Composition for preventing, ameliorating or treating benign prostatic hyperplasia containing hovenia dulcis honey as active ingredient

Abstract

The present invention relates to a composition for preventing, ameliorating or treating benign prostatic hyperplasia, containing Hovenia dulcis honey as an active ingredient. Specifically, the Hovenia dulcis honey of the present invention suppresses the proliferation of prostate cells that are hyperproliferated by dihydrotestosterone (DHT), which is a male hormone, and has the effect of reducing prostate weight in an animal model with induced benign prostatic hyperplasia, and thus can be effectively used as a composition for preventing, ameliorating or treating benign prostatic hyperplasia.

Description

Composition for preventing, improving or treating benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient

[0001] The present invention relates to a composition for preventing, improving or treating benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

[0002]

[0003] This invention is the result of research supported by the Agricultural Policy Support Technology Development Project of the Rural Development Administration (Project Number: 2390000036, 00228817 (NAN2312010).

[0004] Benign prostatic hyperplasia (BPH) is a general term for lower urinary tract symptoms caused by an enlarged prostate and impaired bladder function, resulting in decreased urine flow due to urethral obstruction and various bladder irritation symptoms such as frequent urination, residual urine, and urgency (the inability to hold urine). Treatment options include medication, non-invasive procedures, invasive surgery, and alternative therapies. Testosterone plays a significant role in the growth, development, and pathological state of the prostate through androgen receptors in the prostate. BPH is influenced by androgens, and dihydrotestosterone (DHT) is the most important androgen in the prostate, playing a crucial role in BPH. Recently, herbal medicine has emerged as a promising alternative to the side effects and shortcomings of conventional synthetic drug treatments for BPH and male pattern baldness.

[0005] Hovenia dulcis is a deciduous broad-leaved tree in the buckthorn family, also called hokkae tree or heorikke tree. It is also used as a tonic, baekseok tree, mokmil, and hyeonpori. It grows to a height of 10 to 20 m and a diameter of 40 to 80 cm. It mainly grows in areas such as Seoraksan Mountain, Odaesan Mountain, Jirisan Mountain, and Hallasan Mountain, and grows well in the temperate southern regions rather than the central and northern regions. The fruit stalk and stem have a sweet flavor and have been used for food, especially for fruit wine, and have been used medicinally to eliminate alcoholic toxins. According to the Compendium of Materia Medica, the raw juice of the Hovenia dulcis fruit is said to relieve alcoholic toxins and stop nausea, and the seeds have traditionally been used for alcoholism, blood purification, urinary incontinence, and vomiting, and the fruit stem is said to be effective for strengthening the stomach and nourishing the blood.

[0006] Meanwhile, honey has long been closely associated with humanity. It has been consumed as a nutritional supplement to replenish energy and used as a medicine. While its composition varies depending on the source, it contains sugars such as dextrose, maltose, fructose, and sucrose, as well as vitamins and minerals, making it a nutritious food effective in relieving fatigue. As a medicine, its anti-inflammatory and antibacterial properties have been scientifically proven to treat traumatic injuries such as wounds and burns, as well as sore throats and eye inflammation.

[0007] As for prior art related to benign prostatic hyperplasia, Korean Patent No. 2583293 discloses a composition for treating or preventing benign prostatic hyperplasia or alopecia containing a Salvia miltiorrhiza Bunge extract as an active ingredient, and Korean Patent No. 2556622 discloses a composition for preventing or treating benign prostatic hyperplasia containing ginseng, licorice, and peony extracts. However, no composition for preventing, improving, or treating benign prostatic hyperplasia containing the honey of the present invention as an active ingredient has been disclosed to date.

[0008] The present invention was derived from the above-mentioned needs, and relates to a composition for preventing, improving, or treating benign prostatic hyperplasia containing honey from the Korean walnut tree as an active ingredient. Specifically, the present invention was completed by confirming that honey from the Korean walnut tree inhibits the proliferation of prostate cells hyperproliferated by the male hormone DHT (dihydrotestosterone) and reduces the weight of the prostate in an animal model in which benign prostatic hyperplasia was induced.

[0009] In order to achieve the above purpose, the present invention provides a pharmaceutical composition for preventing or treating benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0010] In addition, the present invention provides a health functional food composition for preventing or improving benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0011] In addition, the present invention provides a veterinary composition for preventing or treating benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

[0012] In addition, the present invention provides a feed additive for preventing or improving benign prostatic hyperplasia containing honey from the walnut tree as an effective ingredient.

[0013] In addition, the present invention provides a herbal medicine composition for preventing or treating benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0014] The present invention relates to a pharmaceutical composition for preventing or treating benign prostatic hyperplasia containing honey from the Korean walnut tree as an active ingredient, and more specifically, honey from the Korean walnut tree has an excellent effect of inhibiting the proliferation of prostate cells hyperproliferated by the male hormone DHT (dihydrotestosterone) and reducing the weight of the prostate in an animal model in which benign prostatic hyperplasia is induced.

[0015] Figure 1 shows the results of confirming cell survival rate when the honey of the present invention was treated at various concentrations to prostate epithelial cells (RWPE-1).

[0016] Figure 2 shows the results of confirming the effect of inhibiting prostate cell proliferation by the treatment with the honey of the present invention in prostate cells hyperproliferated by the androgen DHT (dihydrotestosterone). CON is the control group, DHT is the group in which hyperproliferation of prostate cells was induced by treatment with 10 nM dihydrotestosterone, and Fi is the positive control group treated with 30 μM finasteride, a DHT inhibitor. ### indicates that cell proliferation was statistically significantly increased in the DHT treatment group compared to the control group (CON), and p<0.001. *** indicates that cell proliferation was statistically significantly decreased in the honey of ...

[0017] Figure 3 shows the results of confirming the effect of walnut honey on prostate hypertrophy in an animal model induced with benign prostatic hyperplasia. (A) Daily body weight (g) of each experimental group, (B) photograph of the prostate of each experimental group, (C) prostate weight (mg) of each experimental group, and (D) the relative ratio of prostate weight (PW) to body weight (BW) of each experimental group. CON is the control group, TP is the group induced with benign prostatic hyperplasia by administering 10 mg / kg of testosterone propionate, TP+walnut honey is the group administered 10 mg / kg of testosterone propionate and 600 mg / kg of the walnut honey of the present invention, and TP+Fi is the positive control group administered 10 mg / kg of testosterone propionate and 10 mg / kg of finasteride, an inhibitor of benign prostatic hyperplasia. ### indicates that the prostate weight or PW / BW ratio was statistically significantly increased in the testosterone propionate administration group (TP) compared to the control group (CON), p<0.001. *** indicates that the prostate weight or PW / BW ratio was statistically significantly decreased in the walnut honey administration group (TP+walnut honey) or finasteride administration group (TP+Fi) compared to the testosterone propionate administration group (TP), p<0.001.

[0018] In order to achieve the purpose of the present invention, the present invention provides a pharmaceutical composition for preventing or treating benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0019] The above honey from the walnut tree is characterized by being honey that uses the flowers of the walnut tree as its nectar source.

[0020] The pharmaceutical composition according to the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent.

[0021] Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include various compounds or mixtures including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

[0022] The pharmaceutical composition according to the present invention can be formulated and used in the form of oral formulations such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods.

[0023] When formulated, they are usually prepared using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and these solid preparations are prepared by mixing the pharmaceutical composition with at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspending agents can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. Suppository bases can include withepsol, macrogol, Tween 61, cocoa butter, laurin butter, and glycerogelatin.

[0024] The appropriate dosage of the pharmaceutical composition of the present invention can be prescribed in various ways depending on factors such as the formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity.

[0025] The pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered by topical application to the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc.

[0026] In addition, the present invention provides a health functional food composition for preventing or improving benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0027] The above composition is preferably manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candies, syrups, and beverages, but is not limited thereto.

[0028] When the health functional food composition of the present invention is used as a food additive, the effective ingredient may be added as is or used together with other foods or food ingredients, and may be used appropriately according to a conventional method. The amount of the effective ingredient mixed may be appropriately determined depending on the purpose of use (improvement). Generally, when manufacturing a food or beverage, the composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the raw material. However, in the case of long-term intake for the purpose of health and hygiene or health control, the amount may be below the above range, and since there is no problem in terms of safety, the effective ingredient may also be used in an amount exceeding the above range.

[0029] There are no specific restrictions on the types of the above foods. Examples of foods to which the above active ingredients can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the conventional sense.

[0030] When the composition of the present invention is used as a health beverage, it may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The natural carbohydrates mentioned above are 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. As a sweetener, a natural sweetener such as thaumarin or stevia extract, or a synthetic sweetener such as saccharin or aspartame can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 g of the composition of the present invention. The composition of the present invention may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks. These components may be used independently or in mixtures. The proportion of these additives is not particularly important, but the composition of the present invention is typically selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

[0031] In addition, the present invention provides a veterinary composition for preventing or treating benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

[0032] The veterinary composition comprising the honey of the present invention may further comprise suitable excipients and diluents according to conventional methods. Excipients and diluents that may be included in the veterinary composition comprising the honey of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, ethanol, stearyl alcohol, liquid paraffin, sorbitan monostearate, polysorbate 60, methylparaben, propylparaben, and mineral oil.

[0033] The veterinary composition containing the honey of the present invention may further include fillers, anticoagulants, lubricants, wetting agents, spices, emulsifiers, preservatives, etc. The veterinary composition of the present invention may be formulated using a method well known in the art so as to provide rapid, sustained or delayed release of the active ingredient after administration to an animal, and the formulation may be in the form of a powder, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, suppositories, sterile injectable solutions, sterile external preparations, etc.

[0034] The veterinary composition according to the present invention may vary depending on the age, sex, and weight of the animal, but may be administered once or several times a day, and the dosage may be increased or decreased depending on the route of administration, severity of the disease, sex, weight, age, etc. Therefore, the above dosage does not limit the scope of the present invention in any way.

[0035] In addition, the present invention provides a feed additive for preventing or improving benign prostatic hyperplasia containing honey from the walnut tree as an effective ingredient.

[0036] The feed additive of the present invention corresponds to supplementary feed under the Feed Management Act. The term "feed" in the present invention may mean any natural or artificial diet, meal, etc., or ingredients of the meal, which are intended for or suitable for animals to eat, ingest, and digest. The type of the feed is not particularly limited, and feed commonly used in the relevant technical field may be used. Non-limiting examples of the feed include plant feeds such as grains, roots, fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal, or grain by-products; and animal feeds such as proteins, inorganic substances, oils and fats, mineral substances, oils and fats, single-cell proteins, zooplankton, or food. These may be used alone or in combination of two or more.

[0037] In addition, the present invention provides a herbal medicine composition for preventing or treating benign prostatic hyperplasia containing honey from the walnut tree as an active ingredient.

[0038] The herbal medicine composition according to the present invention refers to a conventional dried medicinal herb used in the manufacture of herbal medicine. The herbal medicine composition of the present invention may be an extract obtained by extraction using a conventional method using an extraction solvent selected from water, a lower alcohol having a concentration of C1 to C4, or a mixture thereof, or may be an extract in powder form obtained by drying the extract. There are no particular restrictions on the formulation. For example, the herbal medicine composition may be manufactured in the form of a pill, tablet, capsule, or liquid.

[0039] Hereinafter, the present invention will be described in detail by examples. However, the following examples are only illustrative of the present invention, and the content of the present invention is not limited to the following examples.

[0040]

[0041] Example 1. Preparation of honey from the walnut tree

[0042] The honey from the walnut tree used in the present invention was provided by the National Institute of Agricultural Sciences.

[0043]

[0044] Example 2. Confirmation of cytotoxicity following treatment with honey from the Chinese juniper tree

[0045] To confirm the cytotoxicity of honey from the walnut tree, cell viability was measured using RWPE-1 cells, a prostate epithelial cell line. RWPE-1 cells, a prostate epithelial cell line, were cultured in K-SFM (Keratinocyte serum-free medium) containing 1% penicillin / streptomycin (1% P / S). The cells were seeded at a density of 5 × 10 per well. 4 The cells were dispensed into 96-well plates at a density of 100 μg / mL, and the honey of the present invention was dissolved in water and treated at different concentrations (1.25, 2.5, 5, and 10 mg / mL). The cells were then cultured for 24 hours, and cell viability was measured using the CCK (Cell Counting Kit)-8 assay. Cell viability was measured at a wavelength of 450 nm using an Epoch® microvolume spectrophotometer system (BioTek Instruments Inc., Winooski, VT, USA).

[0046] As a result, as disclosed in Fig. 1, cell viability was maintained up to a concentration of 10 mg / ㎖ of honey from the Chinese juniper tree, confirming that there was no cytotoxicity.

[0047]

[0048] Example 3. Confirmation of the effect of honey from the walnut tree on improving benign prostatic hyperplasia.

[0049] (1) Measurement of prostate cell viability inhibition

[0050] To confirm the efficacy of honey from the Chinese juniper tree in inhibiting prostate cell proliferation, a CCK (Cell Counting Kit)-8 experiment was performed using RWPE-1 cells, which are prostate epithelial cells.

[0051] RWPE-1 cells were seeded at 5 × 10 per well. 4The cells were seeded in a 96-well plate at a density of 10 μM and pretreated with 10 nM of dihydrotestosterone (DHT), a male hormone, and then treated with various concentrations of honey and 30 μM of finasteride as a positive control. After culturing the cells for 24 hours, they were treated with CCK-8 solution, and 2 hours later, cell proliferation was measured at a wavelength of 450 nm using an Epoch® microvolume spectrophotometer system.

[0052] As a result, as disclosed in Fig. 2, prostate cells were hyperproliferated by DHT treatment, but it was confirmed that the experimental group treated with the honey of the present invention suppressed the proliferation of prostate cells compared to the DHT treatment group.

[0053]

[0054] (2) Changes in prostate weight following administration of honey from the Chinese juniper tree

[0055] For the animal model of benign prostatic hyperplasia (BPH), 4-week-old male C57BL / 6J mice (18–20 g) were purchased from Dooyeol Bio (Korea) and used for experiments. The animals were randomly divided into four groups (n=5): a normal control group (CON), a testosterone propionate group (TP), a honey-testosterone propionate group, and a finasteride-testosterone propionate group.

[0056] Testosterone propionate was administered subcutaneously at a concentration of 10 mg / kg once daily for 5 weeks to induce prostatic hypertrophy. Finasteride, a positive control, was administered intraperitoneally at a concentration of 10 mg / kg once daily for 5 weeks, and walnut honey was administered orally at a concentration of 600 mg / kg once daily for 5 weeks.

[0057] To determine the inhibitory effect of walnut honey on prostate hypertrophy in experimental animals with benign prostatic hyperplasia (BPH), body weight (BW) was measured for 5 weeks (Fig. 3A). At the end of the fifth week, the animals were sacrificed and their prostate tissue weights were measured (Fig. 3B). The prostate weight / body weight (PW / BW) ratio was calculated as follows.

[0058] Prostate weight relative to body weight (PW / BW) = (prostate weight of each experimental group) / (body weight of each experimental group) × 1000

[0059] As a result of measuring the weight of the prostate tissue of the experimental animals, as disclosed in Figures 3C and 3D, it was confirmed that the prostate weight of the TP group, which induced prostatic hypertrophy, significantly increased compared to the control group (CON). In the TP+Fi group or the group administered TP+Hydrangea japonica honey, which was administered the positive control drug finasteride, it was confirmed that the prostate weight and the prostate weight / body weight ratio were significantly reduced compared to the TP group.

[0060] From these results, it was confirmed that the honey from the walnut tree of the present invention has an effect of improving benign prostatic hyperplasia.

Claims

1. A pharmaceutical composition for the prevention or treatment of benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

2. A pharmaceutical composition for preventing or treating benign prostatic hyperplasia, characterized in that the honey from the walnut tree in the first paragraph is honey from the flower of the walnut tree as a nectar source.

3. A pharmaceutical composition for preventing or treating benign prostatic hyperplasia, characterized in that, in addition to the effective ingredient in paragraph 1, it further comprises a pharmaceutically acceptable carrier, excipient or diluent.

4. A pharmaceutical composition for preventing or treating benign prostatic hyperplasia, characterized in that the composition is prepared in any one formulation selected from among capsules, powders, granules, tablets, suspensions, emulsions, syrups, and aerosols in the first paragraph.

5. A health functional food composition containing honey from the Chinese juniper tree as an active ingredient for preventing or improving benign prostatic hyperplasia.

6. A health functional food composition for preventing or improving benign prostatic hyperplasia, characterized in that the composition is manufactured in any one formulation selected from powder, granules, pills, tablets, capsules, candies, syrups, and beverages in the fifth paragraph.

7. A veterinary composition for the prevention or treatment of benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

8. Feed additive for preventing or improving benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

9. A herbal medicine composition for the prevention or treatment of benign prostatic hyperplasia containing honey from the Chinese juniper tree as an active ingredient.

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