COMPOSITION FOR PREVENTING HAIR LOSS OR PROMOTING HAIR GROWTH

Abstract

Provided is a composition for preventing hair loss and promoting hair growth, containing an ingredient for inducing anagen hair growth or hair growth promotion. The composition for preventing hair loss and promoting hair growth, of the presently claimed subject matter, shortens the period of telogen-to-anagen transition in the hair growth cycle, so as to promote hair growth and delay the transition to the catagen stage, thereby having the excellent effects of preventing hair loss and promoting hair growth.

Claims

1.-11. (canceled)

12. A method of alleviating hair loss or promoting hair growth comprising: administering to a subject in need thereof a composition comprising an active ingredient selected from a group consisting of momordin Ic, platycodin D2, polygalacin D, asiaticoside B, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 and ziyuglycoside II, and thereby alleviating hair loss or promoting hair growth in the subject.

13. The method for alleviating hair loss or promoting hair growth according to claim 12, wherein the active ingredient is in an amount of 0.00001-50 wt % based on the total weight of the composition.

14. The method for alleviating hair loss or promoting hair growth according to claim 12, wherein the composition enhances the activity of dermal papilla cells.

15. The method for alleviating hair loss or promoting hair growth according to claim 12, wherein the composition enhances the activity of the Wnt/β-catenin signaling pathway in dermal papilla cells.

16. The method for alleviating hair loss or promoting hair growth according to claim 12, wherein the composition inhibits the action of male hormones.

Description

BEST MODE

[0031] Hereinafter, the present disclosure is described in more detail through examples, etc. However, the examples of the present disclosure may be changed into various forms and it should not be construed that the scope of the present disclosure is not limited by the following examples. The examples of the present disclosure are provided so that the present disclosure is more completely understood by those having ordinary knowledge in the art.

[0032] Preparation of Composition for Treating Hair Loss (Hair Tonic)

[0033] Hair tonic compositions of Examples 1 to 11-2, which contain momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II as an active ingredient, were prepared as described in Table 1.

[0034] The substances and reagents used in the examples of the present disclosure were purchased from cosmetic material manufactures and commercial vendors.

TABLE-US-00001 TABLE 1 Flavorant Castor and Purified Ingredients Ethanol oil Glycerin Active ingredient colorant water Weight Comp. 55 5 3 — Adequate Balance ratio Ex. 1 (100 in (%) Comp. 55 5 3 Minoxidil 2 μg/mL Adequate total) Ex. 2 Comp. 0 5 3 — Adequate Ex. 3 Ex. 1 55 5 3 Momordin Ic 100 μg/mL Adequate Ex. 1-2 0 5 3 Momordin Ic 100 μg/mL Adequate Ex. 2 55 5 3 Platycodin D2 100 μg/mL Adequate Ex. 2-2 0 5 3 Platycodin D2 100 μg/mL Adequate Ex. 3 55 5 3 Polygalacin D 100 μg/mL Adequate Ex. 3-2 0 5 3 Polygalacin D 100 μg/mL Adequate Ex. 4 55 5 3 Asiaticoside B 100 μg/mL Adequate Ex. 4-2 0 5 3 Asiaticoside B 100 μg/mL Adequate Ex. 5 55 5 3 Bacopaside 1 100 μg/mL Adequate Ex. 5-2 0 5 3 Bacopaside 1 100 μg/mL Adequate Ex. 6 55 5 3 Notoginsenoside R2 100 μg/mL Adequate Ex. 6-2 0 5 3 Notoginsenoside R2 100 μg/mL Adequate Ex. 7 55 5 3 Picfeltarraenin IB 100 μg/mL Adequate Ex. 7-2 0 5 3 Picfeltarraenin IB 100 μg/mL Adequate Ex. 8 55 5 3 Pseudoginsenoside 100 μg/mL Adequate RT5 Ex. 8-2 0 5 3 Pseudoginsenoside 100 μg/mL Adequate RT5 Ex. 9 55 5 3 Raddeanin A 100 μg/mL Adequate Ex. 9-2 0 5 3 Raddeanin A 100 μg/mL Adequate Ex. 10 55 5 3 Vina-ginsenoside 100 μg/mL Adequate R4 Ex. 0 5 3 Vina-ginsenoside 100 μg/mL Adequate 10-2 R4 Ex. 11 55 5 3 Ziyuglycoside II 100 μg/mL Adequate Ex. 0 5 3 Ziyuglycoside II 100 μg/mL Adequate 11-2

[0035] Preparation of Composition for Treating Hair Loss (Hair Lotion)

[0036] Hair lotion compositions, which contain momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II as an active ingredient, were prepared as described in Table 2.

TABLE-US-00002 TABLE 2 Weight Ingredients ratio (%) Cetostearyl alcohol 2 Stearyl triethyl ammonium chloride 2 Hydroxyethyl cellulose 0.5 Momordin Ic, platycodin D2, polygalacin D, 0.01 asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II Flavorant and colorant Adequate Purified water Balance (100 in total)

TEST EXAMPLE 1

Enhancement of Activity of Dermal Papilla Cells

[0037] Human-derived dermal papilla cells (DPCs) were purchased from PromoCell. The DPCs were cultured in DMEM (Hyclone Inc., UT, USA) containing 5% fetal bovine serum (FBS; GIBCO, NY, USA), 100 units/mL penicillin and 100 μg/mL streptomycin under the condition of 37° C. and 5% CO.sub.2. The cultured DPCs were seeded onto a 96-well plate at 3,000 cells/well and then cultured for 24 hours under a 0.1% serum condition. Then, the cultured cells were treated and incubated for a day with serum-free DMEM diluted with DMSO (vehicle) to 1:1000 as a control group, 2 μg/mL minoxidil as a positive control group, or each of momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 and ziyuglycoside II, as described in Table 3. After the incubation, the enhancement of cellular activity was evaluated by the CCK method. The cell culture was treated and incubated with CCK-8 at 1:10 for 1 hour. 1 hour later, the absorbance of each well was measured at 450 nm. All the experiments were 3 times and the absorbance was averaged. The result was expressed as percentage of the control group as 100.

TABLE-US-00003 TABLE 3 Activity of Concen- dermal papilla Groups tration cells (%) Untreated — 100% Minoxidil  2 μg/mL 121% Momordin Ic 10 μg/mL 148% Platycodin D2 10 μg/mL 162% Polygalacin D 10 μg/mL 164% Asiaticoside B 10 μg/mL 131% Bacopaside I 10 μg/mL 133% Notoginsenoside R2 10 μg/mL 131% Picfeltarraenin IB 10 μg/mL 139% Pseudoginsenoside RT5 10 μg/mL 141% Raddeanin A 10 μg/mL 130% Vina-ginsenoside R4 10 μg/mL 137% Ziyuglycoside II 10 μg/mL 139%

[0038] As a result, it was confirmed that the treatment with momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II has superior effect of enhancing the activity of dermal papilla cells and promoting the proliferation of the DPCs.

TEST EXAMPLE 2

Enhancement of Mitochondrial Activity of Dermal Papilla Cells

[0039] Human-derived dermal papilla cells (DPCs) were purchased from PromoCell. The DPCs were cultured in DMEM (Hyclone Inc., UT, USA) containing 5% fetal bovine serum (FBS; GIBCO, NY, USA), 100 units/mL penicillin and 100 μg/mL streptomycin under the condition of 37° C. and 5% CO.sub.2. The cultured DPCs were seeded onto a 96-well plate at 3,000 cells/well and then cultured for 24 hours under a 0.1% serum condition. Then, the cultured cells were treated and incubated for a day with serum-free DMEM diluted with DMSO (vehicle) to 1:1000 as a control group, 2 μg/mL minoxidil as a positive control group, or each of momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 and ziyuglycoside II, as described in Table 4. After the incubation, the degree of cell proliferation was evaluated by the JC-1 method. The cell culture was treated and incubated with JC-1 at 1:100 for 1 hour. 1 hour later, the fluorescence of each well was measured at 590 nm and 530 nm. All the experiments were 3 times and the fluorescence intensity was averaged. The result was expressed as percentage of the control group as 100.

TABLE-US-00004 TABLE 4 Mitochondrial Concen- activity of dermal Groups tration papilla cells (%) Untreated group — 100% Minoxidil  2 μg/mL 129% Momordin Ic 10 μg/mL 120% Asiaticoside B 10 μg/mL 151% Bacopaside I 10 μg/mL 110% Notoginsenoside R2 10 μg/mL 117% Pseudoginsenoside RT5 10 μg/mL 112% Vina-ginsenoside R4 10 μg/mL 111% Ziyuglycoside II 10 μg/mL 105%

[0040] As a result, the treatment with momordin Ic, asiaticoside B, bacopaside I, notoginsenoside R2, pseudoginsenoside RT5, vina-ginsenoside R4 or ziyuglycoside II resulted in a superior effect of enhancing the mitochondrial activity of the dermal papilla cells.

TEST EXAMPLE 3

Regulation of Wnt/β-Catenin Signaling in Dermal Papilla Cells

[0041] In general, the Wnt/β-catenin signaling activated in the dermal papillae during transition from the catagen to the anagen transition in the hair growth cycle begins as the hair starts to grow and occurs throughout the anagen phase. In the telogen and catagen phases, the Wnt/β-catenin signaling decreases or disappears, resulting in degeneration of hair follicles and shedding of hair. Therefore, it was investigated in the examples how much the momordin Ic, platycodin D2, polygalacin D or pseudoginsenoside RT5 of the present disclosure contributes to the amplification of Wnt/β-catenin signaling.

[0042] Wnt3a protein was used as a positive control group for amplifying Wnt/β-catenin signaling, and DMSO was used as a negative control group. After seeding Wnt Reporter HEK293A cells in a 96-well culture plate, with 3×10.sup.4 cells per well, and then treating with the momordin Ic, platycodin D2, polygalacin D or pseudoginsenoside RT5 of the present disclosure as described in Table 5, reporter assay was conducted using a Promega's luciferase assay kit (E1960). The experiment was conducted according to the manufacturer's instructions and the activity of the Wnt/β-catenin promoter was measured using a luminometer (Victor; PerkinElmer, Waltham, Mass., USA).

TABLE-US-00005 TABLE 5 Wnt signaling activity for Concen- activating hair Groups tration follicles (%) Untreated group — 100% Minoxidil  2 μg/mL  82% Momordin Ic 10 μg/mL 370% Platycodin D2 10 μg/mL 216% Polygalacin D 10 μg/mL 293% Pseudoginsenoside RT5 10 μg/mL 120%

[0043] As a result, the treatment with momordin Ic, platycodin D2, polygalacin D or pseudoginsenoside RT5 resulted in superior Wnt signaling activity. Accordingly, it was confirmed that the momordin Ic, platycodin D2, polygalacin D or pseudoginsenoside RT5 enhances the activity of the Wnt/β-catenin signaling pathway, which facilitates hair growth by hair follicle stem cells, very superiorly and, therefore, is effective in promoting hair growth.

TEST EXAMPLE 4

Androgenic Activity

[0044] A stable cell line constructed by permanently transfecting androgen receptor-positive 22Rv1 human prostate cancer cells with the pGL4.36-MMTV-Luc vector, which possesses two androgen-responsive elements and a firefly luciferase reporter gene, was used for this experiment. The stable cell line was maintained by subculturing using RPMI1640 and 10% fetal bovine serum (GIBCO BRL, Gaithersburg, Md., USA). For transcriptional activation assay, the cells were seeded in a 96-well plate, with 25,000 cells per well, while replacing the medium with phenol red-free RPMI1640 containing 5% charcoal-stripped fetal bovine serum. After culturing in an incubator at 37° C. for 48 hours and then treating with momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, pseudoginsenoside RT5, raddeanin A or vina-ginsenoside R4 together with 1 nM DHT as described in Table 6, the cells were cultured for 24 hours and the inhibition of luciferase activity increased by DHT was measured using a luciferase assay system (Promega). The result was expressed as the inhibition of the luciferase activity by momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, pseudoginsenoside RT5, raddeanin A or vina-ginsenoside R4 with respect to the luciferase activity increased by treatment with 1 M DHT as 100%. Bicalutamide (Casodex) was used as a positive control group and CCK-8 assay was conducted in parallel to investigate cytotoxicity. The cell culture was treated and incubated with CCK-8 at 1:10 for 2 hours. 2 hour later, the absorbance of each well was measured at 450 nm. All the experiments were 3 times and the absorbance was averaged. The result was expressed as percentage of the group treated with 1 nM DHT as 100%.

TABLE-US-00006 TABLE 6 Inhibition of Concen- androgenic Groups tration activity (%) Untreated group —  0% Bicalutamide 20 μM 85% Minoxidil 2 μg/mL  0% Momordin Ic 10 μg/mL 12% Platycodin D2 10 μg/mL 16% Polygalacin D 10 μg/mL 26% Asiaticoside B 10 μg/mL  6% Bacopaside I 10 μg/mL  6% Notoginsenoside R2 10 μg/mL 29% Pseudoginsenoside RT5 10 μg/mL  8% Raddeanin A 10 μg/mL 10% Vina-ginsenoside R4 10 μg/mL  4%

[0045] As a result, the treatment with platycodin D2, polygalacin D or notoginsenoside R2 resulted in superior effect of inhibiting androgenic activity.

TEST EXAMPLE 5

Hair-Growing Effect of Composition for Treating Hair Loss and Promoting Hair Growth Composition (Hair Tonic)

[0046] The hair-growing effect of the composition for treating hair loss and promoting hair growth of the present disclosure (hair tonic) was tested for a total of 190 males and females who have significantly fewer hairs than normal people or have the symptoms of hair loss. Different compositions were applied on the left and right parts of the scalp of the 190 males and females. The compositions of Comparative Examples 1, 2 and 3 and Examples 1 to 11-2 were applied to the hair and scalp for 6 months, 5 times a week, to 25 groups of 15 people. Then, evaluation was carried out using clinical images and a phototrichogram. The evaluation using clinical images was conducted 2 months and 6 months after the application on a 3-point scale (‘good’, ‘slight’ and ‘no change’; good: 50-75% improved, slight: 25-50% improved, no change: not improved). The evaluation using a phototrichogram was conducted 6 months after the application by measuring the number of hairs per unit area and average hair thickness for Comparative Examples and Examples. The result is shown in Table 7.

TABLE-US-00007 TABLE 7 Evaluation using clinical images Phototrichogram No change Slight Good Average hair (No.) (No.) (No.) Number of hairs per thickness (μm) 2 6 2 6 2 6 unit area (hairs/cm.sup.2) 0 6 months months months months months months 0 month 6 months month months Comp. 14 12 1 1 0 2 103 ± 21 109 ± 22 55 ± 2 58 ± 1 Ex. 1 Comp. 9 2 5 4 1 9 105 ± 23 168 ± 21 62 ± 4 70 ± 2 Ex. 2 Comp. 13 13 2 1 0 1 98 ± 12 102 ± 19 52 ± 4 55 ± 6 Ex. 3 Ex. 1 9 3 5 2 1 10 100 ± 19 219 ± 23 59 ± 3 80 ± 2 Ex. 1-2 10 5 3 4 2 6 101 ± 21 150 ± 28 53 ± 2 70 ± 6 Ex. 2 8 3 4 3 3 9 102 ± 20 224 ± 19 56 ± 6 83 ± 3 Ex. 2-2 11 6 2 5 2 4 100 ± 23 162 ± 17 51 ± 2 68 ± 5 Ex. 3 9 4 3 6 3 5 112 ± 22 180 ± 28 55 ± 3 79 ± 3 Ex. 3-2 10 8 2 5 3 2 103 ± 18 141 ± 13 51 ± 1 72 ± 5 Ex. 4 9 2 2 4 4 9 109 ± 23 192 ± 23 54 ± 2 76 ± 6 Ex. 4-2 12 4 3 6 0 5 100 ± 20 157 ± 19 54 ± 5 64 ± 4 Ex. 5 9 2 2 5 4 8 108 ± 23 178 ± 28 55 ± 3 72 ± 4 Ex. 5-2 11 3 3 7 1 5 105 ± 23 150 ± 24 50 ± 4 73 ± 4 Ex. 6 8 4 3 6 4 5 101 ± 20 171 ± 18 51 ± 2 75 ± 2 Ex. 6-2 10 7 4 6 1 2 107 ± 22 168 ± 26 57 ± 4 69 ± 3 Ex. 7 10 3 4 8 1 4 105 ± 25 158 ± 23 52 ± 7 70 ± 2 Ex. 7-2 13 5 2 7 0 3 102 ± 25 142 ± 18 52 ± 3 65 ± 5 Ex. 8 11 2 3 6 1 7 106 ± 28 181 ± 25 59 ± 8 80 ± 8 Ex. 8-2 12 4 2 7 1 4 106 ± 15 161 ± 30 50 ± 6 73 ± 3 Ex. 9 8 1 5 7 2 7 101 ± 18 150 ± 27 61 ± 5 74 ± 3 Ex. 9-2 10 3 3 6 2 6 102 ± 24 148 ± 18 59 ± 3 67 ± 2 Ex. 10 9 2 4 8 2 5 110 ± 23 178 ± 30 60 ± 4 89 ± 5 Ex. 11 5 2 7 2 3 104 ± 16 142 ± 21 52 ± 6 79 ± 5 10-2 Ex. 11 10 3 4 8 1 4 107 ± 25 169 ± 26 57 ± 5 69 ± 2 Ex. 13 7 2 6 0 2 102 ± 20 151 ± 24 55 ± 4 65 ± 4 11-2

[0047] As a result, it was confirmed that the compositions of Examples 1 to 11-2, which contain momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II, showed the effect of preventing hair loss and promoting hair growth. In particular, the formulations containing ethanol showed better effect of preventing hair loss and promoting hair growth. Through this, it was confirmed that the composition for preventing hair loss and promoting hair growth of the present disclosure, which contains momordin Ic, platycodin D2, polygalacin D, asiaticoside B, bacopaside I, notoginsenoside R2, picfeltarraenin IB, pseudoginsenoside RT5, raddeanin A, vina-ginsenoside R4 or ziyuglycoside II as an active ingredient, can be very usefully used for treatment of hair loss. It will be obvious to those having ordinary knowledge in the art that the formulation examples such as the hair tonic or hair lotion are only the examples of the composition for preventing hair loss or promoting hair growth of the present disclosure and the scope of the present disclosure composition is not limited to the formulations.

[0048] As other examples, a shampoo composition according to an exemplary embodiment of the present disclosure is described in Table 8 and a conditioner composition according to an exemplary embodiment of the present disclosure is described in Table 9.

TABLE-US-00008 TABLE 8 Contents Ingredients (wt %) Active ingredient for preventing 0.01 hair loss and promoting hair growth Polyquaternium-10 0.5 Sodium lauryl sulfate 10 Oil 1 Thickener 5 Flavorant 0.5 Sodium chloride Adequate Citric acid Adequate Water Up to 100 wt %

TABLE-US-00009 TABLE 9 Contents Ingredients (wt %) Active ingredient for preventing 0.01 hair loss and promoting hair growth Stearamidopropyl diethylamine 2 Dicetyldiethylammonium chloride 1 Cetyl alcohol 3 Stearyl alcohol 4 Cyclomethicone 5 Flavorant Adequate Water Up to 100 wt %