KR20170134104A - Composition for promoting the hair growth comprising Hederagenin - Google Patents

Abstract

The present invention relates to a composition for promoting hair loss prevention and hair growth, comprising hederagenin or a cosmetically or pharmaceutically acceptable salt thereof as an active ingredient, and more preferably to a cosmetic or pharmaceutical composition. In detail, the active ingredient hederagenin according to the present invention can provide excellent hair loss prevention effect and hair growth promoting effect through a molecular mechanism related to the inhibition of the male hormone receptor signaling pathway (the androgen receptor signaling pathway).

Description

[0001] The present invention relates to a composition for preventing hair loss and promoting hair growth,

The present invention relates to a composition for promoting hair growth, and more particularly, to a composition for preventing hair loss and promoting hair growth for promoting hair growth containing a component for inducing new growth or promotion of hair growth.

Hair is an important part of the process of increasing interest in beauty as the age changes. Hair is a thin, exfoliated structure produced from the surface of the skin. It acts as a cushion against external impact, protects the human body from external stimuli such as direct sunlight, cold, friction, danger, and discharges the heavy metals such as arsenic, mercury and zinc harmful to the body to the outside of the body. The side is also being emphasized. However, many people are complaining of hair loss due to various causes, including dietary changes and increased internal and external stress.

Human hair has about 100,000 to 150,000 hairs, and each hair has a different growth period. The hair growth cycle consists of three stages: the anagen stage where hair grows most actively, the catagen stage where hair starts to degenerate, and the telogen stage where hair growth stops or rests. .

In general, alopecia refers to an increase in the number of abnormal hair loss due to shortening of hair growth rate in the growing period and increased number of hair in the retrogressive or resting period among these cycles.

The causes of hair loss include male hormone hyperinsulinism, excessive secretion of sebum, poor blood circulation, peroxidation, hypofunction of the scalp due to bacteria, genetic factors, aging, and stress. It is not revealed.

Male hormones play an important role in the growth and elimination of hair follicles. Of the factors regulated by male hormones, TGF-β plays an important role in the inhibition of hair growth by male hormones and the induction of regrowth in hair follicles (Tsuji Y, Denda S, Soma T, Raftery L, Momoi T, Hibino T, A potential suppressor of TGF-beta delays in hair follicles, J Investig Dermatol Symp Proc 2003: 8 (1): 65-68) . In other words, it is expressed in the dermal papilla cells of the hair follicle by the male hormone, causing the apoptosis of the hair follicle stromal cells and extracorporeal keratinocytes, and causing the hair follicle as a regressor, so that when the amount of TGF- (A) and (B), and (C), and (C), respectively. In the present study, we investigated the clinical and histopathologic characteristics of human androgenetic dehiscence Korean Journal of Hairdressing, 2007: 13 (2): 799-810). Thus, TGF-β is known to inhibit follicular growth.

Hederagenin is a kind of triterpenoid extracted from Hedera helix, which is called Western songa.

Prior to the present invention, there is no known effect of hederagen against hair loss prevention and hair growth promoting effects due to anti-male hormone activity.

As a therapeutic agent for the treatment or prevention of alopecia developed so far, there are a female hormone-based agent, minoxidil, finasteride, tricosaccharide, etc. for promoting blood circulation, enhancing hair follicle function, scalp moisturizing and male hormone suppression, And preparations containing trichosaccharide. Minoxidil, a typical anti-depilation treatment, increases blood flow to the scalp. Pinasteride, an oral hair loss treatment, functions to inhibit the activity of 5α-reductase and reduce the production of DHT, the active male hormone. However, these preparations have many limitations in use due to side effects or precautions for use.

Accordingly, the present invention aims to solve the above-mentioned problems, and to provide a new useful use of a new active ingredient, i.e., an active ingredient, which is less harmful to the human body and can act effectively for promoting hair growth or hair growth.

In other words, a problem to be solved by the present invention is to provide a composition comprising the active ingredient having excellent efficacy as an active ingredient.

In order to solve the above problems, the present invention provides a composition for promoting hair growth or hair growth, comprising a compound represented by the following general formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[Chemical Formula 1]

That is, the present invention provides a new use for promoting hair growth or hair growth of the compound represented by the above-mentioned formula (1) or a cosmetically acceptable salt thereof.

The inventors of the present invention have found that, in view of the disadvantages such as the side effects or the precautions on use of the conventional hair loss therapeutic agents and the weak effects of the natural extracts, the male hormone receptors, which are safe for the human body, And a composition for inhibiting the signal transduction (androgen receptor signaling pathway).

The present invention preferably provides a composition for treating, preventing or ameliorating alopecia areata. Alopecia can be caused by various causes such as genetic cause and environment. The present invention is particularly effective for alopecia, which is caused by stimulation of the hair follicle with a modified male hormone such as dihydrotestosterone (DHT) Lt; / RTI >

One embodiment of the present invention can promote Wnt / beta-catenin signaling, enhance the proliferation or differentiation of dermal papillary cells or inhibit senescence, To thereby provide a composition having the effect of preventing hair loss or accelerating hair growth.

The compound represented by Formula 1 is hederagenin, which can be isolated from a natural source such as Hedera helix, but is not limited thereto, and may be chemically synthesized by a method known in the art, Materials can be used.

In addition, the compounds may be in the form of a solvate, a pro-drug or a pharmaceutically acceptable salt thereof, wherein the solvate preferably comprises a hydrate and an ethanolate.

&Quot; Inhibition of signal transduction of male hormone receptor " of the present invention means inhibition of hair loss induced by intracellular male hormone receptor signaling including hair follicle cells.

The "hair loss mechanism" in the present invention is as follows. When male hormone binds to the male hormone receptor and signal transduction occurs, TGF-β production is promoted in cells including hair follicle cells. At this time, TGF-beta binds to the TGF-beta receptor present on the cell surface, resulting in intracellular signal transduction. As a result, expression of various hair-related genes, in which TGF-beta receptor acts in the cell, Of the stromal cells and outer root keratinocytes. As a result, when the amount of TGF-β increases, induction of apoptosis of hair matrix cells and outer root cells induces apoptosis of the growing hair follicle, so that the resting hair follicle is increased and the growing hair follicle becomes a retrograde hair follicle It has been reported that hair is easily changed into thin and short hair.

The composition for inhibiting the signal transduction of the male hormone receptor of the present invention can be administered on the basis of the pathogenesis of such hair loss, so that it can be used as a component of an external skin preparation for improving hair loss prevention and promoting hair growth.

In addition, the composition for inhibiting the signal transduction of male hormone receptor of the present invention can be used as a component of an external preparation for skin restorative skin and can be used as a component of a skin external preparation for scarring such as burns and acne. However, May be used for the amelioration of other diseases or conditions requiring inhibition of receptor production.

In the present invention, "hair loss prevention" means that the phenomenon of hair falling off the hair follicle or scalp is inhibited or weakened.

In the present invention, the term "hair growth" means that the thickness of the hair (hair) generated increases or affects the speed of growth of the hair.

In the present invention, the term " promoting hair growth "means that hair is produced, and is used in a broad sense to increase the hair generation rate and production amount. It also means that the hair follicle function is strengthened, the hair dropping and generation cycle is shortened, and the number of hairs growing in the hair follicle is increased.

The "pharmaceutically acceptable salt" of the present invention may be an acid addition salt formed using an organic acid or inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, The present invention also relates to the use of a compound selected from the group consisting of malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, gluconic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, Benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid-based salts, and inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid and boric acid-based salts. Preferably in the hydrochloride or acetate form, more preferably in the hydrochloride form.

The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable salt of hyderagenin, an extract containing it, or a fraction thereof. The term " pharmaceutically acceptable " as used herein refers to those which are physiologically acceptable and do not normally cause an allergic reaction or a similar reaction when administered to humans, and the salts include pharmaceutically acceptable free acids acid is preferred.

The above-mentioned acid addition salts may be obtained by a) directly mixing the compound of formula 1 and an acid, or b) dissolving and mixing one of them in a solvent or a water solvent, or c) Lt; RTI ID = 0.0 > acid < / RTI > in a solvent and mixing them.

Separately, additionally saltable forms include, but are not limited to, the salts of gabapentin, gabapentin, pregabalin, nicotinate, adipate, hemimarate, cysteine, acetylcysteine, methionine, arginine, lysine, Aspartate and the like.

When the compound of Chemical Formula 1 of the present invention is used as a medicine, it may further contain one or more active ingredients showing the same or similar functions. For example, a known hair growth promoting or hair growth promoting component may be included. In this case, the effect of promoting hair growth or promoting hair growth of the composition of the present invention may be further enhanced. When the above ingredients are added, skin safety, easiness of formulation, and stability of effective ingredients can be considered according to the combined use.

In addition, the pharmaceutical composition composition for preventing hair loss, promoting hair growth or hair growth of the present invention may further comprise a pharmaceutically acceptable carrier.

The term "pharmaceutically acceptable" of the present invention refers to compositions and molecules that are physiologically acceptable and typically do not cause unexpected reactions when administered to humans. Preferably, as used herein, the term " pharmaceutically acceptable "means that it is approved by other commonly known pharmacopoeias for use in mammals and especially humans.

Pharmaceutically acceptable carriers include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose , Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil, and the like. The composition comprising the compound of formula (I) or a pharmaceutically acceptable salt thereof as described above may be formulated together with a carrier.

The pharmaceutical composition of the present invention can be administered parenterally, and can be administered in the form of a general pharmaceutical preparation, for example, various forms of parenteral administration at the time of clinical administration. In the case of formulation, the filler, , A wetting agent, a disintegrant, a surfactant, and the like.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, or lyophilisers. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent.

The pharmaceutical composition of the present invention can provide a desirable hair growth effect or hair growth promoting effect when an effective amount of the compound of Formula 1 is included. In the present invention, the effective amount means the amount of the compound capable of exhibiting hair growth promoting effect, hair growth effect or hair loss prevention effect. An effective amount of the compound of formula (1) contained in the composition of the present invention will vary depending on the form in which the composition is commercialized, how the compound is applied to the skin, and the time on the skin. For example, when the composition is commercialized as a medicine, the composition of the present invention may contain the compound of formula (1) at a higher concentration than a product such as a shampoo, a hair conditioner, and a hair pack that is routinely applied to skin. Therefore, the daily dosage is 0.1 to 100 mg / kg, preferably 1 to 50 mg / kg, more preferably 5 to 20 mg / kg, based on the amount of the compound of formula (1) 6 times a day.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention can also provide a formulation for external skin preparation for promoting hair growth or hair growth comprising the compound of formula (1) as an active ingredient.

When the compound of formula (1) is used as an external preparation for skin, it may further comprise at least one selected from the group consisting of fatty substances, organic solvents, solubilizers, thickeners and gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, , Water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or external preparations for skin And any other ingredients used in the skin sciences. The components can also be introduced in amounts commonly used in the field of dermatology.

When the compound of Formula 1 is provided as an external preparation for skin, it may have a formulation that is applicable to hair, such as, but not limited to, gel, cream, patch, or spray.

The present invention can also provide a cosmetic composition for promoting hair growth comprising the compound of Formula 1 as an active ingredient.

When the compound of Chemical Formula 1 is used as a cosmetic, the cosmetic product containing the compound of Chemical Formula 1 as an active ingredient may be prepared in the form of a general emulsified formulation and a solubilized formulation. For example, they may have formulations such as sprays, hair gels, hair packs, shampoos, hair conditioners, hair lotions, hair essences, patches or sprays.

The cosmetic composition may further contain, in addition to the compound of Formula 1, a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, , Ionic or nonionic emulsifiers, fillers, sequestering and chelating agents, preservatives, vitamins, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, lipid vesicles or cosmetics And may contain adjuvants commonly used in the cosmetics field, such as any of the other ingredients.

Preferably, the composition of the present invention can be prepared in any form that can be applied to the scalp, such as liquid, cream, paste, or solid, and can be prepared by adding ordinary additives such as shampoo, hair conditioner, hair lotion, Liquid type hair growth type, and the like, including aerosol types of these formulations.

The composition of the present invention contains 0.0001 to 10% by weight, preferably 0.005 to 5% by weight, more preferably 0.01 to 3% by weight, of the compound of Formula 1 or a pharmaceutically acceptable salt thereof, .

If the content of the compound of formula (1) is less than 0.0001 wt%, the effect of promoting the induction of hair growth may not be satisfactory. If the content of the compound is more than 10 wt%, the effect is not sufficiently exhibited.

The composition containing the compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof exhibits hair growth promoting effect.

In addition, it exhibits an effect of promoting hair growth as well as an effect of preventing hair loss.

The composition containing the compound of formula (I) of the present invention or a pharmaceutically acceptable salt thereof can be used as safe and excellent cosmetic ingredients and pharmaceutical ingredients.

In addition, the composition of the present invention is free from side effects of conventional hair loss treatment agents and provides a superior hair growth or hair loss prevention effect while being safe for human body.

FIG. 1 is a graph showing the expression of PSA, a prostate cancer specific antigen, by the concentration of hederagenin in LNCaP, a human prostate cancer cell line, and the relative Luciferase activity (RLU) value measured using the Dual Luciferase assay as a transcriptional activity test.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the embodiments described below. The embodiments of the present invention are provided by way of example to facilitate a specific understanding of the present invention.

In the following Experimental Examples and Examples of the present invention, Sample 1 is hederagenin (CAS No. 465-99-6) and purchased from Sigma Aldrich.

Experimental Example 1 Confirmation of Inhibition of Androgen Receptor Signal Transduction by Anti-Androgen Receptor Transcriptional Activity Test

In this experiment, an androgen-dependent human prostate cancer cell line LNCaP is used. LNCaP cell lines were maintained in subculture using RPMI1640 and 10% fetal bovine serum (Gibco BRL, Gaithersburg, MD, USA). For transcriptional assays, 400,000 cells per well are seeded in a 24-well plate and the culture medium is exchanged with phenol-red free RPMI1640 containing 5% charcol-stripped fetal bovine serum. At this time, co-transfection of a vector containing a prostate-specific antigen (PSA) promoter and firefly luciferase, a thymidine kinase promoter for quantification and a vector containing renila luciferase Incubate in a 37 ° C incubator for 24 hours. Lipofectamine 2000 and OPTI-MEM are used for transduction. Twenty-four hours later, hederagenin was treated with 10 nM DHT and incubated again for 24 hours. The degree of inhibition of increased Luciferase activity by DHT was measured using Dual-Luciferase assay system (Promega). The results are as follows: RLU (relative luciferase activity) value obtained by dividing the expression value of firefly luciferase by renila luciferase was determined, and the RLU value increased by 10 nM DHT treatment was set at 100%. The RLU value decreased by the sample treatment (%). ≪ / RTI > Bicalutamide (casodex) was used as an anti-androgen positive control, and the results are shown in FIG. 1 and Table 1.

Name of sample Untreated control group Positive control group hederagenin Bicalutamide 5 ppm 5 ppm 10 ppm Inhibition rate (%) - 83.32% 12.15% 30.91%

As shown in Table 1 above, the heparanin according to the present invention is smaller than bicalutamide, which is a positive control, but significantly decreased the expression of PSA, thereby inhibiting the signal transduction of androgen receptor signal.

From these results, it was confirmed that the hederagenin of the present invention is a naturally derived component and can obtain the effect of inhibiting the signal transduction of the androgen receptor similarly to bicalutamide.

Various formulation examples of the composition according to the present invention will be described in detail based on the above-mentioned effect test results. It should be apparent to those skilled in the art, however, that these formulation examples are merely examples of the composition of the present invention and that the composition of the present invention is not limited to these formulations only.

Formulation Example 1: Hair tonic

Hair tonics were prepared according to the following prescriptions in a conventional manner.

Compounding ingredient Weight ratio (%) ethanol 55 Castor oil 5 glycerin 3 Pyrrotonol amine 0.1 Hederagenin 0.1 Incense and pigment Suitable amount Purified water Balance (100 total)

Formulation Example 2: Shampoo

The shampoo was prepared in the usual manner according to the prescription below.

Compounding ingredient Weight ratio (%) Polyquaternium 0.5 Sodium lauryl sulfate (30%) 20 Sodium polyoxyethylene lauryl sulfate 30 Coconut oil fatty acid diethanolamide 3 Quaternary ammonium cationic surfactant 2 Carbopol-1342 0.3 Paraoxybenzoic acid ester 0.2 Hederagenin 0.1 Incense and pigment Suitable amount Purified water Balance (100 total)

Formulation Example 3: hair  Lotion

The hair lotion was prepared in a conventional manner according to the following prescription.

Compounding ingredient Weight ratio (%) Cetostearyl alcohol 2 Stearyltriethylammonium chloride 2 Hydroxyethyl cellulose 0.5 Pyrrothonol amine 0.1 Hederagenin 0.1 Incense and pigment Suitable amount Purified water Balance (100 total)

≪ Experimental Example 2 > Hairiness test of hair growth composition 1 (hair tonic)

The hair growth composition 1 (hair tonic) of the present invention was used for hair and scalp for six months, five times a week for a total of 20 men and women in whom the number of hairs was significantly lower than that of normal hair, Respectively. After use, the degree of improvement (very good: +3, better: +2, slightly better: +1, no change: 0, slightly worse: -1, worse; -2, and worse; -3) were assessed as average after 3 months and 6 months.

The evaluation results are shown in Table 5 below.

Thickness of hair Density Resilience Overall rating Average score after 3 months 2.3 ± 0.3 2.2 ± 0.2 2.4 ± 0.4 2.3 ± 0.2 Average score after 6 months 2.5 ± 0.3 2.7 ± 0.2 2.6 ± 0.2 2.6 ± 0.2

As shown in Table 5, when the hair thickness, hair density, and elasticity were all considered in the group treated with haderagenin compared to the untreated group, an average of 2.3 was obtained after 3 months, After 6 months, the value of 2.6 was obtained. However, in the case of the untreated group, the average value of 0 ± 0.3 was obtained as a whole after 3 months and the value of 0 ± 0.2 was obtained after 6 months.

From the above results, it was found that the hair growth effect was superior to that of the untreated group.

Claims (5)

A compound represented by Formula 1 below; Or a pharmaceutically or cosmetically acceptable salt thereof, as an active ingredient, for promoting hair loss, hair growth or hair growth.
[Chemical Formula 1]

The composition of claim 1, wherein the composition is a compound represented by Formula 1; Or a pharmaceutically or cosmetically acceptable salt thereof, in an amount of 0.0001 to 10% by weight based on the total weight of the composition. 2. The composition of claim 1, wherein the composition inhibits the signaling of the androgen receptor and inhibits expression of the TGF-beta gene. 2. The composition of claim 1, wherein said composition treats, prevents or ameliorates androgen deprivation. The composition of claim 1, wherein the composition has a formulation of a shampoo, a hair conditioner, a hair lotion, a gel, a pack, an essence, a patch or a spray.

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