5α - Reductase inhibitor and prostate hypertrophy inhibitor

Abstract

To provide a 5α-reductase inhibitor that exhibits excellent 5α-reductase inhibitory action, and a prostatic hyperplasia inhibitor that exhibits excellent prostatic hyperplasia inhibitory action.SOLUTION: The present invention discloses a 5α-reductase inhibitor and a prostatic hyperplasia inhibitor each containing Trapaceae plant extract.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a 5α-reductase inhibitor and a prostate hypertrophy inhibitor.

Background Art

[0002] Regarding prostate hypertrophy, it is known that dihydrotestosterone (DHT) is involved. It is considered that testosterone is reduced to dihydrotestosterone (DHT) by 5α-reductase (3-oxo-5α-steroid-4-dehydrogenase), and prostate hypertrophy occurs due to the action of the reduced dihydrotestosterone. Therefore, it is known that inhibiting the reduction of testosterone to dihydrotestosterone, that is, inhibiting 5α-reductase, is effective for the treatment of prostate hypertrophy.

[0003] On the other hand, it has been reported that an extract of a plant belonging to the genus Vigna has an excellent Maillard reaction inhibitory effect (Patent Document 1).

[0004] In addition, a compound separated from a hot water extract of one or both of the pericarp and fruit of a plant belonging to the family Fabaceae, and having a molecular weight measured by gel filtration chromatography in the range of 70 to 130 and 290 to 380, has been reported to have a high ability to inhibit the formation of advanced glycation end products (Patent Document 2).

[0005] Furthermore, it has also been reported that one or more compounds contained in one or both of the pericarp and fruit of a plant belonging to the family Fabaceae have infertility-improving activity (Patent Document 3).

[0006] In addition, it has also been reported that one or more compounds contained in one or both of the pericarp and fruit of a plant belonging to the family Fabaceae have high adiponectin secretion-promoting activity and preadipocyte differentiation-promoting activity (Patent Document 4).

[0007] One or more compounds contained in one or both of the pericarp and fruit of a plant belonging to the family Fabaceae have high amyloid β aggregation inhibitory activity and BACE1 inhibitory activity, and have been reported as components of an anti-Alzheimer's composition (Patent Document 5).

Prior Art Documents

Patent Documents

[0008]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Summary of the Invention

Problems to be Solved by the Invention

[0009] Thus, it is known that extracts of plants belonging to the genus Momordica have various effects, but it is not known that extracts of plants belonging to the genus Momordica have 5α-reductase inhibitory action and prostate hypertrophy inhibitory action, etc.

[0010] An object of the present invention is to provide a 5α-reductase inhibitor having an excellent 5α-reductase inhibitory action and a prostate hypertrophy inhibitor having an excellent prostate hypertrophy inhibitory action.

Means for Solving the Problems

[0011] As a result of intensive studies to achieve the above object, the present inventors have obtained the finding that the hot water extract of Momordica charantia pericarp exhibits a remarkably excellent 5α-reductase inhibitory effect. Furthermore, the present inventors have also obtained the finding that the hot water extract of Momordica charantia pericarp exhibits a remarkably excellent prostate hypertrophy inhibitory effect.

[0012] Based on these findings, the present invention has been further studied and completed, and provides the following 5α-reductase inhibitors and prostate hyperplasia suppressants.

[0013] Item 1. A 5α-reductase inhibitor containing an extract of a plant belonging to the genus Momordica. Item 2. The 5α-reductase inhibitor according to Item 1, containing an extract of the pericarp of a plant belonging to the genus Momordica. Item 3. The 5α-reductase inhibitor according to Item 1 or 2, wherein the plant belonging to the genus Momordica is Momordica charantia. Item 4. A 5α-reductase inhibitor containing one or more compounds contained in the pericarp and / or fruit of a plant belonging to the family Cucurbitaceae. Item 5. A prostate hyperplasia suppressant containing an extract of a plant belonging to the genus Momordica. Item 6. The prostate hyperplasia suppressant according to Item 5, containing an extract of the pericarp of a plant belonging to the genus Momordica. Item 7. The prostate hyperplasia suppressant according to Item 5 or 6, wherein the plant belonging to the genus Momordica is Momordica charantia. Item 8. A prostate hyperplasia suppressant containing one or more compounds contained in the pericarp and / or fruit of a plant belonging to the family Cucurbitaceae.

Advantages of the Invention

[0014] The extract of a plant belonging to the genus Momordica has a remarkably excellent 5α-reductase inhibitory effect, and thus is useful as an active ingredient of a 5α-reductase inhibitor. Furthermore, the extract of a plant belonging to the genus Momordica has a remarkably excellent prostate hyperplasia inhibitory effect, and thus is also useful as an active ingredient of a prostate hyperplasia suppressant.

[0015] In addition, the extract of a plant belonging to the genus Momordica is a natural-derived component and thus has high safety.

Brief Description of the Drawings

[0016]

Figure 1

Figure 2

Figure 3

Mode for Carrying Out the Invention

[0017] Hereinafter, embodiments of the present invention will be described in detail.

[0018] In the present specification, "containing, comprise" includes the meanings of "essentially consisting of" and "consisting of only".

[0019] The 5α-reductase inhibitor and prostate hypertrophy inhibitor of the present invention are characterized by containing an extract of a plant belonging to the genus Trapa.

[0020] Extract of a plant belonging to the genus Rumex The plant belonging to the genus Trapa is not particularly limited, and examples thereof include Trapa japonica, Trapa natans L. ver. Japonica, Trapa incisa, Trapa bispinosa Roxb., Trapa acornis, Trapa natans, etc. Among them, Trapa bispinosa Roxb. is preferred.

[0021] For the production of an extract from a plant belonging to the genus Momordica, a part or the whole of the plant belonging to the genus Momordica can also be used. Examples of parts of the plant include flowers, flower spikes, pericarp, fruits, pulp, stems, leaves, branches, branch leaves, trunks, barks, rhizomes, root barks, roots, seeds, tendrils, heartwood, aboveground parts, underground parts, etc., and these can be used alone or in combination of multiple parts. As the part of the plant used for the production of the extract, fruits and pericarp are preferred, and pericarp is particularly preferred. Also, for the production of the extract, plants in any state such as raw, dried, cut or ground can be used.

[0022] The method for producing an extract from a plant belonging to the genus Momordica is not particularly limited and can be carried out by a commonly used method. Such methods include, for example, cutting each part of the plant belonging to the genus Momordica as it is or into an appropriate size and performing extraction by squeezing or using a solvent. As the extraction method, hot water extraction is particularly preferred. As such an extraction solvent, water, an organic solvent or a hydrous organic solvent can be used. Examples of the organic solvent include lower alcohols having 1 to 5 carbon atoms such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 2-methyl-2-propanol, 1-pentanol, 2-pentanol, 3-pentanol, etc., ethers such as diethyl ether, esters such as methyl acetate, ethyl acetate, etc., ketones such as acetone, and organic acids such as acetic acid, glacial acetic acid, propionic acid, etc. As the extraction solvent, preferably, water, methanol, ethanol and an aqueous solvent obtained by mixing any two or more of these in an arbitrary ratio, and a particularly preferred extraction solvent is an aqueous solvent obtained by mixing water, ethanol which is an organic solvent approved as a food additive, in an arbitrary ratio.

[0023] The temperature of the extraction solvent can be any temperature exceeding room temperature and below the boiling point of the extraction solvent, and it is preferably determined in consideration of extraction efficiency, heat resistance, volatility, etc. of the substance to be extracted. If necessary, a heated extraction solvent can also be used to improve the extraction efficiency. The extraction time can be in the range of 1 hour to 15 days. When water and aqueous solvents are used as the extraction solvent, acids, bases, salts, etc. can be appropriately included as necessary to improve the extraction efficiency. The pH of the water used for extraction is not particularly limited, and near neutrality is preferred in consideration of use in the living body, more preferably pH 4 to 9, and even more preferably pH 6 to 8.

[0024] Hot water extraction can be carried out by any known method. For example, a method of separating solids by mixing a plant belonging to the genus Momordica in an extraction solvent for a predetermined time and then filtering, centrifuging, decanting, etc., or a continuous extraction method such as the Soxhlet extraction method can be used.

[0025] When removing insoluble matter, etc. by filtration, adsorbents such as activated carbon, bentonite, and celite, and filter aids can be added as necessary to remove impurities. Particularly when used in the state of the extract, it is preferable to perform sterilizing filtration using a membrane filter or the like.

[0026] The solvent extract of a plant belonging to the genus Momordica can be used as it is, and if necessary, it can be purified by ultrafiltration, molecular sieve chromatography (gel filtration), adsorption chromatography, ion exchange chromatography, affinity chromatography, high performance liquid chromatography (HPLC), dialysis, combinations thereof, etc.

[0027] The solvent extract of a plant belonging to the genus Momordica includes the recovered extract (including those further purified if necessary), the concentrated solution obtained by concentrating the extract, solids obtained by removing the solvent of the extract by freeze-drying, spray-drying, etc. Here, concentration, freeze-drying, and spray-drying of the extract can be carried out according to conventional methods.

[0028] 5α-reductase inhibitor and prostate hypertrophy inhibitor The proportion of the extract of the plant belonging to the genus Polygonum contained in the 5α-reductase inhibitor and the prostate hyperplasia inhibitor of the present invention is not particularly limited, and for example, a concentration of 0.01 to 99% by mass can be mentioned.

[0029] The 5α-reductase inhibitor refers to one that inhibits the enzyme activity of 5α-reductase (EC 1.3.1.22) (conversion of testosterone to dihydrotestosterone).

[0030] In the 5α-reductase inhibitor and the prostate hyperplasia inhibitor of the present invention, known components other than the extract of the plant belonging to the genus Polygonum can be appropriately blended within a range that does not interfere with the effects of the present invention.

[0031] The 5α-reductase inhibitor and the prostate hyperplasia inhibitor of the present invention can be used as food and drink products (particularly food and drink products for the purpose of health care, health maintenance, promotion, etc. (for example, health foods, functional foods, dietary supplements, supplements, foods for specified health uses, foods with nutritional functions, or foods with functional claims)), pharmaceuticals (including quasi-drugs), etc. Further, the 5α-reductase inhibitor and the prostate hyperplasia inhibitor of the present invention also include the meaning for additives that impart a 5α-reductase inhibitory action and a prostate hyperplasia inhibitory action, respectively.

[0032] For the above-mentioned food and drink products, the extract of the plant belonging to the genus Polygonum can be used as it is, but if necessary, vitamins, flavonoids, minerals, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, coloring agents, fragrances, stabilizers, preservatives, disintegrants, lubricants, sustained-release regulators, surfactants, solubilizers, wetting agents, etc. can be blended.

[0033] Food and drink products include all food and drink products that can be ingested by animals (including humans). The types of food and drink products are not particularly limited. For example, dairy products; fermented foods (such as yogurt, cheese, etc.); beverages (such as coffee, juice, soft drinks like tea beverages, milk beverages, lactic acid bacteria beverages, beverages containing lactic acid bacteria, yogurt beverages, carbonated beverages, Japanese sake, Western liquor, fruit wine, etc.); spreads (such as custard cream, etc.); pastes (such as fruit paste, etc.); Western confectioneries (such as chocolate, donuts, pies, cream puffs, gums, candies, jelly, cookies, cakes, puddings, etc.); Japanese confectioneries (such as mochi, rice cakes, steamed buns, castella, anmitsu, yokan, etc.); frozen confectioneries (such as ice cream, ice candy, sherbet, etc.); food products (such as curry, beef bowl, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); seasonings (such as dressings, furikake, umami seasonings, soup stock, etc.) and the like can be mentioned.

[0034] The manufacturing method of food and drink products is not particularly limited either, and it can be carried out according to known methods as appropriate.

[0035] The dosage unit form when using food and drink products as supplements is not particularly limited and can be appropriately selected. For example, tablets, capsules, granules, liquids, powders, etc. can be mentioned.

[0036] The intake amount of food and drink products can be appropriately set according to various conditions such as the weight, age, gender, symptoms, etc. of the intake person.

[0037] For the above-mentioned pharmaceuticals, only the extracts of plants belonging to the genus Vicia can also be used, or they can be used in mixture with other pharmaceutical ingredients described in the Japanese Pharmacopoeia such as vitamins and crude drugs.

[0038] When preparing as a pharmaceutical, the extract of the plant belonging to the genus Bistorta can be used as it is, or together with components acceptable in pharmaceuticals, in the form of tablets (including plain tablets, sugar-coated tablets, film-coated tablets, effervescent tablets, chewable tablets, troches, etc.), capsules, pills, powders (powders), fine granules, granules, liquids, suspensions, emulsions, syrups, pastes, injections (including the case of preparing as a liquid by mixing with distilled water or infusion solutions such as amino acid infusion or electrolyte infusion at the time of use), etc., to prepare a pharmaceutical preparation.

[0039] In addition to the extract of the plant belonging to the genus Bistorta, pharmaceuticals can be appropriately formulated with pharmaceutically acceptable components such as excipients, binders, disintegrants, lubricants, suspending agents, thickeners, antioxidants, absorption promoters, pH regulators, coloring agents, preservatives, antiseptics, surfactants, stabilizers, sweeteners, flavoring agents, fragrances, etc. as required.

[0040] The administration method of the pharmaceutical is not particularly limited, and can be carried out, for example, by oral administration, intra-arterial administration, intravenous administration, intraoral administration, rectal administration, enteral administration, transdermal administration, etc.

[0041] The dosage of the pharmaceutical can be appropriately determined according to various conditions such as the patient's weight, age, gender, symptoms, administration method, type of dosage form, etc.

[0042] As the dosage and intake of foods and pharmaceuticals, in the case of humans, generally it is the amount of the active ingredient contained in the preparation, preferably 0.1 - 2000 mg / day per adult. Of course, the dosage and intake vary depending on various conditions, so there may be cases where an amount less than the above dosage and intake is sufficient, or there may be cases where it is necessary to exceed the above range.

[0043] The 5α-reductase inhibitor and prostate hypertrophy inhibitor of the present invention described above are applicable to mammals including humans.

[0044] As shown in the examples described below, the present inventors have found that extracts of plants belonging to the genus Trapa exhibit excellent 5α-reductase inhibitory activity and prostate hypertrophy inhibitory activity. Therefore, since the extracts of plants belonging to the genus Trapa have excellent 5α-reductase inhibitory activity and prostate hypertrophy inhibitory activity, they can be suitably used as active ingredients of 5α-reductase inhibitors and prostate hypertrophy inhibitors.

[0045] In addition, since the extracts of plants belonging to the genus Trapa are natural-derived components, they are highly safe.

Examples

[0046] Hereinafter, examples will be given to explain the present invention in more detail. However, the present invention is not limited to these examples and the like.

[0047] <Measurement sample> Preparation of hot water extract of Trapa plants (hereinafter referred to as "Trapa extract") The fruits of Trapa bispinosa after harvesting were dried, and the dried pericarp was recovered. The dried pericarp was powdered using a food processor and subjected to hot water extraction (using 6 parts by weight of hot water at 90 °C with respect to 1 part by weight of the dried pericarp), and the extract was concentrated at a predetermined concentration rate so that the polyphenol content of the finally obtained Trapa pericarp extract would be 25% by weight or more. Dextrin was added to 67% by weight of the concentrated solution at 33% by weight and spray-dried using a spray dryer. The powder thus obtained (polyphenol content 25% by weight or more) was used as the Trapa extract in the following tests.

[0048] Test Example 1 <Test method> 10 μl of an enzyme solution (20 μg / ml of a rat liver extract fraction), 1 μl of a measurement sample, and 80 μl of a 40 mM potassium phosphate buffer (containing 50 μM NADPH and 1 mM DTT, pH 6.5) were mixed and pre-incubated at 37°C for 15 minutes. Then, after adding 10 μl of a 0.9 μM testosterone solution, the mixture was incubated at 37°C for 30 minutes, and 20 μl of a reaction stop solution (1N hydrochloric acid) was added. Next, after adding 20 μl of a neutralizing solution (1N NaOH), centrifugation was performed for 10 minutes. The supernatant was collected, and the amount of residual testosterone contained in the supernatant was measured using an ELISA kit, and the 5α-reductase inhibition rate was calculated.

[0049] <Results> The results are shown in Fig. 1. The extract of *Hishi* showed a concentration-dependent 5α-reductase inhibitory activity. The IC 50 of the extract of *Hishi* was 32.4 μg / ml, and it was revealed to have 5α-reductase inhibitory activity.

[0050] Test Example 2 <Test method> As shown in Fig. 2, 7-week-old C57BL6 / N mice were subjected to castration surgery, and after a recovery period until the wound healed, on the 6th day of the start of the test, testosterone propionate was administered intraperitoneally at a concentration of 2.0 mg / kg body weight. From the day of testosterone propionate administration, finasteride or the extract of *Hishi* was administered by free drinking (the extract of *Hishi* was dissolved in tap water, and finasteride was suspended in 0.1% carboxymethylcellulose solution). On the 16th day of the start of the test, the mice were euthanized by cervical dislocation and tissues were excised. Then, the seminal vesicle weight and the longitudinal and transverse lengths of the prostate were measured. The test was conducted in the following 4 groups (n = 5). CRL: Control group TP: Testosterone propionate (TP) group 2.0 mg / kg i.p. TP+F: TP + finasteride group 0.08% p.o. TP+WC: TP + extract of *Hishi* group 2% p.o.

[0051] <Results> The results are shown in Figure 3. The extract of Vigna angularis significantly decreased the seminal vesicle weight and the size of the prostate gland, and its effect was the same as or greater than that of finasteride, a type II 5α-reductase inhibitor. Thus, the extract of Vigna angularis showed a significant effect of suppressing prostate hyperplasia by oral administration.

Claims

**Claim 1** A 5α-reductase inhibitor containing an extract of the pericarp of Physalis angulata L., wherein the extraction solvent for the extract is at least one selected from the group consisting of water, methanol, ethanol, 1-propanol, and 2-propanol. **Claim 2** A prostate hypertrophy inhibitor containing an extract of the pericarp of Physalis angulata L., wherein the extraction solvent for the extract is at least one selected from the group consisting of water, methanol, ethanol, 1-propanol, and 2-propanol.

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