WO2015111832A1 - Composition de prévention ou de traitement de maladies liées à la prostate, contenant un extrait de poncirus trifoliata - Google Patents
Composition de prévention ou de traitement de maladies liées à la prostate, contenant un extrait de poncirus trifoliata Download PDFInfo
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- WO2015111832A1 WO2015111832A1 PCT/KR2014/011097 KR2014011097W WO2015111832A1 WO 2015111832 A1 WO2015111832 A1 WO 2015111832A1 KR 2014011097 W KR2014011097 W KR 2014011097W WO 2015111832 A1 WO2015111832 A1 WO 2015111832A1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
Definitions
- the present invention provides a pharmaceutical composition for the prevention or treatment of prostate-related diseases comprising the fruit juice extract or fractions thereof as an active ingredient, a method for preventing or treating prostate-related diseases using the composition, a prostate-related disease comprising the fruit juice extract or fractions thereof. It relates to a food composition, a feed composition, and a quasi-drug composition for prevention or improvement.
- the prostate gland is composed of glands and fibromuscular tissues, and the male gonads may have water bumps or stones, but prostatitis, prostatic hyperplasia, and prostate cancer are the most common diseases.
- Prostate-related diseases in Koreans are characterized by more prostatitis than Westerners, the incidence of prostate cancer is very low, and the prostate hypertrophy is gradually increasing due to an increase in the elderly population.
- Urinary tract disease in patients 50 years and older is most common in the order of enlarged prostate, prostate cancer, and prostatitis.
- prostatic hyperplasia is associated with bladder storage and delayed urination (such as urinary urgency, urinary urge to urinate more than eight times a day, night urination, and strong and sudden urinary in men over 50 years of age. It is the name of testosterone that is a male hormone by 5 alpha-reductase, such as urine coming out by moxibustion), severed urine (breaking up of urine), and urination during urination. Dihydrotestosterone (DHT), which is converted from (testosterone, T), is known to be involved in prostatic hypertrophy (Urology. 2003 Apr; 61 (4 Suppl 1): 2-7.).
- DHT dihydrotestosterone
- the number of prostate hyperplasia patients in Korea has increased sharply from 45,897 people in 2006 to 84,2069 in 2011, which is 83.5%.
- the number of patients with prostatic hyperplasia is 2 to 5 males 60 years old or older, and over 80 years old, more than half complain of enlarged prostate symptoms.
- the number of patients with prostatic hyperplasia is expected to increase in the future due to the rush into the aging society and the improvement of the rate of receipt. Therefore, the demand for the prevention and treatment of prostatic hyperplasia is expected to increase continuously.
- Prostatitis is also a disease that accounts for about 3-12% of all urological patients, but is most common in urological patients under 50 years of age.
- chronic pelvic pain the most prominent symptom of prostatitis
- DHT dihydrotestosterone
- T male hormone testosterone
- Prostate cancer is a malignant tumor that occurs in the prostate, and prostate cancer is also known to be highly related to the conversion of testosterone to dihydrotestosterone by 5 alpha-reductase (J Steroid Biochem Mol Biol. 2002 Nov; 82 (4-5): 393-400.).
- prostate cancer is the most common cancer among men and has a high incidence.
- gastric prostate cancer is difficult to detect early because there is no specific symptom.
- hospitals are visited only after the growth of cancer tissues causes urination, or prostate cancer has spread to other organs such as bones and symptoms such as bone pain. . Therefore, there is a growing demand for prophylactic and therapeutic agents for prostate cancer.
- One object of the present invention to provide a pharmaceutical composition for the prevention or treatment of prostate-related diseases, including as an active ingredient Ponciri Fructus extract or fractions thereof.
- the present invention provides a pharmaceutical composition for the prevention or treatment of prostate-related diseases comprising a fruit extract or a fraction thereof as an active ingredient.
- the term "pile” refers to the unripe fruit of the Pancirus trifoliata Rafinesque, a deciduous broad-leaved ornamental belonging to the Rutaceae family. It is a round shape with a diameter of 3 cm.
- the flowering period of the tanza trees is from May to May, the fruiting season is from September to November, and the harvest time is from September to October. It is known to grow wild on islands such as Jeju Island and Gadeok Island in the south of Korea, and it is cultivated in Gyeongju and South-South of Korea. Ripe fruits are called crust, and crust and crust have different effects and are used for other purposes.
- Jisil is known to exhibit anti-inflammatory effects, efficacy on gastritis and gastric ulcers, effects on metabolic osteoporosis diseases, and anti-cancer activity, but is not known for the treatment of prostate-related diseases.
- the fruit can be purchased commercially, or can be used collected or cultivated in nature.
- extract means the extract of the fruit.
- the extract is a low alcohol having 1 (C1) to 4 (C4) carbon atoms, such as water, methanol, ethanol, etc., in volumes of about 5 to 30 times the dry weight, preferably about 10 to 20 times the dry weight.
- the extraction temperature is 20 °C to 100 °C, preferably 60 °C to 100 °C, extraction period is about
- the extraction temperature is 20 °C to 100 °C, preferably 60 °C to 100 °C
- extraction period is about
- the extract may be an extract extracted by using an extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction, filtration extraction, or ultrasonic extraction for 1 hour to 4 days, but the extract may exhibit a prophylactic or therapeutic effect of a prostate related disease of the present invention.
- the present invention is not limited thereto, and may include any extract, a diluent or concentrate of the extract, a dried product obtained by drying the extract, or all of these modifiers or purified products.
- the extract may be included in an amount of 0.01 to 100% by weight, more preferably 1 to 80% by weight, based on the total weight of the pharmaceutical composition, respectively.
- fraction refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several different components.
- the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. Solvent fractionation by treatment of various solvents, ultrafiltration fractionation through passage of ultrafiltration membranes with constant molecular weight cut-off values, and various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) Chromatography), and combinations thereof.
- Solvent fractionation by treatment of various solvents ultrafiltration fractionation through passage of ultrafiltration membranes with constant molecular weight cut-off values, and various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity) Chromatography), and combinations thereof.
- solvent fractionation by treatment of various solvents was used to obtain a fraction from the extract by treating a predetermined solvent to the extract obtained by extracting the fruit.
- the kind of solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used.
- Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols; And nonpolar solvents such as hexane, ethyl acetate, chloroform, dichloromethane, and the like. These may be used alone or in combination of two or more thereof. In the case of using alcohol in the fractionation solvent, alcohols of C1 to C4 may be preferably used.
- the fraction may be prepared by fractionating the fruit extract with a solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, hexane (hexane), ethyl acetate, and a mixed solvent thereof.
- the fraction may be prepared by fractionating the fruit extract with water, hexane, ethyl acetate, or butanol.
- the present inventors confirmed that the ethyl acetate extract of the fruit-derived extract significantly inhibits the activity of 5 alpha-reductase in a concentration-dependent manner, and thus has an excellent therapeutic effect in prostate-related diseases (FIGS. 5 and 6).
- the fractions may each comprise 0.01 to 100% by weight, more preferably 1 to 80% by weight relative to the total weight of the pharmaceutical composition.
- the composition comprising the fruit juice extract of the present invention can be used for the prevention or treatment of prostate-related diseases by using the activity of reducing the 5 alpha-reductase.
- the term "5 alpha reductase” refers to an enzyme that converts testosterone, a type of male hormone, to dihydrotestosterone (DHT), and the enzymes include type 1 and type 2.
- DHT dihydrotestosterone
- 5 alpha-reductase inhibitors are known to treat prostate-related diseases such as enlarged prostate, which is known to prevent the growth of the prostate.
- the present inventors confirmed that the fruit juice extract has an effect of significantly reducing the activity of 5 alpha-reductase, which is highly related to the induction of prostate-related diseases such as prostatitis, prostatic hyperplasia, and prostate cancer (Experimental Example 1 and FIG. 1).
- the fibrin extract inhibits the increase in prostate weight and significantly inhibits the increase in DHT (dihydro testosterone) levels essential for the development, growth and maintenance of the prostate gland.
- DHT dihydro testosterone
- prostate-related disease means a disease occurring in the prostate gland, which is a reproductive and urinary organ of a male, and for example, one selected from the group consisting of prostatic hyperplasia, prostatitis, prostate cancer, prostate abscess, and prostate calcification
- the above diseases may be included, but are not limited thereto and may include all of various diseases caused by prostate problems.
- Prostate abscess is a disease in which bacteria penetrate into the prostate through the urethra and rapidly form necrotic pouches following acute inflammation, creating necrotic pouches. When a disease develops, a sudden high fever and chills appear. You can't have urinary tract symptoms and you'll feel extreme urination.
- Prostate calcification is a disease caused by the sinking of lime stones in the prostate. The absence means that too much constituent in the body fluids, including urine is not liquefied all means that the remaining calcium, oxalate, phosphate crystallized.
- prevention may refer to any action that inhibits or delays the development of a prostate-related disease by administering to a subject a pharmaceutical composition for preventing or treating a prostate-related disease according to the present invention.
- treatment may mean any action that improves or benefits the symptoms of a prostate-related disease by administering the composition of the present invention to a subject suspected of developing a prostate-related disease.
- the term “improvement” may mean any action that at least reduces the parameters associated with the condition being treated, for example, the extent of symptoms.
- the pharmaceutical composition for preventing or treating prostate-related diseases according to the present invention may further include a pharmaceutically acceptable carrier, and may be formulated together with the carrier to provide food, medicine, feed additives, and drinking water additives.
- a pharmaceutically acceptable carrier may refer to a carrier or diluent that does not interfere with the biological activity and properties of the compound to be administered without stimulating the organism.
- the kind of the carrier usable in the present invention is not particularly limited, and any carrier can be used as long as it is a conventionally used and pharmaceutically acceptable carrier in the art.
- Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in combination of two or more thereof.
- ком ⁇ онентs such as antioxidants, buffers and / or bacteriostatic agents may be added and used, and diluents, dispersants, surfactants, binders, lubricants, and the like may be additionally added to provide a solution such as an aqueous solution, a suspension, an emulsion or the like. It may be formulated into a use formulation, pills, capsules, granules or tablets.
- the mode of administration of the pharmaceutical composition for preventing or treating prostate-related diseases according to the present invention is not particularly limited, and may be in accordance with methods commonly used in the art.
- the composition may be administered by oral or parenteral administration.
- the pharmaceutical composition for preventing, ameliorating or treating the prostate-related disease of the present invention may be prepared in various formulations according to the desired administration method.
- the pharmaceutical composition of the present invention may also be used as a single agent, and may be prepared and used in a combination formulation, further including a drug known to have a recognized prostate-related disease treatment effect, and formulated using a pharmaceutically acceptable carrier or excipient. It may be prepared in unit dose form or incorporated into a multi-dose container.
- the present invention provides a method for preventing or treating a prostate-related disease comprising administering to the individual a pharmaceutical composition for preventing or treating the prostate-related disease.
- a pharmaceutical composition for preventing or treating the prostate-related disease may mean any animal, including humans, who have or are likely to develop a prostate-related disease.
- the method of preventing or treating the present invention may specifically include administering the composition in a pharmaceutically effective amount to a subject having or at risk of developing a prostate-related disease.
- the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, generally in an amount of 0.001 to 1000 mg / kg, preferably 0.05 The amount of to 200 mg / kg, more preferably 0.1 to 100 mg / kg may be administered once to several times daily. However, for the purposes of the present invention, a suitable total daily usage of the composition comprising the extract may be determined by the practitioner within the correct medical judgment and may be administered once or in divided doses.
- the specific therapeutically effective amount for a particular patient is determined by the specific composition, including the type and extent of the reaction to be achieved, whether or not other agents are used in some cases, the age, weight, general health of the patient, It is desirable to apply differently depending on various factors and similar factors well known in the medical field, including sex and diet, time of administration, route of administration and rate of composition, duration of treatment, drugs used with or co-specific with the specific composition.
- compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. In consideration of all the above factors, it is important to administer an amount that can achieve the maximum effect in a minimum amount without causing side effects, and can be easily determined by those skilled in the art.
- the term "administration" refers to introducing the pharmaceutical composition of the present invention to a patient in any suitable manner, the route of administration of the composition of the present invention being oral or parenteral as long as it can reach the target tissue. Administration can be via a variety of routes.
- the mode of administration of the pharmaceutical composition according to the present invention is not particularly limited, and may be in accordance with methods commonly used in the art.
- the composition may be administered by oral or parenteral administration.
- the pharmaceutical compositions according to the invention may be prepared in various formulations depending on the desired mode of administration.
- the frequency of administration of the composition of the present invention is not particularly limited, but may be administered once a day or several times in divided doses.
- the present invention provides a food composition for preventing or ameliorating prostate related diseases.
- the fruit Since the fruit has been used for a long time as a natural material and has been proved to be safe, it can be prepared and consumed in the form of a food that can prevent or improve prostate-related diseases.
- the kind of the food is not particularly limited, and may include all foods in a general sense.
- foods to which the substance may be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, various soups, drinks, tea , A drink, an alcoholic beverage, and a vitamin complex.
- the composition may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
- the food composition may comprise a food acceptable carrier.
- the food composition may be a health functional food.
- Functional food is the same term as food for special health use (FOSHU), and means foods that have high medical effects and medical effects that are processed so that their bioregulatory functions are efficiently displayed in addition to nutrition.
- the food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects in preventing or improving prostate related diseases.
- the content of the extract included in the food is not particularly limited, but may be included in 0.01 to 100% by weight, more preferably 1 to 80% by weight relative to the total weight of the food composition.
- the food when it is a beverage, it may be included in a ratio of 1 to 30 g, preferably 3 to 20 g based on 100 ml.
- the health functional food can be prepared by a method commonly used in the art, and the preparation can be prepared by adding the raw materials and ingredients commonly added in the art.
- the preparation can be prepared by adding the raw materials and ingredients commonly added in the art.
- unlike the general medicine has the advantage that there is no side effect that can occur when taking a long-term use of the drug with food as a raw material, can be excellent in portability.
- the present invention provides a feed composition for the prevention or amelioration of prostate-related diseases.
- the feed composition may include a feed additive.
- the feed additive of the present invention corresponds to a feed supplement in the Feed Control Act.
- feed may refer to any natural or artificial diet, one meal, or the like, or a component of the one meal, for the animal to eat, ingest, and digest.
- the kind of the feed is not particularly limited, and may be used a feed commonly used in the art.
- Non-limiting examples of the feed include, but are not limited to, vegetable feeds such as cereals, fruits, food processing by-products, algae, fibres, pharmaceutical by-products, oils, starches, gourds or grain by-products; And animal feeds such as proteins, minerals, fats and oils, minerals, fats and oils, single cell proteins, zooplankton or foods. These may be used alone or in combination of two or more thereof.
- the present invention provides a quasi-drug composition for preventing or ameliorating prostate-related diseases.
- the composition of the present invention can be added to the quasi-drug composition for the purpose of preventing or treating prostate related diseases.
- the term "quasi drug” refers to a fiber, rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or animal, has a weak action on the human body or does not directly act on the human body, Or non-machinery and the like, or any of the agents used for sterilization, insecticide and similar purposes for the purpose of preventing infection, for the purpose of diagnosing, treating, reducing, treating or preventing human or animal diseases. It may mean an article other than an apparatus, machine or apparatus, and an article which is not an apparatus, machine or apparatus, which is used for the purpose of pharmacologically affecting the structure and function of a human or animal.
- the quasi-drug may include external skin preparations and personal hygiene products.
- it may be, but is not limited to, a disinfectant cleaner, a shower foam, a gagreen, a wet tissue, a detergent soap, a hand wash, or an ointment.
- the composition according to the present invention when used as an quasi-drug additive, the composition may be added as it is, or used together with other quasi-drugs or quasi-drug components, and may be appropriately used according to a conventional method.
- the mixing amount of the active ingredient may be appropriately determined depending on the intended use.
- the present invention provides a drinking water additive for preventing or ameliorating prostate-related diseases including the fibrin extract.
- the drinking water additive of the present invention may be prepared by separately preparing the composition containing the fruit extract in the form of drinking water additives and mixing the drinking water, or may be used by adding directly in the preparation of drinking water.
- the drinking water additive of the present invention may be in a liquid or dry state, preferably in the form of a dry powder.
- the drying method for preparing the drinking water additive of the present invention in the form of a dried powder is not particularly limited, and a method commonly used in the art may be used.
- the drinking water additive of the present invention may further include other additives as necessary.
- Non-limiting examples of the additives that can be used include binders, emulsifiers, preservatives, etc., added to prevent deterioration of drinking water quality; Amino acids, vitamins, enzymes, probiotics, flavors, nonprotein nitrogen compounds, silicates, buffers, colorants, extractants, or oligosaccharides are added to increase the usefulness of feed or drinking water. It can be included as. These may be used alone or two or more kinds may be added together.
- Composition comprising the fruit extract of the present invention as an active ingredient inhibits the activity of the 5 alpha-reductase, there is an effect that can effectively prevent, improve, and treat prostate-related diseases such as enlarged prostate, prostatitis, prostate cancer.
- composition comprising the fruit extract of the present invention as an active ingredient may be applied to various products including a food composition, a composition for animal feed, a cosmetic composition, and a quasi-drug composition for the prevention or improvement of prostate-related diseases as a natural drug.
- composition of the present invention is derived from natural products and can be used safely without causing serious irritation or harmful effects in the body in addition to preventing, treating, and improving efficacy of prostate-related diseases.
- Figure 1 shows the inhibitory effect of the activity of 5 alpha-reductase according to the concentration of the fruit extract.
- Figure 2 shows the measurement of the prostate gland according to the fruit extract extract in the enlarged prostate animal model.
- Figure 3 shows the measurement of the change in DHT (dihydro testosterone) according to the fruit extract extract in the prostatic hypertrophy-derived animal model.
- Figure 4 shows the histopathological changes of the prostate gland according to the fruit extract in the prostatic hypertrophy-derived animal model.
- NC shown in the figure is a normal group
- BPH is a prostatic hyperplasia-induced group
- Fin is a prostatic hyperplasia-induced group + finasteride administration group
- GO-10 is a prostatic hypertrophy-induced group + fibrotic extract administration group.
- Figure 5 shows the inhibitory effect of the activity of 5 alpha-reductase according to the concentration of the fraction of the fruit extract.
- Figure 6 shows the measured prostate weight according to the treatment of the fraction of the fruiting extract in the prostatic hypertrophy-derived animal model (NC: normal group, BPH: prostatic hypertrophy induced group, Fin: prostatic hypertrophy induced group + finasteride administration group, Hexane: Prostatic hyperplasia + fibroblast hexane fraction, EA: prostatic hyperplasia + fibrosyl ethyl acetate fraction, BuOH: prostatic hyperplasia + fission butanol fraction, Water: prostatic hyperplasia + hypoglycemic fraction).
- NC normal group
- BPH prostatic hypertrophy induced group
- Fin prostatic hypertrophy induced group + finasteride administration group
- Hexane Prostatic hyperplasia + fibroblast hexane fraction
- EA prostatic hyperplasia + fibrosyl ethyl acetate fraction
- BuOH prostatic hyperplasia + fission butanol fraction
- Water prostatic
- Example 3 Preparation of Fractions of Fruits Extract (Used in Experimental Examples 3 and 4)
- 5-alpha-reductase converts testosterone to dihydro testosterone, and the inhibition of 5-alpha-reductase activity is pointed to cause prostate-related diseases.
- the activity inhibitory effect of 5 alpha reductase was determined.
- 12-week-old female SD rats (Central experimental animals, Korea) were anesthetized with dieth ether, and then dissected to extract the liver.
- Four-fold buffer solution (10 mM Tris-HCl, pH 7.0), 50 mM EDTA, 5 mM MgCl 2, 50 mM NaCl, 132 mM Sucrose, 0.004% 2-mercaptoethanol) were added and homogenized with a cell disruptor.
- the supernatant obtained by centrifugation (10,000xg) of the hepatocyte crushing solution was again ultracentrifuged (105,000xg) to obtain a microsomal fraction, which was suspended in the buffer solution and stored at -80 ° C.
- the absorbance change was measured three times for each of the following five groups having different concentrations of fruit fruit extract.
- Group 2 a composition comprising 50 ⁇ g of testosterone (T0028, TCI, Japan) added to group 1
- Group 4 a composition in which 70 ⁇ g / ml of the fruiting extract of Example 1 was reacted with group 2
- Group 5 a composition in which Group 2 was reacted with 80 ⁇ g / ml of the fruiting extract of Example 1
- Table 2 shows that for Group 1 and Group 2 without adding the fruit extract, the activity of Group 1 without testosterone, which is a substrate of 5 alpha-reductase based on the activity values of Table 1, was 0%, and 5 alpha-reductase.
- the activity of group 2 containing testosterone, which is a substrate, is converted to 100%. Therefore, in the absence of any inhibitor, the enzyme activity may be compared with the addition of the fruit extract based on 100% of the activity value of the 5 alpha-reductase activity against the testosterone as a substrate.
- the fruit extract in the present invention is an inhibitor of 5-alpha-reductase, which converts testosterone (T) into dihydro testosterone (DHT) and has an effect of inhibiting 5-alpha-reductase, an important enzyme involved in prostate-related diseases. Appeared.
- the concentration of the fruit extract increased, the activity (%) of 5 alpha-reductase decreased rapidly, significantly inhibiting the action of 5-alpha-reductase.
- the fruit extract in the present invention was confirmed to have an excellent activity inhibitory effect of 5 alpha-reductase at a concentration of 0.1 ⁇ g / ml or more and 90 ⁇ g / ml or less.
- Finasteride is an inhibitor of type 2 alpha-reductase, which is now widely used in the art.
- the IC50 of the fruit extract in the present invention was 73.92 ⁇ 0.63 ( ⁇ g / ml)
- the IC50 of finasteride, an inhibitor of 5-alpha-reductase widely used in the art is 0.60 ⁇ 0.12 ( ⁇ M). This can be seen that the 5 alpha-reductase activity inhibitory effect is excellent considering that the fruit extract is a natural extract.
- TP testosterone propionate
- Example 2 One hour before the injection of TP, the fruit extract of Example 2 was orally administered at 200 mg / kg for 4 weeks to prepare an experimental group.
- a positive control group was prepared by orally administering 10 mg / kg of finasteride, a 5 ⁇ -reductase inhibitor used as a prostatic hypertrophy agent.
- corn oil was injected subcutaneously.
- the prostate weight of the prostatic hypertrophy-inducing group (BPH) was more than doubled as compared to the normal group (NC), but the prostate weight was increased in the group (GO-10) to which the fibroblasts were administered. Significant inhibition was confirmed.
- the inhibitory effect appeared very similar to Finasteride (Fin), which is currently used as a therapeutic agent, suggesting that the effect of the fruiting extract is very good.
- Extraction buffer 50 mM Tris pH 8.0, 150 mM NaCl, 0.02% sodium azide, 0.2% SDS, 1 mM PMFS, 10 ⁇ l / ml aprotinin, 1% Igapel 630 (Sigma Chem. Co.
- Protein concentration of the isolated supernatant was measured using a Bio-Rad protein assay kit (Bio-Rad, USA). In order to measure the content of DHT in the supernatant, an ELISA kit (Dakara, Japan) that specifically reacts with DHT was used, and the content of each DHT was measured according to the manufacturer's method. The measured value was converted into relative units of protein quantitative value. Statistical analysis was performed by ANOVA. * P ⁇ 0.05, ** P ⁇ 0.01 is significant difference compared to normal group (NC), # P ⁇ 0.05, ## P ⁇ 0.01 is the trigger group (BPH ) And significant differences were considered.
- the DHT level of the prostatic hypertrophy-inducing group (BPH) was significantly increased compared to the normal group (NC), but the DHT level was increased in the group (GO-10) to which the fibroblasts were administered. Significant inhibition was confirmed.
- the inhibitory effect appeared very similar to Finasteride (Fin), which is currently used as a therapeutic agent, suggesting that the effect of the fruiting extract is very good.
- paraffin embedding was performed after fixation of the ventral prostate tissue with 10% neutral buffer-formalin for 24 hours in the group treated with the glandular extract (GO-10). .
- Embedding tissue was cut to 4 ⁇ m thickness to make sections and stained with hematoxylin and Eosin Y (ThermoShandon, USA). Immediately afterwards, the sections were encapsulated with the encapsulating solution, and the slides after the dyeing and encapsulation were examined under an optical microscope.
- Group 2 a composition comprising 50 ⁇ g of testosterone (T0028, TCI, Japan) added to group 1
- Group 4 a composition in which group 2 was reacted with GO10-EA, GO10-B, and GO10-W at a concentration of 100 ⁇ g / mL
- Group 5 a composition in which group 2 was reacted with GO10-EA, GO10-B, and GO10-W at a concentration of 200 ⁇ g / mL
- TP testosterone propionate
- Example 3 One hour before TP injection, each of the four fractions prepared in Example 3 was orally administered at 100 mg / kg for 4 weeks to prepare an experimental group.
- a positive control group was prepared by orally administering 10 mg / kg of finasteride, a 5 ⁇ -reductase inhibitor used as a prostatic hypertrophy agent.
- corn oil was injected subcutaneously.
- NC normal group
- BPH prostatic hyperplasia group
- Fin prostatic hyperplasia group + finasteride administration group
- Hexane prostatic hyperplasia group + fission hexane fraction
- EA prostate hypertrophy group + hypochlorous ethyl Acetate fraction
- BuOH prostatic hypertrophy-induced group + fission butanol fraction
- Water prostate hypertrophy-induced group + fat chamber water fraction (Example 3-4) administration group.
- the prostate weight of the prostatic hypertrophy-inducing group (BPH) increased more than two times, in the case of the fraction of the fibrin extract significantly inhibited the increase in the prostate weight Confirmed.
- the effects of butanol fraction (BuOH) and water fraction (Water) was excellent.
- the inhibitory effect was found to be very similar to Finasteride (Fin), which is currently used as a therapeutic agent, suggesting that the effect of the fraction of the fruiting extract is very good.
- the fruiting extract and its fractions not only significantly reduce the activity of 5-alpha-reductase, which is highly associated with the induction of prostate-related diseases such as prostatitis, prostatic hyperplasia, and prostate cancer, but also prostatic hypertrophy animal model induced by TP.
- Fruit extracts also inhibited the increase of prostate weight, significantly inhibited the increase of DHT (dihydrotestosterone) level, which is essential for the development, growth and maintenance of the prostate, and significantly inhibited the proliferation of prostate epithelial cells. In particular, it was confirmed that this effect is equivalent to finasteride that is currently used as a treatment for prostate-related diseases.
- fruit juice extract or fractions thereof can be effectively used for the prevention, treatment, and improvement of prostate-related diseases.
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Abstract
La présente invention concerne une composition pharmaceutique pour la prévention ou le traitement de maladies liées à la prostate, contenant un extrait de Poncirus trifoliata ou une fraction de celui-ci en tant qu'ingrédient actif ; un procédé de prévention ou de traitement de maladies liées à la prostate en utilisant la composition ; et une composition alimentaire, une composition fourragère et une composition de quasi-médicament pour la prévention ou le soulagement de maladies liées à la prostate, contenant un extrait de Poncirus trifoliata.
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EP3912632A4 (fr) * | 2019-01-16 | 2022-11-23 | Industry-Academic Cooperation Foundation Gyeongsang National University | Nouvelle utilisation de sida rhombifolia |
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CN106668296A (zh) * | 2017-02-15 | 2017-05-17 | 四川双鑫生物科技有限公司 | 一种治疗前列腺疾病的丸剂药物及其制备方法 |
KR101994618B1 (ko) | 2017-07-18 | 2019-07-02 | 코스맥스 주식회사 | 발효 지실의 추출물을 포함하는 피부 진정용 조성물 |
KR102380248B1 (ko) * | 2019-07-03 | 2022-03-29 | 경희대학교 산학협력단 | 육계 및 금앵자 추출물을 포함하는 전립선비대증 예방 또는 치료용 약학 조성물 |
KR20210131036A (ko) | 2020-04-23 | 2021-11-02 | 한국생명공학연구원 | 지각 추출물을 유효성분으로 포함하는 남성 난임증 예방 또는 치료용 조성물 |
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KR20010100548A (ko) * | 2000-05-03 | 2001-11-14 | 서유헌 | 지실로부터 유효성분의 추출·정제방법 및 그 추출물을함유한 치매치료용 생약 조성물 |
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