KR20210054838A - Composition for preventing hair loss or promoting hair growth comprising cephalothin or pharmaceutically acceptable salt thereof - Google Patents

Abstract

The present invention provides a composition for preventing hair loss or promoting hair growth comprising cephalotin or a pharmaceutically acceptable salt thereof as an active component. It has been found by the present invention that cephalotin or the pharmaceutically acceptable salt thereof activates Wnt/β-catenin signaling, which is known to affect dermal papilla cell proliferation, regeneration, and growth promotion of dermal papilla cells, and also increases the expression of vascular endothelial growth factor (VEGF), etc. Therefore, the composition according to the present invention can be usefully used for preventing hair loss or promoting hair growth.

Description

Composition for preventing hair loss or promoting hair growth comprising cephalothin or a pharmaceutically acceptable salt thereof

The present invention relates to a composition for preventing hair loss or promoting hair growth, comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient.

Hair follicles, which are the physiological organs in the body that produce hair, are during the development process after birth, during the development of hair and during the growth phase in which the generated hair actively grows, the catagen phase in which the hair degenerates, and when the hair falls out. The hair growth cycle divided into a telogen phase and an exogen phase in which hair loss occurs is repeated, and it is involved in hair growth, maintenance, and dropout. Hair follicle activity is caused by dermal papilla cells, and in particular, proliferation and differentiation of dermal papilla cells are primarily involved in the progression of the hair growth cycle and hair formation (Botchkarev VA, Kishimoto J, Molecular control of epithelial-mesenchymal interactions. during hair follicle cycling.J Iinvestig Dermatol Symp Proc 8, 46-55, 2003). Active proliferation and differentiation of dermal papilla cells occurs during the growth phase when hair is actively growing, hair growth is stopped, and these cells are killed during the degenerative phase, the resting phase, and the hair loss phase when hair loss occurs (Botchkarev VA, Batchkareva NV, Nakamura M, Noggin is required for induction of the hair follicle growth phase in postnatal skin.FASEB J 15, 2205-2214, 2001). In addition, cell division and migration in the vicinity of the dermal papilla are closely related to the growth of hair, and hair is newly generated from the dermal papilla during the growth phase. Cells are activated by various cytokines and hormones, resulting in cell migration to the dermal papilla. (Eva MJ Peters, Desmond J Tobin, Migration of melanoblasts into developing murine hair follicle is accompanied by transient c-kit expression, J Histochem Cytochem, 50, 6751-766, 2002; Jahoda CA, Cell movement. in the hair follicle dermis-more than a two-way street J Invest Dermatol, 1221, 1523-1747, 2003).

Therefore, since the proliferation and death of dermal papilla cells are closely related to hair growth and hair loss, prolonging the growth period by inducing the proliferation or suppressing apoptosis and shortening the degenerative period, the resting period, and the hair loss period will be a way to improve and treat hair loss. .

The present inventors believe that cephalotin, one of the first generation cephalosporin antibiotics, or a pharmaceutically acceptable salt thereof, is known to affect dermal papilla cell proliferation and regeneration and growth promotion of dermal papilla cells. Wnt/β-catenin (Wnt/ It was found that it can be usefully used for preventing hair loss or promoting hair growth by activating β-catenin) signal and increasing the expression of growth factors (VEGF, etc.).

Accordingly, an object of the present invention is to provide a composition for preventing hair loss or promoting hair growth, comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient.

According to an aspect of the present invention, there is provided a composition for preventing hair loss or promoting hair growth comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient.

In the composition for preventing hair loss or promoting hair growth of the present invention, the pharmaceutically acceptable salt of cephalotin may be cephalotin sodium.

Cephalotine or a pharmaceutically acceptable salt thereof activates Wnt/β-catenin signaling, which is known to affect dermal papilla cell proliferation, regeneration and growth promotion of dermal papilla cells, and also a growth factor (Vascular endothelial growth factor (VEGF), etc.). It was found by the present invention to increase the expression of ). Therefore, the composition according to the present invention can be usefully used for preventing hair loss or promoting hair growth.

1 shows the results of evaluating the proliferation efficacy of dermal papilla cells by cephalotin sodium in a dermal papilla cell-only medium.
2 shows the results of evaluating the proliferation efficacy of dermal papilla cells by cephalotin sodium in a culture medium without dermal papilla cell growth factor.
3 shows the results of evaluating the proliferation efficacy of dermal papilla cells by cephalotin sodium in a culture medium without dermal papilla cell growth factors and antibiotics.
4 shows the expression levels of representative factors (Wnt5α, GSK3β, β-catenin, etc.) mediating Wnt/β-catenin signaling and expression levels of VEGF, a cell growth factor, after treatment of dermal papilla cells with cephalotin sodium. The measurement result is shown.

The present invention provides a composition for preventing hair loss or promoting hair growth, comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient.

Cephalotin is one of the first generation cephalosporin antibiotics, and has the structure of the following formula (1). Cephalotin has an antibacterial effect against staphylococcus, streptococcus, pneumococcal, and E. coli, and is administered by intravenous or intramuscular injection.

<Formula 1>

According to the present invention, cephalotin or a pharmaceutically acceptable salt thereof (e.g., sodium salt) activates Wnt/β-catenin signals known to affect dermal papilla cell proliferation and regeneration and growth promotion of dermal papilla cells. It was also found to increase the expression of growth factors (VEGF, etc.). Therefore, the composition according to the present invention can be usefully used for preventing hair loss or promoting hair growth.

The composition for preventing hair loss or promoting hair growth of the present invention may be prepared in the form of a pharmaceutical composition or a cosmetic composition comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient. For example, the composition of the present invention may be in the form of a pharmaceutical composition for preventing hair loss or promoting hair growth, comprising cephalotin or a pharmaceutically acceptable salt thereof (preferably cephalotin sodium) as an active ingredient. In addition, the composition of the present invention may be in the form of a cosmetic composition for preventing hair loss or promoting hair growth, including cephalotin or a pharmaceutically acceptable salt thereof (preferably cephalotin sodium).

The pharmaceutical composition may contain a pharmaceutically acceptable carrier, and may be formulated into parenteral formulations such as solutions, suspensions, emulsions, lotions, ointments, and lyophilizers according to a conventional method. Preferably, it may be formulated in a dosage form for transdermal administration such as an external solution, an emulsion, or an ointment. The pharmaceutically acceptable carrier includes aqueous diluents or solvents such as phosphate buffered saline, purified water, and sterile water, and non-aqueous diluents or solvents such as propylene glycol, polyethylene glycol, and olive oil. In addition, if necessary, a wetting agent, a fragrance, a preservative, and the like may be included. The dosage of cephalotin or a pharmaceutically acceptable salt thereof contained in the pharmaceutical composition may be appropriately selected by those skilled in the art according to the condition of the patient, the severity of the disease, the route and duration of administration. For example, cephalotin may be administered to the scalp in an amount of 0.01 to 5 mg per day, preferably 0.1 to 1 mg, and the administration may be administered once or several times a day. May be.

The cosmetic composition may be prepared in various forms according to a conventional cosmetic preparation method. For example, the cosmetic composition of the present invention may be prepared in the form of a perfume product containing cephalotin, a shampoo, a treatment, a hair lotion, a hair cream, a hair gel, a scalp essence, a tonic, etc., which is a conventional cleansing agent. It can be used after diluting with liquid, astringent liquid, and moisturizing liquid. In addition, the cosmetic composition may include conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and fragrances commonly used in the cosmetic composition field. In the cosmetic composition of the present invention, the amount of cephalotin or a pharmaceutically acceptable salt thereof is an amount effective to achieve an effect of preventing hair loss or promoting hair growth, for example, in an amount of 0.0005 to 0.5% by weight based on the total weight of the composition. It may be contained, and preferably may be contained in an amount of about 0.005 to 0.1% by weight.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1: Human dermal papilla cells culture

Human-derived dermal papilla cells are manufactured by Cell Applications, Inc. (USA) was purchased and used. Purchased cells are morphologically confirmed by microscopic observation, 5% fetal bovine serum (FBS), 1% antibiotics (penicillin/streptomycin, amphotericin), and growth factors are included for dermal papillary cell culture only. The medium (ready-to-use media, Cell Applications, USA) was used to incubate in _{a 37°C, 5% CO 2 incubator.} After 24 hours of cell culture, the existing medium was removed, washed with phosphate-buffered saline (PBS), and then the same new medium was added for further culture.

Example 2: Proliferation effect of cephalotin on dermal papilla cells

Cephalotin sodium was purchased and used from MedChemExpress (USA). In each well of a collagen-coated 96-well plate, the dermal papilla cells cultured in Example 1 were seeded at 5×10 ³ cells/well, and the same medium was added and cultured for 24 hours. The cells were observed under a microscope, and the existing medium was removed and washed with PBS. When adding a new culture medium again, cephalotin sodium was treated at different concentrations (10, 100, 300, 600, 900, 1200, 1500 μM), and then _{cultured in a 37°C, 5% CO 2} incubator for 24 hours. As a control, the same volume of PBS was treated instead of cephalotin. Each experimental group was conducted simultaneously in three wells under the same conditions. Cell proliferation efficacy was evaluated by measuring absorbance at a wavelength of 450 nm using the WST-1 assay (Ez-cytox Cell Viability Assay Kit, Daeilbio, Korea) 24 hours after each sample treatment. The results are shown in FIG. 1. As can be seen from the results of Fig. 1, it was observed that the cell proliferation was significantly increased in the experimental group to which cephalotin sodium was added, and showed a cell proliferation effect of 50% or more compared to the control at a concentration between 100 and 600 μM. I got it.

Example 3: Effect of cephalotin proliferation on dermal papilla cells in an environment of changing culture conditions

The results of Example 2 and FIG. 1 show that a culture medium for dermal papilla cells was used (culture conditions-1 in Table 1 below), in order to exclude the effect of growth factors or antibiotics contained in the medium on the proliferation of dermal papilla cells The experiment was performed in the same manner as in Example 2 above with two additional environments different. That is, 5% FBS and antibiotics were included in the dermal papilla cell culture basic medium (basal media, Cell Applications, USA), but the cell growth factor was excluded (culture conditions-2 in Table 1), and 5% FBS in the basic medium. Treated with cephalotin sodium at various concentrations (10, 100, 300, 600, 900, 1200, 1500 μM) in the same manner as in Example 2 in the environment of culture conditions containing only (culture conditions-3 in Table 1 below) And the cell proliferation efficacy was evaluated in the same way.

Culture medium FBS concentration Cell growth factor Antibiotics result Culture condition-1 Dedicated medium for culturing dermal papilla cells (ready-to-use) 5% + + Fig. 1 Culture condition-2 Basic media for culturing dermal papilla cells 5% - + Fig. 2 Culture condition-3 Basic media for culturing dermal papilla cells 5% - - Figure 3

As can be seen from the results of FIGS. 2 and 3, the effect of cephalotin sodium proliferation was observed in a pattern similar to that of Example 2 in two additional cell culture environments.

Treatment of dermal papilla cells with other beta-lactam compounds penicillin, ampicillin, cefazolin, cefadroxil, cephalexin, and cepradine at the same concentration Thus, as a result of observing cell proliferation in the same manner as in Example 2, these compounds had no significant effect on dermal papilla cell proliferation (data not shown).

Example 4: Evaluation of Wnt/β-catenin signal activation on dermal papilla cells

Immunoblot analysis was performed to investigate the efficacy of cephalotin on the expression of VEGF, a representative growth factor in cells, and Wnt/β-catenin signaling, which is known to affect the regeneration and growth of dermal papilla cells. Performed. In each well of a 6-well plate containing dermal papilla cell culture media (ready-to-use media, Cell Applications, USA), seed dermal papilla cells at 3 X 10 ⁵ cells/well in a 37°C, 5% CO ₂ incubator. Cultured. After 24 hours, cephalotin sodium was treated at different concentrations (0.1, 1, 10, 100, 500 μM), cultured for 24 hours, and then the medium was removed and washed with PBS. Cells were lysed and centrifuged with RIPA buffer (Sigma-Aldrich, USA) containing a protease inhibitor cocktail (Sigma-Aldrich, USA). SDS-PAGE was performed on the same amount of proteins obtained from the supernatant, and anti-Wnt5a antibody (Abcam, USA), anti-GSK3β antibody (Cell Signaling Technology, USA), and anti-phosho-GSK3β antibody (Cell Signaling Technology) , USA), anti-β-catenin antibody (Cell Signaling Technology, USA), anti-VEGF antibody (Abcam, USA), and anti-β-actin antibody (Santa Cruz Biotechnology, USA) were used to perform immunoblot analysis. . As can be seen from the results of FIG. 4, the amount of proteins of Wnt5α, GSK3β, and β-catenin, which are representative factors mediating Wnt/β-catenin signaling in the cephalotin sodium-treated group, increased compared to the control group, and as a result It was confirmed that the expression level of VEGF, a cell growth factor, was also significantly increased. On the other hand, there was no significant difference in β-actin protein between the control group and the cephalotin-treated group.

Claims (2)

A composition for preventing hair loss or promoting hair growth, comprising cephalotin or a pharmaceutically acceptable salt thereof as an active ingredient. The composition for preventing hair loss or promoting hair growth according to claim 1, wherein the pharmaceutically acceptable salt of cephalotin is cephalotin sodium.

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