KR100733324B1 - Compositions for Preventing Hair Loss or Stimulating Hair Growth - Google Patents

Abstract

The present invention relates to a composition for preventing hair loss or promoting hair growth, which comprises the extract of Polygonatum odoratum or the solvent fraction of the product. The hair loss prevention or hair growth composition of the present invention promotes keratinocyte cell proliferation and ultimately plays a very good role in preventing hair loss and promoting hair growth in a living body. Moreover, the composition of the present invention is very safe for the human body because it uses the extract or fraction of the wild oleoreum already proved biosafety as an active ingredient.

Hair, keratinocytes, hair growth, hair loss, hair growth

Description

Compositions for preventing hair loss or promoting hair growth {Compositions for Preventing Hair Loss or Stimulating Hair Growth}

1 is a representative photograph when 19 days have passed after removing hair from a mouse, and is a photograph of a mouse used as a control group.

2 is a representative photograph when 12 days have passed after depilation and hair loss-inducing substance treatment for 7 days.

Figure 3 shows the degree of hair growth promotion of the mouse according to the treatment of the round hexane fraction, a representative picture of the group treated with the round hexane fraction extract for 12 days after depilation and hair loss-inducing material treatment for 7 days.

The present invention relates to a composition for preventing hair loss or promoting hair growth, which comprises the extract of the hulling or the hulling fraction.

In modern society that emphasizes appearance, hair is not only a means of protecting the brain and the skulls surrounding it, but also has a growing interest in hair growth, hair growth and hair loss prevention, as it has a decisive influence on human impression and appearance. Human hair is about 100,000-150,000 pieces, and each hair has a different growth cycle. The hair growth cycle consists of three stages: the anagen stage in which hair is most actively growing, the catagen stage in which hair degeneration begins, and the telogen stage in which hair growth stops or enters rest. (Buhl AE. Lab. Invest . 62 (1): 104-107 (1990)). This cycle is repeated over three to six years, resulting in an average of 50-200 hairs per day. Generally, the term alopecia refers to the increase in the number of hairs that fall abnormally due to shortening of the hair growth rate in the growth phase and more hair in the degenerative or resting phase.

The causes of hair loss include excessive male hormone action, excessive sebum secretion, poor blood circulation, peroxide, bacteria, deterioration of scalp function, genetic factors, aging, stress, etc. It is unknown. Recently, due to nutritional imbalances due to changes in diet, environmental pollution, and stress caused by social environment, the number of people who are suffering from hair loss is increasing, and the age is also decreasing, and the hair loss population of women is also increasing.

Conventionally, in the treatment or prevention of such alopecia, a female hormone-based preparation or minoxidil, finastide, trichosaccharide, which promotes blood circulation, strengthens hair follicle function, moisturizes the scalp and inhibits male hormones. Formulations containing the same have been developed. The mechanism of action of minoxidil on the hair growth effect is not clear, but it is thought to induce hair growth due to the increase of nutrient supply through vasodilation and potassium channel opening effect. Pinastide is a 5-α reductase. As an inhibitor, it is used as an agent for the treatment of prostate and hair loss by varying the dosage. Finastide is an excellent drug in terms of convenience and efficacy, but the reagents used to prepare it are expensive or highly toxic, causing problems in manufacturing costs or polluting the environment. In particular, the purity of the target product may be reduced because it is not easy to remove by-products. In addition, there is a problem that mass production is difficult by using a reagent or an active derivative that activity is easily inhibited by water.

Meanwhile, keratinocytes are the major constituent of about 95% of epidermal cells and originate in the ectoderm. Because these cells function not only to produce the epidermal stratum corneum, but also to produce complex fibmental proteins called keratins, which form the structural proteins of hair and armor, to promote hair growth through keratinocyte proliferation. Many attempts have been made (Jang JH. Biotechnol. Lett ., 27 (11): 749-752 (2005)). In addition, studies on skin regeneration through the proliferation of keratinocytes have been made (Akira ito et al. J. Biosci. Bioeng. , 95 (6): 589-593 (2003)).

Korean Patent No. 22442 discloses a homogeneous dissolution of follicular hormone 0.0033-1.0 mg, adrenal cortex hormone 0.018-2.75 mg and vitamin B ₂ 0.085-25.5 mg in 100 ml of purified water, and the weight ratio of follicle hormone / adrenal cortex hormone. To disclose a hair regrowth composition is maintained in the range of 0.01-4.0. Korean Patent No. 157667 discloses a hair regrowth and hair growth agent characterized in that it contains at least one extract of plant extracts of the genus Shrimp orchid, rock orchid, or other imitation caliber of an orchid family as an active ingredient. In addition, Korean Patent No. 165938 discloses a hair growth agent composition containing a dichloromethane extract or a fraction thereof of Cheongho as an active ingredient. On the other hand, Korean Patent No. 300816 discloses a hair growth agent or a wool agent containing N-acylamino acid ester having an acyl group having 13,15 and 17 carbon atoms as an active ingredient.

Throughout this specification, many papers and patent documents are referenced and their citations are indicated. The disclosures of cited papers and patent documents are incorporated herein by reference in their entirety, and the level of the technical field to which the present invention belongs and the contents of the present invention are more clearly explained.

The present inventors screened thousands of natural plant extracts or fractions in order to develop novel substances capable of preventing hair loss or promoting hair growth, and as a result, the extracts and the extracts of keratinocytes promoted keratinocyte cell proliferation. The present invention was completed by confirming at the animal individual level that the extract or fraction can be usefully used for promoting hair growth.

Accordingly, it is an object of the present invention to provide a composition for preventing hair loss or promoting hair growth, which includes the extract of the hulling oleander or the fraction of the hulling.

Other objects and advantages of the present invention will become apparent from the following detailed description, claims and drawings.

According to an aspect of the present invention, the present invention provides a composition for preventing hair loss or hair growth comprising the extract of the dongleule or the dongleol solvent fraction as an active ingredient.

The present inventors screened thousands of natural plant extracts or fractions in order to develop novel substances capable of preventing hair loss or promoting hair growth, and as a result, the extracts and the extracts of keratinocytes promoted keratinocyte cell proliferation. And it was also confirmed at the animal individual level that the extract or fraction can be usefully used for promoting hair growth.

" Polygonatum odoratum " as a material of the extract or fraction used as the active ingredient of the present invention is a perennial herbaceous plant belonging to the Liliaceae, distributed in the mountains and the nation, and blooms in June-July . Young shoots are also used for food, and rhizome is widely used in oriental medicine and civilian for nourishment and tonic purposes, and to improve various weakness, malnutrition, cough caused by pulmonary tuberculosis and coughing due to diabetes It is used as a medicine. It contains a lot of mucus in the roots and stems, and contains steroid glycosides, small amounts of alkaloids and asparagine. Diabetes improvement effects (Sook-Jae et al., Korean J. Soc. Food SCI. 13 (1): 47-55 (1997)), etc. have been reported as the efficacy of the donggulre, and Korea Patent Publication No. 1999-12078 A method for producing a tea with excellent palatability has been described, and known for inhibiting lipid peroxide formation of the hulling extract and fractions (Kim Juhyang et al., Yakhak) Hoeji 46 (4): 242-246 (2002)). However, there is no known keratinocyte growth promoting effect or hair growth promoting effect of the extracts and fractions.

As used herein, the term "hamle extract" means that it is obtained by extracting from various organs or parts (eg, roots, stems, leaves, flowers and fruits) of a manure, preferably means an extract obtained from leaves, roots or stems. Most preferably, it means an extract obtained from the stem of the gorge. Extracts are conventional extraction solvents known in the art, preferably (a) water, (b) anhydrous or hydrous lower alcohols having 1 to 4 carbon atoms (e.g. methanol, ethanol, propanol, butanol, normal-propanol, iso -Propanol and normal-butanol, etc.), (c) the mixed solvent of the lower alcohol with water, (d) acetone, (e) ethyl acetate, (f) chloroform, (g) 1,3-butylene glycol, ( h) hexane, (i) diethyl ether, or (j) butyl acetate.

As used herein, the term "dungle solvent fraction" refers to an active fraction obtained by fractionation having the desired activity in the present invention from the dungle extract using a solvent different from the solvent used in the extraction. The solvent used to obtain the fulfil solvent fraction may be any extraction solvent conventionally used in the art, and preferably, (a) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (e.g. methanol, ethanol, propanol, Butanol, normal-propanol, iso-propanol and normal-butanol, etc.), (b) a mixed solvent of the lower alcohol with water, (c) acetone, (d) ethyl acetate, (e) chloroform, (f) 1, 3-butylene glycol, (g) hexane, (h) diethyl ether, or (i) butyl acetate.

The term "extract" as used herein has the meaning commonly used in the art as crude extract as described above, but broadly also includes the solvent fractions described above.

The roundle extract or solvent fraction of the present invention includes not only those obtained by using the solvent described above, but also those obtained by further applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through the purification method are also included in the extracts or fractions of the present invention.

The extracts or fractions of the present invention may be prepared in powder form by additional processes such as distillation under reduced pressure and freeze drying or spray drying.

The composition of the present invention works very effectively in preventing hair loss or promoting hair growth. As used herein, the term "anti-hair loss" or "promoting hair growth" is used in the same sense, which has the same meaning as another term wool or hair growth promotion used in the art.

According to a preferred embodiment of the present invention, the composition of the present invention may be provided as a pharmaceutical composition, cosmetic composition or food composition.

When the composition of the present invention is made into a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical compositions of the present invention may be administered orally or parenterally, preferably by parenteral administration, more preferably by topical application by application.

Suitable dosages of the pharmaceutical compositions of the present invention may vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion and response to the patient. Can be. Dose of the extract and fractions, which are bioactive substances included in the pharmaceutical composition of the present invention is 0.001-100 mg / kg, preferably 0.1-100 mg / kg, more preferably 5-50 mg / It is in the kg range.

The pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulation may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of extracts, powders, powders, granules, tablets or capsules, and may further comprise dispersants or stabilizers.

When the composition of the present invention is prepared as a cosmetic composition, the composition of the present invention includes not only the above-mentioned extracts or fractions but also components commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, Conventional adjuvants such as pigments and perfumes, and carriers. In addition, the composition of the present invention can be used by mixing together the woolen or hair raising agents that have been conventionally used as long as they do not impair the action (hair growth by the hile extract), in addition to the above-mentioned extracts or fractions.

As the carrier, purified water, monohydric alcohols (ethanol or propyl alcohol), polyhydric alcohols (glycerol, 1,3-butylene glycol or propylene glycol), higher fatty acids (palmitylic acid or linolenic acid), fats and oils (wheat embryo oil, Camellia oil, jojoba oil, olive oil, squalene, sunflower oil, macadamia peanut oil, avocado oil, soybean hydrogenated lecithin or fatty acid glycerides), and the like. In addition, surfactants, bactericides, antioxidants, ultraviolet absorbers, anti-inflammatory agents and refreshing agents may be added as necessary.

Surfactants include polyoxyethylene, hardened castor oil, polyoxyethylene, oleyl ether, monooleic acid polyoxyethylene, polyoxyethylene, glyceryl monostearate, monostearate sorbitan, monooleate polyoxyethylene, sorbitan, sucrose Fatty acid ester, hexaglycerin monolauric acid, polyoxyethylene reduced lanolin, POE, glyceryl pyroglutamic acid, isostearic acid, diester, N-acetyl glutamine and isostearyl ester may be optionally included.

Fungicides may be optionally included in the group consisting of hydroxythiol, trichromic acid, chlorohexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid and zinc pyrithaone. .

Antioxidants can use any of butylhydroxyanisole, glutaric acid, molten acid propyl and erythorbic acid.

UV absorbers include benzophenones such as dihydroxy benzophenone, melanin, ethyl paraaminobenzoic acid, 2-ethylhexyl ester of paradimethylaminobenzoic acid, synoxite, 2-ethylhexyl ester of paramethoxy cinnamic acid, and 2- (2-hydroxy) Oxy-5-methylphenyl) benzotriazole, urokanoic acid and metal oxide fine particles can be used.

As the anti-inflammatory agent, dipotassium glytilinate or allantoin may be used, and as the refreshing agent, capsicum tink or 1-menthol may be used.

The formulation of the composition is any formulation that can combine the extract or fraction as an active ingredient in the form of hair loss prevention or hair growth cosmetics in the form of hair tonic, hair cream, hair lotion, hair shampoo, hair rinse, hair conditioner, hair Sprays, hair aerosols, pomades, powders, gels and the like can be prepared in various forms such as solutions, sol gels, emulsions, oils, waxes, aerosols, but is not limited thereto.

When the composition of the present invention is prepared as a food composition, as an active ingredient, as well as the extracts or fractions, the components commonly added during food preparation, for example, proteins, carbohydrates, fats, nutrients, seasonings and Contains flavors. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents (tauumatin, stevia extract (for example rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.

 For example, when the food composition of the present invention is prepared with a drink, the citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, etc. Can be included.

The hair loss preventing or hair growth composition of the present invention promotes keratinocyte cell proliferation and ultimately plays an excellent role in preventing hair loss and promoting hair growth in a living body. Moreover, the composition of the present invention is very safe for the human body because it uses the extract or fraction of the wild oleoreum already proved biosafety as an active ingredient.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it is to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. Will be self-evident.

Example 1 Preparation of Roundabout Extract

150 g of dongle stems were dried at 50 ° C. for 72 hours, pulverized and powdered, and extracted by chilling with 1,500 ml of 70% ethyl alcohol for 7 days. The extract was filtered and concentrated to prepare 32.3 g of a crude extract.

Example 2: Preparation of Soluble Fractions

32.3 g of crude crude extract of Example 1 was dissolved in 100 ml of distilled water, extracted three times with 100 ml of hexane, and the supernatant was filtered and distilled to obtain 0.2 g of soluble fraction of fulgus hexane.

Example 3: Preparation of Soluble Fraction of Ethyl Acetate

The water-soluble fraction obtained in Example 2 was extracted three times with 100 ml of ethyl acetate and the supernatant was filtered and distilled to obtain 0.2 g of an ethyl acetate soluble fraction.

Example  4: Round  Butyl Alcohol Soluble Fraction  Produce

The water-soluble fraction obtained in Example 3 was extracted three times with 100 ml butyl alcohol and the supernatant was filtered and distilled to obtain 0.5 g of a butyl alcohol soluble fraction.

Experimental Example  One: Keratinocyte  Cell proliferation activity experiment

Cell Proliferation Activity According to the Extract of Solvent Extract and Solvent Fraction

 SCC-25 cell lines purchased from ATCC and HaCaT cell lines derived from humans distributed by Korea University Biotechnology Institute were prepared using DMEMM: F-10 (1: 1) medium containing 10% fetal bovine serum (FBS) in 96-well plates. After culturing (SCC-25 cell line) or (DAC medium containing 10% FBS) (HaCaT cell line), and then replaced with a medium without FBS, the extracts and fractions were treated by concentration and 72 hours (SCC-25 Or 48 hours (HaCaT), and then 10 μl of CCK-8 reagent (Dojindo) was added thereto, followed by 3 hours of incubation, and the absorbance was measured at 450 nm. The effect is expressed as% of absorbance of the untreated control group.

The experimental results show the proliferation rate of keratinocyte cells in% compared to the control group when treated with Examples 1, 2, 3 and 4.

Sample (Ethyl Alcohol Extract) Keratinocyte growth rate (% control) Control 100 10 μg / ml 148.3

Sample (hexane Fraction) Keratinocyte growth rate (% control) Control 100 1 μg / ml 106.1 5 μg / ml 141.8 10 μg / ml 158.0 30 μg / ml 138.1

Sample (Ethyl Acetate Fraction) Keratinocyte growth rate (% control) Control 100 1 μg / ml 104.6 5 μg / ml 111.8 10 μg / ml 126.3

Sample (Butyl Alcohol Fraction) Keratinocyte growth rate (% control) Control 100 1 μg / ml 100.8 5 μg / ml 96.1 10 μg / ml 125.8 30 μg / ml 111.7

As can be seen in Tables 1 to 4, the extracts and fractions of the present invention generally induced keratinocyte cell proliferation in a concentration-dependent manner, in particular, the extract of dongleul hexane was very excellent in keratinocyte cell proliferation effect.

Experimental Example 2: Hair growth promoting effect experiment of the unglong hexane fraction

(1) Experimental method

To prepare a hair growth test animal model, 15 g polyethylene glycol (PEG) 3350 (Fluka) and 85 g polyethylene glycol 400 were dissolved by heating to 65 ° C. in a water bath, and then dehydrotestosterone (hair loss-inducing substance) was added thereto. dihydrotestosteron: DHT, TCI Co.) 20 mg / kg bw was added to mix well to finally prepare a 15% polyethylene glycol ointment formulation. C57BL / 6 mice (25 ± 5 g, females, n = 10) were used for the experimental animals. Hair removal was performed beforehand and the ointment was treated for 7 days, so that the anagen stage before keratinocytes was expanded. Caused. Dihydrotestosterone (DHT) 20 mg / kg b.w. And spray formulation prepared by dissolving 50 mg / kg bw of Donggulle hexane fraction, the most effective of the fractions, in a solvent mixed with 80% ethanol and 20% glycol once a day for 10 days to observe hair growth. It was. As a control group, the experimental animal was not treated with a round hexane fraction extract.

(2) Experiment result

As a result of observation after 19 days after depilation of experimental animals, it was confirmed that hair was normally grown in the depilation group (FIG. 1), and treated with dihydrotestosterone (DHT) for 7 days and after 12 days. Although hair did not grow even after elapsed time (FIG. 2), after treatment with dihydrotestosterone (DHT) for 7 days and observation for 2 days, the time was increased in the group treated with the soluble fraction of the unglong hexane obtained in Example 2 for 10 days. Over time, hair growth was observed similarly to the normal group (FIG. 3). Therefore, it can be seen that the round hexane fraction of the present invention has a very good hair growth promoting effect even in the biological test.

As described above, the present invention provides a composition for preventing hair loss or promoting hair growth, which includes the extract of the donggule or the dongleul fraction. The hair loss prevention or hair growth composition of the present invention promotes keratinocyte cell proliferation and ultimately plays a very good role in preventing hair loss and promoting hair growth in a living body. Moreover, the composition of the present invention is very safe for the human body because it uses the extract or fraction of the wild oleoreum already proved biosafety as an active ingredient.

Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that the specific technology is merely a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (5)

A composition for preventing hair loss or promoting hair growth, comprising an extract of Polygonatum odoratum or a solvent fraction, as an active ingredient, and having an action of promoting the proliferation of keratinocytes. The method of claim 1, wherein the solvent extract fraction of the donggulle extract is an anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms, a mixed solvent of the lower alcohol and water, acetone, ethyl acetate, chloroform, butyl acetate, 1,3-butyl Hair loss prevention or hair growth promoting composition, characterized in that obtained by fractionation with len glycol, hexane or diethyl ether. delete The composition for preventing hair loss or promoting hair growth according to claim 1, wherein the composition is a pharmaceutical composition. The composition for preventing hair loss or promoting hair growth according to claim 1, wherein the composition is a cosmetic composition.

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