted, the mechanism of essential hair loss is not well known. Efforts have also been made to treat hair loss. Nevertheless, so far only two drugs (finasteride and minoxidil) have been approved by the Food and Drug Administration (USA) for hair loss treatment. The 5α-reductase inhibitor, finasteride, has been used to promote hair growth in male androgenetic alopecia. Minoxidil, an anti-hypertensive agent, can promote hair growth by opening the ATP-sensitive K ⁺ -channel. However, the effects of drugs are limited and transient due to unpredictable effects and side effects. There is a need for better new treatments to prevent hair loss and promote hair growth. In the case of preparations such as minoxidil and trichosaccharide, which have been known to prevent hair loss and promote hair growth and have the effect on hair growth, there is a lack of clear efficacy, human safety and skin irritation There is a problem of side effects, and it is urgent to develop a composition having safety and efficacy.

Therefore, the inventors of the present invention have found that, while searching for substances exhibiting hair loss prevention and hair growth promoting effect with little toxicity, Rhodomela confervoides , Polysiphonia 3-bromo-4,5-dihydroxybenzaldehyde (BDB), isolated from red alga such as morrowii and Polysiphonia urceolata , has been shown to prevent hair loss and promote hair growth Thereby completing the present invention.

Korean Patent Publication No. 10-2014-0001618 (Apr.

It is an object of the present invention to provide a pharmaceutical composition for preventing hair loss, which comprises 3-bromo-4,5-dihydroxybenzaldehyde (BDB) as an active ingredient.

Another object of the present invention is to provide a cosmetic composition for promoting hair growth, which comprises 3-bromo-4,5-dihydroxybenzaldehyde as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing hair loss comprising 3-bromo-4,5-dihydroxybenzaldehyde (BDB) as an active ingredient .

The present invention also provides a cosmetic composition for promoting hair growth, which comprises 3-bromo-4,5-dihydroxybenzaldehyde as an active ingredient.

The pharmaceutical composition for preventing hair loss, which comprises 3-bromo-4,5-dihydroxybenzaldehyde (BDB) as an active ingredient, And is involved in the proliferation of dermal papilla cells by activation of the Wnt / β-catenin signaling pathway as well as cell cycle proteins. Therefore, it has been recognized that it is effective to inhibit and prevent hair loss and promote hair growth, And so on.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the structure of 3-bromo-4,5-dihydroxybenzaldehyde (BDB).
FIG. 2 is a graph showing growth of hair follicles according to the concentration of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) according to the present invention.
FIG. 3 is a graph showing the effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) according to the present invention on the growth of dermal papilla cells.
4 shows that 3-bromo-4,5-dihydroxybenzaldehyde (BDB) according to the present invention is involved in the proliferation of dermal papilla cells by activation of the cell cycle protein as well as the Wnt /? - catenin signaling pathway Fig.

Hereinafter, the present invention will be described in detail.

Herein, " hair loss " means prevention of hair loss phenomenon as described above, and " hair loss prevention " Promoting " means not only promoting the generation of new hair but also allowing the existing hair to grow healthily.

In general, "hair growth" occurs in the growing phase, and is induced by the delay from the dormancy to the growth phase and from the growth phase to the retrograde phase. The hair cycle can be divided into three main stages known as growth phase, regressor phase, and quiescent phase. During the growing season, hair growth takes place as the hair follicles grow deep into the skin with rapid cell proliferation. The next phenomenon is the retrogressive period, which is a transitional period in which disruption of cell division is prominent, during which the hair follicles gradually regress and hair growth stops. In the next pause, the regressive hair follicle contains germs with densely packed dermal papilla cells. The onset of a new growth phase in dormancy is induced by rapid cell proliferation in the abdomen, swelling of the papilla and synthesis of basement membrane elements.

Therefore, it is necessary to prevent hair loss by promoting or prolonging the growing period, that is, to prevent hair loss or to induce regrowth of hair, that is, to promote hair growth, and the composition according to the present invention is effective in preventing hair An effect of improving the existing hair such as thickening, and an effect of generating new hair. Dermal papilla cells are believed to play an important role in hair growth through interactions with mosquito cells of hair follicles, which are mesenchymal-derived fibroblasts located at the base of hair follicles (Jahoda CA, meat al ., 1984; Oliver RF, et al., 1986). In addition, minoxidil, which is used as a hair loss treatment, has been shown to increase growth in NIH3T3 fibroblasts with K _ATP- channel opener ( Sanders , et al ., 1996).

The present invention provides a pharmaceutical composition for preventing hair loss comprising 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or a salt thereof as an active ingredient.

The active ingredient 3-bromo-4,5-dihydroxybenzaldehyde (BDB) compound contained in the composition according to the present invention can be used in the form of a salt, preferably a pharmaceutically acceptable salt. The salt is preferably an acid addition salt formed by a pharmaceutically acceptable free acid, and the free acid may be an organic acid or an inorganic acid. The organic acids include, but are not limited to, citric, acetic, lactic, tartaric, maleic, fumaric, formic, propionic, oxalic, trifluroacetic, benzoic, gluconic, methosulfonic, glycolic, succinic, Glutamic acid and aspartic acid. The inorganic acid includes, but is not limited to, hydrochloric acid, bromic acid, sulfuric acid, and phosphoric acid.

The 3-bromo-4,5-dihydroxybenzaldehyde compound according to the present invention can be isolated from nature or can be prepared by chemical synthesis methods known in the art.

The composition of the present invention containing such BDB as an active ingredient is useful as a pharmaceutical composition

.

The pharmaceutical composition of the present invention may be various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories.

Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The pharmaceutical dosage forms of the compositions of the present invention may also be used in the form of their pharmaceutically acceptable salts and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set. The salt is not particularly limited as long as it is pharmaceutically acceptable so long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, , Benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid.

The composition of the present invention may be administered parenterally or orally, and may be administered in one to several divided doses so as to be administered in an amount of 0.1 to 500 mg per kg of body weight per day. The dosage for a particular patient may vary depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate, severity of disease, and the like.

The pharmaceutical composition according to the present invention may be formulated into oral compositions such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations such as ointments and creams, suppositories and sterile injection solutions And may be formulated in any form suitable for pharmaceutical preparations.

The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes such as parenteral, oral, and the like, and all manner of administration can be expected. For example, Or by intravenous, intramuscular, subcutaneous, intramural or intracerebroventricular injection.

Meanwhile, since the composition according to the present invention has no serious toxicity and side effects, it can be safely used for prolonged use for preventive purposes.

In a specific embodiment of the present invention, the concentration of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or its salt of the present invention is preferably 0.001-10 μM, The age, body weight, health condition, sex, route of administration, duration of treatment and the like of the patient.

The present invention also provides a cosmetic composition for promoting hair growth, comprising 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or a salt thereof as an active ingredient.

In a specific embodiment of the present invention, the concentration of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or its salt of the present invention is preferably 0.001-10 μM, The age, body weight, health condition, sex, route of administration, duration of treatment and the like of the patient.

The composition may be used in hair cosmetics such as hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair conditioner, hair treatment, hair cream, hair nutrition cream, hair moisturizing cream, Hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair moisturizers, Mousse, and hair spray. However, the present invention is not limited thereto.

The cosmetic composition may be prepared by dissolving or dispersing at least one compound selected from the group consisting of a fatty substance, an organic solvent, a solubilizer, a thickening agent, a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, Such as cosmetics or skin, such as fillers, sequestering agents, chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or any other ingredient commonly used in cosmetics And may contain adjuvants conventionally used in the scientific field. Such adjuvants are introduced in amounts commonly used in the cosmetics or dermatological fields.

The cosmetic composition according to the present invention can be, for example, a cosmetic composition, and the external form of the cosmetic composition contains a cosmetically or dermatologically acceptable medium or base. It may be in any form suitable for topical application, for example, as a solution, a gel, a solid, a paste anhydrous product, an emulsion obtained by dispersing the oil phase in water, a suspension, a microemulsion, a microcapsule, In the form of a non-ionic follicle dispersing agent, or in the form of creams, skins, lotions, powders, ointments, sprays or conical sticks. These compositions may be prepared according to conventional methods in the art. The composition according to the invention may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The cosmetic composition of the present invention is not particularly limited in its formulation and may be, for example, softening lotion, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, Water, a pack, a powder, a body lotion, a body cream, a body oil and a body essence.

The cosmetic composition as described above may be applied to the skin, or may be applied to the skin using a micro needle or the like.

In addition, the compositions of the present invention may be made into a hair composition comprising a carrier or carrier mixture suitable for application to the hair. The carrier comprises a vehicle component commonly used in a carrier or other carrier or hair protective composition and is present in an amount ranging from about 0.5% to 99.5%, preferably from about 5.0% to 99.5%, and most preferably, About 10.0% to 90.0%. As a carrier, the solvent is selected by the copolymer to be used, regardless of whether the formulated hair composition remains on the hair after use such as hair spray, mousse, tonic, etc., or whether it is cleaned, such as shampoos, conditioners and the like. Suitable solvents for use in the present invention include water, lower alcohols (ethanol, isopropanol, etc.), hydroalcoholic mixtures, hydrocarbons such as isobutane, hexane and decene, acetone, halogenated hydrocarbons such as Freon, Dibutyl phthalate and the like), volatile silicone derivatives, siloxane (phenylpentamethyldisiloxane, methoxypropylheptamethylcyclotetrasiloxane, chloropropylpentamethyldisiloxane, hydroxypropylpentamethyldisiloxane, octamethylcyclotetrasiloxane, decamethyl Cyclopentasiloxane, and the like), and mixtures thereof.

In one embodiment of the present invention, there is provided a composition for preventing hair loss comprising 3-bromo-4,5-dihydroxybenzaldehyde (BDB) according to the present invention as an active ingredient The pharmaceutical composition promotes the growth of hair fiber length as compared to the control group of minoxidil (see Fig. 2), and participates in the proliferation of dermal papilla cells by activating the cell cycle protein as well as the Wnt /? - catenin signaling pathway (Refer to FIG. 3 and FIG. 4) can be usefully used as a pharmaceutical composition for preventing hair loss, and a cosmetic composition for preventing hair loss or promoting hair growth, since hair loss is suppressed and prevented and promotion of hair growth is promoted.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more fully explain the present invention to those skilled in the art.

< Example  1> 3- Bromo -4,5- Of dihydroxybenzaldehyde (BDB) Hair - fiber  Length growth effect analysis

<1-1> Rat  Hair follicles Rat vibrissa follicles ) And culture

Male Wistar rats (3 weeks old) were purchased from central laboratory animals (Japan SLC, Hamamatsu, Janpan) and anesthetized with ethyl ether. Rat left and right mysticial pads were separated and placed in E / P buffer (EBSS, Sigma MO, USA) + phosphate buffer containing 100 units / ml penicillin-100 μg / ml streptomycin (Gibco Inc, NY, USA) -buffered saline (PBS, Sigma MO, USA). The vibrissa follicles were carefully removed by observation under a dissecting microscope. The hair follicles were added to a petri dish containing E / P buffer until the hair follicles were completely separated, and cultured in a 5% CO ₂ incubator at 37 ° C for 1 hour. (Gibco Inc, NY, USA), 10 μg / ml insulin (Sigma MO, USA), 50 nM hydrocortisone (Sigma MO, USA) and 100 units / well of a 24 well plate ml penicillin-100 ㎍ / ml streptomycin was added to 500 μl of William E medium (Gibco Inc, NY, USA). One hair follicle was added to each well and cultured in a 5% CO ₂ incubator at 37 ° C. During the culture medium was changed every 3 days and 3-bromo-4,5-dihydroxybenzaldehyde (BDB) (Matrix

Scientific, Columbia, SC, USA) were treated at concentrations of 0.01, 0.1 and 1 μM. Minoxidil, a positive control, was treated at a concentration of 10 μM.

&Lt; 1-2 > vibrissa follicles ) Measurement of growth

The type of cultured vibrissa follicle was photographed using a microscope (Olympus, Japan). Follicular length was measured using an image analyzer (eXcope; DIXI Optics, Korea). The average value of the hair follicle length changes was obtained and compared with the average length of the control group to measure the degree of growth.

Specifically, 3-bromo-4,5-dihydroxybenzaldehyde (BDB) was measured by measuring the length of hair follicles while culturing for 3 weeks after isolating the growing vibrissa follicles of 3-week- Was examined. All measurements were expressed as means ± standard error. Statistical significance was tested with student's t test. Significance was noted when the p-value was less than 0.05. Statistical analysis was performed using Sigma Stat software (Jandel Scientific Software, USA).

As a result, when the length difference (%) of the hair follicles between the 3-bromo-4,5-dihydroxybenzaldehyde (BDB) treated group and the control group was compared on day 21, 0.01, 0.1 and 1 μM Hair fiber growth was increased to 87.3 ± 17.7%, 98.3 ± 26.3% and 175.7 ± 22.4% (P <0.05), respectively, in the control group. In particular, the effect of increasing the hair fiber growth of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) at a concentration of 1 μM was 136.8 ± 24.0% higher than that of minoxidil (10 μM) used as a positive control (Fig. 2).

< Example  2> 3- Bromo -4,5- Of dihydroxybenzaldehyde  Dermal papilla cells Dermal  papilla cell ) Proliferation effect analysis

Dermal papilla cells are believed to play an important role in hair growth through interactions with mosquito cells of hair follicles, which are mesenchymal-derived fibroblasts located at the base of hair follicles (Jahoda CA, meat al ., 1984; Horne K meat al ., 1986). 3-Bromo-4,5-dihydroxybenzaldehyde (BDB) was examined using hair dermal papilla cells for hair regrowth efficacy.

Specifically, immortalized dermal papilla cells (Rat vibrissa immortalized dermal papilla cell: Filsell W, et . al, 1994) to 100 units / ml penicillin-100 ㎍ / ml streptomycin (Gibco Inc, NY, USA) and 10% heat-inactivated fetal bovine serum (FBS; Gibco Inc, NY, USA) are contained DMEM (Hyclone Inc, USA) at 37 ° C in a 5% CO ₂ incubator and subcultured once every 3 days. The proliferation of dermal papilla cells was measured using MTT assay. 1.0 × 10 ⁴ cells / ml of dermal papilla cells were cultured in DMEM medium containing 1% FBS, and cultured for 24 hours in a 96-well plate. Then, 3-bromo-4,5-dihydroxybenzaldehyde (BDB ) Were treated at concentrations of 0.001, 0.01, 0.1 and 1 μM. The positive control minoxidil (Sigma, MO, USA) was treated at a concentration of 10 μM. After 4 days of incubation, 50 μl of MTT (Sigma, MO, USA) was added and reacted for 4 hours. The supernatant was removed, and 200 μl of DMSO was added to dissolve the precipitate. The absorbance was measured at 540 nm using a VERSAmax microplate reader (Molecular Devices, CA, USA). The average absorbance of each sample group was calculated and compared with the absorbance of the control group. All measurements were expressed as means ± standard error. Statistical significance was tested with student's t test. Significance was noted when the p-value was less than 0.05. Statistical analysis was performed using Sigma Stat software (Jandel Scientific Software, USA).

As a result, when treated with 0.001, 0.01, 0.1 and 1 μM of 3-bromo-4,5-dihydroxybenzaldehyde (BDB), 110.1 ± 8.2% ( P <0.01 ) The proliferation of dermal papilla cells was increased by 111.3 ± 6.2% ( P <0.001 ), 114.1 ± 9.4% ( P <0.001 ) and 107.3 ± 7.7% ( P <0.05 ) This is comparable to or somewhat higher than 109.6 ± 7.6% ( P <0.01 ), the proliferation effect of 10 μM minoxidil used as a positive control, and 3-bromo-4,5-dihydroxybenzaldehyde (BDB) Minoxidil (Fig. 3).

< Example  3> 3- Bromo -4,5- Of dihydroxybenzaldehyde  Cell cycle protein regulation minute three

In order to elucidate the molecular mechanism by which 3-bromo-4,5-dihydroxybenzaldehyde (BDB) increases the growth and proliferation of dermal papilla cells, cell cycle protein expression was observed. It is known that mammalian cells require activation of cyclin E / CDK2 complex, increase of cyclin D1 and increase of phosphorylation of pRB for cell cycle progression which is the main process of cell proliferation. The expression of cyclin D1, phospho-pRB, cyclin E, phospho-CDK2, and CDK2 was examined to determine whether the effect of BDB on the proliferation of dermal papilla cells was regulated by cell cycle proteins.

Specifically, dermal papilla cells were cultured in DMEM medium containing 1% FBS for 24 hours, and then 3-bromo-4,5-dihydroxybenzaldehyde (BDB) and 10 μM minoxidil And then cultured for 24 hours. Cells were washed twice with PBS and then lysed in 200 μl of lysis buffer [50 mM Tris-HCl (pH 7.5), 150 mM NaCl, 2 mM EDTA, 1 mM EGTA, 1 mM NaVO3, 10 mM NaF, 1 mM dithiothreitol ), 1 μM phenylmethylsulfonylfluoride (PMSF), 25 μg / mL aprotinin, 25 μg / mL leupeptin and 1% NP-40] and then lysed at 4 ° C. for 30 minutes. The cell lysate was centrifuged at 15,000 rpm for 15 minutes to obtain supernatant. The cell lysate was stored at -20 ° C until use. Protein concentration was determined by Bradford method using bovine serum albumin (BSA) as a standard. 20-30 μg of lysate was denatured by 8-12% mini gel SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) and stained with polyvinylidene fluoride (PVDF) membranes (Bio-Rad, Hercules, Lt; / RTI &gt; The membrane was blocked for 2 hours in a solution of Tween-20-TBS (T-TBS) (50 mM Tris, pH 7.6, 150 mM NaCl, 0.1% Tween-20) containing 5% nonfat dried milk. Membrane was used to examine the expression of several proteins, including cyclin D1 (1: 1000), phospho (ser780) -pRB (1: 1000), cyclin E (1: 2000), phospho-CDK2 (1: 1000), phospho (ser552) -β-catenin (1: 1000), phospho (ser675) -β- catenin 1000), GSK3β (1: 1000) and β-actin (1: 5000) at 4 ° C overnight. Secondary anbibodies were diluted 1: 5000 with HRP (horse radish peroxidase) conjugated anti-rabbit Ig and anti-mouse IgG for 1 hour at room temperature. Membrane was washed three times with T-TBS and reacted with ECL substrate (Intron, Seoul, Korea) for 1 minute and then sensitized to X-ray film (AGFA, Mortsel, Belgium).

As a result, when treated with 0.1 and 1 μM of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) for 24 hours, cyclin D1, phospho-pRB, cyclin E and phospho-CDK2 (BDB) (Fig. 4A). On the other hand, it was confirmed that the treatment of minoxidil was similar to that of 3- [3-bromo-4,5-dihydroxybenzaldehyde (BDB) -catenin signaling pathway plays an important role in hair growth and cell proliferation regulation (Kwack M, et al., 2011; Wangefjord S, et al., 2013). Activation of Akt induces phosphorylation of β-catenin (ser552) and GSK3β phosphorylation (ser9), PKA phosphorylation of β-catenin (ser552 and ser675 (Hedgepeth C et al., 1997; Hino S et al., 2005; Monick MM, et al., 2001), which induce the Wnt / β-catenin signaling pathway. After that, stabilization of β-catenin and promotion of migration to the nucleus arise and control the expression of the target gene (Hedgepeth C, et al., 1997; Monick MM, et al., 2001). The results of the present invention show that Phospho (ser552) -β-catenin, Phospho (ser675) -β-catenin, Phospho (ser9) -GSK3β Minoxidil treatment similarly activated Wnt / β-catenin pathway similar to 3-bromo-4,5-dihydroxybenzaldehyde (BDB) (FIG. 4B) . Kwack et al. (2000) report that minoxidil exhibits hair regrowth efficacy through regulation of the β-catenin signaling pathway via PKA, Akt and GSK3β activation in human DPCs. (Kwack M, et al., 2011). These results demonstrate that 3-bromo-4,5-dihydroxybenzaldehyde (BDB) is a cell cycle protein such as cyclin D1, cyclin E, phospho-CDK2 and phospho-pRB, as well as Wnt / β-catenin signal transduction pathway in the dermal papilla cells.

Claims (6)

A pharmaceutical composition for preventing hair loss, which comprises 3-bromo-4,5-dihydroxybenzaldehyde (BDB) or a salt thereof as an active ingredient.
The method according to claim 1,
Wherein the composition is a formulation selected from the group consisting of tablets, capsules, injections, creams, gels, patches, sprays, ointments, alerts, lotions, liniments, pastes and cataplasms Gt;
The method according to claim 1,
Characterized in that the composition contains 3-bromo-4,5-dihydroxybenzaldehyde (BDB) in a concentration of 0.001 to 10 [mu] M.
3-bromo-4,5-dihydroxybenzaldehyde or a salt thereof as an active ingredient.
In the fourth aspect,
The composition may be used in hair cosmetics such as hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair conditioner, hair treatment, hair cream, hair nutrition cream, hair moisturizing cream, Hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair dyes, hair moisturizers, Wherein the composition is selected from the group consisting of mousse and hairspray.
In the fourth aspect,
Wherein the composition contains 3-bromo-4,5-dihydroxybenzaldehyde in a concentration of 0.001 to 10 μM.

Images