Cosmetic compositions for preventing, alleviating, or improving hair loss

Abstract

The present invention relates to a cosmetic composition for preventing, alleviating, or improving hair loss. According to the present invention, a cosmetic composition is provided that not only suppresses the action of TGF-β1 factor but also has an inhibitory effect on 5-alpha-reductase, thereby exhibiting excellent effects in preventing, alleviating, or improving hair loss.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority rights under Republic of Korea Patent Application No. 10-2023-0120959 dated September 12, 2023, Republic of Korea Patent Application No. 10-2024-0099301 dated July 26, 2024, and Republic of Korea Patent Application No. 10-2024-0099302 dated July 26, 2024, and all content disclosed in the literature of said Republic of Korea Patent Applications is incorporated herein by reference.

[0002] This invention relates to a cosmetic composition that exhibits effects in preventing, alleviating, or improving hair loss. [Background technology]

[0003] Hair loss can be caused by a variety of factors, including genetics, disease, childbirth, stress, hormones, excessive sebum secretion, poor blood circulation, decreased scalp function, and aging.

[0004] Generally, alopecia refers to a condition in which the proportion of hair in the growth phase decreases and the proportion of hair in the regression or resting phase increases during the hair growth cycle, resulting in an abnormal number of hairs falling out. As hair loss progresses, the growth phase shortens, the transition to the regression and resting phases is accelerated, the volume of the hair papilla decreases, and the hair follicle becomes increasingly smaller. Therefore, in order to treat alopecia, it is important to quickly transition hair follicles in the resting phase to the growth phase and to extend the shortened growth phase. Furthermore, it is important to suppress the action of TGF-β1, a factor that promotes the transition of hair follicle growth to the regression phase.

[0005] On the other hand, male pattern baldness, which accounts for the highest percentage of hair loss cases, is also called androgenic alopecia. Androgenic alopecia occurs when dihydrotestosterone (DHT), produced by the binding of the male hormone testosterone and its active enzyme 5-alpha-reductase, acts on hair follicles to suppress cell division and inhibit hair growth.

[0006] Commercialized hair loss products generally contain active ingredients that are effective in strengthening hair follicle function, moisturizing the scalp, and promoting blood circulation. However, no products have been found that show any significant effect on hair loss symptoms. Furthermore, most 5-alpha-reductase inhibitors are steroid-based ingredients, which have the problem of inducing various side effects. [Overview of the project] [Problems that the invention aims to solve]

[0007] The present invention provides a cosmetic composition for preventing, alleviating, or improving hair loss, comprising a nonsteroidal compound as an active ingredient.

[0008] Furthermore, the present invention provides a pharmaceutical composition for the prevention or treatment of hair loss, comprising a nonsteroidal compound as an active ingredient. [Means for solving the problem]

[0009] According to one embodiment of the invention, a cosmetic composition for preventing, alleviating, or improving hair loss is provided, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0010] According to another embodiment of the invention, the use of 3-hydroxypropionic acid or a derivative thereof for the manufacture of cosmetics for the prevention, alleviation, or improvement of hair loss is provided.

[0011] According to yet another embodiment of the invention, a method is provided for preventing, alleviating, or improving hair loss using a cosmetic composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0012] According to yet another embodiment of the invention, a pharmaceutical composition for the prevention or treatment of hair loss is provided, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0013] According to still other embodiments of the invention, there is provided the use of 3-hydroxypropionic acid or a derivative thereof for the manufacture of a medicament for the prevention or treatment of hair loss.

[0014] According to still other embodiments of the invention, there is provided a method for preventing, alleviating or treating hair loss using a pharmaceutical composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0015] Hereinafter, the cosmetic composition for preventing, alleviating or improving hair loss and the pharmaceutical composition for preventing or treating hair loss according to the embodiments of the invention will be described in more detail.

[0016] The terms and words used in this specification and the claims should not be construed as being limited to ordinary or dictionary meanings. In accordance with the principle that the inventor can appropriately define the concept of the terms in order to explain his invention in the best way, they should be construed in a meaning and concept consistent with the technical idea of the invention.

[0017] Unless otherwise defined herein, all technical and scientific terms have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terms used in the description of the present invention are merely for effectively describing specific examples and are not intended to limit the present invention.

[0018] Although the present invention can be modified in various ways and can have various forms, specific examples are illustrated and described in detail below. However, this is not intended to limit the present invention to a specific disclosed form, and it should be understood that all modifications, equivalents or alternatives included in the above idea and technical scope are included.

[0019] As used herein, the singular forms also include the plural forms unless the context clearly indicates the contrary meaning.

[0020] As used herein, "includes" embodies a particular characteristic, domain, integer, stage, operation, element and / or component, and does not exclude the presence or addition of other particular characteristics, domains, integers, stages, operations, elements, components and / or groups.

[0021] In this specification, when temporal relationships are described using expressions such as "after," "following," "next," or "before," non-continuous events can be included, as long as the expressions "immediately" or "directly" are not used.

[0022] In this specification, the terms "hair loss" or "alopecia" mean a condition in which there is no hair in areas where hair should normally be present due to abnormal hair loss.

[0023] In this specification, the term "prevention" means suppression of the occurrence of symptoms caused by hair loss or symptoms caused by complications of hair loss. In this specification, the term "alleviation" means reduction of symptoms caused by hair loss or complications thereof. And in this specification, the term "improvement" means improvement of symptoms caused by hair loss or complications thereof.

[0024] In this specification, the term "treatment" means the reduction or elimination of symptoms caused by hair loss that has already occurred or symptoms caused by complications of hair loss.

[0025] In this specification, "derivative" means a compound that has been modified to the extent that the structure and properties of the parent compound do not change significantly through reactions such as the introduction of functional groups, oxidation, reduction, or atom substitution.

[0026] In this specification, the term "contains as an active ingredient" means that the composition according to the embodiment of the invention contains 3-hydroxypropionic acid or a derivative thereof in an amount sufficient to achieve the effect of preventing, treating, or improving hair loss.

[0027] As a result of our continued research, we have confirmed that 3-hydroxypropionic acid can show excellent effects in preventing, alleviating, or improving hair loss.

[0028] In particular, 3-hydroxypropionic acid not only inhibits the action of TGF-β1 factor but also has an inhibitory effect on 5-alpha-reductase, and compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can show excellent effects in preventing, alleviating, and improving hair loss.

[0029] According to one embodiment of the invention, a cosmetic composition for preventing, alleviating, or improving hair loss is provided, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0030] The aforementioned cosmetic composition for preventing, alleviating, or improving hair loss contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Preferably, the aforementioned cosmetic composition for preventing, alleviating, or improving hair loss contains 3-hydroxypropionic acid as an active ingredient.

[0031] 3-hydroxypropionic acid can be used as an active ingredient if it is synthesized by chemical or biological methods.

[0032] According to one embodiment, as the active ingredient, 3-hydroxypropionic acid obtained by a biological process such as fermenting a bacterial strain capable of producing 3-hydroxypropionic acid can be preferably used. The 3-hydroxypropionic acid obtained by the above method is a radioactive carbon isotope ( 14 C) May include.

[0033] Preferably, the active ingredient may have a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured according to ASTM D6866-21, and a biocarbon content of 20% by weight or more. Specifically, the active ingredient may have a radioactive carbon isotope content of 20 pMC or more, or 50 pMC or more, or 90 pMC or more, or 100 pMC or more, or 90-110 pMC as measured according to ASTM D6866-21; and a biocarbon content of 20% by weight or more, or 50% by weight or more, or 80% by weight or more, or 90% by weight or more, or 95% by weight or more, or 90-100% by weight.

[0034] The radioactive carbon isotope content (pMC) is the amount of radioactive carbon isotopes contained in 3-hydroxypropionic acid ( 14 C) and radioactive carbon isotopes of modern reference materials ( 14 This refers to the ratio of C). For reference, since the effects of the 1950s nuclear test program are still in effect and have not disappeared, the radioactive carbon isotope content (pMC) may be greater than 100%.

[0035] The biocarbon content mentioned above represents the biocarbon content relative to the total carbon content of 3-hydroxypropionic acid. A higher value indicates a more environmentally friendly compound.

[0036] If the radioactive carbon isotope content (pMC) and biocarbon content of the aforementioned 3-hydroxypropionic acid are excessively low, its environmental friendliness will be reduced, and it will not be considered a bio-derived substance.

[0037] Radioactive carbon isotopes ( 14 C) contains 1 × 10 carbon atoms in the Earth's atmosphere. 12 There is approximately one atom per unit area, and its half-life is approximately 5700 years. Cosmic rays and general nitrogen ( 14 It can be abundant in the upper atmosphere due to nuclear reactions in which N) is involved.

[0038] The radioactive carbon isotope decayed long ago in fossil fuels 14 and the ratio of ¹⁴C can be substantially zero. When using bio-derived substances as raw materials for 3-hydroxypropionic acid or using fossil fuels in combination with them, the content of radioactive carbon isotope (pMC) and the content of bio-carbon contained in 3-hydroxypropionic acid can be measured according to ASTM D6866-21 standard.

[0039] The measurement method can be, for example, making the carbon atoms contained in the compound to be measured into the form of graphite or carbon dioxide gas and measuring with a mass spectrometer, or measuring by liquid scintillation spectrometry. At this time, 14 ¹⁴C ions 12 An accelerator for separating ¹⁴C ions from ¹²C ions may be used, or the two isotopes can be separated and the content and content ratio can be measured with a mass spectrometer.

[0040] The cosmetic composition can suppress the action of TGF-β1 factor secreted from hair follicle cells by the action of the active ingredient. Thereby, the cosmetic composition can exhibit an effect of preventing, alleviating or improving hair loss by suppressing the promotion of the growth phase of hair follicles to the regression phase.

[0041] In addition, the cosmetic composition can suppress the activity of 5α-reductase that generates dihydrotestosterone by the action of the active ingredient. Thereby, the cosmetic composition can exhibit an effect of preventing, alleviating or improving hair loss by preventing the generation of dihydrotestosterone that suppresses cell division in hair follicles and inhibits hair growth.

[0042] According to one embodiment, the cosmetic composition can contain 0.01% to 1.5% by weight of the active ingredient based on the total weight of the cosmetic composition.

[0043] Specifically, the cosmetic composition may contain the active ingredient in an amount of 0.01% or more by weight, or 0.012% or more by weight, and 1.5% or less by weight, or 1.25% or less by weight, or 1.1% or less by weight, or 1.0% or less by weight, based on the total weight of the cosmetic composition.

[0044] In order to ensure that the effects of preventing, alleviating, or improving hair loss are sufficiently achieved by the action of the active ingredient, the cosmetic composition preferably contains 0.01% or more by weight of the active ingredient, or 0.012% or more by weight of the active ingredient.

[0045] However, if the active ingredient is present in excess, the preventive, mitigating, or improving effects on hair loss may decrease, or side effects such as cytotoxicity may occur. For this reason, it is preferable that the cosmetic composition contains the active ingredient in an amount of 1.5% by weight or less, or 1.25% by weight or less, or 1.1% by weight or less, or 1.0% by weight or less.

[0046] Preferably, the cosmetic composition may contain the active ingredient in an amount of 0.01% to 1.5% by weight, or 0.01% to 1.25% by weight, or 0.01% to 1.1% by weight, or 0.01% to 1.0% by weight, or 0.012% to 1.0% by weight, based on the total weight of the cosmetic composition.

[0047] According to one embodiment, the cosmetic composition may have a conventional cosmetic dosage form in the art to which the present invention belongs. For example, the cosmetic composition may be in the form of a solution, emulsion, suspension, paste, gel, cream, lotion, powder, soap, cleanser containing surfactant, oil, powder foundation, emulsion foundation, wax foundation, spray, etc.

[0048] The cosmetic composition may further include a physiologically acceptable medium, which is composed of water or a mixture of an organic solvent and water.

[0049] As an example, the organic solvent can be a C1-C4 lower alcohol such as acetone, ethanol, and isopropyl alcohol; an alkylene glycol such as ethylene glycol and propylene glycol; ethylene glycol monomethyl ether, monoethyl ether, monobutyl ether, or propylene glycol. The physiologically acceptable medium may be applied in an amount of 1 to 90% by weight relative to the total weight of the cosmetic composition.

[0050] The medium can be thickened using a thickening agent commonly used in cosmetics or pharmaceuticals. The thickening agent may be applied in an amount of 0.1 to 5% by weight relative to the total weight of the composition.

[0051] Furthermore, depending on the various embodiments of the cosmetic composition, an ordinary technician can select the auxiliary agents commonly required to manufacture such a composition. As an example, the auxiliary agents that can be used include preservatives, stabilizers, pH adjusters, osmotic pressure modifiers, emulsifying agents, light-blocking agents, antioxidants, fragrances, dyes, anionic surfactants, cationic surfactants, nonionic surfactants, and amphoteric surfactants.

[0052] According to one embodiment, when the dosage form of the cosmetic composition is a powder or a spray, it may contain carrier components such as lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder.

[0053] According to one embodiment, if the dosage form of the cosmetic composition is a paste, gel, or cream, it may contain carrier components such as animal oils, vegetable oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicones, bentonite, silica, talc, and zinc oxide.

[0054] According to one embodiment, when the dosage form of the cosmetic composition is a solution or emulsion, it may contain carrier components such as a solvent, solubilizer, or emulsifier. For example, the solution or emulsion dosage form can include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan.

[0055] According to one embodiment, when the dosage form of the cosmetic composition is a suspension, liquid diluents such as water, ethanol, or propylene glycol; suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester; and microcrystalline cellulose, aluminum methhydroxyl, bentonite, etc. can be used. one

[0056] According to the examples, when the dosage form of the cosmetic composition is a cleanser containing a surfactant, it may contain carrier components such as aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinate monoester, isethionate, imidazolinium derivative, sodium methyl cocoyl taurate, sodium lauroyl sarcosinate, fatty acid amide ether sulfate, alkylamide betaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, and ethoxylated glycerol fatty acid ester.

[0057] According to one embodiment, the cosmetic composition may be for use on hair or scalp.

[0058] For example, the cosmetic composition may have a dosage form such as hair shampoo, hair rinse, hair tonic, hair treatment, scalp treatment, hair lotion, hair cream, hair spray, hair foam, hair gel, hair pack, hair aerosol, hair dye, balm, powder, solid soap, or liquid soap.

[0059] According to another embodiment of the invention, uses of 3-hydroxypropionic acid or its derivatives are provided for the manufacture of cosmetics for the prevention, alleviation, or improvement of hair loss.

[0060] Preferably, uses of 3-hydroxypropionic acid or its derivatives are provided for the manufacture of the above-mentioned cosmetic compositions for preventing, alleviating, or improving hair loss.

[0061] 3-hydroxypropionic acid inhibits the action of TGF-β1 factor and has an inhibitory effect on 5-alpha-reductase. Cosmetic compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can be used for the prevention, alleviation, or improvement of hair loss.

[0062] In the above-mentioned applications, the active ingredient, 3-hydroxypropionic acid or its derivative, may be used in an amount of 0.01% to 1.5% by weight based on the total weight of the cosmetic composition.

[0063] In order to ensure that the preventive, mitigating, or ameliorating effects of the active ingredient are sufficiently achieved, it is preferable that the active ingredient be used in an amount of 0.01% by weight or more, or 0.012% by weight or more, based on the total weight of the cosmetic composition. However, if the active ingredient is used in excess, the above-mentioned effects may decrease, or side effects such as cytotoxicity may occur. For this reason, it is preferable that the active ingredient be used in an amount of 1.5% by weight or less, or 1.25% by weight or less, or 1.1% by weight or less, or 1.0% by weight or less, based on the total weight of the cosmetic composition. Preferably, the active ingredient may be used in an amount of 0.01% to 1.5% by weight, or 0.01% to 1.25% by weight, or 0.01% to 1.1% by weight, or 0.01% to 1.0% by weight, or 0.012% to 1.0% by weight, based on the total weight of the cosmetic composition.

[0064] A further embodiment of the invention provides a method for preventing, alleviating, or improving hair loss using a cosmetic composition containing 3-hydroxypropionic acid or a derivative as an active ingredient. Specifically, a method is provided for suppressing the action of TGF-β1 factor secreted from hair follicle cells using a cosmetic composition containing 3-hydroxypropionic acid or a derivative as an active ingredient. Furthermore, a method is provided for suppressing the activity of 5α-reductase, which produces dihydrotestosterone, using a cosmetic composition containing 3-hydroxypropionic acid or a derivative as an active ingredient.

[0065] Preferably, the method for preventing, mitigating, or improving hair loss may be carried out using the above-described cosmetic composition for preventing, mitigating, or improving hair loss. The method may be carried out for a period of 1 to 6 months, 1 to 7 days a week, and 1 to several times a day (for example, 1 to 5 times or 1 to 3 times). The method may be carried out by applying the cosmetic composition to a part of the human body (e.g., hair or scalp) where prevention, mitigation, or improvement of hair loss is required. Specifically, this may include washing the hair with the cosmetic composition in the form of a hair shampoo, washing or massaging the scalp with the cosmetic composition in the form of a scalp treatment, or applying the cosmetic composition in the form of a balm to the scalp.

[0066] According to yet another embodiment of the invention, a pharmaceutical composition for the prevention or treatment of hair loss is provided, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0067] As a result of our continued research, we have confirmed that 3-hydroxypropionic acid can show excellent effects in preventing and treating hair loss.

[0068] In particular, 3-hydroxypropionic acid not only inhibits the action of TGF-β1 factor but also has an inhibitory effect on 5-alpha-reductase, and compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can show excellent effects in preventing and treating hair loss.

[0069] The aforementioned pharmaceutical composition for the prevention or treatment of hair loss contains 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Preferably, the aforementioned pharmaceutical composition for the prevention or treatment of hair loss contains 3-hydroxypropionic acid as an active ingredient.

[0070] 3-hydroxypropionic acid can be used as an active ingredient if it is synthesized by chemical or biological methods.

[0071] According to one embodiment, as the active ingredient, 3-hydroxypropionic acid obtained by a biological process such as fermenting a bacterial strain capable of producing 3-hydroxypropionic acid can be preferably used. The 3-hydroxypropionic acid obtained by the above method is a radioactive carbon isotope ( 14 C) May include.

[0072] Preferably, the active ingredient may have a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured according to ASTM D6866-21, and a biocarbon content of 20% by weight or more. Specifically, the active ingredient may have a radioactive carbon isotope content of 20 pMC or more, or 50 pMC or more, or 90 pMC or more, or 100 pMC or more, or 90-110 pMC as measured according to ASTM D6866-21; and a biocarbon content of 20% by weight or more, or 50% by weight or more, or 80% by weight or more, or 90% by weight or more, or 95% by weight or more, or 90-100% by weight.

[0073] The aforementioned pharmaceutical composition for preventing or treating hair loss can suppress the action of TGF-β1 factor secreted from hair follicle cells through the action of the active ingredient. As a result, the pharmaceutical composition can exhibit a preventive or therapeutic effect on hair loss by suppressing the acceleration of the hair follicle's growth phase into the regression phase.

[0074] Furthermore, the pharmaceutical composition for preventing or treating hair loss can inhibit the activity of 5α-reductase, which produces dihydrotestosterone through the action of the active ingredient. As a result, the pharmaceutical composition can exhibit a preventive or therapeutic effect on hair loss by preventing the production of dihydrotestosterone, which inhibits cell division in hair follicles and hinders hair growth.

[0075] According to one embodiment, the pharmaceutical composition may contain the active ingredient in an amount of 0.01% to 1.5% by weight, based on the total weight of the pharmaceutical composition.

[0076] Specifically, the pharmaceutical composition may contain the active ingredient in an amount of 0.01% or more by weight, or 0.012% or more by weight, and 1.5% or less by weight, or 1.25% or less by weight, or 1.1% or less by weight, or 1.0% or less by weight, based on the total weight of the pharmaceutical composition.

[0077] In order to ensure that the preventive or therapeutic effect of hair loss is sufficiently achieved by the action of the active ingredient, the pharmaceutical composition preferably contains 0.01% or more by weight of the active ingredient, or 0.012% or more by weight of the active ingredient.

[0078] However, if the active ingredient is present in excess, the preventive or therapeutic effect on hair loss may decrease, or side effects such as cytotoxicity may occur. For this reason, it is preferable that the pharmaceutical composition contains the active ingredient in an amount of 1.5% by weight or less, or 1.25% by weight or less, or 1.1% by weight or less, or 1.0% by weight or less.

[0079] Preferably, the pharmaceutical composition may contain the active ingredient in an amount of 0.01% to 1.5% by weight, or 0.01% to 1.25% by weight, or 0.01% to 1.1% by weight, or 0.01% to 1.0% by weight, or 0.012% to 1.0% by weight, based on the total weight of the composition.

[0080] The aforementioned pharmaceutical composition may further contain a pharmaceutically acceptable carrier.

[0081] The carrier can be any material commonly used in the formulation of pharmaceutical compositions, without any special limitations. For example, the carrier may be sucrose, sorbitol, mannitol, lactose, dextrose, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, propyl 4-hydroxybenzoate, talc, magnesium stearate, mineral oil, etc. Pharmaceutically acceptable carriers and formulations are described in detail in Remington's The Science and Practice of Pharmacy (23rd Edition, 2020).

[0082] The pharmaceutical composition may be administered orally or parenterally. When administered parenterally, methods such as topical application, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, and transdermal administration are applicable.

[0083] The appropriate dosage of the pharmaceutical composition can be determined by comprehensively considering factors such as the patient's age, weight, sex, formulation method, administration method, and administration time.

[0084] The pharmaceutical composition may be formulated by applying pharmaceutically acceptable carriers and / or excipients. The dosage form of the pharmaceutical composition may be a solution in an aqueous medium or oil, a suspension, an emulsion, an ointment, a powder, granules, a tablet, or a capsule.

[0085] According to yet another embodiment of the invention, uses of 3-hydroxypropionic acid or its derivatives are provided for the manufacture of agents for the prevention or treatment of hair loss.

[0086] Preferably, uses of 3-hydroxypropionic acid or its derivatives for the manufacture of the above-mentioned pharmaceutical compositions for the prevention or treatment of hair loss are provided.

[0087] 3-hydroxypropionic acid inhibits the action of TGF-β1 factor and has an inhibitory effect on 5α-reductase. Compositions containing 3-hydroxypropionic acid or its derivatives as an active ingredient can be used for the prevention or treatment of hair loss.

[0088] In the above-mentioned applications, the active ingredient, 3-hydroxypropionic acid or its derivative, may be used in an amount of 0.01% to 1.5% by weight based on the total weight of the pharmaceutical composition.

[0089] In order to ensure that the preventive or therapeutic effect of hair loss is sufficiently achieved by the action of the active ingredient, it is preferable that the active ingredient be used in an amount of 0.01% by weight or more, or 0.012% by weight or more, based on the total weight of the pharmaceutical composition. However, if the active ingredient is used in excess, the above-mentioned effects may decrease, or side effects such as cytotoxicity may occur. For this reason, it is preferable that the active ingredient be used in an amount of 1.5% by weight or less, or 1.25% by weight or less, or 1.1% by weight or less, or 1.0% by weight or less, based on the total weight of the pharmaceutical composition. Preferably, the active ingredient may be used in an amount of 0.01% to 1.5% by weight, or 0.01% to 1.25% by weight, or 0.01% to 1.1% by weight, or 0.01% to 1.0% by weight, or 0.012% to 1.0% by weight, based on the total weight of the pharmaceutical composition.

[0090] A further embodiment of the invention provides a method for preventing or treating hair loss using a pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Specifically, a method is provided for inhibiting the action of TGF-β1 factor secreted from hair follicle cells using a pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient. Furthermore, a method is provided for inhibiting the activity of 5α-reductase, which produces dihydrotestosterone, using a pharmaceutical composition comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

[0091] Preferably, the method for preventing or treating hair loss may be carried out using the above-described pharmaceutical compositions for preventing or treating hair loss. The method may be carried out directly or indirectly to a part of the human body (e.g., the scalp) where the prevention or treatment of hair loss is required. The method may be carried out orally or parenterally. The method may be carried out for a period of 1 to 6 months, 1 to 7 days a week, with an application frequency of 1 to several times a day (for example, 1 to 5 times or 1 to 3 times). The method may be carried out by a standard procedure, taking into account factors such as the patient's age, weight, sex, dosage form of 3-hydroxypropionic acid or its derivatives, method of administration, and timing of administration. [Effects of the Invention]

[0092] According to the present invention, a cosmetic composition that not only suppresses the action of TGF-β1 factor but also has an inhibitory effect on 5-alpha-reductase is provided, which can exhibit excellent effects in preventing, alleviating, or improving hair loss, and a pharmaceutical composition that can exhibit excellent effects in preventing or treating hair loss. [Brief explanation of the drawing]

[0093] [Figure 1] This graph shows the evaluation results of the hair follicle resting phase ratio based on Experiment Example 4. [Figure 2]This graph shows the results of the evaluation of the expression levels of hair follicle cell proliferation-related factor proteins based on Experimental Example 4. [Modes for carrying out the invention]

[0094] The function and effects of the invention will be explained in more detail below through specific embodiments of the invention. However, these are presented as examples for understanding the invention. It is not intended that the scope of the invention's rights be limited in any sense through the following embodiments, and it will be obvious to a person of the skill that various changes and modifications are possible within the scope of the invention and its technical concept.

[0095] Manufacturing Example 1 Recombinant vectors were prepared by introducing genes encoding glycerol dehydratase and aldehyde dehydrogenase, which are known to produce 3-hydroxypropionic acid using glycerol as a substrate. These recombinant vectors were introduced into E. coli W3110 strain to create a strain for 3-hydroxypropionic acid production.

[0096] Specifically, the BtuR gene encoding adenosyltransferase was cloned into a plasmid pCDF containing the genes encoding glycerol dehydratase (dhaB), aldehyde dehydrogenase (aldH), and glycerol dehydratase reactivase (gdrAB) to obtain the pCDF_J23101_dhaB_gdrAB_J23100_aldH_btuR vector. This vector was introduced into the W3110 strain (KCCM40219) using electroporation with an electroporation device (Bio-Rad, Gene Pulser Xcell) to create a strain for 3-hydroxypropionic acid production.

[0097] The aforementioned 3-hydroxypropionic acid production strain was fermented in a 5L fermenter at 35°C using unpurified glycerol as a carbon source to produce 3-hydroxypropionic acid. To prevent a decrease in pH due to the production of 3-hydroxypropionic acid, calcium hydroxide (Ca(OH)2), an alkali metal salt, was added to maintain a neutral pH during fermentation.

[0098] After fermentation culture, cells were removed by centrifugation (4000 rpm, 10 minutes, 4°C), and primary purification was carried out using activated carbon. The concentration of 3-hydroxypropionic acid in the fermentation liquid after the primary purification was at the level of 50-100 g / L, and it was concentrated to 600 g / L using a rotary evaporator (50°C, 50 mbar), and Ca(3HP)2 crystals were produced by stirring at room temperature (300 rpm).

[0099] The crystals were washed three times with ethanol, dried in an oven at 50°C, and finally recovered. The weight of the crystals was measured, and the crystals were dissolved in water to obtain 3-hydroxypropionic acid (3HP) using high-performance liquid chromatography (HPLC).

[0100] Manufacturing Example 2 3-hydroxypropionic acid (3HP) was obtained by a method substantially the same as in Production Example 1, except that Mg(OH)2 was used instead of Ca(OH)2 as the alkali metal salt.

[0101] Example 1 A hair lotion was prepared by mixing 0.025% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining purified water (total 100% by weight).

[0102] Example 2 A hair lotion was prepared by mixing 0.05% by weight of 3-hydroxypropionic acid, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining purified water (total 100% by weight) obtained in Production Example 1.

[0103] Example 3 A hair tonic was prepared by mixing 0.0125% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining amount of purified water (total 100% by weight).

[0104] Example 4 A hair tonic was prepared by mixing 0.025% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining amount of purified water (total 100% by weight).

[0105] Example 5 A hair tonic was prepared by mixing 0.05% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining amount of purified water (total 100% by weight).

[0106] Example 6 A pharmaceutical composition in the form of an ointment was prepared by mixing 0.025% by weight of 3-hydroxypropionic acid, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining amount of purified water (total 100% by weight) obtained in Production Example 1.

[0107] Example 7 A pharmaceutical composition in the form of an ointment was prepared by mixing 0.05% by weight of 3-hydroxypropionic acid, 0.5% by weight of hydroxyethylcellulose, 2% by weight of cetostearyl alcohol, 2% by weight of stearyltriethylammonium chloride, and the remaining amount of purified water (total 100% by weight) obtained in Production Example 1.

[0108] Example 8 A pharmaceutical composition in the form of an emulsion was prepared by mixing 0.0125% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remainder of purified water (total 100% by weight).

[0109] Example 9 A pharmaceutical composition in the form of an emulsion was prepared by mixing 0.025% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining amount of purified water (total 100% by weight).

[0110] Example 10 A pharmaceutical composition in the form of an emulsion was prepared by mixing 0.05% by weight of 3-hydroxypropionic acid obtained in Production Example 1, 55% by weight of ethanol, 3% by weight of glycerin, 5% by weight of castor oil, and the remaining amount of purified water (total 100% by weight).

[0111] Experimental Example 1 (Measurement of radioactive carbon isotope and biocarbon content) The radiocarbon isotope content (pMC) and biocarbon content of 3-hydroxypropionic acid obtained in Production Examples 1 and 2 were measured using ASTM D6866-21 (Method B).

[0112] The biocarbon content refers to the biocarbon content contained in the 3-hydroxypropionate crystals obtained in Production Examples 1 and 2, and the ratio of radiocarbon isotopes (pMC) refers to the radiocarbon isotopes contained in the 3-hydroxypropionate crystals.14 C) and radioactive carbon isotopes of modern reference materials ( 14 This refers to the ratio of C). [Table 1]

[0113] Referring to Table 1 above, it was confirmed that both the 3HP salt crystals of production examples 1 and 2 had a radioactive carbon isotope ratio of 10¹ pMC or higher and a biocarbon content of 100% by weight.

[0114] Experimental Example 2 Human follicle dermal papilla cells (PromoCell GmbH) were cultured at 37°C under 5% CO2 conditions in a culture medium (PromoCell GmbH) supplemented with fetal bovine serum (FCS), bovine pituitary extract (BPE), basic fibroblast growth factor (bFGF), and insulin.

[0115] Cultured human dermal papilla cells were placed in a 96-well plate in a 5 × 10⁶ arrangement. 3 After dividing the samples into individual portions and culturing to over 80%, they were treated with four concentrations of 3-hydroxypropionic acid aqueous solution (3HP concentrations of 0%, 0.0125%, 0.025%, and 0.05%) according to Production Example 1, and then cultured for 24 hours. Subsequently, WST substrate solution (high sensitivity water soluble tetrazolium salt, CCK-8, DOJINDO) was added to the culture medium and cultured at 37°C for 2 hours.

[0116] During the culture period, water-insoluble formazan was produced by the reaction of WST with intracellular dehydrogenase, and its absorbance (OD, wavelength 450 nm) was measured. Cell viability was calculated using Equation 1 below, and the results are shown in Table 1. [Formula 1] Cell viability (%)=[(OD 実験群 -OD 対照群 ) / (OD 陰性対照群 -OD対照群 )] × 100

[0117] In Formula 1 above, the "experimental group" is the group treated with an aqueous solution containing 3HP; the "control group" is the medium containing only the WST substrate; and the "negative control group" is the medium containing the WST substrate treated with an aqueous solution of 0% 3HP. [Table 2]

[0118] Based on the experimental results mentioned above, a high cell viability rate was observed under the aforementioned treatment concentration of 3-hydroxypropionic acid.

[0119] Experimental Example 3 Human follicle dermal papilla cells (PromoCell GmbH) were cultured at 37°C under 5% CO2 conditions in a culture medium (PromoCell GmbH) supplemented with fetal bovine serum (FCS), bovine pituitary extract (BPE), basic fiber cell growth factor (bFGF), and insulin.

[0120] Cultured human dermal papilla cells were placed in a 96-well plate in a 5 × 10⁶ arrangement. 4 The cells were divided into groups, and when more than 80% were cultured, they were treated with 3-hydroxypropionic acid (3HP) according to Production Example 1 at four concentrations (0% by weight, 0.0125% by weight, 0.025% by weight, and 0.05% by weight), and then cultured for 24 hours. Subsequently, total RNA was extracted from the cells, and cDNA was synthesized from the extracted RNA. A real-time polymerization chain reaction was carried out on the synthesized cDNA. Then, relative quantitative analysis of each gene was performed using GAPDH (one of the house-keeping genes). The relative quantification (RQ) value was calculated using Equation 2 below. [Formula 2] RQ = 2 - △△C T △△C T =△C T (Treatment)-△CT (Control) △C T =C T (Target gene)-C T (House-keeping gene)

[0121] In equation 2 above, "Treatment" is the group treated with 3HP; "Control" is the group not treated with 3HP; "Target gene" is Srd5α1 and TGF-β1; and "House-keeping gene" is GAPDH. [Table 3] [Table 4]

[0122] Based on the experimental results described above, it was confirmed that the expression of the TGF-β1 gene and the 5α-reductase gene could be significantly suppressed under the treatment concentration of 3-hydroxypropionic acid.

[0123] Experimental Example 4 The following methods were used to evaluate the ratio of hair follicle resting phases and the expression levels of hair follicle cell proliferation-related factor proteins, depending on whether or not 3-hydroxypropionic acid was applied.

[0124] (1) Tissue culture conditions Human hair follicles or scalp tissue provided for research purposes (IRB No. 4-2023-1052; Yonsei University College of Medicine, Severance Medical Center Bioethics Committee) were washed several times with PBS to remove residual impurities, and then randomly allocated to each group. The hair follicles and scalp tissue were cultured at 37°C and 5% CO2 in a medium containing Williams' Medium E (Sigma) supplemented with 2 mM L-glutamine (Sigma-Aldrich), 10 μg / ml insulin (Sigma-Aldrich), 100 ng / ml hydrocortisone (Sigma-Aldrich), 0.1% fungizone (Gibco, USA), and 1% antibiotic-antimycotic (Gibco), and 1% penicillin-streptomycin (Gibco).

[0125] (2) Evaluation of the hair follicle resting phase ratio Hair follicle tissue in the growth phase was treated with the test composition along with 1 μM dihydrotestosterone (DHT) to induce the resting phase. The culture medium was changed every 3 days, and the follicles were incubated for 6 days. The resting phase ratio of hair follicles was visually evaluated as the percentage of hair follicles that entered the resting phase on day 6 compared to day 0.

[0126] (3) Evaluation of the expression levels of cell proliferation-related factor proteins After treating scalp tissue with the test composition for 24 hours, the resulting tissue was prepared as a frozen block. Using a cryostat microtome (Leica Biosystems, Germany), the tissue sections were frozen to a thickness of 5 μm and mounted onto silane-coated slides. Subsequently, after removing the OCT compound for staining and imaging of the tissue sections, a primary antibody that specifically binds to Ki67 (Anti-Ki67 antibody: ab15580; abcam) was attached, followed by a fluorescently labeled secondary antibody that specifically binds to this primary antibody (Goat pAb to Rb IgG(H+L): a11012; Invitrogen). Finally, a fixative containing blue fluorescent DAPI for staining cell nuclei (VECTASHIELD) was applied. ○RAfter fixing the tissue with mounting medium with DAPI (Vector Laboratories), images were taken at 100x magnification using a fluorescence microscope (M2; Zeiss). From the acquired images, the percentage of cells expressing Ki67 out of the total cells labeled with DAPI was measured. A higher value indicates a greater number of cells expressing Ki67. [Table 5]

[0127] Referring to Table 5 and Figure 1, it was confirmed that the hair follicle resting phase ratio was significantly reduced when 0.1%, 0.5%, and 1.0% 3HP were applied compared to the DHT control group in the evaluation of the hair follicle resting phase ratio. [Table 6]

[0128] Referring to Table 6 and Figure 2 above, it was confirmed that the proliferation effect of hair follicle cells was significantly increased when 0.1% 3HP was applied compared to the negative control group in the evaluation of hair follicle cell proliferation by Ki67 immunofluorescence staining.

[0129] Dosage Form Example 1 A hair tonic is prepared by mixing 0.2% by weight of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 3.0% by weight of glycerin, 2.0% by weight of butylene glycol, 2.0% by weight of propylene glycol, 0.1% by weight of polyacrylic acid, 0.2% by weight of polyethylene glycol-12 noniphenyl ether, 0.4% by weight of polysorbate-80, 10.0% by weight of ethanol, 0.1% by weight of triethanolamine, and the remainder of purified water.

[0130] Dosage Form Example 2 A hair lotion is prepared by mixing 1.0 wt% of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 3.0 wt% of glycerin, 3.0 wt% of butylene glycol, 7.0 wt% of liquid paraffin, 7.0 wt% of beta-glucan, 3.0 wt% of caprylic / capric triglyceride, 5.0 wt% of squalene, 1.5 wt% of cetearyl glucoside, 1.2 wt% of polybravivate-60, 0.4 wt% of sorbitan stearate, 0.1 wt% of polyacrylic acid, 0.1 wt% of triethanolamine, and the remainder of purified water.

[0131] Dosage Form Example 3 A hair shampoo is prepared by mixing 1.0 wt% of 3-hydroxypropionic acid according to the above production example 1, 0.5 wt% of polyquaternium-10, 10 wt% of sodium lauryl sulfate, 30 wt% of polyoxyethylene lauryl ether, 5 wt% of coconut oil fatty acid diethanolamide, 0.5 wt% of citric acid, 0.4 wt% of fragrance, and the remainder of purified water.

[0132] Dosage Form Example 4 A hair dye is prepared by mixing 1.0% by weight of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, 1.0% by weight of a dye (Basic Brown 16), 4.5% by weight of benzyl alcohol, 4.0% by weight of glycerin, 5.0% by weight of polyquaternium-6, and the remaining amount of cream (a cream mainly composed of cetearyl alcohol).

[0133] Dosage Form Example 5 A hair treatment is prepared by mixing 1.0 wt% of 3-hydroxypropionic acid according to the above production example 1, 30 wt% of methylpropanediol, 3 wt% of stearamidopropyldimethylamine, 2 wt% of dipalmitoylethyldimonium chloride, 5 wt% of oil, 12 wt% of cetearyl alcohol, and the remainder of purified water.

[0134] Dosage Form Example 6 A hairspray is prepared by mixing 1.0 wt% of 3-hydroxypropionic acid according to Production Example 1, 0.006 wt% of lecithin, 0.12 wt% of an amphoteric surfactant, 0.02 wt% of a nonionic surfactant, 2.5 wt% of a film-forming polymer, 0.005 wt% of a cationic polymer, 3.0 wt% of a wetting agent, 2.0 wt% of dimethicone, 5.0 wt% of ethanol, 0.5 wt% of a pH adjuster, and the remainder of purified water.

[0135] Dosage Form Example 7 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 200 mg of lactose, and 200 mg of galactooligosaccharide are mixed according to the above production example 1, granulated using a fluid bed dryer, and then 5 mg of sugar ester is added to produce a tablet composition. 500 mg of the tablet composition is compressed into tablets to produce tablets.

[0136] A soft capsule filling solution is prepared by mixing 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 10 mg of hydrogenated vegetable oil, and 9 mg of lecithin according to the above-mentioned Production Example 1. Separately, a soft capsule sheet is prepared by mixing gelatin (65% by weight), glycerin (25% by weight), and sorbitol solution (10% by weight). Soft capsules are prepared by filling each capsule with 400 mg of the soft capsule filling solution.

[0137] Dosage Form Example 9 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 500 mg of starch, and 200 mg of anhydrous crystalline glucose are mixed according to the above-mentioned Production Example 1, formed into granules using a fluid bed granulator, and then filled into packets to produce a granular preparation.

[0138] Dosage Form Example 10 After mixing 8 mg of 3-hydroxypropionic acid, 9 mg of vitamin C, 9 mg of vitamin E, 0.7 g of citric acid, 10 g of glucose, and 25 g of liquid oligosaccharide according to the above production example 1, 300 ml of purified water is added to produce a drinkable composition. The drinkable composition is filled into bottles in 200 ml portions and sterilized at 130°C for approximately 5 seconds to produce a drinkable product.

[0139] Dosage Form Example 11 A solution is prepared by mixing 30 mg of 3-hydroxypropionic acid according to the above-mentioned Production Example 1, an appropriate amount of sterile distilled water for injection, and an appropriate amount of pH adjuster.

[0140] Although the present invention has been described above, even if only by limited embodiments, the present invention is not limited thereto, and of course, a wide range of modifications and variations are possible by persons with ordinary skill in the art to which the present invention pertains, within the equivalent scope of the technical concept of the present invention and the claims described below.

Claims

1. A cosmetic composition for preventing, alleviating, or improving hair loss, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

2. The cosmetic composition for preventing, alleviating, or improving hair loss, as described in claim 1, wherein the cosmetic composition suppresses the action of TGF-β1 factor secreted from hair follicle cells.

3. The cosmetic composition for preventing, alleviating, or improving hair loss according to claim 1, wherein the cosmetic composition inhibits the activity of 5α-reductase, which produces dihydrotestosterone.

4. The cosmetic composition for preventing, alleviating, or improving hair loss according to claim 1, wherein the cosmetic composition contains 0.01% to 1% by weight of the active ingredient based on the total weight of the composition.

5. The cosmetic composition for preventing, alleviating, or improving hair loss according to claim 1, wherein the active ingredient has a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured by ASTM D6866-21 standard, and a biocarbon content of 20% by weight or more.

6. The cosmetic composition for preventing, alleviating, or improving hair loss according to claim 1, further comprising a physiologically acceptable medium.

7. The cosmetic composition for preventing, alleviating, or improving hair loss, as described in claim 1, wherein the cosmetic composition is for hair or scalp.

8. The cosmetic composition for preventing, alleviating, or improving hair loss according to claim 1, wherein the cosmetic composition has a dosage form of hair shampoo, hair rinse, hair tonic, hair treatment, scalp treatment, hair lotion, hair cream, hair spray, hair foam, hair gel, hair pack, hair aerosol, hair dye, balm, powder, solid soap, or liquid soap.

9. A pharmaceutical composition for the prevention or treatment of hair loss, comprising 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

10. The pharmaceutical composition for preventing or treating hair loss according to claim 9, wherein the pharmaceutical composition inhibits the action of TGF-β1 factor secreted from hair follicle cells.

11. The pharmaceutical composition for preventing or treating hair loss according to claim 9, wherein the pharmaceutical composition inhibits the activity of 5α-reductase, which produces dihydrotestosterone.

12. The pharmaceutical composition for preventing or treating hair loss according to claim 9, wherein the pharmaceutical composition contains 0.01% to 1.5% by weight of the active ingredient based on the total weight of the composition.

13. The pharmaceutical composition for the prevention or treatment of hair loss according to claim 9, wherein the active ingredient has a radioactive carbon isotope content of 20 pMC (percent modern carbon) or more as measured by ASTM D6866-21 standard, and a biocarbon content of 20% by weight or more.

14. The pharmaceutical composition for the prevention or treatment of hair loss according to claim 9, further comprising a pharmaceutically acceptable carrier.

15. The pharmaceutical composition for the prevention or treatment of hair loss according to claim 9, wherein the pharmaceutical composition is for oral or parenteral use.

16. Uses of 3-hydroxypropionic acid or its derivatives for the manufacture of cosmetics for the prevention, alleviation, or improvement of hair loss, or for the manufacture of agents for the prevention or treatment of hair loss.

17. A method for preventing, alleviating, improving, or treating hair loss using a cosmetic composition or pharmaceutical composition containing 3-hydroxypropionic acid or a derivative thereof as an active ingredient.

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