KR20210100259A - A composition for prevention or treatment of hair loss comprising 3,4-diamino-3-cyclobutene-1,2-dione deravitives - Google Patents

Abstract

The present invention relates to a composition for preventing, treating, or alleviating hair loss, comprising a 3,4-diamino-3-cyclobutene-1,2-dione derivative or a pharmaceutically acceptable salt thereof as an active component. A compound of the present invention promotes hair growth by proliferating dermal papilla cells and outer root sheath cells and switching from a telogen phase to an anagen phase of a hair growth cycle.

Description

Composition for preventing or treating hair loss comprising 3,4-diamino-3-cyclobutene-1,2-dione derivatives {A COMPOSITION FOR PREVENTION OR TREATMENT OF HAIR LOSS COMPRISING 3,4-DIAMINO-3-CYCLOBUTENE-1 ,2-DIONE DERAVITIVES}

The present invention relates to a composition for preventing, treating, or improving hair loss comprising a 3,4-diamino-3-cyclobutene-1,2-dione derivative or a pharmaceutically acceptable salt thereof as an active ingredient. The compound of the present invention promotes hair growth by proliferating dermal papilla cells and superficial root sheath cells and converting the resting state of the hair growth cycle to the anagen phase.

Human hair is an aggregate of about 100,000 individual hairs, and hair is produced by hair follicles. The hair follicle serves as a repository of stem cells capable of generating all the cell lines needed to reconstruct the hair follicle itself, the epithelium and the sebaceous glands. Hair follicles are composed of dermal papilla cells (DPC), hair germinal matrix cells, outer root sheath cells (ORS), inner root sheath cells (IRS), and the like.

The dermal papilla cells are the core cells responsible for the development and growth of hair, and are located at the bottom of the hair root, which is the subcutaneous root of the hair. In fact, when dermal papilla cells are collected from the scalp and transplanted after culturing, new hair grows. However, there are several difficulties in using dermal papilla cells as a treatment for hair loss. First, it is difficult to separate from the scalp, the culture conditions are difficult, and it is difficult to culture a sufficient amount of cells. In addition, there is a limit in that the hair regeneration ability is significantly reduced when a lot of culture.

Outer root sheath cells are cells that help the growth and development of hair and protect the hair, and are in contact with the basal layer, the innermost layer of the epidermis. Together with the inner root sheath, it protects the hair generated in the follicle, the lower part of the hair follicle, until keratinization is completed, and transports it to the epidermis. Outer root sheath cells are created by cell division near the hair bulb, transport hair to the epidermis and fall off from the scalp after fulfilling its role.

Hair goes through a three-stage cycle of anagen, catagen, and telogen, where it grows, maintains, and falls out. In the growth period, which is the period of hair growth, in the case of adults, hair grows on average about 0.3 mm per day, grows about 1 cm per month, and it is known that it usually lasts for 3 to 7 years. In general, for 10 to 14 days after the growth phase, overall hair follicle cell apoptosis (apoptosis) occurs and hair follicles are reduced in catagen, which is a stage in which the next growth phase is prepared for an average of 3 months (telogen). The hair falls out after passing through, and the reason the length of the hair is different depending on the part is that the duration of the growth phase, which is a unique characteristic of the hair follicle, is different for each part.

As described above, since human hair has a constant hair growth cycle, a constant number of hairs is always maintained. However, as hair loss progresses, the dermal papilla present in the hair root becomes smaller, and when the dermal papilla becomes smaller, the thickness of the hair becomes thinner, and the hair growth cycle is shortened at the same time. Therefore, as hair loss progresses, the hair becomes very thin, and the hair growth cycle becomes shorter and falls out after a little growth.

It is known that factors such as genetic causes and the action of male hormones, as well as endocrine diseases, nutritional deficiency, drug use, childbirth, fever, and severe physical and mental stress such as surgery, are the causes of hair loss. Recently, as well as male pattern hair loss, due to the increase in stress caused by changes in diet, social environment, etc., the female hair loss population is also increasing, and the age is also decreasing.

Currently, the most frequently used hair loss treatments in Korea include finasteride (trade name: Propecia®), dutasteride (trade name: Avodart®), and minoxidil (minoxidil; trade name: Minoxidil® or Rogaine®). Finasteride and dutasteride are 5α-reductase inhibitors that inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT). However, this product exhibits side effects such as decreased libido, erectile dysfunction, and loss of driving and performance. Meanwhile, in the case of minoxidil, the mechanism has not yet been fully elucidated, but it is a potassium channel opener that hyperpolarizes cell membranes, and through vasodilation and potassium channel opening, provides oxygen, blood, nutrients, etc. to the hair follicles. It is believed to make hair follicles healthy by increasing supply. However, this product also has side effects such as itching, erythema, skin irritation, eye irritation, etc. at the application site, and unwanted hair growth in other parts of the body other than the head is also observed. In addition, although hair transplantation has been recently attempted for patients with severe hair loss, high cost and side effects after the procedure are pointed out as limitations.

U.S. Patent Publication No. 2004/0147559 discloses a structure and a method for preparing a 3,4-di-amino cyclobutene-1,2-dione derivative, which is used to treat chemokine-mediated diseases such as inflammatory disorders and cancer. It talks about how to treat it. However, no research has been conducted on the relationship between the derivative and hair loss to date.

US Patent Publication No. 2004/0147559 (July 29, 2004)

An object of the present invention is to provide a composition capable of preventing, treating or improving hair loss by proliferating dermal papilla cells and superficial root sheath cells and inducing the growth phase of the hair growth cycle to promote hair thickness and length growth.

The present invention provides a composition for preventing, treating or improving hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula I]

In the above formula,

R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, alkyl, -OH, -COOH, -NHC(=O)Ra, -NRaRb, -C(=O)NRaRb, -C( =O)NHORa, -C(=O)NRaOH, or -OC(=O)Ra;

R _{6 To} R ₁₀ are each independently hydrogen or alkyl,

Ra or Rb is each independently hydrogen or alkyl.

The composition may be a pharmaceutical composition, a cosmetic composition or a food composition.

In one embodiment, the compound of Formula I or a pharmaceutically acceptable salt thereof proliferates dermal papilla cells and superficial root sheath cells, and converts the resting state of the hair growth cycle to the anagen phase, thereby allowing hair to grow thicker and longer. It can be used for prevention, treatment or amelioration.

The composition of the present invention promotes hair thickness and length growth by inducing proliferation of dermal papilla cells and superficial root sheath cells and entering the growth phase of the hair growth cycle, so it can be usefully used for preventing, treating or improving hair loss due to various causes.

1 and 2 are graphs showing the results of dermal papilla cell proliferation according to the concentration of the compound of Formula II.
3 is a graph showing the results of cell proliferation according to the treatment concentration of the compound of Formula II.
4 is a photograph taken before and after culturing according to the concentration of the compound of Formula II.
5 is a graph showing the length of hair after culture according to the treatment concentration of the compound of Formula II.
6 and 7 show the degree of hair regeneration according to the application concentration of the compound of Formula II.

Hereinafter, with reference to the accompanying drawings, embodiments and examples of the present invention will be described in detail so that those of ordinary skill in the art to which the present invention pertains can easily carry out. However, the present application may be embodied in various forms and is not limited to the embodiments and examples described herein.

Throughout this specification, when a part "includes" a certain component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.

The present invention is characterized in that it was discovered for the first time that the compound of formula (I) prevents or treats hair loss or promotes hair growth. In one embodiment, the present invention provides a pharmaceutical composition for preventing or treating hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient.

[Formula I]

In the above formula,

R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, alkyl, -OH, -COOH, -NHC(=O)Ra, -NRaRb, -C(=O)NRaRb, -C( =O)NHORa, -C(=O)NRaOH, or -OC(=O)Ra;

R _{6 To} R ₁₀ are each independently hydrogen or alkyl,

Ra or Rb is each independently hydrogen or alkyl.

In one embodiment, R 1 , R 2 , R 3 , R 4 or R 5 are each independently hydrogen, C ₁ -C ₆ alkyl, —OH, or —C(=O)NRaRb;

R _{6 To} R ₁₀ are each independently hydrogen or C ₁ -C ₆ alkyl,

Ra or Rb may each independently be hydrogen or C ₁ -C ₆ alkyl.

In another embodiment,

R ₁ or R ₂ are each independently —OH or —C(=O)NRaRb,

R ₆ and R ₁₀ are C ₁ -C ₆ alkyl,

R ₃ , R ₄ , R ₅ , R ₇ , R ₈ and R ₉ are hydrogen,

Ra and Rb may be C ₁ -C ₆ alkyl.

In another embodiment,

R ₁ is —OH,

R ₂ is -C(=O)NRaRb,

R ₆ is ethyl,

R ₁₀ is methyl,

R ₃ , R ₄ , R ₅ , R ₇ , R ₈ and R ₉ are hydrogen,

Ra and Rb may be methyl.

In another embodiment, the compound of the present invention may be a compound having the structure of Formula II:

[Formula II]

Accordingly, the present invention provides a pharmaceutical composition for preventing or treating hair loss comprising the compound of Formula II or a pharmaceutically acceptable salt thereof as an active ingredient. The chemical name of the compound of formula II is "(S)-2-hydroxy-3-(2-(1-(4-isopropyl-5-methylfuran-2-yl)propylamino)-3,4-dioxocyclobut-1-enylamino) -N,N-dimethylbenzamide".

As used herein, "pharmaceutically acceptable salt" refers to a salt that is pharmaceutically acceptable and retains the desired pharmacological activity of the parent compound. The salt is not particularly limited as long as it is pharmaceutically acceptable, and for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , benzenesulfonic acid, toluenesulfonic acid, naphthalenesulfonic acid, and the like can be used.

"Hair loss" of the present invention, regardless of the cause, refers to a state in which there is no hair in the site where hair should normally exist, and includes alopecia areata, hereditary androgen hair loss, telogen hair loss, traumatic hair loss, hair growth wall, pressure hair loss, It may be anagen phase alopecia, alopecia pityis, syphilitic hair loss, seborrheic hair loss, symptomatic hair loss, scarring hair loss, or congenital hair loss, but is not limited thereto.

The compound of the present invention promotes the proliferation of dermal papilla cells and/or superficial root sheath cells and induces hair growth phase, thereby preventing or treating hair loss.

"Treatment" of the present invention refers to any method of beneficially changing hair loss symptoms such as delaying or stopping hair loss by administration of the composition of the present invention, improving hair loss symptoms, or promoting hair growth and hair growth, such as lengthening or increasing the number of hair. means action.

The pharmaceutical composition of the present invention may be administered parenterally or orally according to a desired method, and the dosage may vary depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of disease, etc. Its scope is diverse. In addition, the therapeutically effective amount of the composition may vary depending on the administration method, the target site, and the condition of the patient.

In one embodiment, the pharmaceutical composition of the present invention is an oral dosage form such as powders, granules, tablets, soft or hard capsules, suspensions, emulsions, syrups, and aerosols, ointments, creams, etc., according to a conventional method, respectively. , suppositories, injections, and sterile injection solutions may be formulated and used in any form suitable for pharmaceutical preparations.

It may further include excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, diluents, etc. commonly used for the formulation. For example, excipients that may be included in the pharmaceutical composition of the present invention 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, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate, mineral oil, and the like may be used, but is not limited thereto. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

The present invention also provides a cosmetic composition for preventing or improving hair loss comprising the compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient. Specifically, the cosmetic composition may be, for example, a cosmetic for hair, the formulation thereof is not particularly limited, and may be appropriately selected according to the purpose.

For example, the cosmetic composition is formulated as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing, oil, powder foundation, emulsion foundation, wax foundation and spray. may be, but is not limited thereto. More specifically, it may be a cleaning agent such as shampoo, conditioner, and body cleanser, hair dressing agent such as hair tonic, gel or mousse, and a cosmetic composition for hair such as a hair conditioner or hair dye.

In one embodiment of the present invention, the cosmetic composition may contain various suitable bases and additives as necessary, and the types and amounts of these components can be easily selected by the inventor. It may contain acceptable additives as necessary, for example, may further include components such as preservatives, pigments, and additives conventional in the art.

In another embodiment, the present invention also provides a food composition for preventing or improving hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient, for example, a health functional food. The "health functional food" means a food manufactured and processed using raw materials or ingredients useful for the human body, and "functionality" means a health purpose such as regulating nutrients or physiological action with respect to the structure and function of the human body. It means to consume for the purpose of obtaining a useful effect.

The formulation of the food composition is not particularly limited, but, for example, may be formulated as tablets, granules, powders, liquids such as drinks, caramel, gels, bars, and the like. In addition to the active ingredient, the food composition of each dosage form can be formulated without difficulty by those skilled in the art without difficulty depending on the dosage form or purpose of use of ingredients commonly used in the field.

Justice

Unless defined otherwise, all technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Moreover, numerical values recited herein are intended to include the meaning of “about” unless explicitly stated otherwise. Definitions of residues and substituents as used herein are provided below. Unless otherwise specified, each residue has the following definitions and is used in the sense commonly understood by one of ordinary skill in the art.

The term “alkyl,” as used herein, is a hydrocarbon having primary, secondary, tertiary and/or quaternary carbon atoms, substituted or unsubstituted, and saturated, which may be straight-chain, branched, cyclic, or combinations thereof. contains aliphatic groups. For example, an alkyl group may have 1 to 20 carbon atoms (ie, C ₁ -C ₂₀ alkyl), 1 to 10 carbon atoms (ie, C ₁ -C ₁₀ alkyl), or 1 to 6 carbon atoms (ie, C 1 -C 10 alkyl). C ₁ -C ₆ alkyl). Unless otherwise defined, in a preferred embodiment, alkyl refers to _{C 1} -C _{6 alkyl.} Examples of suitable alkyl groups include methyl (Me, —CH ₃ ), ethyl (Et, —CH ₂ CH ₃ ), 1-propyl (n-Pr, n-propyl, —CH ₂ CH ₂ CH ₃ ), 2-propyl (i-Pr, i-propyl, -CH(CH ₃ ) ₂ ), 1-butyl (n-Bu, n-butyl, -CH ₂ CH ₂ CH ₂ CH ₃ ), 2-methyl-1-propyl (i -Bu, i-butyl, -CH ₂ CH(CH ₃ ) ₂ ), 2-butyl (s-Bu, s-butyl, -CH(CH ₃ )CH ₂ CH ₃ ), 2-methyl-2-propyl ( t-Bu, t-butyl, -C(CH ₃ ) ₃ ), 1-pentyl (n-pentyl, -CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-pentyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₃ ), 3-pentyl (-CH(CH ₂ CH ₃ ) ₂ ), 2-methyl-2-butyl (-C(CH ₃ ) ₂ CH ₂ CH ₃ ), 3-methyl-2-butyl ( -CH(CH ₃ )CH(CH ₃ ) ₂ ), 3-methyl-1-butyl (-CH ₂ CH ₂ CH(CH ₃ ) ₂ ), 2-methyl-1-butyl (-CH ₂ CH(CH _{3 )} )CH ₂ CH ₃ ), 1-hexyl (-CH ₂ CH ₂ CH ₂ CH ₂ CH ₂ CH ₃ ), 2-hexyl (-CH(CH ₃ )CH ₂ CH ₂ CH ₂ CH ₃ ), 3-hexyl ( -CH(CH ₂ CH ₃ )(CH ₂ CH ₂ CH ₃ )), 2-methyl-2-pentyl (-C(CH ₃ ) ₂ CH ₂ CH ₂ CH ₃ ), 3-methyl-2-pentyl (- CH(CH ₃ )CH(CH ₃ )CH ₂ CH ₃ ), 4-methyl-2-pentyl (-CH(CH ₃ )CH ₂ CH(CH ₃ ) ₂ ), 3-methyl-3-pentyl (-C (CH ₃ )(CH ₂ CH ₃ ) ₂ ), 2-methyl-3-pentyl (-CH(CH ₂ CH ₃ )CH(CH ₃ ) ₂ ), 2,3-dimethyl-2-butyl (-C( CH ₃ ) ₂ CH(CH ₃ ) ₂ ), 3,3-dimethyl-2-butyl (-CH(CH ₃ )C(CH ₃ ) ₃ ), and octyl (-(CH ₂ ) ₇ CH ₃ ). may be, but is not limited thereto.

Moreover, the term “alkyl” as used throughout the specification, examples and claims is intended to include both unsubstituted and substituted alkyl groups, the latter of which are trifluoromethyl and 2,2,2-tri refers to an alkyl moiety having a substituent replacing a hydrogen on one or more carbons of the hydrocarbon backbone, including haloalkyl groups such as fluoroethyl, and the like.

As used herein, the term “halo” means halogen and includes chloro, fluoro, bromo, and iodo.

또는

(여기서, R_a, R_b 및 R_b'는 각각 독립적으로 수소 또는 히드로카르빌 기를 나타내거나, 또는 R_a 및 R_b은 이들이 부착된 N 원자와 함께 고리 구조 내에 4 내지 8개의 원자를 갖는 헤테로사이클을 형성함)로 표시될 수 있는 잔기를 지칭하는 것으로 당업계에서 인정된다. 특정 실시양태에서, 아미노는 -NH₂이다.As used herein, the terms “amine” and “amino” refer to unsubstituted and substituted amines and salts thereof, e.g.

or

(wherein R _a , R _b and R _b ′ each independently represent a hydrogen or a hydrocarbyl group, or R _a and R _b together with the N atom to which they are attached are hetero having 4 to 8 atoms in the ring structure. forming a cycle). In certain embodiments, amino is —NH ₂ .

As used herein, the term “substituted” refers to a particular moiety of a compound of the present invention having one or more substituents. The term "substituted", eg, "substituted alkyl" or "substituted amino" with respect to alkyl, amino, etc., means that one or more hydrogen atoms of the alkyl or amino are each independently replaced by a non-hydrogen substituent.

The present invention will be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[Example 1] Measurement of proliferation of dermal papilla cells

Measurement of proliferation of dermal papilla cells in high concentration treatment

In order to determine the effect of the compound of the present invention on the proliferation of dermal papilla cells, cell proliferation was analyzed after treatment with the compound of Formula II in dermal papilla cells.

1x10 ⁴ dermal papilla cells were inoculated into a 24-well plate, and 24 hours later, the compound of Formula II was treated at concentrations of 0.1 μM, 1 μM and 10 μM, respectively, for 72 hours. Thereafter, the medium was removed and the cells were treated with 10% EZ-Cytox cell viability assay reagent for 2 hours using EZ-Cytox cell viability assay reagent (DoGen, Korea), and then the absorbance was measured at 450 nm to determine the number of cells. Confirmed.

As a result, as shown in FIG. 1, when the dermal papilla cells were treated with the compound of Formula II at a concentration of 0.1 μM, 1 μM, or 10 μM, cell proliferation was increased compared to the control group not treated therewith. In particular, the proliferation of cells treated with 0.1 μM was increased by about 19% compared to the control group, and the proliferation of cells treated with 1 μM was increased by about 25% compared to the control group.

Measurement of proliferation of dermal papilla cells in low-dose treatment

1x10 ⁴ dermal papilla cells were inoculated into a 24-well plate, and 24 hours later, the compound of Formula II was treated at concentrations of 0.001 μM, 0.01 μM, 0.1 μM and 1 μM, respectively, for 48 hours. Thereafter, the medium was removed and the cells were treated with 10% EZ-Cytox cell viability assay reagent (DoGen, Korea) for 2 hours, and then the absorbance was measured at 450 nm to determine the number of cells.

As a result, as shown in FIG. 2, when the dermal papilla cells were treated with the compound of Formula II at a concentration of 0.01 μM, 0.1 μM, or 1 μM, cell proliferation was increased compared to the control group not treated therewith.

From this, it was confirmed that the compound of the present invention is effective for the proliferation of dermal papilla cells.

[Example 2] Measurement of proliferation of superficial root sheath cells

In order to confirm the effect of the compound of the present invention on the proliferation of the outer root sheath cells, the cell proliferation was analyzed after treatment with the outer root sheath cells.

1x10 ⁴ outer root sheath cells were inoculated into a 24-well plate, and 24 hours later, the compound of Formula II was treated at concentrations of 0.001 μM, 0.01 μM, 0.1 μM, and 1 μM, respectively, for 72 hours. Thereafter, the medium was removed and the cells were treated with 10% EZ-Cytox cell viability assay reagent (DoGen, Korea) for 2 hours, and then the absorbance was measured at 450 nm to determine the number of cells.

As a result, as shown in FIG. 3, when the outer root sheath cells were treated with the compound of Formula II at concentrations of 0.001 μM, 0.01 μM, 0.1 μM, and 1 μM, cell proliferation was increased in a concentration-dependent manner compared to the control group not treated therewith. did. In particular, the proliferation of cells treated with 0.01 μM was increased by about 18% compared to the control group, and the proliferation of cells treated with 0.1 μM was increased by about 31% compared to the control group, and the cells treated with 1 μM showed a high rate of increase of 59%.

From this, it was confirmed that the compound of the present invention is effective for the proliferation of the outer root sheath cells.

[Example 3] Measurement of hair growth effect

The following experiment was performed to confirm the hair growth effect of the compound of the present invention on hair follicles. To this end, the length of hair grown by treating the compound of Formula II in mustache hair follicles was measured.

Observation under a dissecting microscope, anagen vibrissa follicles of mice were carefully isolated. Add Williams E medium supplemented with 2 mM L-glutamine, 10 µg/mL insulin, 10 ng/mL hydrocortisone, 100 U/mL penicillin, and 100 µg/mL streptomycin without serum to each well of a 48-well plate, Separated hair follicles were put one by one and incubated at _{37 °C, 5% CO 2 incubator.} Compounds of formula II were treated at concentrations of 1 μM, 10 μM and 50 μM. Individual hair follicles were photographed after incubation for 48 hours (Edmund Optics Ltd, UK). The length of 15 mustache hairs grown from the hair follicles was measured and the average value thereof was obtained, and this is shown in FIGS. 4 and 5 .

As shown in FIGS. 4 and 5 , when the hair follicles were treated with the compound of Formula II, the length of the mustache hair was significantly increased compared to the control group not treated therewith.

From this, it was confirmed that the compound of the present invention is effective for hair growth in hair follicles.

[Example 4] Confirmation of hair growth promoting effect in experimental animals

The following experiment was performed to determine whether the hair cycle was induced from telogen to anagen when the compound of the present invention was administered in vivo, thereby exhibiting a hair growth promoting effect. To this end, an animal experiment was performed to confirm the growth of the hair, and the weight of the grown hair was measured.

After removing the hairs on the back of 6-week-old female C3H/HeN mice, a telogen-to-anagen transition model in the telogen phase of the hair growth cycle, 100 uL of the compound of Formula II was added in 0.004% and 0.02% concentration was applied. Skin darkning, which is an indication that the hair growth phase was induced, was monitored, and after 14 days, newly grown hair was pushed on the back and the degree of hair regeneration was examined, and the results are shown in FIGS. 6 and 7 .

As shown in FIG. 6 , it was confirmed that hairs on the back of the rats to which the compound of Formula II was applied grew more and covered the back compared to the control group to which the compound of Formula II was not applied.

In addition, as shown in FIG. 7 , the weight of the hair of mice coated with the compound of Formula II at a concentration of 0.004% increased about 3 times compared to the control group, and the weight of the hair of mice applied with a concentration of 0.02% was the weight of the control group. increased about 7 times compared to

Through this, it was confirmed that the compound of Formula II plays a role in inducing telogen hair to the growth phase, and from this, it was confirmed that the compound of the present invention exhibits an actual hair growth promoting effect.

Claims (13)

A pharmaceutical composition for preventing or treating hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula I]

In the above formula,
R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, alkyl, -OH, -COOH, -NHC(=O)Ra, -NRaRb, -C(=O)NRaRb, -C( =O)NHORa, -C(=O)NRaOH, or -OC(=O)Ra;
R _{6 To} R ₁₀ are each independently hydrogen or alkyl,
Ra or Rb is each independently hydrogen or alkyl.
According to claim 1,
R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, C ₁ -C ₆ alkyl, —OH, or —C(=O)NRaRb;
R _{6 To} R ₁₀ are each independently hydrogen or C ₁ -C ₆ alkyl,
Ra or Rb are each independently hydrogen or C ₁ -C ₆ A pharmaceutical composition for preventing or treating hair loss, characterized in that it is alkyl.
According to claim 1,
R ₁ or R ₂ are each independently —OH or —C(=O)NRaRb,
R ₆ and R ₁₀ are C ₁ -C ₆ alkyl,
R ₃ , R ₄ , R ₅ , R ₇ , R ₈ and R ₉ are hydrogen,
Ra and Rb are C ₁ -C ₆ A pharmaceutical composition for preventing or treating hair loss, characterized in that it is alkyl.
According to claim 1,
R ₁ is —OH,
R ₂ is -C(=O)NRaRb,
R ₆ is ethyl,
R ₁₀ is methyl,
R ₃ , R ₄ , R ₅ , R ₇ , R ₈ and R ₉ are hydrogen,
Ra and Rb are methyl, hair loss prevention or treatment pharmaceutical composition.
A pharmaceutical composition for preventing or treating hair loss comprising a compound of Formula II as an active ingredient:
[Formula II]

.
The hair loss according to any one of claims 1 to 5, wherein the hair loss is alopecia areata, hereditary androgen hair loss, telogen hair loss, traumatic hair loss, hair growth wall, pressure hair loss, anagen phase hair loss, alopecia areata, syphilitic hair loss, seborrheic hair loss , A pharmaceutical composition for preventing or treating hair loss, characterized in that it is selected from the group consisting of symptomatic hair loss, scarring hair loss and congenital hair loss.
The pharmaceutical composition for preventing or treating hair loss according to any one of claims 1 to 5, wherein the compound promotes proliferation of dermal papilla cells to induce hair growth phase.
[Claim 6] The pharmaceutical composition for preventing or treating hair loss according to any one of claims 1 to 5, wherein the compound promotes proliferation of superficial root sheath cells to induce hair growth phase.
The pharmaceutical composition for preventing or treating hair loss according to any one of claims 1 to 5, wherein the compound promotes proliferation of dermal papilla cells and superficial root sheath cells to induce hair growth phase.
A cosmetic composition for preventing or improving hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula I]

In the above formula,
R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, alkyl, -OH, -COOH, -NHC(=O)Ra, -NRaRb, -C(=O)NRaRb, -C( =O)NHORa, -C(=O)NRaOH, or -OC(=O)Ra;
R _{6 To} R ₁₀ are each independently hydrogen or alkyl,
Ra or Rb is each independently hydrogen or alkyl.
A cosmetic composition for preventing or improving hair loss comprising a compound of Formula II as an active ingredient:
[Formula II]

.
A food composition for preventing or improving hair loss comprising a compound of Formula I or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula I]

In the above formula,
R ₁ , R ₂ , R ₃ , R ₄ or R ₅ are each independently hydrogen, alkyl, -OH, -COOH, -NHC(=O)Ra, -NRaRb, -C(=O)NRaRb, -C( =O)NHORa, -C(=O)NRaOH, or -OC(=O)Ra;
R _{6 To} R ₁₀ are each independently hydrogen or alkyl,
Ra or Rb is each independently hydrogen or alkyl.
A food composition for preventing or improving hair loss comprising a compound of Formula II as an active ingredient:
[Formula II]

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