WO2019203338A1 - Composition containing turmeronol a and/or turmeronol b - Google Patents

Composition containing turmeronol a and/or turmeronol b Download PDF

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WO2019203338A1
WO2019203338A1 PCT/JP2019/016764 JP2019016764W WO2019203338A1 WO 2019203338 A1 WO2019203338 A1 WO 2019203338A1 JP 2019016764 W JP2019016764 W JP 2019016764W WO 2019203338 A1 WO2019203338 A1 WO 2019203338A1
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composition
turmeronol
intake
tureronol
present
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PCT/JP2019/016764
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French (fr)
Japanese (ja)
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晋太郎 井出
正恵 上山
直弘 向田
健吾 川▲崎▼
隆正 内尾
知夏 花房
有沙 不破
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ハウスウェルネスフーズ株式会社
ハウス食品グループ本社株式会社
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Publication of WO2019203338A1 publication Critical patent/WO2019203338A1/en

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    • 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
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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

Definitions

  • the present invention relates to compositions that are taken orally.
  • the invention also relates to an anti-inflammatory composition.
  • the present invention also relates to a composition for lowering blood CRP levels.
  • Prostaglandin E2 is produced by leukocytes (macrophages), mast cells, endothelial cells and platelets.
  • Arachidonic acid present as a component of cell membrane phospholipid is cleaved by phospholipase, and PGE2 is synthesized through a cyclooxygenase pathway. The pathway is activated in the process of inflammation, increasing the production of PGE2.
  • PGE2 released from specific cells acts on nearby target cells and induces an inflammatory reaction in the target cells.
  • PGE2 is one of chemical mediators for amplifying an inflammatory response at an inflammatory site, and activates the inflammatory response at the inflammatory site.
  • Nitric oxide is produced by type II nitric oxide synthase (iNOS) of leukocytes (macrophages) induced by inflammatory cytokines and bacterial endotoxins in the course of inflammation (Non-patent Document 1). Since excessively produced NO is converted to peroxynitrite and then shows cytotoxic effects such as DNA damage and LDL oxidation (Non-patent Document 2), excessive NO produced by inflammation can be suppressed. is important. In addition, since NO activates intracellular signal pathways that promote inflammation such as the NF- ⁇ B pathway (Non-patent Document 3), suppressing NO production is also important for exerting an anti-inflammatory effect ( Patent Document 1).
  • Inflammation is a protective reaction that is caused by stimulating factors such as infectious diseases, trauma, and foreign substances, and tries to eliminate self cells and tissues necrotized by the stimulating factor together with the stimulating factor itself.
  • the inflammatory response helps remove harmful stimuli, including infections.
  • inflammation can also damage normal tissues, it may cause damage to the living body, and it is necessary to suppress an excessive inflammatory reaction.
  • Patent Document 2 Examples of PGE2 production inhibitors and anti-inflammatory agents containing natural compounds as active ingredients include those described in Patent Document 2. Further, in Patent Document 1, a mixture of soybean seeds or an extract thereof and chlorophyll activated by light irradiation treatment and / or heat treatment has an activity of suppressing NO production and is useful as an anti-inflammatory agent. It is described that there is.
  • turmeric contains a large number of sesquiterpene compounds, and as a turmeric-derived sesquiterpene compound, a large number of bisaborane compounds such as tureronol A (Turmeronol A) and turmeronol B (Turmeronol B) are known.
  • a turmeric-derived sesquiterpene compound a large number of bisaborane compounds such as tureronol A (Turmeronol A) and turmeronol B (Turmeronol B) are known. (Non-Patent Document 4).
  • Patent Document 3 describes that turmeric rhizomes themselves, polysaccharides and essential oils in turmeric have anti-inflammatory effects.
  • Patent Document 3 further discloses that the active ingredient of turmeric can be divided into an essential oil fraction, a curcuminoid fraction, a turmerin fraction, and a polysaccharide fraction.
  • the essential oil fraction turmeronol A (turmeronol A) and turmeronol B are used together with turmer. It is described that (turmeronol B) is contained, and the essential oil fraction of turmeric rhizome can be extracted by a supercritical carbon dioxide extraction technique.
  • turmeric contains tureronol A and tureronol B as described in Non-Patent Document 4 and Patent Document 3, the effect of turmonol A and turmonol B itself was not clear.
  • Patent Document 3 quantification of turmeronol A and tureronol B in the turmeric extract is not performed.
  • An object of the present invention is to provide a composition having an anti-inflammatory action or a blood CRP value lowering action, which includes a compound derived from a food material rich in food experience and highly safe.
  • the present inventors have a composition containing at least one of turmeronol A and turmeronol B in a total amount of 100 ⁇ g or more, and a composition containing 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per one intake.
  • the product has been found to have an anti-inflammatory action or a blood CRP value lowering action, and has led to the completion of the present invention described below.
  • compositions that is orally ingested and contains 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per intake are derived from a turmeric extract.
  • An anti-inflammatory composition comprising at least one of tureronol A and turmeronol B in a total amount of 100 ⁇ g or more per one intake.
  • a composition for lowering CRP levels in blood comprising at least one of turmeronol A and turmeronol B in a total amount of 100 ⁇ g or more per one intake.
  • An anti-inflammatory composition comprising 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per intake.
  • a composition for lowering the CRP level in blood comprising 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per intake.
  • a composition comprising at least one of turmeronol A and turmeronol B in a total amount of 100 ⁇ g or more per intake for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
  • (15) The use according to (9), the use according to (10), the method according to (11), or the composition according to (12), wherein the composition is taken orally.
  • a composition comprising 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per dose for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
  • the “patient” is a human or non-human animal, preferably a human.
  • composition comprising a compound derived from a food material rich in food experience and having a high safety, and having an anti-inflammatory action or a blood CRP value lowering action.
  • FIG. 1 shows the PGE2 concentration in the culture supernatant of RAW264.7 treated with turmeronol A.
  • FIG. 2 shows the concentration of PGE2 in the culture supernatant of RAW 264.7 treated with tureronol B.
  • FIG. 3 shows the NO 2 ⁇ concentration in the culture supernatant of RAW 264.7 treated with tureronol A.
  • FIG. 4 shows the NO 2 ⁇ concentration in the culture supernatant of RAW 264.7 treated with tureronol B.
  • FIG. 1 shows the PGE2 concentration in the culture supernatant of RAW264.7 treated with turmeronol A.
  • FIG. 2 shows the concentration of PGE2 in the culture supernatant of RAW 264.7 treated with tureronol B.
  • FIG. 3 shows the NO 2 ⁇ concentration in the culture supernatant of RAW 264.7 treated with tureronol A.
  • FIG. 4 shows the NO 2 ⁇ concentration in the culture supernatant of
  • Tameronol A and Tameronol B are compounds having the following planar structures, respectively.
  • tureronol A and turmeronol B are known to have S-configuration at the 6-position carbon in the partial structure of 2-methyl-2-hepten-4-one. is there.
  • tereronol A and tereronol B only have to have the above-described planar structure, and the configuration may be S-form, R-form, S-form and R-form. And a mixture thereof.
  • turmonol A and / or turmonol B is preferably turmonol A and / or turmonol B derived from a turmeric extract.
  • turmonol A and / or turmonol B derived from the turmeric extract may be turmonol A and / or turmonol B separated from the turmeric extract, or turmonol A existing as a component in the turmeric extract.
  • / or tureronol B is preferably turmonol A and / or turmonol B derived from a turmeric extract.
  • turmonol A and / or turmonol B derived from the turmeric extract may be turmonol A and / or turmonol B separated from the turmeric extract, or turmonol A existing as a component in the turmeric extract.
  • / or tureronol B may be turmonol A and / or turmonol B separated from the turmeric extract.
  • the turmeric extract refers to an extract (turmeric extract) of a plant raw material derived from a plant belonging to the genus Turmeric belonging to the ginger family.
  • the turmeric extract is not limited to the solvent extract obtained by extraction with an extraction solvent, but also includes those obtained by further fractionating and purifying the solvent extract by column chromatography or the like.
  • the turmeric extract used in the present invention is obtained from an extract obtained by completing the extraction operation (including fraction purification in the case of fraction purification), a concentrate obtained by partially removing the solvent from the extract, or an extract. It can be in the form of a dry product from which the solvent has been removed.
  • the removal of the solvent from the extract can be performed by volatilizing the solvent by heating and / or reduced pressure. These heating and decompression methods are not particularly limited, and for example, conventionally known methods can be used.
  • plant raw materials examples include Curcuma longa (turmeric), Curcuma aromatica, Curcuma zedoaria, Curcuma phaeocaulis, Curcuma kwangsiens, Curcuminc, and Curcumacurium.
  • a Curcuma longa rhizome is preferred. As the rhizome, one collected from soil may be used, and an appropriate portion of the rhizome may be used as it is, cut into an appropriate size or shape, or pulverized. These plant materials may be appropriately dried.
  • the extraction solvent include at least one selected from the group consisting of water and a hydrophilic organic solvent, a liquid solvent such as hexane, water vapor, and a supercritical fluid.
  • the at least one extraction solvent selected from the group consisting of water and a hydrophilic organic solvent may be any of water, a hydrophilic organic solvent, and a mixed solvent of water and a hydrophilic organic solvent.
  • the hydrophilic organic solvent may be a mixed solvent of plural kinds of hydrophilic organic solvents.
  • Water includes hot water. As hot water, for example, hot water 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 in the case of using a mixed solvent of alcohol and water as the extraction solvent is not particularly limited. For example, the weight ratio is preferably in the range of 10:90 to 90:10, and more preferably in the range of 20:80 to 50:50. .
  • Extraction using steam is also called steam distillation.
  • Supercritical carbon dioxide is preferred as the supercritical fluid.
  • ethanol, hexane or supercritical fluid is preferable to use ethanol, hexane or supercritical fluid as the extraction solvent.
  • Curcumin contained in turmeric is a kind of curcuminoid.
  • the international organization JECFA FAO / WHO Joint Expert Committee on Food Additives
  • ADI permisible daily intake
  • curcuminoids 3 mg / kg body weight / day (eg, 150 mg per day for a person with a body weight of 50 kg). Therefore, when using turmeronol A and / or turmonol B in the form of a turmeric extract, it is preferable to use a turmeric extract containing turmonol A and / or turmonol B and having a low curcuminoid concentration.
  • water particularly hot water
  • hexane water vapor or a supercritical fluid
  • the method for preparing the turmeric extract using the extraction solvent is not particularly limited.
  • Turmonol A and / or turmonol B may be used in the form of a plant material containing it.
  • the plant raw material containing turmonol A and / or turmonol B include the raw materials of the ginger family turmeric genus described above.
  • the rhizome of the ginger family turmeric genus plant contains both iron and turmeronol A and / or turmonol B relatively. Ingestion of large amounts of iron may adversely affect people with specific symptoms such as hepatitis C patients and NASH (non-alcoholic steatohepatitis), so the recommended upper limit of iron intake is 1 6 mg per day. For this reason, it is preferable that turmeronol A and / or turmeronol B are forms other than the rhizome form of the ginger family turmeric genus plant.
  • the composition of the present invention contains at least one of turmeronol A and turmeronol B in a total amount of 100 ⁇ g or more per one intake.
  • the content of one of them may be 100 ⁇ g or more per one intake.
  • the total content of both is included, it may be 100 ⁇ g or more per one intake.
  • the composition according to the first aspect has an action of suppressing inflammation, particularly chronic inflammation, and an action of reducing CRP (c-reactive protein) level in blood when ingested by animals such as humans. Played.
  • the composition according to the first aspect comprises a total of 100 ⁇ g or more of turmeronol A and turmeronol B per intake, and more preferably 80 ⁇ g or more of turmeronol per intake.
  • the composition of the present invention contains 80 ⁇ g or more of turmeronol A and / or 20 ⁇ g or more of turmeronol B per one intake.
  • the composition according to the second aspect has an action of suppressing inflammation, particularly chronic inflammation, and an action of reducing the CRP (c-reactive protein) level in blood when ingested by animals such as humans. Played.
  • the composition according to the second aspect contains 80 ⁇ g or more of turmeronol A and 20 ⁇ g or more of turmeronol B per serving.
  • the method for quantifying tureronol A and tureronol B is not particularly limited, and can be performed, for example, by LC / MS analysis shown in Examples.
  • the tereronol A and / or the turmeronol B is added to the tereronol A and / or tereronol B at the time of completion of production, that is, at the stage of shipment of the production factory as a finished product. It only has to be included in the range.
  • the composition according to the first aspect or the second aspect of the present invention has a curcumin content per intake of less than 30 mg.
  • Compositions with a curcumin content of less than 30 mg per dose will reduce inflammation and blood CRP without exceeding the curcuminoid ADI (permissible daily intake) (150 mg for a 50 kg person). Since it is easy to ingest an amount of turmeronol A and / or turmeronol B effective for lowering the value, it is preferable.
  • a single intake means an amount at which the composition of the present invention is ingested at a time, or continuously over a short time interval (for example, 10 minutes or less, preferably 5 minutes or less). This means the total amount taken multiple times.
  • composition of the present invention is in the form of a liquid or fluid composition
  • 0.1 ml to 500 ml typically 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 300 ml, 350 ml, 400 ml, 450 ml or 500 ml
  • 0.1 g to 500 g typically 50 g, 100 g, 150 g, 200 g, 250 g, 300g, 350g, 400g, 450g or 500g
  • “one intake” is used in this sense.
  • compositions taken orally In a preferred embodiment, the composition according to the first aspect or the second aspect of the present invention is a composition to be taken orally.
  • composition that is orally ingested according to the present invention exhibits preferable effects such as suppression of inflammation and reduction of blood CRP value when animals such as humans are orally ingested.
  • composition to be orally ingested according to the present invention may be a composition in various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, etc. It is more preferable.
  • the foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like.
  • the orally ingested composition of the present invention may be continuously ingested, or may be ingested when necessary.
  • composition according to the first aspect or the second aspect of the present invention is an anti-inflammatory composition.
  • the anti-inflammatory composition of the present invention is useful for the prevention or treatment of inflammation, particularly chronic inflammation, in animals such as humans.
  • Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of an anti-inflammatory composition.
  • Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of an anti-inflammatory drug.
  • Yet another embodiment of the present invention provides: Administering the composition according to the first aspect or the second aspect of the present invention to a patient in need of treatment or prevention of inflammation, and treating or preventing inflammation in the patient, A method of treating or preventing inflammation.
  • composition according to the first aspect or the second aspect of the present invention for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
  • the anti-inflammatory composition, or the composition or pharmaceutical used for the treatment or prevention of inflammation is a composition in various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives and the like. It may be a medicine or a food or drink taken by a human.
  • the foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like.
  • the anti-inflammatory composition or the composition or medicament used for the treatment or prevention of inflammation is preferably in the form of a composition taken orally or nasally, more preferably taken orally. In the form of a composition.
  • the anti-inflammatory composition, or the composition or medicament used for the treatment or prevention of inflammation may be ingested continuously or may be ingested when necessary. Good.
  • the anti-inflammatory composition or the specific form of the composition or medicament used for the treatment or prevention of inflammation will be described later.
  • composition according to the first aspect or the second aspect of the present invention is a composition for lowering the blood CRP value.
  • composition for lowering the blood CRP level of the present invention has the effect of lowering the blood CRP (c-reactive protein) level, which is an indicator of inflammation, particularly chronic inflammation, in animals such as humans.
  • CRP c-reactive protein
  • the blood CRP value is also an index of risk other than inflammation, for example, risk of cardiovascular disease such as arteriosclerosis.
  • CRP is known to be related to exacerbation of arteriosclerosis, and blood CRP measurement is used for predicting the risk of cardiovascular disease.
  • the composition having a blood CRP level lowering action can be used not only for the treatment or prevention of inflammation but also for the treatment or prevention of cardiovascular disease.
  • Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the production of a composition for lowering blood CRP levels.
  • Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of a medicament for lowering the blood CRP value.
  • Yet another embodiment of the present invention provides: Administering the composition according to the first aspect or the second aspect of the present invention to a patient in need of lowering the blood CRP value, and lowering the blood CRP value in the patient; And a method for lowering the CRP level in blood.
  • composition according to the first aspect or the second aspect of the present invention for lowering blood CRP level in a patient in need of lowering blood CRP level.
  • the composition for lowering the blood CRP value, or the composition or medicine used for lowering the blood CRP value includes compositions of various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, etc. It may be a thing, and it is more preferable that it is a pharmaceutical or food or drink taken by humans.
  • the foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like.
  • the composition for lowering the blood CRP value, or the composition or medicament used for lowering the blood CRP value is preferably in the form of a composition taken orally or nasally, more preferably. In the form of a composition to be taken orally.
  • the composition for lowering the blood CRP value, or the composition or medicament used for lowering the blood CRP value may be taken continuously or taken as needed. There may be.
  • composition for lowering the blood CRP value or the specific form of the composition or medicament used for lowering the blood CRP value will be described later.
  • composition of the present invention is an anti-inflammatory composition, composition for lowering blood CRP level, composition or medicine used for treatment or prevention of inflammation, or used for lowering blood CRP level
  • the composition or medicine may be the active ingredient itself (turmeronol A and / or turmeronol B, or a turmeric extract containing the active ingredient).
  • it may be a composition containing the active ingredient and at least one other ingredient.
  • the composition of the present invention contains the active ingredient and at least one other component
  • the composition may be a mixture of the active ingredient and at least one other component
  • a composition in which the active ingredient and at least one other ingredient are formulated by an appropriate means may be used, or a formulation in which the active ingredient and at least one other ingredient are formulated. Further, it may be a composition mixed with other components.
  • 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.
  • the at least one other component that can be contained in the composition of the present invention is not particularly limited, but is preferably acceptable in a final form such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, and the like. Examples of such components that can be taken orally can be exemplified.
  • Such other components include sweeteners, acidulants, vitamins, minerals, thickeners, emulsifiers, antioxidants, and water.
  • Sweeteners include monosaccharides and disaccharides such as glucose, fructose, sucrose, lactose, maltose, palatinose, trehalose, and xylose, isomerized sugar (glucose fructose liquid sugar, fructose glucose liquid sugar, sugar mixed isomerized sugar, etc.) Sugar alcohols (erythritol, xylitol, lactitol, palatinit, sorbitol, reduced starch syrup, etc.), honey, high intensity sweeteners (sucralose, acesulfame potassium, thaumatin, stevia, aspartame, etc.).
  • sour agent 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, karaya gum, agar, gelatin, pectin, soybean polysaccharide, carboxymethylcellulose (CMC) and the like.
  • emulsifier examples include glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, lecithin, vegetable sterol, and saponin.
  • antioxidants examples include vitamin C, tocopherol (vitamin E), enzyme-treated rutin, catechin and the like.
  • compositions such as foods and drinks and pharmaceuticals.
  • composition forms in which the active ingredient and at least one other ingredient are formulated by appropriate means are powders, granules, capsules, tablets (coated tablets such as sugar-coated tablets or multilayer tablets, mouth disintegrants, chewables) It may be in the form of a solid composition such as a tablet or the like, or it may be in the form of a liquid composition such as a solution.
  • the structure of isolated turomerol A is based on the results of instrumental analysis such as 1 H NMR, 13 C NMR, LCMS, and known information (Agric. Biol. Chem., 1990; 54 (9): 2367-71). Identified.
  • Termelonol B was purchased from Nagara Science Co., Ltd., dissolved in dimethyl sulfoxide, and used for the test.
  • the mouse macrophage cell line RAW264.7 was used for the experiment, seeded in a 96-well plate with DMEM (10% FBS) medium to a number of 1.5 ⁇ 10 5 cells, and CO 2 incubator for 24 hours. Incubated until confluent.
  • the mouse macrophage cell line RAW264.7 cultured in a 96-well plate was selected from predetermined concentrations (1.7 ⁇ g / mL, 3.2 ⁇ g / mL, 6.3 ⁇ g / mL, 12.5 ⁇ g / mL, and 25 ⁇ g / mL).
  • LPS lipopolysaccharide
  • control / LPS (+) is the test group in which the same operation is performed except that the cells are not treated with tureronol A or tureronol B, and the same operation as control / LPS (+) is performed except that LPS is not added to the medium during the 12-hour culture.
  • the test group where the test was performed was defined as control / LPS ( ⁇ ).
  • Test food Tablets ingested by subjects in the turmeric extract intake group were prepared using the above-mentioned turmeric extract, maltose, fine silicon dioxide, sucrose fatty acid ester, and brightener.
  • the amount of turmeronol A and turmeronol B in this tablet was measured using LC / MS according to the procedure described later.
  • the amount of curcumin in the tablet was measured using HPLC according to the procedure described later.
  • the single dose (3 tablets) of one subject of this tablet contained 86.5 ⁇ g of turmeronol A, 24.7 ⁇ g of turmeronol B, and 471 ⁇ g of curcumin.
  • Tablets taken by subjects in the placebo intake group were prepared using maltose, pigment, fine silicon dioxide, sucrose fatty acid ester, and brightener.
  • turmeric extract intake group and the placebo intake group consists of 45 subjects who satisfy the following conditions. Men and women aged 50 to 69 years BMI is normally high to obese 1 degree (BMI: 23 to less than 30), or blood pressure is normal blood pressure to I degree hypertension (systolic blood pressure: 120 mmHg to 160 mmHg, or Diastolic blood pressure: 80mmHg or more and less than 100mmHg) A certain number was selected.
  • Placebo-controlled double-blind parallel group comparison study 45 subjects in the turmeric extract intake group orally ingested 3 tablets containing the turmeric extract daily for 12 weeks before dinner.
  • the turmeric extract intake group 2 subjects during the 12-week study became dropouts or exclusion criteria subjects and 43 completed the study.
  • the blood CRP (c-reactive protein) value of each subject was measured to obtain an average value.
  • the blood CRP value was measured by the nephelometry method and the latex agglutination turbidimetry.
  • the measurement by the neferometry method was performed according to the N-latex CRP II kit of Siemens Healthcare Diagnostics.
  • the measurement by latex agglutination turbidimetry was carried out according to the Iatro CRP-EX kit of LSI Rulece.
  • the present invention is useful in the field of food and drink or pharmaceuticals.

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  • Medicines Containing Plant Substances (AREA)

Abstract

The present invention provides a composition having an anti-inflammatory action or a blood CRP value-lowering action, that contains a compound derived from a food material which is highly safe and has a long history of use as a food. The present invention relates to a composition to be taken orally, an anti-inflammatory composition, or a composition for lowering the blood CRP value that contains 100 μg or more of turmeronol A and/or turmeronol B total per intake. The present invention also relates to a composition to be taken orally, an anti-inflammatory composition, or a composition for lowering the blood CRP value that contains 80 μg or more of turmeronol A and/or 20 μg or more of turmeronol B per intake.

Description

ターメロノールＡ及び／又はターメロノールＢを含有する組成物Composition containing tureronol A and / or tureronol B
　本発明は、経口摂取される組成物に関する。
　本発明はまた、抗炎症用組成物に関する。
　本発明はまた、血中ＣＲＰ値低下用組成物に関する。 The present invention relates to compositions that are taken orally.
The invention also relates to an anti-inflammatory composition.
The present invention also relates to a composition for lowering blood CRP levels.
　プロスタグランジンＥ２（ＰＧＥ２）は、白血球（マクロファージ）、肥満細胞、内皮細胞および血小板などで産生される。細胞膜リン脂質の構成成分として存在するアラキドン酸が、ホスホリパーゼによって切り出され、シクロオキシゲナーゼ経路を経て、ＰＧＥ２が合成される。炎症の過程において同経路が活性化し、ＰＧＥ２の産生が増加する。 Prostaglandin E2 (PGE2) is produced by leukocytes (macrophages), mast cells, endothelial cells and platelets. Arachidonic acid present as a component of cell membrane phospholipid is cleaved by phospholipase, and PGE2 is synthesized through a cyclooxygenase pathway. The pathway is activated in the process of inflammation, increasing the production of PGE2.
　特定の細胞から放出されたＰＧＥ２は近傍の標的細胞に作用し、標的細胞における炎症反応を誘導する。ＰＧＥ２は、炎症部位において炎症反応を増幅させるための化学的メディエーターのひとつであり、炎症部位における炎症反応を活性化する。 ¡PGE2 released from specific cells acts on nearby target cells and induces an inflammatory reaction in the target cells. PGE2 is one of chemical mediators for amplifying an inflammatory response at an inflammatory site, and activates the inflammatory response at the inflammatory site.
　一酸化窒素（ＮＯ）は、炎症の過程において、炎症性サイトカインや細菌エンドトキシンにより誘導された白血球（マクロファージ）のＩＩ型一酸化窒素合成酵素（ｉＮＯＳ）により産生される（非特許文献１）。過剰に産生されたＮＯは、ペルオキシ亜硝酸に変換された後、ＤＮＡの障害やＬＤＬの酸化などの細胞障害作用を示す（非特許文献２）ので、炎症で生じる過剰なＮＯを抑制することが重要である。またＮＯは、ＮＦ－κＢ経路などの炎症を促進する細胞内シグナル経路を活性化する（非特許文献３）ことから、ＮＯ産生を抑制することは抗炎症作用を発揮する上でも重要である（特許文献１）。 Nitric oxide (NO) is produced by type II nitric oxide synthase (iNOS) of leukocytes (macrophages) induced by inflammatory cytokines and bacterial endotoxins in the course of inflammation (Non-patent Document 1). Since excessively produced NO is converted to peroxynitrite and then shows cytotoxic effects such as DNA damage and LDL oxidation (Non-patent Document 2), excessive NO produced by inflammation can be suppressed. is important. In addition, since NO activates intracellular signal pathways that promote inflammation such as the NF-κB pathway (Non-patent Document 3), suppressing NO production is also important for exerting an anti-inflammatory effect ( Patent Document 1).
　炎症は感染症、外傷、異物などの刺激因子によって惹起され、刺激因子そのものとともに、刺激因子によって壊死した自己の細胞・組織を排除しようとする防御反応である。炎症反応は、感染をはじめとする有害刺激の除去を助ける。一方で炎症は、正常組織を損傷することもできるので、逆に生体に損害をもたらすことがあり、過剰な炎症反応を抑制することが必要である。 Inflammation is a protective reaction that is caused by stimulating factors such as infectious diseases, trauma, and foreign substances, and tries to eliminate self cells and tissues necrotized by the stimulating factor together with the stimulating factor itself. The inflammatory response helps remove harmful stimuli, including infections. On the other hand, since inflammation can also damage normal tissues, it may cause damage to the living body, and it is necessary to suppress an excessive inflammatory reaction.
　天然化合物を有効成分として含むＰＧＥ２産生抑制剤及び抗炎症剤としては、例えば、特許文献２に記載されたものがある。また、特許文献１では、光照射処理及び／又は加熱処理により活性化された、大豆種子又はその抽出物とクロロフィルとの混合物が、ＮＯ産生を抑制する活性を有し、抗炎症剤として有用であることが記載されている。 Examples of PGE2 production inhibitors and anti-inflammatory agents containing natural compounds as active ingredients include those described in Patent Document 2. Further, in Patent Document 1, a mixture of soybean seeds or an extract thereof and chlorophyll activated by light irradiation treatment and / or heat treatment has an activity of suppressing NO production and is useful as an anti-inflammatory agent. It is described that there is.
　一方、ウコン（Ｃｕｒｃｕｍａ　ｌｏｎｇａ）には、多数のセスキテルペン化合物が含まれており、ウコン由来のセスキテルペン化合物として、ターメロノールＡ（Ｔｕｒｍｅｒｏｎｏｌ　Ａ）、ターメロノールＢ（Ｔｕｒｍｅｒｏｎｏｌ　Ｂ）等の多数のビサボラン化合物が知られている（非特許文献４）。 On the other hand, turmeric (Curcuma longa) contains a large number of sesquiterpene compounds, and as a turmeric-derived sesquiterpene compound, a large number of bisaborane compounds such as tureronol A (Turmeronol A) and turmeronol B (Turmeronol B) are known. (Non-Patent Document 4).
　特許文献３には、ウコン根茎そのもの、ウコン中の多糖類、精油に抗炎症作用があることが記載されている。特許文献３には更に、ウコンの有効成分は精油画分、クルクミノイド画分、ターメリン画分、多糖類画分に分けることができること、精油画分にはターメロンとともにツルメロノールＡ（ターメロノールＡ）、ツルメロノールＢ（ターメロノールＢ）が含まれること、ウコン根茎の精油画分は超臨界二酸化炭素抽出技術によって抽出できることが記載されている。 Patent Document 3 describes that turmeric rhizomes themselves, polysaccharides and essential oils in turmeric have anti-inflammatory effects. Patent Document 3 further discloses that the active ingredient of turmeric can be divided into an essential oil fraction, a curcuminoid fraction, a turmerin fraction, and a polysaccharide fraction. In the essential oil fraction, turmeronol A (turmeronol A) and turmeronol B are used together with turmer. It is described that (turmeronol B) is contained, and the essential oil fraction of turmeric rhizome can be extracted by a supercritical carbon dioxide extraction technique.
国際公開ＷＯ２０１２／１７７９６９International Publication WO2012 / 177969 特開２０１２－０５６９５２号公報JP 2012-056852 A 特表２００９－５３０３０５号公報Special table 2009-530305 gazette
　ウコンがターメロノールＡ及びターメロノールＢを含有することは、非特許文献４、特許文献３に記載の通り従来から知られているが、ターメロノールＡ及びターメロノールＢ自体の作用効果は明らかではなかった。また、特許文献３ではウコン抽出物中でのターメロノールＡ及びターメロノールＢの定量は行われていない。 Although it has been conventionally known that turmeric contains tureronol A and tureronol B as described in Non-Patent Document 4 and Patent Document 3, the effect of turmonol A and turmonol B itself was not clear. In Patent Document 3, quantification of turmeronol A and tureronol B in the turmeric extract is not performed.
　本発明は、食経験が豊富で安全性の高い食品素材に由来する化合物を含み、抗炎症作用又は血中ＣＲＰ値低下作用を有する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 having an anti-inflammatory action or a blood CRP value lowering action, which includes a compound derived from a food material rich in food experience and highly safe.
　本発明者らは、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物、及び、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物が、抗炎症作用又は血中ＣＲＰ値低下作用を有することを見出し、以下の本発明を完成するに至った。
（１）経口摂取される組成物であって、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、組成物。
（２）経口摂取される組成物であって、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、組成物。
（３）前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、（１）又は（２）に記載の組成物。
（４）１回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）～（３）のいずれかに記載の組成物。
（５）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、抗炎症用組成物。
（６）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、血中ＣＲＰ値低下用組成物。
（７）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、抗炎症用組成物。
（８）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、血中ＣＲＰ値低下用組成物。 The present inventors have a composition containing at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more, and a composition containing 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake. The product has been found to have an anti-inflammatory action or a blood CRP value lowering action, and has led to the completion of the present invention described below.
(1) A composition that is orally ingested and contains at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake.
(2) A composition that is orally ingested and contains 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per intake.
(3) The composition according to (1) or (2), wherein the turmonol A and the turmonol B are derived from a turmeric extract.
(4) The composition according to any one of (1) to (3), wherein the curcumin content per intake is less than 30 mg.
(5) An anti-inflammatory composition comprising at least one of tureronol A and turmeronol B in a total amount of 100 μg or more per one intake.
(6) A composition for lowering CRP levels in blood, comprising at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake.
(7) An anti-inflammatory composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per intake.
(8) A composition for lowering the CRP level in blood, comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per intake.
（９）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物の、抗炎症用組成物の製造のための使用。
（１０）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物の、抗炎症用医薬の製造のための使用。
（１１）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物を、炎症の治療又は予防を必要とする患者に投与すること、及び
　前記患者において炎症を治療又は予防すること
を含む、炎症を治療又は予防する方法。
（１２）炎症の治療又は予防を必要とする患者において炎症を治療又は予防するための、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物。
（１３）前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、（９）に記載の使用、（１０）に記載の使用、（１１）に記載の方法、又は、（１２）に記載の組成物。
（１４）前記組成物での、１回の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、（９）に記載の使用、（１０）に記載の使用、（１１）に記載の方法、又は、（１２）に記載の組成物。
（１５）前記組成物が経口摂取される、（９）に記載の使用、（１０）に記載の使用、（１１）に記載の方法、又は、（１２）に記載の組成物。 (9) Use of a composition containing at least one of tereronol A and tereronol B in a total amount of 100 μg or more per one intake for the production of an anti-inflammatory composition.
(10) Use of a composition comprising at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake for production of an anti-inflammatory drug.
(11) administering a composition containing at least one of turmeronol A and turmeronol B to a patient in need of treatment or prevention of inflammation per total intake of 100 μg or more, and inflammation in the patient A method of treating or preventing inflammation, comprising treating or preventing.
(12) A composition comprising at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per intake for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
(13) The use according to (9), the use according to (10), the method according to (11), or the method according to (12), wherein the turmonol A and the turmonol B are derived from a turmeric extract. Composition.
(14) The use according to (9), the use according to (10), the method according to (11), wherein the curcumin content per ingestion in the composition is less than 30 mg, Or the composition as described in (12).
(15) The use according to (9), the use according to (10), the method according to (11), or the composition according to (12), wherein the composition is taken orally.
（１６）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物の、血中ＣＲＰ値低下用組成物の製造のための使用。
（１７）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物の、血中ＣＲＰ値低下用医薬の製造のための使用。
（１８）１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物を、血中ＣＲＰ値の低下を必要とする患者に投与すること、及び
　前記患者において血中ＣＲＰ値を低下させること
を含む、血中ＣＲＰ値を低下させる方法。
（１９）血中ＣＲＰ値の低下を必要とする患者において血中ＣＲＰ値の低下させるための、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む組成物。
（２０）前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、（１６）に記載の使用、（１７）に記載の使用、（１８）に記載の方法、又は、（１９）に記載の組成物。
（２１）前記組成物での、１回の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、（１６）に記載の使用、（１７）に記載の使用、（１８）に記載の方法、又は、（１９）に記載の組成物。
（２２）前記組成物が経口摂取される、（１６）に記載の使用、（１７）に記載の使用、（１８）に記載の方法、又は、（１９）に記載の組成物。 (16) Use of a composition containing at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake for the production of a composition for lowering CRP levels in blood.
(17) Use of a composition containing at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake for the production of a medicine for lowering blood CRP level.
(18) administering a composition containing at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more to a patient in need of a decrease in blood CRP value per one intake; A method for lowering a blood CRP value, comprising lowering a blood CRP value.
(19) A composition comprising at least one of tureronol A and turmeronol B in a total amount of 100 μg or more per intake, for lowering blood CRP level in a patient in need of lowering blood CRP level .
(20) The use according to (16), the use according to (17), the method according to (18), or the method according to (19), wherein the turmonol A and the turmonol B are derived from a turmeric extract Composition.
(21) The use according to (16), the use according to (17), the method according to (18), wherein the curcumin content per ingestion in the composition is less than 30 mg, Or the composition as described in (19).
(22) The use according to (16), the use according to (17), the method according to (18), or the composition according to (19), wherein the composition is taken orally.
（２３）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物の、抗炎症用組成物の製造のための使用。
（２４）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物の、抗炎症用医薬の製造のための使用。
（２５）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物を、炎症の治療又は予防を必要とする患者に投与すること、及び
　前記患者において炎症を治療又は予防すること
を含む、炎症を治療又は予防する方法。
（２６）炎症の治療又は予防を必要とする患者において炎症を治療又は予防するための、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物。
（２７）前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、（２３）に記載の使用、（２４）に記載の使用、（２５）に記載の方法、又は、（２６）に記載の組成物。
（２８）前記組成物での、１回の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、（２３）に記載の使用、（２４）に記載の使用、（２５）に記載の方法、又は、（２６）に記載の組成物。
（２９）前記組成物が経口摂取される、（２３）に記載の使用、（２４）に記載の使用、（２５）に記載の方法、又は、（２６）に記載の組成物。 (23) Use of a composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake for the production of an anti-inflammatory composition.
(24) Use of a composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake for production of an anti-inflammatory drug.
(25) administering a composition comprising 80 μg or more of tureronol A and / or 20 μg or more of turmeronol B to a patient in need of treatment or prevention of inflammation per ingestion; and inflammation in the patient A method of treating or preventing inflammation, comprising treating or preventing.
(26) A composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per dose for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
(27) The use according to (23), the use according to (24), the method according to (25), or the method according to (26), wherein the turmonol A and the turmonol B are derived from a turmeric extract Composition.
(28) The use according to (23), the use according to (24), the method according to (25), wherein the content of curcumin per ingestion in the composition is less than 30 mg, Or the composition as described in (26).
(29) The use according to (23), the use according to (24), the method according to (25), or the composition according to (26), wherein the composition is taken orally.
（３０）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物の、血中ＣＲＰ値低下用組成物の製造のための使用。
（３１）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物の、血中ＣＲＰ値低下用医薬の製造のための使用。
（３２）１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物を、血中ＣＲＰ値の低下を必要とする患者に投与すること、及び
　前記患者において血中ＣＲＰ値を低下させること
を含む、血中ＣＲＰ値を低下させる方法。
（３３）血中ＣＲＰ値の低下を必要とする患者において血中ＣＲＰ値の低下させるための、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む組成物。
（３４）前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、（３０）に記載の使用、（３１）に記載の使用、（３２）に記載の方法、又は、（３３）に記載の組成物。
（３５）前記組成物での、１回の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である、（３０）に記載の使用、（３１）に記載の使用、（３２）に記載の方法、又は、（３３）に記載の組成物。
（３６）前記組成物が経口摂取される、（３０）に記載の使用、（３１）に記載の使用、（３２）に記載の方法、又は、（３３）に記載の組成物。 (30) Use of a composition containing 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake for production of a composition for lowering the CRP level in blood.
(31) Use of a composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake for the production of a medicament for lowering the CRP level in blood.
(32) administering a composition containing 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B to a patient in need of a decrease in blood CRP value per ingestion; A method for lowering a blood CRP value, comprising lowering a medium CRP value.
(33) A composition comprising 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B for each intake, for lowering the blood CRP value in a patient who needs to lower the blood CRP value.
(34) The use according to (30), the use according to (31), the method according to (32), or the method according to (33), wherein the turmonol A and the turmonol B are derived from a turmeric extract. Composition.
(35) The use according to (30), the use according to (31), the method according to (32), wherein the curcumin content per intake in the composition is less than 30 mg, Or the composition as described in (33).
(36) The use according to (30), the use according to (31), the method according to (32), or the composition according to (33), wherein the composition is taken orally.
　本発明の一以上の実施形態において「患者」とはヒト又は非ヒト動物であり、好ましくはヒトである。 In one or more embodiments of the present invention, the “patient” is a human or non-human animal, preferably a human.
　本明細書は本願の優先権の基礎となる日本国特許出願番号２０１８－０８１７００号の開示内容を包含する。 This specification includes the disclosure of Japanese Patent Application No. 2018-081700, which is the basis of the priority of the present application.
　本発明によれば、食経験が豊富で安全性の高い食品素材に由来する化合物を含み、抗炎症作用又は血中ＣＲＰ値低下作用を有する組成物が提供される。 According to the present invention, there is provided a composition comprising a compound derived from a food material rich in food experience and having a high safety, and having an anti-inflammatory action or a blood CRP value lowering action.
図１は、ターメロノールＡにより処理したＲＡＷ２６４．７の培養上清中のＰＧＥ２濃度を示す。FIG. 1 shows the PGE2 concentration in the culture supernatant of RAW264.7 treated with turmeronol A. 図２は、ターメロノールＢにより処理したＲＡＷ２６４．７の培養上清中のＰＧＥ２濃度を示す。FIG. 2 shows the concentration of PGE2 in the culture supernatant of RAW 264.7 treated with tureronol B. 図３は、ターメロノールＡにより処理したＲＡＷ２６４．７の培養上清中のＮＯ２ －濃度を示す。FIG. 3 shows the NO 2 − concentration in the culture supernatant of RAW 264.7 treated with tureronol A. 図４は、ターメロノールＢにより処理したＲＡＷ２６４．７の培養上清中のＮＯ２ －濃度示す。FIG. 4 shows the NO 2 − concentration in the culture supernatant of RAW 264.7 treated with tureronol B. 図５は、ターメロノールＡ及びターメロノールＢを含むウコン抽出物を含む錠剤を１２週間毎日摂取した被験者群と、プラセボ錠剤を１２週間毎日摂取した被験者群の、試験開始前、４週間後、８週間後、１２週間後の血中のＣＲＰ値の平均値を示す。FIG. 5 shows a group of subjects who took a tablet containing turmeric extract containing tureronol A and turmeronol B every day for 12 weeks and a group of subjects who took a placebo tablet every day for 12 weeks before the start of the study, 4 weeks and 8 weeks later. The average value of the CRP value in the blood after 12 weeks is shown.
＜有効成分＞
　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。 <Active ingredient>
Tameronol A and Tameronol 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
　なお、ウコン抽出物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体であることが公知である。しかし、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 product separated from the turmeric extract, tureronol A and turmeronol B are known to have S-configuration at the 6-position carbon in the partial structure of 2-methyl-2-hepten-4-one. is there. However, in the present invention, tereronol A and tereronol B only have to have the above-described planar structure, and the configuration may be S-form, R-form, S-form and R-form. And a mixture thereof.
　本発明において、ターメロノールＡ及び／又はターメロノールＢは、好ましくは、ウコン抽出物に由来するターメロノールＡ及び／又はターメロノールＢである。ここで、ウコン抽出物に由来するターメロノールＡ及び／又はターメロノールＢは、ウコン抽出物から分離されたターメロノールＡ及び／又はターメロノールＢであってもよいし、ウコン抽出物中の成分として存在するターメロノールＡ及び／又はターメロノールＢであってもよい。 In the present invention, turmonol A and / or turmonol B is preferably turmonol A and / or turmonol B derived from a turmeric extract. Here, turmonol A and / or turmonol B derived from the turmeric extract may be turmonol A and / or turmonol B separated from the turmeric extract, or turmonol A existing as a component in the turmeric extract. And / or tureronol B.
　ここでウコン抽出物とは、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ー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。 Here, the turmeric extract refers to an extract (turmeric extract) of a plant raw material derived from a plant belonging to the genus Turmeric belonging to the ginger family. The turmeric extract is not limited to the solvent extract obtained by extraction with an extraction solvent, but also includes those obtained by further fractionating and purifying the solvent extract by column chromatography or the like. The turmeric extract used in the present invention is obtained from an extract obtained by completing the extraction operation (including fraction purification in the case of fraction purification), a concentrate obtained by partially removing the solvent from the extract, or an extract. It can be in the form of a dry product from which the solvent has been removed. The removal of the solvent from the extract can be performed by volatilizing the solvent by heating and / or reduced pressure. These heating and decompression methods are not particularly limited, and for example, conventionally known methods can be used.
　前記植物原料としては、ショウガ科ウコン属の植物であるＣｕｒｃｕｍａ　ｌｏｎｇａ（ウコン）、Ｃｕｒｃｕｍａ　ａｒｏｍａｔｉｃａ、Ｃｕｒｃｕｍａ　ｚｅｄｏａｒｉａ、Ｃｕｒｃｕｍａ　ｐｈａｅｏｃａｕｌｉｓ、Ｃｕｒｃｕｍａ　ｋｗａｎｇｓｉｅｎｓｉｓ、Ｃｕｒｃｕｍａ　ｗｅｎｙｕｊｉｎ、及び／又は、Ｃｕｒｃｕｍａ　ｘａｎｔｈｏｒｒｈｉｚａ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 plant raw materials include Curcuma longa (turmeric), Curcuma aromatica, Curcuma zedoaria, Curcuma phaeocaulis, Curcuma kwangsiens, Curcuminc, and Curcumacurium. A Curcuma longa rhizome is preferred. As the rhizome, one collected from soil may be used, and an appropriate portion of the rhizome may be used as it is, cut into an appropriate size or shape, or pulverized. These plant materials may be appropriately dried.
　抽出溶媒としては、水及び親水性有機溶媒からなる群から選択される少なくとも１種、ヘキサン等の液体溶媒、水蒸気、超臨界流体等が例示できる。 Examples of the extraction solvent include at least one selected from the group consisting of water and a hydrophilic organic solvent, a liquid solvent such as hexane, water vapor, and a supercritical fluid.
　水及び親水性有機溶媒からなる群から選択される少なくとも１種の抽出溶媒としては、水、親水性有機溶媒、水と親水性有機溶媒の混合溶媒のいずれであってもよい。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。 The at least one extraction solvent selected from the group consisting of water and a hydrophilic organic solvent may be any of water, a hydrophilic organic solvent, and a mixed solvent of water and a hydrophilic organic solvent. The hydrophilic organic solvent may be a mixed solvent of plural kinds of hydrophilic organic solvents. “Water” includes hot water. As hot water, for example, hot water 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 in the case of using a mixed solvent of alcohol and water as the extraction solvent is not particularly limited. For example, the weight ratio is preferably in the range of 10:90 to 90:10, and more preferably in the range of 20:80 to 50:50. .
　水蒸気を用いる抽出は水蒸気蒸留とも呼ばれる。
　超臨界流体としては超臨界二酸化炭素が好ましい。
　ウコンから、ターメロノールＡ及びターメロノールＢを効率的に抽出する観点からは、抽出溶媒として、エタノール、ヘキサン又は超臨界流体を用いることが好ましい。 Extraction using steam is also called steam distillation.
Supercritical carbon dioxide is preferred as the supercritical fluid.
From the viewpoint of efficiently extracting tureronol A and tureronol B from turmeric, it is preferable to use ethanol, hexane or supercritical fluid as the extraction solvent.
　ウコンに含まれるクルクミンはクルクミノイドの一種である。国際機関ＪＥＣＦＡ（ＦＡＯ／ＷＨＯ合同食品添加物専門家会議）は、クルクミノイドのＡＤＩ（１日許容摂取量）を３ｍｇ／ｋｇ体重／日（例：体重５０ｋｇの人で１日あたり１５０ｍｇ）と設定していることから、ターメロノールＡ及び／又はターメロノールＢをウコン抽出物の形態で用いる場合、ターメロノールＡ及び／又はターメロノールＢを含みクルクミノイドの濃度が低いウコン抽出物を用いることが好ましい。このようなウコン抽出物を得るためには、抽出溶媒として、水（特に熱水）、ヘキサン、水蒸気又は超臨界流体を用いることが好ましい。
　抽出溶媒を用いたウコン抽出物の調製方法は特に限定されない。 Curcumin contained in turmeric is a kind of curcuminoid. The international organization JECFA (FAO / WHO Joint Expert Committee on Food Additives) sets the ADI (permissible daily intake) of curcuminoids to 3 mg / kg body weight / day (eg, 150 mg per day for a person with a body weight of 50 kg). Therefore, when using turmeronol A and / or turmonol B in the form of a turmeric extract, it is preferable to use a turmeric extract containing turmonol A and / or turmonol B and having a low curcuminoid concentration. In order to obtain such a turmeric extract, it is preferable to use water (particularly hot water), hexane, water vapor or a supercritical fluid as an extraction solvent.
The method for preparing the turmeric extract using the extraction solvent is not particularly limited.
　ターメロノールＡ及び／又はターメロノールＢは、それを含む植物原料の形態で用いられてもよい。ターメロノールＡ及び／又はターメロノールＢを含む植物原料としては、上記で説明した、ショウガ科ウコン属植物の原料が挙げられる。一方で、ショウガ科ウコン属植物の根茎は、ターメロノールＡ及び／又はターメロノールＢともに、鉄を比較的多く含む。鉄を多量に摂取することは、Ｃ型肝炎患者、ＮＡＳＨ（非アルコール性脂肪性肝炎）等の特定の症状を持つ人には悪影響がある可能性があるため、鉄分の摂取上限推奨量は１日あたり６ｍｇとされている。このため、ターメロノールＡ及び／又はターメロノールＢは、ショウガ科ウコン属植物の根茎の形態以外の形態であることが好ましい。 Turmonol A and / or turmonol B may be used in the form of a plant material containing it. Examples of the plant raw material containing turmonol A and / or turmonol B include the raw materials of the ginger family turmeric genus described above. On the other hand, the rhizome of the ginger family turmeric genus plant contains both iron and turmeronol A and / or turmonol B relatively. Ingestion of large amounts of iron may adversely affect people with specific symptoms such as hepatitis C patients and NASH (non-alcoholic steatohepatitis), so the recommended upper limit of iron intake is 1 6 mg per day. For this reason, it is preferable that turmeronol A and / or turmeronol B are forms other than the rhizome form of the ginger family turmeric genus plant.
＜有効成分の含有量＞
　本発明の組成物は、第１の態様において、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む。この第１の態様に係る組成物は、ターメロノールＡ及びターメロノールＢの一方のみを含む場合、含まれる一方の含有量が１回の摂取量当たり１００μｇ以上であればよく、ターメロノールＡ及びターメロノールＢの両方を含む場合、両方の合計含有量が１回の摂取量当たり１００μｇ以上であればよい。第１の態様に係る組成物は、ヒト等の動物が摂取することで、炎症、特に慢性炎症、を抑制する作用、及び、血中のＣＲＰ（ｃ－リアクティブプロテイン）値を低下する作用が奏される。第１の態様に係る組成物は、より好ましくは、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢを含み、より好ましくは、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含み、最も好ましくは、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び２０μｇ以上のターメロノールＢを含む。 <Content of active ingredient>
In the first embodiment, the composition of the present invention contains at least one of turmeronol A and turmeronol B in a total amount of 100 μg or more per one intake. In the case where the composition according to the first aspect contains only one of turmonol A and turmonol B, the content of one of them may be 100 μg or more per one intake. When the total content of both is included, it may be 100 μg or more per one intake. The composition according to the first aspect has an action of suppressing inflammation, particularly chronic inflammation, and an action of reducing CRP (c-reactive protein) level in blood when ingested by animals such as humans. Played. More preferably, the composition according to the first aspect comprises a total of 100 μg or more of turmeronol A and turmeronol B per intake, and more preferably 80 μg or more of turmeronol per intake. A and / or 20 μg or more of turmeronol B, most preferably 80 μg or more of turmeronol A and 20 μg or more of turmeronol B per serving.
　本発明の組成物は、第２の態様において、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む。第２の態様に係る組成物は、ヒト等の動物が摂取することで、炎症、特に慢性炎症、を抑制する作用、及び、血中のＣＲＰ（ｃ－リアクティブプロテイン）値を低下する作用が奏される。第２の態様に係る組成物は、より好ましくは、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び２０μｇ以上のターメロノールＢを含む。 In the second embodiment, the composition of the present invention contains 80 μg or more of turmeronol A and / or 20 μg or more of turmeronol B per one intake. The composition according to the second aspect has an action of suppressing inflammation, particularly chronic inflammation, and an action of reducing the CRP (c-reactive protein) level in blood when ingested by animals such as humans. Played. More preferably, the composition according to the second aspect contains 80 μg or more of turmeronol A and 20 μg or more of turmeronol B per serving.
　ターメロノールＡ及びターメロノールＢの定量方法は特に限定されないが、例えば、実施例に示すＬＣ／ＭＳ分析により行うことができる。 The method for quantifying tureronol A and tureronol B is not particularly limited, and can be performed, for example, by LC / MS analysis shown in Examples.
　本発明の、前記第１の態様又は前記第２の態様に係る組成物は、製造完了時、すなわち、完成製品として少なくとも製造工場を出荷される段階において、ターメロノールＡ及び／又はターメロノールＢを上記の範囲で含んでいればよい。 In the composition according to the first aspect or the second aspect of the present invention, the tereronol A and / or the turmeronol B is added to the tereronol A and / or tereronol B at the time of completion of production, that is, at the stage of shipment of the production factory as a finished product. It only has to be included in the range.
　本発明の、前記第１の態様又は前記第２の態様に係る組成物は、更に好ましくは、１回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回の摂取量当たりのクルクミンの含有量が３０ｍｇ未満である組成物は、クルクミノイドのＡＤＩ（１日許容摂取量）（体重５０ｋｇの人で１５０ｍｇ）を超えることなく、炎症の抑制及び血中ＣＲＰ値の低下に有効な量のターメロノールＡ及び／又はターメロノールＢを摂取することが容易であるため好ましい。 More preferably, the composition according to the first aspect or the second aspect of the present invention has a curcumin content per intake of less than 30 mg. Compositions with a curcumin content of less than 30 mg per dose will reduce inflammation and blood CRP without exceeding the curcuminoid ADI (permissible daily intake) (150 mg for a 50 kg person). Since it is easy to ingest an amount of turmeronol A and / or turmeronol B effective for lowering the value, it is preferable.
　本発明において「１回の摂取量」とは、本発明の組成物が一度に摂取される量、あるいは短い時間間隔（例えば１０分以下、好ましくは５分以下の時間）をおいて連続的に複数回で摂取される総量を意味する。本発明の組成物が液状又は流動状の組成物の形態である場合には例えば０．１ｍｌ～５００ｍｌ（典型的には５０ｍｌ、１００ｍｌ、１５０ｍｌ、２００ｍｌ、２５０ｍｌ、３００ｍｌ、３５０ｍｌ、４００ｍｌ、４５０ｍｌ又は５００ｍｌ）がその量であり、ゲル状、半固形状又は固形状等の他の形状の組成物である場合には例えば０．１ｇ～５００ｇ（典型的には５０ｇ、１００ｇ、１５０ｇ、２００ｇ、２５０ｇ、３００ｇ、３５０ｇ、４００ｇ、４５０ｇ又は５００ｇ）がその量である。以下でも「１回の摂取量」をこの意味で用いる。 In the present invention, “a single intake” means an amount at which the composition of the present invention is ingested at a time, or continuously over a short time interval (for example, 10 minutes or less, preferably 5 minutes or less). This means the total amount taken multiple times. When the composition of the present invention is in the form of a liquid or fluid composition, for example, 0.1 ml to 500 ml (typically 50 ml, 100 ml, 150 ml, 200 ml, 250 ml, 300 ml, 350 ml, 400 ml, 450 ml or 500 ml) ) Is the amount, and in the case of a composition in another shape such as gel, semi-solid or solid, for example, 0.1 g to 500 g (typically 50 g, 100 g, 150 g, 200 g, 250 g, 300g, 350g, 400g, 450g or 500g) is the amount. In the following, “one intake” is used in this sense.
＜経口摂取される組成物＞
　本発明の、前記第１の態様又は前記第２の態様に係る組成物は、好ましい一実施形態において、経口摂取される組成物である。 <Compositions taken orally>
In a preferred embodiment, the composition according to the first aspect or the second aspect of the present invention is a composition to be taken orally.
　本発明の経口摂取される組成物は、ヒト等の動物が経口摂取することにより、炎症の抑制や、血中ＣＲＰ値の低下といった好ましい作用を奏する。 The composition that is orally ingested according to the present invention exhibits preferable effects such as suppression of inflammation and reduction of blood CRP value when animals such as humans are orally ingested.
　本発明の経口摂取される組成物としては、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、ヒトにより経口摂取される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 to be orally ingested according to the present invention may be a composition in various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, etc. It is more preferable. The foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like.
　本発明の経口摂取される組成物は、継続的に経口摂取されるものであってもよいし、必要時に経口摂取されるものであってもよい。 The orally ingested composition of the present invention may be continuously ingested, or may be ingested when necessary.
　本発明の経口摂取される組成物の具体的な形態については後述する。 The specific form of the orally ingested composition of the present invention will be described later.
＜抗炎症用組成物＞
　本発明の、前記第１の態様又は前記第２の態様に係る組成物は、好ましい他の一実施形態において、抗炎症用組成物である。 <Anti-inflammatory composition>
In another preferable embodiment, the composition according to the first aspect or the second aspect of the present invention is an anti-inflammatory composition.
　本発明の抗炎症用組成物は、ヒト等の動物における、炎症、特に慢性炎症の予防又は治療に有用である。 The anti-inflammatory composition of the present invention is useful for the prevention or treatment of inflammation, particularly chronic inflammation, in animals such as humans.
　本発明の更に別の実施形態は、本発明の、前記第１の態様又は前記第２の態様に係る組成物の、抗炎症用組成物の製造のための使用である。 Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of an anti-inflammatory composition.
　本発明の更に別の実施形態は、本発明の、前記第１の態様又は前記第２の態様に係る組成物の、抗炎症用医薬の製造のための使用である。 Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of an anti-inflammatory drug.
　本発明の更に別の実施形態は、
　本発明の、前記第１の態様又は前記第２の態様に係る組成物を、炎症の治療又は予防を必要とする患者に投与すること、及び
　前記患者において炎症を治療又は予防すること
を含む、炎症を治療又は予防する方法である。 Yet another embodiment of the present invention provides:
Administering the composition according to the first aspect or the second aspect of the present invention to a patient in need of treatment or prevention of inflammation, and treating or preventing inflammation in the patient, A method of treating or preventing inflammation.
　本発明の更に別の実施形態は、
　炎症の治療又は予防を必要とする患者において炎症を治療又は予防するための、本発明の、前記第１の態様又は前記第２の態様に係る組成物である。 Yet another embodiment of the present invention provides:
The composition according to the first aspect or the second aspect of the present invention for treating or preventing inflammation in a patient in need of treatment or prevention of inflammation.
　本発明において抗炎症用組成物、或いは、炎症の治療又は予防のために用いる組成物又は医薬としては、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、ヒトにより摂取される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。本発明において抗炎症用組成物、或いは、炎症の治療又は予防のために用いる組成物又は医薬は、好ましくは、経口又は経鼻により摂取される組成物の形態であり、より好ましくは、経口摂取される組成物の形態である。 In the present invention, the anti-inflammatory composition, or the composition or pharmaceutical used for the treatment or prevention of inflammation is a composition in various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives and the like. It may be a medicine or a food or drink taken by a human. The foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like. In the present invention, the anti-inflammatory composition or the composition or medicament used for the treatment or prevention of inflammation is preferably in the form of a composition taken orally or nasally, more preferably taken orally. In the form of a composition.
　本発明において抗炎症用組成物、或いは、炎症の治療又は予防のために用いる組成物又は医薬は、継続的に摂取されるものであってもよいし、必要時に摂取されるものであってもよい。 In the present invention, the anti-inflammatory composition, or the composition or medicament used for the treatment or prevention of inflammation may be ingested continuously or may be ingested when necessary. Good.
　本発明において抗炎症用組成物、或いは、炎症の治療又は予防のために用いる組成物又は医薬の具体的な形態については後述する。 In the present invention, the anti-inflammatory composition, or the specific form of the composition or medicament used for the treatment or prevention of inflammation will be described later.
＜血中ＣＲＰ値低下用組成物＞
　本発明の、前記第１の態様又は前記第２の態様に係る組成物は、好ましい更に他の一実施形態において、血中ＣＲＰ値低下用組成物である。 <Composition for lowering CRP level in blood>
In still another preferred embodiment, the composition according to the first aspect or the second aspect of the present invention is a composition for lowering the blood CRP value.
　本発明の血中ＣＲＰ値低下用組成物は、ヒト等の動物において、炎症、特に慢性炎症の指標である血中ＣＲＰ（ｃ－リアクティブプロテイン）値を低下させる作用を有する。 The composition for lowering the blood CRP level of the present invention has the effect of lowering the blood CRP (c-reactive protein) level, which is an indicator of inflammation, particularly chronic inflammation, in animals such as humans.
　血中ＣＲＰ値はまた、炎症以外のリスク、例えば、動脈硬化等の心血管疾患のリスクの指標でもある。ＣＲＰは動脈硬化の増悪に関わることが知られており、血中ＣＲＰ測定は心血管疾患のリスク予知に活用されている。このため、血中ＣＲＰ値低下作用を有する組成物は、炎症の治療又は予防の用途だけでなく、心血管疾患の治療又は予防の用途にも利用することができる。 The blood CRP value is also an index of risk other than inflammation, for example, risk of cardiovascular disease such as arteriosclerosis. CRP is known to be related to exacerbation of arteriosclerosis, and blood CRP measurement is used for predicting the risk of cardiovascular disease. For this reason, the composition having a blood CRP level lowering action can be used not only for the treatment or prevention of inflammation but also for the treatment or prevention of cardiovascular disease.
　本発明の更に別の実施形態は、本発明の、前記第１の態様又は前記第２の態様に係る組成物の、血中ＣＲＰ値低下用組成物の製造のための使用である。 Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the production of a composition for lowering blood CRP levels.
　本発明の更に別の実施形態は、本発明の、前記第１の態様又は前記第２の態様に係る組成物の、血中ＣＲＰ値低下用医薬の製造のための使用である。 Still another embodiment of the present invention is the use of the composition according to the first aspect or the second aspect of the present invention for the manufacture of a medicament for lowering the blood CRP value.
　本発明の更に別の実施形態は、
　本発明の、前記第１の態様又は前記第２の態様に係る組成物を、血中ＣＲＰ値の低下を必要とする患者に投与すること、及び
　前記患者において血中ＣＲＰ値を低下させること
を含む、血中ＣＲＰ値を低下させる方法である。 Yet another embodiment of the present invention provides:
Administering the composition according to the first aspect or the second aspect of the present invention to a patient in need of lowering the blood CRP value, and lowering the blood CRP value in the patient; And a method for lowering the CRP level in blood.
　本発明の更に別の実施形態は、
　血中ＣＲＰ値の低下を必要とする患者において血中ＣＲＰ値の低下させるための、本発明の、前記第１の態様又は前記第２の態様に係る組成物である。 Yet another embodiment of the present invention provides:
The composition according to the first aspect or the second aspect of the present invention for lowering blood CRP level in a patient in need of lowering blood CRP level.
　本発明において血中ＣＲＰ値低下用組成物、或いは、血中ＣＲＰ値低下のために用いる組成物又は医薬としては、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、ヒトにより摂取される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。本発明において血中ＣＲＰ値低下用組成物、或いは、血中ＣＲＰ値低下のために用いる組成物又は医薬は、好ましくは、経口又は経鼻により摂取される組成物の形態であり、より好ましくは、経口摂取される組成物の形態である。 In the present invention, the composition for lowering the blood CRP value, or the composition or medicine used for lowering the blood CRP value includes compositions of various forms such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, etc. It may be a thing, and it is more preferable that it is a pharmaceutical or food or drink taken by humans. The foods and drinks include foods in the form of functional display foods, foods for specified health use, supplements for nutritional supplements, and the like. In the present invention, the composition for lowering the blood CRP value, or the composition or medicament used for lowering the blood CRP value is preferably in the form of a composition taken orally or nasally, more preferably. In the form of a composition to be taken orally.
　本発明において血中ＣＲＰ値低下用組成物、或いは、血中ＣＲＰ値低下のために用いる組成物又は医薬は、継続的に摂取されるものであってもよいし、必要時に摂取されるものであってもよい。 In the present invention, the composition for lowering the blood CRP value, or the composition or medicament used for lowering the blood CRP value may be taken continuously or taken as needed. There may be.
　本発明において血中ＣＲＰ値低下用組成物、或いは、血中ＣＲＰ値低下のために用いる組成物又は医薬の具体的な形態については後述する。 In the present invention, the composition for lowering the blood CRP value, or the specific form of the composition or medicament used for lowering the blood CRP value will be described later.
＜本発明の組成物の形態＞
　本発明の経口摂取される組成物、抗炎症用組成物、血中ＣＲＰ値低下用組成物、炎症の治療又は予防のために用いる組成物又は医薬、或いは、血中ＣＲＰ値低下のために用いる組成物又は医薬（以下、「本発明の組成物」と称す）は、有効成分（ターメロノールＡ及び／又はターメロノールＢ、或いは、それを含むウコン抽出物、植物原料の原体）自体であってもよいし、前記有効成分と、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、前記有効成分と、少なくとも１種の他の成分とを含む場合、前記有効成分と、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、前記有効成分と、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、前記有効成分と、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。 <Form of the composition of the present invention>
Orally ingested composition of the present invention, anti-inflammatory composition, composition for lowering blood CRP level, composition or medicine used for treatment or prevention of inflammation, or used for lowering blood CRP level The composition or medicine (hereinafter referred to as “the composition of the present invention”) may be the active ingredient itself (turmeronol A and / or turmeronol B, or a turmeric extract containing the active ingredient). Alternatively, it may be a composition containing the active ingredient and at least one other ingredient. When the composition of the present invention contains the active ingredient and at least one other component, the composition may be a mixture of the active ingredient and at least one other component, A composition in which the active ingredient and at least one other ingredient are formulated by an appropriate means may be used, or a formulation in which the active ingredient and at least one other ingredient are formulated. Further, it may be a composition mixed with other components.
　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 at least one other component that can be contained in the composition of the present invention is not particularly limited, but is preferably acceptable in a final form such as pharmaceuticals, foods and drinks, feeds, food additives, feed additives, and the like. Examples of such components that can be taken orally can be exemplified.
　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, and water. Moreover, you may add a pigment | dye, a fragrance | flavor, a preservative, an antiseptic | preservative, a fungicide, a further physiologically active substance, etc. as needed.
　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, isomerized sugar (glucose fructose liquid sugar, fructose glucose liquid sugar, sugar mixed isomerized sugar, etc.) Sugar alcohols (erythritol, xylitol, lactitol, palatinit, sorbitol, reduced starch syrup, etc.), honey, high intensity sweeteners (sucralose, acesulfame potassium, thaumatin, stevia, aspartame, etc.).
　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 sour agent 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。 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, karaya gum, agar, gelatin, pectin, soybean polysaccharide, carboxymethylcellulose (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, and saponin.
　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、カテキン等が挙げられる。 Examples of antioxidants include vitamin C, tocopherol (vitamin E), enzyme-treated rutin, catechin 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 above-mentioned other components can be appropriately blended in an amount within the range usually employed by those skilled in the art for compositions such as foods and drinks and pharmaceuticals.
　前記有効成分と、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。 Composition forms in which the active ingredient and at least one other ingredient are formulated by appropriate means are powders, granules, capsules, tablets (coated tablets such as sugar-coated tablets or multilayer tablets, mouth disintegrants, chewables) It may be in the form of a solid composition such as a tablet or the like, or it may be in the form of a liquid composition such as a solution.
＜実験１：ターメロノールＡ及びターメロノールＢの抗炎症作用＞
１．調製方法
　ウコン根茎から熱水抽出し、熱水抽出物を得た。次に熱水抽出物から９０％メタノール（メタノール／水＝９０／１０（ｖ／ｖ））で抽出し、９０％メタノール抽出物を得た。次に９０％メタノール抽出物を酢酸エチル／水の液液分配に供し、酢酸エチル画分を得た。ターメロノールＡは、酢酸エチル画分を逆相カラムクロマトグラフィーで精製した後、ジメチルスルホキシドに溶解して試験に用いた。 <Experiment 1: Anti-inflammatory action of tureronol A and tureronol B>
1. Preparation Method Hot water extraction was performed from turmeric rhizomes to obtain a hot water extract. Next, 90% methanol (methanol / water = 90/10 (v / v)) was extracted from the hot water extract to obtain a 90% methanol extract. Next, the 90% methanol extract was subjected to ethyl acetate / water liquid-liquid partition to obtain an ethyl acetate fraction. Turmeronol A was used in the test after the ethyl acetate fraction was purified by reverse phase column chromatography and then dissolved in dimethyl sulfoxide.
　単離されたターメロノールＡの構造は、１Ｈ　ＮＭＲ、１３Ｃ　ＮＭＲ、ＬＣＭＳ等の機器分析の結果及び公知の情報（Ａｇｒｉｃ．Ｂｉｏｌ．　Ｃｈｅｍ．，１９９０；５４（９）：２３６７－７１）に基づき特定した。 The structure of isolated turomerol A is based on the results of instrumental analysis such as 1 H NMR, 13 C NMR, LCMS, and known information (Agric. Biol. Chem., 1990; 54 (9): 2367-71). Identified.
　ターメロノールＢは、長良サイエンス株式会社の市販品を購入し、ジメチルスルホキシドに溶解して試験に用いた。 Termelonol B was purchased from Nagara Science Co., Ltd., dissolved in dimethyl sulfoxide, and used for the test.
２．抗炎症作用の評価
　実験にはマウスマクロファージ細胞株ＲＡＷ２６４．７を用い、ＤＭＥＭ（１０％ＦＢＳ）培地で９６穴プレートに１．５×１０５セル数になるように播種して２４時間ＣＯ２インキュベーターでコンフルエントになるまで培養した。９６穴プレートで培養したマウスマクロファージ細胞株ＲＡＷ２６４．７を、所定濃度（１．７μｇ／ｍＬ、３．２μｇ／ｍＬ、６．３μｇ／ｍＬ、１２．５μｇ／ｍＬ、及び、２５μｇ／ｍＬから選択される複数の濃度）の、ターメロノールＡ又はターメロノールＢで、１時間前処理した後、２０ｎｇ／ｍＬのリポポリサッカリド（ＬＰＳ、炎症誘導因子）を添加し、１２時間培養した。その後、上清を回収し、競合ＥＬＩＳＡ法で上清に放出されたプロスタグランジンＥ２（ＰＧＥ２）量を測定した。また、上清に放出されたＮＯ２ －量（ＮＯの酸化物で、ＮＯ量を反映）をＧｒｉｅｓｓ法で測定した。なお、各成分による処理の際は１０％ＦＢＳを含まないＤＭＥＭを使用した。細胞をターメロノールＡ又はターメロノールＢで処理しない以外は同じ操作を行う試験区をコントロール／ＬＰＳ（＋）とし、１２時間培養時の培地中にＬＰＳを添加しない以外はコントロール／ＬＰＳ（＋）と同じ操作を行う試験区をコントロール／ＬＰＳ（－）とした。 2. Evaluation of anti-inflammatory action The mouse macrophage cell line RAW264.7 was used for the experiment, seeded in a 96-well plate with DMEM (10% FBS) medium to a number of 1.5 × 10 5 cells, and CO 2 incubator for 24 hours. Incubated until confluent. The mouse macrophage cell line RAW264.7 cultured in a 96-well plate was selected from predetermined concentrations (1.7 μg / mL, 3.2 μg / mL, 6.3 μg / mL, 12.5 μg / mL, and 25 μg / mL). (2) at 20 mg / mL lipopolysaccharide (LPS, inflammation-inducing factor), and cultured for 12 hours. Thereafter, the supernatant was recovered, and the amount of prostaglandin E2 (PGE2) released into the supernatant was measured by a competitive ELISA method. Further, the amount of NO 2 − released into the supernatant (NO oxide, reflecting NO amount) was measured by the Griess method. In addition, in the process by each component, DMEM which does not contain 10% FBS was used. Control / LPS (+) is the test group in which the same operation is performed except that the cells are not treated with tureronol A or tureronol B, and the same operation as control / LPS (+) is performed except that LPS is not added to the medium during the 12-hour culture. The test group where the test was performed was defined as control / LPS (−).
３．結果
　ターメロノールＡにより処理したＲＡＷ２６４．７の培養上清中のＰＧＥ２濃度を図１に示す。 3. Results The PGE2 concentration in the culture supernatant of RAW264.7 treated with tureronol A is shown in FIG.
　ターメロノールＢにより処理したＲＡＷ２６４．７の培養上清中のＰＧＥ２濃度を図２に示す。 The PGE2 concentration in the culture supernatant of RAW264.7 treated with tureronol B is shown in FIG.
　ターメロノールＡにより処理したＲＡＷ２６４．７の培養上清中のＮＯ２ －濃度を図３に示す。 The NO 2 − concentration in the culture supernatant of RAW264.7 treated with turmeronol A is shown in FIG.
　ターメロノールＢにより処理したＲＡＷ２６４．７の培養上清中のＮＯ２ －濃度を図４に示す。 The NO 2 − concentration in the culture supernatant of RAW264.7 treated with turmeronol B is shown in FIG.
　図１～４において「＋」は１２時間培養時の培地中に２０ｎｇ／ｍＬのＬＰＳを添加したことを指し、「－」はＬＰＳを添加しなかったことを指す。 1-4, “+” indicates that 20 ng / mL LPS was added to the medium during 12 hours of culture, and “−” indicates that LPS was not added.
　図１～４に示す結果は、ターメロノールＡ及びターメロノールＢがＰＥＧ２産生抑制活性及びＮＯ産生抑制活性を有することを裏づける。 The results shown in FIGS. 1 to 4 confirm that tureronol A and tureronol B have PEG2 production inhibitory activity and NO production inhibitory activity.
＜実験２：ターメロノールＡ及びターメロノールＢを含むウコン抽出物のヒトにおける抗炎症作用＞
１．ウコン抽出物
　ウコン抽出物は、ウコン（Ｃｕｒｃｕｍａ　ｌｏｎｇａ）の根茎部分を熱水抽出し、減圧濃縮および噴霧乾燥をして水分を除去することにより調製した。 <Experiment 2: Anti-inflammatory action in human of turmeric extract containing tureronol A and tureronol B>
1. Turmeric extract The turmeric extract was prepared by hot water extraction of the curcuma longa rhizome part, vacuum concentration and spray drying to remove moisture.
２．試験食品
　ウコン抽出物摂取群の被験者が摂取した錠剤は、上述のウコン抽出物、麦芽糖、微粒二酸化ケイ素、ショ糖脂肪酸エステル、光沢剤を用いて作製した。本錠剤中のターメロノールＡ及びターメロノールＢの量を、後述する手順によりＬＣ／ＭＳを用いて測定した。同じく、本錠剤中のクルクミンの量を、後述する手順によりＨＰＬＣを用いて測定した。その結果、本錠剤の被験者１人の１回摂取量（３錠）には、８６．５μｇのターメロノールＡ、２４．７μｇのターメロノールＢ、４７１μｇのクルクミンを含有することを確認した。 2. Test food Tablets ingested by subjects in the turmeric extract intake group were prepared using the above-mentioned turmeric extract, maltose, fine silicon dioxide, sucrose fatty acid ester, and brightener. The amount of turmeronol A and turmeronol B in this tablet was measured using LC / MS according to the procedure described later. Similarly, the amount of curcumin in the tablet was measured using HPLC according to the procedure described later. As a result, it was confirmed that the single dose (3 tablets) of one subject of this tablet contained 86.5 μg of turmeronol A, 24.7 μg of turmeronol B, and 471 μg of curcumin.
　プラセボ摂取群の被験者が摂取した錠剤は、麦芽糖、色素、微粒二酸化ケイ素、ショ糖脂肪酸エステル、光沢剤を用いて作製した。 Tablets taken by subjects in the placebo intake group were prepared using maltose, pigment, fine silicon dioxide, sucrose fatty acid ester, and brightener.
３．ターメロノールＡ及びターメロノールＢの分析
　前述のウコン抽出物摂取群の被験者が摂取した錠剤を粉砕して秤量し、水と酢酸エチルを加え、遠心分離して得られた上清を活性炭カラムに通した後、窒素濃縮し、アセトニトリルに溶解した。得られた液を測定試料として、ＬＣ／ＭＳ分析に供した。ＬＣ／ＭＳ分析は以下の条件で行った。
　分析装置：Ｔｈｅｒｍｏ　Ｆｉｓｈｅｒ　Ｓｃｉｅｎｔｉｆｉｃ社　Ｏｒｂｉｔｒａｐ　ＬＣＭＳ（Ｏｒｂｉｔｒａｐ　Ｖｅｌｏｓ　Ｐｒｏ）
　流速：０．５ｍＬ／分
　移動相：アセトニトリル、０．１％ギ酸水溶液
　送液グラジエント：
Figure JPOXMLDOC01-appb-T000003
 　使用カラム：ＵＮＩＳＯＮ　ＵＫ－Ｃ１８（２５０ｍｍ×４．６ｍｍ、３μｍ）
　カラム温度：３０℃ 3. Analysis of tureronol A and tureronol B After pulverizing and weighing the tablets ingested by the subjects of the turmeric extract intake group, water and ethyl acetate were added, and the supernatant obtained by centrifugation was passed through an activated carbon column. Concentrated with nitrogen and dissolved in acetonitrile. The obtained liquid was subjected to LC / MS analysis as a measurement sample. LC / MS analysis was performed under the following conditions.
Analyzer: Thermo Fisher Scientific Orbitrap LCMS (Orbitrap Velos Pro)
Flow rate: 0.5 mL / min Mobile phase: Acetonitrile, 0.1% formic acid aqueous solution Feed gradient:
Figure JPOXMLDOC01-appb-T000003
 Column used: UNISON UK-C18 (250 mm × 4.6 mm, 3 μm)
Column temperature: 30 ° C
４．クルクミンの分析
　前述のウコン抽出物摂取群の被験者が摂取した錠剤を粉砕して秤量し、メタノール水溶液を加え、振とう撹拌後に遠心分離して得られた上清を測定試料としてＨＰＬＣ分析に供した。ＨＰＬＣ分析は以下の条件で行った。
　分析装置：日立ハイテクノロジーズ社　Ｃｈｒｏｍａｓｔｅｒ５０００　ＨＰＬＣ
　流速：１ｍＬ／分
　移動相：アセトニトリル：トリフルオロ酢酸水溶液（ｐＨ３．３）＝４５％：５５％
　使用カラム：Ｌ－Ｃｏｌｕｍｎ　ＯＤＳ（２５０ｍｍ×４．６ｍｍ、５μｍ）
　カラム温度：４０℃ 4). Analysis of curcumin The tablets ingested by the subjects of the above-mentioned turmeric extract intake group were crushed and weighed, added with aqueous methanol, centrifuged after shaking and stirring, and subjected to HPLC analysis using the supernatant obtained as a measurement sample . HPLC analysis was performed under the following conditions.
Analyzer: Hitachi High-Technologies Corporation Chromamaster 5000 HPLC
Flow rate: 1 mL / min Mobile phase: Acetonitrile: Trifluoroacetic acid aqueous solution (pH 3.3) = 45%: 55%
Column used: L-Column ODS (250 mm × 4.6 mm, 5 μm)
Column temperature: 40 ° C
５．被験者
　ウコン抽出物摂取群及びプラセボ摂取群は、それぞれ、以下の条件を満たす４５名の被験者からなる。
　年齢が５０歳～６９歳の男女
　ＢＭＩが正常高値～肥満１度の方（ＢＭＩ：２３以上３０未満）、又は血圧が正常血圧～Ｉ度高血圧の方（収縮期血圧：１２０ｍｍＨｇ以上１６０ｍｍＨｇ未満、又は拡張期血圧：８０ｍｍＨｇ以上１００ｍｍＨｇ未満）
　から一定数を選定した。 5). Subjects Each of the turmeric extract intake group and the placebo intake group consists of 45 subjects who satisfy the following conditions.
Men and women aged 50 to 69 years BMI is normally high to obese 1 degree (BMI: 23 to less than 30), or blood pressure is normal blood pressure to I degree hypertension (systolic blood pressure: 120 mmHg to 160 mmHg, or Diastolic blood pressure: 80mmHg or more and less than 100mmHg)
A certain number was selected.
６．プラセボ対照二重盲検並行群間比較試験
　ウコン抽出物摂取群の４５名の被験者は、ウコン抽出物を含有する前記錠剤３粒を１２週間にわたり毎日夕食前に経口摂取した。ウコン抽出物摂取群では１２週間の試験中２名の被験者が脱落者又は除外基準対象者となり４３名が試験を完了した。 6). Placebo-controlled double-blind parallel group comparison study 45 subjects in the turmeric extract intake group orally ingested 3 tablets containing the turmeric extract daily for 12 weeks before dinner. In the turmeric extract intake group, 2 subjects during the 12-week study became dropouts or exclusion criteria subjects and 43 completed the study.
　プラセボ摂取群の４５名の被験者は、ウコン抽出物を含有しない前記錠剤３粒を１２週間にわたり毎日夕食前に摂取した。プラセボ摂取群では１２週間の試験中１名の被験者が脱落者又は除外基準対象者となり４４名が試験を完了した。 45 subjects in the placebo intake group ingested the 3 tablets containing no turmeric extract every day for 12 weeks before dinner. In the placebo ingestion group, one subject was a dropout or exclusion criteria subject during the 12-week study, and 44 subjects completed the study.
　試験開始前、４週間後、８週間後、１２週間後に各被験者の血中ＣＲＰ（ｃ－リアクティブプロテイン）値を測定し平均値を求めた。血中ＣＲＰ値は、ネフェロメトリー法およびラテックス凝集比濁法により測定した。ネフェロメトリー法による測定は、シーメンスヘルスケア・ダイアグノティクス社のＮ－ラテックスＣＲＰ　ＩＩキットに準拠して行った。ラテックス凝集比濁法による測定は、ＬＳＩメディエンス社のイアトロＣＲＰ－ＥＸキットに準拠して行った。 Before the start of the test, 4 weeks, 8 weeks, and 12 weeks later, the blood CRP (c-reactive protein) value of each subject was measured to obtain an average value. The blood CRP value was measured by the nephelometry method and the latex agglutination turbidimetry. The measurement by the neferometry method was performed according to the N-latex CRP II kit of Siemens Healthcare Diagnostics. The measurement by latex agglutination turbidimetry was carried out according to the Iatro CRP-EX kit of LSI Medience.
　結果を図５に示す。ウコン抽出物摂取群では、ウコン抽出物含有錠剤の摂取開始から８週間後及び１２週間後に、プラセボ群と比較し有意に血中ＣＲＰ値が低減した。ターメロノールＡ及びターメロノールＢを含むウコン抽出物が、抗炎症作用、又は、心血管疾患を治療又は予防する作用を有することが示唆された。 The results are shown in FIG. In the turmeric extract ingestion group, the CRP level in blood significantly decreased compared to the placebo group 8 and 12 weeks after the start of ingestion of the turmeric extract-containing tablet. It was suggested that the turmeric extract containing tureronol A and tureronol B has an anti-inflammatory action or an action to treat or prevent cardiovascular disease.
　本発明は、飲食品又は医薬品の分野において有用である。 The present invention is useful in the field of food and drink or pharmaceuticals.
　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 are incorporated herein by reference in their entirety.

Claims (8)

  1. 　経口摂取される組成物であって、１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、組成物。 A composition that is orally ingested and contains at least one of tureronol A and tureronol B in a total amount of 100 μg or more per one intake.
  2. 　経口摂取される組成物であって、１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、組成物。 A composition that is orally ingested and contains 80 μg or more of tureronol A and / or 20 μg or more of tereronol B per one intake.
  3. 　前記ターメロノールＡ及び前記ターメロノールＢがウコン抽出物に由来する、請求項１又は２に記載の組成物。 The composition according to claim 1 or 2, wherein the turmeronol A and the turmonol B are derived from a turmeric extract.
  4. 　１回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１～３のいずれか１項に記載の組成物。 The composition according to any one of claims 1 to 3, wherein the curcumin content per intake is less than 30 mg.
  5. 　１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、抗炎症用組成物。 An anti-inflammatory composition comprising at least one of tureronol A and tureronol B in a total amount of 100 μg or more per intake.
  6. 　１回の摂取量当たり、合計で１００μｇ以上の、ターメロノールＡ及びターメロノールＢの少なくとも一方を含む、血中ＣＲＰ値低下用組成物。 A composition for lowering CRP levels in blood, comprising at least one of turmeronol A and tureronol B in a total amount of 100 μg or more per one intake.
  7. 　１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、抗炎症用組成物。 An anti-inflammatory composition comprising 80 μg or more of tureronol A and / or 20 μg or more of turmeronol B per one intake.
  8. 　１回の摂取量当たり、８０μｇ以上のターメロノールＡ及び／又は２０μｇ以上のターメロノールＢを含む、血中ＣＲＰ値低下用組成物。 A composition for lowering the CRP level in blood, comprising 80 μg or more of tureronol A and / or 20 μg or more of turmeronol B per one intake.
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