Stimulation of hair growth

Abstract

Compositions and methods that can enhance or stimulate hair growth, as well as new chemical entities that affect hair growth and hair loss.

Description

Technical Field

[0001] Claims of Priority This application claims the benefit of U.S. Provisional Patent Application No. 62 / 959,594, filed on January 10, 2020. The entire contents of the above provisional patent application are incorporated herein by reference.

[0002] The present disclosure relates to hair care compositions and methods that can stimulate or accelerate hair growth. The present disclosure also relates to a novel chemical compound, di(trifluoromethyl)propyl ester of squaric acid (CF3-SADBE), and methods of using the same.

Background Art

[0003] Most mammals are covered with hair. Hair loss, also known as alopecia or baldness, is a condition that involves the complete or partial loss of hair growth and affects a significant portion of the population. Hair loss may be desirable for some people, while it can be a concern for those who wish to maintain a younger appearance. The treatments currently used for baldness have had little success and cause significant side effects to patients, including anti-androgen related toxicity or inflammation of the skin.

Summary of the Invention

[0004] This disclosure is at least in part based on the development of novel compounds. This disclosure is also based on the discovery of novel compounds that may help stimulate, enhance, densen, or accelerate hair growth. The disclosure is also at least in part based on novel therapeutic methods for inhibiting, reducing, delaying, or treating hair loss. As described herein, hair loss can be reduced, inhibited, delayed, or treated by applying an effective amount of the compositions and formulations described herein to the scalp and / or hair follicles. As described herein, hair growth can be stimulated, enhanced, densen, or accelerated by applying an effective amount of the compositions and formulations described herein to the scalp and / or hair follicles. In some cases, the compositions described herein may contain di(trifluoromethyl)propyl squamate (CF3-SADBE) or a physiologically acceptable salt thereof. In some cases, the compositions contain SADBE or diphenylcyclopropenone (DPCP).

[0005] The compositions and methods described herein may help stimulate, enhance, or accelerate hair growth. In some cases, the compositions and methods described herein exhibit less inflammation than known treatments.

[0006] In one embodiment, the present disclosure relates to a compound of formula (1):

[0007] [ka]

[0008] Alternatively, di(trifluoromethyl)propyl squamate (CF3-SADBE) is provided. In some embodiments, the compound is a physiological salt of CF3-SADBE. In other embodiments, the disclosure provides pharmaceutical compositions comprising, or substantially comprising, the compound of formula (1) and a pharmaceutically acceptable carrier. In some embodiments, the composition further comprises one or more anti-inflammatory agents. The anti-inflammatory agents may be glucocorticoids, calcipotriol, immunosuppressants, and / or antihistamines. In some cases, the composition may also comprise agents selected from minoxidil, finasteride, SADBE, DPCP, and combinations thereof. In some embodiments, the composition is formulated for topical or subcutaneous administration.

[0009] In other embodiments, the disclosure provides pharmaceutical compositions for enhancing hair growth in mammals requiring such composition, comprising, or substantially comprising, an effective amount of a compound of formula (1) and a pharmaceutically or dermatologically acceptable carrier.

[0010] In other embodiments, the disclosure provides hair care compositions for enhancing hair growth in mammals requiring such compositions, comprising, or substantially comprising, an effective amount of the compound of formula (1) and a dermatologically acceptable carrier.

[0011] In other embodiments, the disclosure is the percentage of hair follicles in the growth phase of the subject. To promote and hair follicles in the resting phase of Combine decrease A method is provided, comprising or substantially comprising administering an effective amount of the compound of formula (1) to a subject in need thereof. In some embodiments, the subject has alopecia.

[0012] In other embodiments, the disclosure provides a method for treating hair loss in a subject, the method comprising, or substantially comprising, administering a therapeutically effective amount of the compound of formula (1) to a subject in need thereof. In some cases, the hair loss is related to alopecia.

[0013] In other embodiments, the disclosure provides methods for stimulating hair growth, methods for promoting hair growth, and methods for inhibiting hair loss, each comprising or substantially comprising administering a therapeutically effective amount of the compound of formula (1).

[0014] In other embodiments, the disclosure provides a method for promoting hair growth in a subject, the method comprising, consisting of or substantially thereof, topically applying an effective amount of a formulation to a hair follicle and / or the skin covering the hair follicle, the formulation comprising, consisting of or substantially thereof, a compound of formula (1) and an acceptable carrier, the formulation being applied one, two, three, or more times. In other embodiments, the disclosure provides methods for promoting the transition of hair follicles into the growth phase, for denser hair, and for reducing hair loss, each method comprising, consisting of or substantially thereof, administering a composition comprising, consisting of or substantially thereof, an effective amount of formula (1).

[0015] In other embodiments, the disclosure provides a pharmaceutical composition for promoting hair growth in a mammal requiring it, comprising, or substantially comprising, an effective amount of SADBE and / or DPCP and a pharmaceutically or dermatologically acceptable carrier, the mammal not having an autoimmune disease.

[0016] In other embodiments, the disclosure provides a method for promoting the transition of hair follicles from the resting to the growth phase, the method comprising, or substantially comprising, administering an effective amount of SADBE and / or DPCP to a subject in need thereof, the subject not having an autoimmune disease. In some embodiments, the subject has alopecia.

[0017] In other embodiments, the disclosure provides a method for treating hair loss in question, the method comprising, or substantially comprising, administering a therapeutically effective dose of SADBE and / or DPCP, and the hair loss is not related to an autoimmune disease. In some embodiments, the hair loss is related to a non-autoimmune alopecia.

[0018] In other embodiments, the disclosure provides methods for stimulating hair growth in a subject in need, methods for enhancing hair growth in a subject in need, and methods for inhibiting hair loss in a subject in need, each method comprising, or substantially comprising, administering a therapeutically effective dose of SADBE and / or DPCP, wherein the subject does not have an autoimmune disease.

[0019] In other embodiments, the disclosure provides a method for promoting hair growth in a subject requiring it, the method comprising, consisting of or substantially comprising, topically applying an effective amount of the formulation to the hair follicles and / or the skin covering the hair follicles, the formulation comprising, consisting of or substantially comprising, SADBE and / or DPCP and an acceptable carrier, the formulation is applied one, two, three or more times, and the subject does not have hair loss associated with an autoimmune disease.

[0020] In other embodiments, the disclosure provides methods for promoting the transition of hair follicles from the resting to the growth phase in a subject requiring such methods, for densifying the hair in a subject requiring such methods, and for reducing hair thinning in a subject requiring such methods, each method comprising administering a composition comprising, comprising, or substantially comprising an effective amount of SADBE or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

[0021] In some embodiments of all aspects, alopecia are acne keloids (e.g., keloid folliculitis, nape acne keloids), alopecia areata (autoimmune alopecia; e.g., serpentine alopecia), complete alopecia, generalized alopecia, anagenous alopecia, androgenous alopecia (e.g., male and female pattern alopecia), block alopecia, central centrifugal scarring alopecia, scarring alopecia (e.g., primary scarring alopecia), congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, discoid (lesional) lupus erythematous (DLE), dissociative cellulitis (e.g., perifollicular inflammation, abscessive puncture folliculitis), Examples of alopecia include "terminal" or "untreatable" scarring alopecia, female pattern hair loss, alopecia areata, frontal sclerosing alopecia, hair shaft abnormalities, hyperandrogenicity, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris (e.g., diffuse), lipoderma alopecia (lipoderma scalp), male pattern baldness (e.g., bilateral skull), non-scarring alopecia, psoriasis, psoriasis-like alopecia, compression (postoperative) alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis. In some embodiments of all aspects, alopecia associated with autoimmune diseases include alopecia areata.In some embodiments of all aspects, alopecia not associated with autoimmune diseases (e.g., non-autoimmune alopecia) includes acne keloidalis (e.g., keloid folliculitis, acne keloidalis nuchae), alopecia totalis, alopecia universalis, telogen effluvium, androgenetic alopecia (e.g., male and female pattern hair loss), block alopecia, central centrifugal cicatricial alopecia, scarring alopecia (e.g., primary cicatricial alopecia), congenital alopecia, congenital hypotrichosis, diffuse circular alopecia, discoid (lesional) lupus erythematosus (DLE), dissecting cellulitis (e.g., perifolliculitis, acne keloidalis suppurativa), "end-stage" or "refractory" scarring alopecia, female pattern hair loss, folliculitis decalvans, frontal fibrosing alopecia, hair shaft abnormalities, hyperandrogenism, hypotrichosis, hereditary alopecia, lichen planus, lichen planopilaris (e.g., diffuse), lipedematous alopecia (lipedematous scalp), male pattern hair loss (e.g., bitemporal), non-scarring alopecia, psoriasis, psoriatic alopecia, pressure (post-operative) alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangular alopecia, tinea capitis, TNF-α inhibitor-induced psoriatic alopecia, traction alopecia, trichorrhexis nodosa, trichotillomania, and tufted folliculitis.

[0022] In some embodiments of all aspects, the compound, formulation, or composition is administered to the skin, hair, or scalp of a mammal, patient, or subject that needs it.

[0023] In some embodiments of all aspects, the methods described herein also include administering an agent selected from the group consisting of minoxidil, finasteride, DPCP, SADBE, and combinations thereof.

[0024] In some embodiments, the methods described herein enhance hair growth by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30%.

[0025] In some embodiments of all aspects, the methods described herein also include administering one or more steroids.

[0026] In some embodiments of all aspects, the methods described herein also include administering one or more agents to reduce the sensitivity of the scalp or skin of a mammal (e.g., a patient or subject) that needs it.

[0027] In some embodiments of all aspects, the methods described herein also include administering one or more agents to modulate inflammation.

[0028] In some embodiments of all aspects, the formulations described herein also include one or more of an aqueous gel, an alcohol gel, an ointment, an oil, an alcoholic or aqueous liquid, an oil-in-water emulsion, a water-in-oil emulsion, and a silicone-in-water emulsion.

[0029] In some embodiments of all aspects, the formulations described herein also include acceptable subcomponents selected from the group consisting of xanthan gum, glycerin, EDTA, sodium benzoate, phenoxyethanol, 2-hydroxy fatty alcohol alkoxylate, sodium polyacrylate, polysorbate 20, BHT, disaccharide gum, ethylhexyl glycerin, carbomer, butylene glycol, acrylate polymer, PEG-40 hydrogenated castor oil, methylisothiazolinone, methylchloroisothiazolinone, propylene glycol, potassium sorbate, polyglyceryl caprylate, fragrance, and water.

[0030] Unless otherwise noted, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Methods and materials are described herein for use in the present disclosure, and other suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are hereby incorporated by reference in their entirety. In case of conflict, this specification, including definitions, will control.

[0031] Other features and advantages of the disclosure will be apparent from the following detailed description and figures, as well as from the claims. [Brief explanation of the drawing]

[0032] [Figure 1] (Figures 1A-1D) Topical application of SADBE and DPCP demonstrates induction of the growth phase and hair growth in mice. Figure 1A shows the molecular structures of SADBE and DPCP. Both are contact sensitizers (haptens). Figure 1B is a schematic diagram showing the schedule for topical administration of haptens to the skin of mice in which hair follicles have been arrested in the resting phase. Figure 1C is a collection of photographs of mice treated topically with haptens. Red circles indicate that the treated flanks demonstrate the growth phase and hair growth. Green circles indicate that the untreated flanks demonstrate the resting phase. Treatment with contact sensitizers often results in skin inflammation (red "*"). Figure 1D is a graph showing relative induction of the growth phase, measured by enhanced skin pigmentation intensity (a marker of the growth phase) on the treated side as a percentage of the untreated side (relative to) the baseline. [Figure 2] (Figures 2A-2C) Novel compounds that induce the growth phase and hair growth are shown. Figure 2A shows the molecular structures of synthesized SADBE derivatives that showed improved growth phase induction and / or reduced inflammation. Figure 2B shows images of mice administered with SADBE, CF3-SADBE, and CCl-SADBE. CF3-SADBE appeared to induce the growth phase and hair growth at least as efficiently as SADBE, which caused less inflammation. CCl-SADBE did not produce either inflammation or growth phase and hair growth. Red circles indicate treated flanks demonstrating the growth phase and hair growth. Green circles indicate untreated flanks demonstrating the resting phase. Red circles indicated by dotted lines show flanks treated with CCl-SADBE with hair remaining in the resting phase. (Red "*") indicates inflammation in flanks treated with SADBE. Figure 2C is a graph showing the relative growth-stage induction for SADBE and its derivatives. [Figure 3](Figures 3A-3B) CF3-SADBE efficiently induces the growth phase and hair growth with less inflammation than SADBE. Figure 3A shows that treatment with 100 mM SADBE induces the growth phase with substantial inflammation by day 14 (blue "*", blue circle), while the same amount of CF3-SADBE induces the growth phase with very little visible inflammation (red circle). Healthy hair growth is observed in the treated flanks by day 17. Figure 3B is a graph showing the relative induction of the growth phase as the percentage of the untreated side compared to the baseline, measured over time for both treatments. [Figure 4] (Figures 4A-4C) These images show that CF3-SADBE treatment induces telogenous hair follicles to enter the anagen phase. Figure 4A shows the macroscopic appearance of a mouse with the left flank treated with 100 mM CF3-SADBE and the right flank untreated. Figure 4B shows skin treated with CF3-SADBE stained with hematoxylin and eosin (H&E) (red "*"), indicating anagen hair follicles, and Figure 4C shows hair follicles in untreated skin remaining in the telogen phase (green "*"). [Figure 5] This image shows the growth phase and hair growth induced by CF3-SADBE, which is earlier and causes less inflammation than SADBE. Treatment with CF3-SADBE causes a clear growth phase by day 10, while SADBE does not (purple arrows). SADBE also causes more pronounced inflammation by day 14 (blue asterisks). Healthy hair growth is observed on the treated flank by day 17. [Modes for carrying out the invention]

[0033] Compositions for treating hair loss are not well developed, and currently available treatments involve the administration of compounds that have had little success and cause discomfort to patients.

[0034] hair growth composition As described herein, we have developed numerous hapten derivative compounds. These compounds enhance or stimulate hair growth. Some compounds enhance hair growth while minimizing skin inflammation. We synthesized the compound of formula (1):

[0035] [ka]

[0036] Subsequently, topical delivery of the compound, overall after prior shaving, resulted in accelerated hair growth in mice compared to the treated contralateral skin of the vehicle control. In some cases, topical delivery of the novel compound (e.g., CF3-SADBE) also showed less inflammation than known treatments. Furthermore, CF3-SADBE also appeared to exhibit an enhanced effect, such as that measured by the early induction of the growth phase at the time of topical delivery.

[0037] An unspecified list of useful hapten derivatives developed herein includes the following compounds:

[0038] [Table 1]

[0039] To improve the therapeutic activity and safety of topical hair growth agents, we designed this hapten derivative compound. In an attempt to improve solubility and potential skin penetration properties, we replaced the dibutyl ester moiety by introducing PEG or saturated alkyl long chains. However, neither compound was active in promoting hair growth in animal models.

[0040] Subsequently, shorter alkyl chains were introduced. CF3 or CL-substituted alkyl chains were designed. It was hypothesized that both compounds might have similar crosslinking reactivity. Surprisingly, the CF3-substituted compounds were active in promoting hair growth, while the CL-substituted compounds showed low activity. This indicated that hair growth promoting activity is not simply related to the reactivity of the compound as a crosslinking agent.

[0041] CF3 compounds (e.g., CF3-SADBE or MGH-CS-4 mentioned above) showed accelerated hair growth and seemingly slightly reduced inflammation compared to known treatments.

[0042] Synthesis of CF3-SADBE

[0043] [ka]

[0044] A solution of square acid (9 mmol) and alcohol (36 mmol) in toluene (9 ml) was refluxed at 100°C for 16 hours using a Dean-Stark apparatus. After the reaction was complete, the toluene was concentrated under vacuum, and the resulting solution was diluted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate solution, and then with brine. The volatile components were concentrated under vacuum, and the compounds were purified by column chromatography to obtain each compound.

[0045] Use of compositions to stimulate hair growth The compounds described herein can be used in compositions for treating hair loss, promoting hair growth, reducing hair loss, stimulating hair growth, thickening hair, or reducing thinning hair. Hair loss can be caused by a variety of conditions. Some of these conditions are related to autoimmune diseases, while some are not related to autoimmunity.

[0046] Use of CF3-SADBE and other novel compounds to promote hair growth As described herein, CF3-SADBE can be used in the treatment of hair loss and / or to promote hair growth in subjects requiring such treatment. CF3-SADBE can be useful in the treatment of alopecia associated with autoimmune diseases (e.g., alopecia areata) or alopecia not associated with autoimmune diseases. An unspecified list of alopecia conditions (autoimmune-related alopecia and non-autoimmune alopecia) includes: acne keloids (e.g., keloid folliculitis, nape acne keloids), alopecia areata (autoimmune alopecia; e.g., serpentine alopecia), complete alopecia, generalized alopecia, anagenous alopecia, androgenous alopecia (e.g., male and female pattern hair loss), block alopecia, central centrifugal scarring alopecia, scarring alopecia (e.g., primary scarring alopecia), congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, discoid (lesional) lupus erythematous (DLE), dissociative cellulitis (e.g., perifolliculitis, abscessive perifolliculitis) Folliculitis), "terminal" or "untreatable" scarring alopecia, female pattern hair loss, alopecia folliculitis, frontal sclerosing alopecia, hair shaft abnormalities, hyperandrogenicity, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris (e.g., diffuse), lipoderma alopecia (lipoderma scalp), male pattern hair loss (e.g., bilateral skull), non-scarring alopecia, psoriasis, psoriasis-like alopecia, compression (postoperative) alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis (e.g., Bolognia, et. al., Dermatology. Elsevier Health Sciences, June 8, 2012. Pages 1163-1187. Section 11: Hair, Nails, and Mucous Membranes. 69: Alopecias).Methods for diagnosing these conditions or identifying subjects with these conditions are publicly known in the art, see, for example, Bolognia, et. al., Dermatology. Elsevier Health Sciences, June 8, 2012. Pages 1163-1187. Section 11: Hair, Nails, and Mucous Membranes. 69: Alopecias.

[0047] Use of SADBE or DPCP for the treatment of alopecia beyond autoimmune alopecia. Surprisingly, as described herein, the compounds SADBE and DPCP can also be used to treat alopecia not associated with autoimmune diseases (e.g., for the treatment of alopecia conditions other than alopecia areata). SADBE and DPCP have been used to treat alopecia areata, autoimmune-associated alopecia. However, prior to this disclosure, it was not known that DPCP and / or SADBE could enhance hair growth in mammals without autoimmune diseases. As shown herein, SADBE enhanced (e.g., accelerated) hair growth in mammals without autoimmune diseases. DPCP also showed enhanced hair growth in mammals without autoimmune diseases.

[0048] An unspecified list of non-autoimmune-related alopecia includes: acne keloids (e.g., keloid folliculitis, nape acne keloids), complete alopecia, generalized alopecia, pubertal alopecia, androgen-induced alopecia (e.g., male and female pattern hair loss), nerve block alopecia, central centrifugal scarring alopecia, scarring alopecia (e.g., primary scarring alopecia), congenital alopecia, congenital malformation, diffuse alopecia areata, discoid (lesional) lupus erythematous (DLE), dissociative cellulitis (e.g., perifollicular inflammation, abscessive puncture folliculitis), "terminal" or "drug-induced" Examples of conditions for which treatment is ineffective include scarring alopecia, female pattern hair loss, alopecia folliculitis, frontal sclerosing alopecia, hair shaft abnormalities, hyperandrogenicity, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris (e.g., diffuse), lipoderma alopecia (lipoderma scalp), male pattern baldness (e.g., bilateral skull), non-scarring alopecia, psoriasis, psoriasis-like alopecia, pressure (postoperative) alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis. Methods for diagnosing these conditions or identifying subjects with these conditions are publicly known in the art, see, for example, Bolognia, et. al., Dermatology. Elsevier Health Sciences, June 8, 2012. Pages 1163-1187. Section 11: Hair, Nails, and Mucous Membranes. 69: Alopecias.

[0049] Combination therapy In some embodiments, the methods described herein may include administering combination therapy. A non-limiting list of therapeutic options that can be administered by the compositions and methods described herein includes: topical corticosteroids, oral corticosteroids, and intralesional corticosteroids (e.g., clobetasol, fluocinonide), topical stimulants (e.g., anthraline, tazarotene, azelaic acid), topical minoxidil, topical finasteride, dutasteride, topical immunotherapy, systemic corticosteroids (e.g., pulsed administration), oral finasteride (e.g., type II 5α-reductase inhibitors), and Examples include oral tetracyclines (e.g., doxycycline, minocycline), oral rifampin and clindamycin, TNF-α inhibitors, PPAR-γ agonists (e.g., pioglitazone hydrochloride), isotretinoin, oral zinc sulfate, oral antimalarial drugs (e.g., hydroxychloroquine), systemic JAK / STAT pathway inhibitors (e.g., tofacitinib or ruxolitinib), topical or oral photochemotherapy, excimer lasers, systemic corticosteroids (e.g., chronic), and systemic cyclosporine.

[0050] Administration of formulations and compositions The disclosed compositions can be used in a variety of ways. For example, they may be components of dry formulations or wet solutions. They may be provided as components of injectable compositions that are injected (e.g., intradermally or subcutaneously) into bald areas (e.g., scalp). Alternatively, the compounds described herein may be components of compositions that are applied topically to bald or hair loss areas. This can be done for the purpose of densening the appearance of hair. These compositions may be optionally applied in combination with any known non-toxic delivery and / or penetration agents.

[0051] The disclosed compositions may be administered topically or by infusion. The required dose depends on the choice of route of administration; the nature of the formulation; the nature of the condition of the subject; the size of the subject, the surface area of ​​treatment, age, and sex; other medications administered; and the judgment of the attending physician. In some embodiments, the appropriate dose is in the range of 0.01 to 500.0 mg / kg. The various doses required are expected to take into account the different efficiencies of various routes of administration. These dose level variations may be adjusted by standard empirical practices for optimization, as is well understood in the art. Administration may be a single dose or multiple doses (e.g., 2, 3, 4, 6, 8, 10, 20, 50, 100, 150, or more multiples). The disclosed compositions may also be administered in a single topical treatment. The disclosed compositions may also be administered in multiple topical treatments. Multiple doses may be daily, every other day, twice a week, weekly, bi-weekly, monthly, or any combination thereof. The compositions described herein may be administered daily, weekly, monthly, yearly, or for longer periods. Encapsulation of the compounds into a suitable delivery vehicle (e.g., cream, emulsion, aqueous solution, or solid) may enhance the efficiency of delivery. The required dosage also depends on skin variability. Dose differences may be necessary due to different skin thickness at the hair-supporting sites, number of applications, skin type, different symptoms (e.g., different causes of alopecia), and / or different tolerances depending on the subject.

[0052] The compositions of this application can be prepared for storage by mixing them with one or more of the various pharmaceutically acceptable carriers, additives, or stabilizers known in the art. Acceptable carriers, additives, or stabilizers are nontoxic to the recipient at the dose and concentration used and include: buffers such as phosphates, citrates, and other non-toxic organic acids; antioxidants such as ascorbic acid; low molecular weight (less than 10 residues) polypeptides; proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextran; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as Tween, Pluronic, or PEG.

[0053] The composition may be in any form suitable for application to the scalp and / or hair, such as a solution, suspension, lotion, cream, gel, cosmetic liquid, stick, pencil, spray, aerosol, ointment, liquid cleanser and solid bar, shampoo and hair conditioner, paste, foam, milk, pup, water-oil two-layer composition, water-oil-powder three-layer composition, serum, powder, mousse, shaving cream, wipe, strip, patch, hydrogel, film-forming product, disposable applicator, etc. The composition may be a shampoo, hair conditioner, or hair lotion. The form of the composition may be obtained from a selected specific dermatologically acceptable carrier, if present in the composition. The composition may be in the form of an aqueous, aqueous-alcohol, or oily solution, lotion or serum-type dispersion, or emulsion (e.g., a milk-type emulsion of liquid or semi-liquid consistency). The composition may be in the form of an aqueous or anhydrous cream or gel-type suspension or emulsion, or microcapsules or particles, or ionic and / or nonionic vesicle dispersions. The composition may be anhydrous or aqueous.

[0054] The compositions described herein may include a dermatologically acceptable carrier (also referred to herein simply as “carrier”). The expression “dermatologically acceptable carrier” means, as used herein, that the carrier is suitable for topical application to hair / scalp, has good aesthetic properties, is miscible with the hair anti-aging agents in the composition, and does not cause inappropriate safety or toxicity concerns. An appropriate carrier is selected to obtain the desired product form. Furthermore, the solubility or dispersibility of the components may affect the form and characteristics of the carrier. In some embodiments, the carrier is present at levels of about 50% to about 99% by weight, about 60% to about 98% by weight, about 70% to about 98% by weight, or or about 80% to about 95% by weight of the composition.

[0055] The carrier can take on a variety of forms. Examples, though not limited to them, include simple solutions (e.g., aqueous, organic solvent, or oily), emulsions, and solid forms (e.g., gels, sticks, fluid solids, or amorphous materials). In some embodiments, the dermatologically acceptable carrier is in the form of an emulsion. Emulsions can generally be classified into those having a continuous aqueous phase (e.g., oil-in-water and water-in-oil in-water) or a continuous oil phase (e.g., water-in-oil and oil-in-water in oil). The oil phase of this disclosure may include silicone oils, hydrocarbon oils, non-silicone oils such as esters and ethers, and mixtures thereof.

[0056] The aqueous phase includes water, such as demineralized water or distilled water. Other acceptable carriers that may be used in the aqueous carrier include, but are not limited to, alcohol compounds such as ethanol. According to one embodiment, the composition comprises alcohol, dipropylene glycol, and / or water.

[0057] The composition has a pH in the range of about 3.0 to about 10 (for example, about pH 4.0 to about pH 9.0, about pH 5.0 to about pH 9.0, or about pH 6.0 to about pH 8.0) and can be measured by direct pH measurement using a standard hydrogen electrode of the composition at 25°C. Therefore, the pH of the composition may be in the range of, for example, about 6 to about 9.

[0058] The emulsion may further contain an emulsifier. The composition may contain any suitable proportion of emulsifier to adequately emulsify the carrier. Suitable weight ranges include emulsifiers of about 0.1% to about 10% or about 0.2% to about 5% relative to the weight of the composition. The emulsifier may be nonionic, anionic, or cationic. Suitable emulsifiers are disclosed, for example, in U.S. Patent Nos. 3,755,560 and 4,421,769, and McCutcheon's Detergents and Emulsifiers, North American Edition, pages 317-324 (1986), the entirety of which is incorporated herein by reference. Suitable emulsions may have a wide range of viscosities depending on the desired product form. Examples of emulsifiers, though not limited to them, include glyceryl stearate, polysorbate 60, and the PEG-6 / PEG-32 / glycerol stearate mixture sold by Gattefosse under the name Trefose®. The emulsion may contain a fatty phase that may amount to about 5% to about 80% by weight (e.g., about 5% to about 50% by weight) of the composition. Any of the emulsions described herein may contain one or more agents selected from the group of oils, waxes, emulsifiers, and co-emulsifiers. Examples of oils, waxes, emulsifiers, and co-emulsifiers used in hair care compositions are well known in the art. Emulsifiers and co-emulsifiers may be present in the composition in amounts ranging from 0.3% to about 30% by weight (e.g., about 0.5% to about 20% by weight) of the composition. The emulsion may contain lipid vesicles.

[0059] The composition (for example, any of the compositions described herein) may contain hydrophilic gelling agents (e.g., carboxyvinyl polymers, acrylic copolymers (e.g., acrylate / alkyl acrylate copolymers), polyacrylamides, polysaccharides (e.g., hydroxypropyl cellulose), natural gums, and clays), lipophilic gelling agents (e.g., modified clays (e.g., betones), metal salts of fatty acids (e.g., aluminum stearate), and hydrophobic silica, ethyl cellulose, and polyethylene), hydrophilic or lipophilic additives, preservatives, antioxidants, solvents (e.g., ethanol, isopropanol, and propylene glycol), fragrances, fillers, odor absorbers, dyes, oils (e.g.) The composition may contain one or more of the following: mineral oil (e.g., liquid paraffin), vegetable oil (e.g., shea butter or sunflower oil), animal oil (e.g., perhydrosqualene), synthetic oil (e.g., pure serine oil) or silicone oil), wax (e.g., cyclomethicone, beeswax, carnauba wax or paraffin wax), surfactants, preservatives, metal ion chelating agents, water-soluble polymers, thickeners, pigments, UV protection agents, humectants, antioxidants, pH adjusters, cleansing agents, and drying agents (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12), for example, one or more of each agent present in the composition in an amount of about 0.01% to about 10% by weight of the composition.

[0060] Any of the compositions provided herein may contain at least one preservative and / or dye.

[0061] The terms “subject” or “patient” are defined herein to include animals. In some embodiments, animals are mammals, but are not limited to primates (e.g., humans), cattle, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In some embodiments, the subject is a human. In some embodiments, the subject is a child.

[0062] Use of compounds in cosmetic compositions This disclosure is at least in part based on the development of cosmetic compositions that can help stimulate, enhance, densen, or accelerate hair growth. These cosmetic compositions may be used in subjects with or without alopecia. As described herein, hair growth can be stimulated, enhanced, densen, or accelerated, for example, by temporarily applying a cosmetically effective amount of the compositions and formulations described herein to the scalp and / or hair follicles. As described herein, hair loss can be reduced, inhibited, delayed, or treated by applying a cosmetically effective amount of the compositions and formulations described herein to the scalp and / or hair follicles.

[0063] In some embodiments, this disclosure provides cosmetic compositions comprising one or more of the compounds described herein and a pharmaceutically acceptable carrier. In some cases, the cosmetic composition also comprises one or more anti-inflammatory agents. The anti-inflammatory agents may be glucocorticoids, calcipotriols, antihistamines, and / or other immunosuppressants. The compositions described herein may also include any hair growth agents known in the art, for example, minoxidil or finasteride.

[0064] The cosmetic compositions described herein may be formulated for topical or subcutaneous administration.

[0065] In some embodiments, the Disclosure provides cosmetic compositions for promoting hair growth in mammals requiring it, comprising one or more effective amounts of the compounds described herein and a pharmaceutically or dermatologically acceptable carrier. Also described herein are methods for promoting hair growth, comprising applying one or more effective amounts of the formulation topically to hair follicles and / or the skin covering the hair follicles, wherein the formulation comprises one or more of the compounds described herein and a cosmetically acceptable carrier. The cosmetically acceptable carrier may include one or more aqueous gels, alcohol gels, ointments, oils, alcoholic or aqueous liquids, water-in-oil emulsions, oil-in-water emulsions, and water-in-silicone emulsions. In some cases, the compositions described herein also include cosmetically acceptable auxiliary components selected from the group consisting of xanthan gum, glycerin, EDTA, sodium benzoate, phenoxyethanol, 2-hydroxyfatty alcohol alkoxylate, sodium polyacrylate, polysorbate 20, BHT, disaccharide gum, ethylhexylglycerin, carbomer, butylene glycol, acrylate polymer, PEG-40 hydrogenated castor oil, methylisothiazolinone, methylchloroisothiazolinone, propylene glycol, potassium sorbate, polyglyceryl caprylate, fragrance, and water. [Examples]

[0066] The compositions and methods of this disclosure are further described in the following examples and do not limit the scope of the disclosure set forth in the claims.

[0067] [Example 1] Topical administration of SADBE and DPCP To measure the effects of SABDE and DPCP (see Figure 1a) on hair growth, both flanks of six 8-week-old female C57BL / 6 mice were shaved four days prior to topical administration of the compounds (-4 days). During this period, the mice were visually monitored to confirm the absence of hair growth and that the entire shaved area was in the telogen phase, as expected from 8-week-old mice. On the day of administration (day 0), 2% SABDE or 2% DCPC was administered topically to the shaved left flank of each of the three mice using a cotton swab (see Figure 1b). Images were taken on days 9 and 16 to visualize hair growth and inflammation (see Figure 1c). Skin pigmentation intensity was quantified using ImageJ. The growth-inducing index was calculated as the change in skin pigmentation intensity (a marker of the growth phase) on the treated side compared to the untreated side (i.e., as a percentage) (see Figure 1d).

[0068] The growth-inducing index can be determined by any method known in the art, including, for example, histological methods (e.g., H&E, with or without staining) and / or other visual morphological methods (e.g., methods for measuring the biological parameters of hair growth). This value is then standardized for a specific experiment (individual mice) and expressed as relative growth induction by the intensity of skin pigmentation on the treated side (a marker of growth) as a percentage of the reference value to the untreated side. Analysis of the growth phase (or other stages) can be carried out by any method known in the art, including, for example, tissue biopsy and / or morphological analysis.

[0069] Inflammation can be measured by known methods such as histological grading, visual identification, and quantification of lesions. Present skin lesions (e.g., blue in Figure 3a) * The number, size, and extent of the references can be visualized and quantified using any method known in the art, including, for example, histological methods (e.g., H&E, other staining or no staining) and / or other visual morphological methods.

[0070] [Example 2] Local administration of novel compounds To compare the effects of SABDE, CF3-SABDE, or CCl-SABDE (see Figure 2a) on hair growth, the chests of three 8-week-old female C57BL / 6 mice were pre-sensitized with 2% of each compound four days before the first treatment, and both flanks were shaved (Day 0). On days 3, 5, and 7, 2% of SABDE, CF3-SABDE, or CCl-SABDE was administered topically to the shaved left flank of each mouse using a cotton swab. Images were taken on day 17 to visualize hair growth and inflammation (see Figures 2B and 2C).

[0071] [Example 3] Comparison of known and novel compounds The effects of local therapeutic doses of SADBE or CF3-SADBE were measured using the method described in Example 1. In Figure 3, the local therapeutic dose used was 50 μL of 100 mM SADBE or CF3-SADBE.

[0072] [Example 4] Induction of growth phase by CF3-SADBE The effects of local therapeutic doses of CF3-SADBE were measured and visualized using the method described in Example 1. Macroscopic images of mice treated with CF3-SADBE were obtained (see Figure 4a). CF3-SADBE was administered to the left flank at a dose of 100 μL of 100 mM CF3-SADBE (see Figure 4B). The right flank remained untreated (see Figure 4C).

[0073] [Example 5] Early growth induction with CF3-SADBE, which causes less inflammation than SADBE. The effects of topical treatment with 100 mM CF3-SADBE on growth spurt induction and inflammation were measured and visualized using the method described in Example 1. Treatment with 100 mM CF3-SADBE induced a clear growth spurt by day 10. Treatment with 100 mM SADBE did not induce a clear growth spurt by day 10 (see purple arrow in Figure 5). This indicates the improved efficacy of CF3-SADBE. SADBE also caused more pronounced inflammation by day 14 (see blue arrow in Figure 5). * (See reference). Healthy hair growth was observed on the treated flank by day 17. Other Embodiments

[0074] The disclosure is described in detail, but the foregoing description is intended to illustrate the scope of the disclosure and is not intended to limit it, which is understood to be defined by the attached claims. Other aspects, advantages, and modifications fall within the following claims. The present invention includes the following embodiments. [1] Formula (1): [ka] A compound of [unclear]. [2] A pharmaceutical composition comprising the compound described in [1] above and a pharmaceutically acceptable carrier. [3] The pharmaceutical composition according to [2] above, further comprising one or more anti-inflammatory agents. [4] The pharmaceutical composition according to [3] above, wherein the anti-inflammatory agent is selected from the group consisting of glucocorticoids, calcipotriol, immunosuppressants, and antihistamines. [5] The pharmaceutical composition according to [2] above, further comprising an agent selected from minoxidil, finasteride, SADBE, DPCP, and combinations thereof. [6] The pharmaceutical composition described above [2], which is formulated for topical or subcutaneous administration. [7] A pharmaceutical composition for promoting hair growth in mammals requiring it, comprising an effective amount of the compound described in [1] above and a pharmaceutically or dermatologically acceptable carrier. [8] A hair care composition for promoting hair growth in mammals requiring it, comprising an effective amount of the compound described in [1] above and a dermatologically acceptable carrier. [9] Percentage of hair follicles in the growth phase To promote and hair follicles in the resting phase of Combine decrease A method for causing, the method comprising administering an effective amount of the compound described in [1] above to a subject in need thereof.

[10] The subject is a person having alopecia, according to the method described in [9] above.

[11] The aforementioned alopecia include acne keloids, alopecia areata, complete alopecia, generalized alopecia, pubertal alopecia, male hormone-induced alopecia, block alopecia, central centrifugal scarring alopecia, scarring alopecia, congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, lupus discoid (DLE), dissociative cellulitis, "terminal" or "untreatable" scarring alopecia, female pattern alopecia, alopecia areata, frontal sclerosing alopecia, and hair shaft abnormalities. The method according to

[10] above, selected from the group consisting of hyperandrogenism, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris, lipoderma alopecia, male pattern baldness, non-scarring alopecia, psoriasis, psoriasis-like alopecia, pressure alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis.

[12] A method for treating hair loss in a subject, the method comprising administering a therapeutically effective amount of the compound described in [1] above to a subject in need thereof.

[13] The hair loss is related to alopecia, as described in

[12] above.

[14] The method according to

[12] above, wherein the compound is administered to the skin, hair, or scalp of a mammal that requires it.

[15] A method for stimulating hair growth, comprising administering a therapeutically effective amount of the compound described in [1] above.

[16] A method for promoting hair growth, comprising administering a therapeutically effective amount of the compound described in [1] above.

[17] A method for inhibiting hair loss, comprising administering a therapeutically effective amount of the compound described in [1] above.

[18] A method for promoting hair growth of a target, the method comprising topically applying an effective amount of a formulation to the hair follicles of the target and / or the skin covering the hair follicles, the formulation comprising the compound described in [1] above and an acceptable carrier, the formulation being applied 1, 2, 3, or more times.

[19] The method according to

[18] above, wherein the acceptable carrier includes one or more aqueous gels, alcohol gels, ointments, oils, alcoholic or aqueous liquids, water-in-oil emulsions, oil-in-water emulsions, and water-in-silicone emulsions.

[20] The method according to

[18] , wherein the preparation further comprises an acceptable auxiliary component selected from the group consisting of xanthan gum, glycerin, EDTA, sodium benzoate, phenoxyethanol, 2-hydroxyfatty alcohol alkoxylate, sodium polyacrylate, polysorbate 20, BHT, disaccharide gum, ethylhexylglycerin, carbomer, butylene glycol, acrylate polymer, PEG-40 hydrogenated castor oil, methylisothiazolinone, methylchloroisothiazolinone, propylene glycol, potassium sorbate, polyglyceryl caprylate, fragrance, and water. [twenty one] The method according to

[18] above, wherein the preparation further comprises an agent selected from the group consisting of minoxidil, finasteride, DPCP, SADBE, and combinations thereof. [twenty two] The method described above is the method described in

[18] , which increases hair growth by at least about 10%. [twenty three] The method described above is the method described in

[21] , which increases hair growth by at least about 15%. [twenty four] The method described above is the method according to

[21] , which increases hair growth by at least about 20%. [twenty five] The method according to

[18] above, further comprising administering one or more steroids.

[26] The method according to

[18] above, further comprising administering one or more drugs to reduce the sensitivity of the scalp or skin of a mammal in need thereof.

[27] The method according to

[18] above, further comprising administering one or more drugs to modulate inflammation.

[28] A method for promoting the transition of hair follicles to the growth phase, the method comprising administering a composition containing an effective amount of compound 1.

[29] A method for denser hair, comprising administering a composition containing an effective amount of compound 1.

[30] A method for reducing hair loss, comprising administering a composition containing an effective amount of compound 1.

[31] A pharmaceutical composition for promoting hair growth in mammals requiring it, comprising an effective amount of SADBE and / or DPCP, and a pharmaceutically or dermatologically acceptable carrier, The aforementioned mammal does not have an autoimmune disease, and the pharmaceutical composition.

[32] A method for promoting the transition of hair follicles from the resting phase to the growth phase, wherein the method involves administering an effective amount of SADBE and / or DPCP to a subject in need thereof, the subject not having an autoimmune disease.

[33] The subject is a person having alopecia, according to the method described in

[32] above.

[34] The aforementioned alopecia include acne keloids, complete alopecia, generalized alopecia, pubertal alopecia, male hormone-induced alopecia, block alopecia, central centrifugal scarring alopecia, scarring alopecia, congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, lupus discoid (DLE), dissociative cellulitis, "terminal" or "ineffective" scarring alopecia, female pattern alopecia, alopecia folliculitis, frontal sclerosing alopecia, hair shaft abnormalities, and hyperalopecia. The method according to

[33] above, selected from the group consisting of ndrogenosis, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris, lipoderma alopecia, male pattern baldness, non-scarring alopecia, psoriasis, psoriasis-like alopecia, pressure alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis.

[35] A method for treating hair loss, the method comprising administering a therapeutically effective dose of SADBE and / or DPCP, The aforementioned hair loss is not related to an autoimmune disease.

[36] The hair loss described above is related to non-autoimmune alopecia, as described in

[35] above.

[37] The aforementioned non-autoimmune alopecia include acne keloids, complete alopecia, generalized alopecia, pubertal alopecia, male hormone-induced alopecia, nerve block alopecia, central centrifugal scarring alopecia, scarring alopecia, congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, lupus discoid (DLE), dissociative cellulitis, "terminal" or "untreatable" scarring alopecia, female pattern hair loss, alopecia alopecia, frontal sclerosing alopecia, and hair shaft abnormalities. The method according to

[36] above, selected from the group consisting of hyperandrogenism, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris, lipoderma alopecia, male pattern baldness, non-scarring alopecia, psoriasis, psoriasis-like alopecia, pressure alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriasis-like alopecia, traction alopecia, trichorrhizosis nodosa, trichotillomania, and tufted folliculitis.

[38] The method according to

[35] above, wherein the compound is administered to the skin, hair, or scalp of a mammal that requires it.

[39] A method for stimulating hair growth in a subject requiring such stimulation, the method comprising administering a therapeutically effective dose of SADBE and / or DPCP, wherein the subject does not have an autoimmune disease.

[40] A method for promoting hair growth in a subject requiring such treatment, the method comprising administering a therapeutically effective dose of SADBE and / or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

[41] A method for suppressing hair loss in a subject requiring such treatment, the method comprising administering a therapeutically effective dose of SADBE and / or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

[42] A method for promoting hair growth in a subject requiring such promotion, the method comprising topically applying an effective amount of a formulation to a hair follicle and / or the skin covering the hair follicle, the formulation comprising SADBE and / or DPCP, and an acceptable carrier, the formulation being applied 1, 2, 3, or more times, and the subject not having hair loss associated with an autoimmune disease.

[43] The method according to

[42] above, wherein the acceptable carrier includes one or more aqueous gels, alcohol gels, ointments, oils, alcoholic or aqueous liquids, water-in-oil emulsions, oil-in-water emulsions, and water-in-silicone emulsions.

[44] The method according to

[42] , wherein the formulation further comprises an acceptable auxiliary component selected from the group consisting of xanthan gum, glycerin, EDTA, sodium benzoate, phenoxyethanol, 2-hydroxyfatty alcohol alkoxylate, sodium polyacrylate, polysorbate 20, BHT, disaccharide gum, ethylhexylglycerin, carbomer, butylene glycol, acrylate polymer, PEG-40 hydrogenated castor oil, methylisothiazolinone, methylchloroisothiazolinone, propylene glycol, potassium sorbate, polyglyceryl caprylate, fragrance, and water.

[45] The method according to

[42] above, wherein the preparation comprises an agent selected from the group consisting of minoxidil, finasteride, DPCP, SADBE, and combinations thereof.

[46] The method described above is the method described in

[42] , which increases hair growth by at least about 10%.

[47] The method described above is the method described in

[42] , which increases hair growth by at least about 15%.

[48] The method described above is the method described in

[42] , which increases hair growth by at least about 20%.

[49] The method according to

[42] above, further comprising administering one or more steroids.

[50] The method according to

[42] above, further comprising administering one or more drugs to reduce the sensitivity of the scalp or skin of a mammal in need thereof.

[51] The method according to

[42] above, further comprising administering one or more drugs to modulate inflammation.

[52] A method for promoting the transition from the resting phase to the growth phase of hair follicles in a subject requiring such action, the method comprising administering a composition comprising an effective amount of SADBE or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

[53] A method for densening the hair of a subject who requires it, the method comprising administering a composition containing an effective amount of SADBE or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

[54] A method for reducing hair loss in a subject requiring such reduction, the method comprising administering a composition containing an effective amount of SADBE or DPCP, wherein the subject does not have hair loss associated with an autoimmune disease.

Claims

1. Formula (1): 【Chemistry 1】 A compound of [unclear].

2. A pharmaceutical composition comprising the compound described in claim 1 and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition according to claim 2, further comprising one or more anti-inflammatory agents.

4. The pharmaceutical composition according to claim 3, wherein the anti-inflammatory agent is selected from the group consisting of glucocorticoids, calcipotriol, immunosuppressants, and antihistamines.

5. The pharmaceutical composition according to claim 2, further comprising an agent selected from minoxidil, finasteride, dibutyl squamate (SADBE), diphenylcyclopropenone (DPCP), and combinations thereof.

6. The pharmaceutical composition according to claim 2, wherein the composition is formulated for topical or subcutaneous administration.

7. A pharmaceutical composition for promoting hair growth in mammals requiring the same, comprising an effective amount of the compound described in claim 1 and a pharmaceutically or dermatologically acceptable carrier.

8. A hair care composition for promoting hair growth in mammals requiring the use of the same, comprising an effective amount of the compound described in claim 1 and a dermatologically acceptable carrier.

9. A pharmaceutical composition comprising an effective amount of the compound described in claim 1, for increasing the proportion of hair follicles in the growth phase and decreasing the proportion of hair follicles in the resting phase.

10. The subject is the pharmaceutical composition according to claim 9, which has alopecia.

11. The aforementioned alopecia include acne keloids, alopecia areata, complete alopecia, generalized alopecia, pubertal alopecia, male hormone-induced alopecia, block alopecia, central centrifugal scarring alopecia, scarring alopecia, congenital alopecia, congenital hypotrichosis, diffuse alopecia areata, lupus discoid (DLE), dissociative cellulitis, "terminal" or "untreatable" scarring alopecia, female pattern alopecia, alopecia alopecia, frontal sclerosing alopecia, and hair shaft dysplasia. The pharmaceutical composition according to claim 10, selected from the group consisting of common hyperandrogenicity, hypotrichosis, hereditary alopecia, lichen planus, keratosis pilaris, lipoderma alopecia, male pattern baldness, non-scarring alopecia, psoriasis, psoriatic alopecia, pressure alopecia, seborrheic dermatitis psoriasis, telogen effluvium, temporal triangle alopecia, tinea capitis, TNF-α inhibitor-induced psoriatic alopecia, traction alopecia, trichorrhizosis nodosa, and folliculitis latifoliata.

12. A pharmaceutical composition for treating a target hair loss, comprising a therapeutically effective amount of the compound described in claim 1.

13. The pharmaceutical composition according to claim 12, wherein the hair loss is related to alopecia.

14. The pharmaceutical composition according to claim 12, wherein the hair loss is related to trichotillomania.

15. The pharmaceutical composition according to claim 12, wherein the compound is administered to the skin, hair, or scalp of a mammal that requires it.

16. A pharmaceutical composition for stimulating hair growth, comprising a therapeutically effective amount of the compound described in claim 1.

17. A pharmaceutical composition for promoting hair growth, comprising a therapeutically effective amount of the compound described in claim 1.

18. A pharmaceutical composition for inhibiting hair loss, comprising a therapeutically effective amount of the compound described in claim 1.

19. A pharmaceutical composition for promoting hair growth of a target, comprising the compound described in claim 1 and an acceptable carrier, wherein an effective amount of the compound described in claim 1 is applied topically to the hair follicles and / or the skin covering the hair follicles, the pharmaceutical composition being applied one, two, three, or more times.

20. The pharmaceutical composition according to claim 19, wherein the acceptable carrier comprises one or more of the following: an aqueous gel, an alcohol gel, an ointment, an oil, an alcoholic or aqueous liquid, an oil-in-oil emulsion, an oil-in-water emulsion, and a silicone-in-water emulsion.

21. The pharmaceutical composition according to claim 19, further comprising an acceptable auxiliary component selected from the group consisting of xanthan gum, glycerin, EDTA, sodium benzoate, phenoxyethanol, 2-hydroxyfatty alcohol alkoxylate, sodium polyacrylate, polysorbate 20, BHT, disaccharide gum, ethylhexylglycerin, carbomer, butylene glycol, acrylate polymer, PEG-40 hydrogenated castor oil, methylisothiazolinone, methylchloroisothiazolinone, propylene glycol, potassium sorbate, polyglyceryl caprylate, fragrance, and water.

22. The pharmaceutical composition according to claim 19, further comprising an agent selected from the group consisting of minoxidil, finasteride, diphenylcyclopropenone (DPCP), dibutyl squamate (SADBE), and combinations thereof.

23. The pharmaceutical composition according to claim 19, wherein the pharmaceutical composition increases hair growth by at least 10%.

24. The pharmaceutical composition according to claim 22, wherein the pharmaceutical composition increases hair growth by at least 15%.

25. The pharmaceutical composition according to claim 22, wherein the pharmaceutical composition increases hair growth by at least 20%.

26. Furthermore, the pharmaceutical composition according to claim 19, wherein one or more steroids are administered.

27. The pharmaceutical composition according to claim 19, further comprising the administration of one or more agents for reducing the sensitivity of the scalp or skin of a mammal.

28. Furthermore, the pharmaceutical composition according to claim 19, wherein one or more agents for modulating inflammation are administered.

29. A composition for promoting the transition of hair follicles to the growth phase, comprising an effective amount of the compound described in claim 1.

30. A composition for densening hair, comprising an effective amount of the compound described in claim 1.

31. A composition for reducing hair thinning, comprising an effective amount of the compound described in claim 1.

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