KR102709727B1 - Composition for inhibiting growth of body hair comprising the Mallotus japonicus or the fraction thereof - Google Patents

Abstract

The present invention relates to a composition for inhibiting hair growth comprising an extract of the yeduk tree or a fraction thereof. Specifically, the composition of the present invention can inhibit hair growth by inhibiting the development and/or proliferation of hair papilla cells. In addition, the composition of the present invention can provide safety even for long-term administration, unlike existing hair removal agents, by utilizing natural materials.

Description

Composition for inhibiting growth of body hair comprising the Mallotus japonicus or the fraction thereof

The present invention relates to a composition containing an extract of the yeduk tree or a fraction thereof and a use thereof. Specifically, the extract of the yeduk tree and the like can inhibit the growth of body hair by inhibiting the development of hair papilla cells and further provide a hair removal effect.

Humans have about 100,000 to 150,000 hairs, and hair has functioned as one of the body's important defense mechanisms to protect the body's organs from external stimuli. However, body hair, excluding the scalp, is gradually losing its function or role as a defense mechanism. Recently, as more women have entered society and their appearance has greatly influenced their image, the number of women who take meticulous care of not only their faces but also their bodies and private parts has increased. In addition, as warmer seasons have increased due to global warming, women's exposure has increased, and in particular, methods that effectively remove hair from women's armpits, arms, and legs have become popular as a type of manner.

In general, hair removal products (Depilatory) can be broadly represented by the following three types. First, adhesive/removable hair removal agents (Strips) are products that are attached to the area to be removed and then removed like tape, removing the hair. Second, there are products that shave the hair using a razor, shaving foam, and gel. Third, there are products that melt and remove the hair using chemicals (thioglycolic acid or its derivatives). The first type has the advantage of being easy to use, and although it is possible to remove relatively long hair, it is not easy to remove short, thick hair, and it is painful to remove. Second, although the hair is removed cleanly in an instant, there is a problem that it does not have a lasting effect and the hair grows thicker. Lastly, the third is that it has the advantage of excellent long-lasting effects after hair removal and is easy to remove both long and short hair, but the physicochemical stability of the main ingredient, thioglycolic acid or its derivatives, is low, making the product very unstable. In addition, there are disadvantages such as skin irritation caused by these chemicals and a large difference in efficacy depending on the product.

That is, hair removal methods that pull out body hair using mechanical or physical means have the side effects of pain, and existing chemical means using hair removal creams or wax are not only painful but also have concerns about skin damage due to chemical components. In addition, existing methods have the disadvantage that they are still insufficient in terms of hair growth inhibition, or have short-term effects, requiring hair removal treatment again after a certain period of time depending on hair growth. Therefore, research is needed on materials that can provide a safe, long-term hair growth inhibition effect and extend the duration of the hair growth inhibition effect.

Meanwhile, "Yeduk tree (Mallotus japonicus)" is a deciduous broadleaf small tree that grows in sunny places such as seasides, mountainsides, valleys, wastelands, and cleared lands. When young, the stem is covered with star-shaped scales and is reddish, but gradually turns gray-white. The branches are thick and the bark is gray-white. The leaves are egg-shaped and shallowly divided into three lobes, with smooth edges, all arranged alternately, and have long petioles with a reddish tinge. The flowers are dioecious, and greenish-yellow flowers bloom in a panicle around June. The fruit is a capsule that ripens around October, has thorns, and contains three reddish-black seeds.

The present invention aims to provide a cosmetic composition for hair growth inhibition comprising an extract of the yeduk tree or a fraction thereof.

The present invention aims to provide a pharmaceutical composition for inhibiting hair growth comprising an extract of the yeduk tree or a fraction thereof.

The present invention provides a health functional food, health functional food supplement or food composition containing an extract of the yeduk tree or a fraction thereof for inhibiting hair growth.

The present invention provides a method for producing an extract of the yeduk tree or a fraction thereof.

According to one embodiment of the present invention,

A cosmetic composition for inhibiting hair growth comprising an extract of the yeduk tree or a fraction thereof is provided.

According to another embodiment of the present invention,

The present invention provides a pharmaceutical composition for inhibiting hair growth comprising an extract of the plant or a fraction thereof.

According to another embodiment of the present invention,

A health functional food, health supplement or food composition for hair growth inhibition containing an extract of the yeduk tree or a fraction thereof is provided.

According to another embodiment of the present invention,

The present invention provides a method for producing an extract of the yeduk tree or a fraction thereof.

A composition containing an extract of a deciduous tree according to a specific example of the present invention can inhibit hair growth by inhibiting the development and growth of hair papilla cells and reducing the activity of alkaline phosphatase (ALP), a hair growth factor.

In addition, since the composition of the present invention utilizes natural materials, it is safer than existing mechanical and chemical methods for removing body hair. Accordingly, a composition containing extracts of the yeduk tree, etc., can be utilized as cosmetics, medicines, foods, etc. for inhibiting body hair growth.

Figure 1 shows an evaluation of the developmental ability of maternal papilla cells of extracts from the Yedeok tree. Specifically, the developmental level of maternal papilla cells of extracts from different parts of the Yedeok tree, different extraction solvents, and different concentrations is depicted using a microscope.
Figure 2 is a quantitative diagram illustrating the developmental ability of mammary gland cells by extracts of different parts of the Yedeok tree, different extraction solvents, and different concentrations, in terms of ALP activity.
Figures 3 and 4 show the evaluation of the safety of extracts by part of the Yedeok tree, extraction solvent, and concentration. Specifically, Figure 3 shows the evaluation of the proliferation ability of mammary papilla cells by extracts by part of the Yedeok tree, extraction solvent, and concentration, and Figure 4 shows the evaluation of the safety of extracts by part of the Yedeok tree, extraction solvent, and concentration on keratinocytes.

The present invention can be achieved by the following description. It should be understood that the following description describes specific examples of the present invention, and the present invention is not necessarily limited thereto. In addition, it should be understood that the attached drawings are for the purpose of helping understanding, and the present invention is not limited thereto.

The embodiments of the present invention can be modified in various ways and implemented in various forms. Therefore, it should be understood that all modifications, equivalents, or substitutes are included within the scope that the identity of the spirit and technical features of the present invention is recognized.

Unless otherwise specified, all numbers used herein should be understood as being modified in all instances by the term “about.” The modifier “about” is intended to have the commonly recognized meaning of approximately, which can be more precisely interpreted as meaning within a certain percentage of the modified value, and more specifically can mean ±20%, ±10%, ±5%, ±2%, or ±1% or less.

According to one specific example of the present invention,

A composition for inhibiting hair growth comprising an extract of the yeduk tree or a fraction thereof can be provided. The composition can be a cosmetic composition, a pharmaceutical composition, a health functional food composition, a health supplement composition, or a food composition.

The above “Mallotus japonicus” is a deciduous broadleaf small tree, with a trunk covered with star-shaped scales when young, which are reddish but gradually turn gray-white. The branches are thick and the bark is gray-white. The leaves are egg-shaped and shallowly divided into three lobes, with smooth margins, all arranged alternately, and have long petioles tinged with red. The flowers are dioecious, and greenish-yellow flowers bloom in panicles around June. The fruit is a capsule, ripens around October, has thorns, and contains three reddish-black seeds.

The above-mentioned deciduous tree may be the entire deciduous tree, a single part thereof, or a combination of each part. Specifically, the deciduous tree may be an above-ground or underground part of the deciduous tree, and the deciduous tree may be at least one of a deciduous tree root, a deciduous tree trunk, a deciduous tree branch, a deciduous tree leaf, a deciduous tree flower, a deciduous tree fruit, a deciduous tree trunk bark, a deciduous tree pulp, a deciduous tree pericarp, and a deciduous tree seed, but is not limited thereto. More specifically, the deciduous tree may be a deciduous tree fruit, leaf, or branch.

The term "extract" includes not only the extraction result obtained by treating the extractive solvent on the yeduk tree, but also a processed product that is formulated (e.g., powdered) so that the yeduk tree itself can be administered to animals. In addition, the "extract" has the meaning commonly used in the art as a crude extract as described above, but in a broad sense, it may also include a fraction obtained by further fractionating the extract. That is, the yeduk tree extract may include not only one obtained by using an extraction solvent, but also one obtained by additionally applying a purification process thereto. For example, the extract may include fractions obtained by various purification methods, such as a fraction obtained by passing the extract through an ultrafiltration membrane having a certain molecular weight cut-off value, fractions separated by various chromatographies (designed for separation according to size, charge, hydrophobicity, or affinity). In addition, the terms "extract" and "fraction" used herein may include not only the extract and fraction obtained by extraction, but also a dilution or concentrate of the extract and fraction, a dried product obtained by drying the extract and fraction, or a crude or purified product of the extract and fraction.

The above extraction solvent is sufficient as long as it can maintain a liquid state during extraction and extract effective ingredients from the yeduk tree. Specifically, it may be at least one selected from the group consisting of water, alcohol, chlorinated hydrocarbons, acetonitrile, tetrahydrofuran, alkyl (methyl or ethyl) acetate, and acetone, but is not limited thereto.

The alcohol may be, for example, a C ₁ -C ₆ alcohol, for example, a C ₁ -C ₄ alcohol or a mixture thereof. The C ₁ -C _{6 alcohol may be a primary to tertiary alcohol. The C 1 -C 6 alcohol may} be at least one selected from the group consisting of methanol, ethanol, propanol, isopropanol, 1,3-propanediol, butanol, pentanol and hexanol.

The above chlorinated hydrocarbon may be, but is not limited to, chloroform (CHCl ₃ ) or dichloromethane (CH ₂ Cl ₂ ).

The solvent may be a mixture of two different organic solvents. For example, it may be a mixture of water and alcohol, i.e. an aqueous alcohol solution, a mixture of alcohol and a chlorinated hydrocarbon, a mixture of water and acetonitrile, or a mixture of water and an alkyl acetate. The alcohol concentration of the alcohol aqueous solution may be, for example, about 0 to about 100 (v/v)%, for example, about 10 to about 100 (v/v)%, for example, about 20 to about 100 (v/v)%, for example, about 30 to 100 (v/v)%, for example, about 40 to 100 (v/v)%, about 50 to 100 (v/v)%, about 70 to 100 (v/v)%, about 80 to 100 (v/v)%, about 90 to 100 (v/v)%, or about 95 to 100 (v/v)%. In this case, a 0% alcohol aqueous solution may mean 100% water. The above alcohol aqueous solution may be an alcohol aqueous solution selected from the group consisting of methanol, ethanol, propanol, isopropanol, 1,3-propanediol, butanol, pentanol, and hexanol, but is not limited thereto. The solvent may be fermentation alcohol.

The above extraction may include adding the extraction solvent to the yeduk tree in an amount of about 1 to about 100 (volume/weight) times, for example, about 1 to about 50 (volume/weight) times, about 3 to about 20 (volume/weight) times, about 3 to about 50 (volume/weight) times, about 3 to about 10 (volume/weight) times, or about 3 to about 7 times. For example, for 1 kg of the above-mentioned Yedeok tree, the extraction solvent may be added in an amount of about 1 to about 100 L, for example, about 3 to about 50 L, for example, about 5 to about 30 L, for example, about 10 to about 30 L, for example, about 15 to about 25 L, for example, about 3 to about 25 L, for example, about 10 to about 25 L.

The above extraction can be performed by stirred extraction, pressurized liquid extraction, pressurized liquid extraction (PLE), microwave assisted extraction (MAE), subcritical extraction (SE), or a combination thereof. The subcritical extraction can be subcritical water extraction (SWE). Subcritical water extraction is also called superheated water extraction or pressurized hot water extraction (PHWE). The warm liquid extraction can be reflux extraction.

The above extraction can be expressed in a range of any two values selected from 1°C, 10°C, 20°C, 30°C, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, 130°C, 140°C and 150°C. Specifically, it can be performed at, for example, about 1°C to about 150°C, for example, about 10°C to about 130°C, for example, about 10°C to about 100°C, for example, about 10°C to about 70°C, for example, about 10°C to about 50°C, for example, about 10°C to about 30°C.

The extraction time is, for example, about 0.1 hour to about 2 months, for example, about 0.1 hour to about 10 days, for example, about 0.1 hour to about 5 days, for example, about 0.5 hour to about 2 months, for example, about 1 hour to about 1 month, for example, about 1 hour to about 15 days, for example, about 1 hour to about 10 days, for example, about 1 hour to about 5 days, for example, about 1 hour to about 3 days, for example, about 3 hours to about 1 month, for example, about 5 hours to about 15 days, for example, about 5 hours to about 10 days, for example, about 5 hours to about 5 days, for example, about 5 hours to about 3 days, for example, about 10 hours to about 1 month, for example, about 10 hours to about 15 days, for example, about 10 hours to about 10 days, for example, about 10 hours to about 5 days, for example It can take anywhere from about 10 hours to about 3 days.

The above extraction may include mixing the yeduk tree, a part thereof, or a material derived therefrom in the above solvent and leaving it for a certain period of time. The leaving may include appropriate stirring. The above extraction may be repeated, for example, 1 to 5 times. The above repetition may mean that the extraction is performed one or more times, the extract is filtered, and the remaining yeduk tree, etc. are immersed in the extraction solvent again to perform the extraction.

The above extract can be separated from plant residues by a known method such as filtration or centrifugation. Specifically, it can be atmospheric filtration, reduced pressure filtration, or pressurized filtration, and can use filter paper. Reduced pressure filtration can be a method of filtering by making a post-filtration portion centered on the filter paper into a vacuum state, and pressurized filtration can be a method of filtering by applying pressure to a pre-filtration portion centered on the filter paper. The centrifugation can be a method of separating a supernatant by rotating a sample at high speed and settling solids by centrifugal force. The conditions for the centrifugation are sufficient if they can settling solids, and can be performed by a commonly known method.

The extraction may also include removing the solvent from the obtained extract by a known method, such as concentration under reduced pressure. The extraction may also include preparing a dry extract by drying the obtained extract. The drying may include drying under reduced pressure, boiling drying, spray drying, room temperature drying or freeze drying.

According to one specific example of the present invention,

In the above composition, the term "fraction" may mean dividing the Yedeok tree extract by a certain standard. The fraction may be obtained by solvent fractionation. The solvent fractionation may be mixing the Yedeok tree extract with a solvent under certain conditions and separating a substance present in the solvent, for example, separating by polarity of the solvent, or separating by molecular weight of the component, but is not limited thereto. The fraction may be a hexane fraction, a dichloromethane fraction, an ethyl acetate fraction, an n-butanol fraction, a water fraction, or a combination thereof obtained by sequentially fractionating the Yedeok tree extract into hexane, dichloromethane, ethyl acetate, and n-butanol after suspending it in water.

According to another specific embodiment of the present invention,

The above fraction may be a composition obtained by refining an extract or fraction by performing chromatography. Specifically, it may be, for example, chromatography according to polarity, chromatography according to molecular weight, or chromatography according to a combination thereof. More specifically, it may be a fraction obtained by liquid-liquid chromatography using different immiscible solvents, a fraction obtained by column chromatography in which the solvent is passed through a column gradually changing in polarity, or a fraction obtained by passing the column through a column composed of porous particles according to molecular size, but is not limited thereto. Alternatively, it may be another fraction obtained by gradually changing the ratio of solvents of different polarities using column chromatography on the extract or fraction. Specifically, it may be a fraction obtained by using column chromatography on a mixture in which the ratio of A:B in two different solvents A and B causes a stepwise change in polarity of 0:100, 1:99, 5:95, 10:90, 20:80, 30:70, 40:60, 50:50, 60:40, 70:30, 80:20, 90:10 and 100:0. For example, it may be a fraction obtained by using column chromatography on a stepwise mixture of 50%, 60%, 70%, 80% and 90% aqueous methanol and 100% methanol. Or it can be a fraction obtained by using column chromatography with a mixture of CHCl ₃ and 100% methanol, for example, 100% CHCl ₃ , 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% methanol dissolved. The packing of the column chromatography can be a normal phase or reverse phase silica gel, and can be a packing having porous particles. The fractionation can be repeated 1 to 5 times.

The above fractions can be separated by a known method such as filtration. Specifically, it can be atmospheric filtration, reduced pressure filtration or pressurized filtration, and can use a filter paper. Reduced pressure filtration is a method of filtering by making a post-filtration portion centered on the filter paper into a vacuum state, and pressurized filtration is a method of filtering by applying pressure to a pre-filtration portion centered on the filter paper. The fractionation can also include removing a solvent from the obtained fraction by a known method such as reduced pressure concentration. The fractionation can also include preparing a dry extract by drying the obtained fraction. The drying can include reduced pressure drying, boiling drying, spray drying, room temperature drying or freeze drying.

In the present invention, “inhibition of hair growth” may be inhibition of the development of hair papilla cells, or reduction of hair growth factors, or inhibition of the proliferation of hair papilla cells, but is not limited thereto. The hair papilla cells are cells present at the base of hair follicles and supply oxygen and nutrients to the cells constituting the hair follicles, thereby controlling hair growth and the hair follicle cycle. Therefore, by inhibiting the development or proliferation of hair papilla cells, hair growth can be inhibited, thereby reducing hair.

The above hair growth factor may be a cell division activator that the human body is born with, which stimulates cells with impaired function to extend the hair growth period. The growth factor includes, but is not limited to, fibroblast growth factor (bFGF, basic Fibroblast Growth Factor), vascular endothelial growth factor (VEGF, vascular endothelial Growth Factor), insulin-like growth factor (IGF-1, Insulinlike Growth Factor), Noggin (hair follicle-stimulating growth factor), stem cell proliferation factor (SCF, Stem Cell Factor), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), alkaline phosphatase (ALP), etc.

According to one specific example of the present invention,

A pharmaceutical composition for inhibiting hair growth comprising an extract of the plant or a fraction thereof can be provided.

The composition may contain an extract of the yeduk tree or a fraction thereof, expressed in a range of any two values selected from among 0.001 wt%, 0.01 wt%, 0.05 wt%, 0.1 wt%, 0.5 wt%, 1.0 wt%, 3 wt%, 5 wt%, 10 wt%, 20 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt% and 90 wt%, based on the total weight of the composition. For example, about 0.001 wt % to about 95 wt %, about 0.01 wt % to about 90 wt %, about 0.01 wt % to about 80 wt %, about 0.01 wt % to about 70 wt %, about 0.01 wt % to about 60 wt %, about 0.01 wt % to about 50 wt %, about 0.01 wt % to about 30 wt %, about 0.05 wt % to about 25 wt %, about 0.05 wt % to 15 wt %, about 0.05 wt % to 5 wt %, about 0.1 wt % to about 20 wt %, about 1.0 wt % to 10 wt %, about 1.0 wt % to about 5 wt %, about 5 wt % to about 50 wt %, about 5 wt % to about 40 wt %, or about 10 wt % to about 50 wt % of the yeduk tree. It may include an extract or a fraction thereof.

The pharmaceutical composition may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may include, but is not limited to, at least one selected from the group consisting of a binder, a lubricant, a disintegrant, an excipient, a solubilizer, a dispersant, a stabilizer, a suspending agent, a coloring agent, and a flavoring agent for oral administration. In the case of injections, a buffer, a preservative, an analgesic, a solubilizer, an isotonic agent, or a stabilizer may be mixed and used, and in the case of topical administration, a base, an excipient, a lubricant, or a preservative may be mixed and used.

The formulation of the pharmaceutical composition of the present invention can be variously prepared by mixing with a pharmaceutically acceptable carrier as described above. For example, the pharmaceutical composition can be prepared as an oral formulation by being prepared as a tablet, a capsule, a dry syrup, an orally disintegrating tablet, a pak-kal tablet, an effervescent tablet, a powder, a sublingual tablet, a liquid or a chewable tablet, and in the case of an injection, it can be prepared in the form of a unit dosage ampoule or a multiple dosage form, and can also be formulated as a solution, a suspension, a tablet, a capsule, a sustained-release preparation, etc.

Meanwhile, examples of carriers, excipients or diluents suitable for formulation include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate or mineral oil. In addition, fillers, anticoagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like can be additionally included.

The routes of administration of the pharmaceutical composition according to the present invention include, but are not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual, or rectal. The administration may be systemic or local. The pharmaceutical composition of the present invention may also be administered in the form of a suppository for rectal administration.

The above administration may be to administer 0.1 mg to 1,000 mg of the extract of the yeduk tree or a fraction thereof at a single administration, 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 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg.

The dosage of the composition may be, for example, about 0.001 mg/kg to about 100 mg/kg on an adult basis, for example, about 0.01 mg/kg to about 10 mg/kg, or for example, about 0.1 mg/kg to about 1 mg/kg. The frequency of administration may be once a day, multiple times a day, 2 to 3 times a week, 1 to 4 times a month, or 1 to 12 times a year.

When the composition is administered, the final concentration of the extract of the yeduk tree in the maternal papilla cells may be expressed as a range of any two values selected from 0.001 μg/ml, 0.01 μg/ml, 0.05 μg/ml, 0.1 μg/ml, 0.3 μg/ml, 0.5 μg/ml, 1 μg/ml, 3 μg/ml, 5 μg/ml, 10 μg/ml, 15 μg/ml, 20 μg/ml, 25 μg/ml, 30 μg/ml, 40 μg/ml, 50 μg/ml, 60 μg/ml, 70 μg/ml, 100 μg/ml, 150 μg/ml, 200 μg/ml, 300 μg/ml, 500 μg/ml, and 1,000 μg/ml. Specifically, when the composition is administered, the final concentration of the extract of the yeduk tree in the maternal papilla cells may be, for example, about 0.001 μg/ml to about 1,000 μg/ml, for example, about 0.01 μg/ml to about 1,000 μg/ml, for example, about 0.05 μg/ml to about 1,000 μg/ml, for example, about 0.1 μg/ml to about 1,000 μg/ml, for example, about 0.1 μg/ml to about 500 μg/ml, for example, about 0.1 μg/ml to about 100 μg/ml, for example, about 1 μg/ml to about 1,000 μg/ml, for example, about 1 μg/ml to about 500 μg/ml, for example, about 1 μg/ml to about 200μg/ml, and for example can be from about 10μg/ml to about 1,000μg/ml, and for example can be from about 10μg/ml to about 500μg/ml, and for example can be from about 10μg/ml to about 300μg/ml, and for example can be from about 10μg/ml to about 200μg/ml, and for example can be from about 10μg/ml to about 100μg/ml, and for example can be from about 20μg/ml to about 500μg/ml, and for example can be from about 20μg/ml to about 300μg/ml, and for example can be from about 20μg/ml to about 200μg/ml, and for example can be from about 20μg/ml to about 100μg/ml, and for example can be from about 0.001μg/ml to about It can be 10μg/ml, for example, from about 0.01μg/ml to about 10μg/ml, for example, from about 0.01μg/ml to about 5μg/ml, for example, from about 0.01μg/ml to about 3μg/ml, for example, from about 0.1μg/ml to about 5μg/ml, for example, from about 0.1μg/ml to about 3μg/ml, for example, from about 0.3μg/ml to about 5μg/ml, for example, from about 0.3μg/ml to about 3μg/ml, for example, from about 1μg/ml to about 5μg/ml, for example, from about 1μg/ml to about 3μg/ml.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using laser treatment, hormone treatment, and chemotherapy for hair growth inhibition. The concentration of the effective ingredient included in the composition of the present invention can be determined in consideration of the treatment purpose, the patient's condition, the required period, etc., and is not limited to a specific range of concentrations. The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, the 'pharmaceutically effective amount' means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dosage level can be determined according to the type and severity of the patient's disease, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration, and the excretion rate, the treatment period, the concurrently used drugs, and other factors well known in the medical field. The pharmaceutical composition of the present invention can be administered as an individual therapeutic agent, or can be administered in combination with a therapeutic agent for another disease, and can be administered simultaneously, separately, or sequentially with a conventional therapeutic agent, and can be administered singly or in multiple doses. Taking all of the above factors into consideration, it is important to administer the amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by those skilled in the art.

According to one specific example of the present invention,

A cosmetic composition for hair growth inhibition comprising an extract of the yeduk tree or a fraction thereof can be provided. The cosmetic composition can further comprise a cosmetically acceptable excipient or carrier. The carrier can be an excipient, a disintegrant, a binder, a glidant, or a combination thereof. The excipient can be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant can be sodium starch glycolate, calcium hydrogen phosphate anhydrous, or a combination thereof. The binder can be polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, hydroxypropyl cellulose, or a combination thereof. The glidant can be magnesium stearate, silicon dioxide, talc, or a combination thereof.

The above cosmetic composition may be formulated as a parenteral administration formulation. The parenteral administration formulation may be an injection or a skin external preparation. The skin external preparation may be a cream, a gel, an ointment, a skin emulsifier, a skin suspension, a transdermal patch, a drug-containing bandage, a lotion, or a combination thereof. The skin external preparation may appropriately blend ingredients commonly used in skin external preparations such as cosmetics or medicines, such as aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, ultraviolet absorbers, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, and various skin nutrients, as needed. The above skin external preparation may also appropriately contain metal sequestrants such as sodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, and gluconic acid; caffeine, tannin, bellapamil, licorice extract, glablidin, hot water extract of the fruit of Kalin; various herbal medicines, tocopheryl acetate, glycyrrhizic acid, tranexamic acid and derivatives or salts thereof; and sugars such as vitamin C, magnesium ascorbic acid phosphate, ascorbic acid glucoside, arbutin, kojic acid, glucose, fructose, and trehalose.

The cosmetic composition according to the present invention can be manufactured in a formulation including a toner (skin lotion), a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisture lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisture cream, a hand cream, a foundation, an essence, a nutrition essence, a pack, a soap, a cleansing foam, a cleansing lotion, a cleansing cream, a body lotion, a body cleanser, a suspension, a gel, a powder, a paste, a mask pack, or a sheet or aerosol composition. The composition in such a formulation can be manufactured according to a method conventional in the art. The cosmetic composition can further include a preservative, a stabilizer, a surfactant, a solubilizer, a moisturizer, an emollient, an ultraviolet absorber, an antiseptic, a bactericide, an antioxidant, a pH adjuster, an organic and inorganic pigment, a fragrance, a cooling agent or an antiperspirant, etc. The amount of the additional ingredients, such as the above-mentioned moisturizer, can be easily selected by those skilled in the art within a range that does not impair the purpose and effect of the present invention, and the amount may be about 0.001 to about 10 wt%, specifically about 0.01 to about 3 wt%, based on the total weight of the composition.

The cosmetic composition of the present invention can be used alone or in combination with other methods for hair growth inhibition or hair removal. Specifically, the cosmetic composition of the present invention can be used in combination with or sequentially with mechanical means for removing hair, such as an electric shaver, a hair removal device, ultrasound, or a laser; physical means, such as an adhesive tape; or chemical means, such as a hair removal cream, wax, or gel. The cosmetic composition of the present invention can be used in combination with another cosmetic composition for hair growth inhibition. The cosmetic composition of the present invention may further include another composition within a range that does not impair the purpose of the present invention, and at this time, the other composition may be a pharmaceutical composition, a cosmetic composition, or a food composition for hair growth inhibition or hair removal, but is not limited thereto. In addition, at this time, even if the other composition is not a composition for hair growth inhibition or hair removal, it is sufficient if it exhibits a synergistic effect of hair growth inhibition or hair removal when included with, co-administered, or sequentially administered with the composition of the present invention.

According to another specific embodiment of the present invention,

A food composition for hair growth inhibition containing an extract of the yeduk tree or a fraction thereof can be provided. The food composition may include, but is not limited to, a health functional food composition, a health supplement composition, or a general food composition.

The above health functional food, health supplement or food composition can be used alone or in combination with other food ingredients using the extract of the yeduk tree or its fractions, and can be used appropriately according to a conventional method. The amount of the active ingredient 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 per 100 parts by weight of 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 a conventional beverage. The natural carbohydrate can be a monosaccharide such as glucose and fructose, a disaccharide such as maltose and sucrose, a polysaccharide such as dextrin and cyclodextrin, a sugar alcohol such as xylitol, sorbitol and erythritol. As a sweetener, natural sweeteners such as thaumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame can be used. The health functional food composition may also contain a nutrient, a vitamin, an electrolyte, a flavoring agent, a coloring agent, pectic acid and its salts, alginic acid and its salts, an organic acid, a protective colloid thickener, a pH regulator, a stabilizer, a preservative, glycerin, alcohol, a carbonating agent used in carbonated beverages, or a combination thereof. The health functional food composition may also contain fruit pulp for the production of natural fruit juice, fruit juice beverage, or vegetable beverage, or a combination thereof.

According to one specific example of the present invention,

a) Step for preparing the yeduk tree;

b) a step of immersing the yeduk tree in an extraction solvent; and

c) A method for producing an extract of a deciduous tree, comprising the step of extracting, may be provided.

The above a) preparation step may be a step for preparing a maple tree to suit the purpose of the present invention. For example, the a) preparation step may include a step of collecting a maple tree, for example, a step of removing impurities from a maple tree, a step of washing a maple tree, a step of drying a maple tree, a step of cutting a maple tree, but is not limited thereto.

In the above b) immersion step, the extraction solvent may be water (e.g., distilled water or sterile distilled water), an alcohol having 1 to 4 carbon atoms, or a combination thereof. Specifically, the extraction solvent may be 0 to 100% of an aqueous solution of an alcohol having 1 to 4 carbon atoms, and more specifically, may be 100% water, 50% ethanol aqueous solution, or 100% ethanol.

The above b) soaking step may include adding the extraction solvent to the yeduk tree in an amount of about 1 to about 100 (volume/weight) times, for example, about 1 to about 50 (volume/weight) times, about 3 to about 20 (volume/weight) times, about 3 to about 50 (volume/weight) times, about 5 to about 25 (volume/weight) times, or about 4 to about 30 times.

The above c) extraction step may be to transfer a substance contained in the extraction target to an extraction solvent. At this time, in the c) extraction step, the extraction environment such as temperature and time may be adjusted or maintained constant. Specifically, in the c) extraction step, the extraction temperature may be 10°C to 50°C, 10°C to 45°C, 10°C to 40°C, 10°C to 35°C, 10°C to 30°C, 10°C to 25°C, 15°C to 50°C, 15°C to 45°C, 15°C to 40°C, 15°C to 35°C, 15°C to 30°C, 15°C to 25°C, 20°C to 50°C, 20°C to 45°C, 20°C to 40°C, 20°C to 35°C, 20°C to 30°C or 20°C to 25°C.

In the above c) extraction step, the extraction time may be 0.5 hours to 100 hours, 1 hour to 90 hours, 6 hours to 80 hours, 6 hours to 70 hours, 12 hours to 60 hours, 12 hours to 50 hours, 20 hours to 50 hours, or 24 hours to 48 hours.

The above manufacturing method may further include d) a filtration step, e) a concentration step, etc.

The extract of the yeduk tree manufactured by the above method can increase hair removal efficacy while increasing economic efficiency.

The present invention is described in more detail through the following examples. However, the present invention is not limited to these examples.

Example 1: Preparation of extract of the yeduk tree

20 g each of the fruit, leaves, and branches of the Yedeok tree were extracted by adding 100% distilled water, 50% ethanol, and 400 mL of 100% ethanol at room temperature for 72 hours. After extraction, the sample was filtered through filter paper, frozen in a -80℃ ultra-low temperature freezer, and lyophilized. The completed Yedeok tree extract was diluted in sterilized water and used in the experiment.

Example 2: Culturing of human follicle dermal papilla cells (HFDPCs)

Human follicle dermal papilla cells (HFDPCs) were cultured as primary cells in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% Fetal Bovine Serum (FBS) and 1% penicillin in an incubator controlled at 37°C, 5% CO2, and 95% humidity.

Example 3: Evaluation of the developmental ability of maternal papilla cells by extracts of the yeduk tree

In order to evaluate the developmental ability of the extract of the yeduk tree in the development of maternal papilla cells, the morphological changes in maternal papilla cells were observed and it was confirmed whether ALP, a developmental indicator of maternal papilla cells, was activated.

Specifically, human dermal papilla cells were cultured at a density of 1 × 10 ⁴ cells/well in a 96-well plate and continuously cultured for 6 days under each test condition. The medium was re-treated every 2 days at different concentrations, and after 6 days of culture, the ALP activity of human dermal papilla cells was measured using an ALP assay kit. After washing with PBS, the cells were lysed in 0.1 M NaNO3-Na2CO3 buffer containing 1% (v/v) Triton X-100 (Sigma) and 2 mM MgSO4. Subsequently, 6 mM p-nitrophenyl phosphate was added to each well and incubated at 37 °C for 30 min. Finally, the enzyme-substrate reaction was stopped by adding 1.5 M NaOH (Sigma). Optical density (OD) readings were performed at a wavelength of 405 nm using a SpectraMax 190 microplate reader (Molecular Devices, Sunnyvale, CA, USA).

According to Fig. 1, when extracts of different parts, extraction solvents, and concentrations of the Yedeok tree were treated to maternal papilla cells, it was shown that all extracts showed a concentration-dependent decrease in maternal papilla cells stained with ALP. In particular, according to Fig. 1, it was confirmed that maternal papilla cells decreased from low concentrations of the fruit extract. Next, according to Fig. 2, it was shown that ALP activity of the Yedeok tree fruit extract decreased as the treatment concentration increased regardless of the extraction solvent. In other words, the Yedeok tree fruit extract suppressed the development biomarker of maternal papilla cells in a concentration-dependent manner, which means that the Yedeok tree fruit extract inhibited the development of maternal papilla cells. In other words, all extraction solvents of the Yedeok tree fruit, leaf, and branch extracts showed a concentration-dependent inhibition effect on maternal papilla cell development, and in particular, the fruit extract was found to have the best inhibition effect on maternal papilla cell development.

Example 4: Analysis of proliferation of maternal papilla cells using extracts of the yeduk tree

Human Follicle Dermal Papilla Cells (HFDPC) were seeded at a concentration of 1 × 10 ⁵ cells/㎖ in a 96-well plate (100 ㎕) and cultured in a CO2 incubator controlled at 37℃, 95% humidity, and 5% CO2 for 24 h. The fresh medium was treated with the extract of the deciduous tree in a concentration range that did not show cytotoxicity and cultured for 6 days. To measure the viability of the cell line, the absorbance was measured at 450 nm with a microplate reader (Molecular Devices, Versa Max ELISA Microplate Reader, USA) using Cell Counting Kit-8 (CCK-8, Dojindo Mol. Tech., Rockville., MD, USA). The cell regeneration efficacy was expressed as the absorbance of the sample-treated group compared to the untreated control group.

The survival rate of the extract of the fruit of the yeduk tree was significantly reduced at concentrations exceeding 10 μg/ml. It can be seen that the extract of the fruit of the yeduk tree exhibited cytotoxicity against mammary papilla cells at concentrations above the concentration, regardless of the extraction solvent of the present invention.

When Figures 2 and 3 are combined, it was confirmed that the extract of the fruit of the Yedeok tree showed a significant inhibition effect on the development of mammary papilla cells while being safe in terms of cytotoxicity at a final intracellular concentration of approximately 3 μg/ml.

Meanwhile, extracts of the leaves or branches of the Yedeok tree were found to have a slight inhibitory effect on the proliferation of mammary papilla cells at 100 μg/ml when extracted with 100% water.

Example 5: Safety evaluation of extracts from the yeduk tree on human keratinocytes

The toxicity of the extract of the Chinese juniper tree to human epidermal keratinocytes was evaluated.

Human keratinocytes were seeded in a 96-well plate at a concentration of 1×105 cells/well and cultured in a CO2 incubator controlled at 37℃, 95% humidity, and 5% CO2 for 24 hours. Each sample was treated to the cells in fresh medium at a concentration of 0.3-100 ㎍/㎖ and cultured for 6 days. Cell toxicity was expressed as the absorbance of the sample-treated group compared to the untreated control group.

According to Figure 4, it was confirmed that the extract of the fruit of the Yedeok tree significantly reduced the viability of skin keratinocytes in a concentration-dependent manner, regardless of the extraction solvent. However, it was confirmed that the fruit extract in all extraction solvents was safe at a concentration of 3 μg/ml or less.

Meanwhile, extracts of the leaves or branches of the Chinese juniper tree did not affect the viability of keratinocytes, or showed some inhibitory effects only at high concentrations.

In summary, it was confirmed that the fruit of the yeduk tree strongly inhibited the development and/or proliferation of hair papilla cells regardless of the extraction solvent. Alternatively, the fruit of the yeduk tree strongly inhibited the development of hair papilla cells regardless of the extraction solvent, but showed marked cytotoxicity at high concentrations. However, the extract of the yeduk tree fruit showed significant inhibitory efficacy without cytotoxicity at a final intracellular concentration of 3 μg/ml or less regardless of the extraction solvent. Therefore, the extract of the yeduk tree fruit is judged to be safe and have excellent hair growth inhibition efficacy at the corresponding concentration.

Meanwhile, extracts of leaves or branches of the yeduk tree were confirmed to inhibit the development of mammary papilla cells in a concentration-dependent manner. Specifically, water extracts of leaves or branches of the yeduk tree were confirmed to be relatively safe as they showed almost no cytotoxicity even at high concentrations, while also having the effect of inhibiting the development of mammary papilla cells.

Claims (13)

A pharmaceutical composition for inhibiting hair growth comprising an extract of Mallotus japonicus or a fraction thereof. In the first paragraph,
The above-mentioned extract of the Yedeok tree is a pharmaceutical composition which is an extract of fruit, leaf or branch. In the second paragraph,
A pharmaceutical composition wherein the final concentration of the extract of the fruit of the above-mentioned Yedeok tree in the mammary papilla cells is 0.3 μg/ml to 5 μg/ml. In the second paragraph,
A pharmaceutical composition wherein the above extract of the leaves or branches of the Yedeok tree is a 100% water extract. In paragraph 4,
A pharmaceutical composition wherein the final concentration of the extract of the leaves or branches of the above-mentioned Yedeok tree in the hair papilla cells is 30 μg/ml to 300 μg/ml. In any one of paragraphs 1 to 5,
The pharmaceutical composition for inhibiting hair growth is a pharmaceutical composition that inhibits at least one of basic Fibroblast Growth Factor (bFGF), vascular endothelial Growth Factor (VEGF), insulin-like growth factor (IGF-1), Noggin (hair follicle-stimulating growth factor), stem cell growth factor (SCF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and alkaline phosphatase (ALP). In Article 6,
The above composition is a pharmaceutical composition that inhibits the development of mammary papilla cells. In Article 7,
The composition is a pharmaceutical composition comprising 0.01 to 90 wt% of a deciduous tree extract or a fraction thereof based on the total weight of the composition. In Article 8,
The above composition is a pharmaceutical composition in the form of a tablet, a capsule, a dry syrup, an orally disintegrating tablet, a tablet, an effervescent tablet, a powder, a sublingual tablet, a liquid or a chewable tablet. A cosmetic composition for hair removal comprising an extract of the yeduk tree. In Article 10
The above cosmetic composition is a cosmetic composition in the form of a toner (skin lotion), a skin softener, a skin toner, an astringent, a lotion, a milk lotion, a moisture lotion, a nutrition lotion, a massage cream, a nutrition cream, a moisture cream, a hand cream, a foundation, an essence, a nutrition essence, a pack, a soap, a cleansing foam, a cleansing lotion, a cleansing cream, a body lotion, a body cleanser, a suspension, a gel, a powder, a paste, a mask pack, a sheet, or an aerosol. A hair removal method comprising a step of applying a hair removal cosmetic composition of claim 10 to an animal. A food composition for hair removal containing an extract of the yeduk tree.