5α-reductase inhibitors, androgen receptor binding inhibitors, benign prostatic hyperplasia inhibitors, hair growth agents, and acne prevention and improvement agents.

Abstract

This invention provides a new 5α-reductase inhibitor, a new androgen receptor binding inhibitor, a new benign prostatic hyperplasia inhibitor, a new hair growth agent, and a new acne prevention and treatment agent. [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 enlargement 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, a prostatic hypertrophy inhibitor, a hair growth agent, and an acne prevention and improvement agent.

Background Art

[0002] 5α - reductase is a type of enzyme that has the effect of enhancing the action of testosterone by converting testosterone, a male hormone, into dihydrotestosterone (DHT). Excessive production of dihydrotestosterone is involved in problems such as prostatic hypertrophy and hair loss.

[0003] For example, prostatic hypertrophy is a disease specific to men, in which the prostate hypertrophies and compresses the urethra and bladder, causing various urinary disorders such as frequent urination and a feeling of incomplete urination. The incidence of prostatic hypertrophy increases with age and is said to increase rapidly after the age of 50. Prostatic hypertrophy is thought to be caused by dihydrotestosterone binding to androgen receptors (AR) in prostatic cells and promoting the proliferation of prostatic cells.

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

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] The object of the present invention is to provide a novel 5α-reductase inhibitor, a novel androgen receptor binding inhibitor, a novel benign prostatic hyperplasia inhibitor, a novel hair growth agent, and a novel acne prevention and improvement agent. [Means for solving the problem]

[0007] The inventors of this invention have conducted extensive research to solve the above problems and have found that the following invention is suitable for the above purpose, leading to the present invention. That is, the present invention relates to the following 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> A prostate enlargement inhibitor containing p-coumaroylaminobutan-1-ol as the active ingredient. <4> A hair growth tonic containing p-coumaroylaminobutan-1-ol as an active ingredient. <5> An acne prevention and treatment agent containing p-coumaroylaminobutan-1-ol as an active ingredient. [Effects of the Invention]

[0009] According to the present invention, a novel 5α-reductase inhibitor, a novel androgen receptor binding inhibitor, a novel benign prostatic hyperplasia inhibitor, a novel hair growth agent, and a novel acne prevention and improvement agent are provided. [Brief explanation of the drawing]

[0010] [Figure 1] This figure shows the results of the 5α-reductase inhibitory activity evaluation test. [Figure 2] This figure shows the results of an androgen receptor binding inhibition test. [Modes for carrying out the invention]

[0011] The embodiments of the present invention will be described in detail below, but the description of the constituent elements described below is just one example (representative example) of an embodiment of the present invention, and the present invention is not limited to the following unless its gist is changed. In this specification, when the expression "~" is used, it is used to mean an expression that includes the numerical value or physical property value before and after it.

[0012] <5α-reductase inhibitors> This invention relates to a 5α-reductase inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. Because p-coumaroylaminobutan-1-ol inhibits the action of 5α-reductase, it can be used as an active ingredient in 5α-reductase inhibitors. 5α-reductase is an enzyme that converts testosterone to dihydrotestosterone, and inhibiting the action of 5α-reductase can suppress the production of dihydrotestosterone.

[0013] <Androgen receptor binding inhibitors> This invention relates to an androgen receptor binding inhibitor containing p-coumaroylaminobutan-1-ol as an active ingredient. Because p-coumaroylaminobutan-1-ol inhibits the binding of androgens to androgen receptors, it can be used as an active ingredient in androgen receptor binding inhibitors. Androgens are a type of steroid hormone that functions in the body. Also known as male hormones, testosterone is a representative example. Androgens exert their effects by binding to androgen receptors (ARs). Inhibiting the binding of androgens to androgen receptors can suppress the effects of androgens.

[0014] <Anti-Benign Prostatic Hyperplasia (BPH) Suppressant> This invention relates to a prostate enlargement 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 the enlargement of the prostate. Since p-coumaroylaminobutan-1-ol has 5α-reductase inhibitory activity and activity that inhibits binding to androgen receptors, it can suppress the production of dihydrotestosterone and the action of androgens, thereby suppressing prostate enlargement. For this reason, p-coumaroylaminobutan-1-ol can be used as an active ingredient in a prostate enlargement inhibitor.

[0015] <Hair growth tonic> This invention relates to a hair growth agent containing p-coumaroylaminobutan-1-ol as an active ingredient. Dihydrotestosterone, converted from testosterone by 5α-reductase in hair follicles, sebaceous glands, etc., is considered to be one of the causes of hair loss and thinning hair. Because p-coumaroylaminobutan-1-ol has 5α-reductase inhibitory activity and inhibits binding to androgen receptors, it can suppress the production of dihydrotestosterone and the action of androgens, thereby suppressing hair loss and thinning hair. For this reason, p-coumaroylaminobutan-1-ol can be used as an active ingredient in hair growth agents.

[0016] <Acne prevention and treatment agent> This invention relates to an acne prevention and improvement agent containing p-coumaroylaminobutan-1-ol as an active ingredient. Dihydrotestosterone, converted from testosterone by 5α-reductase in the sebaceous glands, is considered to be one of the causes of acne. Since p-coumaroylaminobutan-1-ol has 5α-reductase inhibitory activity and inhibits binding to androgen receptors, it can suppress the production of dihydrotestosterone and the action of androgens, thereby suppressing acne. For this reason, p-coumaroylaminobutan-1-ol can be used as an active ingredient in acne prevention and improvement agents.

[0017] Hereinafter, the "5α-reductase inhibitor of the present invention", the "androgen receptor binding inhibitor of the present invention", the "prostatic hypertrophy inhibitor of the present invention", the "hair growth agent of the present invention", and the "acne prevention / improvement agent of the present invention" are collectively referred to as the "agent of the present invention".

[0018] <p-coumaroylaminobutan-1-ol> p-coumaroylaminobutan-1-ol has two types of structural isomers depending on the position of the substituent substituting the carbon of the double bond. Specifically, 1,4-[(E)-p-coumaroylamino]butan-1-ol represented by the following formula (1) (hereinafter sometimes referred to as the "E form"), or 1,4-[(Z)-p-coumaroylamino]butan-1-ol represented by the following formula (2) (hereinafter sometimes referred to as the "Z form").

[0019]

Chemical formula

[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 formulated into the agent of the present invention. Also, p-coumaroylaminobutan-1-ol can be derived from plants, and a plant processed product (e.g., a pulverized product, a crushed product, a juice, a puree, an extract, a dried product, etc.) obtained by processing a plant (the whole or an organ) containing p-coumaroylaminobutan-1-ol may be formulated into the agent of the present invention. Further, a processed product of a plant containing p-coumaroylaminobutan-1-ol (the above-mentioned plant processed product) may be used as the agent of the present invention, or the above-mentioned plant processed product may be further processed or formulated to be used as the agent of the present invention.

[0022] The agent of the present invention is intended for use in animals, including humans. Examples of animals other than humans include dogs and cats. Furthermore, the agent may also be used in healthy individuals (i.e., people who are not suffering from diseases or illnesses).

[0023] The embodiments of the agent of the present invention are not particularly limited and can be in the form of food, quasi-drugs, pharmaceuticals, cosmetics, etc.

[0024] <Food Composition> The agent of the present invention can be in the form of a food composition. From the viewpoint of ease of daily, long-term intake, it is preferable to use a food composition. Specifically, it can be a food composition containing p-coumaroylaminobutan-1-ol itself, a processed plant product made from 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 consumed for the purpose of maintaining and promoting health, such as foods for special dietary uses, foods for specified health uses, foods with functional claims, nutritional functional foods, nutritional supplements, health supplements, and supplements. Among these, foods for specified health uses, foods with functional claims, and nutritional functional foods are preferred embodiments.

[0025] The shape of the food composition is not particularly limited and may be solid, liquid, semi-solid, gel, sol, or any other form. The food and beverages are not particularly limited and, for example, food items include sausages, ham, processed seafood products, jelly, candy, and chewing gum. Beverages include various fruit juices, teas, soft drinks, alcoholic beverages, and nutritional drinks. The food composition may also contain additives such as flavorings, colorants, preservatives, thickeners and stabilizers, antioxidants, bleaching agents, antibacterial and antifungal agents, acidulants, seasonings, emulsifiers, fortifiers, flavorings, and sweeteners.

[0026] The p-coumaroylaminobutan-1-ol content is not particularly limited as long as it can achieve the effects of the present invention, and is designed according to the method of intake, etc., so that the amount of p-coumaroylaminobutan-1-ol ingested corresponds to the target daily intake for one adult human. For example, the food composition can contain p-coumaroylaminobutan-1-ol in amounts such as 0.00001μg~10000μg, 0.0001μg~9500μg, 0.001μg~9000μg, 0.01μg~8500μg, 0.1μg~8000μg, 0.5μg~7500μg, 1μg~7000μg, 5μg~6000μg, 10μg~5000μg, etc., as a daily intake for one adult human, but is not limited thereto. Furthermore, to achieve the desired intake, it may be taken once a day or divided into multiple doses per day (for example, 2 to 4 times). The daily intake refers to the total amount taken in one day, and if taken in multiple doses per day, it will be the sum of these amounts. In addition, the food composition can be taken continuously, and can be taken continuously for several days to several weeks or even several months.

[0027] <Pharmaceutical composition> The agent of the present invention can be a pharmaceutical composition. This pharmaceutical composition may be either a pharmaceutical or a quasi-drug. 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, it can be a pharmaceutical composition containing p-coumaroylaminobutan-1-ol itself, a plant-derived product obtained by processing a plant containing p-coumaroylaminobutan-1-ol, or a pharmaceutical composition containing a plant-derived product.

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

[0029] The content of p-coumaroylaminobutan-1-ol is not particularly limited as long as it can achieve the effects of the present invention, and the amount of p-coumaroylaminobutan-1-ol ingested is designed according to the method of administration so that it corresponds to the target daily intake for one adult human. The method of administration of the pharmaceutical composition is appropriately selected according to the sex, weight, age, and purpose of use of the recipient, and may be administered orally (oral ingestion) or parenterally, but oral administration is preferred. For example, in the case of oral administration, the pharmaceutical composition can be formulated so that the daily dose for one adult human is 0.00001 μg to 10000 μg, 0.0001 μg to 9500 μg, 0.001 μg to 9000 μg, 0.01 μg to 8500 μg, 0.1 μg to 8000 μg, 0.5 μg to 7500 μg, 1 μg to 7000 μg, 5 μg to 6000 μg, 10 μg to 5000 μg, etc., but is not limited to these. Furthermore, it may be taken once a day or divided into multiple doses per day (for example, 2 to 4 times) to achieve the desired dose. The daily dose refers to the total amount administered in one day, and if administered in multiple doses per day, it will be the sum of these amounts. Furthermore, the pharmaceutical composition can be administered continuously and can be taken continuously for several days to several weeks or even several months.

[0030] <Cosmetics> The agent of the present invention can be used in cosmetics. Specifically, it can be used in cosmetics containing p-coumaroylaminobutan-1-ol itself, or in cosmetics containing plant-derived products obtained by processing plants that contain p-coumaroylaminobutan-1-ol.

[0031] The form of the cosmetic is not particularly limited and may be any form, such as liquid (aqueous solution, emulsion, dispersion, etc.), semi-solid (gel, ointment, paste, etc.), or solid. Examples include liquid preparations, gel preparations, cream preparations, gel preparations, ointments, patches, packs, and aerosol preparations. Specifically, examples include lotions, cosmetic liquids, creams, emulsions, sunscreens, cleansers, packs, cosmetic oils, body rinses, massage products, scalp products, shampoos, hair rinses, lip care cosmetics, etc.

[0032] When used in the form of a cosmetic, it can be manufactured by methods known in the fields of cosmetics and pharmaceuticals. Depending on the dosage form, one or more various base materials and additives used in the fields of cosmetics and pharmaceuticals can be used in combination with p-coumaroylaminobutan-1-ol. Ingredients that can be blended with p-coumaroylaminobutan-1-ol include binders, excipients, thickeners, diluents, pH adjusters, stabilizers, preservatives, dispersants, emulsifiers, solubilizers, dissolving aids, chelating agents, surfactants, gelling agents, antioxidants, UV absorbers, humectants, antioxidants, bactericides, antibacterial agents, whitening agents, pigments, fragrances, etc.

[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 and method of use of the cosmetic. The usage and dosage of the cosmetic are not particularly limited, and it can usually be used by applying an appropriate amount to the skin several times a day, depending on the dosage form and the user's condition.

[0034] The agent of the present invention may be used for dogs, cats, and other animals, and may be used as an animal food composition such as pet food or an animal pharmaceutical composition. Specifically, it can be in the form of an animal food composition or animal pharmaceutical composition containing p-coumaroylaminobutan-1-ol itself, a processed product made from a plant containing p-coumaroylaminobutan-1-ol, or an animal food composition or animal pharmaceutical composition containing a processed plant. [Examples]

[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 unless its essence is changed.

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

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

[0038] (Test method) (1) Preparation of crude enzyme Rat prostates were placed in four times the volume of buffer solution (0.32 M sucrose, 1 mM dithiothreitol, 20 mM sodium phosphate, pH 6.5) and homogenized. The homogenized solution was centrifuged at 10,000 rpm for 10 minutes, and the resulting supernatant was used as a crude enzyme solution containing 5α-reductase for the test.

[0039] (2) 5α-reductase inhibition test A mixture of 150 μM testosterone, 167 μM NADPH, 60 μL crude enzyme, and 30 μL of each test substance at the concentrations shown in Figure 1 was prepared and reacted at 37°C for 30 minutes. 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). Additionally, a similar test was conducted without the test substance as a control.

[0040] (result) The results are shown in Figure 1. As shown in Figure 1, compared to the control group, dihydrotestosterone production was suppressed in the group treated with p-coumaroylaminobutan-1-ol. 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 (a mixture of E and Z isomers) • Flutamide (positive control) • β-sitosterol (comparative) • Saw palmetto oil (for comparison)

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

[0043] (result) The results are shown in Figure 2. As shown in Figure 2, compared to the control group, the group treated with p-coumaroylaminobutan-1-ol showed 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, it showed approximately 22.5% binding inhibitory activity. [Industrial applicability]

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

Claims

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. A prostate enlargement inhibitor containing p-coumaroylaminobutan-1-ol as the active ingredient.

4. A hair growth product containing p-coumaroylaminobutan-1-ol as an active ingredient.

5. An acne prevention and treatment agent containing p-coumaroylaminobutan-1-ol as an active ingredient.

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