KR102698238B1 - A cosmetic composition containing complex of Magnolia officinalis extract, brewer's yeast extract, biotin, niacinamide as active ingredients for strengthening hair root, activating hair growth or alleviating stress-related hair loss - Google Patents

Abstract

The present invention relates to a hair cosmetic composition containing a complex of a Mackerel extract, a Brewer's yeast extract, biotin, and niacinamide as an active ingredient. The composition containing the complex has a hair root strengthening effect by enhancing the expression of VEGF (Vascullar Endotherial Growth Factor) and β-Catenin in hair papilla cells or hair follicle cells, a stress-induced hair loss alleviation effect by inhibiting the expression of TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α), and a hair growth effect by increasing the expression of IGF-1 (Insulin-like Growth Factor), and thus can be used as a next-generation hair multi-care cosmetic composition.

Description

{A cosmetic composition containing complex of Magnolia officinalis extract, brewer's yeast extract, biotin, niacinamide as active ingredients for strengthening hair root, activating hair growth or alleviating stress-related hair loss}

The present invention relates to a cosmetic composition for strengthening hair roots, promoting hair growth, and alleviating stress-induced hair loss, containing a complex of a cinnamon extract, a brewer's yeast extract, biotin, and niacinamide as active ingredients.

Human hair plays a role in protecting the skin and scalp, and in particular, scalp hair accounts for about 20% of human hair, and is recognized as a very important element because it plays a unique role in social and sexual communication. However, recently, as the frequency of exposure to various environments has increased due to the development of industrialization, the number of people suffering from hair loss and scalp problems has increased.

In the past, most hair loss cases occurred in middle-aged and older people in their 50s or older, but recently, due to excessive use of shampoos and mousses, damage to the hair and scalp due to perms, dyeing, and use of hair dryers, increased environmental stress, and nutritional imbalances caused by increased intake of processed foods, hair loss has been occurring noticeably in young people in their 20s and 30s, and not only male-pattern baldness but also female-pattern baldness is on the rise. In particular, according to the National Health Review and Assessment Service, the number of people who visited hospitals for hair loss increased from about 200,000 in 2014 to about 220,000 in 2018, and the Korean Society for Hair Loss Treatment estimates that the potential hair loss population in Korea is 10 million.

The lifespan of hair consists of the growth phase (anagen phase), regression phase (catagen phase), and resting phase (telogen phase), and hair is maintained by repeating the above hair cycle. The hair cycle is determined by the activity cycle of the dermal papilla (DP), with the growth phase lasting 5-6 years, the catagen phase lasting 2-3 weeks, and the resting phase lasting approximately 2-3 months. When the final stage of the resting phase arrives, the development phase in which new hair is naturally generated begins, and the hair is maintained anew, so hair loss is considered a natural phenomenon for the generation of new hair. However, alopecia, which is recognized as a hair loss disease, refers to a symptom in which the activity of the dermal papilla stops, resulting in a relative increase in the proportion of hair in the resting phase or in the failure of hair regeneration.

Although research has been conducted on the causes and mechanisms of alopecia, the cause of alopecia has not yet been clearly identified. The main factors affecting hair growth include inhibition of proliferation or decreased function of the dermal papilla related to hair cycle regulation, abnormality of the hair cycle due to androgen action, abnormal changes in the hair cycle due to decreased blood flow to the scalp, anti-stress drugs, mental stress, physical stimulation, and environmental pollution.

Accordingly, the development of hair loss treatments is progressing worldwide, and various methods such as topical application agents, oral administration agents, health supplements, gene transplant surgery, hair transplant surgery, and alternative medicine are being implemented as treatment methods for hair loss, but it is known that there is no treatment method or substance that has shown satisfactory results as of yet.

In particular, although there are thousands of hair growth tonics on the market worldwide, there are not many products that are actually recognized by the Hair Growth Society, and currently, only minoxidil and Propecia have been approved by the Food and Drug Administration (FDA) as drugs that promote hair growth. It is known that the topical application 'minoxidil' or the oral medication 'Propecia (ingredient: finasteride)' can slow down the progression of hair loss to some extent in the early stages of hair loss, but it is difficult to return to normal for hair loss that has already progressed, and side effects such as hair growth in unwanted areas, erectile dysfunction, decreased libido, dizziness, headaches, edema, and skin rashes may occur. In addition, there is a concern that taking them can cause birth defects, so there is a problem that they cannot be prescribed to women.

Moreover, since hair loss prevention and hair growth products are applied directly to the scalp or taken ingested, efforts are required to explore natural ingredients that do not contain chemical components, extract effective ingredients that are beneficial to scalp and hair health, and develop products containing these ingredients.

Republic of Korea Publication Patent No. 10-2020-0091611 (Title of invention: Functional shampoo composition for preventing hair loss containing beer yeast extract, Applicant: Seongsu Kim, Publication date: 2019.01.23.) Republic of Korea Publication Patent No. 10-2019-0094913 (Title of the invention: Composition for preventing hair loss or strengthening the scalp containing natural extracts as effective ingredients, Applicant: Ulsan National University of Science and Technology Industry-Academic Cooperation Foundation, Publication date: 2018.02.06.) Korean Patent Registration No. 10-0975819 (Title of the invention: Composition for preventing hair loss and promoting hair growth containing extract of Mackerel or 4-0-methylhonokiol isolated therefrom, Applicant: Hyundai Bioland Co., Ltd., Registration date: 2008.03.04.) Korean Patent Registration No. 10-2064599 (Title of the invention: Cosmetic composition for preventing hair loss containing extract of Ubangja, niacinamide and menthyl PCA, Applicant: Koreana Cosmetics Co., Ltd., Registration date: 2020.01.03.)

The purpose of the present invention is to provide a cosmetic composition for strengthening hair roots, promoting hair growth, and alleviating stress-induced hair loss, which contains a complex of a cinnamon extract, a brewer's yeast extract, biotin, and niacinamide as effective ingredients.

The present invention relates to a cosmetic composition for strengthening hair roots, containing a complex of a cinnamon extract, a brewer's yeast extract, biotin, and niacinamide as effective ingredients.

The above complex is characterized by enhancing the expression of at least one gene selected from VEGF (Vascullar Endotherial Growth Factor) and β-Catenin.

In addition, the above complex may have an effect of alleviating stress-induced hair loss and may inhibit the expression of one or more genes selected from TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α).

The above complex has hair growth effects and enhances the gene expression of IGF-1 (Insulin-like Growth Factor).

Accordingly, the above complex can be applied as a composition for external skin application for the prevention or treatment of stress-induced hair loss.

The complex of the present invention comprises a mixture of 20 to 40 wt% of a Mackerel extract of 10,000 ppm or more and 60 to 80 wt% of a Brewer's yeast extract of 10,000 ppm or more, and is characterized in that 0.02 to 0.05 wt% of biotin and 0.30 to 0.90 wt% of niacinamide are added based on 100 wt% of the mixture. Accordingly, the concentration of the Mackerel extract or the Brewer's yeast extract, or the mixture thereof, may preferably be 10,000 to 13,000 ppm.

The above beer yeast extract may be a mixture of malt extract and hop extract fermented with yeast.

Hereinafter, the present invention will be described in detail.

The complex of the present invention is characterized in that, when treated at a concentration of 100 ppm, VEGF (Vascullar Endotherial Growth Factor) increases by 220-250% or more, β-Catenin expression increases by 125-140%, and IGF-1 (Insulin-like Growth Factor) expression increases by about 135-160%. In addition, TGF-β2 (Transforming growth factor-beta2) decreases by 15-25%, and TNF-α (Tumor necrosis factor-α) expression decreases by about 55-65%.

The above beer yeast extract may be a mixture of malt extract and hop extract fermented with yeast, and may be obtained by mixing 50 to 200 parts by weight of hop extract based on 100 parts by weight of liquid malt extract, adding yeast (Saccharomyces cerevisiae) to the mixed extract, and fermenting at room temperature of 20 to 40°C for 1 to 2 days. After fermentation using yeast, it is recommended to heat at 80 to 85°C for 30 minutes to inactivate the yeast.

The extract of Mackerel, malt extract or hop extract used in the present invention can be extracted from each raw material sample of Mackerel, malt or hops using water, C1 to C4 alcohol or a mixed solution thereof, ethyl acetate or chloroform as a solvent, and the C1 to C4 alcohol can be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol. The extract can also be a water or a 30 to 90% (v/v) alcohol aqueous solution extract, preferably a water or a 50 to 80% (v/v) alcohol aqueous solution extract, and preferably a water extract.

The solvent used in the production of the above extract can be used in an amount 1 to 40 times the volume (1 to 40 ℓ per 1 kg) or 1 to 40 times the weight based on the weight of the raw material sample used, preferably 5 to 40 times the volume or 5 to 40 times the weight can be used, and most preferably 5 to 20 times the volume or 5 to 20 times the weight can be used. The extraction temperature of each extract can be 20 to 100°C for 1 to 48 hours, but preferably 40 to 60°C for 3 to 8 hours. The above process can be repeated 1 to 4 times.

As the extraction device of the above extract, a conventional extraction device, an ultrasonic grinding extractor or a fractionator can be used. The extract prepared in this way can be dried by hot air, dried under reduced pressure or freeze-dried to remove the solvent. In addition, the extract can be purified using column chromatography and used.

The above extract can be fractionated or purified and used by using a method known in the art for separating and extracting plant components, such as extraction using an organic solvent (alcohol, ether, acetone, etc.), distribution of hexane and water, or column chromatography, either singly or in a suitably combined manner.

The above chromatography can be selected from silica gel column chromatography, LH-20 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography, thin layer chromatography (TLC), silica gel vacuum liquid chromatography, and high performance liquid chromatography.

In addition, the present invention provides a pharmaceutical composition for preventing or treating stress-induced hair loss, which contains a complex of a cinnamon extract, a brewer's yeast extract, biotin, and niacinamide as an effective ingredient. The complex can be added to the pharmaceutical composition of the present invention in an amount of 0.001 to 30 wt%.

The above pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods. Carriers, excipients, and diluents that can be included in the above pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When formulated, it is prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants that are commonly used. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the extract of the present invention with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, flavoring agents, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents can be used, such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases can be used, such as witepsol, macrogol, Tween 61, cocoa butter, laurin butter, and glycerogelatin.

The dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, and weight of the subject to be treated, the specific disease or pathological condition to be treated, the severity of the disease or pathological condition, the route of administration, and the judgment of the prescriber. The determination of the dosage based on these factors is within the level of those skilled in the art, and the dosage is generally in the range of 0.01 mg/kg/day to about 2000 mg/kg/day. A more preferred dosage is 1 mg/kg/day to 500 mg/kg/day. The administration may be administered once a day or divided into several times. The above dosage does not limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as mice, livestock, and humans by various routes. All modes of administration can be expected, and for example, it can be administered orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine, or intracerebrovascular injection. The composition of the present invention has almost no toxicity and side effects, so it is a drug that can be safely used even for long-term administration for preventive purposes.

The formulation of the above cosmetic composition is not particularly limited, but may be formulated into various cosmetic compositions, preferably for hair growth, hair loss improvement, scalp improvement, etc. Preferably, the hair products include shampoo, rinse, treatment, hair oil, milk, scrub, mousse, hair lotion, hair gel, hair pack, hair ampoule, soap, etc., and the formulation is not particularly limited, and more specifically, the hair products may be selected from hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, hair moisture cream, hair massage cream, hair wax, hair aerosol, hair pack, hair nutrition pack, hair soap, hair cleansing foam, hair oil, hair drying agent, hair preservation agent, hair dye, hair waving agent, hair bleaching agent, hair gel, hair glaze, hair dressing agent, hair lacquer, hair moisturizer, hair mousse, or hair spray.

More specifically, when the formulation of the cosmetic composition of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide can be used as a carrier component. When the formulation of the cosmetic composition of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder can be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane-butane or dimethyl ether can be additionally included. When the formulation of the cosmetic composition of the present invention is a solution or an emulsion, a solvent, a solvating agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan. When the formulation of the cosmetic composition of the present invention is a suspension, 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, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, and the like can be used as a carrier component. When the formulation of the cosmetic composition of the present invention is a surfactant-containing cleansing, an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an acethionate, an imidazolinium derivative, a methyl taurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl amidobetaine, a fatty alcohol, a fatty acid glyceride, a fatty acid diethanolamide, a vegetable oil, a linolenic derivative, or an ethoxylated glycerol fatty acid ester may be used as a carrier component. The cosmetic composition of the present invention may additionally contain excipients including a fluorescent substance, a fungicide, a hydrotropism inducer, a moisturizer, a fragrance, a fragrance carrier, a protein, a solubilizer, a sugar derivative, a sunscreen, vitamins, a plant extract, and the like. The addition amounts of the above components may be selected within a range that does not impair the inherent effects of the cosmetic composition depending on the formulation or intended use. The amount of the above components may be, for example, 0.1 to 10 wt%, preferably 0.1 to 6 wt%, based on the total weight of the composition, but is not limited thereto.

The present invention relates to a hair cosmetic composition containing a complex of a Mackerel extract, a Brewer's yeast extract, biotin, and niacinamide as an active ingredient. The composition containing the complex has a hair root strengthening effect by enhancing the expression of VEGF (Vascullar Endotherial Growth Factor) and β-Catenin in hair papilla cells or hair follicle cells, a stress-induced hair loss alleviation effect by inhibiting the expression of TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α), and a hair growth effect by increasing the expression of IGF-1 (Insulin-like Growth Factor), and thus can be used as a next-generation hair multi-care cosmetic composition.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, the contents introduced herein are provided to sufficiently convey the idea of the present invention to those skilled in the art so that they are thorough and complete.

<Preparation of raw materials>

In the present invention, the root strengthening effect of a complex of extracts of mugwort, yeast extract, biotin, and niacinamide was confirmed. Accordingly, each raw material was prepared as follows.

First, for the production of the extract of the cinnamon bark, the cinnamon bark purchased from a traditional market was extracted using 10 times its weight in purified water as a solvent under the conditions of 60℃ for 5 hours. Next, the extract of the cinnamon bark was obtained by sequentially filtering it through filters with pore sizes of 250 Mesh, 1 μm, and 0.5 μm.

For the production of beer yeast extract, first, malt (Jeju Plant Resources Research Institute) and hops (HOP, Hopideun) were extracted using 10 times their weight of purified water as a solvent under the conditions of 50℃ for 5 hours. Next, malt extract and hop extract were obtained by sequentially filtering through filters with pore sizes of 250 Mesh, 1 μm, and 0.5 μm, respectively. The malt extract and hop extract obtained in this way were mixed in a weight ratio of 1:1, and 0.1 g of yeast (Saccharomyces cerevisiae, Vision Biochem) was added per 100 g of the mixed extract of malt and hops, and fermented at room temperature for 48 hours. After that, beer yeast extract was obtained by going through an inactivation process at 80℃ for 30 minutes.

The liquid extracts of each of the obtained extracts of the bark and the yeast of the brewer were freeze-dried to confirm their solid concentrations. Each was found to be over 10,000 ppm (approximately 10,000 to 13,000 ppm). These were adjusted to the same concentration of 10,000 ppm using water as a solvent and used in the experiment.

Biotin was prepared by purchasing a product from HANGZHOU KEXING BIOCHEM CO., Ltd. Niacinamide was prepared by purchasing a product from Sigma-Aldrich.

<Manufacturing Examples 1 to 3 and Comparative Manufacturing Examples 1 to 3. Preparation of a mixture of a perilla extract and a brewer's yeast extract>

Prior to preparing a complex of the extract of Mackerel, brewer's yeast extract, biotin, and niacinamide, first, in order to confirm the main efficacy of the extract of Mackerel and brewer's yeast extract, they were mixed as shown in Table 1 below and prepared as a main composition. The concentration of each prepared mixture liquid was 10,000 ppm.

Sample Macula extract (g) Brewer's yeast extract (g) Total (g) Manufacturing example 1 20 80 100 Manufacturing example 2 30 70 100 Manufacturing example 3 40 60 100 Comparative manufacturing example 1 0 100 100 Comparative manufacturing example 2 10 90 100 Comparative manufacturing example 3 50 50 100 Comparative manufacturing example 4 70 30 100 Comparative manufacturing example 5 90 10 100 Comparative manufacturing example 6 100 0 100

<Experimental Example 1. Confirmation of the efficacy of a mixture of extracts of Magnolia chinensis and brewer's yeast on hair bulb strength according to VEGF mRNA expression>

Each sample in Table 1 was treated to 1% (100 ppm) of the final concentration on human hair papilla cells (HDP), and the expression of VEGF (Vascullar Endotherial Growth Factor) mRNA was confirmed through qRT-PCR to confirm whether the root strengthening effect was observed.

To this end, dermal papilla cells were seeded in a 6-well plate, cultured for 24 hours, and each well was replaced with human dermal papilla growth medium containing 1% serum, and the samples were treated and cultured for 24 hours.

Each cultured cell was washed with PBS (phosphate buffered saline), then treated with QIAzol ^® (QIAGENL ^® , USA) to perform cell lysis, and total RNA was isolated using the protocol provided by the manufacturer (QIAGENL ^® ). The isolated RNA was quantified using the Qubit ^™ RNA BR assay kit, and cDNA was synthesized to perform real-time PCR. cDNA synthesis was performed using a cDNA synthesis kit (qPCRBIO cDNA Synthesis Kit, PCRBIOSYSTEMS, London, UK) and the experiment was performed according to the kit's method. Real-time PCR was performed to amplify genes using a Real-time PCR Kit (2x qPCRBIO SyGreen Blue mix Lo-ROX, PCRBIOSYSTEMS, London, UK), and then quantitatively analyze the amplified products.

In addition, the primer sequence to be used in the gene amplification experiment of the present invention was synthesized by Cosmogenetec (Korea) as follows.

Primer Sense Antisense VEGF 5'-TGC AGA TTA TGC GGA TCA AAC C-3' 5'-TGC ATT CAC ATT TGT TGT GCT GTA G-3' β-actin 5'-GGC ACC CAG CAC AAT GAA G-3' 5'-CCG ATC CAC ACG GAG TAC TTG-3'

Sample Average Stdev. p-value Control group (untreated group) 100 1.45 1.000 Manufacturing example 1 161.2 1.23 0.000 Manufacturing example 2 162.7 1.48 0.000 Manufacturing example 3 160.2 2.42 0.002 Comparative manufacturing example 1 120.2 2.04 0.002 Comparative manufacturing example 2 131.4 2.12 0.000 Comparative manufacturing example 3 149.6 1.38 0.000 Comparative manufacturing example 4 150.4 2.07 0.000 Comparative manufacturing example 5 137.6 1.98 0.000 Comparative manufacturing example 6 141.2 1.82 0.000

As confirmed by the results in Table 3, it was confirmed that the mixture of manufacturing examples 1 to 3 (20 to 40 wt% of the extract of Phellodendron amurense and 60 to 80 wt% of the extract of brewer's yeast) at a final concentration of 1% (100 ppm) had the best VEGF expression rate.

<Examples 1 to 12. Preparation of complex composition for strengthening hair roots>

The mixtures of Manufacturing Examples 1 to 3 (containing extract of Mackerel and extract of brewer's yeast) confirmed in Experimental Example 1 were heated to 50°C, biotin and niacinamide were added, and then the mixture was stirred at 1,000 rpm for 1 hour while maintaining the temperature at 50°C so that the biotin and niacinamide were well dissolved, thereby manufacturing the complex compositions of Examples 1 to 12.

Complex
Sample A mixture of extracts of cinnamon and brewer's yeast Biotin
(g) Niacin
Amide
(g) Total
(g) Manufacturing example 1
mixture
(g) Manufacturing example 2
mixture
(g) Manufacturing example 3
mixture
(g) comparison
Manufacturing example 3
mixture
(g) comparison
Manufacturing example 4
mixture
(g) Example 1 0 100 0 0 0 0.05 0.90 100.95 Example 2 0 100 0 0 0 0.05 0.75 100.80 Example 3 0 100 0 0 0 0.05 0.60 100.65 Example 4 0 100 0 0 0 0.05 0.45 100.50 Example 5 0 100 0 0 0 0.05 0.30 100.35 Example 6 0 100 0 0 0 0.02 0.70 100.72 Example 7 0 100 0 0 0 0.03 0.50 100.53 Example 8 0 100 0 0 0 0.04 0.35 100.39 Example 9 100 0 0 0 0 0.02 0.90 100.92 Example 10 100 0 0 0 0 0.05 0.75 100.80 Example 11 0 0 100 0 0 0.05 0.30 100.35 Example 12 0 0 100 0 0 0.05 0.75 100.80

<Comparative Examples 1 to 20. Preparation of Comparative Compositions>

Comparative examples 1 to 20 were prepared by the same method as in Example 1, except that a mixture of a perilla extract and a brewer's yeast extract, and biotin and niacinamide were added under the conditions shown in Table 5 below.

Complex
Sample A mixture of extracts of cinnamon and brewer's yeast Biotin
(g) Niacin
Amide
(g) Total
(g) Manufacturing example 1
mixture
(g) Manufacturing example 2
mixture
(g) Manufacturing example 3
mixture
(g) comparison
Manufacturing example 3
mixture
(g) comparison
Manufacturing example 4
mixture
(g) Comparative Example 1 0 100 0 0 0 0.05 0.95 101.00 Comparative Example 2 0 100 0 0 0 0.05 0.15 100.20 Comparative Example 3 100 0 0 0 0 0.07 1.00 101.07 Comparative Example 4 0 0 100 0 0 0.50 0.3 100.80 Comparative Example 5 0 0 0 100 0 0.05 0.75 100.80 Comparative Example 6 0 0 0 0 100 0.05 0.75 100.80 Comparative Example 7 0 100 0 0 0 0 0.80 100.80 Comparative Example 8 0 100 0 0 0 0 0.75 100.75 Comparative Example 9 0 100 0 0 0 0 0.90 100.90 Comparative Example 10 0 100 0 0 0 0 0.60 100.60 Comparative Example 11 0 100 0 0 0 0 0.45 100.45 Comparative Example 12 0 100 0 0 0 0 0.30 100.30 Comparative Example 13 0 100 0 0 0 0 0.15 100.15 Comparative Example 14 0 100 0 0 0 0.80 0 100.80 Comparative Example 15 0 100 0 0 0 0.06 0 100.06 Comparative Example 16 0 100 0 0 0 0.05 0 100.05 Comparative Example 17 0 100 0 0 0 0.04 0 100.04 Comparative Example 18 0 100 0 0 0 0.03 0 100.03 Comparative Example 19 0 100 0 0 0 0.02 0 100.02 Comparative Example 20 0 100 0 0 0 0.01 0 100.01

<Experimental Example 2. Confirmation of cytotoxicity of each complex>

HDP (Human Dermal Papilla Cell) and HHGMC (Human Hair Germinal Matrix Cell) were used as experimental cells for cytotoxicity.

HDP cells were cultured in Human dermal papilla growth medium (CellBio) containing 4% fetal bovine serum (FBS) and 0.5% penicillin/streptomycin solution (P/S), and HHGMC cells were cultured in MSCM (Mesenchymal Stem Cell Medium) containing 5% fetal bovine serum (FBS), 1% penicillin/streptomycin solution (P/S), and 1% mesenchymal stem cell growth supplement (MSCGS).

Experimental Example 2-1. Confirmation of cytotoxicity in mammary papilla cells

A cytotoxicity test on human papilla cells (HDP) was conducted for the complex of the present invention. The experimental method is as follows. Cells were seeded in a 48-well plate and cultured for 24 hours. The medium was replaced with 1% serum, and the complex samples of Examples 1 to 12 and Comparative Examples 1 to 20 were treated at various concentrations and cultured for 24 hours. After that, EZ-Cytox was treated and reacted, and the absorbance was measured at 450 nm with an ELISA reader. Cytotoxicity was expressed as a percentage of absorbance compared to the control group.

After confirming the results of each experiment, all the composite samples of Examples 1 to 12 and Comparative Examples 1 to 20 showed a survival rate of more than 80% of each cell within a treatment concentration of 3%, and therefore, each subsequent experiment was conducted at a concentration of 1% (100 ppm).

Among the experimental results, the experimental results of the extract of Example 2 are shown in Table 6 below by concentration as a representative example.

Sample Conc. Average Stdev. p-value Control 100.0 1.70 1.0000 Example 2 0.1 101.3 2.50 0.5089 0.5 106.2 3.58 0.0546 1 98.5 3.41 0.0682 2 90.0 5.06 0.0317 3 81.1 1.49 0.0004

Experimental Example 2-2. Confirmation of cytotoxicity in mother cells

For the complex of the present invention, a cytotoxicity test on human hypodermic gelatin (HHGMC) cells was performed. The experimental method is as follows. Cells were seeded in a 48-well plate and cultured for 24 hours, then replaced with a new medium and the complex samples of Examples 1 to 12 and Comparative Examples 1 to 20 were treated at various concentrations and cultured for 24 hours. After that, EZ-Cytox was treated and reacted, and the absorbance was measured at 450 nm with an ELISA reader. Cytotoxicity was expressed as a percentage of absorbance compared to the control group.

As confirmed by each experimental result, similar to the results in the mammary papilla cells, all the composite samples of Examples 1 to 12 and Comparative Examples 1 to 20 showed that each cell survived more than 80% within a treatment concentration of 3%. Among the experimental results, the experimental results of the extract of Example 2 are representatively shown by concentration in Table 7 below.

Sample Conc. Average Stdev. p-value Control 100.0 3.10 1.0000 Example 2 0.1 103.0 1.79 0.2245 0.5 109.2 7.09 0.1084 1 105.1 2.79 0.1009 2 89.6 0.51 0.8558 3 82.4 8.10 0.9124

<Experimental Example 3. Confirmation of hair root strengthening efficacy according to VEGF mRNA and β-Catenin expression of complex composition>

Experimental Example 3-1. Confirmation of VEGF mRNA expression

In the same manner as Experimental Example 1, the complex samples of Examples 1 to 12 and Comparative Examples 1 to 20 were each treated with a final cell treatment concentration of 1%, and mRNA extraction, cDNA synthesis, and Real-time PCR were performed to confirm the effect of the addition of biotin and niacinamide on the VEGF mRNA expression of the mixture of the existing Magnolia dentata extract and brewer's yeast extract. The results of VEGF mRNA expression of each complex are shown in Table 8 below.

Sample (1%) Average Stdev. p-value Control (untreated group) 100.0 1.45 1.000 Adenosine 0.75 mM 249.2 3.95 0.000 Example 1 230.8 2.34 0.000 Example 2 238.7 1.96 0.002 Example 3 225.3 1.42 0.000 Example 4 224.2 1.79 0.000 Example 5 222.2 2.02 0.000 Example 6 226.5 1.44 0.000 Example 7 222.2 2.53 0.000 Example 8 225.6 1.02 0.000 Example 9 225.3 1.96 0.000 Example 10 222.4 2.45 0.000 Example 11 225.2 2.23 0.000 Example 12 222.0 1.52 0.000 Comparative Example 1 186.4 2.30 0.000 Comparative Example 2 188.8 1.94 0.000 Comparative Example 3 162.5 2.23 0.000 Comparative Example 4 135.2 1.24 0.001 Comparative Example 5 136.0 2.50 0.000 Comparative Example 6 175.0 1.23 0.000 Comparative Example 7 156.0 1.05 0.000 Comparative Example 8 176.4 2.62 0.002 Comparative Example 9 153.3 1.43 0.000 Comparative Example 10 156.2 2.24 0.000 Comparative Example 11 162.5 1.31 0.000 Comparative Example 12 165.2 1.80 0.000 Comparative Example 13 146.4 1.55 0.001 Comparative Example 14 165.0 2.22 0.000 Comparative Example 15 164.8 1.96 0.002 Comparative Example 16 185.4 2.34 0.000 Comparative Example 17 179.5 1.42 0.000 Comparative Example 18 175.7 1.79 0.000 Comparative Example 19 170.4 2.02 0.000 Comparative Example 20 165.3 1.94 0.000

Referring to Table 8, it can be confirmed that the VEGF mRNA expression was significantly increased under the conditions in which each complex was treated under the conditions of Examples 1 to 12, indicating excellent root strengthening efficacy. However, even though the mixture of the extract of Magnolia chinensis and the extract of brewer's yeast contained both biotin and niacinamide, the increase in VEGF mRNA expression was minimal under the conditions of Comparative Examples 1 and 2.

In addition, in the case of Comparative Examples 5 and 6, the 'amounts of biotin and niacinamide added' were the same as in Example 2, but since the VEGF mRNA expression efficacy of the 'mixture of the extract of Mackerel and the extract of brewer's yeast' applied in Comparative Examples 5 and 6 was already presented as being minimal in Experimental Example 1, the same effect as the complex of Example 2 was not observed.

Therefore, it can be seen that it is essential that the composition of the complex of the present invention includes a mixture containing 20 to 40 wt% of a perilla extract and 60 to 80 wt% of a brewer's yeast extract, and that 0.02 to 0.05 wt% of biotin and 0.30 to 0.90 wt% of niacinamide are added based on 100 wt% of the mixture.

Experimental Example 3-2. Confirmation of β-Catenin mRNA expression

The expression of β-Catenin mRNA was confirmed by applying the cDNA of Experimental Example 3-1 and the primers of Table 9 below, and the results are shown in Table 10 below.

Primer Sense Antisense β-Catenin 5'-GCT GGT GAC AGG GAA GAC AT-3' 5'-CCA TAG TGA AGG CGA ACT GC-3' β-actin 5'-GGC ACC CAG CAC AAT GAA G-3' 5'-CCG ATC CAC ACG GAG TAC TTG-3'

Sample (1%) Average Stdev. p-value Control (untreated group) 100.0 0.00 1.0000 Adenosine 0.75 mM 168.3 8.28 0.0001 Example 1 135.2 2.53 0.0002 Example 2 138.7 5.33 0.0128 Example 3 134.2 3.66 0.0000 Example 4 132.0 5.33 0.0003 Example 5 129.4 3.44 0.0000 Example 6 128.8 4.66 0.0034 Example 7 132.5 2.48 0.0000 Example 8 136.3 3.69 0.0034 Example 9 137.2 5.55 0.0000 Example 10 136.3 2.03 0.0000 Example 11 134.7 3.42 0.0000 Example 12 134.0 4.53 0.0000 Comparative Example 1 110.2 5.24 0.0000 Comparative Example 2 114.2 2.23 0.0032 Comparative Example 3 115.0 3.20 0.0000 Comparative Example 4 107.2 5.52 0.0001 Comparative Example 5 105.3 6.34 0.0000 Comparative Example 6 114.6 3.56 0.0000 Comparative Example 7 112.3 4.36 0.0000 Comparative Example 8 109.4 2.31 0.0032 Comparative Example 9 108.5 6.45 0.0000 Comparative Example 10 108.6 3.36 0.0045 Comparative Example 11 109.6 4.03 0.0000 Comparative Example 12 113.3 2.35 0.0020 Comparative Example 13 104.4 3.42 0.0000 Comparative Example 14 105.2 5.63 0.0000 Comparative Example 15 107.3 4.24 0.0000 Comparative Example 16 116.4 5.36 0.0001 Comparative Example 17 113.5 6.43 0.0000 Comparative Example 18 114.6 3.54 0.0000 Comparative Example 19 115.6 4.66 0.0000 Comparative Example 20 112.6 2.36 0.0000

Referring to Table 10, the expression level in the Control was set as 100%, and the expression levels of the β-Catenin gene in the complex samples of Examples 1 to 12 and Comparative Examples 1 to 20 were compared based on this. As a result, β-Catenin in the complex samples of Examples 1 to 12 It can be confirmed that the expression of the gene increases significantly, and through this, it can be confirmed that it has a root strengthening effect. However, the composite samples of Comparative Examples 1 to 20 have β-Catenin Gene expression appears to be very weak, indicating little effect.

<Experimental Example 4. Evaluation of Hair Loss Relief Efficacy (Stress-Hair Loss)>

To evaluate the efficacy of alleviating stress-induced hair loss, the expression of genes for hair loss and inflammation-inducing factors, TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α), was performed using qRT-PCR.

Experimental Example 4-1. Confirmation of TGF-β2 (Transforming growth factor-beta2) expression

6-well multi plate was seeded with human papilla cells (HDP) and cultured for 24 hours, then replaced with fresh medium and treated with Substance P (SP) and Acetate salt hydrate (SP) (Sigma Aldrich, S6883), which are secreted when stress occurs, and each complex sample was treated at a final concentration of 1% and cultured for 16 hours. After washing with PBS, total RNA was extracted from the cultured cells using QIAzol Lysis Reagent (QIAGEN) according to the manufacturer's instructions, and the isolated RNA was quantified using a Qubit™ fluorometer with RNA BR assay kit, followed by cDNA synthesis and real-time PCR. The cDNA synthesis was performed using a qPCRBIO cDNA Synthesis kit according to the kit's method, and real-time PCR (QST 7500 Fast Real Time, Applied Biosystems™) was performed using 2x qPCRBIO SyGreen Blue mix Lo-ROX.

Primer Sense Antisense TGF-β2 5'-CAC CAT AAA GAC AGG AAC CTG-3' 5'-GGA GGT GCC ATC AAT ACC TGC-3' β-actin 5'-GGC ACC CAG CAC AAT GAA G-3' 5'-CCG ATC CAC ACG GAG TAC TTG-3'

Sample Average Stdev. p-value Control 77.6 3.85 0.0005 Substance P 2.5 nM 100.0 0.00 1.0000 Substance P 2.5 nM + Caffeine 5 ppm 82.6 3.02 0.0006 Substance P 2.5 nM + Example 1 complex 1% 79.3 1.24 0.0008 Substance P 2.5 nM + Example 2 Complex 1% 78.4 2.74 0.0042 Substance P 2.5 nM + Example 3 complex 1% 80.2 2.10 0.0002 Substance P 2.5 nM + Example 4 complex 1% 79.0 1.47 0.0000 Substance P 2.5 nM + Example 5 complex 1% 81.2 2.91 0.0000 Substance P 2.5 nM + Example 6 complex 1% 82.3 1.50 0.0002 Substance P 2.5 nM + Example 7 complex 1% 81.9 1.36 0.0000 Substance P 2.5 nM + Example 8 complex 1% 83.2 2.24 0.0000 Substance P 2.5 nM + Example 9 complex 1% 84.3 2.43 0.0004 Substance P 2.5 nM + Example 10 complex 1% 81.2 2.05 0.0000 Substance P 2.5 nM + Example 11 complex 1% 81.0 1.65 0.0000 Substance P 2.5 nM + Example 12 complex 1% 79.9 2.46 0.0005 Substance P 2.5 nM + Comparative Example 1 Complex 1% 91.0 2.43 0.0000 Substance P 2.5 nM + Comparative Example 2 Complex 1% 92.2 1.56 0.0000 Substance P 2.5 nM + Comparative Example 3 Complex 1% 89.3 2.35 0.0012 Substance P 2.5 nM + Comparative Example 4 Complex 1% 96.2 2.43 0.0000 Substance P 2.5 nM + Comparative Example 5 Complex 1% 94.9 3.52 0.0000 Substance P 2.5 nM + Comparative Example 6 Complex 1% 96.6 2.23 0.0000 Substance P 2.5 nM + Comparative Example 7 Complex 1% 93.3 1.05 0.0001 Substance P 2.5 nM + Comparative Example 8 Complex 1% 94.4 2.66 0.0000 Substance P 2.5 nM + Comparative Example 9 Complex 1% 96.5 1.53 0.0000 Substance P 2.5 nM + Comparative Example 10 Complex 1% 93.6 2.24 0.0000 Substance P 2.5 nM + Comparative Example 11 Complex 1% 94.0 1.35 0.0001 Substance P 2.5 nM + Comparative Example 12 Complex 1% 92.9 2.56 0.0000 Substance P 2.5 nM + Comparative Example 13 Complex 1% 93.6 2.03 0.0000 Substance P 2.5 nM + Comparative Example 14 Complex 1% 94.3 1.62 0.0000 Substance P 2.5 nM + Comparative Example 15 Complex 1% 94.4 2.43 0.0000 Substance P 2.5 nM + Comparative Example 16 Complex 1% 92.5 1.54 0.0000 Substance P 2.5 nM + Comparative Example 17 Complex 1% 93.0 2.49 0.0000 Substance P 2.5 nM + Comparative Example 18 Complex 1% 94.3 1.60 0.0000 Substance P 2.5 nM + Comparative Example 19 Complex 1% 92.4 1.26 0.0000 Substance P 2.5 nM + Comparative Example 20 Complex 1% 93.5 2.35 0.0000

Referring to Table 12, when the expression level in the Substance P alone treatment group is set as 100%, the expression levels of the TGF-β2 gene in the complexes of Examples 1 to 12 are compared based on this, and it can be seen that the expression of the TGF-β2 gene is greatly reduced, confirming that the composition has a stress-induced hair loss alleviation effect.

Experimental Example 4-2. Confirmation of TNF-α mRNA expression

The expression of TNF-α mRNA was confirmed by applying the cDNA of Experimental Example 4-1 and the primers of Table 13 below, and the results are shown in Table 14 below.

Primer Sense Antisense TNF-α 5'-CCC AGG GAC CTC TCT CTA ATC-3' 5'-GGT TTG CTA CAA CAT GGG CTA CA-3' β-actin 5'-GGC ACC CAG CAC AAT GAA G-3' 5'-CCG ATC CAC ACG GAG TAC TTG-3'

Sample Average Stdev. p-value Control 38.7 2.75 0.0000 Substance P 2.5 nM 100.0 0.00 1.0000 Substance P 2.5 nM + Caffeine 5 ppm 41.6 1.89 0.0000 Substance P 2.5 nM + Example 1 complex 1% 41.2 1.41 0.0034 Substance P 2.5 nM + Example 2 Complex 1% 39.1 0.70 0.0000 Substance P 2.5 nM + Example 3 complex 1% 40.3 1.24 0.0004 Substance P 2.5 nM + Example 4 complex 1% 43.6 2.13 0.0000 Substance P 2.5 nM + Example 5 complex 1% 40.1 1.70 0.0000 Substance P 2.5 nM + Example 6 complex 1% 42.2 2.78 0.0000 Substance P 2.5 nM + Example 7 complex 1% 43.5 1.52 0.0000 Substance P 2.5 nM + Example 8 complex 1% 43.6 1.33 0.0000 Substance P 2.5 nM + Example 9 complex 1% 44.4 1.45 0.0000 Substance P 2.5 nM + Example 10 complex 1% 39.3 0.56 0.0001 Substance P 2.5 nM + Example 11 complex 1% 41.9 1.23 0.0000 Substance P 2.5 nM + Example 12 complex 1% 43.0 2.54 0.0000 Substance P 2.5 nM + Comparative Example 1 Complex 1% 65.6 1.26 0.0000 Substance P 2.5 nM + Comparative Example 2 Complex 1% 63.0 1.56 0.0001 Substance P 2.5 nM + Comparative Example 3 Complex 1% 65.3 1.23 0.0000 Substance P 2.5 nM + Comparative Example 4 Complex 1% 89.2 1.44 0.0000 Substance P 2.5 nM + Comparative Example 5 Complex 1% 84.1 2.32 0.0000 Substance P 2.5 nM + Comparative Example 6 Complex 1% 77.0 2.43 0.0023 Substance P 2.5 nM + Comparative Example 7 Complex 1% 67.3 1.54 0.0000 Substance P 2.5 nM + Comparative Example 8 Complex 1% 67.4 2.62 0.0000 Substance P 2.5 nM + Comparative Example 9 Complex 1% 74.6 1.33 0.0001 Substance P 2.5 nM + Comparative Example 10 Complex 1% 64.6 1.05 0.0000 Substance P 2.5 nM + Comparative Example 11 Complex 1% 74.3 1.83 0.0000 Substance P 2.5 nM + Comparative Example 12 Complex 1% 75.4 1.34 0.0000 Substance P 2.5 nM + Comparative Example 13 Complex 1% 73.5 2.45 0.0000 Substance P 2.5 nM + Comparative Example 14 Complex 1% 82.6 1.56 0.0001 Substance P 2.5 nM + Comparative Example 15 Complex 1% 73.6 1.36 0.0000 Substance P 2.5 nM + Comparative Example 16 Complex 1% 75.3 1.62 0.0000 Substance P 2.5 nM + Comparative Example 17 Complex 1% 69.4 1.23 0.0000 Substance P 2.5 nM + Comparative Example 18 Complex 1% 76.5 1.34 0.0000 Substance P 2.5 nM + Comparative Example 19 Complex 1% 76.5 1.45 0.0000 Substance P 2.5 nM + Comparative Example 20 Complex 1% 87.3 1.66 0.0000

Referring to Table 14, the expression level in the SP only treatment group was set as 100%, and the expression level of the TNF-α gene of the example was compared based on this. As a result, it was confirmed that the expression of the TNF-α gene was significantly reduced in the treatment groups of Examples 1 to 12, thereby having a stress-induced hair loss alleviation effect.

<Experimental Example 5. Evaluation of Hair Growth Efficacy (Hair Growth)>

To evaluate the hair growth efficacy, IGF-1 (Insulin-like Growth Factor) gene expression experiment was performed using qRT-PCR. Hair growth cells (HHGMC) were seeded in a 6-well multi plate and cultured for 24 hours, then replaced with fresh medium and each complex sample was treated at a final concentration of 1% and cultured for 48 hours. After that, the cultured cells were washed with PBS, and total RNA was extracted from the cultured cells using QIAzol Lysis Reagent (QIAGEN) according to the manufacturer's instructions. The isolated RNA was quantified using a Qubit™ fluorometer with RNA BR assay kit, and then cDNA was synthesized and real-time PCR was performed. The cDNA synthesis was performed using the qPCRBIO cDNA Synthesis Kit according to the kit's method, and real-time PCR (QST 7500 Fast Real Time, Applied Biosystems™) was performed using 2x qPCRBIO SyGreen Blue mix Lo-ROX.

Primer Sense Antisense IGF-1 5'-AGC CTG TCC ACC CTT GAG AA-3' 5'-CCC TGG AGC CAC AGA GCA T-3' β-actin 5'-GGC ACC CAG CAC AAT GAA G-3' 5'-CCG ATC CAC ACG GAG TAC TTG-3'

Sample (1%) Average Stdev. p-value Control (untreated group) 100.0 0.00 1.0000 Minoxidil 5 μM 137.9 9.52 0.0023 Caffeine 5 ppm 125.8 9.47 0.0092 Example 1 145.3 4.65 0.0000 Example 2 146.1 7.01 0.0003 Example 3 145.6 5.45 0.0000 Example 4 144.0 4.20 0.0000 Example 5 140.6 6.45 0.0000 Example 6 145.3 4.34 0.0000 Example 7 146.6 6.63 0.0000 Example 8 142.6 3.46 0.0000 Example 9 141.4 4.56 0.0000 Example 10 139.5 6.34 0.0000 Example 11 138.6 3.98 0.0000 Example 12 141.3 4.53 0.0000 Comparative Example 1 121.4 6.52 0.0000 Comparative Example 2 125.2 3.53 0.0000 Comparative Example 3 131.0 4.63 0.0000 Comparative Example 4 109.4 6.53 0.0000 Comparative Example 5 106.2 3.41 0.0000 Comparative Example 6 119.4 4.35 0.0034 Comparative Example 7 121.5 6.63 0.0000 Comparative Example 8 118.7 7.45 0.0000 Comparative Example 9 114.6 5.63 0.0023 Comparative Example 10 115.5 4.33 0.0000 Comparative Example 11 116.4 6.53 0.0000 Comparative Example 12 123.6 5.46 0.0000 Comparative Example 13 118.0 6.34 0.0001 Comparative Example 14 109.5 4.03 0.0000 Comparative Example 15 120.4 5.66 0.0000 Comparative Example 16 113.5 6.34 0.0000 Comparative Example 17 115.6 4.42 0.0001 Comparative Example 18 122.3 6.03 0.0000 Comparative Example 19 113.5 5.56 0.0000 Comparative Example 20 115.0 5.34 0.0000

Referring to Table 16, it can be confirmed that the expression of the IGF-1 gene of the complexes of Examples 1 to 12 strongly increases, and this result supports the hair growth effect.

Claims (10)

A cosmetic composition for strengthening hair roots containing a complex of extract of mugwort, yeast extract, biotin and niacinamide as active ingredients,
A cosmetic composition for strengthening hair roots, characterized in that the complex comprises a mixture of 20 to 40 wt% of a perilla extract and 60 to 80 wt% of a brewer's yeast extract, and 0.02 to 0.05 wt% of biotin and 0.30 to 0.90 wt% of niacinamide are added based on 100 wt% of the mixture. In the first paragraph,
A cosmetic composition for strengthening hair roots, characterized in that the complex enhances the expression of at least one gene selected from VEGF (Vascullar Endotherial Growth Factor) and β-Catenin. In the first paragraph,
A cosmetic composition for strengthening hair roots, characterized in that the above complex has an effect of alleviating stress-induced hair loss. In the third paragraph,
A cosmetic composition for strengthening hair roots, characterized in that the complex inhibits the expression of at least one gene selected from among TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α). In the first paragraph,
The above complex is a cosmetic composition for strengthening hair roots, characterized in that it has a hair growth effect. In paragraph 5,
A cosmetic composition for strengthening hair roots, characterized in that the composition has the effect of enhancing the expression of IGF-1 (Insulin-like Growth Factor). A composition for external skin application for the prevention or treatment of stress-induced hair loss, containing a complex of extracts of mugwort, yeast extract, biotin and niacinamide as active ingredients and having the effect of strengthening hair roots.
A composition for external application to the skin for the prevention or treatment of stress-induced hair loss, characterized in that the complex comprises a mixture of 20 to 40 wt% of a perilla extract and 60 to 80 wt% of a brewer's yeast extract, and 0.02 to 0.05 wt% of biotin and 0.30 to 0.90 wt% of niacinamide are added based on 100 wt% of the mixture. In Article 7,
A composition for external application to the skin for the prevention or treatment of stress-induced hair loss, characterized in that the complex enhances the expression of at least one gene selected from VEGF (Vascullar Endotherial Growth Factor) and β-Catenin. In Article 7,
A composition for external application to the skin for the prevention or treatment of stress-induced hair loss, characterized in that the complex inhibits the expression of at least one gene selected from among TGF-β2 (Transforming growth factor-beta2) and TNF-α (Tumor necrosis factor-α). In Article 7,
A composition for external application to the skin for the prevention or treatment of stress-induced hair loss, characterized in that the complex has the effect of enhancing the expression of IGF-1 (Insulin-like Growth Factor).