5α-reductase inhibitor, androgen receptor binding inhibitor, prostate hyperplasia inhibitor, hair growth agent, and acne prevention / improvement agent

Abstract

The present invention provides a new 5α-reductase inhibitor, a new androgen receptor binding inhibitor, a new agent for suppressing benign prostatic hyperplasia, a new hair growth agent, and a new agent for preventing and improving acne. [Solution] A 5α-reductase inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. An androgen receptor binding inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. A prostate hyperplasia inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. A hair growth agent containing p-coumaroylaminobutan-1-ol as an active ingredient. An acne prevention and improvement agent containing p-coumaroylaminobutan-1-ol as an active ingredient.

Description

[Technical Field]

[0001] The present invention relates to a 5α-reductase inhibitor, an androgen receptor binding inhibitor, an agent for suppressing benign prostatic hyperplasia, a hair growth agent, and an agent for preventing and ameliorating acne. [Background technology]

[0002] 5α-reductase is an enzyme that converts the male hormone testosterone into dihydrotestosterone (DHT), enhancing the effects of testosterone. Excessive production of DHT is involved in problems such as benign prostatic hyperplasia and hair loss.

[0003] For example, benign prostatic hyperplasia (BPH) is a disease specific to men in which the enlarged prostate gland puts pressure on the urethra and bladder, causing various urinary problems such as frequent urination and a feeling of incomplete urination. The incidence of BPH increases with age, with a sharp increase after the age of 50. BPH is thought to be caused by dihydrotestosterone binding to the androgen receptor (AR) in prostate cells and promoting the proliferation of prostate cells.

[0004] Therefore, various substances having 5α-reductase inhibitory activity have been proposed (for example, Patent Documents 1 and 2). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 2024-025391 [Patent Document 2] Japanese Patent Publication No. 2023-037173 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a new 5α-reductase inhibitor, a new androgen receptor binding inhibitor, a new agent for suppressing benign prostatic hyperplasia, a new hair growth agent, and a new agent for preventing and improving acne. [Means for solving the problem]

[0007] The present inventors have conducted extensive research to solve the above problems and have found that the following inventions meet the above objectives, thereby completing the present invention.

[0008] <1> A 5α-reductase inhibitor containing p-coumaroylaminobutan-1-ol as the active ingredient. <2> An androgen receptor binding inhibitor containing p-coumaroylaminobutan-1-ol as the active ingredient. <3> An agent for suppressing benign prostatic hyperplasia containing p-coumaroylaminobutan-1-ol as the active ingredient. <4> A hair growth agent containing p-coumaroylaminobutan-1-ol as an active ingredient. <5> An acne prevention and treatment agent containing p-coumaroylaminobutan-1-ol as the active ingredient. [Effects of the Invention]

[0009] According to the present invention, there are provided a new 5α-reductase inhibitor, a new androgen receptor binding inhibitor, a new agent for suppressing benign prostatic hyperplasia, a new hair growth agent, and a new agent for preventing and ameliorating acne. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 shows the results of a test to evaluate 5α-reductase inhibitory activity. [Figure 2] FIG. 1 shows the results of an androgen receptor binding inhibition test. DETAILED DESCRIPTION OF THE INVENTION

[0011] The following describes in detail an embodiment of the present invention, but the following description of the constituent elements is one example (typical example) of an embodiment of the present invention, and the present invention is not limited to the following content unless the gist of the present invention is changed. Note that when the expression "to" is used in this specification, it is used as an expression including the numerical values ​​or physical property values ​​before and after it.

[0012] <5α-reductase inhibitor> The present invention relates to a 5α-reductase inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. p-Coumaroylaminobutan-1-ol has the effect of inhibiting the activity of 5α-reductase, and can therefore be used as the active ingredient of 5α-reductase inhibitors. 5α-reductase is an enzyme that converts testosterone to dihydrotestosterone, and inhibiting the activity of 5α-reductase can suppress the production of dihydrotestosterone.

[0013] <Androgen receptor binding inhibitor> The present invention relates to an androgen receptor binding inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. p-Coumaroylaminobutan-1-ol has the effect of inhibiting the binding of androgens to androgen receptors, and therefore can be used as the active ingredient of an androgen receptor binding inhibitor. Androgens are a type of steroid hormone that function in the body. Androgens are also called male hormones, with testosterone being the most representative male hormone. Androgens exert their androgen effects by binding to the androgen receptor (AR). By inhibiting the binding of androgens to the androgen receptor, the action of androgens can be suppressed.

[0014] <Benign prostatic hyperplasia inhibitor> The present invention relates to a prostatic hyperplasia inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. As described above, in the prostate, testosterone is converted to dihydrotestosterone by 5α-reductase, and this dihydrotestosterone is involved in prostatic hyperplasia. p-Coumaroylaminobutan-1-ol has 5α-reductase inhibitory activity and inhibits binding to the androgen receptor, thereby suppressing the production of dihydrotestosterone and the action of androgens, thereby suppressing prostatic hyperplasia. Therefore, p-Coumaroylaminobutan-1-ol can be used as an active ingredient in a prostatic hyperplasia inhibitor.

[0015] <Hair growth agent> The present invention relates to a hair growth agent containing p-coumaroylaminobutan-1-ol as an active ingredient. Dihydrotestosterone, which is converted from testosterone by 5α-reductase in hair follicles, sebaceous glands, etc., is thought to be one of the causes of hair loss and thinning hair. p-Coumaroylaminobutan-1-ol has 5α-reductase inhibitory activity and inhibits binding to the androgen receptor, thereby suppressing the production of dihydrotestosterone and the action of androgens, thereby preventing hair loss and thinning hair. Therefore, p-coumaroylaminobutan-1-ol can be used as an active ingredient in hair growth agents.

[0016] <Acne prevention and treatment agent> The present invention relates to an acne prevention and amelioration agent containing p-coumaroylaminobutan-1-ol as an active ingredient. Dihydrotestosterone, which is converted from testosterone by 5α-reductase in sebaceous glands and other tissues, is thought to be one of the causes of acne. p-Coumaroylaminobutan-1-ol inhibits 5α-reductase and inhibits binding to androgen receptors, thereby suppressing the production of dihydrotestosterone and the action of androgens, thereby suppressing acne. Therefore, p-coumaroylaminobutan-1-ol can be used as an active ingredient in acne prevention and amelioration agents.

[0017] Hereinafter, the "5α-reductase inhibitor of the present invention", the "androgen receptor binding inhibitor of the present invention", the "prostate hyperplasia inhibitor of the present invention", the "hair growth agent of the present invention" and the "acne prevention and amelioration agent of the present invention" will be collectively referred to as the "agent of the present invention".

[0018] <p-クマロイルアミノブタン-1-オール> p-Coumaroylaminobutan-1-ol exists as two structural isomers depending on the position of the substituent on the double bond carbon. Specifically, it has a structure of 1,4-[(E)-p-coumaroylamino]butan-1-ol (hereinafter sometimes referred to as "E isomer") represented by the following formula (1), or 1,4-[(Z)-p-coumaroylamino]butan-1-ol (hereinafter sometimes referred to as "Z isomer") represented by the following formula (2).

[0019] [ka]

[0020] The agent of the present invention may contain either the E-form or the Z-form of p-coumaroylaminobutan-1-ol, or may contain both.

[0021] p-Coumaroylaminobutan-1-ol itself (i.e., an isolated product or a synthetic product) can be incorporated into the agent of the present invention. Furthermore, p-Coumaroylaminobutan-1-ol can be derived from a plant, and a processed plant product (e.g., pulverized material, crushed material, juice, puree, extract, dried material, etc.) obtained by processing a plant (whole or organ) containing p-Coumaroylaminobutan-1-ol can be incorporated into the agent of the present invention. Furthermore, a processed plant product containing p-Coumaroylaminobutan-1-ol (the processed plant product) can be used as the agent of the present invention, or the processed plant product can be further processed or incorporated into the agent of the present invention.

[0022] The agent of the present invention is used in animals including humans. Examples of non-human animals include dogs and cats. The agent may also be used in healthy individuals (i.e., individuals not suffering from any disease or illness).

[0023] The form of the agent of the present invention is not particularly limited, and it can be a food, a quasi-drug, a pharmaceutical, a cosmetic, or the like.

[0024] <Food composition> The agent of the present invention can be formulated as a food composition. From the viewpoint that a food composition facilitates daily long-term intake, it is preferable to formulate it as a food composition. Specifically, it can be a food composition containing p-coumaroylaminobutan-1-ol itself, a processed plant product obtained by processing a plant containing p-coumaroylaminobutan-1-ol, or a food composition containing a processed plant product. This food composition includes not only general foods, but also foods and / or beverages taken for the purpose of maintaining or improving health, such as foods for specified health uses, foods with functional claims, foods with nutrient functions, nutritional supplements, health supplements, and supplements. Among these, foods with health claims, such as foods for specified health uses, foods with functional claims, and foods with nutrient functions, are preferred embodiments.

[0025] The form of the food composition is not particularly limited, and may be any of solid, liquid, semi-solid, gel, sol, etc. Foods and beverages are not particularly limited, and examples of foods include sausage, ham, processed seafood products, jelly, candy, chewing gum, etc. Beverages include various fruit juice drinks, teas, soft drinks, alcoholic beverages, energy drinks, etc. Food compositions may also contain additives such as seasonings, coloring agents, preservatives, thickening stabilizers, antioxidants, bleaching agents, antibacterial and antifungal agents, acidulants, seasonings, emulsifiers, strengthening agents, fragrances, and sweeteners.

[0026] The content of p-coumaroylaminobutan-1-ol is not particularly limited as long as it is within a range that can achieve the effects of the present invention, and is designed according to the method of ingestion, etc., so that the intake amount of p-coumaroylaminobutan-1-ol is the desired intake amount per adult human per day. For example, the food composition can be designed so that the intake amount per adult human per day of p-coumaroylaminobutan-1-ol is 0.00001 μg to 10,000 μg, 0.0001 μg to 9,500 μg, 0.001 μg to 9,000 μg, 0.01 μg to 8,500 μg, 0.1 μg to 8,000 μg, 0.5 μg to 7,500 μg, 1 μg to 7,000 μg, 5 μg to 6,000 μg, 10 μg to 5,000 μg, etc., but is not limited thereto. Furthermore, to achieve the desired intake amount, the food composition may be taken once a day or divided into multiple doses (e.g., 2 to 4 times) per day. The daily intake amount refers to the total amount taken in one day, and if the food composition is taken in multiple doses per day, it is the total amount of these doses. Furthermore, the food composition can be taken continuously over several days, weeks, or months.

[0027] <Pharmaceutical Composition> The agent of the present invention can be a pharmaceutical composition. This pharmaceutical composition includes both pharmaceuticals and quasi-drugs. When used as a pharmaceutical composition, the agent of the present invention basically contains p-coumaroylaminobutan-1-ol or a material containing it, and a pharmaceutically acceptable carrier. Specifically, the agent can be a pharmaceutical composition containing p-coumaroylaminobutan-1-ol itself, a processed plant product obtained by processing a plant containing p-coumaroylaminobutan-1-ol, or a pharmaceutical composition containing a processed plant product.

[0028] The dosage form of the pharmaceutical composition is not particularly limited and may be a solid or liquid preparation. Specific examples include powders, granules, tablets, capsules, lozenges, suspensions, emulsions, syrups, and elixirs. Pharmaceutically acceptable carriers include binders, stabilizers, excipients, diluents, pH buffers, thickeners, colorants, dispersants, emulsifiers, suspending agents, preservatives, disintegrants, solubilizers, and dissolution aids.

[0029] The content of p-coumaroylaminobutan-1-ol is not particularly limited as long as it is within a range that can achieve the effects of the present invention, and is designed according to the method of ingestion, etc., so that the intake amount of p-coumaroylaminobutan-1-ol is the desired intake amount per day for an adult human. The method of administration of the pharmaceutical composition is appropriately selected depending on the sex, weight, age, purpose of use, etc. of the subject, and may be oral administration (oral ingestion) or parenteral administration, with oral administration being preferred. For example, in the case of oral administration, the pharmaceutical composition can be prepared so that the daily dose of p-coumaroylaminobutan-1-ol administered to an adult human is 0.00001 μg to 10,000 μg, 0.0001 μg to 9,500 μg, 0.001 μg to 9,000 μg, 0.01 μg to 8,500 μg, 0.1 μg to 8,000 μg, 0.5 μg to 7,500 μg, 1 μg to 7,000 μg, 5 μg to 6,000 μg, or 10 μg to 5,000 μg, but is not limited thereto. Furthermore, the composition may be taken once a day or divided into multiple doses (e.g., 2 to 4 times) per day to achieve the desired dosage. The daily dose refers to the total amount administered in one day, and when administered multiple times a day, it refers to the sum of these amounts. Furthermore, the pharmaceutical composition can be administered continuously, and can be taken continuously over a period of several days to several weeks or months.

[0030] <Cosmetics> The agent of the present invention can be used as a cosmetic preparation, specifically, a cosmetic preparation containing p-coumaroylaminobutan-1-ol itself, or a cosmetic preparation containing a processed plant product obtained by processing a plant containing p-coumaroylaminobutan-1-ol.

[0031] The form of the cosmetic is not particularly limited, and may be any of liquids such as aqueous solutions, emulsions, dispersions, and emulsions; semi-solids such as gels, ointments, and pastes; and solids. Examples include liquids, gels, creams, ointments, patches, packs, and aerosols. Specific examples include lotions, cosmetic liquids, creams, emulsions, sunscreens, cleansers, packs, cosmetic oils, body rinses, massage products, scalp products, hair washes, hair rinses, and lip care cosmetics.

[0032] When used as a cosmetic preparation, it can be produced by a method known in the fields of cosmetics and pharmaceuticals. Furthermore, depending on the formulation, p-coumaroylaminobutan-1-ol can be used in combination with one or more of various base materials and additives used in the fields of cosmetics and pharmaceuticals. Examples of ingredients that can be blended with p-coumaroylaminobutan-1-ol include binders, excipients, thickeners, diluents, pH adjusters, stabilizers, antiseptics, preservatives, dispersants, emulsifiers, solubilizers, solubilizers, chelating agents, surfactants, gelling agents, antioxidants, UV absorbers, moisturizers, antioxidants, disinfectants, antibacterial agents, whitening agents, pigments, and fragrances.

[0033] The content of p-coumaroylaminobutan-1-ol is not particularly limited as long as it is within a range that can achieve the effects of the present invention, and can be appropriately set depending on the form of the cosmetic, the method of use, etc. The method and dosage of the cosmetic are not particularly limited, and can usually be used by applying an appropriate amount to the skin several times a day, depending on the dosage form and the condition of the user.

[0034] The agent of the present invention may be used for dogs, cats, etc., and may be in the form of an animal food composition such as pet food or an animal pharmaceutical composition. Specifically, it may be in the form of an animal food composition or animal pharmaceutical composition containing p-coumaroylaminobutan-1-ol itself, a processed product obtained by processing a plant containing p-coumaroylaminobutan-1-ol, or an animal food composition or animal pharmaceutical composition containing a processed plant product. [Example]

[0035] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples as long as the gist of the present invention is not changed.

[0036] (5α-reductase inhibitory activity evaluation test) Substrate: Testosterone Enzyme source: Rat prostate Detection method: LC-QTOF / MS

[0037] (Test substance) p-Coumaroylaminobutan-1-ol (mixture of E and Z isomers) Linoleic acid (positive control)

[0038] (Test Method) (1) Preparation of crude enzyme The rat prostate was placed in a four-fold volume of buffer solution (0.32 M sucrose, 1 mM dithiothreitol, 20 mM sodium phosphate, pH 6.5) and homogenized using a homogenizer. The homogenate was centrifuged at 10,000 rpm for 10 minutes, and the resulting supernatant was used as a crude enzyme solution containing 5α-reductase.

[0039] (2) 5α-reductase inhibition test The substrates, 150 μM testosterone, 167 μM NADPH, 60 μL of crude enzyme, and 30 μL of each test substance at the concentrations shown in Figure 1, were mixed and reacted for 30 minutes at 37°C. After 30 minutes, sodium hydroxide was added to stop the reaction, and the production of dihydrotestosterone was evaluated using a liquid chromatography mass spectrometer (LC-QTOF / MS). As a control, a similar test was carried out without the test substance.

[0040] (result) The results are shown in Figure 1. As shown in Figure 1, dihydrotestosterone production was suppressed in the group to which p-coumaroylaminobutan-1-ol was added, compared to the control. In particular, dihydrotestosterone production was significantly suppressed at concentrations of 250, 500, and 1000 μg / mL.

[0041] (Androgen receptor binding inhibition test) (Test substance) p-Coumaroylaminobutan-1-ol (mixture of E and Z isomers) Flutamide (positive control) β-sitosterol (control) Saw palmetto oil (control)

[0042] (Test Method) The binding activity of androgens to the androgen receptor was evaluated using the PolarScreen® Androgen Receptor Competitor Assay Kit according to existing protocols. As a control, a similar test was also performed without the test substance.

[0043] (result) The results are shown in Figure 2. As shown in Figure 2, compared to the control, the group to which p-coumaroylaminobutan-1-ol was added exhibited concentration-dependent androgen receptor binding inhibitory activity, particularly at concentrations of 10 μg / mL, 100 μg / mL, and 1000 μg / mL. At a concentration of 1000 μg / mL, approximately 22.5% of the binding inhibitory activity was observed. [Industrial Applicability]

[0044] The agent of the present invention is useful in the fields of food and medicine.

Claims

1. A 5α-reductase inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient (excluding compositions containing hemp seed extract and / or hemp seed oil).

2. An androgen receptor binding inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient (excluding compositions containing hemp seed extract and / or hemp seed oil).

3. An agent for suppressing benign prostatic hyperplasia containing p-coumaroylaminobutan-1-ol as an active ingredient (excluding compositions containing hemp seed extract and / or hemp seed oil).

4. A hair growth agent containing p-coumaroylaminobutan-1-ol as an active ingredient (excluding compositions containing hemp seed extract and / or hemp seed oil).

5. An acne prevention and improvement agent containing p-coumaroylaminobutan-1-ol as an active ingredient (excluding compositions containing hemp seed extract and / or hemp seed oil).

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