Composition for preventing, alleviating, or treating hair loss containing rheum undulatum l. extract as active ingredient and method for preparing same

Abstract

The present invention relates to a composition for promoting hair growth or preventing, alleviating, or treating hair loss, the composition comprising a Rheum undulatum L. extract as an active ingredient. More specifically, the present invention relates to a pharmaceutical, cosmetic, or health functional food composition for promoting hair growth or preventing, alleviating, or treating hair loss, the composition comprising a Rheum undulatum L. extract as an active ingredient. The composition for promoting hair growth or preventing, alleviating, or treating hair loss, according to the present invention, is composed of a Rheum undulatum L. extract, which is a naturally derived component, and thus can provide a better hair loss treatment effect than Minoxidil, which is an existing hair loss treatment agent, while having fewer side effects.

Description

Composition for promoting hair growth, preventing, improving or treating hair loss, containing rheum extract as an active ingredient

[0001] The present invention relates to a composition for promoting hair growth, preventing, improving or treating hair loss, containing a rheum extract as an active ingredient, and more specifically, the rheum extract is characterized in that it contains a compound isolated from rheum as an active ingredient.

[0002] Hair loss refers to the loss of hair from the scalp, typically involving terminal hair (coarse, dark hair). Unlike vellus hair, which is colorless and fine, terminal hair can cause cosmetic problems if lost. Koreans have an estimated 50,000-70,000 hairs, and it's normal for people to lose about 50-70 hairs per day. However, losing more than 100 hairs may indicate ongoing hair loss.

[0003] Traditionally, hair loss was considered to be a problem that only occurred in men after middle age and was not a problem for young men and women, but recently, it tends to occur in anyone regardless of age or gender, and as hair loss progresses, it can cause great stress due to cosmetic and appearance problems.

[0004] Conventional treatments for hair loss typically involve medications like minoxidil. However, these medications are known to be less effective for some individuals and, if discontinued, hair loss can recur. Furthermore, minoxidil can cause side effects such as flaking, skin rashes, flushing, headaches, dizziness, and eye irritation. Because it causes vasodilation, it is contraindicated for those with cardiovascular disease, those under 18, and pregnant women.

[0005] Therefore, there is a growing need for new treatment methods with fewer side effects, and interest in alternative medicine, especially those made from natural ingredients, is growing.

[0006] The present invention provides a pharmaceutical composition for promoting hair growth, preventing, improving or treating hair loss, containing a rheum extract as an active ingredient.

[0007] Another object of the present invention is to provide a cosmetic composition for promoting hair growth or preventing or improving hair loss, which contains a rheum extract as an active ingredient.

[0008] Another object of the present invention is to provide a health functional food composition for promoting hair growth and preventing or improving hair loss, which contains a rheum extract as an active ingredient.

[0009] The technical problems to be solved by the invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by a person having ordinary skill in the art from the description of the present invention.

[0010] The present invention provides a pharmaceutical composition for promoting hair growth; preventing, improving or treating hair loss; comprising a rheum extract as an active ingredient.

[0011] In the present invention, the rheum extract includes a compound separated from rheum, and the compound separated from rheum includes at least one selected from the group consisting of compounds represented by the following chemical formulas 1 to 37.

[0012] In the present invention, the compound isolated from the above-mentioned rheum is characterized by increasing the protein expression of β-catenin, GSK3β, IGF-1, AKT, and cyclin D1 compared to a control group that was not treated with the compound isolated from the above-mentioned rheum.

[0013] In the present invention, the compound separated from the above-mentioned rheum is characterized by being separated from an ethyl acetate fraction prepared by suspending a methanol extract of the rheum in water and then fractionating it using ethyl acetate.

[0014] In the present invention, the rheum extract is characterized in that it is prepared by mixing ethanol with the rheum root, extracting it at 40 to 70°C for 6 to 24 hours, and then concentrating under reduced pressure.

[0015] In addition, the present invention provides a cosmetic composition for promoting hair growth, preventing or improving hair loss, and containing a rheum extract as an active ingredient.

[0016] In the present invention, the rheum extract includes a compound separated from rheum, and the compound separated from rheum includes at least one selected from the group consisting of compounds represented by the following chemical formulas 1 to 37.

[0017] In addition, the present invention provides a composition for promoting hair growth; preventing or improving hair loss; and a health functional food, which contains a rheum extract as an active ingredient.

[0018] In the present invention, the rheum extract includes a compound separated from rheum, and the compound separated from rheum includes at least one selected from the group consisting of compounds represented by the following chemical formulas 1 to 37.

[0019] The present invention can provide a pharmaceutical composition for promoting hair growth, preventing, improving or treating hair loss, containing a rheum extract as an active ingredient.

[0020] In addition, the present invention can provide a cosmetic composition for promoting hair growth or preventing or improving hair loss, which contains a rheum extract as an active ingredient.

[0021] In addition, the present invention can provide a health functional food composition for promoting hair growth and preventing or improving hair loss, which contains a rheum extract as an active ingredient.

[0022] The composition of the present invention has a superior hair loss treatment effect than minoxidil, a conventional hair loss treatment agent.

[0023] The effects of the present invention are not limited to the effects mentioned above, and other effects not mentioned will be clearly understood by those skilled in the art from the description of the claims.

[0024] Figure 1 shows the results of a Western blot analysis of protein changes related to hair loss caused by rheum extract in keratinocytes (HaCaT).

[0025] Figure 2 shows the results of a Western blot analysis of changes in hair loss-related proteins caused by rheum extract in human umbilical vein cells (HUVEC).

[0026] Figure 3 shows the results of a Western blot analysis of changes in hair loss-related proteins caused by rheum extract in human hair follicle dermal papilla cells (HFDPC).

[0027] Figure 4 is a diagram showing changes in β-catenin protein expression caused by 37 compounds isolated from rheum rhizome.

[0028] Figure 5 is a diagram showing changes in GSK3β protein expression caused by 37 compounds isolated from rheum rhizome.

[0029] Figure 6 is a diagram showing changes in IGF-1 protein expression caused by 37 compounds isolated from rheum rhizome.

[0030] Figure 7 is a diagram showing changes in AKT protein expression caused by 37 compounds isolated from rheum rhizome.

[0031] Figure 8 is a diagram showing changes in Cyclin D1 protein expression caused by 37 compounds isolated from rheum rhizome.

[0032] The terms used in this specification have been selected from widely used, current terms, taking into account the functions of the present invention. However, these terms may vary depending on the intentions of those skilled in the art, precedents, the emergence of new technologies, etc. Furthermore, in certain cases, terms may be arbitrarily selected by the applicant, and in such cases, their meanings will be described in detail in the relevant description of the invention. Therefore, the terms used in this invention should not be defined simply as names, but rather based on their inherent meanings and the overall content of the present invention.

[0033] Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with their meaning in the context of the relevant technology, and shall not be interpreted in an idealized or overly formal sense unless explicitly defined herein.

[0034] Numerical ranges are inclusive of the numbers defined in the ranges above. Every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if that lower numerical limitation were explicitly stated. Every minimum numerical limitation given throughout this specification includes every higher numerical limitation, as if that higher numerical limitation were explicitly stated. Every numerical limitation given throughout this specification will include every better numerical range within that broader numerical range, as if that narrower numerical limitation were explicitly stated.

[0035]

[0036] Hereinafter, the present invention will be described in detail.

[0037]

[0038] Method for producing rheum extract

[0039] The term "extract" used in the present invention refers to a liquid component obtained by immersing a target substance in various solvents and then extracting it for a certain period of time at room temperature, low temperature, or elevated temperature, and a solid component obtained by removing the solvent from the liquid component. In addition, it can be comprehensively interpreted to include a dilution of the resultant, a concentrate thereof, a dried product obtained by drying the extract, and a controlled or purified product thereof.

[0040] The method for extracting the above extract is not particularly limited, and extraction can be performed according to methods commonly used in the relevant technical field. Non-limiting examples of the above extraction methods include solvent extraction, ultrasonic extraction, filtration, and reflux extraction, and these may be performed alone or in combination of two or more methods.

[0041]

[0042] Preferably, the rheum extract of the present invention may refer to a rheum hot water extract or a rheum ethanol extract.

[0043] The above-mentioned hot water extract of rheum rhizome can be prepared by mixing rheum rhizome with distilled water, extracting it with hot water at 90 to 110°C for 12 to 36 hours, and then concentrating under reduced pressure. More preferably, it can be prepared by mixing rheum rhizome with distilled water, extracting it with hot water at 100°C for 24 hours, and then concentrating under reduced pressure.

[0044] The above rheum ethanol extract can be prepared by mixing ethanol with rheum rhizome, extracting at 40 to 70°C for 6 to 24 hours, and then concentrating under reduced pressure. Preferably, 40 to 60%, 41 to 59%, 42 to 58%, 43 to 57%, 44 to 56%, 45 to 55%, 46 to 54%, 47 to 53%, or 48 to 52% ethanol is mixed with rheum rhizome, and extracted at 40 to 70°C, 50 to 70°C, 51 to 69°C, 52 to 68°C, 53 to 67°C, 54 to 66°C, 55 to 65°C, 56 to 64°C, 57 to 63°C, or 58 to 62°C for 6 to 24 hours, 6 to It can be manufactured by extracting for 18 hours, 7 to 17 hours, 8 to 16 hours, 9 to 15 hours, 10 to 14 hours, or 11 to 13 hours and then concentrating under reduced pressure, and more preferably, it can be manufactured by mixing 49 to 51% ethanol with the rhizome of rheum licorice and extracting at 59 to 61°C for 11.5 to 12.5 hours and then concentrating under reduced pressure.

[0045]

[0046] Compounds isolated from rheum

[0047] The compound isolated from the rheum of the present invention may be a compound represented by the following chemical formulas 1 to 37.

[0048] [Chemical Formula 1]

[0049]

[0050] [Chemical Formula 2]

[0051]

[0052] [Chemical Formula 3]

[0053]

[0054] [Chemical Formula 4]

[0055]

[0056] [Chemical Formula 5]

[0057]

[0058] [Chemical Formula 6]

[0059]

[0060] [Chemical Formula 7]

[0061]

[0062] [Chemical Formula 8]

[0063]

[0064] [Chemical Formula 9]

[0065]

[0066] [Chemical Formula 10]

[0067]

[0068] [Chemical Formula 11]

[0069]

[0070] [Chemical Formula 12]

[0071]

[0072] [Chemical Formula 13]

[0073]

[0074] [Chemical Formula 14]

[0075]

[0076] [Chemical Formula 15]

[0077]

[0078] [Chemical Formula 16]

[0079]

[0080] [Chemical Formula 17]

[0081]

[0082] [Chemical Formula 18]

[0083]

[0084] [Chemical Formula 19]

[0085]

[0086] [Chemical Formula 20]

[0087]

[0088] [Chemical Formula 21]

[0089]

[0090] [Chemical Formula 22]

[0091]

[0092] [Chemical Formula 23]

[0093]

[0094] [Chemical Formula 24]

[0095]

[0096] [Chemical Formula 25]

[0097]

[0098] [Chemical Formula 26]

[0099]

[0100] [Chemical Formula 27]

[0101]

[0102] [Chemical Formula 28]

[0103]

[0104] [Chemical Formula 29]

[0105]

[0106] [Chemical Formula 30]

[0107]

[0108] [Chemical Formula 31]

[0109]

[0110] [Chemical Formula 32]

[0111]

[0112] [Chemical Formula 33]

[0113]

[0114] [Chemical Formula 34]

[0115]

[0116] [Chemical Formula 35]

[0117]

[0118] [Chemical Formula 36]

[0119]

[0120] [Chemical Formula 37]

[0121]

[0122] The compounds of the above chemical formulas 1 to 37 can be manufactured according to the following manufacturing method.

[0123] The above manufacturing method may include the steps of preparing a dried product of the rhizome of Rheum japonica; extracting the dried product with methanol to prepare a Rheum japonica methanol extract; suspending the Rheum japonica methanol extract in water (H2O) and then fractionating it using chloroform and ethyl acetate to prepare an ethyl acetate fraction; and performing chromatography on the ethyl acetate fraction to separate compounds.

[0124]

[0125] The step of manufacturing the above-mentioned rheum methanol extract may be characterized by reacting the dried material and methanol in a ratio of 6:3 to 7 (w:v) and then performing ultrasonic extraction at a temperature of 20 to 40°C for 3 to 5 hours, preferably by reacting the dried material and methanol in a ratio of 6:4 to 6 (w:v) and then performing ultrasonic extraction at a temperature of 25 to 35°C for 3.5 to 4.5 hours, and more preferably by reacting the dried material and methanol in a ratio of 6:4.5 to 5.5 (w:v) and then performing ultrasonic extraction at a temperature of 28 to 32°C for 3.8 to 4.2 hours.

[0126] The step of preparing the above-mentioned rheum methanol extract may further include the step of concentrating the above-mentioned rheum methanol extract under reduced pressure.

[0127]

[0128] pharmaceutical composition

[0129] The present invention can provide a pharmaceutical composition for promoting hair growth; preventing, improving or treating hair loss; containing a rheum extract as an active ingredient.

[0130] In addition, the above-mentioned rheum extract may contain a compound isolated from rheum as an effective ingredient.

[0131] The compound separated from the above-mentioned rheum may be characterized as being at least one compound selected from the group consisting of compounds represented by the above-mentioned chemical formulas 1 to 37, and preferably may be one compound selected from the compounds represented by the above-mentioned chemical formulas 1 to 37.

[0132] The compound separated from the above-mentioned rheum can be characterized by being manufactured according to the manufacturing method described above.

[0133] The above pharmaceutical composition may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods, but is not limited thereto.

[0134]

[0135] Cosmetic composition

[0136] The present invention can provide a cosmetic composition for promoting hair growth; for preventing, improving or treating hair loss; and for containing a rheum extract as an active ingredient.

[0137] In addition, the above-mentioned rheum extract may contain a compound isolated from rheum as an effective ingredient.

[0138] The compound separated from the above-mentioned rheum may be characterized as being at least one compound selected from the group consisting of compounds represented by the above-mentioned chemical formulas 1 to 37, and preferably may be one compound selected from the compounds represented by the above-mentioned chemical formulas 1 to 37.

[0139] The compound separated from the above-mentioned rheum can be characterized by being manufactured according to the manufacturing method described above.

[0140] The above cosmetic composition may be characterized in that it is manufactured in any one formulation selected from the group consisting of hair tonic, hair conditioner, hair essence, hair lotion, hair nourishing lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair wax, hair aerosol, hair pack, hair soap, hair cleansing foam, hair drying agent, hair preservation treatment agent, hair dye, hair waving agent, hair bleaching agent, hair gel, hair glaze, hair dressing agent, hair lacquer, hair moisturizer, hair mousse, and hair spray, but is not limited thereto.

[0141]

[0142] Health functional food composition

[0143] The present invention can provide a composition for promoting hair growth; preventing, improving or treating hair loss; and a health functional food composition containing a rheum extract as an active ingredient.

[0144] In addition, the above-mentioned rheum extract may contain a compound isolated from rheum as an effective ingredient.

[0145] The compound separated from the above-mentioned rheum may be characterized as being at least one compound selected from the group consisting of compounds represented by the above-mentioned chemical formulas 1 to 37, and preferably may be one compound selected from the compounds represented by the above-mentioned chemical formulas 1 to 37.

[0146] The compound separated from the above-mentioned rheum can be characterized by being manufactured according to the manufacturing method described above.

[0147] The above health functional food composition may be in the form of a tablet, capsule, pill or liquid, and examples of foods to which the above health functional food composition may be added include, but are not limited to, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, powdered milk, snacks, raw food, fermented milk with lactic acid bacteria, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes.

[0148] Hereinafter, examples of the present invention will be described in detail, but it is obvious that the present invention is not limited to the following examples.

[0149]

[0150] Example 1. Preparation of 50% ethanol extract of Rheum japonica

[0151] The rhizome of Rheum japonica was purchased and prepared at Gyeongdong Market in Seoul in 2015. To prepare a 50% ethanol extract of the Rheum japonica root, 50% ethanol was mixed with the Rheum japonica root and extracted in a water bath set at 60°C for 12 hours. Afterwards, the extract was concentrated using a vacuum concentrator (Buchi R-220) to prepare a 50% ethanol extract of Rheum japonica.

[0152]

[0153] Experimental Example 1. Analysis of changes in hair loss-related protein expression caused by rheum extract in keratinocytes (HaCaT)

[0154] Keratinocytes (HaCaT cells) were seeded at 3×10 in a 6-well plate. 5 The cells were seeded so as to be 10 cells / well and cultured for 24 hours under 37°C and 5% CO2 conditions for stabilization. The cultured cells were treated with 50% ethanol extract of Rheum japonicus obtained in the same manner as Example 1 at concentrations of 0, 10, and 20 mg / ml, and then cultured for 24 hours under 37°C and 5% CO2 conditions. As a positive control, 10 uM minoxidil (MNX) was treated.

[0155] Afterwards, the changes in VEGF, β-catenin, and P-GSK protein expression caused by the extract of Jonghwang were analyzed through western blot, and the experimental method of the western blot is as follows.

[0156] The cell culture medium from each well treated with the minoxidil and rheum extract at various concentrations was removed, washed with PBS, and then cell lysate was prepared using M-per Buffer. The supernatant obtained by centrifugation at 14,000 rpm for 20 minutes at 4℃ was used as the total protein extract. The protein concentration was quantified using Bradford Assay and electrophoresed on 10% Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). After electrophoresis, the protein was transferred to a PVDF membrane, and then immersed in TBST containing 5% Non-Fat Dry Milk and incubated at room temperature for 1 hour to block non-specific proteins, and then washed with TBST. The blocked membrane was treated with primary antibodies and reacted at 4°C for 15 hours, then washed with TBST and reacted with secondary antibodies matching the treated primary antibodies at room temperature for 1 hour. Afterwards, the membrane was washed again with TBST and reacted with an ECL (enhanced chemiluminescence) kit, and the expression levels of VEGF, β-catenin, and P-GSK proteins were confirmed using a Chemidoc image analyzer (Vilber Fusion FX5, Germany). The results of Experimental Example 1 are shown graphically in Fig. 1.

[0157] Referring to Figure 1, VEGF and β-catenin protein expression slightly increased in the minoxidil-treated group (Minoxidil, MNX) compared to the untreated group (NC). On the other hand, when rheum extract was treated at a concentration of 20 μg / ml, VEGF and β-catenin protein expression increased compared to the minoxidil-treated group.

[0158] In addition, referring to Figure 1, phospho-GSK (p-GSK) protein expression increased in the minoxidil-treated group compared to the untreated group. When rheum rhizome extract was treated at a concentration of 10 or 20 μg / ml, p-GSK protein expression increased further compared to the minoxidil-treated group.

[0159] In summary, this means that rheum extract is more effective in treating hair loss than minoxidil.

[0160]

[0161] Experimental Example 2. Analysis of changes in hair loss-related protein expression caused by rheum extract in human umbilical vein cells (HUVECs).

[0162] Human umbilical vein cells (HUVEC cells) were seeded at 3×10 in a 6-well plate. 5 The cells were seeded so as to be 10 cells / well and cultured for 24 hours under 37°C and 5% CO2 conditions for stabilization. The cultured cells were treated with 50% ethanol extract of Rheum japonicus obtained in the same manner as Example 1 at concentrations of 0, 10, and 20 mg / ml, and then cultured for 24 hours under 37°C and 5% CO2 conditions. As a positive control, 10 uM minoxidil (MNX) was treated.

[0163] Afterwards, changes in VEGF, β-catenin, and P-GSK protein expression caused by the rheum extract were analyzed through western blot, and the western blot was performed in the same manner as in Experimental Example 1. The results of Experimental Example 2 are shown graphically in Fig. 2.

[0164] Referring to Figure 2, VEGF and β-catenin protein expression slightly increased in the minoxidil-treated group (Minoxidil, MNX) compared to the untreated group (NC). On the other hand, when the rheum extract was treated at a concentration of 10 or 20 μg / ml, VEGF and β-catenin protein expression increased compared to the minoxidil-treated group.

[0165] In addition, referring to Figure 2, the expression of p-GSK protein did not increase in the minoxidil-treated group compared to the untreated group and was expressed almost the same, but when the rheum extract was treated at a concentration of 20 ㎍ / ㎖, the expression of p-GSK protein increased significantly compared to the minoxidil-treated group.

[0166] In summary, this means that rheum extract is more effective in treating hair loss than minoxidil.

[0167]

[0168] Experimental Example 3. Analysis of changes in hair loss-related protein expression caused by rheum extract in human hair follicle dermal papilla cells (HFDPC).

[0169] Human hair follicle dermal papilla cells (HFDPC cells) were seeded at 3×10 in a 6-well plate. 5 The cells were seeded so as to be 10 cells / well and cultured for 24 hours under 37°C and 5% CO2 conditions for stabilization. The cultured cells were treated with 50% ethanol extract of Rheum japonicus obtained in the same manner as Example 1 at concentrations of 0, 10, and 20 mg / ml, and then cultured for 24 hours under 37°C and 5% CO2 conditions. As a positive control, 10 uM minoxidil (MNX) was treated.

[0170] Afterwards, changes in VEGF and β-catenin protein expression caused by the rheum extract were analyzed through western blot, and the western blot was performed in the same manner as in Experimental Example 1. The results of Experimental Example 3 are shown graphically in Fig. 3.

[0171] Referring to Figure 3, VEGF and β-catenin protein expression increased in the minoxidil-treated group compared to the untreated group. On the other hand, when rheum extract was treated at a concentration of 10 or 20 μg / ml, VEGF and β-catenin protein expression increased further compared to the minoxidil-treated group.

[0172] In summary, this means that rheum extract is more effective in treating hair loss than minoxidil.

[0173]

[0174] Example 2. Preparation of 37 compounds isolated from rheum rhizome

[0175] 6 kg of dried rheum rhizome was added with 5 L of 100%-MeOH (HPLC grade) and ultrasonically extracted at 30°C for 4 hours. The same process was repeated three times to obtain an extract. Afterwards, the extract was concentrated using a vacuum concentrator (Buchi R-220) to prepare a rheum methanol extract. The rheum methanol extract was suspended in H2O and fractionated using chloroform and ethyl acetate to obtain chloroform (7.7 g), ethyl acetate (118.0 g), and water (335.0 g) fractions. Repeated chromatography experiments were performed on the ethyl acetate fraction obtained in the process, and 37 single compounds were isolated from it.

[0176] 1D and 2D-NMR spectral analyses were performed on the 37 compounds isolated above, and their chemical structures were identified by comparison with previously reported literature values. The compound names of the 37 compounds are as follows.

[0177] (1) piceatannol 3'-O-β-6''-4-hydroxybenzoyl)-β-D-glucopyranoside;

[0178] (2) piceatannol 3'-O-(6''-E-cinnamoyl)-β-D-glucopyranoside;

[0179] (3) 6''-4-hydroxybenzoylrhaponticin;

[0180] (4) (E)-4b-methoxy-3b-hydroxy-(-)-ε-viniferin;

[0181] (5) (E)-4b-methoxy-3b-hydroxy-(-)-scirpusin A;

[0182] (6) resveratrol;

[0183] (7) piceatannol;

[0184] (8) deoxyrhapontigenin;

[0185] (9) rhapontigenin;

[0186] (10)cis-rhapontigenin;

[0187] (11) piceatannol 3'-O-β-D-glucopyranoside;

[0188] (12) piceatannol 3'-O-β-D-xylopyranoside;

[0189] (13) deoxyrhaponticin;

[0190] (14) 6''-galloyl deoxyrhaponticin;

[0191] (15) rhaponticin;

[0192] (16)cis-rhapontin;

[0193] (17) rhapontigenin 3'-O-β-D-glucopyranoside;

[0194] (18) 6''-galloyl rhaponticin;

[0195] (19) (-)-ε-viniferin;

[0196] (20) scirpusin A;

[0197] (21) trans-δ-viniferin;

[0198] (22) cassigarol E;

[0199] (23) pallidol;

[0200] (24) (-)-rhododendrol 4'-O-β-D-glucopyranoside;

[0201] (25) 4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside;

[0202] (26) lindleyin;

[0203] (27) (3R)-Thunberginol C;

[0204] (28) 3,5-dihydroxy-2-[2-(4-hydroxyphenyl)acetyl]benzoic acid;

[0205] (29) emodin;

[0206] (30) aloe emodin;

[0207] (31) chrysophanol 1-O-β-D-glucopyranoside;

[0208] (32) chrysophanol 8-O-β-D-glucopyranoside;

[0209] (33) chrysophanol 8-O-(6'-galloyl)-β-D-glucopyranoside;

[0210] (34) rosin;

[0211] (35) Coumaroyl 1-O-β-D-glucopyranoside;

[0212] (36) torachrysone-8-O-β-D-glucopyranoside;

[0213] (37) chrysophanol;

[0214] The names, structural formulas, chemical formulas, and molecular weights of the 37 compounds are shown in Table 1 below.

[0215] Compound number FormulaMolecular weight1C 27 H 26 O 11526.492C 29 H 28 O 10 536.533C 28 H 28 O 11 540.524C 29 H 24 O7484.505C 29 H 24 O8500.506C 14 H 12 O3228.257C 14 H 12 O4244.258C 15 H 14 O3242.279C 15 H 14 O4258.2710C 15 H 14 O4258.2711C 20 H 22 O9406.3912C 19 H 20 O8376.3513C 21 H 24 O8404.4214C 28 H 28 O 12 556.5215C 21 H 24 O9420.4116C 21 H 24 O9420.4117C 21 H 24 O9420.4118C 28 H 28 O 13 572.5119C 28 H 22 O6454.4820C 28 H 22 O7470.4821C 28 H 22 O6454.4722C 28 H 22 O8486.4823C 28 H 22 O6454.4824C 16 H 24 O7328.3625C 16 H 22 O7326.3526C 23 H 26 O 11478.4527C 15 H 12 O5272.2628C 15 H 12 O6288.2629C 15 H 10 O5270.2430C 15 H 10 O5270.2431C 21 H 20 O9430.4132C 21 H 20 O9430.4133C 28 H 24 O 13 568.4934C 15 H 20 O6296.3235C 15 H 18 O8326.1036C 20 H 24 O9408.4037C 15 H 10 O4254.24

[0216]

[0217] The structural formulas of the 37 compounds above are as follows.

[0218] [Chemical Formula 1]

[0219]

[0220] [Chemical Formula 2]

[0221]

[0222] [Chemical Formula 3]

[0223]

[0224] [Chemical Formula 4]

[0225]

[0226] [Chemical Formula 5]

[0227]

[0228] [Chemical Formula 6]

[0229]

[0230] [Chemical Formula 7]

[0231]

[0232] [Chemical Formula 8]

[0233]

[0234] [Chemical Formula 9]

[0235]

[0236] [Chemical Formula 10]

[0237]

[0238] [Chemical Formula 11]

[0239]

[0240] [Chemical Formula 12]

[0241]

[0242] [Chemical Formula 13]

[0243]

[0244] [Chemical Formula 14]

[0245]

[0246] [Chemical Formula 15]

[0247]

[0248] [Chemical Formula 16]

[0249]

[0250] [Chemical Formula 17]

[0251]

[0252] [Chemical Formula 18]

[0253]

[0254] [Chemical Formula 19]

[0255]

[0256] [Chemical Formula 20]

[0257]

[0258] [Chemical Formula 21]

[0259]

[0260] [Chemical Formula 22]

[0261]

[0262] [Chemical Formula 23]

[0263]

[0264] [Chemical Formula 24]

[0265]

[0266] [Chemical Formula 25]

[0267]

[0268] [Chemical Formula 26]

[0269]

[0270] [Chemical Formula 27]

[0271]

[0272] [Chemical Formula 28]

[0273]

[0274] [Chemical Formula 29]

[0275]

[0276] [Chemical Formula 30]

[0277]

[0278] [Chemical Formula 31]

[0279]

[0280] [Chemical Formula 32]

[0281]

[0282] [Chemical Formula 33]

[0283]

[0284] [Chemical Formula 34]

[0285]

[0286] [Chemical Formula 35]

[0287]

[0288] [Chemical Formula 36]

[0289]

[0290] [Chemical Formula 37]

[0291]

[0292]

[0293] Experimental Example 4. Analysis of changes in hair loss-related protein expression caused by 37 compounds isolated from rheum rhizome.

[0294] First, human hair follicle dermal papilla cells (HFDPC cells) were cultured and prepared in the same manner as in Experimental Example 3, and then the 37 compounds isolated in Example 2 were treated to the cultured cells. As a positive control, 10 uM minoxidil (MNX) was treated.

[0295] Afterwards, the protein expression changes of β-catenin, GSK3β, IGF-1, AKT, and cyclin D1 by the 37 compounds of the above chemical formulas 1 to 37 isolated from the rheum rhizome were analyzed through western blot. The western blot was performed in the same manner as in Experimental Example 1, and the results are shown in Table 2 and FIGS. 4 to 8. More specifically, FIG. 4 shows the change in β-catenin expression by the 37 compounds, FIG. 5 shows the change in GSK3β expression by the 37 compounds, FIG. 6 shows the change in IGF-1 expression by the 37 compounds, FIG. 7 shows the change in AKT expression by the 37 compounds, and FIG. 8 shows the change in cyclin D1 expression by the 37 compounds.

[0296] Referring to Table 2 and Figure 4, compounds of chemical formulas 2 to 9, 19, 22, and 29 to 31 increased β-catenin expression compared to the minoxidil treatment group.

[0297] Referring to Table 2 and Figure 5, compounds of chemical formulas 1 to 9, 11 to 15, 17 to 18, 20 to 25, 27, and 29 to 37 increased GSK3β expression compared to the minoxidil treatment group.

[0298] Referring to Table 2 and Figure 6, compounds of chemical formulae 1, 2, 4, 5, 7, 11, 13, 14, 16, 17, 22, 23, 24, 26, 28, and 34 increased IGF-1 expression compared to the minoxidil treatment group.

[0299] Referring to Table 2 and Figure 7, compounds of chemical formulas 1 to 8, 12, 17, 21, and 25 increased AKT expression compared to the minoxidil treatment group.

[0300] Referring to Table 2 and Figure 8, compounds of chemical formulas 1 to 2, 4 to 11, 13, 15, 17, 18, 20 to 24, and 27 to 36 increased Cyclin D1 expression compared to the minoxidil treatment group.

[0301]

[0302] Concentration of rhubarb compoundsβ-cateninGSK3β 　 AKT 　 cyclin D1 　 IGF-1 　 μM% compared to untreated groupControl-100±8.6 　 100±7.6100±3.2100±4.7100±0.5Minoxidil10119±5.3128±5.0104±1.9123±3.1105±2.6110112±6.6189±6.4 *** 108±2.4119±3.9 * 114±0.0 ** 210132±6.6 * 185±6.4*** 112±2.4 * 126±3.9 *** 116±0.6 ** 310139±2.6 ** 148±2.5 *** 117±1.0 *** 94±1.6104±0.6410130±6.6172±6.4 *** 113±2.4 * 121±3.9 ** 118±0.6 ** 510153±6.6 *** 149±6.3 *** 112±2.4 * 139±3.9 *** 113±1.1 ** 610146±7.2163±7.0108±2.7132±4.3 *** 96±0.8710138±8.0 ** 182±7.7 *** 116±2.9 *** 134±4.8 *** 120±1.1 ** 810139±6.6 ** 165±6.3 *** 111±2.4 *** 137±3.9 *** 85±1.7910136±2.6 ** 200±2.5 *** 98±1.0 *** 146±1.6 *** 92±0.41010120±4.6115±4.4101±1.7122±2.8 ** 102±2.81110125±6.6197±6.4 *** 105±2.4153±3.9 *** 107±2.0 * 1210119±9.2173±8.8 *** 118±3.4 *** 105±5.5 　 103±1.0 　 1310123±5.3158±5.0 *** 101±1.9148±3.1 *** 113±0.5 ** 1410112±6.6 　 152±6.3*** 100±2.4 　 106±3.9111±1.6 ** 1510106±5.5195±5.3 *** 96±2.0130±3.3 *** 104±0.51610107±7.0105±6.7109±2.5104±4.2112±1.1 ** 1710120±7.9178±7.6 *** 117±2.9 *** 119±4.7 * 108±1.1 ** 1810117±6.6 　 184±6.4 *** 107±2.4136±3.9 *** 102±2.1 　 1910138±9.2 ** 103±8.8102±3.4111±5.592±1.02010116±7.0149±6.7 *** 100±2.5119±4.2 * 86±0.92110113±7.0140±6.7 ** 120±2.5 *** 133±4.2 *** 99±2.72210129±7.9156±7.6 *** 105±2.9119±4.7 * 110±1.1 ** 2310121±4.7 　 164±4.6 *** 96±1.7130±2.8 *** 116±2.6 ** 241086±7.2 　 192±7.0 *** 90±2.7132±4.3 *** 112±0.5 ** 2510119±8.5170±8.2 *** 110±3.1116±5.1 　 98±1.0261096±7.0 　 113±6.786±2.5104±4.2111±0.0 ** 2710122±4.2159±4.1 *** 97±1.5124±2.5 **78±3.22810119±6.6111±6.3101±2.4133±3.9 *** 114±0.5 ** 2910138±6.6 ** 191±6.3 *** 105±2.4133±3.9 *** 82±0.0 　 3010139±3.9 ** 205±3.8 *** 107±1.4141±2.4 *** 68±1.13110129±6.6154±6.4 *** 108±2.4134±3.9 *** 92±0.03210123±6.7166±6.5 *** 104±2.5128±4.0 *** 87±2.53310108±6.6189±6.3 *** 102±2.4141±3.9 *** 106±0.53410115±7.0200±6.7 *** 109±2.5148±4.2 *** 129±0.5 ** 3510126±6.7136±6.5 ** 107±2.5146±4.0 *** 105±0.03610123±6.6175±6.4 *** 100±2.4131±3.9 *** 106±2.2 　 3710125±6.6185±6.3 *** 100±2115±3.995±0.9

[0303]

[0304] From the above description, those skilled in the art will understand that the present invention can be implemented in other specific forms without altering its technical spirit or essential features. In this regard, it should be understood that the embodiments described above are illustrative in all respects and are not limiting.

Claims

1. A pharmaceutical composition for promoting hair growth, preventing, improving or treating hair loss, containing a rheum extract as an active ingredient.

2. In paragraph 1, The above rhubarb extract Contains a compound isolated from rheum, A pharmaceutical composition for promoting hair growth; preventing, improving or treating hair loss; comprising at least one compound isolated from the above-mentioned rheum, selected from the group consisting of compounds represented by the following chemical formulas 1 to 37. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] [Chemical Formula 10] [Chemical Formula 11] [Chemical Formula 12] [Chemical Formula 13] [Chemical Formula 14] [Chemical Formula 15] [Chemical Formula 16] [Chemical Formula 17] [Chemical Formula 18] [Chemical Formula 19] [Chemical Formula 20] [Chemical Formula 21] [Chemical Formula 22] [Chemical Formula 23] [Chemical Formula 24] [Chemical Formula 25] [Chemical Formula 26] [Chemical Formula 27] [Chemical Formula 28] [Chemical Formula 29] [Chemical Formula 30] [Chemical Formula 31] [Chemical Formula 32] [Chemical Formula 33] [Chemical Formula 34] [Chemical Formula 35] [Chemical Formula 36] [Chemical Formula 37] 3. In paragraph 1, The compound isolated from the above-mentioned rheum is A pharmaceutical composition for promoting hair growth; preventing, improving or treating hair loss; characterized in that it increases the protein expression of β-catenin, GSK3β, IGF-1, AKT and cyclin D1 compared to a control group not treated with a compound isolated from the above-mentioned rheum.

4. In paragraph 1, The compound isolated from the above-mentioned rheum is A pharmaceutical composition for promoting hair growth; for preventing, improving or treating hair loss; characterized by being separated from the ethyl acetate fraction prepared by suspending the methanol extract of Rhizoma japonica in water and fractionating it using ethyl acetate.

5. In paragraph 1, The above rhubarb extract A pharmaceutical composition for promoting hair growth; for preventing, improving or treating hair loss; characterized in that it is manufactured by mixing ethanol with the rhizome of rheum rhizome, extracting it at 40 to 70°C for 6 to 24 hours, and then concentrating under reduced pressure.

6. A cosmetic composition for promoting hair growth, preventing or improving hair loss, containing a rheum extract as an active ingredient.

7. In paragraph 6, The above rhubarb extract Contains a compound isolated from rheum, A hair growth promoting; hair loss prevention or improvement; cosmetic composition characterized in that the compound separated from the above-mentioned rheum is at least one compound selected from the group consisting of compounds represented by the following chemical formulas 1 to 37. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] [Chemical Formula 10] [Chemical Formula 11] [Chemical Formula 12] [Chemical Formula 13] [Chemical Formula 14] [Chemical Formula 15] [Chemical Formula 16] [Chemical Formula 17] [Chemical Formula 18] [Chemical Formula 19] [Chemical Formula 20] [Chemical Formula 21] [Chemical Formula 22] [Chemical Formula 23] [Chemical Formula 24] [Chemical Formula 25] [Chemical Formula 26] [Chemical Formula 27] [Chemical Formula 28] [Chemical Formula 29] [Chemical Formula 30] [Chemical Formula 31] [Chemical Formula 32] [Chemical Formula 33] [Chemical Formula 34] [Chemical Formula 35] [Chemical Formula 36] [Chemical Formula 37] 8. A composition for promoting hair growth, preventing or improving hair loss, and a health functional food, containing a rheum extract as an active ingredient.

9. In paragraph 8, The above rhubarb extract Contains a compound isolated from rheum, A composition for promoting hair growth; preventing or improving hair loss; and a health functional food, characterized in that the compound separated from the above-mentioned rheum is at least one compound selected from the group consisting of compounds represented by the following chemical formulas 1 to 37. [Chemical Formula 1] [Chemical Formula 2] [Chemical Formula 3] [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] [Chemical Formula 7] [Chemical Formula 8] [Chemical Formula 9] [Chemical Formula 10] [Chemical Formula 11] [Chemical Formula 12] [Chemical Formula 13] [Chemical Formula 14] [Chemical Formula 15] [Chemical Formula 16] [Chemical Formula 17] [Chemical Formula 18] [Chemical Formula 19] [Chemical Formula 20] [Chemical Formula 21] [Chemical Formula 22] [Chemical Formula 23] [Chemical Formula 24] [Chemical Formula 25] [Chemical Formula 26] [Chemical Formula 27] [Chemical Formula 28] [Chemical Formula 29] [Chemical Formula 30] [Chemical Formula 31] [Chemical Formula 32] [Chemical Formula 33] [Chemical Formula 34] [Chemical Formula 35] [Chemical Formula 36] [Chemical Formula 37]

Images