Composition for preventing, improving, or treating prostate disease, comprising hemp seed oil

Abstract

The present invention provides a composition for improving, preventing, or treating prostate disease, comprising hemp seed oil as an active ingredient. A functional composition comprising hemp seed oil as an active ingredient, according to the present invention, reduces the prostate weight of benign prostatic hyperplasia patients, reduces blood prostate-specific antigen (PSA), dihydrotestosterone (DHT), and 5-alpha reductase I levels, and also has excellent cell growth inhibitory ability with respect to prostate cancer cells. Thus, the functional composition comprising hemp seed oil as an active ingredient, according to the present invention, is expected to be capable of exhibiting a preventive, relieving, or therapeutic effect on prostate disease including benign prostatic hyperplasia and prostate cancer.

Description

Composition for preventing, improving or treating prostate disease containing hemp seed oil

[0001] [Cross-reference with related applications]

[0002] This application claims the benefit of priority from Republic of Korea Patent Application No. 10-2023-0102822, filed August 7, 2023, the entire contents of which are incorporated herein by reference.

[0003] [Technical Field]

[0004] The present invention relates to a composition for preventing, improving or treating prostate diseases, comprising hemp seed oil.

[0005] Hempseed (Cannabis sativa) is the seed of the hemp plant, an annual plant of the hemp family. It is edible after removing the hallucinogenic component tetrahydrocannabinol (THC) contained in the husk. It is native to Central Asia and is currently cultivated in various regions around the world. Hempseed has a nutty yet soft texture, similar to other nuts, and is nutritionally excellent due to its high protein, essential amino acids, and mineral content. It also has a high fat content (25-35%), so it is pressed and extracted to produce edible oil.

[0006] Hempseed oil is rich in polyunsaturated fatty acids such as alpha-linolenic acid (ALA) and gamma-linolenic acid (GLA), and is known to be effective in reducing cholesterol, alleviating vascular inflammation, and reducing skin diseases and atopy.

[0007] Hemp seeds and hemp seed oil are attracting attention for their rich nutritional value, and research into functional compositions utilizing them is ongoing. Products containing hemp seeds or hemp seed oil must meet the THC content standards established by the Ministry of Food and Drug Safety (hemp seeds: 5 mg / kg or less, hemp seed oil: 10 mg / kg or less).

[0008] The present inventors have confirmed that when cannabis seed oil is administered to rats with benign prostatic hyperplasia, it reduces prostate weight and blood prostate specific antigen (PSA), dihydrotestosterone (DHT), and 5-alpha reductase Ⅰ, and that when cannabis seed oil is treated to human prostate cancer cell lines, it has an excellent effect in inhibiting cell growth, and thus completed the present invention.

[0009] The present invention is a functional composition containing hemp seed oil, and specifically aims to provide a functional composition having the effect of improving prostate disease, etc.

[0010] One aspect of the present invention provides a composition for improving, preventing or treating prostate disease, comprising hemp seed oil as an active ingredient.

[0011] The functional composition comprising hemp seed oil according to the present invention as an active ingredient reduces prostate weight in patients with benign prostatic hyperplasia, reduces blood levels of prostate-specific antigen (PSA), dihydrotestosterone (DHT), and 5-alpha reductase I, and also exhibits excellent cell growth inhibition properties against prostate cancer cells. Therefore, the functional composition comprising hemp seed oil according to the present invention as an active ingredient is expected to exhibit preventive, ameliorating, or therapeutic effects on prostate diseases, including benign prostatic hyperplasia and prostate cancer.

[0012] Figure 1 is a graph showing that the weight of the prostate is significantly reduced when the hemp seed oil according to the present invention is administered to a rat with induced prostatic hypertrophy.

[0013] Figure 2 is a graph showing that blood prostate-specific antigen (PSA) is reduced when hemp seed oil according to the present invention is administered to rats with induced prostatic hyperplasia.

[0014] Figure 3 is a graph showing that blood dihydrotestosterone (DHT) is reduced when hemp seed oil according to the present invention is administered to rats with induced prostatic hypertrophy.

[0015] Figure 4 is a graph showing that blood 5-alpha reductase I is reduced when hemp seed oil according to the present invention is administered to rats with induced prostatic hypertrophy.

[0016] Figure 5 is a graph showing that cell growth is inhibited by treatment with hemp seed oil, as a result of confirming cytotoxicity against a human prostate cancer cell line (LNCap).

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

[0018] The terms and words used in this specification and claims should not be interpreted as limited to their usual or dictionary meanings, but should be interpreted as meanings and concepts that conform to the technical idea of ​​the present invention, based on the principle that the inventor can appropriately define the concept of the term to explain his or her own invention in the best way.

[0019] 1. Method for producing hemp seed oil

[0020] One aspect of the present invention provides a functional composition comprising hemp seed oil as an active ingredient.

[0021] In the present invention, hemp seed oil is oil extracted from hemp seeds by any method, and hemp seeds are hemp seeds that meet the THC content standard (5 mg / kg or less) established by the Ministry of Food and Drug Safety.

[0022] Hemp seed oil can be obtained by separating and extracting fat-soluble components contained in hemp seeds using conventional extraction methods known in the art, such as pressing extraction, solvent extraction, supercritical fluid extraction, ultrasonic extraction, filtration, and reflux extraction. Preferably, it can be produced using solvent extraction or supercritical fluid extraction. The above extraction process can be repeated several times, and additional steps such as concentration or drying can be performed thereafter.

[0023] The pressing extraction method can be performed using either cold pressing or hot pressing. Cold pressing is performed using an oil press at a temperature of 30°C to 50°C, or 40°C to 50°C. Cold pressing has the advantage of minimal change in the active ingredient. Hot pressing is performed using an oil press at a temperature exceeding 50°C, preferably 100°C to 300°C, or 200°C to 300°C. Hot pressing may result in changes in the active ingredient.

[0024] As an example, in the present invention, hemp seed oil can be produced by a production method including: 1) a step of removing the outer seed coat from hemp seeds using a dehuller; 2) a step of drying the seeds to a moisture content of 5.0% or less at a temperature of 50°C or lower; and 3) a step of producing oil using a cold-pressed oil press at 40°C or lower.

[0025] In addition, the manufacturing method may additionally perform, prior to step 1), a step of washing the hemp seeds with water; and / or a step of drying the hemp seeds at a temperature of 50°C or lower to a moisture content of 9% or lower.

[0026] In addition, the above manufacturing method may additionally include, after step 3), a step of obtaining a supernatant by settling the milking oil at 5°C or lower for 1 to 3 weeks.

[0027] According to the solvent extraction method, the type of extraction solvent is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water, C1-C4 lower alcohols such as methanol, ethanol, propyl alcohol, butyl alcohol, etc.; polyhydric alcohols such as glycerin, butylene glycol, propylene glycol, etc.; and hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, tetrahydrofuran, petroleum ether, dipropyl ether, benzene, hexane, diethyl ether, dichloromethane, etc.; or mixtures thereof. For example, the extraction may be performed using water, C1-C4 lower alcohols, or a mixed solvent thereof, or water, hexane, or a mixed solvent thereof.

[0028] As an example, the extraction solvent used in extracting hemp seed oil is an aqueous ethanol solution. More preferably, the aqueous ethanol solution may be an aqueous ethanol solution of 50% (v / v) to 99% (v / v), an aqueous ethanol solution of 60% (v / v) to 98% (v / v), or an aqueous ethanol solution of 70% (v / v) to 97% (v / v), or an aqueous ethanol solution of 80% (v / v) to 96% (v / v), or an aqueous ethanol solution of 90% (v / v) to 95% (v / v).

[0029] When solvent extraction is performed, the extraction may be performed at 20°C to 60°C, preferably at 22°C to 50°C, and more preferably at 23°C to 32°C, but is not limited thereto. The extraction may be performed for 6 to 30 hours, preferably at 10 to 28 hours, and more preferably at 12 to 24 hours, but is not limited thereto.

[0030] In solvent extraction, extraction may be performed 1 to 8 times, preferably 1 to 6 times, and more preferably 1 to 5 times, but is not limited thereto, and the extract may be a single extract obtained from each extraction or a mixed extract of extracts obtained from each extraction.

[0031] Supercritical fluid extraction (SFE) is an extraction method that utilizes supercritical fluids, which appear when temperature and pressure exceed a certain critical point. It is an extraction method that combines the advantages of both liquids and gases, such as high solubility, rapid mass and heat transfer, low viscosity, and rapid penetration into micropores due to high diffusion coefficient. In general, supercritical fluids have the property that their solubility and density change with changes in temperature and pressure, and the activity of the extract may also vary accordingly. Therefore, extraction methods using supercritical fluids can set high-density conditions by manipulating pressure and temperature, so they have excellent selectivity for fractionation and separation, and can obtain high-purity natural active ingredients. In addition, since the extraction is performed at a relatively low temperature, it prevents loss of natural active ingredients due to heat.

[0032] Carbon dioxide, a supercritical fluid with a critical point close to room temperature, is non-toxic, non-flammable, and very inexpensive. Supercritical fluid extraction conditions can be adjusted to enhance the prostate disease prevention or treatment effects of the final product, hemp seed oil. For example, temperature, time, and pressure can be controlled during supercritical extraction, and these conditions are described in detail below.

[0033] When extracting with a supercritical fluid, the temperature may be 40°C to 100°C, preferably 50°C to 90°C, and more preferably 60°C to 80°C, but is not limited thereto. If the temperature during extraction is outside the appropriate range, the yield of the extract decreases, and the production cost increases, which has the disadvantage of increasing the cost of the product.

[0034] When extracting with a supercritical fluid, the extraction time may be 0.5 to 10 hours, preferably 1 to 9 hours, more preferably 2 to 8 hours or 2 to 5 hours, but is not limited thereto.

[0035] In addition, the conditions for supercritical extraction may be to maintain the pressure at 10 MPa to 50 MPa, preferably at 15 MPa to 45 MPa, more preferably at 10 MPa to 40 MPa or 25 MPa to 35 MPa, but are not limited thereto.

[0036] The hemp seed oil of the present invention can be obtained by applying a thin film distillation process to an extract obtained through supercritical extraction. Thin film distillation can be performed using a commonly used thin film distillation device. Thin film distillation is a process that maximizes the surface area of ​​the mixture in contact with the heat source by physically forming a thin film on the mixture liquid to be separated, thereby increasing the evaporation rate. The thin film distillation device comprises a cylindrical heat transfer vessel equipped with a heating jacket and a rotating blade (wiper) inside the vessel. The extract to be distilled is supplied from the top of the heat transfer vessel and distributed circumferentially by a distributor installed on the top of the rotary blade. The extract is stirred by the rotary blade and simultaneously flows down the heat transfer wall by the blade, forming a uniform and stable liquid film. During this process, components within the extract that are not related to improving prostate disease are heated by the jacket heating source, vaporized, separated, and condensed for removal.

[0037] During the above thin film distillation, the temperature inside the still may be 150°C to 350°C, preferably 200°C to 300°C, and more preferably 230°C to 270°C, but is not limited thereto. If the temperature inside the still is below the lower limit, the prostate disease improvement effect of the final product, hemp seed oil, obtained by applying the thin film distillation process after supercritical extraction is low. If the temperature inside the still exceeds the upper limit, there is a problem of loss of effective ingredients.

[0038] During the above thin film distillation, the vacuum may be 0.001 torr to 100 torr, preferably 0.01 torr to 50 torr, and more preferably 0.1 torr to 20 torr, but is not limited thereto. If the vacuum is below the lower limit, the prostate disease improvement effect of hemp seed oil is low even when the thin film distillation process is applied after supercritical extraction. If the vacuum exceeds the upper limit, there is a problem that the purification effect is reduced, resulting in a lower quality, and the prostate disease improvement effect of the obtained extract is low.

[0039] In the above thin film distillation, the distillation time may be 1 to 48 hours, preferably 2 to 24 hours, and more preferably 4 to 10 hours, but is not limited thereto. If the distillation time is below the lower limit, the prostate disease improvement effect of hemp seed oil is low even when the thin film distillation process is applied after supercritical extraction. If the distillation time exceeds the upper limit, the quality deteriorates due to changes in the components, and the prostate disease improvement effect of hemp seed oil is low.

[0040] In the above thin film distillation, the input speed of the extract may be 0.1 Hz to 100 Hz, preferably 5 Hz to 60 Hz, and more preferably 10 Hz to 30 Hz, but is not limited thereto. If the input speed of the extract is less than the lower limit, the thin film is not properly formed, and the prostate disease improvement effect of the final product, hemp seed oil, obtained by applying the thin film distillation process after supercritical extraction is low. If the input speed of the extract exceeds the upper limit, there is a problem that the purification effect is reduced, resulting in a lower quality, and the prostate disease improvement effect of the obtained extract is low.

[0041] The above hemp seed oil may be obtained by additionally performing a conventional fractionation process on the above extract. For example, the hemp seed oil extract according to the present invention may be obtained by passing a fraction through an ultrafiltration membrane having a certain molecular weight cut-off value, and the active fractions obtained through various purification methods additionally performed, such as separation by various chromatographies (designed for separation according to size, charge, hydrophobicity, or affinity), are also included in the hemp seed oil of the present invention. By separating the hemp seed oil containing various components according to the properties of the active components through concentration gradient column chromatography, etc., a specific active fraction having a higher effect in preventing or treating prostate diseases can be prepared. The column chromatography may be performed multiple times by selecting an appropriate filler as needed, but is not limited thereto. When using the above chromatography, the elution solvent, elution speed, and elution time may be applied to the solvent, speed, or time generally used in the present technical field.

[0042] The hemp seed oil of the present invention may contain THC in an amount of 10 mg / kg or less and cannabidiol (CBD) in an amount of 20 mg / kg or less to meet the standards established by the Ministry of Food and Drug Safety.

[0043] Additionally, the hemp seed oil of the present invention may have an omega-6 / omega-3 ratio of 4 or less.

[0044] 2. Use of compositions containing hemp seed oil

[0045] The functional composition containing the above-mentioned hemp seed oil as an active ingredient can be used for improving, preventing, or treating prostate diseases. Therefore, one aspect of the present invention provides a functional composition containing hemp seed oil as an active ingredient for improving, preventing, or treating prostate diseases.

[0046] In the present invention, "prostate disease" may be one or more diseases selected from the group consisting of benign prostatic hyperplasia, prostatitis, prostate cancer, prostatic abscess, and prostatic calcification, but is not limited thereto and may include all various diseases caused by problems with the prostate. Benign prostatic hyperplasia is a disease in which the size of the prostate increases, and the enlarged prostate presses on the urethra passing through the prostate, and various symptoms such as obstruction of urine discharge due to this urethral compression appear. Prostatitis refers to inflammation of the prostate, and when the cause is bacteria, it is called bacterial prostatitis, and when it is not bacteria, it is called nonbacterial prostatitis. Prostate cancer is a malignant tumor that develops in the prostate and exists as if surrounding the urethra. Therefore, when prostate cancer occurs, the urethra is compressed by its growth, causing various symptoms such as difficulty urinating, emptying the bladder, a feeling of residual urine, nocturia, urgency to urinate, and discomfort in the lower abdomen. A prostatic abscess is a disease in which bacteria penetrate the prostate through the urethra, causing acute inflammation and the formation of a pus pocket, which rapidly necrosis of the surrounding prostatic tissue. When it occurs, a high fever and chills suddenly appear, and urinary retention symptoms such as the inability to urinate even when wanting to urinate are felt, causing severe pain during urination. Prostatic calcification is a disease that occurs when calcium stones settle in the prostate. The stones are formed when calcium, oxalate, and phosphate, which remain when too many components in body fluids including urine cannot be liquefied, crystallize.

[0047] In the present invention, "prevention" refers to any action that suppresses or delays prostate disease using the composition, and "treatment" refers to any action that improves or beneficially alters prostate disease using the composition. In the present invention, "improvement" refers to any action that includes improving, suppressing, or delaying symptoms, and may be used interchangeably with the terms "prevention" and "treatment."

[0048] The above hemp seed oil may be included in an amount of 0.0001 to 20 wt%, or 0.001 to 15 wt%, or 0.01 to 12 wt%, or 0.05 to 10 wt%, or 0.1 to 1 wt%, based on 100 wt% of the total weight of the functional composition. If the effective content of the hemp seed oil is less than 0.0001 wt%, it is difficult to prevent or treat prostate disease, and if it exceeds 20 wt%, the significant increase in efficacy due to the increase in content may be reduced, which may be uneconomical.

[0049] In a specific embodiment of the present invention, it was confirmed that when hemp seed oil was administered to rats with induced benign prostatic hyperplasia, the prostate weight was reduced and the blood prostate-specific antigen (PSA), dihydrotestosterone (DHT), and 5-alpha reductase Ⅰ levels were reduced. Specifically, in the negative control group with induced benign prostatic hyperplasia, the prostate weight significantly increased compared to the normal group, but when hemp seed oil was administered, the prostate weight was reduced.

[0050] In addition, in the negative control group in which benign prostatic hyperplasia was induced, prostate-specific antigen (PSA) increased by 34% compared to the normal group, and when hemp seed oil was administered, it decreased by 58%, which showed a greater reduction effect than the 50% of the positive control group (finasteride). As the size of the prostate increases, the level of prostate-specific antigen (PSA) tends to increase, and the correlation between prostate diseases including benign prostatic hyperplasia and blood PSA levels has been consistently reported. Therefore, it can be seen that the decrease in blood PSA levels by hemp seed oil intake is the result of alleviating benign prostatic hyperplasia by reducing the size of the enlarged prostate.

[0051] In addition, in the negative control group in which prostate enlargement was induced, dihydrotestosterone (DHT) increased by 79% compared to the normal group, but decreased by 36% when cannabis seed oil was administered. In the negative control group in which prostate enlargement was induced, 5-alpha reductase Ⅰ increased by 31% compared to the normal group, but decreased by 31% when cannabis seed oil was administered. Testosterone is converted to dihydrotestosterone (DHT) by 5-alpha reductase, and dihydrotestosterone (DHT) acts on androgen receptors 10 times more potently than testosterone. Therefore, from the fact that dihydrotestosterone (DHT) and 5-alpha reductase Ⅰ in the blood were reduced, it can be expected that cannabis seed oil intake will block the conversion of testosterone to dihydrotestosterone (DHT), thereby inhibiting the growth of prostate size and thus showing an effect in treating prostate hyperplasia.

[0052] In addition, in a specific embodiment of the present invention, the cytotoxicity against human prostate cancer cell line (LNCap) was confirmed, and it was confirmed that excellent cell growth inhibition ability was exhibited when treated with hemp seed oil.

[0053] The functional composition containing the above hemp seed oil as an active ingredient may be a pharmaceutical composition, a food composition, or a health functional food composition.

[0054] The above pharmaceutical composition may be manufactured in a unit dosage form or may be manufactured by placing it in a multi-dose container by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method that can be easily performed by a person having ordinary skill in the art to which the present invention pertains, and the like. In this case, the formulation may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granules, tablets, capsules or gel (e.g., hydrogel), and may additionally include a dispersant or stabilizer.

[0055] Additionally, the hemp seed oil contained in the pharmaceutical composition may be delivered in a pharmaceutically acceptable carrier such as a colloidal suspension, powder, saline solution, lipid, liposome, microspheres, or nano-spheres. These may be complexed or associated with a carrier, and may be delivered in vivo using a carrier system known in the art, such as a lipid, liposome, microparticle, gold, nanoparticle, polymer, condensation agent, polysaccharide, polyamino acid, dendrimer, saponin, adsorption enhancing agent, or fatty acid.

[0056] In addition, pharmaceutically acceptable carriers may include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia, gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate, and mineral oil, which are commonly used in formulations. In addition, lubricants, wetting agents, sweetening agents, flavoring agents, emulsifiers, suspending agents, preservatives, etc. may be further included in addition to the above ingredients. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

[0057] The above pharmaceutical composition can be administered orally or parenterally during clinical administration, and can be used in the form of a general pharmaceutical preparation. That is, the pharmaceutical composition of the present invention can be administered in various oral and parenteral dosage forms during actual clinical administration. When formulated, it is prepared using diluents or excipients such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations are prepared by mixing a herbal extract or fermented herbal product 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, solutions, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, they may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions 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, cacao butter, laurin butter, glycerol, and gelatin.

[0058] The above pharmaceutical composition can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers to prevent or improve the prevention or treatment of prostate diseases.

[0059] The concentration of the active ingredient included in the above pharmaceutical composition can be determined in consideration of the therapeutic purpose, the patient's condition, the required period, etc., and is not limited to a specific concentration range. The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dosage level can be determined according to the type and severity of the patient's disease, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the excretion rate, the treatment period, factors including concurrently used drugs, and other factors well known in the medical field. The pharmaceutical composition can be administered as an individual therapeutic agent or in combination with a therapeutic agent for another prostate disease, and can be administered simultaneously, separately, or sequentially with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects by taking all of the above factors into consideration, and this can be easily determined by those skilled in the art.

[0060] Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, weight, absorption rate of the active ingredient in the body, inactivation rate, excretion rate, type of disease, and concomitantly administered drugs, and may increase or decrease depending on the administration route, severity of the disease, sex, weight, age, etc., and for example, about 0.0001 ㎍ to 500 mg, for example, 0.01 ㎍ to 100 mg, may be administered per 1 kg of the patient's body weight per day. In addition, it may be administered in divided doses several times a day at regular intervals, for example, 2 to 3 times a day, depending on the judgment of a doctor or pharmacist.

[0061] The present invention provides a method for preventing or treating prostate disease, comprising administering the pharmaceutical composition to a subject.

[0062] The subject may be a human or a non-human animal, and may be free of prostate disease or may have prostate disease. If the subject is free of prostate disease, the prostate disease can be prevented by administering a pharmaceutically effective amount of the pharmaceutical composition to the subject, and if the subject is free of prostate disease, the prostate disease can be treated by administering a pharmaceutically effective amount of the pharmaceutical composition to the subject.

[0063] The formulation, administration method, dosage, and concentration of the active ingredient contained in the pharmaceutical composition are as described above.

[0064] Additionally, in the food composition, the food means a food that includes both edible raw materials and processed materials, and contains various digestible nutrients.

[0065] When the above food composition is used as a food additive, the food composition may be added as is or used together with other foods or food ingredients, and may be used appropriately according to a conventional method.

[0066] There are no special restrictions on the types of the above foods. Foods to which the above food composition can be added are not particularly limited, and include, for example, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea drinks, alcoholic beverages, vitamin complexes, and fermented foods, and include all health foods in the conventional sense.

[0067] In addition, the food composition can be manufactured into a food, particularly a functional food. The functional food includes ingredients commonly added during food manufacturing, such as proteins, carbohydrates, fats, nutrients, and seasonings. For example, when manufactured into a drink, it may include natural carbohydrates or flavoring agents as additional ingredients in addition to the active ingredient. The natural carbohydrates are preferably monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrin, cyclodextrin, etc.), or sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). The flavoring agent can be a natural flavoring agent (e.g., thaumatin, stevia extract, etc.) or a synthetic flavoring agent (e.g., saccharin, aspartame, etc.).

[0068] In the above health functional food composition, a health functional food is a food that uses raw materials or ingredients that have functionality useful to the human body, and refers to a food that has the functionality to maintain and improve health by maintaining the normal function of the human body or activating physiological functions. The health functional food of the present invention corresponds to a health functional food under the Health Functional Food Act. Since the hemp seed oil has the effect of reducing the weight of the prostate and reducing blood indicators of benign prostatic hyperplasia, the hemp seed oil can be included as an active ingredient in a health functional food as a functional raw material that has the function of preventing or improving prostate disease in humans or non-human animals.

[0069] The above health functional food composition can be manufactured in the form of tablets, granules, soft capsules, hard capsules, syrups, beverages, pills, soft extracts, and double boiling solutions. More specifically, the health food composition of the present invention can be manufactured in the form of tablets, granules, soft capsules, hard capsules, syrups, beverages, pills, soft extracts, dry extracts, and double boiling solutions. In addition, the health food composition of the present invention may further include, in addition to the ingredients described above in each formulation, ingredients that are typically added in the manufacture of health functional foods, such as excipients, 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, flavoring agents, coloring agents, preservatives, and the like. The ratio of the above-mentioned added ingredients is not particularly important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health functional food composition.

[0070] Meanwhile, another aspect of the present invention provides a method for improving, preventing or treating a prostate disease, comprising administering the hemp seed oil to a subject suffering from a prostate disease or having a high probability of developing the prostate disease.

[0071] Another aspect of the present invention also provides the use of hemp seed oil for improving, preventing, or treating prostate disease in a subject suffering from or at high risk of developing a prostate disease.

[0072] Hereinafter, the present invention will be described in detail by examples.

[0073] However, the following examples are only intended to illustrate the present invention, and the content of the present invention is not limited by the following manufacturing examples, examples, and experimental examples.

[0074] Example

[0075] Manufacturing Example 1. Manufacturing of hemp seed oil - cold pressing

[0076] Hemp seeds (Cannabis sativa seeds) harvested in 2022 (from Canada) were purchased and used. Dehulled hemp seeds (500 g) were preheated at 40–50°C for 5–10 minutes. The heated seeds were placed in an oil press (Requip Oil Press LOP-G3) and pressed once or twice at room temperature. After filtering using a 5 μm filter, 65 g of hemp seed oil was obtained.

[0077] Experimental Example 1. Confirmation of the effect of improving benign prostatic hyperplasia.

[0078] 1-1. Animal testing methods

[0079] In order to confirm the efficacy of cannabis seed oil in improving prostate hyperplasia in an animal model of benign prostatic hyperplasia, the method disclosed in the literature reported by Shin IS et al. (Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia, Food Chem Toxicol., 2012, 50, 884-888) was applied and the following experiment was conducted. Rats were castrated to eliminate the influence of endogenous testosterone, and testosterone propiponate (TP, T0028, TCI, JAPAN) was injected subcutaneously into the castrated rats for 8 weeks to induce benign prostatic hyperplasia. In addition to the administration of TP, cannabis seed oil and finasteride (a treatment for prostatic hyperplasia) were administered orally, respectively, and the effect of improving prostate hyperplasia was confirmed.

[0080] Specifically, 7-week-old male Sprague Dawley rats weighing 260-300 g were supplied by Joongang Laboratory Animal Co., Ltd. (Korea) and acclimatized for 7 days. They were allowed free access to food and water, and temperature (23 ± 2℃), humidity (55 ± 5%), and light / dark cycle (12 h) were automatically controlled. Castration was performed to exclude the influence of internal testosterone in the rats. After inhalation anesthesia, male SD rats were placed face down with their backs facing the surgeon, except for the normal group, and then the skin at the tip of the scrotum was incised, and the left and right testes and epididymis were resected. The incisions were then sutured to perform the surgery. After castration, the rats were stabilized for 10 days to allow the wounds at the surgical site to heal, and then TP was administered to the castrated rats to begin the experiment. Each group consisted of 8 rats with approximately the same body weight. Except for the normal group, the remaining experimental animals (negative control group, positive control group, and experimental group) were administered TP subcutaneously at 3 mg / kg / day for 8 weeks until the end of the experiment according to the change in body weight to induce prostatic hyperplasia. To minimize experimental error, the total injection volume was 100 μL dissolved in corn oil as a vehicle based on the weight measured every 7 days, and the normal group was injected with 100 μL of corn oil alone without TP.

[0081] The negative control group excludes the influence of endogenous testosterone and administers external testosterone. The positive control group excludes the influence of endogenous testosterone and administers external testosterone and finasteride (F1293, Sigma, USA), which has a therapeutic effect on benign prostatic hyperplasia. Finasteride was dissolved in corn oil as a vehicle at a concentration of 10 mg / kg / day and administered orally together with TP administration for 8 weeks. The experimental group excludes the influence of endogenous testosterone and administers external testosterone and the hemp seed oil of Preparation Example 1. Hemp seed oil was dissolved in corn oil as a vehicle at a dose of 100 mg / kg / day and administered for 8 weeks along with TP administration. After 8 weeks of administration, prostate weight was measured and blood prostate-specific antigen (PSA), dihydrotestosterone (DHT), and 5-alpha reductase I were analyzed.

[0082] 1-2. Measurement of prostate weight

[0083] The abdomen of the sacrificed rats was incised, the prostate was removed, washed once in PBS, lightly removed, and weighed. The results were calculated as the prostate ratio (prostate weight (mg) / body weight (100 g) × 100) and converted to 100% of the negative control group, and are shown in Figure 1 below.

[0084] From the above results, it can be confirmed that the negative control group that induced benign prostatic hyperplasia had a significantly increased prostate weight compared to the normal group, the positive control group had a 47% decrease in prostate weight to the level of the normal group, and the experimental group administered hemp seed oil had a decrease of approximately 26%.

[0085] 1-3. Prostate-specific antigen (PSA) measurement

[0086] The serum isolated from the sacrificed rats was diluted 200-fold and measured for prostate-specific antigen (PSA) using a PSA ELISA kit (Cusabio). The results are shown in Figure 2. After analysis, the values ​​measured at 450 nm were calculated based on a standard curve and plotted on a graph. The results were converted to 100% relative to the negative control group.

[0087] From the above results, it can be confirmed that in the negative control group in which prostate hypertrophy was induced, prostate-specific antigen (PSA) increased by 34% compared to the normal group, and when hemp seed oil and positive control substances were administered, it decreased by 58% and 50%, respectively.

[0088] Prostate-specific antigen (PSA) is a glycoprotein produced in small amounts by prostate cells and is used as a semi-quantitative indicator of prostate volume in benign prostatic hyperplasia or prostate cancer, and elevated blood PSA levels are commonly observed in patients with benign prostatic hyperplasia.

[0089] Although the exact mechanism between BPH and serum prostate-specific antigen (PSA) levels is unknown, PSA levels tend to increase with prostate size, and a correlation between PSA levels and prostate diseases, including BPH, has been consistently reported. Therefore, the decreased PSA levels caused by hemp seed oil intake are thought to be due to the reduction in enlarged prostate size, thereby alleviating BPH.

[0090] 1-4. Measurement of dihydrotestosterone (DHT)

[0091] To measure changes in blood DHT, the level of DHT was measured in the serum of sacrificed rats using an ELISA kit (Finetest, Wuhan, China), and the results were converted to 100% of the negative control group and shown in Figure 3.

[0092] From the above results, it can be confirmed that in the negative control group in which prostate enlargement was induced, DHT increased by 79% compared to the normal group, and when hemp seed oil and positive control substances were administered, it decreased by 36% and 39%, respectively.

[0093] 1-5. Measurement of 5-alpha reductase I

[0094] To measure changes in blood 5-alpha reductase I, the level of 5-alpha reductase I was measured in the serum of sacrificed rats using an ELISA kit (Cusabio, Wuhan, Hubei, China), and the results were converted to 100% of the negative control group and shown in Figure 4.

[0095] From the above results, it can be confirmed that in the negative control group in which prostate enlargement was induced, 5-alpha reductase I increased by 31% compared to the normal group, and when hemp seed oil and positive control substances were administered, it decreased by 31% and 32%, respectively.

[0096] Experimental Example 2. Confirmation of the Prostate Cancer Inhibitory Effect

[0097] To confirm the growth inhibitory effect of prostate cancer cells, cytotoxicity against human prostate cancer cell line (LNCap) was measured using WST-1 assay. LNcaP cells were cultured in RPMI 1640 (Gibco. Grand Island, USA) medium containing 10% FBS in a cell incubator at 37°C and 5% CO2.

[0098] Prepared LNcaP cells were seeded in 96-well plates at 2 × 10 4 The cells / well were divided into 10 cells / well and cultured for 24 hours, and then treated with 200 μg / ml of hemp seed oil from Manufacturing Example 1 and 1 μM of finasteride as a positive control for 72 hours. Afterwards, the culture medium was removed, and the cell growth inhibition ability was evaluated using a cell viability assay kit (EZ-Cytox, DOGENBIO, KOREA). The results were converted to 100% of the untreated group and are shown in Figure 5.

[0099] Manufacturing Example 2. Manufacturing of a pharmaceutical composition

[0100] 2-1. Manufacturing of Sanje

[0101] 2g of hemp seed oil of manufacturing example 1

[0102] 1g lactose

[0103] The above ingredients were mixed and filled into a sealed bag to prepare a powder.

[0104] 2-2. Manufacturing of tablets

[0105] 100 mg of hemp seed oil of manufacturing example 1

[0106] 100 mg of corn starch

[0107] 100 mg of lactose

[0108] Magnesium stearate 2 mg

[0109] After mixing the above ingredients, tablets were manufactured by pressing them according to a conventional tablet manufacturing method.

[0110] 2-3. Manufacturing of capsules

[0111] 100 mg of hemp seed oil of manufacturing example 1

[0112] 100 mg of corn starch

[0113] 100 mg of lactose

[0114] Magnesium stearate 2 mg

[0115] After mixing the above ingredients, the mixture was filled into a gelatin capsule according to a conventional capsule manufacturing method to produce a capsule.

[0116] 2-4. Manufacturing of rings

[0117] 1g of hemp seed oil of manufacturing example 1

[0118] 1.5g lactose

[0119] 1g of glycerin

[0120] 0.5g xylitol

[0121] After mixing the above ingredients, it was manufactured to have 4g per pill according to the usual method.

[0122] 2-5. Preparation of granules

[0123] 150 mg of hemp seed oil of manufacturing example 1

[0124] 50 mg of soybean extract

[0125] 200 mg of glucose

[0126] 600 mg of starch

[0127] After mixing the above ingredients, 100 mg of 30% ethanol was added, dried at 60°C to form granules, and then filled into a bag.

[0128] Manufacturing Example 3. Manufacturing of health functional food

[0129] 3-1. Manufacturing of wheat flour products

[0130] 0.5 to 5.0 parts by weight of hemp seed oil of Manufacturing Example 1 was added to wheat flour, and bread, cake, cookies, crackers, and noodles were manufactured using this mixture.

[0131] 3-2. Preparation of soups and gravies

[0132] 0.1 to 5.0 parts by weight of hemp seed oil of Manufacturing Example 1 was added to soup and broth to manufacture meat products, soup and broth for noodles.

[0133] 3-3. Production of ground beef

[0134] Ground beef was prepared by adding 10 parts by weight of hemp seed oil of Manufacturing Example 1 to ground beef.

[0135] 3-4. Manufacturing of dairy products

[0136] 5 to 10 parts by weight of hemp seed oil of Manufacturing Example 1 was added to milk, and various dairy products such as butter and ice cream were manufactured using the milk.

[0137] 3-5. Preparation of pre-prepared food

[0138] Brown rice, barley, glutinous rice, and Job's tears were alpha-processed and dried using a known method, and then distributed and then manufactured into a powder with a particle size of 60 mesh using a grinder.

[0139] Black beans, black sesame seeds, and perilla seeds were steamed and dried using a known method, and then distributed and ground into a powder with a particle size of 60 mesh using a grinder.

[0140] The hemp seed oil of Manufacturing Example 1 was concentrated under reduced pressure in a vacuum concentrator, dried using a spray dryer, and the resulting dried product was ground to a particle size of 60 mesh using a grinder to obtain a dry powder.

[0141] The grains, seeds, and hemp seed oil of Manufacturing Example 1 manufactured above were mixed in the following ratios to manufacture the product.

[0142] Grains (30 parts by weight of brown rice, 15 parts by weight of Job's tears, 20 parts by weight of barley), seeds (7 parts by weight of perilla seeds, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds), hemp seed oil of Manufacturing Example 1 (3 parts by weight), lingzhi (0.5 parts by weight), rehmannia glutinosa (0.5 parts by weight)

[0143] 3-6. Manufacturing of health functional beverages

[0144] 5g of hemp seed oil of Manufacturing Example 1 was homogeneously mixed with auxiliary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), and water (75%), and then instantaneously sterilized and packaged in small containers such as glass bottles and PET bottles.

[0145] 3-7. Preparation of vegetable juice

[0146] Vegetable juice was prepared by adding 5 g of hemp seed oil of Manufacturing Example 1 to 1,000 ml of tomato or carrot juice.

[0147] 3-8. Production of fruit juice

[0148] Fruit juice was prepared by adding 1 g of hemp seed oil of Manufacturing Example 1 to 1,000 ml of apple or grape juice.

Claims

1. A composition for improving, preventing or treating prostate disease, comprising hemp seed oil as an active ingredient.

2. In claim 1, The above hemp seed oil: 1) A step of removing the outer seed coat from hemp seeds using a peeler; 2) A step of drying at a temperature of 50℃ or lower to a moisture content of 5.0% or lower; and 3) A composition manufactured by a manufacturing method including a step of manufacturing milking oil in a cold-pressed milking machine at a temperature of 40°C or lower.

3. In claim 2, The above manufacturing method is, before step 1), A step of washing hemp seeds with water; and A composition further comprising a step of drying hemp seeds at a temperature of 50°C or lower to a moisture content of 9% or lower.

4. In claim 2, The above manufacturing method further comprises a step of 4) obtaining a supernatant by settling the milk oil at 5°C or lower for 1 to 3 weeks.

5. In claim 1, A composition wherein the above prostate disease is selected from the group consisting of benign prostatic hyperplasia, prostatitis, prostate cancer, prostatic abscess, and prostatic calcification.

6. In claim 5, The above prostate disease is benign prostatic hyperplasia, and the hemp seed oil is a composition that reduces the weight of the prostate in a patient with benign prostatic hyperplasia, or reduces blood prostate-specific antigen (PSA), dihydrotestosterone (DHT), or 5-alpha reductase I.

7. In claim 5, The above prostate disease is prostate cancer, and the composition wherein the hemp seed oil inhibits the growth of prostate cancer cells.

8. In any one of claims 1 to 7, The composition above is a cosmetic composition, a health food composition, or a pharmaceutical composition.

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