KR20240078932A - Composition for Hair Growth Stimulation or Hair Loss Prevention Using an Extract of Hepatica maxima - Google Patents

Abstract

The present invention discloses a composition for promoting hair growth or inhibiting hair loss using an extract of Hepatica chinensis, which has the activity of promoting the proliferation of human dermal papilla cells and human hair hair cells.

Description

Composition for promoting hair growth or inhibiting hair loss using extract of Hepatica maxima {Composition for Hair Growth Stimulation or Hair Loss Prevention Using an Extract of Hepatica maxima}

The present invention relates to a composition for promoting hair growth or inhibiting hair loss using Hepatica maxima extract.

Hair is formed from hair follicles. There are about 5 million hair follicles in an adult, which are distributed throughout the entire human skin except for the palms and sea gourds. There are 1 million in the head, and 100,000 of these are in the scalp. (Bulletin of Food Technology 2009, 22(4):651-663). Scalp hair accounts for about 20% of human hair, and has the function of protecting the head from shock by cushioning the head in addition to the physiological functions of hair such as evaporation of sweat and regulating body temperature, and is suitable for modern people's tendency to value appearance. It also has an important social function in creating an individual's personality and image (Clin Dermatol 2001, 19(2):161-166).

Each hair grows from a hair follicle, and the hair follicle is composed of dermal papilla cells, hair germinal matrix cells, an outer and inner layer, and a bulge. do. In particular, hair follicle dermal papilla cell (hDPC) is a cell located in the dermal papillae at the bottom of the hair follicle and regulates the development and growth of the hair follicle (J Cell Sci 2011; 124(8): 1179-1182).

Hair repeats the growth cycle of anagen, catagen, and telogen. During the anagen phase, hair dermal papilla cells and human hair germinal matrix cells develop, This is the period when keratinocytes keratinize and hair grows. The catagen phase is the period when cell division stops, hair growth stops and the shape of the hair is maintained, and the telogen phase is when hair cells begin to become active and new hair is generated. This is the time to shed old hair.

Therefore, factors that affect the proliferation of dermal papilla cells or hair follicle cells in hair development, growth, and shedding are important targets for improving hair loss or hair growth.

Meanwhile, alopecia refers to the turning of terminal hair into vellus hair or the loss of hair that should normally exist. Usually, about 50 to 100 hairs fall out per day, but if there are more than 100 hairs, it is highly likely that it is alopecia. Alopecia is divided into cicatricial alopecia, which is permanent hair loss in which the hair follicles are damaged and hair does not regenerate, and non-scarring alopecia, which is treatable because the hair follicles are maintained (Bong-Hyeon Joo et al., 2014). As the average human lifespan increases, alopecia is considered a disease rather than a force majeure, and alopecia prevention and hair growth are receiving attention from many people (Ann N Y Acad Sci. 1991. 26(642):11).

The exact mechanism of hair growth and hair loss is not completely known to date, but the causes of hair loss include a decrease in hair follicle function due to the involvement of male hormones, a decrease in the metabolic function of the hair follicle and hair bulb, local blood flow disturbance due to scalp tension, poor nutrition, It is very diverse, including stress, side effects from medications, genetic factors, autoimmunity, local infections, chemicals, diseases such as leukemia and tuberculosis, and abuse of hair products.

Currently, the most commonly used drugs for hair loss treatment are substances that inhibit the activity of type 2 5α-reductase, including Minoxidil (see U.S. Patent Nos. 4,139,619 and 4,596,812) and finasteride (U.S. Patent Nos. Examples include No. 5547957, No. 5760046 or Republic of Korea Patent No. 375083.

Hair loss treatment requires long-term treatment, so minimizing side effects is key. Accordingly, efforts are being made to discover new hair growth ingredients or materials from natural products that have relatively few side effects on the human body.

Accordingly, the present invention discloses the hair loss inhibiting activity of the Hepatica chinensis extract.

The purpose of the present invention is to provide a composition for promoting hair growth or inhibiting hair loss using extract of Hepatica chinensis.

Other or specific purposes of the present invention will be presented below.

The present invention was completed by confirming that the extract of Hepatica chinensis promotes the proliferation of human dermal papilla cells and human hair hair cells, as confirmed in the examples and experimental examples below.

The present invention is provided based on the results of these experiments, and the composition for promoting hair growth or suppressing hair loss of the present invention is characterized in that it contains extract of Hepatica chinensis as an active ingredient.

In this specification, “extract” refers to the stem, leaf, fruit, flower, root, etc. of the plant to be extracted, mixed with water, lower alcohol with 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), methylene chloride, ethylene, acetone, hexane, Extract obtained by leaching using ether, chloroform, ethyl acetate, butylacetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or mixed solvents thereof. , refers to an extract obtained using a supercritical extraction solvent such as carbon dioxide or pentane, or a fraction obtained by fractionating the extract. The extraction method is cold immersion, reflux, heating, and ultrasonic radiation, taking into account the polarity of the active substance, degree of extraction, and degree of preservation. , any method such as supercritical extraction can be applied. In the case of a fractionated extract, the extract is suspended in a specific solvent and then mixed with a solvent of different polarity to form a fraction obtained by adsorbing the crude extract onto a column filled with silica gel and then mixed with a hydrophobic solvent, a hydrophilic solvent, or a mixture of these. It is meant to include fractions obtained using the mobile phase. In addition, the meaning of the extract includes concentrated liquid extract or solid extract from which the extraction solvent has been removed by methods such as freeze-drying, vacuum drying, hot air drying, and spray drying. Preferably, it refers to an extract obtained by using water, ethanol, or a mixed solvent thereof as an extraction solvent, and more preferably, an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

In addition, in this specification, the term "hair loss" should be understood as including all symptoms classified as hair loss in the art, regardless of the direct or indirect cause of its occurrence. Specifically, it includes all symptoms of hair loss due to poor blood circulation, excessive secretion of sebum due to excessive production of dihydrotestosterone, deterioration of scalp function due to peroxides or bacteria, aging, genetic factors, stress, and their combined effects. .

In addition, in this specification, “active ingredient” refers to an ingredient that exhibits the desired activity alone or can exhibit activity in combination with a carrier that is not active on its own.

The composition of the present invention may contain the active ingredient in any amount (effective amount) depending on the use, formulation, purpose of formulation, etc., as long as it can exhibit ankle-promoting or hair loss-inhibiting activity. The typical effective amount is based on the total weight of the composition. It will be determined within the range of 0.001% by weight to 20.0% by weight. Here, “effective amount” means that when the composition of the present invention is administered to mammals, preferably humans, to which it is applied during the administration period recommended by medical experts, etc., it can exhibit the intended functional and pharmacological effects, such as hair growth promotion. It refers to the amount of active ingredient contained in the composition of the invention. Such effective amounts can be determined experimentally within the scope of the ordinary ability of those skilled in the art.

In addition to the active ingredients, the composition of the present invention has already been tested for safety in the art in order to increase or reinforce the effect of promoting hair growth or inhibiting hair loss, or to improve the convenience of taking or ingesting through the addition of similar activities such as blood pressure regulating activity. and may further include any compounds or natural extracts known to have the corresponding activity. These compounds or extracts include compounds, extracts, and pharmaceuticals listed in compendial documents such as the Pharmacopoeia of each country (in Korea, the “Korean Pharmacopoeia”) and the Code of Health Functional Foods of each country (in Korea, it is the “Standards and Specifications for Health Functional Foods” notified by the Ministry of Food and Drug Safety). The laws of each country that govern the manufacture and sale of compounds or extracts and health functional foods that have received product approval in accordance with the laws of each country (in Korea, this is the Pharmaceutical Affairs Act) (in Korea, it is the “Health Functional Foods Act”) 」) includes compounds or extracts whose functionality has been individually recognized.

For example, dexpanthenol, biotin, L-menthol, zinc pyrithione, etc., which are ingredients with hair loss symptom alleviating functionality listed in the Ministry of Food and Drug Safety Notification “Functional Cosmetics Standards and Test Methods” in accordance with the Korean Cosmetic Act, are listed in the Korean Health Functional Food Act. GABA-containing powder derived from L-glutamic acid, katsuobushi oligo peptide, Natto bacteria culture powder, Somoktae peptide complex, salmon peptide, Olive leaf extract, sardine peptide, casein hydrolyzate, coenzyme Q10, grape seed enzymatically digested extract powder, Haitai oligopeptide, etc. may be examples of these compounds or extracts.

In a specific embodiment, the composition of the present invention can be considered a food composition.

The food composition of the present invention can be manufactured in any form, for example, beverages such as tea, juice, carbonated beverages, and electrolyte drinks, processed oils such as milk and yogurt, gums, rice cakes, Korean snacks, bread, snacks, noodles, etc. It can be manufactured into health functional food preparations such as foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars, etc.

In addition, the food composition of the present invention can have any product classification in terms of legal and functional classification as long as it complies with the enforcement laws and regulations at the time of manufacture and distribution. For example, it is a health functional food according to the Korean 「Act on Health Functional Foods」, or confectionery, beans, tea, and beverages according to each food type according to the food code of the Korean 「Food Sanitation Act」 (Ministry of Food and Drug Safety Notification 「Food Standards and Specifications」) , special purpose food, etc.

The food composition of the present invention may contain food additives in addition to the active ingredients. Food additives can generally be understood as substances that are added to, mixed with, or infiltrated into food when manufacturing, processing, or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be guaranteed. In the food additive code of each country that regulates the manufacturing and distribution of food (in Korea, it is the Food Sanitation Act), food additives with guaranteed safety are limited in terms of ingredients or functions. In the Korea Food Additive Code (Ministry of Food and Drug Safety Notification “Food Additive Standards and Specifications”), food additives are classified into chemical synthetics, natural additives, and mixed preparations in terms of composition. These food additives are classified into sweeteners and flavors in terms of function. It is classified into preservatives, emulsifiers, acidulants, thickeners, etc.

Sweeteners are used to impart an appropriate sweetness to foods, and both natural and synthetic ones can be used in the food composition of the present invention. Preferably, a natural sweetener is used, and natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

Flavoring agents are used to improve taste or aroma, and both natural and synthetic ones can be used. Preferably, natural products are used. When using natural products, they can serve the purpose of enhancing nutrition in addition to flavor. Natural flavoring agents may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or may be obtained from green tea leaves, coriander leaves, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, etc. You can also use things obtained from ginseng (red ginseng), bamboo shoots, aloe vera, and ginkgo nuts. Natural flavoring agents may be liquid concentrates or solid extracts. In some cases, synthetic flavoring agents may be used, and as synthetic flavoring agents, esters, alcohols, aldehydes, terpenes, etc. may be used.

Preservatives include calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc., and emulsifiers include acacia gum, carboxymethyl cellulose, xanthan gum, and pectin. etc. may be used, and as acidulants, acidic acid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. may be used. In addition to improving taste, acidulants may be added to ensure that the food composition has an appropriate acidity for the purpose of suppressing the growth of microorganisms. As a thickening agent, a suspending agent, settling agent, gel forming agent, bulking agent, etc. may be used.

In addition to the food additives described above, the food composition of the present invention may contain bioactive substances or minerals known in the art and whose safety is guaranteed as food additives for the purpose of supplementing and reinforcing functionality and nutrition.

Such physiologically active substances include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, etc., and minerals include calcium preparations such as calcium citrate and magnesium stearate. Magnesium preparations such as iron citrate, iron preparations such as chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, etc. are included.

The food composition of the present invention may contain the above-described food additives in an appropriate amount to achieve the purpose of addition depending on the product type.

Regarding other food additives that can be included in the food composition of the present invention, each country's food code or food additive code can be referred to.

The composition of the present invention may be considered a pharmaceutical composition in other specific embodiments.

The pharmaceutical composition of the present invention contains a pharmaceutically acceptable carrier in addition to the active ingredient and can be prepared into an oral formulation or a parenteral formulation depending on the route of administration by a conventional method known in the art. Here, the route of administration may be any suitable route, including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and for specifics, reference can be made to the pharmacopoeia of each country, including the “Korean Pharmacopoeia.”

When the pharmaceutical composition of the present invention is prepared as an oral dosage form, it can be prepared as powder, granules, tablets, pills, sugar-coated tablets, capsules, solutions, gels, syrups, suspensions, and wafers along with a suitable carrier according to methods known in the art. It can be manufactured in a dosage form such as: Examples of suitable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, and wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Cellulose such as hydroxypropylmethylcellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, grease. Serol, etc. can be mentioned. When formulating, appropriate binders, lubricants, disintegrants, colorants, diluents, etc. can be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch ferrite, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, and wax, and as a lubricant, oleic acid. Examples include sodium, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, its magnesium and calcium salts, and polydethylene glycol. Disintegrants include starch and methyl cellulose. , agar, bentonite, xanthan gum, starch, alginic acid or its sodium salt, etc. Additionally, diluents include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, etc.

When the pharmaceutical composition of the present invention is prepared as a parenteral formulation, it can be formulated in the form of injections, transdermal administration, nasal inhalation, and suppositories along with a suitable carrier according to methods known in the art. When formulated as an injection, an aqueous isotonic solution or suspension can be used as a suitable carrier. Specifically, an isotonic solution such as PBS (phosphate buffered saline) containing triethanolamine, sterile water for injection, or 5% dextrose can be used. . When formulated for transdermal administration, it can be formulated in the form of ointments, creams, lotions, gels, external solutions, paste preparations, linear preparations, and aerol preparations. In the case of nasal inhalation, it can be formulated in the form of an aerosol spray using suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, and carbon dioxide. When formulated as a suppository, the carrier is Wethepsol ( witepsol), Tween 61, polyethylene glycols, cocoa fat, laurel paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, sorbitan fatty acid esters, etc. can be used.

Regarding the specific formulation of pharmaceutical compositions, it is known in the art, and references can be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). The above documents are considered a part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, gender, age, patient's severity, and administration route. It may be in the /kg range. Administration can be done once a day or divided into several times. These dosages should not be construed as limiting the scope of the invention in any respect.

In another specific aspect, the composition of the present invention can be considered a cosmetic composition.

Even if the composition of the present invention is identified as a cosmetic composition, the cosmetic composition may be classified as an arbitrary product in terms of its use and by law, and is specifically used for purposes such as alleviating hair loss, promoting hair growth, improving skin troubles, and improving atopic dermatitis. It can be functional cosmetics, non-functional general cosmetics, etc. The product form can take any product form, specifically solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, shampoo, surfactant-containing cleansing, oil, powder foundation, emulsion foundation. It can take the form of products such as wax foundation, spray, etc. Specific product forms may include softening lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray, or powder.

In addition to the active ingredient, the cosmetic composition of the present invention may contain ingredients commonly used in cosmetic compositions, such as stabilizers, solubilizers, surfactants, vitamins, conventional auxiliaries such as pigments and flavorings, and carriers.

When the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier ingredient. You can.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient. In particular, when the formulation is a spray, chlorofluorohydrocarbon and propane may be used as carrier ingredients. /May contain propellants such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan, etc. can be used.

When the formulation of the present invention is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystals. Cellulose, aluminum metahydroxide, bentonite, agar, etc. can be used.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

The cosmetic composition of the present invention can be manufactured according to a cosmetic composition manufacturing method commonly used in the art, except that it contains active ingredients that exhibit hair growth promoting activity, etc.

As described above, according to the present invention, it is possible to provide a composition for promoting hair growth or suppressing hair loss using an extract of Hepatica chinensis.

The composition of the present invention can be commercialized into foods, drugs, hair cosmetics, etc.

Figure 1 is a result showing the effect of the Hepatica chinensis extract on promoting the proliferation of human dermal papilla cells.
Figure 2 is a result showing the effect of the Hepatica chinensis extract on promoting the proliferation of human hair cells.

Hereinafter, the present invention will be described with reference to examples and experimental examples. However, the scope of the present invention is not limited to these examples and experimental examples.

<Example> Preparation of Hepatica chinensis extract

10 times the weight of 70% ethanol was added to the dried powder of Hepatica maxima Nakai, leached at room temperature for 24 hours, filtered with Whatman filter paper No. 2, and the filtrate was concentrated under reduced pressure. A solid extract of Hepatica chinensis was prepared by freeze-drying.

<Experimental example> Evaluation of the proliferation effect of human hair papilla cells and human hair blast cells

<Experimental Example 1> Evaluation of human dermal papilla cell proliferation effect

The effect of the extract on cell growth of human hair dermal papilla cells was evaluated as follows.

Human dermal papilla cells (Innoprot, cat. no. P10881) were added to MSC (Mesenchymal Stem Cell) medium (Innoprot, cat. no. P60115), a dedicated medium containing 5% FBS (fetal bovine serum) and MSCGS. ×10 ⁴ cells/ were inoculated into a 96-well plate and cultured at 37°C under 5% CO ₂ humidified conditions for 24 hours, and then cultured for 24 hours in serum-free medium. The cells were treated with concentrations of 25, 50, and 100 μg/ml and cultured for 72 hours. As a positive control, 10 μl of Minoxidil (Sigma) was added and cultured as above.

Afterwards, 20 ㎕ of MTS (CellTiter 96ⓡ AQueous One Solution Cell proliferation assay kit, Promega) reagent was added and cultured in a cell incubator for 2 hours. Then, the degree of cell growth was measured by measuring the absorbance at 490 nm using an ELISA reader.

The effect of the Hepatica chinensis extract on the proliferation of human dermal papilla cells is shown in Figure 1. The extract of the Hepatica chinensis on human dermal papilla cell proliferation generally showed a concentration-dependent effect.

<Experimental Example 2> Evaluation of human hairblast proliferation effect

The effect of the extract on cell growth of human hair germinal matrix cells was evaluated as follows.

Hair cells (Innoprot, cat. no. P10882) 1 The cells were inoculated into a 96-well plate at a density of ⁴ cells and cultured at 37°C under 5% CO ₂ humidified conditions for 24 hours with serum free medium. The cells were treated with concentrations of 50 and 100 μg/ml and cultured for 72 hours. As a positive control, 10 μl of Minoxidil (Sigma) was added and cultured in the same manner as above.

Afterwards, 20 ㎕ of MTS (CellTiter 96ⓡ AQueous One Solution Cell proliferation assay kit, Promega) reagent was added and cultured in a cell incubator for 2 hours. Then, the degree of cell growth was measured by measuring the absorbance at 490 nm using an ELISA reader.

The effect of the Hepatica chinensis extract on the proliferation of human hair cells is shown in Figure 2. The extract of the Hepatica chinensis showed a concentration-dependent effect on the proliferation of human hair cells.

Claims (5)

A composition for promoting hair growth or inhibiting hair loss containing extract of Hepatica chinensis as an active ingredient.
According to paragraph 1,
A composition for promoting hair growth or inhibiting hair loss, wherein the extract is an extract of water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
According to claim 1 or 2,
A composition for promoting hair growth or inhibiting hair loss, characterized in that the composition is a food composition.
According to claim 1 or 2,
A composition for promoting hair growth or inhibiting hair loss, characterized in that the composition is a pharmaceutical composition.
According to claim 1 or 2,
The composition is a composition for promoting hair growth or inhibiting hair loss, characterized in that it is a hair cosmetic composition.