Composition for strengthening hair roots comprising metal-phenolic complex and melanin or precursor thereof

Abstract

The present invention relates to a composition for strengthening hair roots, and the like. The composition not only has no cytotoxicity, but also promotes the expression of growth factors in dermal papilla cells, thereby having an effect of strengthening hair roots or preventing, alleviating, or treating hair loss without skin irritation.

Description

Composition for strengthening hair roots comprising a metal-phenol complex and melanin or a precursor thereof

[0001] The present invention relates to a composition for strengthening hair roots, etc.

[0002] Human hair is incredibly important, not only because it protects the skin and scalp, but also because it plays a unique role in social and sexual communication. Strengthening hair roots is particularly crucial for healthy hair, as it not only promotes healthy hair but also makes it more resilient to various factors that can lead to hair loss.

[0003] Meanwhile, the number of people experiencing hair loss continues to increase due to environmental pollution, drug abuse, and other side effects, as well as social stress. Hair loss is becoming increasingly prevalent, especially among younger people. This shift in social attitudes toward appearance has led to the development of new hair loss prevention products. Currently available hair loss prevention products, particularly those based on synthetic compounds, have been linked to various skin side effects. Therefore, the development of safe, non-irritating materials is crucial.

[0004] One aspect is to provide a composition comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients.

[0005] One aspect provides a composition comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients.

[0006] In one embodiment, it was confirmed that a metal-phenol complex, melanin, or a precursor thereof was not cytotoxic to human keratinocytes and promoted the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) in hair papilla cells. Therefore, the composition can strengthen hair follicles and prevent, improve, or treat hair loss without irritating the skin, and thus can be used for strengthening hair follicles and preventing, improving, or treating hair loss.

[0007] As used herein, the term "metal-phenolic complex (MPC)" is formed by the interaction of a metal ion and a phenol compound under specific conditions, and is stabilized by electronic interaction between the positive charge of the metal ion and the negative charge of the phenol. The metal may include a transition metal or an alkali metal. The transition metal may be, for example, iron(II) D-gluconate hydrate, copper (Cu), silver (Ag), zinc (Zn), platinum (Pt), gold (Au), etc., and the alkali metal may be, for example, at least one selected from the group consisting of lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), barium (Ba), calcium (Ca), nickel (Ni), cobalt (Co), manganese (Mn), and magnesium (Mg). In addition, the phenol compound may be at least one selected from the group consisting of tannic acid, gallic acid, methyl gallate, ethyl gallate, propyl gallate, octyl gallate, lauryl gallate, epicatechin gallate, epigallocatechin gallate, gallocatechin gallate, theaflavin-3-gallate, flavones, and anthocyanins.

[0008] In one specific example, the metal-phenol complex may be formed by mixing iron(II) D-gluconate hydrate, gallic acid, and tannic acid in a weight ratio of 1:0.01 to 10:0.01 to 5. The iron(II) D-gluconate hydrate, gallic acid, and tannic acid may be mixed in a concentration ratio of, for example, 1:0.01 to 10:0.01 to 5, 1:0.01 to 10:0.01 to 3, 1:0.01 to 5:0.01 to 0.5, 1:0.1 to 5:0.05 to 3, or 1:0.1 to 2.5:0.05 to 1.5. At this time, if the mixing ratio of the D-gluconate iron (II) hydrate and gallic acid and tannic acid is below the above range, there is a problem that the metal-phenol complex is not sufficiently formed, and thus the synergistic effect of the cosmetic composition cannot be sufficiently exerted. If it exceeds the above range, there is a problem that the particle size of the metal-phenol complex increases and the particles precipitate.

[0009] As used herein, the term "melanin" refers to a general term for black or brown pigments present in tissues such as skin, hair, and eyes, and "melanin precursor" plays a role in the biosynthesis of melanin, and its amount determines skin color, body hair color including hair, eye color, etc. Accordingly, the composition can be used not only to prevent or improve graying by promoting melanin production, but also to dye hair, eyelashes, or skin.

[0010] In one specific example, the melanin precursor may be at least one selected from the group consisting of poly-dihydroxylindole (PHI), L-dopaquinone, hydroxytryptophan, tyrosine, 3,4-dihydroxyphenylalanine (DOPA), dopaquinone, leucodopachrome, dopachrome, and indole-5,6-quinone. The poly-dihydroxyindole is an indole-based compound found in plant and animal tissues, and primarily plays a role in the biosynthesis of melanin, a skin pigment. In particular, the poly-dihydroxyindole has an antioxidant effect, which can help protect the skin from oxidation and environmental damage.

[0011] The above composition may additionally include a pomegranate extract as a plant extract having hair root strengthening or hair loss prevention activity.

[0012] The above pomegranate extract is obtained by extracting a pomegranate tree with water, a lower alcohol having C1 to C4, or a mixture thereof, and specifically, the pomegranate extract may be an extract of flowers, fruits, seeds, leaves, branches, stems, roots, or a mixture thereof of the pomegranate tree. When extracting, the dried pomegranate tree is cut into pieces, and then water, alcohol, or a mixture thereof is added in an amount of 2 to 20 times the weight of the pomegranate tree to extract. The extraction may be performed at a temperature of 20 to 100°C for 1 to 10 hours. As the extraction method, any of cold steeping, ultrasonic extraction, and reflux cooling extraction methods may be used, and the extraction may be repeated 1 to 5 times.

[0013] In one specific example, the pomegranate extract may be a butylene glycol fraction obtained by extracting a pomegranate tree with water, a lower alcohol having C1 to C4, or a mixture thereof, and then refining the fraction with butylene glycol. The lower alcohol used for extracting the pomegranate tree may be ethanol or methanol. During extraction, the dried pomegranate tree may be cut into pieces, and then water, alcohol, or a mixture thereof may be added in an amount of 2 to 20 times the weight of the pomegranate tree to perform the extraction. The extraction temperature may be 30 to 100°C. The extraction time may be 1 to 10 hours. The extraction method may utilize a cold steeping, ultrasonic extraction, or reflux cooling extraction method. The number of extractions may be 1 to 5 repeated extractions.

[0014] In another specific example, the pomegranate extract may contain an active compound. The active compound may be ellagic acid or a derivative thereof. The ellagic acid derivative may be a sodium salt, calcium salt, or amine salt derivative of ellagic acid, an ellagic acid derivative having a saturated or unsaturated acyl group having 2 to 22 carbon atoms bonded to it, or a form in which glucose is bonded to one or more hydroxyl groups of ellagic acid in a single or multiple ether form. In addition, the ellagic acid or a derivative thereof may be contained in an amount of 400 ppm or more per 100 g of the pomegranate extract.

[0015] The composition is comprised of 0.001 wt% to 80 wt%, for example, 0.01 wt% to 60 wt%, 0.01 wt% to 40 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.05 wt% to 60 wt%, 0.05 wt% to 40 wt%, 0.05 wt% to 30 wt%, 0.05 wt% to 20 wt%, 0.05 wt% to 10 wt%, 0.05 wt% to 5 wt%, 0.1 wt% to 60 wt%, 0.1 wt% to 40 wt%, 0.1 wt% to 30 wt%, 0.1 wt% to 20 It may include a metal-phenol complex, and melanin or a precursor thereof, in an amount of 0.1 wt% to 10 wt%, or 0.1 wt% to 5 wt%. In this case, if the content of the metal-phenol complex and melanin or a precursor thereof is less than the above range, there is a problem in that the effect of strengthening hair roots or preventing, improving, or treating hair loss is not sufficiently exerted.

[0016] In this specification, the term "including as an active ingredient" means that the metal-phenol complex of this specification and melanin or a precursor thereof are added to an extent capable of exhibiting the above-mentioned effect, and includes formulation in various forms by adding various components as auxiliary components for drug delivery and stabilization, etc.

[0017] In one specific example, the composition may be a cosmetic composition.

[0018] The above cosmetic composition may have, for example, a cosmetic formulation of a softening toner, a nourishing toner, a massage cream, a nourishing cream, an essence, a pack, a gel, an ampoule, or a skin adhesive type.

[0019] The ingredients included in the above cosmetic composition may include ingredients commonly used in cosmetic compositions in addition to the composition as an active ingredient, and may include, for example, conventional auxiliary agents and carriers such as stabilizers, solubilizers, vitamins, pigments, and fragrances.

[0020] In another embodiment, the composition may be a pharmaceutical composition.

[0021] The pharmaceutical composition may additionally comprise a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof. The carrier may be an excipient, a disintegrant, a binder, a glidant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be calcium carboxymethylcellulose, sodium starch glycolate, calcium dihydrogen phosphate anhydrous, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.

[0022] The pharmaceutical composition may be formulated as an oral or parenteral dosage form. The oral dosage form may be a granule, powder, liquid, tablet, capsule, dry syrup, or a combination thereof. The parenteral dosage form may be an injection.

[0023] In another specific example, the composition may be a composition for external use in the skin.

[0024] The above-mentioned external preparation for skin may be a cream, gel, ointment, skin emulsifier, skin suspension, transdermal patch, drug-containing bandage, lotion, or a combination thereof. The above-mentioned external preparation for skin may be appropriately mixed with ingredients commonly used in external preparations for skin such as cosmetics or medicines, such as aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, UV absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, various skin nutrients, or a combination thereof, as needed. The above skin external preparation may also appropriately contain metal sequestrants such as disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glabridin, hot water extract of the fruit of Kalin; various herbal medicines; drugs such as tocopherol acetate, glycyrrhizic acid, tranexamic acid and derivatives or salts thereof; vitamin C, magnesium ascorbic acid phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, and trehalose; and the like.

[0025] In another specific example, the composition may be a health functional food composition.

[0026] The above health functional food composition can be used alone or in combination with other foods or food ingredients, and can be used appropriately according to a conventional method. The amount of the active ingredients mixed can be appropriately determined depending on the purpose of use (prevention, health, or therapeutic treatment). Generally, when manufacturing a food or beverage, the composition of the present specification can be added in an amount of 15 parts by weight or less based on the raw material. There is no particular limitation on the type of the health functional food. Among the types of health functional foods, the beverage composition can contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. The natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a sweetener, a natural sweetener such as thaumatin and stevia extract, or a synthetic sweetener such as saccharin and aspartame can be used. The health food composition may also contain nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, or combinations thereof. The health functional food composition may also contain fruit pulp for the production of natural fruit juice, fruit juice drinks, vegetable drinks, or combinations thereof.

[0027] Another aspect provides a method for preventing, improving, or treating a skin condition in a subject, comprising administering to the subject an effective amount of the composition, the specific details of which are as described above.

[0028] As used herein, the terms "administering," "introducing," and "implanting" are used interchangeably and may refer to placement of a composition according to one embodiment into a subject by a method or route that results in at least partial localization of the composition to a desired site according to one embodiment.

[0029] Administration may be by any method known in the art. Administration may be administered directly to the subject by any means, including intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal, or subcutaneous administration. Administration may be systemic or local.

[0030] The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an object in need of skin beauty improvement, such as skin moisturization, skin barrier strengthening, or skin wrinkle improvement.

[0031] The above administration is 0.1 mg to 1,000 mg per day per individual of the composition according to one specific example, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg, 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to It may be administered at 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg. However, the dosage may be prescribed in various ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity, and a person skilled in the art can appropriately adjust the dosage by considering these factors. The number of administrations may be once a day or twice or more within the range of clinically acceptable side effects, and the administration site may be administered at one or more sites, and the total number of administration days may be from 1 to 30 days per treatment at intervals of 2 to 5 days daily or every day. If necessary, the same treatment may be repeated after an appropriate period. For animals other than humans, the same dosage per kg as for humans may be administered, or the dosage may be converted to the above dosage based on the volume ratio (e.g., average value) of the organs (heart, etc.) of the target animal and humans.

[0032] Another aspect provides a composition comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients for strengthening hair roots.

[0033] Another aspect provides a composition comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients for use in preventing, improving or treating hair loss.

[0034] The composition according to the aspect is not only non-cytotoxic but also effective in strengthening hair roots or preventing, improving or treating hair loss without skin irritation by promoting the expression of growth factors in hair papilla cells.

[0035] Figure 1 shows the results of confirming the cytotoxicity of the compositions of examples / comparative examples according to one aspect.

[0036] Figure 2 shows the results of confirming the expression level of vascular endothelial growth factor (VEGF) in breast papilla cells according to treatment with the composition of Example / Comparative Example according to one aspect.

[0037] Figure 3 shows the results of confirming the expression level of fibroblast growth factor (FGF) in mammary papilla cells according to treatment with the composition of Example / Comparative Example according to one aspect.

[0038] Hereinafter, preferred examples are presented to aid in understanding the present invention. However, the following examples are provided solely to facilitate a better understanding of the present invention, and the scope of the present invention is not limited by the following examples.

[0039]

[0040] [Example]

[0041] Compositions of Examples 1 to 4

[0042] An exemplary composition comprising a metal-phenolic complex (MPC), poly-dihydroxyindole, and / or pomegranate extract was prepared.

[0043] First, iron(Ⅱ) D-gluconate dehydrate (699014-53-4), gallic acid, and tannic acid were mixed in a 1:2:1 ratio and then freeze-dried to prepare a metal-phenol complex. Next, a pomegranate extract with increased ellagic acid content was prepared. Specifically, 150 g of raw powder of the whole pomegranate tree, which contains more than 90 wt% of pomegranate flower, was extracted with a 70% ethanol solution at 60℃ for 5 hours. Afterwards, it was filtered using a 250 mesh, 5 ㎛ filter and concentrated until the amount of raw powder became 20 wt% of the initial amount. The pomegranate ethanol extract was prepared by diluting it with 1,3-butylene glycol so that the content of ellagic acid was more than 400 ppm.

[0044] Thereafter, the metal-phenol complex, poly-dihydroxyindole (PHI), and pomegranate extract were mixed to contain the concentrations (ppm) shown in Table 1 below to prepare compositions of Examples 1 to 4.

[0045] Example 1 Example 2 Example 3 Example 4 MPC1515PHI0.50.50.50.5 Pomegranate extract--0.010.01

[0046]

[0047] [Comparative example]

[0048] Comparative Example 1. Preparation of a metal-phenol complex

[0049] A metal-phenol complex was prepared using the same method as in the above example.

[0050]

[0051] Comparative Example 2. Preparation of poly-dihydroxyindole

[0052] Poly-dihydroxyindole was purchased and prepared from CM Tech Co., Ltd.

[0053]

[0054] Comparative Example 3. Preparation of pomegranate extract

[0055] A pomegranate extract was prepared using the same method as in the above example.

[0056]

[0057] [Experimental Example]

[0058] Experimental Example 1. Confirmation of cytotoxicity

[0059] The cytotoxicity of different compositions was confirmed in one aspect. Specifically, human hair follicle dermal papilla cells (HFDPC) were seeded in 96-well plates at a density of 2x10 4 After dividing into the number of cells, they were cultured in an incubator at 37°C and 5% CO2 for 24 hours. Afterwards, the medium was replaced with one containing nothing, and the above Comparative Examples 1 to 3 were treated with 0.01, 0.1, 1, and 10 ppm, respectively, and further cultured for 24 hours. After 24 hours, the medium in each well was removed, washed once with DPBS (Dulbecco's phosphate buffered saline), and then replaced with a medium containing 500 μl of 0.5 mg / mL MTT tetrazolium (Sigma-aldrich, St. Louis, USA) per well, and reacted at 37°C for 4 hours. Afterwards, the absorbance was measured at 570 nm using Victor 3. The viability of the cells was expressed as a percentage of the average absorbance value, with the case of treating the medium containing nothing set as the negative control (None).

[0060] As a result, as shown in Fig. 1, Comparative Examples 1 and 2 according to the aspect did not exhibit cytotoxicity, but it was confirmed that the pomegranate extract of Comparative Example 3 showed a decrease in cell viability depending on the treatment concentration.

[0061]

[0062] Experimental Example 2. Confirmation of hair root strengthening effect

[0063] The effect of strengthening hair roots or preventing hair loss of the composition according to the daily aspect was confirmed. Specifically, 3x10 human hair papilla cells (HFDPC) were seeded in a 6-well plate. 5 After dividing cells per well, they were cultured for 24 hours under cell culture conditions. After 24 hours, the medium was discarded, washed with PBS, and then the cells were starved using medium that did not contain FBS. The next day, medium that did not contain FBS, 10 ppm of minoxidil, and the above Examples 1 to 4 and Comparative Examples 1 to 3 were treated to a final concentration of 0.01 ppm, 0.1 ppm, 1 ppm, or 10 ppm, and further cultured for 24 hours. Thereafter, the cultured cells were harvested, and RNA was isolated from the cells using an RNeasy Mini Kit (Qiagen), and then RNA was quantified at 260 nm using a nanodrop. Then, 2 μg of RNA was used for each RNA to synthesize cDNA in an amplifier (C1000 Thermal Cycler, Bio-Rad, USA). The synthesized cDNA was amplified using a mixture of target protein VEGF and FGF primers and cyanine dye CyberGreen (SYBR Green supermis, Applied Biosystems, USA) using a real-time PCR machine. After polymerase activation at 94°C for 5 minutes, the polymerization reaction was performed for 40 cycles under the conditions of 95°C for 30 seconds, 60°C for 30 seconds, and 72°C for 30 seconds, to evaluate the final expression levels of the VEGF and FGF genes. The final analysis was made by correction for the β-actin gene, and minoxidil (MXD) was used as a positive control. The gene expression levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) in dermal papilla cells are shown in Figures 2 and 3, respectively.

[0064] As a result, Comparative Examples 1 to 3 increased the VEGF expression level to a level lower than or similar to that of the positive control group, whereas the composition of Example 3 among the examples of the present invention, in particular, was confirmed to have a synergistic effect in increasing the VEGF expression level by containing a metal-phenol complex, poly-dihydroxyindole, and pomegranate extract at a specific concentration (Fig. 2).

[0065] In addition, while Comparative Examples 1 to 3 showed a low level of increase in FGF expression compared to the positive control group, it was confirmed that the composition of Example 4 among the examples of the present invention, in particular, had a synergistic effect in increasing FGF expression by containing a metal-phenol complex, poly-dihydroxyindole, and pomegranate extract at a specific concentration (Fig. 3).

[0066]

[0067] The foregoing description of the present invention is provided for illustrative purposes only. Those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive.

Claims

1. A composition for strengthening hair roots, comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients.

2. A composition for strengthening hair roots, according to claim 1, wherein the composition further comprises a pomegranate extract.

3. A composition for strengthening hair roots, wherein the pomegranate extract according to claim 2 is an extract of flowers, fruits, seeds, leaves, branches, stems, roots, or a mixture thereof of a pomegranate tree.

4. In claim 1, the metal-phenol complex comprises at least one metal selected from the group consisting of iron(II) D-gluconate hydrate, copper (Cu), silver (Ag), zinc (Zn), platinum (Pt), gold (Au), lithium (Li), sodium (Na), potassium (K), rubidium (Rb), cesium (Cs), barium (Ba), calcium (Ca), nickel (Ni), cobalt (Co), manganese (Mn), and magnesium (Mg); and A composition for strengthening hair roots, wherein one or more phenols or polyphenols selected from the group consisting of tannic acid, gallic acid, methyl gallate, ethyl gallate, propyl gallate, octyl gallate, lauryl gallate, epicatechin gallate, epigallocatechin gallate, gallocatechin gallate, theaflavin-3-gallate, flavones, and anthocyanins are combined to form a composition.

5. A composition for strengthening hair roots, wherein the melanin precursor in claim 1 is at least one selected from the group consisting of poly-dihydroxyindole, L-dopaquinone, hydroxytryptophan, tyrosine, 3,4-dihydroxyphenylalanine (DOPA), dopaquinone, leucodopachrome, dopachrome, and indole-5,6-quinone.

6. A composition for preventing, improving or treating hair loss, comprising a metal-phenolic complex (MPC) and melanin or a precursor thereof as active ingredients.

Images