WO2020261538A1 - Composition for lowering blood pressure - Google Patents

Composition for lowering blood pressure Download PDF

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Publication number
WO2020261538A1
WO2020261538A1 PCT/JP2019/025839 JP2019025839W WO2020261538A1 WO 2020261538 A1 WO2020261538 A1 WO 2020261538A1 JP 2019025839 W JP2019025839 W JP 2019025839W WO 2020261538 A1 WO2020261538 A1 WO 2020261538A1
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Prior art keywords
blood pressure
composition
lowering blood
turmericol
present
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PCT/JP2019/025839
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French (fr)
Japanese (ja)
Inventor
隆正 内尾
室山　幸太郎
健吾 川▲崎▼
室▲崎▼　伸二
Original Assignee
ハウスウェルネスフーズ株式会社
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Application filed by ハウスウェルネスフーズ株式会社 filed Critical ハウスウェルネスフーズ株式会社
Priority to PCT/JP2019/025839 priority Critical patent/WO2020261538A1/en
Priority to JP2021527279A priority patent/JP7452776B2/en
Publication of WO2020261538A1 publication Critical patent/WO2020261538A1/en

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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a composition for lowering blood pressure.
  • Hypertension is an important risk factor for cerebrovascular diseases such as cerebrovascular disorders and coronary artery diseases, as well as organ disorders such as heart failure and chronic kidney disease, and hypertension in middle age also increases the risk of vascular dementia in old age.
  • systolic blood pressure of less than 120 mmHg
  • the risk of morbidity and mortality such as cerebrocardiovascular, stroke, myocardial infarction, and chronic kidney disease increases ( Non-Patent Document 1). Therefore, lowering the blood pressure of hypertensive persons is important in the prevention of various cardiovascular diseases.
  • turmeric is known to contain a large number of bioactive substances.
  • Patent Document 1 discloses that blood pressure decreased in humans who ingested an herbal composition containing a combination of a turmeric extract having a curcumin concentration of 95% and an extract of another plant.
  • Patent Document 2 discloses that intraperitoneal administration of a fat-soluble extract of turmeric (turmeric oil) containing turmeric and the like to hypertensive rats reduced blood pressure, and Patent Document 2 uses the turmeric oil. It has been disclosed that treatment of rat-derived aorta suppressed norepinephrine-induced vascular constriction.
  • turmeric turmeric oil
  • Patent Document 3 the ethanol extract of turmeric, along with other plant extracts, is described as a component having an action of treating or preventing hypertension.
  • Patent Document 3 does not describe the experimental results supporting that the ethanol extract of turmeric actually has a blood pressure lowering effect.
  • Patent Document 4 describes that a composition containing a spring turmeric precursor is effective in treating hypertension.
  • Non-Patent Document 2 describes that the ethyl acetate extract of turmeric inhibited the activity of angiotensin II converting enzyme, suggesting that it is effective in treating hypertension.
  • Non-Patent Document 3 discloses that when a methanol extract of turmeric was administered to normotensive rats, the blood pressure decreased in a dose-dependent manner.
  • An object of the present invention is to provide a composition effective for lowering blood pressure.
  • the present inventors have found that blood pressure was significantly reduced in humans who ingested tablets containing turmeric extract containing turmericol A, turmericol B and bisacurone every day for 12 weeks, and completed the following invention. ..
  • a composition for lowering blood pressure which contains at least one of Termeronol A, Termeronol B and Bisacurone as an active ingredient.
  • a composition for lowering blood pressure which contains at least one of turmericol A, turmericol B and bisaclone, and contains a turmeric extract of water or a mixed solvent of water and a hydrophilic organic solvent as an active ingredient.
  • the composition for lowering blood pressure according to any one of (1) to (3) which contains 20 ⁇ g or more of turmeronol A and turmeronol B in total per daily intake.
  • the composition for lowering blood pressure according to any one of (1) to (4) which contains 17 ⁇ g or more of turmeronol A per daily intake.
  • composition for lowering blood pressure according to any one of (1) to (6) which contains 80 ⁇ g or more of bisacron per daily intake.
  • a turmeric extract containing water or a mixed solvent of water and a hydrophilic organic solvent containing at least one of turmericol A, turmericol B and bisaclone, or at least one of turmericol A, turmericol B and bisaclone Use for the manufacture of drugs for lowering blood pressure.
  • the composition or medicine for lowering blood pressure preferably contains 20 ⁇ g or more of turmeronol A and turmeronol B in total per daily intake.
  • the blood pressure lowering composition or medicine preferably contains 17 ⁇ g or more of turmeronol A per daily intake.
  • the blood pressure lowering composition or medicine preferably contains 5 ⁇ g or more of Termeronol B per daily intake.
  • the blood pressure lowering composition or medicine preferably contains 80 ⁇ g or more of bisacron per daily intake.
  • the content of curcumin per daily intake is preferably less than 30 mg.
  • a method of lowering blood pressure which comprises administering to a subject in need of lowering blood pressure and lowering blood pressure in the subject.
  • a method for treating or preventing hypertension which comprises administering to a subject in need of treatment or prevention of hypertension, and treating or preventing hypertension in the subject.
  • (13) Water containing at least one of turmericol A, turmericol B and bisacurone, or at least one of turmericol A, turmericol B and bisacurone for lowering blood pressure in a subject in need of lowering blood pressure.
  • a turmeric extract using a mixed solvent of water and a hydrophilic organic solvent.
  • the active compound or the turmeric extract of the above (13) is preferably for lowering blood pressure by administering 20 ⁇ g or more of turmericol A and turmericol B per day to the subject.
  • the active compound or the turmeric extract of (13) is preferably for lowering blood pressure by administering 17 ⁇ g or more of Termeronol A per day to the subject.
  • the active compound or turmeric extract of (13) is preferably for lowering blood pressure by administering 5 ⁇ g or more of Termeronol B per day to the subject.
  • the active compound or the turmeric extract of the (13) is preferably for lowering blood pressure by administering 80 ⁇ g or more of bisacron per day to the subject.
  • the active compound or the turmeric extract of (13) is preferably for lowering blood pressure by administering to the subject so that the daily dose of curcumin is less than 30 mg.
  • a composition for lowering blood pressure is provided.
  • Hidden-lilies refers to plants belonging to the genus Hidden-lilies of the family Hidden-lilies, and specifically, Curcuma longa (autumn turmeric), Curcuma aromatica, Curcuma zedoraia, Curcuma phaeocaulis, Curcuma kwangisinsia, Curcuma kwangisiensis, Therefore, Curcuma longa is particularly preferable.
  • a portion containing a rhizome as turmeric.
  • turmeric used in the present invention is not particularly limited, and may be crushed turmeric, squeezed juice, extracts, processed products thereof, etc., and turmeric extract is particularly preferable. Hereinafter, preferred embodiments of the turmeric extract will be described.
  • the turmeric extract refers to an extract (turmeric extract) of a plant material derived from a plant belonging to the genus Turmeric of the family Zingiberaceae.
  • the turmeric extract is not limited to the solvent extract obtained by extraction with an extraction solvent, but also includes a solvent extract further fractionally purified by column chromatography or the like.
  • the turmeric extract used in the present invention is derived from an extract in which an extraction operation (including a fraction purification operation in the case of fractional purification) has been completed, a concentrate in which a solvent is partially removed from the extract, or an extract. It can be in the form of a dried product from which the solvent has been removed.
  • the removal of the solvent from the extract can be carried out by volatilizing the solvent by heating and / or reducing the pressure. These heating and depressurizing methods are not particularly limited, and for example, conventionally known methods can be used.
  • the plant raw material examples include the rhizomes of turmeric mentioned above, and in particular, the rhizomes of Curcuma longa and the like are preferable.
  • the rhizome one collected from the soil may be used, and an appropriate part of the rhizome may be used as it is, cut into an appropriate size or shape, or in the form of a crushed product.
  • These plant raw materials may be appropriately dried.
  • the extraction solvent water or a mixed solvent of water and a hydrophilic organic solvent can be used.
  • the hydrophilic organic solvent may be a mixed solvent of a plurality of types of hydrophilic organic solvents.
  • Water also includes hot water.
  • hot water for example, hot water having a temperature of 95 ° C. or higher can be used.
  • the hydrophilic organic solvent include at least one alcohol (may be a mixed solvent of a plurality of alcohols), and the alcohol is not particularly limited, but ethanol is preferable.
  • the mixing ratio when a mixed solvent of alcohol and water is used as the extraction solvent is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, more preferably in the range of 20:80 to 50:50. ..
  • supercritical carbon dioxide can be used as the extraction solvent.
  • the method for extracting turmeric extract from plant raw materials is not particularly limited.
  • a turmeric extract from the extraction solvent containing at least one of turmericol A, turmericol B and bisaclone as the turmeric extract, and the extraction solvent containing at least turmericol A and turmericol B. It is more preferable to use the turmeric extract according to the above, and it is more preferable to use the turmeric extract from the extraction solvent containing turmericol A, turmericol B and bisaclone.
  • Termeronol A and Termeronol B are compounds having the following planar structures, respectively.
  • turmericol A and turmericol B have the S-form configuration of the 6-position carbon in the partial structure of 2-methyl-2-hepten-4-one, but in the present invention, turmericol A and turmericol B may have the above-mentioned planar structure, and the three-dimensional arrangement may be an S body, an R body, or a mixture of an S body and an R body.
  • Bisacurone is a compound having the following planar structure.
  • Bisacurone has an asymmetric carbon at the position marked with * in the planar structural formula and may contain a plurality of optical isomers.
  • Bisacurone may be any optical isomer and two or more kinds. It may be a mixture of optical isomers.
  • At least one of Termeronol A, Termeronol B and Bisacurone used in the present invention may be derived from a plant or may be artificially synthesized. Good.
  • active compound a compound that can be found in Bioscii Biotechnol Biochem. It can be synthesized by the method described in 1993; 57 (7): 1137-40.
  • turmeronol A, turmeronol B, and bisacurone may each have the above-mentioned planar structure, and may be any optical isomer or a mixture of a plurality of optical isomers.
  • the active compound used in the present invention is more preferably derived from a plant raw material, and more preferably derived from a plant belonging to the genus Turmeric of the family Zingiberaceae. Specific examples of plants of the genus Turmeric of the family Zingiberaceae and their sites are as described above.
  • the active compound can be obtained from a site such as a rhizome of a plant belonging to the genus Turmeric of the family Zingiberaceae.
  • the active compound can be extracted from the plant material containing it.
  • the extraction method is as described above.
  • the active compound may be in the form of a plant extract, particularly a turmeric extract with water or a mixed solvent of water and a hydrophilic organic solvent.
  • a fraction obtained by purifying the active compound from the plant extract containing the active compound may be used in the present invention or may be blended in the composition of the present invention.
  • a plant extract containing an active compound can be subjected to a liquid-liquid distribution of ethyl acetate / water to purify the active compound in the ethyl acetate fraction.
  • a plant extract containing an active compound or a fraction thereof can be subjected to a purification treatment by chromatography to obtain a highly purified active compound.
  • chromatography reverse phase column chromatography, normal phase thin layer chromatography and the like can be used.
  • the plant extract containing the active compound or its fraction may be processed by a conventional method such as drying, powdering, granulation, and solution.
  • the active compound preferably contains at least turmeronol A and turmeronol B, and more preferably contains turmeronol A, turmeronol B and bisacurone.
  • composition for lowering blood pressure of the present invention has an action of lowering blood pressure.
  • the blood pressure lowering composition of the present invention has an action of lowering either systolic blood pressure or diastolic blood pressure, and typically has an action of lowering systolic blood pressure.
  • the target of the blood pressure lowering composition of the present invention is typically human, but is not limited to humans and may be other non-human animals such as mammals other than humans.
  • the target of the composition for lowering blood pressure of the present invention is a target that requires lowering of blood pressure, and preferably a target having hypertension or having a blood pressure exceeding a normal value.
  • Targets that require a decrease in blood pressure are, in particular, humans whose systolic blood pressure exceeds normal values, for example, humans whose systolic blood pressure is 130 mmHg or more, and in particular, humans whose systolic blood pressure is 130 mmHg or more and less than 160 mmHg.
  • the composition for lowering blood pressure of the present invention can be used for the prevention or treatment of hypertension.
  • the composition for lowering blood pressure of the present invention is effective not only for subjects suffering from hypertension and subjects with high blood pressure, but also for healthy subjects.
  • the composition for lowering blood pressure of the present invention may be a composition in each form such as a pharmaceutical product, a food or drink, a feed, a food additive, or a feed additive, and is more preferably a pharmaceutical product or a food or drink.
  • Foods and drinks also include foods with functional claims, foods for specified health uses, supplements for nutritional supplements, and the like.
  • composition for lowering blood pressure of the present invention is preferably in the form of a composition ingested or administered orally or nasally, and more preferably in the form of a composition ingested or administered orally.
  • “daily intake” means the total amount of the composition of the present invention ingested or administered in one day, preferably the composition of the present invention by one person, particularly one adult. It means the total amount of an object ingested or administered in one day.
  • the amount of the composition of the present invention is 0.1 g to 500 g in the case of oral or nasal, preferably oral, ingestion or administration. It can be illustrated.
  • the composition of the present invention may be continuously ingested or administered, or may be ingested or administered when necessary.
  • the shape of the composition of the present invention is not particularly limited, and may be any shape such as liquid, fluid, gel, semi-solid, or solid.
  • composition of the present invention may further contain at least one other component in addition to the active compound or the turmeric extract.
  • the composition of the present invention may contain at least one other component, which is not particularly limited, but is preferably accepted in the final form of pharmaceuticals, foods and drinks, feeds, food additives, feed additives and the like. Examples of the components that can be taken orally.
  • Such other components include sweeteners, acidulants, vitamins, minerals, thickeners, emulsifiers, antioxidants, water and the like. Further, if necessary, pigments, fragrances, preservatives, preservatives, fungicides, further bioactive substances and the like may be added.
  • Sweeteners include monosaccharides and disaccharides such as glucose, fructose, sucrose, lactose, maltose, palatinose, trehalose, and xylose, and isomerized sugar (high fructose corn syrup, fructose-fructose syrup, sugar mixed isomerized sugar, etc.) , Sugar alcohol (erythritol, xylitol, lactitol, palatinit, sorbitol, reduced water candy, etc.), honey, high-sweetness sweeteners (sclarose, acesulfam potassium, somatin, stevia, aspartame, etc.) and the like.
  • the acidulant examples include citric acid, malic acid, gluconic acid, tartaric acid, lactic acid, phosphoric acid, and salts thereof, and one or more of these can be used.
  • vitamins examples include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, niacin, inositol and the like.
  • minerals include calcium, magnesium, zinc, iron and the like.
  • thickener examples include carrageenan, gellan gum, xanthan gum, gum arabic, tamarind gum, guar gum, locust bean gum, carrage gum, agar, gelatin, pectin, soybean polysaccharide, carboxymethyl cellulose (CMC) and the like.
  • emulsifier examples include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, lecithin, vegetable sterol, saponin and the like.
  • antioxidant examples include vitamin C, tocopherol (vitamin E), enzyme-treated rutin and the like.
  • the other ingredients can be appropriately blended in an amount within a range normally adopted by those skilled in the art for compositions such as foods and drinks and pharmaceuticals.
  • the form of the composition obtained by formulating the active compound or the turmeric extract and at least one other component by an appropriate means is a powder, granules, capsules, tablets (coated tablets such as sugar-coated tablets).
  • it may be in the form of a solid composition such as a multi-layer tablet, a disintegrant in the mouth, a chewable tablet, etc., or in the form of a liquid composition such as a solution.
  • composition for lowering blood pressure containing at least one of Termeronol A, Termeronol B and Bisacurone as an active ingredient
  • the content of the active compound or the turmeric extract containing the active compound in the composition for lowering blood pressure of the present invention is not particularly limited, and may be any content effective for lowering blood pressure.
  • the composition for lowering blood pressure according to the present invention is preferably 20 ⁇ g or more, more preferably 37 ⁇ g or more, particularly preferably 55 ⁇ g or more, still more preferably 74 ⁇ g or more, and most preferably 100 ⁇ g or more of Termeronol A per daily intake. And turmeronol B.
  • the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
  • the upper limit of the total content of turmeronol A and turmeronol B is not particularly limited, but the composition for lowering blood pressure according to the present invention typically has a total daily intake of 1100 ⁇ g or less, preferably 550 ⁇ g or less.
  • turmeronol A and turmeronol B preferably 330 ⁇ g or less, particularly preferably 220 ⁇ g or less, still more preferably 170 ⁇ g or less, and most preferably 125 ⁇ g or less.
  • the total amount of turmericol A and turmericol B is in the above range. As such, it is preferable to contain the turmeric extract.
  • the composition for lowering blood pressure according to the present invention contains turmeronol A of preferably 17 ⁇ g or more, more preferably 28 ⁇ g or more, particularly preferably 43 ⁇ g or more, still more preferably 57 ⁇ g or more, and most preferably 77 ⁇ g or more per daily intake. To do.
  • the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
  • the upper limit of the content of turmeronol A is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 900 ⁇ g or less, preferably 430 ⁇ g or less, more preferably 260 ⁇ g or less, particularly, per daily intake.
  • the composition contains 175 ⁇ g or less, more preferably 130 ⁇ g or less, and most preferably 95 ⁇ g or less of Termeronol A.
  • the composition contains the turmeric extract so that the amount of turmericol A is in the above range. Is preferable.
  • the composition for lowering blood pressure according to the present invention contains turmeronol B of preferably 5 ⁇ g or more, more preferably 8 ⁇ g or more, particularly preferably 12 ⁇ g or more, still more preferably 16 ⁇ g or more, and most preferably 22 ⁇ g or more per daily intake. To do.
  • the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
  • the upper limit of the content of turmeronol B is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 250 ⁇ g or less, preferably 123 ⁇ g or less, more preferably 74 ⁇ g or less, particularly preferably, per daily intake.
  • the composition contains the turmeric extract so that the amount of turmericol B is in the above range. Is preferable.
  • the composition for lowering blood pressure according to the present invention contains bisacron of preferably 80 ⁇ g or more, more preferably 133 ⁇ g or more, particularly preferably 200 ⁇ g or more, still more preferably 267 ⁇ g or more, and most preferably 360 ⁇ g or more per daily intake. ..
  • the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
  • the upper limit of the content of Bisacurone is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 4000 ⁇ g or less, preferably 2000 ⁇ g or less, more preferably 1200 ⁇ g or less, particularly preferably 1200 ⁇ g or less per daily intake.
  • the composition when Bisacurone is in the form of a turmeric extract containing it, the composition may contain the turmeric extract so that the amount of Bisacurone is within the above range. preferable.
  • the composition for lowering blood pressure according to the present invention has a curcumin content of less than 30 mg, preferably 5 mg or less, more preferably 2.5 mg or less, and particularly preferably 1.5 mg per daily intake. Hereinafter, it is more preferably 1 mg or less, further preferably 700 ⁇ g or less, and most preferably 520 ⁇ g or less. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
  • the composition for lowering blood pressure according to the present invention is preferably a composition that is continuously ingested, specifically, once or twice a day or more, preferably for 4 weeks or more, more preferably. Is a composition that is continuously ingested for 8 weeks or longer, most preferably for 12 weeks or longer.
  • the composition for lowering blood pressure according to the present invention may be the active compound or the turmeric extract itself containing the active compound, the active compound or the turmeric extract containing the active compound, and at least one other component. It may be a composition containing and.
  • the composition of the present invention contains the active compound or the turmeric extract containing the active compound and at least one other component, the active compound or the turmeric extract containing the active compound and at least one other component.
  • the composition may be a mixture of the above components, or the active compound or the turmeric extract containing the active compound and at least one other component may be formulated by an appropriate means.
  • the composition may be a mixture of the active compound or the turmeric extract containing the active compound and a formulated composition of at least one other component, and further mixed with other components.
  • a further aspect of the present invention is water or a mixed solvent of water containing at least one of turmericol A, turmericol B and bisacurone, or at least one of turmericol A, turmericol B and bisacurone, and a hydrophilic organic solvent.
  • the present invention relates to a method for lowering blood pressure, which comprises administering a turmeric extract to a subject in need of lowering blood pressure, and lowering blood pressure in the subject.
  • the active compound or the turmeric extract used in the method according to this embodiment can be in the above-mentioned form of the composition of the present invention.
  • the method according to this aspect may be a medical method or a non-medical method.
  • the target in the method according to this aspect is typically a human, but may be a mammal other than a human.
  • Subjects who require a decrease in blood pressure are preferably those who have hypertension or whose blood pressure is above normal.
  • Targets that require a decrease in blood pressure are, in particular, humans whose systolic blood pressure exceeds normal values, for example, humans whose systolic blood pressure is 130 mmHg or more, and in particular, humans whose systolic blood pressure is 130 mmHg or more and less than 160 mmHg.
  • oral or nasal administration is preferable as the administration route, and oral administration is particularly preferable.
  • the dose of the active compound or the turmeric extract administered to the subject is not particularly limited as long as it is an effective amount for lowering blood pressure.
  • the subject when the subject is an adult, it is preferable to administer the active compound or the turmeric extract to the subject so as to administer a total of 20 ⁇ g or more of turmericol A and turmericol B per day.
  • the subject when the subject is an adult, it is preferred to administer the active compound or the turmeric extract to the subject such that 17 ⁇ g or more of Termeronol A is administered per day.
  • it is preferred to administer the active compound or the turmeric extract to the subject when the subject is an adult, it is preferred to administer the active compound or the turmeric extract to the subject such that 5 ⁇ g or more of Termeronol B is administered per day.
  • the subject when the subject is an adult, it is preferable to administer the active compound or the turmeric extract to the subject so as to administer 80 ⁇ g or more of bisacron per day. Further, it is preferable to administer the active compound or the turmeric extract to the subject so that the daily dose of curcumin is less than 30 mg. More preferably, the active compound or the turmeric is administered so that each active compound in the weight described as a preferable amount of each active compound per daily intake of the composition for lowering blood pressure according to the present invention is administered per day. It is preferable to administer the extract to the subject.
  • turmeric extract was prepared by extracting the rhizome portion of turmeric (Curcuma linga) with water and drying the obtained extract under reduced pressure to remove water.
  • the amounts of turmericol A (TA) and turmericol B (TB) in the turmeric extract were measured using LC / MS, and the amounts of bisacron and curcumin were measured using HPLC.
  • test food is a tablet containing 86.5 ⁇ g of TA, 24.7 ⁇ g of TB, 400 ⁇ g of Bisacurone, and 471 ⁇ g of curcumin per 3 tablets.
  • the test food is a tablet obtained by mixing a turmeric extract, an excipient, a brightener, a coloring agent and a manufacturing agent (fine silicon dioxide, sucrose fatty acid ester) and then tableting.
  • the placebo food is a tablet prepared by substituting the turmeric extract of the above test food with an excipient.
  • FIG. 1 shows the measurement results of systolic blood pressure at each time point.
  • the systolic blood pressure of the group ingesting the test food containing the turmeric extract (turmeric extract group) 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion is as described above. It was significantly lower than the systolic blood pressure at each time point in the group that ingested the placebo food (placebo group). From these results, it was clarified that the intake of turmeric extract lowers blood pressure.

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Abstract

The present invention provides a composition for lowering blood pressure, including a turmeric-derived component as an effective component. The present invention relates to a composition for lowering blood pressure, including at least one of turmeronol A, turmeronol B and bisacurone. This composition for lowering blood pressure may contain a combined total of 20 μg or more of turmeronol A and turmeronol B per daily intake, may contain 17 μg or more of turmeronol A per daily intake, may contain 5 μg or more of turmeronol B per daily intake, and may contain 80 μg or more of bisacurone per daily intake.

Description

血圧降下用組成物Composition for lowering blood pressure
　本発明は、血圧降下用組成物に関する。 The present invention relates to a composition for lowering blood pressure.
　高血圧は脳血管障害や冠動脈疾患などの脳心血管病ならびに心不全、慢性腎臓病などの臓器障害の重要なリスクファクターであり、中年期の高血圧は高齢期の血管性認知症リスクも上昇させる。また、至適血圧（収縮期血圧１２０ ｍｍＨｇ未満）を超えて血圧が高くなると、脳心血管、脳卒中、心筋梗塞、慢性腎臓病などの罹患リスクや死亡リスクが高くなることが報告されている（非特許文献１）。そのため、高血圧者の血圧を低下させることは様々な循環器疾患の予防において重要である。 Hypertension is an important risk factor for cerebrovascular diseases such as cerebrovascular disorders and coronary artery diseases, as well as organ disorders such as heart failure and chronic kidney disease, and hypertension in middle age also increases the risk of vascular dementia in old age. In addition, it has been reported that when the blood pressure exceeds the optimum blood pressure (systolic blood pressure of less than 120 mmHg), the risk of morbidity and mortality such as cerebrocardiovascular, stroke, myocardial infarction, and chronic kidney disease increases ( Non-Patent Document 1). Therefore, lowering the blood pressure of hypertensive persons is important in the prevention of various cardiovascular diseases.
　一方、ウコンには、多数の生理活性物質が含まれることが知られている。 On the other hand, turmeric is known to contain a large number of bioactive substances.
　特許文献１では、クルクミン濃度が９５％のウコン抽出物と、他の植物の抽出物との組み合わせを含むハーブ組成物を摂取したヒトにおいて、血圧が低下したことが開示されている。 Patent Document 1 discloses that blood pressure decreased in humans who ingested an herbal composition containing a combination of a turmeric extract having a curcumin concentration of 95% and an extract of another plant.
　特許文献２では、ターメロン等を含むウコンの脂溶性抽出物（ウコン油）を高血圧ラットに腹腔内投与すると、血圧が低下したことが開示されている、また、特許文献２では、前記ウコン油でラット由来の大動脈を処理すると、ノルエピネフリンが誘導する血管の収縮が抑制されたことが開示されている。 Patent Document 2 discloses that intraperitoneal administration of a fat-soluble extract of turmeric (turmeric oil) containing turmeric and the like to hypertensive rats reduced blood pressure, and Patent Document 2 uses the turmeric oil. It has been disclosed that treatment of rat-derived aorta suppressed norepinephrine-induced vascular constriction.
　特許文献３では、他の植物抽出物とともに、ウコンのエタノール抽出物が、高血圧症を治療又は予防する作用を有する成分として記載されている。しかし特許文献３には、ウコンのエタノール抽出物が実際に血圧降下作用を有することを裏付ける実験結果は記載されていない。 In Patent Document 3, the ethanol extract of turmeric, along with other plant extracts, is described as a component having an action of treating or preventing hypertension. However, Patent Document 3 does not describe the experimental results supporting that the ethanol extract of turmeric actually has a blood pressure lowering effect.
　特許文献４では、春ウコン原体を含む組成物が高血圧症治療に有効であると記載されている。 Patent Document 4 describes that a composition containing a spring turmeric precursor is effective in treating hypertension.
　非特許文献２では、ウコンの酢酸エチル抽出物は、アンジオテンシンＩＩ変換酵素の活性を阻害したことから、高血圧の治療に有効であることが示唆されたと記載されている。 Non-Patent Document 2 describes that the ethyl acetate extract of turmeric inhibited the activity of angiotensin II converting enzyme, suggesting that it is effective in treating hypertension.
　非特許文献３では、ウコンのメタノール抽出物を正常血圧ラットに投与したところ、用量依存的に血圧が低下したことが開示されている。 Non-Patent Document 3 discloses that when a methanol extract of turmeric was administered to normotensive rats, the blood pressure decreased in a dose-dependent manner.
特表２００７－５３０５７４号公報Special Table 2007-530574A 特表２００５－５１６９３０号公報Special Table 2005-516930 国際公開ＷＯ０２／４７６９９International release WO 02/4769 特開２００８－２８０３３３号公報Japanese Unexamined Patent Publication No. 2008-280333
　本発明は、血圧降下のために有効な組成物を提供することを目的とする。 An object of the present invention is to provide a composition effective for lowering blood pressure.
　本発明者らは、ターメロノールＡ、ターメロノールＢ及びビサクロンを含有するウコン抽出物を含む錠剤を毎日１２週間摂取したヒトにおいて血圧が有意に低下したことを見出し、以下の本発明を完成するに至った。
（１）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を有効成分として含有する、血圧降下用組成物。
（２）前記ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を含有する、（１）に記載の血圧降下用組成物。
（３）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を有効成分として含有する、血圧降下用組成物。
（４）１日の摂取量当たり合計で２０μｇ以上のターメロノールＡ及びターメロノールＢを含有する、（１）～（３）のいずれかに記載の血圧降下用組成物。
（５）１日の摂取量当たり１７μｇ以上のターメロノールＡを含有する、（１）～（４）のいずれかに記載の血圧降下用組成物。
（６）１日の摂取量当たり５μｇ以上のターメロノールＢを含有する、（１）～（５）のいずれかに記載の血圧降下用組成物。
（７）１日の摂取量当たり８０μｇ以上のビサクロンを含有する、（１）～（６）のいずれかに記載の血圧降下用組成物。
（８）１日の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、（１）～（７）のいずれかに記載の血圧降下用組成物。 The present inventors have found that blood pressure was significantly reduced in humans who ingested tablets containing turmeric extract containing turmericol A, turmericol B and bisacurone every day for 12 weeks, and completed the following invention. ..
(1) A composition for lowering blood pressure, which contains at least one of Termeronol A, Termeronol B and Bisacurone as an active ingredient.
(2) The composition for lowering blood pressure according to (1), which contains water or a turmeric extract in a mixed solvent of water and a hydrophilic organic solvent, which contains at least one of the turmericol A, turmericol B and bisaclone. ..
(3) A composition for lowering blood pressure, which contains at least one of turmericol A, turmericol B and bisaclone, and contains a turmeric extract of water or a mixed solvent of water and a hydrophilic organic solvent as an active ingredient.
(4) The composition for lowering blood pressure according to any one of (1) to (3), which contains 20 μg or more of turmeronol A and turmeronol B in total per daily intake.
(5) The composition for lowering blood pressure according to any one of (1) to (4), which contains 17 μg or more of turmeronol A per daily intake.
(6) The composition for lowering blood pressure according to any one of (1) to (5), which contains 5 μg or more of turmeronol B per daily intake.
(7) The composition for lowering blood pressure according to any one of (1) to (6), which contains 80 μg or more of bisacron per daily intake.
(8) The composition for lowering blood pressure according to any one of (1) to (7), wherein the content of curcumin per daily intake is less than 30 mg.
（９）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物の、血圧降下用組成物の製造のための使用。
（１０）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物の、血圧降下用医薬の製造のための使用。
　前記血圧降下用組成物又は医薬は、好ましくは、１日の摂取量当たり合計で２０μｇ以上のターメロノールＡ及びターメロノールＢを含有する。前記血圧降下用組成物又は医薬は、好ましくは、１日の摂取量当たり１７μｇ以上のターメロノールＡを含有する。前記血圧降下用組成物又は医薬は、好ましくは、１日の摂取量当たり５μｇ以上のターメロノールＢを含有する。前記血圧降下用組成物又は医薬は、好ましくは、１日の摂取量当たり８０μｇ以上のビサクロンを含有する。前記血圧降下用組成物又は医薬において、好ましくは、１日の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である。
（１１）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を、血圧降下を必要とする対象に投与すること、及び
　前記対象において血圧を降下すること
を含む、血圧を降下する方法。
（１２）ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を、高血圧症の治療又は予防を必要とする対象に投与すること、及び
　前記対象において高血圧症を治療又は予防すること
を含む、高血圧症を治療又は予防する方法。
（１３）血圧の降下を必要とする対象において、血圧を降下するための、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物。
　前記（１３）の前記活性化合物又は前記ウコン抽出物は、好ましくは、１日当たり合計で２０μｇ以上のターメロノールＡ及びターメロノールＢを前記対象に投与することで血圧を降下するためのものである。前記（１３）の前記活性化合物又は前記ウコン抽出物は、好ましくは、１日当たり１７μｇ以上のターメロノールＡを前記対象に投与することで血圧を降下するためのものである。前記（１３）の前記活性化合物又は前記ウコン抽出物は、好ましくは、１日当たり５μｇ以上のターメロノールＢを前記対象に投与することで血圧を降下するためのものである。前記（１３）の前記活性化合物又は前記ウコン抽出物は、好ましくは、１日当たり８０μｇ以上のビサクロンを前記対象に投与することで血圧を降下するためのものである。前記（１３）の前記活性化合物又は前記ウコン抽出物は、好ましくは、１日当たりのクルクミンの投与量が３０ｍｇ未満となるように前記対象に投与することで血圧を降下するためのものである。 (9) A turmeric extract containing water or a mixed solvent of water and a hydrophilic organic solvent containing at least one of turmericol A, turmericol B and bisaclone, or at least one of turmericol A, turmericol B and bisaclone. Use for the manufacture of compositions for lowering blood pressure.
(10) A turmeric extract containing water or a mixed solvent of water and a hydrophilic organic solvent containing at least one of turmericol A, turmericol B and bisaclone, or at least one of turmericol A, turmericol B and bisaclone. Use for the manufacture of drugs for lowering blood pressure.
The composition or medicine for lowering blood pressure preferably contains 20 μg or more of turmeronol A and turmeronol B in total per daily intake. The blood pressure lowering composition or medicine preferably contains 17 μg or more of turmeronol A per daily intake. The blood pressure lowering composition or medicine preferably contains 5 μg or more of Termeronol B per daily intake. The blood pressure lowering composition or medicine preferably contains 80 μg or more of bisacron per daily intake. In the composition or medicine for lowering blood pressure, the content of curcumin per daily intake is preferably less than 30 mg.
(11) A turmeric extract containing water or a mixed solvent of water and a hydrophilic organic solvent containing at least one of turmericol A, turmericol B and bisaclone, or at least one of turmericol A, turmericol B and bisaclone. A method of lowering blood pressure, which comprises administering to a subject in need of lowering blood pressure and lowering blood pressure in the subject.
(12) A turmeric extract containing water or a mixed solvent of water and a hydrophilic organic solvent containing at least one of turmericol A, turmericol B and bisaclone, or at least one of turmericol A, turmericol B and bisaclone. A method for treating or preventing hypertension, which comprises administering to a subject in need of treatment or prevention of hypertension, and treating or preventing hypertension in the subject.
(13) Water containing at least one of turmericol A, turmericol B and bisacurone, or at least one of turmericol A, turmericol B and bisacurone for lowering blood pressure in a subject in need of lowering blood pressure. Alternatively, a turmeric extract using a mixed solvent of water and a hydrophilic organic solvent.
The active compound or the turmeric extract of the above (13) is preferably for lowering blood pressure by administering 20 μg or more of turmericol A and turmericol B per day to the subject. The active compound or the turmeric extract of (13) is preferably for lowering blood pressure by administering 17 μg or more of Termeronol A per day to the subject. The active compound or turmeric extract of (13) is preferably for lowering blood pressure by administering 5 μg or more of Termeronol B per day to the subject. The active compound or the turmeric extract of the (13) is preferably for lowering blood pressure by administering 80 μg or more of bisacron per day to the subject. The active compound or the turmeric extract of (13) is preferably for lowering blood pressure by administering to the subject so that the daily dose of curcumin is less than 30 mg.
　本発明によれば、血圧降下用組成物が提供される。 According to the present invention, a composition for lowering blood pressure is provided.
図１は、ウコン抽出物を含有する被験食品を摂取した群（ウコン抽出物群、ｎ＝２５）及びプラセボ食品を摂取した群（プラセボ群、ｎ＝２０）の、摂取前、摂取４週間後、摂取８週間後、摂取１２週間後の各時点での収縮期血圧の測定値を示す。FIG. 1 shows the group ingesting the test food containing the turmeric extract (turmeric extract group, n = 25) and the group ingesting the placebo food (placebo group, n = 20) before and 4 weeks after ingestion. , The measured values of systolic blood pressure at each time point 8 weeks after ingestion and 12 weeks after ingestion are shown.
＜ウコン＞
　本発明においてウコンは、ショウガ科ウコン属の植物を指し、具体的には、Ｃｕｒｃｕｍａ　ｌｏｎｇａ（秋ウコン）、Ｃｕｒｃｕｍａ　ａｒｏｍａｔｉｃａ、Ｃｕｒｃｕｍａ　ｚｅｄｏａｒｉａ、Ｃｕｒｃｕｍａ　ｐｈａｅｏｃａｕｌｉｓ、Ｃｕｒｃｕｍａ　ｋｗａｎｇｓｉｅｎｓｉｓ、Ｃｕｒｃｕｍａ　ｗｅｎｙｕｊｉｎ、及び／又は、Ｃｕｒｃｕｍａ　ｘａｎｔｈｏｒｒｈｉｚａが挙げられ、Ｃｕｒｃｕｍａ　ｌｏｎｇａが特に好ましい。 <Turmeric>
In the present invention, Hidden-lilies refers to plants belonging to the genus Hidden-lilies of the family Hidden-lilies, and specifically, Curcuma longa (autumn turmeric), Curcuma aromatica, Curcuma zedoraia, Curcuma phaeocaulis, Curcuma kwangisinsia, Curcuma kwangisiensis, Therefore, Curcuma longa is particularly preferable.
　本発明においてウコンとして、根茎を含む部分を用いることが好ましい。 In the present invention, it is preferable to use a portion containing a rhizome as turmeric.
　本発明で用いるウコンの形態は特に限定されず、ウコンの破砕物、搾汁、抽出物、それらの処理物等であってよく、特に好ましくは、ウコン抽出物である。以下に、ウコン抽出物の好ましい実施形態について説明する。 The form of turmeric used in the present invention is not particularly limited, and may be crushed turmeric, squeezed juice, extracts, processed products thereof, etc., and turmeric extract is particularly preferable. Hereinafter, preferred embodiments of the turmeric extract will be described.
＜ウコン抽出物＞
　本発明においてウコン抽出物とは、ショウガ科ウコン属の植物に由来する植物原料の抽出溶媒による抽出物（ウコンエキス）をいう。ウコン抽出物は、抽出溶媒による抽出により得られた溶媒抽出物に限らず、溶媒抽出物を更に、カラムクロマトグラフィ等で分画精製したものをも包含する。本発明で用いるウコン抽出物は、抽出操作（分画精製を行う場合は分画精製操作も含む）の完了した抽出液、抽出液から溶媒を部分的に除去した濃縮物、或いは、抽出液から溶媒を除去した乾燥物の形態であることができる。抽出物からの溶媒の除去は、加熱及び／又は減圧等により溶媒を揮発することにより行うことができる。これらの加熱、減圧の方法は特に限定されず、例えば従来公知の方法を使用することができる。 <Turmeric extract>
In the present invention, the turmeric extract refers to an extract (turmeric extract) of a plant material derived from a plant belonging to the genus Turmeric of the family Zingiberaceae. The turmeric extract is not limited to the solvent extract obtained by extraction with an extraction solvent, but also includes a solvent extract further fractionally purified by column chromatography or the like. The turmeric extract used in the present invention is derived from an extract in which an extraction operation (including a fraction purification operation in the case of fractional purification) has been completed, a concentrate in which a solvent is partially removed from the extract, or an extract. It can be in the form of a dried product from which the solvent has been removed. The removal of the solvent from the extract can be carried out by volatilizing the solvent by heating and / or reducing the pressure. These heating and depressurizing methods are not particularly limited, and for example, conventionally known methods can be used.
　前記植物原料としては上記で挙げたウコンの根茎等が挙げられ、特に、Ｃｕｒｃｕｍａ　ｌｏｎｇａの根茎等が好適である。根茎は土中から採取したものを使用してよく、根茎の適当な部位を原型のまま、あるいは適当な寸法又は形状にカットしたもの、あるいは粉砕物の形態にしたものを使用することができる。これらの植物原料は適宜乾燥されたものであってよい。 Examples of the plant raw material include the rhizomes of turmeric mentioned above, and in particular, the rhizomes of Curcuma longa and the like are preferable. As the rhizome, one collected from the soil may be used, and an appropriate part of the rhizome may be used as it is, cut into an appropriate size or shape, or in the form of a crushed product. These plant raw materials may be appropriately dried.
　抽出溶媒としては、水又は水と親水性有機溶媒との混合溶媒を用いることができる。親水性有機溶媒は複数種の親水性有機溶媒の混合溶媒であってもよい。「水」とは熱水も包含する。熱水としては例えば９５℃以上の熱水が使用できる。親水性有機溶媒としては少なくとも１種のアルコール（複数種のアルコールの混合溶媒であってもよい）が挙げられ、アルコールとしては、特に限定されないが、エタノールが好ましい。抽出溶媒としてアルコールと水との混合溶媒を用いる場合の混合比は特に限定されないが、例えば重量比で１０：９０～９０：１０の範囲が好ましく、２０：８０～５０：５０の範囲がより好ましい。 As the extraction solvent, water or a mixed solvent of water and a hydrophilic organic solvent can be used. The hydrophilic organic solvent may be a mixed solvent of a plurality of types of hydrophilic organic solvents. "Water" also includes hot water. As the hot water, for example, hot water having a temperature of 95 ° C. or higher can be used. Examples of the hydrophilic organic solvent include at least one alcohol (may be a mixed solvent of a plurality of alcohols), and the alcohol is not particularly limited, but ethanol is preferable. The mixing ratio when a mixed solvent of alcohol and water is used as the extraction solvent is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, more preferably in the range of 20:80 to 50:50. ..
　また、抽出溶媒として、超臨界二酸化炭素を用いることもできる。 Also, supercritical carbon dioxide can be used as the extraction solvent.
　植物原料からのウコン抽出物の抽出方法は特に限定されない。 The method for extracting turmeric extract from plant raw materials is not particularly limited.
　本発明では、ウコン抽出物として、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、前記抽出溶媒によるウコン抽出物を用いることが好ましく、少なくともターメロノールＡ及びターメロノールＢを含有する、前記抽出溶媒によるウコン抽出物を用いることがより好ましく、ターメロノールＡ、ターメロノールＢ及びビサクロンを含有する、前記抽出溶媒によるウコン抽出物を用いることがより好ましい。
　ターメロノールＡ及びターメロノールＢは、それぞれ、以下の平面構造を有する化合物である。 In the present invention, it is preferable to use a turmeric extract from the extraction solvent containing at least one of turmericol A, turmericol B and bisaclone as the turmeric extract, and the extraction solvent containing at least turmericol A and turmericol B. It is more preferable to use the turmeric extract according to the above, and it is more preferable to use the turmeric extract from the extraction solvent containing turmericol A, turmericol B and bisaclone.
Termeronol A and Termeronol B are compounds having the following planar structures, respectively.
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000001
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
　ウコンから分離される天然物においてターメロノールＡ及びターメロノールＢは、２－メチル－２－ヘプテン－４－オンの部分構造における６位炭素の立体配置がＳ体であるが、本発明においてターメロノールＡ及びターメロノールＢは上記の平面構造を有していればよく、前記立体配置がＳ体であってもよいし、Ｒ体であってもよいし、Ｓ体とＲ体との混合物であってもよい。 In the natural products separated from turmeric, turmericol A and turmericol B have the S-form configuration of the 6-position carbon in the partial structure of 2-methyl-2-hepten-4-one, but in the present invention, turmericol A and turmericol B may have the above-mentioned planar structure, and the three-dimensional arrangement may be an S body, an R body, or a mixture of an S body and an R body.
　本発明においてビサクロンとは、以下の平面構造を有する化合物である。ビサクロンは平面構造式中＊印で示した位置に不斉炭素を有し、複数の光学異性体を含み得るが、本発明においてビサクロンはいずれの光学異性体であってもよく、２種以上の光学異性体の混合物であってもよい。 In the present invention, Bisacurone is a compound having the following planar structure. Bisacurone has an asymmetric carbon at the position marked with * in the planar structural formula and may contain a plurality of optical isomers. However, in the present invention, Bisacurone may be any optical isomer and two or more kinds. It may be a mixture of optical isomers.
Figure JPOXMLDOC01-appb-C000003
 ＜ターメロノールＡ、ターメロノールＢ及びビサクロン＞
　本発明で用いるターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種（以下「活性化合物」という場合がある）は植物に由来するものであってもよいし、人為的に合成されたものであってもよい。例えば光学活性の（＋）－ターメロノールＡは、Ｂｉｏｓｃｉ　Ｂｉｏｔｅｃｈｎｏｌ　Ｂｉｏｃｈｅｍ．　１９９３；５７（７）：１１３７－４０に記載の方法により合成することできる。
Figure JPOXMLDOC01-appb-C000003
 <Termeronol A, Termeronol B and Bisacurone>
At least one of Termeronol A, Termeronol B and Bisacurone used in the present invention (hereinafter, may be referred to as "active compound") may be derived from a plant or may be artificially synthesized. Good. For example, the optically active (+)-termeronol A can be found in Bioscii Biotechnol Biochem. It can be synthesized by the method described in 1993; 57 (7): 1137-40.
　本発明においてターメロノールＡ、ターメロノールＢ及びビサクロンはそれぞれ上記の平面構造を有していればよく、いずれの光学異性体であってもよく、複数の光学異性体の混合物であってもよい。 In the present invention, turmeronol A, turmeronol B, and bisacurone may each have the above-mentioned planar structure, and may be any optical isomer or a mixture of a plurality of optical isomers.
　本発明で用いる活性化合物はより好ましくは植物原料に由来するものであり、より好ましくは、ショウガ科ウコン属植物に由来するものである。ショウガ科ウコン属植物及びその部位の具体例は上記の通りである。ショウガ科ウコン属の植物の根茎等の部位から活性化合物を得ることができる。 The active compound used in the present invention is more preferably derived from a plant raw material, and more preferably derived from a plant belonging to the genus Turmeric of the family Zingiberaceae. Specific examples of plants of the genus Turmeric of the family Zingiberaceae and their sites are as described above. The active compound can be obtained from a site such as a rhizome of a plant belonging to the genus Turmeric of the family Zingiberaceae.
　活性化合物は、それを含む植物原料から抽出することができる。抽出方法は既述の通りである。活性化合物は、植物抽出物、特に、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物の形態であってよい。 The active compound can be extracted from the plant material containing it. The extraction method is as described above. The active compound may be in the form of a plant extract, particularly a turmeric extract with water or a mixed solvent of water and a hydrophilic organic solvent.
　また、活性化合物を含む植物抽出物から、活性化合物を高純度化した画分を、本発明に使用してもよく、本発明の組成物に配合してもよい。例えば、活性化合物を含む植物抽出物を酢酸エチル／水の液液分配に供し、酢酸エチル画分に活性化合物を高純度化することができる。また、活性化合物を含む植物抽出物又はその画分を、クロマトグラフィによる精製処理に供して、高純度化した活性化合物を得ることもできる。クロマトグラフィとしては、逆相カラムクロマトグラフィ、順相薄層クロマトグラフィ等を使用することができる。 Further, a fraction obtained by purifying the active compound from the plant extract containing the active compound may be used in the present invention or may be blended in the composition of the present invention. For example, a plant extract containing an active compound can be subjected to a liquid-liquid distribution of ethyl acetate / water to purify the active compound in the ethyl acetate fraction. In addition, a plant extract containing an active compound or a fraction thereof can be subjected to a purification treatment by chromatography to obtain a highly purified active compound. As the chromatography, reverse phase column chromatography, normal phase thin layer chromatography and the like can be used.
　活性化合物を含む植物抽出物又はその画分は、常法により、乾燥、粉末化、顆粒化、溶液化等の加工を施したものであってもよい。 The plant extract containing the active compound or its fraction may be processed by a conventional method such as drying, powdering, granulation, and solution.
　前記活性化合物は、好ましくは、少なくともターメロノールＡ及びターメロノールＢを含有し、より好ましくは、ターメロノールＡ、ターメロノールＢ及びビサクロンを含有する。 The active compound preferably contains at least turmeronol A and turmeronol B, and more preferably contains turmeronol A, turmeronol B and bisacurone.
＜血圧降下用組成物＞
　本発明の血圧降下用組成物は、血圧を降下する作用を有る。 <Composition for lowering blood pressure>
The composition for lowering blood pressure of the present invention has an action of lowering blood pressure.
　本発明の血圧降下用組成物は、収縮期血圧又は拡張期血圧のいずれかを降下する作用を有し、典型的には、収縮期血圧を降下する作用を有する。本発明の血圧降下用組成物の対象は典型的にはヒトであるが、ヒトには限定されず他の非ヒト動物、例えばヒト以外の哺乳類であってもよい。 The blood pressure lowering composition of the present invention has an action of lowering either systolic blood pressure or diastolic blood pressure, and typically has an action of lowering systolic blood pressure. The target of the blood pressure lowering composition of the present invention is typically human, but is not limited to humans and may be other non-human animals such as mammals other than humans.
　本発明の血圧降下用組成物の対象は、血圧の降下を必要とする対象であり、好ましくは、高血圧症を有する又は血圧が正常値を上回る対象である。血圧の降下を必要とする対象としては特に、収縮期血圧が正常値を上回るヒト、例えば収縮期血圧が１３０ｍｍＨｇ以上のヒトであり、特に、収縮期血圧が１３０ｍｍＨｇ以上、１６０ｍｍＨｇ未満のヒトである。 The target of the composition for lowering blood pressure of the present invention is a target that requires lowering of blood pressure, and preferably a target having hypertension or having a blood pressure exceeding a normal value. Targets that require a decrease in blood pressure are, in particular, humans whose systolic blood pressure exceeds normal values, for example, humans whose systolic blood pressure is 130 mmHg or more, and in particular, humans whose systolic blood pressure is 130 mmHg or more and less than 160 mmHg.
　本発明の血圧降下用組成物は、高血圧症の予防又は治療のために用いることができる。本発明の血圧降下用組成物は、高血圧症を患う対象や、血圧が高めの対象だけでなく、健常な対象に対しても有効である。 The composition for lowering blood pressure of the present invention can be used for the prevention or treatment of hypertension. The composition for lowering blood pressure of the present invention is effective not only for subjects suffering from hypertension and subjects with high blood pressure, but also for healthy subjects.
　本発明の血圧降下用組成物は、医薬品、飲食品、飼料、食品添加剤、飼料添加剤等の各形態の組成物であってよく、医薬品又は飲食品であることがより好ましい。飲食品は、機能性表示食品、特定保健用食品、栄養補給のためのサプリメント等の形態のものも包含する。 The composition for lowering blood pressure of the present invention may be a composition in each form such as a pharmaceutical product, a food or drink, a feed, a food additive, or a feed additive, and is more preferably a pharmaceutical product or a food or drink. Foods and drinks also include foods with functional claims, foods for specified health uses, supplements for nutritional supplements, and the like.
　本発明の血圧降下用組成物は、好ましくは、経口又は経鼻により摂取又は投与される組成物の形態であり、より好ましくは、経口により摂取又は投与される組成物の形態である。 The composition for lowering blood pressure of the present invention is preferably in the form of a composition ingested or administered orally or nasally, and more preferably in the form of a composition ingested or administered orally.
　本発明において「１日の摂取量」とは、本発明の組成物の、一日間で摂取又は投与される量の総量を意味し、好ましくは、ヒト一人、特に成人一人により、本発明の組成物が一日間で摂取又は投与される量の総量を意味する。本発明の組成物の「１日の摂取量」の具体例として、経口又は経鼻による、好ましくは経口による、摂取又は投与の場合に、本発明の組成物の量として０．１ｇ～５００ｇが例示できる。本発明の組成物は、継続的に摂取又は投与されてもよいし、必要時に摂取又は投与されてもよい。 In the present invention, "daily intake" means the total amount of the composition of the present invention ingested or administered in one day, preferably the composition of the present invention by one person, particularly one adult. It means the total amount of an object ingested or administered in one day. As a specific example of the "daily intake" of the composition of the present invention, the amount of the composition of the present invention is 0.1 g to 500 g in the case of oral or nasal, preferably oral, ingestion or administration. It can be illustrated. The composition of the present invention may be continuously ingested or administered, or may be ingested or administered when necessary.
　本発明の組成物の形状は、特に限定されず、例えば、液体状、流動状、ゲル状、半固形状、又は固形状などの何れの形状であってもよい。 The shape of the composition of the present invention is not particularly limited, and may be any shape such as liquid, fluid, gel, semi-solid, or solid.
　本発明の組成物は、前記活性化合物又は前記ウコン抽出物に加えて、少なくとも１種の他の成分を更に含んでいてもよい。本発明の組成物が含み得る、少なくとも１種の他の成分としては、特に限定されないが、好ましくは、医薬品、飲食品、飼料、食品添加剤、飼料添加剤等の最終的な形態において許容される成分であって、経口摂取可能な成分が例示できる。 The composition of the present invention may further contain at least one other component in addition to the active compound or the turmeric extract. The composition of the present invention may contain at least one other component, which is not particularly limited, but is preferably accepted in the final form of pharmaceuticals, foods and drinks, feeds, food additives, feed additives and the like. Examples of the components that can be taken orally.
　このような他の成分としては例えば、甘味料、酸味料、ビタミン類、ミネラル類、増粘剤、乳化剤、酸化防止剤、水等が挙げられる。また、必要により、色素、香料、保存料、防腐剤、防かび剤、更なる生理活性物質等を添加してもよい。 Examples of such other components include sweeteners, acidulants, vitamins, minerals, thickeners, emulsifiers, antioxidants, water and the like. Further, if necessary, pigments, fragrances, preservatives, preservatives, fungicides, further bioactive substances and the like may be added.
　甘味料としては、ブドウ糖、果糖、ショ糖、乳糖、麦芽糖、パラチノース、トレハロース、キシロース等の単糖や二糖、異性化糖（ブドウ糖果糖液糖、果糖ブドウ糖液糖、砂糖混合異性化糖等）、糖アルコール（エリスリトール、キシリトール、ラクチトール、パラチニット、ソルビトール、還元水飴等）、はちみつ、高甘味度甘味料（スクラロース、アセスルファムカリウム、ソーマチン、ステビア、アスパルテーム等）等が挙げられる。 Sweeteners include monosaccharides and disaccharides such as glucose, fructose, sucrose, lactose, maltose, palatinose, trehalose, and xylose, and isomerized sugar (high fructose corn syrup, fructose-fructose syrup, sugar mixed isomerized sugar, etc.) , Sugar alcohol (erythritol, xylitol, lactitol, palatinit, sorbitol, reduced water candy, etc.), honey, high-sweetness sweeteners (sclarose, acesulfam potassium, somatin, stevia, aspartame, etc.) and the like.
　酸味料としては、クエン酸、リンゴ酸、グルコン酸、酒石酸、乳酸、リン酸、又はこれらの塩等があり、これらのうちの１種又は２種以上を利用することができる。 Examples of the acidulant include citric acid, malic acid, gluconic acid, tartaric acid, lactic acid, phosphoric acid, and salts thereof, and one or more of these can be used.
　ビタミン類としては、ビタミンＡ、ビタミンＢ１、ビタミンＢ２、ビタミンＢ６、ビタミンＥ、ナイアシン、イノシトール等が挙げられる。 Examples of vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, niacin, inositol and the like.
　ミネラル類としては、カルシウム、マグネシウム、亜鉛、鉄等が挙げられる。 Examples of minerals include calcium, magnesium, zinc, iron and the like.
　増粘剤としては、カラギーナン、ジェランガム、キサンタンガム、アラビアガム、タマリンドガム、グアーガム、ローカストビーンガム、カラヤガム、寒天、ゼラチン、ペクチン、大豆多糖類、カルボキシメチルセルロース（ＣＭＣ）等が挙げられる。 Examples of the thickener include carrageenan, gellan gum, xanthan gum, gum arabic, tamarind gum, guar gum, locust bean gum, carrage gum, agar, gelatin, pectin, soybean polysaccharide, carboxymethyl cellulose (CMC) and the like.
　乳化剤としては、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、レシチン、植物性ステロール、サポニン等が挙げられる。 Examples of the emulsifier include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, lecithin, vegetable sterol, saponin and the like.
　酸化防止剤としては、ビタミンＣ、トコフェロール（ビタミンＥ）、酵素処理ルチン等が挙げられる。 Examples of the antioxidant include vitamin C, tocopherol (vitamin E), enzyme-treated rutin and the like.
　前記他の成分は、それぞれ当業者が飲食品、医薬品等の組成物に通常採用する範囲内の量で適宜配合することができる。 The other ingredients can be appropriately blended in an amount within a range normally adopted by those skilled in the art for compositions such as foods and drinks and pharmaceuticals.
　本発明において、前記活性化合物又は前記ウコン抽出物と、少なくとも１種の他の成分とを適当な手段で製剤化した組成物の形態は、粉末、顆粒、カプセル剤、錠剤（糖衣錠等のコーティング錠又は多層錠、口中崩壊剤、チュアブル錠等を含む）等の固形組成物の形態であってもよいし、溶液剤等の液体組成物の形態であってもよい。 In the present invention, the form of the composition obtained by formulating the active compound or the turmeric extract and at least one other component by an appropriate means is a powder, granules, capsules, tablets (coated tablets such as sugar-coated tablets). Alternatively, it may be in the form of a solid composition such as a multi-layer tablet, a disintegrant in the mouth, a chewable tablet, etc., or in the form of a liquid composition such as a solution.
＜ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を有効成分として含有する血圧降下用組成物＞
　本発明の血圧降下用組成物における、前記活性化合物又はそれを含む前記ウコン抽出物の含有量は特に限定されず、血圧降下のために有効な含有量であればよい。 <Composition for lowering blood pressure containing at least one of Termeronol A, Termeronol B and Bisacurone as an active ingredient>
The content of the active compound or the turmeric extract containing the active compound in the composition for lowering blood pressure of the present invention is not particularly limited, and may be any content effective for lowering blood pressure.
　本発明に係る血圧降下用組成物は、１日の摂取量当たり合計で好ましくは２０μｇ以上、より好ましくは３７μｇ以上、特に好ましくは５５μｇ以上、更に好ましくは７４μｇ以上、最も好ましくは１００μｇ以上のターメロノールＡ及びターメロノールＢを含有する。この場合に、本発明に係る血圧降下用組成物は血圧降下作用が特に高い。ターメロノールＡ及びターメロノールＢの合計の含有量の上限は特に限定されないが、本発明に係る血圧降下用組成物は、１日の摂取量当たり合計で典型的には１１００μｇ以下、好ましくは５５０μｇ以下、より好ましくは３３０μｇ以下、特に好ましくは２２０μｇ以下、更に好ましくは１７０μｇ以下、最も好ましくは１２５μｇ以下のターメロノールＡ及びターメロノールＢを含有する。本発明に係る血圧降下用組成物において、ターメロノールＡ及びターメロノールＢの少なくとも１種がそれを含むウコン抽出物の形態である場合、前記組成物は、ターメロノールＡ及びターメロノールＢの合計量が前記範囲となるように、前記ウコン抽出物を含有することが好ましい。 The composition for lowering blood pressure according to the present invention is preferably 20 μg or more, more preferably 37 μg or more, particularly preferably 55 μg or more, still more preferably 74 μg or more, and most preferably 100 μg or more of Termeronol A per daily intake. And turmeronol B. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect. The upper limit of the total content of turmeronol A and turmeronol B is not particularly limited, but the composition for lowering blood pressure according to the present invention typically has a total daily intake of 1100 μg or less, preferably 550 μg or less. It contains turmeronol A and turmeronol B, preferably 330 μg or less, particularly preferably 220 μg or less, still more preferably 170 μg or less, and most preferably 125 μg or less. In the composition for lowering blood pressure according to the present invention, when at least one of turmericol A and turmericol B is in the form of a turmeric extract containing the same, the total amount of turmericol A and turmericol B is in the above range. As such, it is preferable to contain the turmeric extract.
　本発明に係る血圧降下用組成物は、１日の摂取量当たり好ましくは１７μｇ以上、より好ましくは２８μｇ以上、特に好ましくは４３μｇ以上、更に好ましくは５７μｇ以上、最も好ましくは７７μｇ以上のターメロノールＡを含有する。この場合に、本発明に係る血圧降下用組成物は血圧降下作用が特に高い。ターメロノールＡの含有量の上限は特に限定されないが、本発明に係る血圧降下用組成物は、１日の摂取量当たり、典型的には９００μｇ以下、好ましくは４３０μｇ以下、より好ましくは２６０μｇ以下、特に好ましくは１７５μｇ以下、更に好ましくは１３０μｇ以下、最も好ましくは９５μｇ以下のターメロノールＡを含有する。本発明に係る血圧降下用組成物において、ターメロノールＡがそれを含むウコン抽出物の形態である場合、前記組成物は、ターメロノールＡの量が前記範囲となるように、前記ウコン抽出物を含有することが好ましい。 The composition for lowering blood pressure according to the present invention contains turmeronol A of preferably 17 μg or more, more preferably 28 μg or more, particularly preferably 43 μg or more, still more preferably 57 μg or more, and most preferably 77 μg or more per daily intake. To do. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect. The upper limit of the content of turmeronol A is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 900 μg or less, preferably 430 μg or less, more preferably 260 μg or less, particularly, per daily intake. It contains 175 μg or less, more preferably 130 μg or less, and most preferably 95 μg or less of Termeronol A. In the blood pressure lowering composition according to the present invention, when turmericol A is in the form of a turmeric extract containing it, the composition contains the turmeric extract so that the amount of turmericol A is in the above range. Is preferable.
　本発明に係る血圧降下用組成物は、１日の摂取量当たり好ましくは５μｇ以上、より好ましくは８μｇ以上、特に好ましくは１２μｇ以上、更に好ましくは１６μｇ以上、最も好ましくは２２μｇ以上のターメロノールＢを含有する。この場合に、本発明に係る血圧降下用組成物は血圧降下作用が特に高い。ターメロノールＢの含有量の上限は特に限定されないが、本発明に係る血圧降下用組成物は、１日の摂取量当たり典型的には２５０μｇ以下、好ましくは１２３μｇ以下、より好ましくは７４μｇ以下、特に好ましくは５０μｇ以下、更に好ましくは３７μｇ以下、最も好ましくは２７μｇ以下のターメロノールＢを含有する。本発明に係る血圧降下用組成物において、ターメロノールＢがそれを含むウコン抽出物の形態である場合、前記組成物は、ターメロノールＢの量が前記範囲となるように、前記ウコン抽出物を含有することが好ましい。 The composition for lowering blood pressure according to the present invention contains turmeronol B of preferably 5 μg or more, more preferably 8 μg or more, particularly preferably 12 μg or more, still more preferably 16 μg or more, and most preferably 22 μg or more per daily intake. To do. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect. The upper limit of the content of turmeronol B is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 250 μg or less, preferably 123 μg or less, more preferably 74 μg or less, particularly preferably, per daily intake. Contains 50 μg or less, more preferably 37 μg or less, and most preferably 27 μg or less of Termeronol B. In the blood pressure lowering composition according to the present invention, when turmericol B is in the form of a turmeric extract containing it, the composition contains the turmeric extract so that the amount of turmericol B is in the above range. Is preferable.
　本発明に係る血圧降下用組成物は、１日の摂取量当たり好ましくは８０μｇ以上、より好ましくは１３３μｇ以上、特に好ましくは２００μｇ以上、更に好ましくは２６７μｇ以上、最も好ましくは３６０μｇ以上のビサクロンを含有する。この場合に、本発明に係る血圧降下用組成物は血圧降下作用が特に高い。ビサクロンの含有量の上限は特に限定されないが、本発明に係る血圧降下用組成物は、１日の摂取量当たり典型的には４０００μｇ以下、好ましくは２０００μｇ以下、より好ましくは１２００μｇ以下、特に好ましくは８００μｇ以下、更に好ましくは６００μｇ以下、最も好ましくは４４０μｇ以下のビサクロンを含有する。本発明に係る血圧降下用組成物において、ビサクロンがそれを含むウコン抽出物の形態である場合、前記組成物は、ビサクロンの量が前記範囲となるように、前記ウコン抽出物を含有することが好ましい。 The composition for lowering blood pressure according to the present invention contains bisacron of preferably 80 μg or more, more preferably 133 μg or more, particularly preferably 200 μg or more, still more preferably 267 μg or more, and most preferably 360 μg or more per daily intake. .. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect. The upper limit of the content of Bisacurone is not particularly limited, but the composition for lowering blood pressure according to the present invention is typically 4000 μg or less, preferably 2000 μg or less, more preferably 1200 μg or less, particularly preferably 1200 μg or less per daily intake. It contains 800 μg or less, more preferably 600 μg or less, and most preferably 440 μg or less of bisaclone. In the blood pressure lowering composition according to the present invention, when Bisacurone is in the form of a turmeric extract containing it, the composition may contain the turmeric extract so that the amount of Bisacurone is within the above range. preferable.
　本発明に係る血圧降下用組成物は、１日の摂取量当たりのクルクミンの含有量が、典型的には３０ｍｇ未満、好ましくは５ｍｇ以下、より好ましくは２．５ｍｇ以下、特に好ましくは１．５ｍｇ以下、更に好ましくは１ｍｇ以下、更に好ましくは７００μｇ以下、最も好ましくは５２０μｇ以下である。この場合に、本発明に係る血圧降下用組成物は血圧降下作用が特に高い。 The composition for lowering blood pressure according to the present invention has a curcumin content of less than 30 mg, preferably 5 mg or less, more preferably 2.5 mg or less, and particularly preferably 1.5 mg per daily intake. Hereinafter, it is more preferably 1 mg or less, further preferably 700 μg or less, and most preferably 520 μg or less. In this case, the composition for lowering blood pressure according to the present invention has a particularly high blood pressure lowering effect.
　本発明に係る血圧降下用組成物は、継続的に摂取される組成物であることが好ましく、具体的には、１日１回又は２回以上の頻度で、好ましくは４週間以上、より好ましくは８週間以上、最も好ましくは１２週間以上にわたり継続して摂取される組成物である。 The composition for lowering blood pressure according to the present invention is preferably a composition that is continuously ingested, specifically, once or twice a day or more, preferably for 4 weeks or more, more preferably. Is a composition that is continuously ingested for 8 weeks or longer, most preferably for 12 weeks or longer.
　本発明に係る血圧降下用組成物は、前記活性化合物又はそれを含む前記ウコン抽出物自体であってもよいし、前記活性化合物又はそれを含む前記ウコン抽出物と、少なくとも１種の他の成分とを含む組成物であってもよい。本発明の組成物が、前記活性化合物又はそれを含む前記ウコン抽出物と、少なくとも１種の他の成分とを含む場合、前記活性化合物又はそれを含む前記ウコン抽出物と、少なくとも１種の他の成分とを混合した組成物であってもよいし、前記活性化合物又はそれを含む前記ウコン抽出物と、少なくとも１種の他の成分とを適当な手段で製剤化した組成物であってもよいし、前記活性化合物又はそれを含む前記ウコン抽出物と、少なくとも１種の他の成分との製剤化した組成物を、更に他の成分と混合した組成物であってもよい。 The composition for lowering blood pressure according to the present invention may be the active compound or the turmeric extract itself containing the active compound, the active compound or the turmeric extract containing the active compound, and at least one other component. It may be a composition containing and. When the composition of the present invention contains the active compound or the turmeric extract containing the active compound and at least one other component, the active compound or the turmeric extract containing the active compound and at least one other component. The composition may be a mixture of the above components, or the active compound or the turmeric extract containing the active compound and at least one other component may be formulated by an appropriate means. Alternatively, the composition may be a mixture of the active compound or the turmeric extract containing the active compound and a formulated composition of at least one other component, and further mixed with other components.
＜ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種の投与により血圧を降下する方法＞
　本発明の更なる一態様は、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種、或いは、ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を、血圧降下を必要とする対象に投与すること、及び
　前記対象において血圧を降下すること
を含む、血圧を降下する方法に関する。 <Method of lowering blood pressure by administration of at least one of Termeronol A, Termeronol B and Bisacurone>
A further aspect of the present invention is water or a mixed solvent of water containing at least one of turmericol A, turmericol B and bisacurone, or at least one of turmericol A, turmericol B and bisacurone, and a hydrophilic organic solvent. The present invention relates to a method for lowering blood pressure, which comprises administering a turmeric extract to a subject in need of lowering blood pressure, and lowering blood pressure in the subject.
　本態様に係る方法に用いる前記活性化合物又は前記ウコン抽出物は、本発明の組成物の上述した形態であることができる。本態様に係る方法は、医療的方法であってもよいし、非医療的方法であってもよい。 The active compound or the turmeric extract used in the method according to this embodiment can be in the above-mentioned form of the composition of the present invention. The method according to this aspect may be a medical method or a non-medical method.
　本態様に係る方法での対象としては、典型的にはヒトであるが、ヒト以外の哺乳動物であってもよい。血圧の降下を必要とする対象とは、好ましくは、高血圧症を有する又は血圧が正常値を上回る対象である。血圧の降下を必要とする対象としては特に、収縮期血圧が正常値を上回るヒト、例えば収縮期血圧が１３０ｍｍＨｇ以上のヒトであり、特に、収縮期血圧が１３０ｍｍＨｇ以上、１６０ｍｍＨｇ未満のヒトである。 The target in the method according to this aspect is typically a human, but may be a mammal other than a human. Subjects who require a decrease in blood pressure are preferably those who have hypertension or whose blood pressure is above normal. Targets that require a decrease in blood pressure are, in particular, humans whose systolic blood pressure exceeds normal values, for example, humans whose systolic blood pressure is 130 mmHg or more, and in particular, humans whose systolic blood pressure is 130 mmHg or more and less than 160 mmHg.
　本態様に係る方法において、投与経路としては経口又は経鼻投与が好ましく、経口投与が特に好ましい。 In the method according to this aspect, oral or nasal administration is preferable as the administration route, and oral administration is particularly preferable.
　本態様に係る方法において、前記活性化合物又は前記ウコン抽出物を、対象に投与する投与量は、血圧を降下するための有効量であれば良く特に限定されない。例えば、一実施形態では、対象が成人である場合、１日当たり合計で２０μｇ以上のターメロノールＡ及びターメロノールＢを投与するように前記活性化合物又は前記ウコン抽出物を、対象に投与することが好ましい。別の一実施形態では、対象が成人である場合、１日当たり１７μｇ以上のターメロノールＡを投与するように前記活性化合物又は前記ウコン抽出物を、対象に投与することが好ましい。別の一実施形態では、対象が成人である場合、１日当たり５μｇ以上のターメロノールＢを投与するように前記活性化合物又は前記ウコン抽出物を、対象に投与することが好ましい。別の一実施形態では、対象が成人である場合、１日当たり８０μｇ以上のビサクロンを投与するように、前記活性化合物又は前記ウコン抽出物を、対象に投与することが好ましい。更に、１日当たりのクルクミンの投与量が３０ｍｇ未満となるように、前記活性化合物又は前記ウコン抽出物を、対象に投与することが好ましい。更に好ましくは、本発明に係る血圧降下用組成物の１日摂取量当たりの各活性化合物の好ましい量として記載した重量の各活性化合物が１日当たりに投与されるように、前記活性化合物又は前記ウコン抽出物を対象に投与することが好ましい。 In the method according to this aspect, the dose of the active compound or the turmeric extract administered to the subject is not particularly limited as long as it is an effective amount for lowering blood pressure. For example, in one embodiment, when the subject is an adult, it is preferable to administer the active compound or the turmeric extract to the subject so as to administer a total of 20 μg or more of turmericol A and turmericol B per day. In another embodiment, when the subject is an adult, it is preferred to administer the active compound or the turmeric extract to the subject such that 17 μg or more of Termeronol A is administered per day. In another embodiment, when the subject is an adult, it is preferred to administer the active compound or the turmeric extract to the subject such that 5 μg or more of Termeronol B is administered per day. In another embodiment, when the subject is an adult, it is preferable to administer the active compound or the turmeric extract to the subject so as to administer 80 μg or more of bisacron per day. Further, it is preferable to administer the active compound or the turmeric extract to the subject so that the daily dose of curcumin is less than 30 mg. More preferably, the active compound or the turmeric is administered so that each active compound in the weight described as a preferable amount of each active compound per daily intake of the composition for lowering blood pressure according to the present invention is administered per day. It is preferable to administer the extract to the subject.
１．ウコン抽出物の作製方法
　ウコン抽出物は、ウコン（Ｃｕｒｃｕｍａ　ｌｏｎｇａ）の根茎部分を水にて抽出し、得られた抽出液を減圧加熱乾燥して水分を除去することにより調製した。ウコン抽出物中のターメロノールＡ（ＴＡ）及びターメロノールＢ（ＴＢ）の量は、ＬＣ／ＭＳを用いて測定し、ビサクロン及びクルクミンの量は、ＨＰＬＣを用いて測定した。 1. 1. Method for Producing Turmeric Extract The turmeric extract was prepared by extracting the rhizome portion of turmeric (Curcuma linga) with water and drying the obtained extract under reduced pressure to remove water. The amounts of turmericol A (TA) and turmericol B (TB) in the turmeric extract were measured using LC / MS, and the amounts of bisacron and curcumin were measured using HPLC.
２．被験食品
　被験食品は、３錠当たりウコン抽出物を、ＴＡとして８６．５μｇ、ＴＢとして２４．７μｇ、ビサクロンとして４００μｇ、クルクミンとして４７１μｇ含有する錠剤である。被験食品は、ウコン抽出物、賦形剤、光沢剤、着色料及び製造用剤（微粒二酸化ケイ素、ショ糖脂肪酸エステル）を混合した後、打錠して錠剤としたものである。 2. 2. Test food The test food is a tablet containing 86.5 μg of TA, 24.7 μg of TB, 400 μg of Bisacurone, and 471 μg of curcumin per 3 tablets. The test food is a tablet obtained by mixing a turmeric extract, an excipient, a brightener, a coloring agent and a manufacturing agent (fine silicon dioxide, sucrose fatty acid ester) and then tableting.
　プラセボ食品は、上記被験食品のウコン抽出物を賦形剤に置換して調製された錠剤である。 The placebo food is a tablet prepared by substituting the turmeric extract of the above test food with an excipient.
３．血圧評価試験
　５０～６９歳の男女で、収縮期血圧が１３０ ｍｍＨｇ（正常高値血圧）以上、１６０ｍｍＨｇ未満の４５名の被験者を２群に割り付け（プラセボ群：２０名、ウコン抽出物群：２５名）、二重盲検下で、前記のウコン抽出物を含有する被験食品もしくは当該抽出物が不含の前記プラセボ食品を１日１回、３錠を夕食前に１２週間摂取させた。前記被験食品又は前記プラセボ食品の摂取前、摂取４週間後、摂取８週間後、摂取１２週間後に収縮期血圧を測定した。 3. 3. Blood pressure evaluation test Forty-five subjects aged 50 to 69 years with systolic blood pressure of 130 mmHg (normally high blood pressure) or higher and less than 160 mmHg were assigned to two groups (placebo group: 20 subjects, turmeric extract group: 25 subjects). ), Under double-blinding, the test food containing the turmeric extract or the placebo food containing no extract was ingested once a day for 3 tablets for 12 weeks before dinner. The systolic blood pressure was measured before, 4 weeks, 8 weeks, and 12 weeks after ingestion of the test food or the placebo food.
　図１に各時点の収縮期血圧の測定結果を示した。図１に示したように、前記のウコン抽出物を含有する被験食品を摂取した群（ウコン抽出物群）の摂取４週間後、摂取８週間後、摂取１２週間後の収縮期血圧は、前記プラセボ食品を摂取した群（プラセボ群）の各時点での収縮期血圧と比べて、有意に低値であった。これらの結果から、ウコン抽出物の摂取は血圧を低下させることが明らかとなった。 FIG. 1 shows the measurement results of systolic blood pressure at each time point. As shown in FIG. 1, the systolic blood pressure of the group ingesting the test food containing the turmeric extract (turmeric extract group) 4 weeks after ingestion, 8 weeks after ingestion, and 12 weeks after ingestion is as described above. It was significantly lower than the systolic blood pressure at each time point in the group that ingested the placebo food (placebo group). From these results, it was clarified that the intake of turmeric extract lowers blood pressure.
　本明細書で引用した全ての刊行物、特許及び特許出願はそのまま引用により本明細書に組み入れられるものとする。 All publications, patents and patent applications cited in this specification shall be incorporated herein by reference as is.

Claims (7)

  1. 　ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を有効成分として含有する、血圧降下用組成物。 A composition for lowering blood pressure containing at least one of Termeronol A, Termeronol B and Bisacurone as an active ingredient.
  2. 　前記ターメロノールＡ、ターメロノールＢ及びビサクロンの少なくとも１種を含有する、水又は水と親水性有機溶媒との混合溶媒によるウコン抽出物を含有する、請求項１に記載の血圧降下用組成物。 The composition for lowering blood pressure according to claim 1, which contains water or a turmeric extract in a mixed solvent of water and a hydrophilic organic solvent, which contains at least one of the turmericol A, turmericol B and bisaclone.
  3. 　１日の摂取量当たり合計で２０μｇ以上のターメロノールＡ及びターメロノールＢを含有する、請求項１又は２に記載の血圧降下用組成物。 The composition for lowering blood pressure according to claim 1 or 2, which contains 20 μg or more of turmeronol A and turmeronol B in total per daily intake.
  4. 　１日の摂取量当たり１７μｇ以上のターメロノールＡを含有する、請求項１～３のいずれか１項に記載の血圧降下用組成物。 The composition for lowering blood pressure according to any one of claims 1 to 3, which contains 17 μg or more of turmeronol A per daily intake.
  5. 　１日の摂取量当たり５μｇ以上のターメロノールＢを含有する、請求項１～４のいずれか１項に記載の血圧降下用組成物。 The composition for lowering blood pressure according to any one of claims 1 to 4, which contains 5 μg or more of turmeronol B per daily intake.
  6. 　１日の摂取量当たり８０μｇ以上のビサクロンを含有する、請求項１～５のいずれか１項に記載の血圧降下用組成物。 The composition for lowering blood pressure according to any one of claims 1 to 5, which contains 80 μg or more of bisacron per daily intake.
  7. 　１日の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、請求項１～６のいずれか１項に記載の血圧降下用組成物。 The composition for lowering blood pressure according to any one of claims 1 to 6, wherein the content of curcumin per daily intake is less than 30 mg.
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