Composition for preventing or treating prostatic hyperplasia containing benzophenone derivatives as an active ingredient

Abstract

The present invention relates to a composition for the prevention or treatment of benign prostatic hyperplasia comprising a benzophenone derivative as an active ingredient. A composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide, a benzophenone derivative according to the present invention, as an active ingredient exhibits excellent effects in reducing the size of the prostate, reducing the weight of the prostate, and reducing the thickness of the prostatic epithelial tissue. Therefore, the benzophenone derivative according to the present invention can be usefully utilized as a pharmaceutical composition or a health functional food composition for the prevention or treatment of benign prostatic hyperplasia.

Description

Technology Field

[0001] The present invention relates to a composition for the prevention or treatment of benign prostatic hyperplasia comprising a benzophenone derivative as an active ingredient. Background Technology

[0003] The prostate is the primary male gonad involved in male fertility, related to sperm activation and receptivity, and serves as a direct target for benign and malignant diseases such as prostatitis, benign prostatic hyperplasia, and prostate cancer. The incidence of urological diseases increases in middle-aged men, and the prevalence rises with age.

[0004] Benign prostatic hyperplasia (BPH) is a condition in which an enlarged prostate compresses the urethra, causing lower urinary tract symptoms such as frequent urination, urinary incontinence, urgency, and delayed urination. The primary precipitating factors for BPH are increasing age and male hormones; histological enlargement of the prostate begins at age 35, appearing in 60% of men in their 60s and 90% of men in their 80s, with 50% of these patients complaining of urinary dysfunction due to the enlargement. Male hormones in the prostate are deeply involved in the growth, development, and pathological state of the prostate through male hormone receptors. In particular, type 2 5-alpha reductase present in the prostate plays a crucial role in the development of BPH by converting male hormones into dihydrotestosterone (DHT), a more potent male hormone.

[0005] Drug treatments for benign prostatic hyperplasia (BPH) primarily consist of selective alpha-blockers and 5-alpha-reductase inhibitors (androgen inhibitors). Alpha-blockers are medications that reduce pressure and tension in the prostatic urethra; commercially available alpha-blockers include terazosin, doxazosin, tamsulosin, and alfuzosin. However, alpha-blockers are only a temporary treatment as they do not reduce the enlargement of the prostate, and side effects such as dizziness, lethargy, headache, and visual disturbances have been reported. 5-alpha-reductase inhibitors are drugs that prevent prostate enlargement by inhibiting 5-alpha-reductase, which plays a key role in the process of prostate enlargement. Finasteride and dutasteride are commercially available 5-alpha-reductase inhibitors. However, these drugs take a long time to show effects after taking them and have side effects related to sexual function.

[0006] Accordingly, the inventors of the present invention sought to develop a treatment for benign prostatic hyperplasia that is effective, safe, and free from side effects, and completed the present invention by confirming that N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (NJK14047), among benzophenone derivatives, is effective in treating benign prostatic hyperplasia. Prior art literature

[0008] Korean Registered Patent Publication No. 10-2114394 The problem to be solved

[0009] The object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0010] In addition, another objective of the present invention is to provide a method for treating benign prostatic hyperplasia comprising the step of administering the above pharmaceutical composition to an individual other than a human who has developed or is at risk of developing benign prostatic hyperplasia.

[0011] In addition, another objective of the present invention is to provide a food composition for preventing or improving benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0012] In addition, another objective of the present invention is to provide a health functional food composition for improving prostate health comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient. means of solving the problem

[0014] To achieve the above objectives, the present invention provides a pharmaceutical composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0015] Next, the present invention provides a method for treating benign prostatic hyperplasia comprising the step of administering the above pharmaceutical composition to an individual other than a human who has developed or is at risk of developing benign prostatic hyperplasia.

[0016] Furthermore, the present invention provides a food composition for preventing or improving benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0017] In addition, the present invention provides a health functional food composition for improving prostate health comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient. Effects of the invention

[0019] A composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide, a benzophenone derivative according to the present invention, as an active ingredient exhibits excellent effects in reducing the size of the prostate, reducing the weight of the prostate, and reducing the thickness of the prostatic epithelial tissue. Therefore, the benzophenone derivative according to the present invention can be usefully utilized as a pharmaceutical composition or a health functional food composition for the prevention or treatment of benign prostatic hyperplasia. Brief explanation of the drawing

[0021] Figure 1 is a figure showing the results of confirming the prostate size reduction effect of NJK14047 in one embodiment of the present invention. Figure 2 is a figure showing the results of confirming the prostate weight reduction effect of NJK14047 in one embodiment of the present invention. Figure 3 is a figure showing the results of confirming the effect of NJK14047 on reducing prostate weight per body weight in one embodiment of the present invention. Figure 4 is a figure showing the results of confirming the relative prostate weight reduction effect of NJK14047 in one embodiment of the present invention. Figure 5 is a figure showing the results of measuring the thickness of the prostate epithelial tissue of experimental animals following the administration of NJK14047 in one embodiment of the present invention. Figure 6 is a figure showing the results of confirming the effect of NJK14047 on reducing the thickness of prostate epithelial tissue in one embodiment of the present invention. Specific details for implementing the invention

[0022] Hereinafter, the present invention will be described in detail with reference to the attached drawings for embodiments of the present invention. However, the following embodiments are presented as examples of the present invention, and if it is determined that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the essence of the present invention, such detailed description may be omitted, and the present invention is not limited by this. The present invention is capable of various modifications and applications within the scope of the claims set forth below and the equivalent scope interpreted therefrom.

[0023] Furthermore, the terminology used in this specification is used to appropriately describe preferred embodiments of the present invention, and may vary depending on the intent of the user or operator, or the conventions of the field to which the present invention belongs. Accordingly, the definitions of these terms should be based on the content throughout this specification. Throughout the specification, when a part is described as “comprising” a certain component, unless specifically stated otherwise, this means that it does not exclude other components but may include additional components.

[0024] Throughout this specification, '%' used to indicate the concentration of a particular substance is (w / w) % for solid / solid, (w / v) % for solid / liquid, and (v / v) % for liquid / liquid, unless otherwise noted.

[0026] In one aspect, the present invention provides a pharmaceutical composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0027] In one embodiment of the present invention, the molecular formula of N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide is C 27 H27 It is NO5, and its IUPAC name is N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide, and it has a molecular weight of 445.51 g / mol. In addition, this compound has a chemical structure as shown in Chemical Formula 1 below.

[0028] [Chemical Formula 1]

[0029]

[0030] In one embodiment of the present invention, the composition may reduce the size of the prostate, but is not limited thereto.

[0031] In one embodiment of the present invention, the composition may reduce the weight of the prostate, but is not limited thereto.

[0032] In one embodiment of the present invention, the composition may reduce the thickness of the prostate epithelial tissue, but is not limited thereto.

[0033] The pharmaceutical composition of the present invention may additionally include an adjuvant in addition to the active ingredient N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide. Any adjuvant known in the art may be used without limitation, but, for example, a complete or incomplete adjuvant of Freund may be additionally included to increase the immunogenicity.

[0034] The pharmaceutical composition according to the present invention may be prepared in a form in which the active ingredient N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide is incorporated into a pharmaceutically acceptable carrier. Herein, the pharmaceutically acceptable carrier comprises a carrier, excipient, and diluent commonly used in the pharmaceutical field. Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention are not limited to these, but include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

[0035] The pharmaceutical composition of the present invention may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external formulations, suppositories, or sterile injectable solutions, each according to conventional methods.

[0036] When formulating, the product may be prepared using diluents or excipients such as commonly used fillers, volume expanders, binders, wetting agents, disintegrants, and surfactants. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and such solid dosage forms may be prepared by mixing at least one excipient, such as starch, calcium carbonate, sucrose, lactose, gelatin, etc., with the active ingredient. In addition, lubricants such as magnesium stearate and talc may also be used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, and syrups, and may contain various excipients, such as wetting agents, sweeteners, flavoring agents, and preservatives, in addition to commonly used diluents such as water and liquid paraffin. Preparations for parenteral administration include sterile aqueous solutions, water-insoluble solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Water-insoluble solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Bases for suppositories may include Witepsol, Tween 61, cocoa paste, laurin paste, glycerogelatin, etc.

[0037] The pharmaceutical composition according to the present invention may be administered to an individual by various routes. Any mode of administration may be anticipated, for example, by oral, intravenous, intramuscular, subcutaneous, or intraperitoneal injection.

[0038] The dosage of the pharmaceutical composition according to the present invention is selected by taking into consideration the age, weight, gender, physical condition, etc. of the individual. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be selected in various ways depending on the subject, and preferably, it is included in the pharmaceutical composition at a concentration of 0.01 to 5,000 μg / ml. If the concentration is less than 0.01 μg / ml, pharmaceutical activity may not appear, and if it exceeds 5,000 μg / ml, it may exhibit toxicity to the human body.

[0039] The above pharmaceutical composition can be formulated into various oral or parenteral administration forms.

[0040] Oral dosage forms include, for example, tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, granules, etc., and these dosage forms may additionally contain diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine) and lubricants (e.g., silica, talc, stearic acid and its magnesium or calcium salts and / or polyethylene glycol) in addition to the active ingredient. Furthermore, the tablet may contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidine, and in some cases may contain disintegrants or boiling mixtures such as starch, agar, alginic acid or its sodium salt and / or absorbents, coloring agents, flavoring agents and sweeteners. The above formulation can be prepared by conventional mixing, granulation, or coating methods.

[0041] In addition, representative formulations for parenteral administration are injectable preparations, and solvents for injectable preparations include water, Ringer's solution, isotonic saline, or suspensions. The sterile fixation oil of the above injectable preparation can be used as a solvent or suspension medium, and any non-irritating fixation oil, including mono- and di-glycerides, can be used for this purpose.

[0042] In addition, the above-mentioned injectable formulation may use fatty acids such as oleic acid.

[0044] In one aspect, the present invention provides a method for treating benign prostatic hyperplasia comprising the step of administering the pharmaceutical composition to an individual other than a human who has developed or is at risk of developing benign prostatic hyperplasia.

[0045] The term "administration" in this invention means introducing a specific substance to an individual by an appropriate method.

[0046] The term "individual" in this invention refers to animals other than humans, such as rats, mice, and livestock, that have developed or may develop benign prostatic hyperplasia. More specifically, it may be non-human primates, mice, rats, and mammals such as dogs, cats, horses, and cattle.

[0047] The pharmaceutical composition of the present invention may be administered in a therapeutically effective amount or a pharmaceutically effective amount.

[0048] In the present invention, the term "therapeutically effective amount" refers to a pharmaceutically acceptable amount of salt of a composition effective for preventing or treating a target disease, and the therapeutically effective amount of the composition of the present invention may vary depending on various factors, such as the method of administration, the target site, the patient's condition, etc. Therefore, when used in humans, the dosage should be determined as an appropriate amount by considering both safety and efficacy. It is also possible to estimate the amount used in humans from the effective amount determined through animal experiments. Such matters to be considered when determining the effective amount are described, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; and EW Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

[0049] In the present invention, the term “pharmaceuticalally effective amount” means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and that does not cause side effects, and the effective dose level may be determined based on factors including the patient’s health condition, type and severity of the disease, drug activity, sensitivity to the drug, method of administration, time of administration, route of administration and elimination rate, duration of treatment, drugs used in combination or concurrently, and other factors well known in the medical field.

[0050] The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses. Taking all of the above-mentioned factors into consideration, it is important to administer an amount that obtains maximum effect with a minimum amount without side effects, and this can be easily determined by a person skilled in the art.

[0051] The composition of the present invention may be administered at a dose of 0.0001 to 100 mg / kg body weight per day based on solid content, more specifically at a dose of 0.001 to 100 mg / kg body weight. The above recommended dose may be administered once a day or divided into several doses.

[0052] In the method for preventing or treating benign prostatic hyperplasia according to the present invention, the route and method of administration for administering the composition are not particularly limited and may follow any route and method of administration as long as the composition containing the composition can reach the intended site. Specifically, the composition may be administered through various routes of oral or parenteral administration, and non-limiting examples of such routes of administration include administration through the mouth, rectum, local, intravenous, intraperitoneal, intramuscular, intra-arterial, transdermal, nasal, or inhalation.

[0054] In one aspect, the present invention provides a food composition for preventing or improving benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0055] The food composition of the present invention can be formulated into various forms such as tablets, pills, granules, capsules, liquid preparations, and beverages, and added to food. There are no specific restrictions on the type of food. Examples of foods to which the N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide of the present invention can be added include drinks, meat, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, alcoholic beverages, vitamin complexes, dairy products and dairy processed products, and include both health foods and health functional foods in the conventional sense.

[0056] The health food and health functional food compositions containing N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide according to the present invention may be added directly to food or used together with other food or food ingredients, and may be used appropriately according to conventional methods. N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide may be appropriately determined according to its intended use (for prevention or improvement). Generally, the amount of the above composition in the health food and health functional food may be added in an amount of 0.1 to 90 parts by weight of the total food weight. However, in the case of long-term consumption for the purpose of maintaining health or regulating health, the above amount may be less than the above range, and since there are no issues regarding safety, the active ingredient may be used in an amount greater than the above range.

[0057] The health food and health functional food compositions of the present invention contain the N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide of the present invention as an essential ingredient in the indicated proportions, and there are no special restrictions on other ingredients, and they may contain various flavoring agents or natural carbohydrates, etc., as additional ingredients, as in ordinary beverages. Examples of the natural carbohydrates described above are monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, etc.; polysaccharides, e.g., dextrin, cyclodextrin, etc., and conventional sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. Natural flavoring agents other than those described above (taumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) may be advantageously used. The ratio of the above natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100g of the health functional food composition of the present invention.

[0058] In addition to the above, the health food and health functional food compositions containing N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide of the present invention may contain various nutritional supplements, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. Furthermore, the health food and health functional food compositions of the present invention may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, and vegetable beverages.

[0059] These ingredients may be used independently or in combination. Although the proportion of these additives is not that important, it is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide of the present invention.

[0061] In one aspect, the present invention provides a health functional food composition for improving prostate health comprising N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient.

[0062] In one embodiment of the present invention, the improvement of prostate health may be to maintain prostate health by preventing or improving benign prostatic hyperplasia, but is not limited thereto.

[0063] The term "health functional food" as used in this invention is synonymous with "food for special health use (FosHU)," and refers to a food with high medical or therapeutic effects that is processed to efficiently exhibit bio-regulatory functions in addition to nutritional supply. Here, "function" refers to obtaining useful effects for health purposes, such as regulating nutrients or physiological actions regarding the structure and function of the human body. The health functional food of this invention can be manufactured by methods commonly used in the industry, and during such manufacturing, raw materials and ingredients commonly added in the industry may be added. Furthermore, the formulation of the health functional food can be manufactured without restriction as long as it is a formulation recognized as a food. The health functional food of this invention can be manufactured in various forms of formulations. Unlike general pharmaceuticals, it uses food as a raw material, offering the advantage of not causing side effects that may occur with long-term use of pharmaceuticals. Additionally, due to its excellent portability, the health functional food of this invention can be consumed as an adjuvant to enhance the effect of improving the intestinal microbiome.

[0064] The aforementioned health functional food refers to a food that possesses active effects of maintaining or promoting health compared to general food, and health supplement food refers to a food intended for the purpose of health support. In some cases, the terms health functional food, health food, and health supplement food are used interchangeably.

[0065] Specifically, the above-mentioned health functional food is a food prepared by adding the composition of the present invention to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspension, and means that consuming it brings about specific health effects. Unlike general medicines, it has the advantage of not having side effects that may occur when taking medicine for a long period of time because it is made from food.

[0066] The above-mentioned health functional food may additionally include a physiologically acceptable carrier, the type of carrier is not particularly limited, and any carrier commonly used in the relevant technical field may be used.

[0067] In addition, the above-mentioned health functional food may include additional ingredients that are commonly used in food to improve smell, taste, visual appearance, etc. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu); and amino acids such as lysine, tryptophan, cysteine, and valine.

[0068] In addition, the above-mentioned health functional food may include food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder and high-grade bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.), coloring agents (tar dyes, etc.), colorants (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG, monosodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), leavening agents (alum, potassium hydrogen tartrate, etc.), reinforcing agents, emulsifiers, thickeners (sizing agents), coating agents, gum bases, antifoaming agents, solvents, and improvers. The above additives can be selected according to the type of food and used in appropriate amounts.

[0069] As an example of a health functional food of the present invention, it may be used as a health beverage composition, in which case it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The natural carbohydrates described above may be monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; and sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners may include natural sweeteners such as taumatin and stevia extract; and synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrates may generally be about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g, per 100 mL of the health beverage composition of the present invention.

[0070] In addition to the above, the health drink composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, or carbonating agents. Furthermore, it may contain fruit pulp for the production of natural fruit juices, fruit juice beverages, or vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health drink composition of the present invention.

[0072] As described above, specific embodiments of the present invention have been described in detail; however, those skilled in the art who understand the spirit of the present invention will be able to easily propose other inventions that are inferior or other embodiments included within the scope of the spirit of the present invention by adding, changing, or deleting other components within the same spirit. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts should be interpreted as being included within the scope of the present invention.

[0074] <Example 1> Preparation of N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (NJK14047)

[0075] 1-1. Preparation of N-cyclopropyl-4'-(4-((2,2-dimethyl-1,3-dioxolane-4-yl)methoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide

[0076] The N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (NJK14047) used in the present invention was prepared with reference to Heo et al., 2015.

[0077] In order to prepare N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (NJK14047) used in the present invention, N-cyclopropyl-4'-(4-((2,2-dimethyl-1,3-dioxolane-4-yl)methoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide was prepared.

[0079] Compound (4-bromophenyl)(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)methanone (229 mg, 0.585 mmol) and compound NAfter dissolving cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (153 mg, 0.508 mmol) in DMF (5 mL), K2CO3 (162 mg, 1.169 mmol) and Pd(PPh3)4 (61 mg, 0.053 mmol) were added at room temperature. The reaction mixture was stirred at 100 °C overnight, cooled to room temperature, and then 2 N The reaction was terminated by adding -HCl and diluted with EtOAc. The organic layer from the reaction mixture obtained above was washed with brine and water, dried with MgSO4, and concentrated under vacuum. The residue obtained above was purified by flash (silica) column chromatography (EtOAc : n-hexane = 1:2 → 2:1) to obtain the target compound N -cyclopropyl-4'-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide was prepared (yield 52%). The reaction scheme for this preparation is shown in Reaction Scheme 1 below.

[0081] [Reaction Equation 1]

[0082]

[0084] 1-2. Preparation of N-cyclopropyl-4'-(4-(2,3-dihydrooxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (NJK14047)

[0085] The compound obtained in Example 1-1 above N -cyclopropyl-4'-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide (40 mg, 0.084 mmol) was dissolved in a MeOH / H2O (2:0.5, 2.5 mL) mixed solvent, and p-Toluenesulfonic acid (10 mg, 0.050 mmol) was added at room temperature. The reaction mixture obtained above was stirred at 50 °C overnight, cooled to room temperature, and then an aqueous solution of NaHCO3 was added to terminate the reaction, and the mixture was diluted with EtOAc. The organic layer of the reaction mixture obtained above was washed with brine and water, dried with MgSO4, and concentrated under vacuum. The residue obtained above was purified by flash (silica) column chromatography (EtOAc : n-hexane = 1:1 → 5:1) to prepare the target compound NJK14047 (yield 53%). The reaction scheme for this preparation is shown in Reaction Scheme 2 below.

[0086] 1 H NMR (400 MHz, CDCl3) δ 7.85 - 7.79 (dd, J = 15.0, 8.0 Hz, 3H), 7.67 (d, J = 8.2 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.42 - 7.39 (m, 3H), 7.34 (d, J = 7.6 Hz, 1H), 7.16 (m, 1H), 4.14 - 4.12 (m, 3H), 3.87 - 3.85 (m, 2H), 2.92 (m, 1H), 2.31 (s, 3H), 0.86 (d, J = 5.9 Hz, 2H), 0.63 (s, 2H);

[0087] LR-MS (DART) m / z (M + ) 445;

[0088] HR-MS (DART) calculated for (M + ) 445.1884; found 445.1909.

[0090] [Reaction Equation 2]

[0091]

[0093] <Experimental Example 1> Confirmation of the prostate size reduction effect of NJK14047

[0094] To confirm the effect of NJK14047 prepared in Example 1 above on alleviating prostate enlargement, mice were subcutaneously injected with 5 mg / kg of testosterone for 4 weeks excluding weekends, while the positive control group, Fina group, was orally administered 5 mg / kg of finasteride, and the drug groups, NJK2.5 group or NJK5 group, were orally administered 2.5 mg / kg or 5 mg / kg of NJK14047.

[0095] Subsequently, prostate tissue was obtained by dislocating the cervical vertebrae of anesthetized mice, weighing the tissue, and visually observing the size of the prostate, as shown in Fig. 1. The top of Fig. 1 is a photograph of the mouse's genitourinary system, and the bottom is a photograph of the mouse's prostate.

[0096] As shown in Figure 1, the size of the prostate in the BPH group with induced prostate enlargement was significantly increased compared to the control group, but when finasteride or NJK14047 was administered to improve prostate enlargement, the size of the prostate decreased.

[0097] Through this, it was confirmed that NJK14047 has the effect of reducing prostate size.

[0099] <Experimental Example 2> Confirmation of the prostate weight reduction effect of NJK14047

[0100] 2-1. Confirmation of the prostate weight reduction effect of NJK14047

[0101] The prostate weight of the experimental group obtained in Experimental Example 1 above was compared and is shown in Figure 2.

[0102] As shown in Figure 2, the weight of the prostate in the BPH group with induced prostate enlargement was significantly increased compared to the control group, but when finasteride or NJK14047 was administered to improve prostate enlargement, the weight of the prostate decreased.

[0104] 2-2. Confirmation of the effect of NJK14047 on reducing prostate weight per unit of body weight

[0105] The prostate weight per body weight of the experimental group obtained in Experimental Example 1 above was compared and is shown in Figure 3.

[0106] As shown in Figure 3, the prostate weight per body weight of the BPH group with induced prostate enlargement was significantly increased compared to the control group, but when finasteride or NJK14047 was administered to improve prostate enlargement, the prostate weight per body weight decreased.

[0108] 2-3. Confirmation of the relative prostate weight reduction effect of NJK14047

[0109] The relative prostate weight ratio of the experimental group obtained in Experimental Example 1 above was compared and is shown in Fig. 4.

[0110] As shown in Figure 4, the relative prostate weight of the BPH group with induced prostate enlargement was significantly increased compared to the control group, but when finasteride or NJK14047 was administered to improve prostate enlargement, the relative prostate weight decreased.

[0111] Through this, it was confirmed that NJK14047 has the effect of reducing prostate weight.

[0113] <Experimental Example 3> Confirmation of the effect of NJK14047 in reducing prostate epithelial tissue thickness

[0114] The thickness of the epithelial tissue of the experimental group obtained in Experimental Example 1 above was compared and is shown in Figures 5 and 6.

[0115] As shown in Figure 5, the epithelial tissue thickness of the control group was 15.8 μm, whereas the epithelial tissue thickness of the BPH group with induced prostate enlargement was significantly increased to 27.0 μm. When finasteride was administered to improve prostate enlargement, the epithelial tissue thickness decreased to 20.9 μm; when NJK14047 2.5 mg / kg was administered, it decreased to 21.4 μm; and when NJK14047 5 mg / kg was administered, it decreased to 15.8 μm.

[0116] As shown in Figure 6, when finasteride or NJK14047 was administered to a BPH group with induced prostate enlargement, the thickness of the prostate epithelial tissue decreased.

[0117] Through this, it was confirmed that NJK14047 has the effect of reducing the thickness of prostate epithelial tissue.

[0119] The present invention has been described above with reference to preferred embodiments and experimental examples. Those skilled in the art will understand that the present invention may be embodied in modified forms without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the invention is defined by the claims, not by the foregoing description, and all variations within the scope of the claims should be interpreted as being included in the invention.

Claims

Claim 1 A pharmaceutical composition for the prevention or treatment of benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient, wherein said N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide is represented by the following Chemical Formula 1, said composition reduces prostate weight, said reduction of prostate weight is a reduction of prostate weight per body weight or relative prostate weight, and said composition reduces prostate epithelial tissue thickness: [Chemical Formula 1] . Claim 2 delete Claim 3 A method for treating benign prostatic hyperplasia comprising the step of administering the pharmaceutical composition of claim 1 to an individual other than a human who has developed or is at risk of developing benign prostatic hyperplasia, wherein the composition reduces the weight of the prostate, the reduction of the weight of the prostate is a reduction of the weight of the prostate per body weight or a relative weight of the prostate, and the composition reduces the thickness of the prostate epithelial tissue. Claim 4 A food composition for preventing or improving benign prostatic hyperplasia comprising N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient, wherein the N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide is represented by the following Chemical Formula 1, the composition reduces prostate weight, the reduction of prostate weight is a reduction in prostate weight per body weight or relative prostate weight, and the composition reduces prostate epithelial tissue thickness: [Chemical Formula 1] . Claim 5 A health functional food composition for improving prostate health comprising N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide as an active ingredient, wherein the N-cyclopropyl-4'-(4-(2,3-dihydroxypropoxy)benzoyl)-6-methyl-[1,1'-biphenyl]-3-carboxamide is represented by the following Chemical Formula 1, the composition reduces prostate weight, the reduction of prostate weight is a reduction in prostate weight per body weight or relative prostate weight, and the composition reduces prostate epithelial tissue thickness. [Chemical Formula 1] . Claim 6 A health functional food composition for improving prostate health according to claim 5, wherein the improvement of prostate health is to maintain prostate health by preventing or improving benign prostatic hyperplasia.

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